January 2011 Volume 7, Number 1 www.drugdiscoverynews.com Global News

6

Instruments & Informatics

12

Diagnostics 16 23

research & development

27

GOVERNMENT WATCH

31

what’s inside

Omics & Systems Biology

finance.........................................................3 Markets........................................................4 Editorial/commentary..............................10 new products............................................37 facts & figures..........................................38

From courtship to screening formal engagement

Special Report

First installment of a multi-part series See page 34

Research at the speed of light High-throughput screening technology leads to advances in drug discovery

Plus:

Billions of screens have produced… what? Critics of high-throughput screening ask: Is the approach of building a bigger haystack really the best way to find more needles?

After months of talking and speculation, Johnson & Johnson makes official its $2.3 billion bid to acquire Dutch biotech Crucell By Jeffrey Bouley NEW BRUNSWICK, N.J.—There have been a few bumps in the road in Johnson & Johnson’s quest to acquire Leiden, the Netherlandsbased Crucell NV—Crucell’s second-largest shareholder grumbling about the offer price being too low and problems at the company’s South Korean manufacturing plant begin the most notable—but J&J officially made its $32.30 per-share bid for the company in early December. The Dutch biotech firm’s CEO, Ronald Brus, along with the Crucell management

board and the Crucell supervisory board, are urging shareholders to accept J&J’s longawaited $2.3 billion bid. The offer represents a premium of 58 percent over the closing price of the ordinary shares as of Sept. 16, 2010, the day before J&J and Crucell announced they were in negotiations for a merger and acquisition deal, and a premium of 63 percent over the 30-day trading average of the ordinary shares of Sept. 16. J&J, which already owns an 18 percent stake in the company, is looking in part to expand in the arena of influenza vaccinations after losing patent protection on a couple former top-selling drugs. “Crucell would give J&J a vaccine platform at a time when the vaccine business is becoming increasingly attractive because of its costeffectiveness, limited exposure to generics j&j continued on page 7

Johnson & Johnson, which already owns an 18 percent stake in Crucell, is looking to expand in the arena of influenza vaccinations after losing patent protection on several former top-selling drugs.

An Avid acquisition Merck plays it smart

Lilly acquires Avid Radiopharmaceuticals for upfront payment of $300 million

Pharma acquires SmartCells and a unique preclinical insulin injection program for more than $500 million

By David Hutton INDIANAPOLIS—Taking

its innovation-based strategy to heart, Eli Lilly & Co. has signed an agreement to acquire Avid Radiopharma­ ceuticals Inc., a privately held company developing novel molecular imaging compounds intended for the detection and monitoring of chronic human diseases. Based in Philadelphia, Avid’s lead program in development is AVID continued on page 19

By Amy Swinderman BEVERLY, Mass.—Seeking to claim a stake in the rapidly grow-

Eli Lilly & Co. has said that it hopes to combat generic competition by conducting smarter and cheaper research in-house, while adding in promising compounds from outside through bolton deals. While the acquisition of Avid doesn’t fill a specific void in Lilly’s pipeline, it does provide some near-term benefits, as Avid’s lead program florbetapir could be an important diagnostic to help physicians and researchers identify the presence of amyloid beta plaque in Alzheimer’s patients.

inside this issue

Technology Trends

ing, multibillion-dollar diabetes market, Merck & Co. Inc. announced in December that it will acquire SmartCells Inc., a young, low-profile private company located here. The deal—which gives Merck access to SmartCells’ SmartInsulin, a preclinical insulin injection for the treatment of types 1 and 2 diabetes—involves an unspecified upfront cash payment and development and regulatory milestone and sales payments that could exceed $500 million. SMART continued on page 30

Start of a new era Palm Springs plays host to the last distinct LabAutomation meeting as former ALA members look toward mingling with former SBS members in a single annual meeting in 2012 See page 20

finance

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January 2011 • Drug Discovery News  3

Sutro Biopharma secures $36.5 million in Series C financing SAN FRANCISCO—Sutro Biopharma, a biopharmaceutical company that develops novel protein therapeutics and biosuperiors with site-directed modifications, recently announced that it secured $36.5 million in a Series C financing. According to the company, the funds will support the company’s ongoing development of novel biotherapeutics and advance the its biochemical protein synthesis platform to meet current Good Manufacturing Practice (cGMP) standards. According to Sutro, its synthesis technology “opens up opportunities to create protein therapeutics that cannot be produced using conventional methods.” The company is using this technology to introduce novel chemical modifications, including non-natural amino acids, into proteins to make “biobetters” with improved pharmaceutical properties, as well as novel therapeutics. Sutro says its technology enables the rapid and systematic exploration of many protein drug variants to identify drug candidates. Once identified, production of these protein drug candidates can be scaled up to

Catabasis secures $14.5M in Series A financing CAMBRIDGE, Mass.—Catabasis Pharmaceuticals, a biopharmaceutical company using omega-3 fatty acids to create dual-action medicines to treat inflammatory and metabolic diseases, recently achieved development milestones in advancing its lead compound toward human clinical trials, triggering a second tranche of $14.5 million in its Series A financing from its current investors. In April, Catabasis announced the completion of a $39.6 million Series A financing led by SV Life Sciences, Clarus Ventures, MedImmune Ventures and Advanced Technology Ventures. Proceeds from the second tranche will be used to progress the company’s lead compound to treat type 2 diabetes into clinical studies, further advance two additional programs in the areas of metabolic diseases and inflammation, and continue to support the growth of the company. The lead program is expected to enter human clinical trials in the second half of 2011. Founded in 2008, Cata­basis says its approach “dramatically enhances the therapeutic potential of DHA and EPA, two essential fatty acids found in fish oil, by improving the delivery, potency and efficacy.” ddn

commercial levels. In addition to developing its own drug pipeline, Sutro is also collaborating with select pharmaceutical and biotech companies in the development of novel protein therapeutics that cannot be designed, produced or studied with current technologies. Led by Skyline Ventures, the financing round, which consisted of two tranches, included participa-

“Securing this major investment in the current economic environment demonstrates our investors’ enthusiasm and belief in the transformative potential of our programs and our biochemical protein synthesis technology,” says William Newell, CEO of Sutro Biopharma. “The financing provides us with sufficient capital to drive our own programs to the clinic and to support our collaborative relationships, which focus on therapeutic proteins that have been inaccessible until now.” To date, the company has raised a total of $59.5 million in financing.

tion from new investors Lilly Ventures and Amgen Ventures and existing investors SV Life Sciences and Alta Partners. In conjunction with the financing, Dr. Leon Chen, partner at Skyline Ventures, and Dr. Armen Shanafelt, venture partner at Lilly Ventures, have joined Sutro’s board of directors. Sutro also recently appointed Dr. Trevor Hallam as chief scientific officer. ddn

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markets

4  Drug Discovery News • January 2011

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Pharmaceutical and Biotech Market Indices Amex Pharmaceutical Index

Burrill Select 350

315.62 304.60 307.82

307.56

282.01 284.59 289.74

287.90

305.13

317.16

302.88 307.85

300

1200

1076.11 1062.42

1021.85 1027.96

976.13

954.87

976.37

949.4

1007.89

1043.5 1056.72 1070.12 1000

250 800 200 600

150

400

100 50

200

0

0

A

Source: Yahoo Finance

Source: Burrill & Co.

ccording to venture capital firm Burrill & Co., the industry closed the month with a collective market cap of $351.91 billion (up 0.4 percent for the month and up 0.8 percent for the year). The decliners outpaced the gainers in the Burrill Biotech Select Index; On the plus side, shares of Exelixis soared 30 percent in November after the company reported positive data from studies that are testing its drug candidate XL184 as a treatment for ovarian cancer and prostate cancer. The top five biotech companies by market cap are: Amgen ($49.8 billion, share price down 8 percent in November); Gilead Sciences ($29.6 billion, share price down 8 percent in November); Celgene ($27.9 billion, share price down 4 percent in November); Genzyme ($18.4 billion, share price down 1.4 percent in November); and Biogen ($15.2 billion, up 1.5 percent for November). In addition, 52 biotech companies—or 17 percent—have market caps greater than $1 billion, compared to 49 companies at the same time last year, and 90 biotech companies—or 30 percent—have market caps less than $100 million compared to 39 percent—or 122 companies—at the same time last year.

Burrill Mid-Cap Biotech and Small-Cap Biotech 956.1

1008.21 921.54

878.86 856.09

950.77

1085.65

1055.6 958.48

1008.15

952.87

896.06

920.51

963.7 1001.04 909.86

912.17 782.03 762.03

1025.23

1064.99

1200 1000

937.21

977.74 800

826.79

600 400 200 MID-CAP SM A L L-C AP

0

Source: Burrill & Co.

Biotech posts lackluster performance in November By Burrill & Co. SAN FRANCISCO—After

surging 6 percent in October, the biotech industry came down to earth in November, with the Burrill Biotech Select Index dropping 1.5 percent, according to venture capital firm Burrill & Co. The capital markets fared little better, with the Dow Jones Industrial Average closing the month down 1 percent and the Nasdaq Composite Index down 0.37 percent. Dragging on the markets toward the end of the month was a concern that Europe’s debt crisis will continue to spread and much of the world’s economy continues to sputter, Burrill says. “It is interesting to note that the Burrill Biotech Select Index has climbed 16.5 percent in value year-over-year, with the Dow up 13 percent in the same period,” says G. Steven Burrill, CEO of the Bay Area firm. “It has been linked to the stellar stock performances of companies such as Genzyme, Dendreon, Illumina and Pharmasset.” Many of biotech’s blue-chip companies, in fact, have had sub-par years, Burrill adds. For example, Amgen is down 7 percent year-todate and Vertex Pharmaceuticals is down almost 23 percent for the same period. “The unevenness can also be seen in biotech’s newly minted public companies,” notes Burrill. “This year, 16 new biotech issues have debuted on the U.S. market, but most of them have been plagued by lackluster receptions, and their average market performance at the end of November is down 13.2 percent.” Burrill also notes that despite investor enthusiasm for the oversubscribed $23 billion

General Motors initial public offering, this failed to carry over to the biotech sector, where three IPOs were completed: Complete Genomics, Zogenix and Anacor Pharma­ ceuticals all debuted with pricing well below what company managers hoped to fetch. DNA sequencing firm Complete Genomics went public, raising $54 million after scaling back its deal price more than 30 percent to get it done. Founded in 2005, it is one of a handful of sequencing companies racing to offer complete sequencing of the human genome for

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Bayer reports rise in Q3 sales, but falls victim to generic competition LEVERKUSEN, Germany—Bayer AG

significantly raised sales and underlying earnings in the third quarter. Bayer’s Q3 pharmaceuticals sales rose 7 percent to $3.7 billion, despite a drop in revenue from the company’s YAZ oral contraceptives due to generic competition. Overall profit increased 12 percent to $389 million, falling well behind analysts’ expectations of $686 million as Bayer recorded legal charges, including $69 million, for anticipated defense costs in connection with YAZ. Group sales

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the opioid hydrocodone and to fund the ongoing commercialization of its DosePro device. The company’s shares closed down 3.7 percent from the offering. Finally, Anacor Pharmaceuticals raised $60 million through the sale of 12 million shares at $5 per share, priced far short of the $16 to $18 range in which it had hoped for. The company plans to use the funds to pay off debt and to fund late stage clinical trials of AN2690 for fungal nail infections and AN2728 for psoriasis. ddn

less than $1,000. Shares closed the month at $7.72, down 14 percent. Zogenix sold 14 million shares at $4 each on Nov. 23 in an offering the company had postponed since August 2008. Its first commercial product, Sumavel DosePro, is a needle-free drug delivery system launched in January 2010 for the acute treatment of migraine and cluster headache. The company plans to use the net proceeds from the offering to fund late-stage clinical trials and development for ZX002, its controlled-release formulation of

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grew 16 percent to $11.9 billion. Based on these results, CEO Marijn Dekkers says Bayer will “have to thoroughly address the current challenges,” particularly in the company’s HealthCare division. “

BioClinica’s Q3 service revenues increase to $15.8 million NEWTOWN, Pa.—BioClinica

Inc., a global provider of clinical trial management ser vices, recently announced that its third-quarter service revenues were $15.8 million, compared to $14.1 million in the same period last year. GAAP income from operations was $1.1 million as compared to $1.2 million in Q3

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2009. GAAP net income was $714,000, or $0.05 per fully diluted share, compared to $701,000, or $0.05 per fully diluted share, in Q3 2009. Non-GAAP income from operations was $1.7 million, compared to $2 million in Q3 2009. Non-GAAP net income was $1.1 million, or $0.07 per fully diluted share, compared to $1.2 million, or $0.08 per fully diluted share, in Q3 2009.

Beckman Coulter sees turnaround in Q3 BREA, Calif.— Beckman

Coulter Inc.’s third-quarter profit soared following a disappointing 2010. Stocks had been down 22 percent this year as Beckman reported

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reduced earnings in prior quarters amid weak demand in developed markets and cut its forecast for the year twice. However, for the third quarter, Beckman posted earnings of $67 million, or 95 cents a share, up from $1.5 million, or 2 cents a share, in the third quarter of 2009. Excluding acquisition and other impacts, earnings rose to $1 from 89 cents as revenue increased 8.6 percent to $893.8 million, with recurring revenue up 6.9 percent. Both were up partly on Beckman’s August 2009 acquisition of Tokyobased Olympus Corp.’s diagnostics system business. Analysts polled by Thomson Reuters had expected earnings of 88 cents on $885 million in revenue.

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6  Drug Discovery News • January 2011

b r i e f s

Source BioScience acquires imaGenes for $3.1 million BERLIN—Source BioScience recently acquired

imagines, a developer of genomic products essential for determining and manipulating gene and protein function, for $3.1 million in cash. The Nottingham, England-based life sciences, healthcare and pharmaceutical firm says the deal will help it to expand into European markets, create new cross-selling opportunities and boost its consumer base. Source BioScience also says that its ongoing investment in nextgeneration DNA sequencing will be complemented by the high-end bioinformatics expertise offered by imaGenes. Dr. Nick Ash, CEO of Source BioScience, says the transaction fits his company’s stated objective of continued expansion through targeted acquisitions and development of existing business.

Cisbio Bioassays and IGF launch CNS drug discovery research program BAGNOLS-SUR-CÈZE, France—Cisbio Bioassays

recently launched the GluSense research and development program in partnership with the Functional Genomics Institute (IGF) of Montpellier, France. The project, financed by a $1.2 million grant from France’s National Research Agency, will focus on the development of central nervous system (CNS) drug discovery research tools. The GluSense project involves sensors that enable real-time detection of responses from glutamate receptors, which are part of a family of G-protein coupled receptor (GPCR) targets that are related to CNS disorders such as Parkinson’s disease and depression. Cisbio and IGF have also created a joint laboratory at IGF to investigate technologies that facilitate the study of interactions between biomolecules on the surface of living cells. These technologies will be applied to research projects focused on GPCRs, and following a technology transfer from the laboratory to Cisbio Bioassays, developed into products for use by pharmaceutical and biotechnology companies.

Advinus and Corning bring Epic technology to India DELHI, India—Research-based pharmaceutical company Advinus Therapeutics and specialty glass and ceramics manufacturer Corning Inc. have announced a collaboration to bring Corning’s Epic label-free detection technology to India. Epic combines biochemical detection and cellular analysis on a single label-free platform to enable a better understanding of biological activity for a wide range of research applications. According to the companies, their partnership enables Advinus to leverage Epic to enhance its own drug discovery capabilities and to provide assay development and screening services to companies both in India and abroad. Further details were not released.

For more information, visit www.DrugDiscoveryNews.com



Thermo turns up heat on Asia-Pacific expansion plans Company plans to acquire Dionex Corp. for $2.1 billion and Lomb Scientific for undisclosed sum By Jeffrey Bouley WALTHAM, Mass.— The tail end of fall 2010 saw Thermo Fisher Scientific announce two important acquisitions, both of which factor significantly into the company’s plans to increase its footprint in the Asia-Pacific region. The first acquisition announcement involved Lomb Scientific—a provider of laboratory chemicals, consumables and instruments in Australia and New Zealand— in late November for an undisclosed sum. The second was a much more attentiongetting $2.1 billion acquisition of Sunnyvale, Calif.-based Dionex Corp., a manufacturer and marketer of chromatography systems, in mid-December. “Both the Dionex and Lomb transactions are consistent with our strategy of investing thermo continued on page 8

With an eye toward expanding its Asia-Pacific region footprint, Thermo Fisher Scientific Inc. recently acquired two companies: Lomb Scientific, a provider of laboratory chemicals, consumables and instruments in Australia and New Zealand, and Dionex Corp., a manufacturer and marketer of chromatography systems.

A lot to digest Companies Axcan gobbles up Eurand for almost $600 million By Kimberley Sirk AMSTERDAM, The Netherlands—

Eurand NV, a global specialty pharmaceutical company, and Axcan Holdings Inc., a pharmaceutical company focused on the treatment of gastrointestinal disorders, announced Dec. 1 an agreement under which Axcan will ingest all the outstanding shares of Eurand. The independent directors of Eurand, composed entirely of non-management, non-majorityshareholder directors and acting on behalf of Eurand’s board, have unanimously approved the acquisition agreement and recommended to Eurand shareholders that they tender their shares into the offer. The companies estimate that the fully diluted equity value of the transaction is $583 million. Under the terms of the agree-

converge on pain

ment, it is anticipated that a wholly owned subsidiary of Axcan will present a tender offer for all of the outstanding shares of Eurand. The transaction is expected to close in the second quarter. Gastroenterology, Axcan’s specialty, is defined as the diagnosis and treatment of diseases affecting the entire digestive system including the esophagus, the stomach, the small and large intestines, the liver, the pancreas and the gall bladder. Irritable bowel syndrome and dyspepsia are some of the most common functional GI disorders. Such disorders are diagnosed based on symptoms, and lifelong treatments are often required to alleviate these symptoms. The symptoms due to such disorders can cause discomfort, ranging from inconvenience to debilitation. Much remains unknown about gastrointestinal diseases and dis-

CAMBRIDGE, England—In a move calculated to capture a chunk of the global chronic pain market, newly established GlaxoSmithKline (GSK) spin-out Convergence Pharmaceuticals has joined forces with contract research organization (CRO) Selcia Ltd. to identify and develop more effective drugs for treating chronic pain. Convergence, focused on the development of novel and highvalue analgesic medicines, and Selcia, a CRO, have pooled their resources to meet shared goals, the companies state. Under the terms of the agreement, Convergence Pharmaceuticals will apply its ion channel biology platform, medicinal chemistry know-how and preclinical development expertise, formed out of GSK in October, to Selcia’s medicinal chemistry support services, according to reports. Financial terms were not disclosed. “Following the successful launch of Convergence Pharmaceuticals with a $35 million fundraising, and in line with our business strategy, this collaboration uniquely enables our goal of identifying novel, high-quality, targeted molecules for

gastro continued on page 8

pain continued on page 9

UK’s Convergence Pharmaceuticals, Selcia join forces to develop new drugs for chronic pain By Lori Lesko

global news

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j&j

continued from page 1

and growth opportunities,” notes Larry Biegelsen, an analyst at Wells Fargo Securities in New York. According to an August 2010 report by market research company Kalorama Information, the global market for vaccines totaled $22.1 billion in 2009, up from $19 billion in 2008, and will expand 9.7 percent annually in the next five years. Despite assertions since September by Van Herk Groep, which has a 9.6 percent stake in Crucell, that the current offer is “meager” and came too early, Tom Muller, an analyst at Theodoor Gilissen Bankiers NV, says the offer represents “a nice premium” and adds, “It shows that the company has created value over the past years. The shareholders will be willing to sell.” He currently has a “buy” rating for Crucell. “There will not be a higher bid,” predicted Fabian Smeets, an analyst at Rabo Securities in Amsterdam, in an early December interview with Bloomberg, adding: “The shareholder base is very diverse, and it will be difficult to band them together to force a higher bid.” In a shareholders meeting in Amsterdam on Dec. 10, Brus said that Crucell’s future prospects were brighter being part of a larger pharmaceuticals group with more financial and other resources to drive research. J&J possesses a large marketing and sales operation that would be available to Crucell, he notes, which would allow the company to compete more effectively with rivals that are backed by Big Pharma or who had already been absorbed into Big Pharma. “Crucell will become the vaccines center within J&J while we can keep our own identity,” Brus told shareholders. “We are very confident that J&J wants us for our know-how and our people. That is why we are enthusiastic about becoming part of the biggest healthcare firm in the world.” In fact, J&J has said that it plans to keep Crucell’s facilities, retain senior management and maintain employment levels. “Crucell’s strength in the manufacture, discovery and commercialization of vaccines would create a strong platform for Johnson & Johnson,” J&J officials agreed in a statement. While there have been sour grapes from Van Herk Groep, Delta Lloyd Asset Management, which owns around 5 percent of the outstanding stocks, has been more positive about the acquisition, with Jack Jonk, head of equities at Delta Lloyd, saying the proposal seems to be a move “in the right direction” and one that makes sense strategically. Noting that the vaccine market has just about tripled over the past half-decade, and noting that “vaccines are increasingly regarded as a key revenue generator for Big Pharma, as they are generics-proof,”

January 2011 • Drug Discovery News  7



Giles Somers, a senior healthcare analyst at Datamonitor, says, “Strategically, J&J has already made a number of acquisitions in infectious diseases, so the fit is very good. Furthermore, backed by J&J’s global sales and marketing capabilities, Crucell could compete more effectively with the Big Pharma players already in the vaccines space.” The only other significant hitch that has arisen were problems at a South Korean vaccine production plant, which had a material impact on Crucell’s third-quarter earnings

J&J possesses a large marketing and sales operation that will allow Crucell to compete more effectively with rivals that are backed by Big Pharma or that have already been absorbed into Big Pharma. core cause of the sterility problem is still under investigation, the facility is expected to resume production in February. Crucell noted that the immediate financial impact of these issues would not alone constitute a “material adverse effect” on the J&J bid. However, any Korea-

and full-year outlook. This forced the company to cease shipments of its pediatric vaccine Quinvaxem and its hepatitis B vaccine HepavaxGene in October of last year, pending an investigation into whether sterilization operations were compromised at the plant. Although the

related effects associated with the period prior to commencement of the share-purchase offer, along with any further developments that may arise, may need to be taken under consideration. The acceptance period for the J&J offer began Dec. 9, 2010, and ends— unless extended for some reason— on Feb. 16. Crucell will convene an extraordinary general meeting related to the acquisition offer on Feb. 8 at the Okura Hotel in Amsterdam. ddn EDITCONNECT: E011101

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8  Drug Discovery News • January 2011

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A star is born Boehringer Ingelheim draws a bead on multiple antibody targets and therapeutic areas in a collaboration with Austria’s f-star By Lloyd Dunlap V I E N NA— f- s t a r B i o t e c h n o l o g i s c h e Forschungs-und Entwicklungsges mbH recently inked a licensing agreement with Boehringer Ingelheim (BI) for joint discovery of new antibody-derived therapeutic products based on f-star’s Modular Antibody Technology, which involves the introduction of antigen binding sites into parts of the antibody molecule that normally do not participate in the antibodyantigen interaction. The technology is modular in the sense that one Fcab can act as a module for the construction of numerous mAb2s. BI will nominate up to seven targets, which may span multiple therapeutic areas, against which the parties will collaborate to jointly discover Fcabs for further global development and commercialization by BI, either as therapeutic products in their own right, or as modules for the generation of bispecific mAb2 products. Fcabs are the Fc regions of normal antibodies (IgGs) that have an antigen binding site engineered into the loops found at the very bottom of the CH3 domains; mAb2s are bispecific antibodies in which an existing antibody with specificity for a target of interest is modified by replacing its Fc region with an Fcab that binds to a second target of interest. Although the two parties aren’t divulging details concerning their working relationship, Dr. Kevin FitzGerald, CEO of f-star, did explain the rationale for the collaboration: “Because the discovery technologies associated with conventional antibodies are now old and expiring, it is not easy for developers of conventional antibodies to establish an intellectual property ring-fence around new therapeutic mAbs

thermo continued from page 6

to increase our footprint in Asian markets, such as China and India, as well as other strategic growth markets like Brazil,” Marc N. Casper, president and CEO of Thermo Fisher Scientific, tells ddn. He notes that Thermo Fisher built its first factory in Shanghai around a decade ago and followed with a second factory and a demo lab in 2005—and now the company has four factories in China. In addition, he notes that in 2008, Thermo introduced the first Fisher Scientific laboratory supply catalogue in Chinese, “and that has been a very successful move,” Casper says. “Last year, we moved the headquarters of our Environmental Instruments business to China so we can more effectively serve three of the fastest-growing markets in Asia:

Boehringer Ingelheim’s partnership with Vienna, Austria-based f-star aims to develop new antibodyderived therapeutic products based on f-star’s Modular Antibody Technology, which involves the introduction of antigen binding sites into parts of the antibody molecule that normally do not participate in the antibody-antigen interaction.

to a given target,” he says. “Companies that have proprietary antibody technology that can claim biological and clinical differentiation from conventional antibodies are therefore of growing interest to pharma.” Under the terms of the agreement, f-star will receive an initial technology access fee, and research-based funding, and is eligible to receive additional license fees, development, regulatory and commercial milestones and undisclosed tiered royalties on product sales. BI can select several therapeutic products from each of seven discovery programs. The total payment to f-star for each of these programs, excluding royalty payments, could reach up to $238 million in case of full commercial success of multiple therapeutic products. Typical antibody-antigen interaction takes place through contacts with loops in the antibody variable domains called the CDRs or Complementarity Determining Regions. f-star is able to modify any of the other loops in the antibody molecule in order to create antigen binding sites—such loops being polypeptide sequences that join the numerous beta-strands that are contained within the various immunoglobulin domains that form an antibody’s overall

air quality, water quality and radiation monitoring. This summer, we opened a new China Technology Center. Through the center, we will have the ability to tap into the large pool of Chinese engineers graduating from universities to work with us to design products in China, for China.” Looking to the specific acquisition deals in late 2010, Casper notes that Dionex currently generates approximately 35 percent of its revenues in the Asia-Pacific region and other emerging high-growth geographies, while the Lomb transaction significantly strengthens Thermo’s laboratory product offerings in the region, particularly chemicals used in life sciences, research and industrial applications. “We have invested in technology innovation, Asia expansion and complementary acquisitions—all to strengthen our growth opportunities in attractive end markets,”

structure. Non-CDR loops are therefore present in the variable domains, opposite the CDR loops, and in all of the constant domains within the antibody. f-star’s Modular Antibody Technology facilitates the introduction of additional antigen-binding sites into antibodies and antibody fragments by engineering the non-CDR loops of constant or variable domains. This allows the company’s scientists to generate antibody fragments with full antibody functionality and long halflife, but with much smaller size (Fcab) and full antibodies with additional functionality or bispecificity (mAb2). FitzGerald notes that the agreement with BI holds promise of delivering novel therapeutic proteins to patients with poorly treated illnesses. “f-star’s antibody-based products are clearly differentiated from conventional antibodies and other protein-based drugs,” he says. “This partnership will enable our company to expand the exploitation of our technology by combining with the impressive global research and development capabilities and resources of Boehringer Ingelheim.” ddn EDITCONNECT: E011107

Casper says of the advantages and rewards of the Asia push. “We are focused on these strategic investments because they create value for all our key stakeholders—customers, employees and shareholders.” The deal with Dionex in particular makes strategic sense, according to Jefferies & Co. analyst Jon Wood, because the two companies have few overlapping products, and Dionex does more business in China than does Thermo. Also, he says, Dionex has been experiencing faster growth than Thermo Fisher. Although Zacks Investment Research remains neutral regarding the purchase of Thermo Fisher stock, the firm does note that a strong cash balance at Thermo “augurs well for suitable acquisitions and it has been noted that the acquisitions made over the past 12 thermo continued on page 9

gastro continued from page 6

orders. Consequently, there is an ongoing need for research, and Axcan has operated in that space for the past 25 years. Eurand is a specialty pharmaceutical company that develops, manufactures and commercializes enhanced pharmaceutical and biopharmaceutical products using proprietary drug formulation technologies. A publicly traded company, Eurand has operating units in the United States and Europe. Eurand’s business strategy is focused in sales and marketing of specialty healthcare products in the United States, including the research, development and commercialization of products for use in the treatment of cystic fibrosis and gastrointestinal-related diseases. The company also works on the development and licensing of products and technologies with other companies for outlicensing worldwide. Eurand has had six products approved by the U.S. Food and Drug Administration since 2001 and has a pipeline of product candidates in development for itself and its collaboration partners. Its technology platforms include bioavailability enhancement of poorly soluble drugs, custom release profiles and taste-masking/orally disintegrating tablet formulations. Neither company was willing to offer comment on the transactions as 2010 drew to a close. Gearóid Faherty, outgoing chairman and CEO of Eurand, said in a statement that the last several years have been transformational for his company. “ The last several years have seen Eurand evolve from being a license and development, drug formulation company into a fully integrated, specialty pharmaceutical business with the development and launch of ZENPEP,” Faherty stated. “I am very proud of the achievements of the Eurand team and this transaction shows the attractiveness of the business that we have created.” Faherty will surrender the reins of Eurand at the dawn of 2011. At that time, John J. Fraher, currently chief commercial officer of Eurand, will become CEO. The combined company will have an enhanced presence in the specialty pharmaceuticals sector and will be led by Dr. Frank Verwiel, president and CEO of Axcan. Verwiel stated that he looks forward to both the new challenges and opportunities. “Through combining the organizations, we look to create a new organization with an enhanced product portfolio, broader geographic reach, a robust research and development pipeline, innovative pharmaceutical development and manufacturing platforms, and a world-class sales force,” Verwiel said in a prepared statement. The transaction is subject the condition that a minimum of 80 percent of Eurand shares be tendered, as well as receipt of antitrust approval. Affiliates of Warburg Pincus, which own approximately 55 percent of Eurand’s outstanding shares in the aggregate, and Faherty, who owns approximately 3.7 percent of Eurand’s outstanding shares in the aggregate, have entered into agreements to tender their shares into the offer. Remaining shareholders were given time at the end of 2010 to tender their shares for $12 each in cash, less taxes. ddn EDITCONNECT: E011105

global news

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thermo

pain

months have been performing better than the company average. Consequently, acquisitions are considered to be significant contributors to growth and profitability going forward.” Under the terms of the agreement to acquire Dionex, Thermo Fisher will commence a tender offer to acquire all of the outstanding shares of Dionex common stock for $118.50 per share in cash. The consideration represents a 21 percent premium to Dionex’s closing stock price on Dec. 10, 2010, the last trading day prior to the deal’s announcement, and a 32 percent premium to Dionex’s average closing stock price over the last 60 trading days. Thermo Fisher expects to realize total operating synergies of $60 million in the third year following the transaction’s close through a combination of cost savings and revenue enhancements. The transaction is expected to be immediately accretive to Thermo Fisher’s adjusted earnings per share by $0.13 to $0.15 in the first 12 months following the close. “We are pleased to be joining Thermo Fisher and are excited about the opportunities

the treatment of chronic pain,” says Ged Giblin, head of chemistry and preclinical development at Convergence. “We have a team of highly experienced pain scientists … and look forward to maximizing the capabilities of Selcia’s expert medicinal and synthetic chemists.” Convergence’s pipeline currently has two candidates in clinical development, and six earlier-stage compounds, he says. L ead neuropathic pain candidate CNV1014802 is a small-molecule, statedependent sodium channel blocker targeting the Nav1.7 sodium channel, Giblin says. The compound is ready to undergo Phase II proofof-concept evaluation. Pain candidate CNV2197944 is a first-inclass, small-molecule, state-dependent calcium channel blocker designed to selectively inhibit highly active Cav2.2 channels, he says. This candidate is poised to start in Phase I trials. Dr. Hans Fliri, managing director of Ongan, Essex, England-based Selcia, says, “We have a proven track record of delivering both clinical candidates and added value to our partners’ research programs. Our customers are able to utilize a flexible, experienced, productive resource and … proprietary technology.” In the U.K. alone, four out of five initial visits to the general practitioner involve pain as the primary symptom, and prescription rates for analgesic medications are the second highest, Selcia states. By 2023, the chronic pain market in the seven major pharmaceutical markets is predicted to reach more than $47 billion. In the same seven pharmaceutical markets, 160 million people are estimated to suffer from osteoarthritis, 36 million people are estimated to suffer from chronic low back pain and sciatica and more than 10 million people are estimated to suffer from neuropathic pain, according to reports.

continued from page 8

“Thermo Fisher’s commitment to innovation will fuel our ongoing technology development, and their global manufacturing and commercial presence will significantly strengthen our ability to deliver quality products and services to our customers around the world.”

continued from page 6

The five major European markets (Germany, France, Italy, Spain and the U.K.) collectively will grow at a 1 to 3 percent pace, as will Canada, according to IMS Health. The United States will remain the single largest pharmaceutical market, with 3 to 5 percent growth expected next year. Pharmaceutical sales in the U.S. will reach $320 to $330 billion in 2011, up from $310 billion forecast for this year—not including the impact of off-invoice discounts or rebates. Commenting on the launch of Convergence in October and the successful fundraising, Dr. Clive Dix, CEO of Convergence, said, “We are delighted to have worked closely with GSK to successfully transfer these clinical assets to Convergence Pharmaceuticals. The lead compounds offer critical advantages for the development and commercialization of novel analgesics to address the need for innovative treatments in the high-value chronic pain market. “Our team of experts bring a strong knowledge of the science and pipeline and will focus on advancing these drugs through clinical

development,” Dix adds. “We look forward to exploring commercial opportunities for these compounds at the relevant time. Given market conditions, we are pleased to have raised such a significant amount of funding, one of the largest European biotechnology Series A funding rounds in recent years, and feel this is a strong endorsement of the quality of the company, its products, science and the staff within it.” Selcia has two operating divisions, Selcia Discovery and Selcia Radiolabeling, operating from a modern facility in Ongar. Selcia Discovery provides integrated drug discovery services to pharmaceutical and biotechnology industries. These services include in vitro biology, screening, fragment screening, medicinal, organic and analytical chemistry and in vitro ADME/PK evaluation, as well as in vivo PK with a strategic partner. Selcia’s scientists act as integrated project teams within the customer group striving to produce viable drug candidates against its partners’ biological targets, the company states. ddn EDITCONNECT: E011106

Selcia and Gilead Sciences extend liver disease drug discovery collaboration ONGAR, U.K.—Selcia Ltd. also recently announced that it has expanded an ongoing drug discovery collaboration agreement with Gilead Sciences Inc. Building on an established partnership following significant progress made to date, Selcia’s chemists and biologists will continue to provide integrated drug discovery services to support Gilead’s liver disease research programs. According to the companies, scientists from both companies have interacted well together and have made successful progress against some difficult targets. “This represents a significant step forward in the development of Selcia’s Discovery services and further cements our position as a strategic and trusted partner for integrated drug discovery,” says Selcia Managing Director Dr. Hans Fliri. “We look forward to continuing to support Gilead in their search for new drugs to treat liver diseases and in fulfilling their longer term objectives.” ddn

Cambridge Healthtech Institute’s Tenth Annual

—Frank Witney, president and CEO of Dionex we will have as part of the world leader in serving science,” said Frank Witney, president and CEO of Dionex, in the news release about the deal. “Thermo Fisher’s commitment to innovation will fuel our ongoing technology development, and their global manufacturing and commercial presence will significantly strengthen our ability to deliver quality products and services to our customers around the world. This transaction offers immediate and significant value for our shareholders, as well as the opportunity for our customers and employees to benefit from combining two highly complementary organizations.” As for the Lomb deal, no specifics were released as to the price attached to the definitive agreement to acquire the company. Thermo did note in the news release about the deal that Lomb’s customers include leading hospitals, universities, research and analytical laboratories in both Australia and New Zealand, as well as a growing portion of Asia and the Middle East. Lomb has approximately 100 employees and had full-year revenue of about $34.1 million in 2009. ddn

January 2011 • Drug Discovery News  9



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A positive image never goes out of style

P

lagued by the economic downturn, generic competition, sluggish innovation and concerns over drug safety and efficacy, the pharma and biotech industries in recent years have undergone serious makeovers in the form of cost-cutting, layoffs, reorganization, mergers and acquisitions—but are these industries putting their best faces forward? While pharma and biotech companies have been going through various processes of reinvention in the past three years or so, some basic marketing and public perception campaigns have fallen by the wayside. Like a busy mom on the go, they are so preoccupied with keeping investors happy and staying afloat in turbulent times that they have been caught at the grocery store wearing pajama pants. In other words, matters such as late-stage clinical trial failures are more of a priority than how these companies are viewed by the general public. That will happen when you go into what I like to call “survival mode.” Following these industries as closely as we do, I’m always aware of screaming headlines about civil lawsuits over drug side effects, sudden resignations of key company officials or government investigations into alleged illegal practices. And frankly, I get a lot of, “how can you stand writing about such a corrupt industry?” from friends and family. But it wasn’t until I took a few hours off from work to catch a movie over New Year’s weekend that I began to seriously contemplate the image crisis facing Big Pharma. The movie was “Little Fockers,” the third installment in the “Meet the Fockers” comedy franchise starring actors Ben Stiller and Robert De Niro. It’s not a serious or thought-provoking film by any means—truth be told, I purposely chose it to give myself about 90 minutes to “veg out.” But as Stiller’s character, Greg, is a nurse manager at a prominent Chicago hospital and visited by a pharma sales rep promoting a new drug, I found myself sitting up and paying attention instead of mindlessly munching popcorn

(don’t you hate when that happens?). The sales rep, “Andi with an ‘I’,” portrayed by actress Jessica Alba, works for a fictional pharma and quite literally explodes into Greg’s life to ask if he will consider promoting Amy Swinderman, Sustengo, an impotence ddn Chief Editor drug that is safe for heart disease patients. Andi is the very definition of a pharma rep stereotype: She’s a perky former cheerleader dressed in the latest designer fashions who tools around town in a candy apple-red convertible with a license plate that reads, “PHRMAGRRL.” The character is actually a former nurse—and by her own admittance, a great one—who turns to pharmaceutical sales to “earn more dough.” She also pops her own samples like candy and posts “remix” videos of Greg’s presentation at a medical conference on YouTube. Ah, today’s generation … Pretty far out there, huh? Well, I thought so too, until I started Googling public reaction to this character and actually found a Wikipedia page devoted to a serious discussion about Sustengo. “Sustengo (generic name pendenadil doltrate) is a fictional drug featured in the 2010 film Little Fockers. The drug is marketed by the fictional Boston Pharmaceuticals. In the film, the drug is advertised as safe and effective for ‘heart patients’ as it not only increases penile blood flow, but also acts as a beta-blocker to keep the heart rate down during intercourse. Theoretically, this would seem to be beneficial as beta-adrenergic blockade would not drastically reduce penile blood flow. However, a theoretical concern with this concomitant effect is therapeutic duplication of betablockers (most MI patients will have been prescribed a beta-blocker after experiencing a myo-

cardial infarction). In addition, the selectivity of the beta-blockade is not mentioned; non-selective beta blockade could trigger respiratory distress in certain susceptible patients. Furthermore, ‘heart patient’ encompasses a number of other potential cardiac disease states for which Sustengo’s beta-blockade effects would potentially be unsuitable or dangerous.” All this for a product created not by an actual drugmaker, but by Hollywood. Wow. And with pop culture dominating media coverage—even CNN’s top stories are mostly related to the entertainment biz—you have to wonder how this latest pharma stereotype will be digested by moviegoers who generally aren’t in a position to make informed decisions about the state of the pharma industry. For the next few days, mainstream media headlines jumped out at me, decrying the latest “bad news” for the industry: “Inspire Pharma shares dive on failed study,” “AstraZeneca feels Big Pharma’s pain,” “Academic docs kept speaking on Big Pharma’s dime, despite bans,” “15 dirty Big Pharma tricks that rip you off and risk your health,” to mention a few. Even “good” news was cast in a negative light: We can’t have pharma companies turning a profit, can we? They can continue to make important therapies without that, right? I’m not suggesting that Big Pharma isn’t guilty of a few sins. After all, trial data doesn’t lie. But what is the industry doing to protect and improve its reputation as an entity responsible for healing the sick and improving the lives of patients? In the next decade, the pharma and biotech industries need to boost consumer faith and trust if they wish to continue to innovate and successfully serve patients in need. Here’s hoping that in 2011 and beyond, these industries invest in an image makeover, so they aren’t a running punchline in a ‘B’ movie. Perhaps by this time next year, we won’t be contemplating which companies are on the “worstdressed” list, but instead, which companies “wore it best.” ddn

Oversaturation vs. tunnel vision

O

ne of the things that drives

me nuts when I go to the grocery story is heading down the aisles and seeing a slew of new products that seem to be designed solely to part me with my money, and make less space for established items that I already like more than they do to enhance my life. Truly, I have to wonder if adding marshmallow bits to a cereal or making a chocolate version of a healthy oat-based staple of the breakfast table is really necessary. And cheeseburger-flavored Doritos? Don’t get me started. I admit that I sometimes feel the same way when I see multiple iterations of drugs, whether over-the-counter or prescription, or when I see large-scale research efforts that cover the same ground but with different budgets and different researchers. Then I realize that it’s just that growing “grumpy old guy” persona that started to kick in just before I officially entered middle age. Yes, sometimes pharma companies do simply re-tool a product or create a knock-off version of something for the sole purpose of capturing market share and providing something that seems new, but really isn’t. But so many other times, products that seem similar—particularly when it’s a new chemical

compound from the same company for the same target or a similaracting one from a rival company—need to be pursued for the very reason that subtle differences can have big impacts in terms of efficacy, adverse reactions and off-target effects. I Jeffrey Bouley, was reminded of that ddn Managing Editor recently in writing an article on Amarin’s promising new omega-3based triglyceride-lowering drug, which on the surface seems a lot like GSK’s Lovaza, but which has some clear and distinct advantages and limitations. On the research side, I also got the reminder of how looks can be deceiving when I wrote two stories for the December issue of ddn that covered the 1000 Genomes Project and the PGP-1K, respectively. When you have two high-profile projects doing complete human genome sequencing with the magic number 1,000 involved, you start to ask questions like: “How is your project different from that one?” But the fact is they do have different focuses and different approaches, and because of that,

they aren’t duplicated efforts that are redundantly spending money, but rather two projects doing work that will likely provide support to each other’s efforts in the long run, as well as each provide distinct and unique contributions to genomics. Because, in the end, if there’s anything we’ve learned from decades of pharma and biotech breakthroughs, failures and other newsworthy outcomes, the human body and human diseases are an arena where we aren’t ever likely to have all the answers, and might be lucky to get even a handful of them, no matter how many similar or even duplicative efforts we have. Too much money poured into certain areas, even important ones like cancer, can mean oversaturation and dilution of research dollars that might be needed on other disease areas. But too little diversity in the research and development sphere, and we can end up with tunnel vision— and look where that got us when we took our eyes off new antibiotic research and ended up with a whole lot of resistant pathogens and not enough ways to fight them. ddn This is an updated version of a column that appeared at our blog, which launched in late August. To check out our other blog posts and comment on this one or any others, visit http://ddnonline.wordpress.com/.

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January 2011 • Drug Discovery News  11

GUEST COMMENTARY: Similar or not

similar: That is the question Scientific hurdles face approval of biosimilars versus generics

T

By Dr. Marie Rock he U.S. Food and Drug Admin­

istration (FDA) will issue new regulations governing the approval of biosimilar drugs later this year. This topic has captured the attention of many in and around the healthcare industry. Scientists, regulatory agencies, pharmaceutical companies, patients and healthcare providers find themselves in a situation where they all have something to gain, but not without controversy. Even the most enthusiastic supporters of biological therapeutics agree that no matter how rigorous the physiochemical characterization, the biological nature of the drug as well as the production process leaves room for differences that may have profound effects upon the protein’s safety and efficacy. In the late 1990’s, a small change in the formulation of Eprex, which was not done by a follow-on manufacturer, but by the originator, resulted in a severe immunogenic response, leaving some patients with the inability to make red blood cells. Despite being approved for safety and efficacy for years, the change in formulation forced nearly 200 patients to get frequent blood transfusions for survival. Fortunately, a collaboration of American and European medical experts and regulatory bodies intervened and reduced the incidence of pure red-cell aplasia due to Eprex by more than 80 percent. The event heightened the concern regarding the complex nature of the bio-

Care Act in March 2010. Section 7002 of the act provides a regulatory pathway for the creation of FOBs and stipulates that the FOB must be “highly similar” to the originator with “no clinically meaningful differences between the biological product and the reference product in terms of safety, purity and potency of the product.” Unlike small-molecule drugs and their generics, it is Dr. Marie Rock not always possible to chemically and technically characterize biologics and FOBs. As a result, the determination of a “highly similar” assessment is based on the nature of the biologic and a possible harmful immunological response. Small and simple vs. large and complex

The nature of the production process and the end product is well defined for small-molecule drugs. All chemically synthesized drugs can be scientifically characterized because of their chemically definable structure. Every drug has a defined weight and melting point and can be tested using crystallization and chromatography, which produce precise quantitative data. The production process of generic drugs is reproducible, which makes developing a generic a feasible task. Pharmaceutical companies can simply obtain the originator patent information from the U.S. Patent and Trademark Office or information in published literature. With the chemical formula in hand, creating a generic becomes an intricate but solvable stoichiometric problem. Unlike small-molecule drugs, biologic drugs are large, complex molecules that are

Even the most enthusiastic supporters of biological therapeutics agree that no matter how rigorous the physiochemical characterization, the biological nature of the drug as well as the production process leaves room for differences that may have profound effects upon the protein’s safety and efficacy.” logic production process, and demonstrated that even in the hands of the most careful and experienced companies mishaps can occur. The current landscape of biosimilar approval: Where are we now?

Approval of biosimilars, otherwise known as follow-on biologics (FOBs), in the United States has been handled under the Drug Price Competition and Patent Term Restoration Act (Hatch-Waxman Act), passed in 1984 to regulate the approval of small-molecule drugs and their generic counterparts. However, the protocol outlined by Hatch-Waxman does not take into account the crucial differences between chemically and biologically derived drugs. A biosimilar pathway has been in effect in the European Union since 2005. In an effort to better regulate biosimilars in the United States, President Barack Obama signed into law the Patient Protection and Affordable

difficult to characterize and define using tests. Biologics are produced using recombinant technology and are generally proteins, which can be very complex. Choices made during production can influence the nature of the FOB including the cell type (animal or plant), development of the genetically modified cell, purification process and formulation of the therapeutic protein. Because of these complexities, originator companies still have problems replicating their own production process, despite years of experience with the drug under patent protection. It is impossible to produce FOBs that are identical to the originators, hence the benchmark of “highly similar” in Section 7002. The approval pathway for generics: Bioequivalency

Following Hatch-Waxman’s guidelines, generic drug companies are spared the costs of expensive clinical trials because all they

need to prove is that their drug’s active ingredient is “bioequivalent” and works in the same way in the same amount of time as the name brand originator. One measure of a generic drug’s bioequivalency is its bioavailability—the amount of the drug in the bloodstream, the time it takes to get there, and the time it takes to exit the body. Drug absorption and concentration are tested using chromatography. If the concentration and absorption of the generic meets statistical requirements set by the originator, then the generic is considered to be bioequivalent. Another advantage in the approval process of a generic drug is that pharmaceutical companies generally do not need to test for safety or efficacy. Pharmaceutical companies submit chemistry, manufacturing and control documents to prove that their products have the same active ingredient and follow the same quality manufacturing standards. Because the purity and safety of the originator is thoroughly tested and documented, additional testing for the generic is unnecessary and costly. The challenges associated with FOB approval

Fewer advantages are afforded to biopharmaceutical companies developing biosimilars than those producing generic drugs. Because some manufacturing details about the originator are kept confidential and because biologics have an unpredictable nature, it is impossible to develop a follow-on that exactly replicates the active molecule of the originator. Variables such as protein folding, aggregate formation and glycosylation can affect the performance and efficacy of the biologic. As a result, regulators require clinical trials to provide analytical evidence of biosimilarity. Two of the most important and most difficult aspects of FOB clinical testing are providing evidence of bioequivalency (purity and potency) and immunogenicity (safety). Bioequivalency

As with generics, the bioequivalency of biosimilars must be established through assays using antibodies to “extract” the biologic from the sample. Because antibodies can be limited in quality or not commercially available, the producer of the biosimilar may have to generate antibody reagents themselves. Biologic drug assays are highly diverse and results vary from test to test. For example, an assay that shows similar profiles between an originator and FOB does not necessarily indicate that the two are bioequivalent. If the antibody binds to the same molecular component in both the originator and the FOB, differences may still exist in the other parts of the drug. On the other hand, an antibody may bind differently to an originator and FOB due to their unique glycosylation patterns and other conformational differences. Though they may

be bioequivalent, they cannot be considered biosimilar because the antibodies “see” them differently. These differences may affect the effectiveness of FOBs and the way the body reacts to them. Ideally, antibody assays should be designed to recognize both the originator and the FOB in the same way. By establishing a standard curve with reference material—in this case the originator—researchers can assay concentrations of the originator and the FOB. The originator can be obtained in its market form, but it cannot be used as an assay calibrator due to the quantities and purified amounts required for assay calibration. The practical approach is to use the FOB drug as a calibrator for the standard curve. Immunogenicity

Immunogenicity tests for generics are not necessary because small molecule drugs may lack bioavailability or potency, but do not cause an immunogenic response. With biological drugs, the slightest presence of any impurities, degraded protein, or aggregates can trigger an antibody response. An antidrug antibody response can lead to a range of outcomes from neutralization of the drug’s therapeutic action to more serious consequences such as a cross-reaction with an endogenous protein. Prior to recent regulatory developments, many biopharmaceutical companies compared results of their FOB immunogenicity tests to literature published on the originator. Biopharmaceutical companies now need to do immunogenicity testing using side-by-side analytical tests for more stringent performance criteria. Why go through all the trouble?

Along with bioequivalency and immunogenicity testing, biopharmaceutical companies need to establish FOB efficacy through biomarker development. All of this testing is time consuming and makes FOBs a more expensive venture than developing a generic. But despite the challenges, FOBs may have major therapeutic benefits for patients. Innovation of FOBs should continue because it is precisely their complex nature that makes it so difficult to establish biosimilarity that also makes them valuable. Patients who take biologics may begin to experience decreased therapeutic efficacy as their immune system begins to adjust by producing antibodies against the biologic or the related impurities. Patients that become antibody positive to the originator have an option for an alternative therapy provided by the FOB. Since the FOB is not likely to be identical to the originator, there is a chance that the antibodies to the originator will not interfere with the efficacy of the FOB. Biopharmaceutical companies are driven to produce FOBs for several very important reasons—there’s a strong possibility of efficacy, a reduction in development costs and the establishment of a therapeutic alternative for patients. ddn Marie Rock is the vice president of the Protein Bioanalysis group of Midwest BioResearch, a WIL Research company in Skokie, Ill.

12  Drug Discovery News • January 2011

b r i e f s

Aushon and LightArray to offer protein biomarker services in China BEIJING—Aushon

BioSystems Inc. announced recently a partnership with LightArray Biotech Co. Ltd., to provide Aushon’s suite of multiplex biomarker products and services in mainland China. LightArray operates a comprehensive drug development services laboratory in Wuxi, China, and will provide researchers with a local, centralized protein biomarker testing lab employing Aushon’s protein biomarker technologies including a growing menu of more than 300 validated assays; multiplex biomarker sample testing service; multiplex protein biomarker kits; custom arrays and assay development; and array imaging and analysis systems. “The adoption of biomarkers as a critical research tool in preclinical and clinical studies is growing rapidly in China, and our ability to provide local, regional access to the proven Aushon multiplex technology platform will be vital,” says Alan Zhang, president and CEO of LightArray.

BioCision’s CoolProduct range now available from SANYO MILL VALLEY, Calif.—BioCision LLC has signed a product distribution agreement with SANYO E&E Europe BV, SANYO’s biomedical division in Europe, under which SANYO will market BioCision’s CoolProduct portfolio, a modular system of benchtop lab tools based on BioCision’s technology for temperature change and control of benchtop biomedical samples. This agreement, one of a series of partnership deals for BioCision that expands its presence geographically and into new business segments, includes CoolRack, highly thermo-adaptive cryo tube, microfuge and PCR sample holders; the CoolBox, a portable ice-free cooling and freezing sample management product; and CoolCell, an alcohol-free device for precise rate-controlled cell freezing. BioCision’s growing global distribution network now includes some 30 partners in North America, Europe, the Middle East and Asia.

Tecan and Covaris team up on acoustic sample prep tech MANNENDORF, Switzerland—Tecan is collabo-

rating with Covaris Inc. to co-­p romote the Freedom EVO liquid handling platform with integrated Adaptive Focused Acoustics (AFA). The co-marketing agreement will allow customers to benefit from the capabilities of Tecan’s Freedom EVO systems and Covaris’ controlled non-contact acoustic sample preparation technology. Covaris’ AFA systems have already been successfully integrated into the Freedom EVO platform for many applications, and this joint offering will now be available to customers worldwide for sample preparation, compound management and next-generation sequencing applications.

For more information, visit www.DrugDiscoveryNews.com



Passing the screen(ing) test DiscoveRx acquires KINOMEscan, creating largest portfolio of proprietary GPCR and kinase assays By Kimberley Sirk FREMONT, Calif.—DiscoveRx Corp. announced in mid-November that it has purchased the KINOMEscan kinase screening services division of San Diegobased Ambit Biosciences. The addition of this new business unit will further strengthen DiscoveRx’s market position as a leader in novel, proprietary and validated G-protein-coupled receptors (GPCR) and kinase assays for high-throughput screening and profiling and will enable customers to improve research productivity and effectiveness. By combining the two businesses, the new DiscoveRx offers one of the largest collection of

assays, composed of more than 400 functional cell-based GPCR and kinase assays as well as an industry-leading panel of 442 kinase assays. Product areas include cancer, metabolic diseases, pain and inflammation, the cardiovascular system, and central nervous system disorders such as Alzheimer’s and Parkinson’s. Sailaja Kuchibhatla, senior vice president for business development for DiscoveRx, says that the enhanced DiscoveRx can now become the leader in both specialities of the two companies. “We are now the leader in kinases and GPCRs,” Kuch­ ibhatla says. “This will bring together our large portfolio of cell-based kinases with KINOMEscan’s biochemical assays. The result will be a kinase ‘center of excllence.’ Now, we have the biggest porfolio of GPCRs and leading-edge discoveries that are IP-protected.” Ku c h i b h a t l a a d d s t h a t kinase continued on page 15

KINOMEscan’s TREEspot Compound Visualization Tool is an enhanced rendering of the human kinase dendrogram for data visualization. This dendrogram incorporates several customer-requested enhancements and updated nomenclature to reflect advances in kinase biology. TREEspot is an artistic representation of the human kinome phylogenetic tree based on extensive published research through a secure access, web-based, compound profile visualization tool for analysis of KINOMEscan screening data.

Arriving at destination Thomson Reuters acquires ‘GPS in pathway analysis’ GeneGo By Lloyd Dunlap LONDON— Thomson

Reuters has acquired GeneGo, the self-described “GPS in pathway analysis,” which provides biology and disease information, analytics and decision-support

The acquisition enables Thomson Reuters to provide the pharmaceutical, biotechnology and academic research communities with solutions based on the underlying mechanism of disease and potential therapies. GeneGo’s scientific expertise and assets in biology-driven drug discovery complement the Thomson Reuters life sciences portfolio that covers drug pipeline competitive intelligence, patents and chemistry. The two com-

“Thomson Reuters now provides comprehensive decision-support solutions to help researchers striving to bring more effective medications to market. There is an increasing need for biology content, detailed disease insights and analytics to support R&D productivity and to enable a more personalized approach to medicine.”

Asuragen to collaborate with Novartis on the development of BCR-ABL1 RNA IS calibrators and laboratory software reporting tool By Jeffrey Bouley

panies now serve many of the same customers, says Jon Brett-Harris, executive vice president at Thomson Reuters. “The goal is to design, discover and bring

AUSTIN, Texas— In early December, Asuragen Inc. announced that it had entered into an exclusive agreement with Novartis to develop worldwide Armored RNA Quant (ARQ) BCRABL1 RNA International Scale (IS) Calibrators, as well as laboratory software reporting tools. According to Rollie Carlson, Asuragen’s president, this effort is intended to aid laboratories with standardization of BCR-ABL1 RT-qPCR testing to the International Scale.

genego continued on page 14

RNA continued on page 13

— Jon Brett-Harris, executive vice president at Thomson Reuters solutions for pharmaceutical research and development. Effective immediately, GeneGo will become part of the Healthcare & Science business of Thomson Reuters. Financial terms of the transaction were not disclosed.

Of standards and armored RNA

For more information, visit www.DrugDiscoveryNews.com

Instruments & informatics 

January 2011 • Drug Discovery News  13

Sending the right signals Activiomics signs technology agreement with UCB By David Hutton LONDON—Activiomics

has taken the wraps off a technology agreement with Belgian biopharma UCB to apply its novel TIQUAS (Targeted In-depth Quantification of cell Signaling) phospho-proteomics platform in a collaborative effort to elucidate signaling mechanisms of therapeutic antibodies in relevant cell-based systems. Activiomics is a privately owned spin-off company from the Institute of Cancer at Barts and the London School of Medicine and Dentistry at Queen Mary, University of London. UCB, based in Brussels, Belgium, is a biopharmaceutical company dedicated to the research, development and commercialization of innovative medicines with a focus on the fields of central nervous system and immunology disorders. Financial terms of the agreement have not been released. “We have engaged with Activiomics because we recognize that their TIQUAS technology has advantages for our inflammatory program over other methods available,” says Simon Lamb, project leader at UCB. “It is quantitative, label-free and applicable to cell and tissue samples. This technology will enable us to better understand cell signaling mechanisms of our therapeutic antibodies and could enable us to identify important biomarkers.” According to Activiomics CEO Mark Warne, UCB was an attractive partner for this collaboration because it “is a global biophar-

Activiomics’ core technology is TIQUAS, or Targeted Quantification of Cell Signaling. TIQUAS quantifies global kinase activity without the need for labeling or antibody isolation. According to Activiomics, unlike other phosphoproteomics techniques, TIQUAS can comprehensively profile and cross-compare phosphopeptides, ensuring accurate and reproducible data.

maceutical company that has strong market presence in over 40 countries and a reputation for engaging high-value strategic partnerships across the industry. The agreement represents a further endorsement of our technology, which we believe has significant advantages over existing methods.” He adds that the team at UCB is seeking to better understand signaling mechanisms of its therapeutic antibodies. “This partnership brings together UCB’s therapeutic antibody capabilities with Activiomics’ expertise in cell signaling pathway analysis to provide the best chance of identifying high-value biomarkers,” he says. “The teams have already established a good working relationship and both look forward to a fruitful partnership.” UCB is developing antibodies and small molecules to treat a range of autoimmune diseases including Crohn’s disease, rheumatoid arthritis and systemic lupus erythematosus. The company is targeting mole-

cules that regulate the immune system’s inappropriate response to the environmental or intrinsic factors that trigger inflammatory disease. Under the collaboration, for UCB’s therapeutic antibody program many of the experimental materials will be provided directly by UCB. “Activiomics will be responsible for phosphoproteomics using its proprietary TIQUAS technology and will provide world-leading expertise in cell signaling,” Warne notes. The goal of the collaboration, according to Warne, is “to elucidate signaling mechanisms of a therapeutic antibody using relevant cellbased systems with the potential of identifying therapeutically relevant biomarkers. This activity is part of UCB’s inflammatory program and will incorporate human primary samples.” TIQUAS, Warne explains, is a label-free phosphoproteomics platform that quantifies global kinase activity without the need for

RNA

“We have engaged with Activiomics because we recognize that their TIQUAS technology has advantages for our inflammatory program over other methods available. It is quantitative, label-free and applicable to cell and tissue samples. This technology will enable us to better understand cell signaling mechanisms of our therapeutic antibodies and could enable us to identify important biomarkers.” —Simon Lamb, project leader at UCB

notes. “Near-term success will be measured by completion of project goals.” Earlier this year, Activiomics signed a commercial agreement with GlaxoSmithKline through its Respiratory Centre of Excellence for Drug Discovery (CEDD), in a collaborative effort to investigate inflammatory signaling mechanisms. ddn EDITCONNECT: E011111

that Asuragen and Life Tech­ nologies Corp. achieved CE-marking and commercial launch in Europe of the BCR/ABL1 Quant Test, Asuragen’s clinically validated and cGMP manufactured test intended to aid clinicians in the monitoring and treatment of individuals afflicted with chronic myeloid leukemia. Asuragen manufacturers the monitoring test, which is exclusively distributed by Life Technologies and runs on the company’s Applied

continued from page 12

“Our development of the BCRABL1 RNA IS Calibrators and software tool leverages both our expertise in molecular diagnostics assay development and our proprietary Armored RNA technology,” says Carlson. “We are pleased to be working with Novartis in order to develop a standardization of BCRABL1 molecular testing for the entire global testing community.” Under the terms of this agreement, if Asuragen is successful in the development efforts, it will distribute both the ARQ BCR-ABL1 IS RNA Calibrators and the software reporting tools to laboratories globally. Such distribution will be either directly from Asuragen or through its distributors or both, Carlson notes. The BCR-ABL1 RNA IS Cali­ brators are intended to be compatible with several widely used assays, including both commercially available and laboratorydeveloped tests. In addition to facilitating the stan-

labeling or antibody isolation. “Unlike other phosphoproteomics techniques, TIQUAS can comprehensively profile and cross-compare phosphopeptides, ensuring accurate and reproducible data,” he says. “Activiomics’ technology works by using a protease to break down a cell or tissue extract into peptide fragments. Phosphopeptide enrichment, mass spectrometry and our proprietary TIQUAS software enable thousands of phosphopeptides to be quantified from a given sample through the incorporation of a reference phosphopeptide database. Crosscomparison of treated samples enables biomarker discovery and/or drug profiling to be performed giving TIQUAS broad application across the drug discovery space.” The partnership could prove to be a boon for both Activiomics and UCB. “Ultimate success for our partnership would arise from the identification of a novel biomarker that could be developed further into a companion diagnostic product,” Warne

Under an exclusive agreement signed in December, Novartis and Asuragen Inc. will develop worldwide Armored RNA Quant (ARQ) BCR-ABL1 RNA International Scale (IS) Calibrators, as well as laboratory software reporting tools, in an effort to aid laboratories with standardization of BCR-ABL1 RT-qPCR testing to the International Scale.

dardization of BCR-ABL1 RT-qPCR results to the International Scale, Carlson says the RNA Calibrators should “provide unmatched internal and external assay calibration.” The software reporting tool is expected to help standardize how BCR-ABL1 RT-qPCR results are reported according to the IS.

Carlson notes that his company’s Armored RNA products in general serve as excellent controls for molecular diagnostics, which is quickly becoming a part of routine clinical laboratory testing. More big news about Asuragen’s BCR/ABL1 testing abilities came back in mid-July 2010, with reports

Biosystems CE-marked 7500 Fast Dx Real-Time PCR Instrument. “The BCR/ABL1 Quant Test provides several advantages over current methods by enabling multiplex detection of all targets in a single reaction and providing unmatched standardization through the use of our proprietary Armored RNA Quant technology for external calibrators and process controls,” Carlson says. ddn EDITCONNECT: E011110

“The BCR/ABL1 Quant Test provides several advantages over current methods by enabling multiplex detection of all targets in a single reaction and providing unmatched standardization through the use of our proprietary Armored RNA Quant technology for external calibrators and process controls.” —Rollie Carlson, president of Asuragen

14  Drug Discovery News • January 2011

genego continued from page 12

to market drugs that will be especially helpful for specific cohorts of patients,” Harris says. Although a GeneGo spokesperson deferred to Thomson Reuters without comment, the company’s website describes its mission in the following terms: “At GeneGo, we believe that pathway analysis of inherently complex high-throughput biological and chemistry data must be based on a fundamental

Instruments & informatics 

ity—such as coordinated expression of multiple genes to bring about a prescribed function, gene alleles in form of SNPs and mutations, RNA splice variants, protein isoforms, complexes and families—GeneGo has developed a database of novel architecture. The key aspect of its data schema is semantic consistency between the entities from fields of study as different as human genetics, medicinal chemistry, toxicity, systems biology and translational medicine. This consistency enables

understanding of human and mammalian biology. Over the last nine years, we have developed a unique approach of systems reconstruction for extracting invaluable knowledge from experimental articles and patents, structuring it in computer-readable form and storing in a semantically consistent database.” The derived data can then be used for functional analysis by a series of cheminformatics and bioinformatics software tools. “To accommodate the complex aspects of mammalian functional-

For more information, visit www.DrugDiscoveryNews.com

application of sophisticated analytical and search tools such as pathway analysis and data mining not available in public domain.” Brett-Harris says, “Thomson Reuters now provides comprehensive decision-support solutions to help researchers striving to bring more effective medications to market. There is an increasing need for biology content, detailed disease insights and analytics to support R&D productivity and to enable a more personalized approach to medicine.”

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Harris notes that his company’s healthcare and science business totaled $830 million in 2009. GeneGo will be integrated into the science space, which seeks to accelerate research and discovery among academic, pharmaceutical and biotechnology organizations. “GeneGo is biology-driven and has a very strong domain understanding of diseases and the biology behind them,” he says. The San Diego-based company’s capabilities include its MetaBase systems biology knowledge base, its expertise in analytics, data management and value-added services and its successful track record deploying decision-support systems. The management and employees have all been given contracts, and from GeneGo’s perspective, it will be “very much business as usual,” Harris states. The company’s founder, Tatiana Nikolskaya, will become chief scientific officer of Thomson Reuters’ science business. Thomson Reuters, with 2009 revenue of $13 billion, is a leading source of information for businesses and professionals in the financial, legal, tax and accounting, healthcare and science and media markets. With headquarters in New York and major operations in London and Eagan, Minn., the company employs 55,000 people and operates in more than 100 countries. ddn EDITCONNECT: E011108

GeneGo and Agilent integrate bioinformatics technologies ST. JOSEPH, Mich.—GeneGo

Inc. also recently announced an agreement with Agilent Technologies Inc. to integrate Agilent’s GeneSpring Bioinformatics Solution with GeneGo’s MetaCore. GeneSpring GX 11.5 introduces a multiomics microarray and mass spectrometry-based analysis suite to handle transcriptomics, genomics, metabolomics and proteomics data in one application. GeneSpring GX 11.5 includes a direct connection to the MetaCore pathway analysis engine that allows users to seamlessly upload expression data analyzed in GeneSpring for pathway analysis in MetaCore. This connection is part of every expression workflow in GeneSpring, allowing automatic experiment creation and entity annotation in MetaCore. “This will allow our joint customers to seamlessly work with ’omics data in the context of pathways,” explains Julie Bryant, GeneGo’s vice president of business development. “MetaCore can concurrently visualize multiple types of data and will be able to take advantage of this new functionality in GeneSpring which will be very helpful to our joint customers.” Financial terms of the partnership were not disclosed. ddn

For more information, visit www.DrugDiscoveryNews.com

kinase continued from page 12

DiscoveRx had been looking into business deals with other companies for the past five or six years, and that KINOMEscan had been on the radar for about the past two or three. “We are moving into this particular screening space, and KINOME­ scan’s people were also an important part of this deal,” Kuchibhatla says. “KINOMEscan has 18 or 19 people in San Diego, and we intend to keep all of them.” DiscoveRx assay solutions are based on the company’s core prop r i e t a r y E n z y m e Fr ag m e nt Complementation (EFC) technology that is established in clinical diagnostics and now further enhanced to provide unique solutions to drug discovery research. EFC technology is a proven, established screening technology in most major pharmaceutical companies. Through its HitHunter, Path­ Hunter, and EFC technologies, DiscoveRx offers assay solutions for every major class of drug target, including GPCRs, kinases, proteases, nuclear hormone receptors, transcription factors and secreted proteins. The company’s EFC-based HitHunter cAMP assays are the market leader in GPCR screening applications. PathHunter technology, an adaptation of EFC technology, is an innovative and comprehensive assay system that enables live cell-based assays for pathway profiling and screening. “The acquisition of KINOMEscan represents our commitment to build a company and a brand that positions us as the leading solution provider across the drug discovery continuum. We are a leader in nextgeneration GPCR and kinase technology with our award-winning PathHunte r and HitHunter brands,” says DiscoveRx President and CEO Dr. Pyare Khanna. “With the majority of pharmaceutical drug discovery programs centered around the GPCR and kinase target classes, the addition of the KINOMEscan platform, a proven technology for highthroughput kinase screening and profiling, complements our PathHunter and HitHunter cellbased kinase and GPCR assay platforms,” Khanna concludes. KINOMEscan also prides itself on its TREEspot Compound Visualization Tool, which is an enhanced rendering of the human kinase dendrogram for data visua l i z at i o n . Th i s de n d r o g r a m incorporates several customerrequested enhancements and updated nomenclature to reflect advances in kinase biolog y. TREEspot is an artistic representation of the human kinome phylogenetic tree based on extensive published research through a secure access, web-based, compound profile visualization tool

Instruments & informatics

for analysis of KINOMEscan screening data. The deal was sealed at the end of 2010, with the KINOMEscan website now referring back to the DiscoveRx website. KINOMEscan representatives did not respond to requests for comment by press time. Founded in 2000, DiscoveRx is a privately held, venture-backed c o m p a ny h e a d q u a r t e r e d i n Fremont, Calif., with an additional office in Birmingham, England. The company pioneered the use of



β-galactosidase enzyme fragment complementation in biochemical and cell-based assays for discovery research and holds extensive intellectual property in this area. DiscoveRx is dedicated to the development and commercialization of innovative solutions to study GPCRs, kinases and other major drug target classes, and many of its products have been widely adopted in pharmaceutical and biotech drug screening laboratories worldwide. ddn EDITCONNECT: E011109

January 2011 • Drug Discovery News  15

“With the majority of pharmaceutical drug discovery programs centered around the GPCR and kinase target classes, the addition of the KINOMEscan platform, a proven technology for high-throughput kinase screening and profiling, complements our PathHunter and HitHunter cell-based kinase and GPCR assay platforms.” —Dr. Pyare Khanna, DiscoveRx president and CEO

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16  Drug Discovery News • January 2011

b r i e f s

Scripps and Aileron to develop stabilized peptide and protein therapeutics LA JOLLA, Calif.—The Scripps Research Institute and Aileron Therapeutics have entered into an agreement that will add Scripps Research’s “Click” chemistry to Aileron’s proprietary stabilized peptide and protein technology platforms, which includes the Stapled Peptide technology. Click chemistry describes synthetic chemistry tailored to generate substances quickly and reliably by joining (“clicking”) small, reactive molecular building blocks together selectively and covalently to drive a spontaneous and irreversible binding reaction. The agreement provides Aileron exclusive worldwide rights to use Click chemistry for therapeutics and non-exclusive worldwide rights for diagnostics with Aileron’s stabilized peptide and protein technology platforms. Financial terms were not disclosed.

Compendia and Althea develop breast cancer assay as companion Dx platform ANN ARBOR, Mich.—Compendia

Bioscience and Althea Diagnostics recently announced that they will develop a product and service offering called the Breast Cancer Segregation Panel as a platform for companion diagnostic development. The panel measures 96 genes that represent key molecular variability of breast cancer and have been derived from a proprietary metaanalysis of cancer genomic profiles from more than 5,000 clinical samples. The assay has been optimized by Althea to measure the genes using quantitative RT-PCR from formalin-fixed tissue (FFPE) samples to enable rapid translation to real-world clinical settings. Compendia will analyze the data generated by the assay and perform correlation studies to end-points of interest such as drug response, allowing for development of multiple drug-specific companion diagnostics from a standardized platform. The companies also plan to develop similar assays for other cancer disease types.

For more information, visit www.DrugDiscoveryNews.com

In vitro to in vivo Seeking to bridge gap between in-vitro assays and in-vivo results, Caliper acquires CRi for $20 million By Amy Swinderman HOPKINTON, Mass.—Since Caliper Life Sciences

Inc., a developer of microfluidics, lab automation, liquid handling and optical imaging technologies, evolved into its own entity in

what it calls an “I-to-I Bridge” strategy, one that that aims to help its customer “bridge” the gaps that exist in bringing in-vitro assays to in-vivo results—and that strategy recently manifested itself in the form of Caliper’s acquisition of Cambridge Research & Instrumentation (CRi), a privately held company that develops optical imaging systems to advance biomedical research and molecular-based drug and diagnostic development. Under the terms of the acquisition agree-

“Similar to the approach we used in our successful commercialization of other disruptive technologies such as microfluidic LabChips and wholeanimal optical imaging systems, we see an opportunity to leverage CRi’s advanced multiplex technology towards unmet needs in a rapidly changing market, in this case the billion-dollar tissue imaging and digital pathology clinical research market.”

Pfizer and SIRS-Lab to develop molecular Dx tests for sepsis BERLIN—Pfizer Pharma GmbH and molecular diagnostics company SIRS-Lab GmbH recently announced that they will collaborate on the development of molecular diagnostic tests to achieve the earliest and most accurate targeting of anti-infective therapy for sepsis patients. The initial focus of the collaboration is on severe fungal blood-stream infections, with the goal to examine the impact of molecular test-based diagnosis on the clinical outcome of patients with sepsis, as well as on the pharmacoeconomics of such interventions. Sepsis affects more than 2 million people per year in Europe and North America, and is one of the leading causes of death in hospitals.



By Lori Lesko ELMWOOD PARK, N.J.— Targeted toward expanding personalized medicine for cancer patients, Bio-Reference Laboratories and Massachusetts General Hospital (MGH) have entered into a definitive agreement to collaborate in the development of clinical diagnostic tests for the identification and treatment of solid tumors. The independent clinical laboratory and Boston-based general hospital made the announcement Nov. 30. This joint project is based on innovative technology that may prove superior to current diagnostic methodologies, according to a joint press release. The agreement will build upon a solid tumor genotyping and pharmacogenomics testing platform that MGH has been offering to its patients for the past few years. This genotyping platform will allow for the simultaneous assessment of more than 100 cancer mutations in clinical tumor specimens, allowing for the optimal choice of targeted thera-

By Lloyd Dunlap

pies in each patient. In addition, the agreement is expected to accelerate research, especially involving clinical correlations with drug responses that will be accessible to other entities, including pharmaceutical companies that are expected to cooperate in the development of personalized medicine therapies. Amar Kamath, vice president of marketing for BioReference Laboratories, says the collaboration began with a cup of coffee. “BioReference CEO Dr. Marc Grodman met Dr. Daniel Haber of MGH at a meeting and the two discussed an opportunity to work together,” Kamath tells ddn. “This was followed-up by a capabilities meeting where several topics were discussed, and the cancer personalized medicine project was selected as the best first opportunity to implement.” BioReference brought to the table an existing oncologist client base, as well as a dedicated oncology sales team, Kamath says, adding, “MGH believes that it has developed a valuable approach to personalized method and sought a partner with content expertise and commercialization skills.” MGH “will be responsible to transfer the tumors continued on page 19

mdx continued on page 17

ment, announced Dec. 9, Caliper will acquire Woburn, Mass.-based CRi for $20 million, including net debt. In exchange for all of CRi’s bridge continued on page 18

Opportunity knocks Bio-Reference Laboratories joins with Massachusetts General Hospital to refine diagnostic tests, expand personalized medicine

Addition of high-growth business accelerates company’s expansion into molecular diagnostics OMAHA, Neb.—Explaining that the sale of its “non-core diagnostic business was the final piece in our transition to a drug development program with a new drug now under review at FDA, plus others in stage III and stage II trials,” according to a company spokesperson, Clinical Data Inc. has signed a definitive agreement to transfer its diagnostic business to Transgenomic Inc. The acquisition includes a suite of proprietary genetic commercial tests, certain proprietary biomarker assays and the CLIA-certified laboratory operations of Clinical Data for a purchase price of approximately $15.4 million, primarily in cash and notes. Closing of the transaction is subject to customary regulatory approvals and closing conditions. Craig Tuttle, Transgenomic’s CEO, considers the deal a significant transaction for the company. “It brings us a well-established and growing molecular diagnostic business, a substantial and established revenue base and validated new biomarker assays, along with a talented diagnostic team,” he says. “Importantly, the acquisition provides us with multiple growth opportunities through continued growth of the 11 test FAMILION product portfolio of molecular assays for inherited cardiac disorders, plus several proprietary assays for testing patients’ response to important cancer treatments and patients’ drug metabolism of a variety of drugs. This acquisition will significantly improve our competitive position and enhance our customer support and patient care capabilities. We look forward to completing this acquisition and integrating these assets into Transgenomic as quickly as possible.” The fit looks right, since Trans­ genomic develops and markets a number of molecular diagnostic tests and services for oncology, cardiology,

—Kevin Hrusovsky, Caliper’s president and CEO 2003, the company has grown about 21 percent annually. With the lofty goal to become a $240 million company by 2014, Caliper is continuing that rapid growth by deploying

Transgenomic Inc. acquires Clinical Data’s diagnostic unit

For more information, visit www.DrugDiscoveryNews.com

diagnostics

January 2011 • Drug Discovery News  17



Creating biomarkers to strike disease early Ariana Pharma enters viral hepatitis partnership with Bio-Rad, Inserm and Beaujon Hospital By Jeffrey Bouley PARIS—Ariana Pharma, which provides decision support tools and services to accelerate the development and optimal use of drugs and biomarker discovery, announced recently that it has entered into a partnership to improve the diagnosis and prognosis of chronic hepatitis (HCV). In this effort, it will be collaborating with Paris-based Beaujon Hospital and the French National Institute of Health and Medical Research (Inserm), as well Bio-Rad France. Together, the groups will help Ariana to apply its novel technology to the discovery of new biomarkers, under a three-year effort they are calling the Hepachronix project. Pooling their collective expertise, they will identify, develop and market new tools for the early diagnosis of fibrosis and for the prognosis of resistance to treatment. The project aims to deepen understanding of the processes by which liver fibrosis in HCV patients evolves from an early, mild stage to serious liver diseases such as cirrhosis and hepatoma carcinoma. Detecting patients at the early stages of fibrosis is critical, the organizations note, in order to treat them as early as possible. However, roughly 40 percent of HCV-infected patients do not respond to standard antiviral treatment, so the Hepachronix project aims to develop additional biomarkers to characterize patient responder status, and to adapt the therapy. Taking part in the Hepacronix project helps to demonstrate Ariana’s commitment to the field of biomarker identification and validation, as well as its leading position in identifying biomarkers and the strength of its Knowledge Extraction and Management (KEM) platform for disease diagnosis. “Ariana Pharma is looking forward to applying its expertise and KEM technology to the diagnosis and prognosis of hepatitis which chronically affects many hundred million patients worldwide,” says Mohammad

mdx

continued from page 16

hematology, inherited disorders and diseases of aging. These include the WAVE System and associated consumables specifically designed for use in genetic variation detection and single- and double-strand DNA/RNA analysis and purification. More than 1,450 systems have been shipped to customers in more than 50 countries, the company states. The SURVEYOR Mutation Detection Kits and SURVEYOR Check-It Kit provide reagents and protocols for high-sensitivity detection of mutations in DNA. “Clinical Data has built the commercial, managed care and CLIAcertified laboratory infrastructure and capabilities to support its currently marketed tests including the FAMILION family of genetic tests

Viral conditions, including hepatitis C, are among the major focus areas for the Institut National de la Santé et de la Recherche Médicale in France, more commonly known as INSERM, which is working with Ariana on biomarkers for chronic hepatitis. Pictured here is Inserm’s Laboratory P4 JeanMérieux in Lyons, France, a virus research center.

Afshar, CEO of Ariana Pharma. “The identification and validation of new sets of biomarkers have the potential to improve diagnosis and treatment of these major public health problems.” Ariana Pharma and its partners will share the expected royalties from sales of the eventual in vitro diagnostic reagents that would be marketed by Bio-Rad Laboratories. Afshar notes that KEM will be used to “complement traditional statistical tools” so that it can help identify signature probes and he adds that it “has the ability to combine genomic and proteomic data with patient characteristics to maximize the probability of an effective test.” The KEM system is able to generate, assess and prioritize hypotheses, handle missing data and optimize multiple objectives, thus enhancing conventional methods of analysis, Ariana notes. The KEM platform is designed to comprehensively mine data, including data other systems neglect, and helps scientists take simultaneous decisions involving multiple criteria and objectives, Afshar notes, adding that the Paris-based company has established a rap-

for inherited heart diseases and PGxPredic tests for predicting drug response,” Tuttle notes. The diagnostic business includes the FAMILION family of 11 commercialized proprietary tests; contracts with private and government health insurers for test reimbursement, with coverage policies that offer access to genetic testing for an estimated 280 million patients; established academic and medical society guidelines, as well as the Heart Failure Society of America guidelines, including genetic testing that can be identified by FAMILION tests which detect genetic mutations that cause cardiac channelopathies or cardiomyopathies; pipeline opportunities that include the Fc gamma receptor family of oncology tests and a clopidogrel response test; marketing resources; testing and customer

idly growing software business through collaboration and licensing agreements with some of the largest pharmaceutical and biotechnology companies since its founding in 2003. Inserm’s interest in this effort derives from

vention and antibiotics, new problems have arisen in the last two decades, among them the worldwide spread of HIV and other chronic viral infections such as hepatitis C, prion infections, emerging infections like SARS and pandemic flu, antimicrobial resistance and nosocomial diseases. The news of all this activity in France follows another recent announcement that Afshar notes is also very significant to Ariana: a collaboration with the U.S. Food and Drug Administration (FDA). Under that deal, Ariana is providing its KEM Biomarker technology to help enable FDA reviewers to analyze pharmacogenomic data combined with patient characteristics for biomarker signatures submitted through the FDA’s Voluntary Exploratory Data Submission (VXDS) program. This collaboration directly relates to the FDA’s desire to develop better tools for the analysis of genomic data in the context of the development of personalized medicine. The collaboration is also intended to help the FDA systematically identify potential genomic “fingerprints” and develop recommendations for the analysis of genomic data prior to submission of biomarker signatures. “We are looking forward to this collaboration to help the agency systematically analyze all equivalent signatures combining both

“Ariana Pharma is looking forward to applying its expertise and KEM technology to the diagnosis and prognosis of hepatitis which chronically affects many hundred million patients worldwide. The identification and validation of new sets of biomarkers have the potential to improve diagnosis and treatment of these major public health problems.” —Mohammad Afshar, CEO of Ariana Pharma its strong interest in infectious and parasitic diseases, which the organization notes are the second-leading cause of death worldwide, but which strike countries unequally depending on where the latter are located and their level of development. Inserm notes that even in northern countries, after a clear improvement through the 1970s with better hygiene, pre-

genomic and phenotypical date, this increasing chances of selecting the best biomarker signature,” says Dr. Federico Goodsaid, associate director for operations in genomics for the Office of Clinical Pharmacology at the FDA’s Center for Drug Evaluation and Research. ddn EDITCONNECT: E011116

“This acquisition will significantly improve our competitive position and enhance our customer support and patient care capabilities. It brings us a well-established and growing molecular diagnostic business, a substantial and established revenue base and validated new biomarker assays, along with a talented diagnostic team.” —Craig Tuttle, CEO of Transgenomic service capabilities; intellectual property and rights; a state-of-the art facility; and equipment. The purchase price of $15.4 mil-

lion consists of $6 million in cash, $8.5 million in a three-year note issued to Clinical Data bearing interest of 10 percent per annum

with a principal repayment schedule beginning in May 2012, and a second note of $932,000 for facility improvements made to the CLIAcertified laboratory at 6.5 percent interest for a 12-month period. Additionally, following the closing of the transaction, Clinical Data will be entitled to receive milestone payments upon the successful development and commercialization of multiple new products, royalty payments based on certain reimbursements received by the company in connection with the performance of certain biomarker assays, a percentage of certain account receivables collected during the 18-month period following the closing and a percentage of the aggregate proceeds received by the company in connection with certain transfers of certain biomarker assay technology. ddn EDITCONNECT: E011115

diagnostics

18  Drug Discovery News • January 2011



For more information, visit www.DrugDiscoveryNews.com

Roche inks several important diagnostic deals By Amy Swinderman BASEL, Switzerland—Last

month, Roche announced that it signed three important collaboration deals in the diagnostic arena: one with Genzyme Corp. to develop a diagnostic assay for the detection of Epidermal Growth-Factor Receptor (EGFR) mutations; one with OSI Pharmaceuticals Inc. (OSI) for the development of a PCR-based companion diagnostic test to identify people with non-small cell lung cancer (NSCLC) that harbors EGFR activating mutations; and finally, one with CapitalBio, a Beijingbased developer and marketer of diagnostic biochips, microarray related instruments and microarray services, which will target molecular diagnostic applications and the development of technologies to fill the unmet needs of researchers worldwide. The EGFR mutation assay involved in the Genzyme agreement will run on Roche’s cobas 4800 System, currently approved for use in detecting infectious microorganisms such as human papillomavirus (HPV), chlamydia and gonorrhea. In addition to testing for the EGFR mutation,

Although it can’t share financial details about any of them, Roche is more than happy to express how important three recent deals are to advancing its business: one with Genzyme for a diagnostic assay that detects EFGR mutations; one with OSI for the development of a PCR-based companion diagnostic test for non-small cell lung cancer; and one with China’s CapitalBio for molecular diagnostic applications.

Roche is exploring other oncology applications for the cobas 4800 platform.

bridge continued from page 16

outstanding equity securities, Caliper will issue common stock valued at approximately $10.5 million, pay cash of approximately $7.5 million and assume CRi indebtedness of approximately $2 million. According to Kevin Hrusovsky, Caliper’s president and CEO, CRi’s patented preclinical and tissue-based multiplexed analysis systems will expand Caliper’s life sciences tools portfolio, particularly as it bridges into clinical research, pathology and clinical market applications. “CRi’s advanced platforms add an important new dimension of capability to our suite of next-generation life science tools, and positions Caliper to further address biomarker discovery and companion diagnostics solutions for personalized medicine development programs,” says Kevin Hrusovsky, Caliper’s president and CEO. The acquisition also extends the reach of Caliper’s proprietary offerings along the invitro to in-vivo bridge by filling the gap in tissue analysis platforms, he adds. “Five years ago, we had a lot of customers tell us that they were getting phenomenal results with in-vitro assays, thinking they had a great drug, but when they moved into testing on small animals, they found all kinds of side effects,” says Hruosovsky. “They needed testing platforms to expand that continuum.” That’s when Caliper made the decision to acquire Xenogen Biosciences, a provider of in-vivo preclinical CRO services, in 2006. “After that happened, one of my customers at Johnson & Johnson called me to ask, ‘what are you doing buying Xenogen? You should be buying CRi. It has a phenomenal fluorescence technology that would be a great complement to your offerings,’” Hruosvsky says.

Daniel O’Day, head of Roche’s diagnostics division, says the companion diagnostic test involved in

“Over the last few years, we could see the technologies CRi was building out, and could see them fitting into our long-term quest to become a major companion diagnostics partner for Big Pharma.” CRi brings to the table $12 million in expected revenues for 2010, and Caliper expects its technologies to deliver a 20 percent growth rate once it has been absorbed into Caliper’s portfolio and operations. Those

“[We] could see the technologies CRi was building out, and could see them fitting into our long-term quest to become a major companion diagnostics partner for Big Pharma.” —Kevin Hrusovsky, president and CEO of Caliper technologies include Nuance and TRIO for multispectral imaging on brightfield and fluorescence microscopes; inForm automated image analysis software; Vectra for highthroughput slide imaging and analysis; and Maestro for in-vivo optical imaging. Ultimately, Caliper’s entry into the emerging digital and multiplexed pathology market segment has the potential to deliver a substantially greater growth profile, Hrusovsky says. “Similar to the approach we used in our successful commercialization of other disruptive technologies such as microfluidic LabChips and whole-animal optical imaging systems, we see an opportunity to leverage CRi’s advanced multiplex technology towards unmet needs in a rapidly changing market, in this case the billion-dollar tissue imaging and digital pathology clinical research market,” he says. “With CRi’s technologies in our toolkit, we will be able to offer a more comprehensive suite of tools and services to address

the OSI agreement will “enhance physicians’ ability to customize the use of Tarceva for people with advanced NSCLC.” Tarceva is the only EGFR inhibitor approved by both the U.S. Food and Drug Admin­ istration and European Medicines Agency for use in maintenance and second-line treatment settings for the treatment of patients with advanced or metastatic NSCLC with and without EGFR activating mutations. The partnership with Capital­ Bio plans to focus initially on the research and development of instruments and products to enhance and automate the Roche NimbleGen microarray workflow and the application of this workflow in preventive and personalized diagnostics. According to the partners, this new collaboration builds on the genomics and diagnostics expertise of the two companies and will focus on furthering microarray technologies and complementary products for molecular diagnostic applications. CapitalBio recently established an Independent Medical Testing Laboratory in Chengdu, China,

the important emerging trend toward personalized medicine.” Hrusovsky also notes that CRi has relationships with several universities, medical institutions and pharmaceutical and biotechnology companies. Pfizer, Merck, Novartis, the Dana Farber Cancer Center, Stanford and Baylor College of Medicine are a few standout customers that have used CRi’s products to perform high-throughput, quantitative imaging of intact tissue, simultaneous analysis of multiple biomarkers and multispectral imaging of small animals. “When we look at that customer list, it’s duplicative to the list we have today,” Hrusosvky says. “So it’s not so much that this acquisition opens us up to new markets, but creates more one-stop shopping for our customers.” By mid-2011, CRi’s headquarters and manufacturing operations will be consolidated into Caliper’s facilities in Hopkinton, Mass., and CRi’s Woburn facility will close. Nearly three-quarters of CRi’s 49 employees will be offered employment with Caliper. CRi did not respond to a request for comment. In a statement announcing the deal, George Abe, president and CEO of CRi, said, “Caliper’s market leadership and extensive corporate relationships within the biotech and pharmaceutical industries, coupled with its rich culture of nurturing and commercializing innovative technologies, make Caliper the right partner to fully realize the market potential of CRi’s portfolio of multiplexed imaging technologies.” Abe will join Caliper as senior vice president of cellular and tissue analysis and will be responsible for directing the growth and strategic direction of the tissue analysis business. Overall, Caliper expects to incur restructuring, integration and initial capital investment costs of approximately $2.5 million,

and has expanded its Microarray Genomics Service Facility at its Beijing headquarters. The partnership plans closer cooperation and collaboration across a broad range of advanced molecular diagnostic assays for clinical diagnostics and medical research, including the use of 454 Life Sciences’ next-generation sequencing for medical services. Special focus will be placed on cooperation in education on the benefits and use of molecular diagnostics that exploit novel technologies involving microarrays and their related products and next-generation sequencing in both the greater China and international markets. The partnership also plans to establish educational facilities across China for molecular R&D and the application of clinical molecular diagnostics. “This agreement is a significant step for Roche in forming closer relations with China’s premier biochip development company,” says Dr. Manfred Baier, head of Roche Applied Science. Roche tells ddn the financial details of these agreements are confidential. ddn

occurring mainly in 2011, in order to achieve anticipated business combination synergy cost benefits of $2.5 million to $3 million per year, which will be fully phased in by the end of 2011. The transaction is expected to be EBITDA accretive in 2011. And Hrusovsky hints that this acquisition may soon be followed by others, as Caliper sets its sites on becoming a $240 million company within the next three years. “What we need to do to achieve that is do some other acquisitions in the range of another $40 million during that period,” he says. “What we’re most interested in doing is finding a reagents company to be part of this family. And as our value goes up, it is going to be easier to acquire one of these companies.” ddn EDITCONNECT: E011112

ddn Editconnect: Your key to additional story content At the end of every bylined story in ddn, you’ll find an Editconnect code, like the one in the CaliperCRi story above: E011112. Simply click the Editconnect button on our home page, enter the code and access our story archives.

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tumors continued from page 16

technology and provide control specimens for validation, while BioReference will be responsible for assay development, validation, informatics, marketing and sales,” he says. The venture will enhance personal medicine in many ways. “There is a large gap in our knowledge of the genetic basis of cancers and how it impacts therapy,” Kamath says. “Most people know about the current markers— HER2, KRAS, BRAF, EGFR—and warfarin genomics has received a lot of publicity recently.” However, “there is still a large unknown about all the other—over 100 at last count—genetic markers that have a role in cancer,” he says. “This venture will try to advance our knowledge of these markers and their role in cancer therapy.”

avid

continued from page 1

florbetapir F 18, a molecular imaging agent under investigation for detecting the presence of amyloid plaque in the brain. Under the terms of the agreement, Lilly will acquire all outstanding shares of Avid for an upfront payment of $300 million, subject to adjustment based on existing cash on hand at closing. Avid stockholders will also be eligible for up to $500 million in additional payments contingent upon potential future regulatory and commercial milestones for florbetapir. After the deal is completed, Avid will continue to operate from its facility in Philadelphia, and will provide uninterrupted support for ongoing academic clinical trials,

diagnostics 

January 2011 • Drug Discovery News  19

“There is still a large unknown about all the other—over 100 at last count— genetic markers that have a role in cancer. This venture will try to advance our knowledge of these markers and their role in cancer therapy.”

Today, oncologists and cancer patients do not have a lot of choice, Kamath says, adding, “Therapies have variable effectiveness and many side effects. If the relationship between cancer, therapy and the biomarkers can be properly established, then the personalized medicine can truly be implemented for these patients. “This would help us make sure the right patients get the right therapy in the right amount,” he says. Matching new, targeted drugs to specific genetic alterations in tumors has proven “incredibly effective,” Kamath says. The MGHBio-Reference Laboratories collaboration will allow a “more rapid realization of this approach for many more cancer patients.” Grodman says that personalized therapies in the treatment of solid tumors “hold great promise that still remains largely untapped.” Since starting “our discussions

with Dr. Daniel Haber, Dr. John Iafrate and the other physicians of the MGH Cancer Center, I have been delighted not only in the shared vision, but shared values in bringing the latest clinical understanding to physician clients,” Grodman says. Haber and his colleagues “have taken a leap of faith in making pharmacogenomics a reality for thousands of patients undergoing cancer care at Mass General, and we look forward to working with them to

expand access and knowledge to these critical and timely services,” he adds. Iafrate, director of Molecular Diagnostics at MGH, hopes the collaboration will lead to giving more patients the chance to benefit from optimal therapy, Iafrate says. BioReference is a national laboratory in certain specialized areas of clinical medicine, as well as one of the largest full service clinical laboratories in the NYC super regional area. BioReference serves

focused national clinical markets in oncology specializing in hematopathology under GenPath, in women’s health under GenPap, in genetics through its GeneDx subsidiary and in correctional healthcare. GeneDx, along with GenomeDx, is based on a CGH array platform. Its next-gen sequence offerings that are currently offered in cardiology will be offered in the future in other disease specific areas, the company states. ddn

ward to partnering with Avid’s experts during the regulatory process for florbetapir, and are intent on gaining FDA approval for this promising diagnostic intended to help clinicians and researchers identify the presence of beta-amyloid plaque in the brain.” Beta-amyloid plaque is a defining pathology of Alzheimer’s disease, a chronic neurodegenerative condition that currently affects more than 5 million Americans. Alzheimer’s is a fatal form of dementia that causes progressive decline in memory and other aspects of cognition. It occurs when neurons in the brain begin dying prematurely. Researchers do not know exactly what causes Alzheimer’s, but one hypothesis is that the amyloid beta protein plays an important role. Florbetapir, used with positron

head, said in an interview with Reuters that the company is pinning its hopes on conducting smarter and cheaper research in-house, while adding in promising compounds from the outside through bolt-on deals. “We are looking into a number of opportunities,” Lundberg said, noting these could range from outright acquisitions to licensing deals to partnering tie-ups with other pharmaceutical companies. “A very high priority would be to get products or late-stage compounds with high quality that could bring in income in the short term before we have the launches of the greater magnitude of the current portfolio.” While the acquisition of Avid doesn’t fill a specific void in Lilly’s pipeline, it does provide some nearterm benefits, according to Judy Kay

identify the presence of amyloid beta plaque in living patients.” Moore notes that amyloid beta plaque is a key characteristic Alzheimer’s disease, regardless if the amyloid hypothesis is correct or not. “Because of this, there would be a benefit to patients, their families and their physicians to be able to accurately detect plaques in the brain of living patients,” she says. The acquisition also opens up myriad opportunities for Avid, according to the company’s founder and CEO, Dr. Daniel Skovronsky. “We are very excited to join the great scientific team at Lilly and continue our work to develop new molecular imaging agents capable of

changing the medical management of significant chronic human diseases,” he says. “We’ve had a productive and longstanding relationship with Lilly, and believe in their approach to providing improved outcomes for individual patients.” Avid is also developing diagnostic agents for other areas, including Parkinson’s disease and diabetes. Lilly has a potential Alzheimer’s treatment in late-stage testing and others under development. The transaction is contingent upon clearance under the HartScott-Rodino Antitrust Improvements Act and other customary closing conditions, including requisite approval of Avid stockholders. ddn

—Amar Kamath, vice president of marketing for BioReference Laboratories

EDITCONNECT: E011113

EDITCONNECT: E011103

Lilly will acquire all of the outstanding shares of Avid for $300 million and Avid stockholders will be eligible for up to $500 million in additional payments contingent upon various milestones for florbetapir. “We’ve had a productive and longstanding relationship with Lilly, and believe in their approach to providing improved outcomes for individual patients.” —Dr. Daniel Skovronsky, Avid’s founder and CEO

including the Alzheimer’s Disease Neuroimaging Initiative (ADNI), as well as ongoing clinical trials for other pharmaceutical companies. “The acquisition of Avid Radiopharmaceuticals aligns well with Lilly’s innovation-based strategy, offers a potential near-term revenue opportunity, leverages our neuroscience expertise and will immediately bolster our diagnostics capabilities,” says John Lechleiter, Lilly’s chairman and CEO. “We look for-

emission tomography (PET) technology is being assessed for the ability to detect beta amyloid plaque deposits in living patients. Florbetapir was the first beta amyloid imaging compound to enter multicenter, IND clinical studies in the United States, and has now been studied in more than a dozen trials in over 700 subjects ranging from cognitively normal individuals to those with Alzheimer’s dementia. Jan Lundberg, Lilly’s research

Moore, a Lilly spokesperson. “Lilly currently has a pipeline of nearly 70 potential new medicines, the largest in its history,” she says. “With that said, florbetapir represents a potential nearterm revenue opportunity for Lilly as we continue to innovate and also pursue deals that are in the best interest of patients and our company. If it’s approved, this test could be an important diagnostic to help physicians and researchers More Info@ adv-connect.com

20  Drug Discovery News • January 2011

LabAutomation2011 

Palm Springs Convention Center b r i e f s

LabAutomation2011 Innovation AveNEW participants selected PALM SPRINGS, Calif.— In

addition to the Innovation Award finalists (see page 22), SLAS’s Laboratory Automation Section also has named which four start-up companies will take part in its fifth annual Innovation AveNEW program at LabAutomation2011: Flourescence Innovations of Bozeman, Mont.; Freeslate of Sunnyvale, Calif.; Librede Inc. of Los Angeles; and Inovia Technologies SA of Bex, Switzerland. The mission for Innovation AveNEW is to give what SLAS thinks are emerging and elite startup companies the opportunity to actively engage and participate in a world-class event by offering the participants free exhibit space and travel. The program helps participants to grow and scale their business as well as directly connects them with more than 4,000 purchasing influencers and decision-makers from more than 40 countries. Innovation AveNEW will be presented in a specially designated area on the LabAutomation2011 exhibit floor. “Innovation AveNEW has become a highly competitive, integral part of LabAutomation2011, as start-up companies are eager to showcase their innovative products and service concepts that advance the laboratory automation field,” says Michelle Palmer, SLAS president. “The program is a prime example of the SLAS commitment to bring together our community, as well as develop our presence in the global marketplace and emerging industry sectors.”

Students, post-docs and junior faculty funded to attend LabAutomation2011 ST. CHARLES, Ill.—The Laboratory Automation Section of the SLAS also has selected 51 upand-coming scientists and engineers from around the world who will receive complimentary travel, hotel accommodations and conference registration to attend and present at LabAutomation2011. This is funded through Tony B. Academic Travel Award, a program to which as much as $50,000 is allocated each year to select an elite group of students to attend the meeting. The SLAS Education Committee conducts a comprehensive evaluation to select an elite group of students for most of these travel awards, but a smaller number of participants receive the award by the SLAS working in concert with some of the world’s top prestigious scientific conferences, institutions and educational forums to identify participants for the SLAS Young Scientist Award program.

n

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January 29 -- February 2, 2011

Start of a new era Palm Springs plays host to the last distinct LabAutomation meeting as former ALA members look toward mingling with former SBS members in a single annual meeting in 2012 By Jeffrey Bouley PALM SPRINGS, Calif.—The recent merger of the Association for Laboratory Automation (ALA) and the Society for Biomolecular Sciences (SBS) to form the Society for Laboratory Automation and Screening (SLAS) won’t mean any notable content changes for the LabAutomation2011 meeting in Palm Springs, Calif., compared to last year. However, the merger may mean a lot of talk around the proverbial water cooler about what the unification of ALA and SBS means and what members need and want going forward. The SLAS recently drafted a strategic plan for the organization to provide a solid foundation on which to build and plan for the future, and this meeting in Palm Springs—as well as the SBS annual meeting in Orlando, Fla., in March—will be a key opportunity to make sure the plan resonates with SLAS members. “The critical thing now is to get that plan out to the members and see what they have to say about it and whether they think this is the right direction for the organization,” says Dr. Michelle Palmer, the president of SLAS. “One of the key things that has made this merger as smooth as it has been is good communication, and we need to continue that with the rollout of the strategic plan and beyond that.

As with last year, the Palm Springs Convention Center will play host for the LabAutomation meeting. This will the last year that members of the Association for Laboratory Automation (ALA) and the Society for Biomolecular Sciences (SBS) attend distinct annual meetings, because they merged in spring to become the Society for Laboratory Automation and Screening (SLAS) and will have a single joint annual meeting starting in 2012.

What I’ve been hearing from members is that they are positive and see great value in the merger, but even so, they will be looking hard to see what the next six to 12 months will bring and where they will actually see the ‘1 + 1 = 3’ effect we’ve promised.” “We’ll be holding events like town hall meetings and we’ll probably be doing surveys, too, because we need to get out there and talk

LabAutomation meetings have always presented an ideal opportunity for both learning and networking, whether on the exhibit floor, at various events or otherwise.

to members,” notes Greg Dummer, CEO of SLAS. “When the voting on the merger took place, there was a 95 percent approval rating, so clearly this move was the right thing at the right time; now we need to make sure we keep doing the right things. And the board members and other key people with SLAS will be at LabAutomation and other meeting to engage with members and hear what they have to say about how we’re doing and where we plan on going.” While there are no significant programming changes to LabAutomation2011 subsequent to the merger—since so much of the event was planned long before the ALA and SBS came together as one—Dummer notes that attendees will begin to see the clear emergence of SLAS as the “host entity” as some of the branding efforts begin to see play with a large group of people. As for what you can expect at the show, the usual large assortment of educational, social and career advancement opportunities will be available—too much to cover here, frankly, particularly since SLAS has an entire area on its website for the show at www.slas.org/ LA11/index.cfm. But some highlights are slas continued on page 22

For more information, visit www.DrugDiscoveryNews.com

Labautomation2011

Spin through the air with the greatest of ease take a scenic ride in less than nine minutes that would otherwise require hours of hiking by foot By Jeffrey BouLey PALM SPRINGS, Calif.—If you want to get near the top of

San Jacinto Peak all you need to do is head to the rugged Chino Canyon on the north edge of Palm Springs and buy a ticket on the Palm Springs Aerial Tramway. Well, you could also hike for several hours from Idyllwild to get to the top of the mountain, but the question is whether you have the time or the legs for that kind of journey. Plus, you’d miss out on the bird’s-eye view in what is reportedly the largest rotating aerial tramway in the world. The roughly 15-minute, 2.5-mile ride begins at the Valley Station and passes up North America’s sheerest mountain face to the Mountain Station at 8,516 feet above sea level in a trip that goes through so many life zones and climatic changes along the way that they trip has been likened by some as traveling from the Sonora desert to the Canadian tundra. As such, you might need to bring a sweater for the ride, as the temperature up top tends to be 30 degrees Fahrenheit cooler than at the base, and sometimes as much as 40 degrees or so cooler. More than 12 million people have been carried along by the tram since it opened for its inaugural ride in September 1963, though a modernization program began in 1998 that ended in September 2000 with the construction and installation of new cars and updating of its facilities—so that passengers were then riding the world’s largest rotating Tram cars. Some of the original cars remain on display outside the tram station.

January 2011 • Drug Discovery News

Cozy up to desert weather Yes, it can get chilly at night during the winter, but “chilly” is a relative term when many attendees will be arriving in Palm Springs from snowy locales around the nation.

The Palm Springs Aerial Tram gives you a 25-mile-per-hour rotating journey from the floor of the Coachella Valley to almost the top of the San Jacinto Mountains.

Average high (January): 70.4°f / 21.3°c Average high (february): 74.8°f / 23.8°c Average low (January): 44.2°f / 6.8°c Average low (february): 47.2°f / 8.4°c

Tools to Study Genomic Instability and Genotoxic Stress Knockdown Cell Lines There are over 150 human proteins with functional roles in DNA repair. Trevigen is now offering a growing collection of knockdown (KD) cell lines each deficient in a DNA repair gene mRNA transcript.

The view at Mountain Station reportedly can stretch northward for more than 200 miles on a clear day, all the way to Mount Charleston near Las Vegas and as far as 75 miles to the east and west. Also, California’s Salton Sea is visible to the southeast. Children ride for $16.25, adults for $23.35 and seniors for $21.25. For a few dollars more after 3 p.m., you can pay for the Ride ‘n’ Dine Price, which includes roundtrip tram fare and dining in Pines Cafe. ddn

Cell lines harboring a unique shRNA lentivirus targeted to a specific DNA repair gene mRNA transcript were constructed using the LN428 glioma cell line. The percent knock down is reported as the percent reduction of the targeted transcript in reference to a control cell line.

A prickly (but scenic) situation Visit cacti and other desert plants from many locales at a unique botanical garden

Trevigen’s knockdown cell lines can be used individually or in combination, making it possible to specifically identify the gene responsible for the DNA repair mechanism being studied.

By Jeffrey BouLey

in the desert flora could mean some hiking, but if you want to get it all in one place, and maybe a guided tour to boot, check out the Moorten Botanical Garden, founded by the Moorten family—all desert plant specialists— who turned their residence estate into a living museum of desert lore. According to the website, “There’s something of interest for everyone with glistening crystals, colorful rocks, ancient fossils, pioneer and gold-mine relics.” Located at 1701 South Palm Canyon Dr. in Palm Springs, the one-acre Moorten Botanical

PALM SPRINGS, Calif.—Taking

How LabAutomation2011 is shaping up (Figures as of Dec. 27, 2010)

21

The Moorten Botanical Garden was established in 1939 by Patricia and Chester “Cactus Slim” Moorten—the latter having been one of the original “Keystone Cops.” The Moortens collected many of their own specimen plants from Baja California and mainland Mexico, and even as far south as Guatemala.

Garden boasts a collection of more than 3,000 varieties of plants designed in concentrated habitats along a natural trail. Desert cacti and other desert plants are grouped by eight geographic regions: Arizona-Sonoran DesertYuma Desert; Baja California Peninsula; California-High Desert-Mojave Desert and Low Desert-Colorado Desert-Yuha Desert; Colorado Plateau-Great Basin Desert; Sonora, MexicoGran Desierto de Altar; South

Africa-Succulent Karoo; South America-Monte DesertPatagonian Desert; and TexasChihuahuan Desert. In addition to the outdoor collections, there is also a “Cactarium” greenhouse collection with many different plants. Guided tours are available for groups of all types and ages. For more information, you can call (760) 327-6555 or visit their website at www.moortenbotanicalgarden.com. ddn

exhibit floor status: 105 percent sold Sponsorship status: 110 percent sold Attendee registrations: outpacing 2009 and 2010 levels

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www.TREVIGEN.com 8405 Helgerman Court • Gaithersburg, MD 20877 • 1-800-873-8443 Trevigen is a registered trademark of Trevigen, Inc.

22  Drug Discovery News • January 2011

LabAutomation2011 

For more information, visit www.DrugDiscoveryNews.com

Animal magnetism Living Desert Zoo and Gardens brings visitors close to desert wildlife

SLAS names Innovation Award finalists for LabAutomation2011

By Jeffrey Bouley PALM SPRINGS, Calif.—In

the Sonoran Desert of the Coachella Valley and Santa Rosa Mountains foothills near Palm Springs, you can find what is said to be the only American zoo and botanic garden combination dedicated solely to the deserts of the world: the Living Desert Zoo and Gardens. This public desert botanical garden, formerly known as the Living Desert Museum, is dedicated to desert conservation through preservation, education and appreciation, and in particular, to preserve a portion of the Colorado Desert in its natural state. Established in 1970 as a 360-acre wilderness preserve by the Palm Springs Desert Museum, the zoo and gardens now span 1,800 acres, a thousand of which remain in their natural state. The park features animals and plants that thrive in deserts from all around the world, including all four deserts of North America. One of the first stops on a tour through the park is the small animals exhibit, located on the entrance patio, which showcases small desert animals, many active mainly at night and eager to escape the heat of the day, making them hard to see up close otherwise. Along the pathways in the North America portion of the park, visitors can see such birds of prey as hawks, falcons, eagles and vultures, and such mammals as coyotes, badgers, wolves, mountain lions, bobcats, desert bighorn and the endangered Peninsular pronghorn. In addition, many birds, insects and reptiles roam free through the park, and visitors might even

The décor in and around the Palm Springs Convention Center— as well as at many other venues in the area—celebrates the fauna, flora and lifestyle of the desert Southwest.

glimpse a chuckwalla, which is the largest lizard in the natural desert of the Palm Springs area. The African portion of the park houses slenderhorned gazelles, hornbills, weaver finches, meerkats, rock hyrax, warthogs, sand cats, fennec foxes, giraffes, ostriches, cheetahs, Cuvier’s gazelle and the rare Grevy’s Zebra. Moreover, the park features the Village WaTuTu, which is a replica of a village found in northeast Africa. Mud-walled huts with grass-thatched roofs circle a shady Elder’s Grove where you can hear African rhythms or African and Native American folklore spun by master storytellers. There is also a playground area for kids called Gecko Gulch, camel rides, the Wildlife Wonders Show, a carousel and more. General admission is $14.25. Children ages 3 to 12 get in for $7.75, and children under 3 years of age are free. Special senior, military and AAA rates are $12.75 per person. The park is open every day from Oct. 1 to May 31 from 9 a.m. to 5 p.m. ddn

slas

continued from page 20

worth mentioning right now. For one thing, the Laboratory Automation Section of the SLAS has announced that three industry partners will host briefings at LabAutomation2011: the Analytical & Life Science Systems Association (ALSSA); Laboratory Products Association (LPA); and the SiLA Consortium for Standardisation in Lab Automation (SiLA). In collaboration with these entities, SLAS is bringing to meeting attendees informational briefings about recent developments and trends. The exclusive, invitation-only ALSSA breakfast briefing will assess several recent developments and trends in laboratory automation technologies and applications and the strategic implications for users and suppliers. The LPA briefing will announce the preliminary results of the 2010 North American Laboratory Purchasing Trends Report, addressing emerging trends such as the building of new laboratories, personnel issues and purchasing green products. Officials from the SiLA Consortium in Basel, Switzerland, will report on reference installations and new technology products applying or supporting SiLA standards, and provide an overview and update on current automation standards

While many meeting attendees at LabAutomation2011 will be coming from wintry climates, they aren’t likely to see much in the way of snow unless they have time to head way up into the mountains.

development projects. On the learning side of things, key education tracks at LabAuto­ mation2011 will be: Detection and Separation; Micro- and Nano­ technologies; High-Throughput Technologies; Informatics; and Evolving Applications of Laboratory Automation—with a focus on agriculture and food. The primary industries at which program content is aimed are drug discovery and development, clinical diagnostics, agriculture and food, forensics and security and energy generation and

petrochemicals. Also notable is the Late Night With LRIG: Rapid-Fire Innovation Session on Jan. 31 in the Mojave Learning Center at the Renaissance Hotel Palm Springs. Organized by SLAS’s Laboratory Robotics Interest Group (LRIG), this highly interactive forum—now in its fifth year—weaves together all the constituent audiences attending LabAutomation2011 to learn about and discuss the latest innovations in laboratory automation and technology products and services. According to SLAS, the evening offers quick, discerning informationbites from more than a dozen companies or institutions serving the many industries employing the science of laboratory automation in a venue specifically designed for companies to showcase their latest products and technology improvements. “The intent from the attendee perspective is to provide an efficient way to learn about news and trends on the commercial front,” notes the SLAS. “Attendee participants will enjoy fertile ground for questionand-answer in an open-space atmosphere serving complimentary refreshments and beverages.” Seating will be limited on a firstcome, first-served basis. Admission is free, simply requiring all participants to register as an exhibit-only attendee. ddn

ST. CHARLES, Ill.—The Society for Laboratory Automation and Screening’s Laboratory Automation Section, formerly known as the Association for Laboratory Automation, has announced the top candidates for its $10,000 Innovation Award at LabAutomation2011. The Innovation Award recognizes the top LabAutomation2011 podium presenters who put forth research that demonstrates outstanding innovation and contributes to the exploration of automation technologies in the laboratory. A panel of judges will evaluate the top candidates’ podium presentations at LabAutomation2011 and then select the overall best presentation as the $10,000 Innovation Award winner. “This year’s high-quality submissions show that LabAutomation continues to be the premier forum for the laboratory automation community to introduce new innovations in research and technologies,” says Dr. Jorg Kutter, chair of the SLAS Innovation Award Panel of Judges, who adds that the award recipient will be announced Feb. 2 during the LabAutomation2011 closing plenary session featuring Dr. John M. Butler of the National Institute of Standards and Technology. The finalists are: Dino Di Carlo of the University of California, Los Angeles; Scott Fulton of BioSystem Development LLC; Guillermo Garcia-Cardena of Harvard Medical School; Elliot Hui and Michelle Khine, both of the University of California, Irvine; Thomas Laurell of Lund University in Sweden; David Nolte of Purdue University; Kamlesh Patel of Sandia National Laboratories; Paul van Midwoud of the University of Groningen in The Netherlands; and Yama Abassi of ACEA Biosciences.

Plenary to appreciate SLAS welcomes trio of plenary speakers that exemplify visionary outlooks in lab automation By Jeffrey Bouley PALM SPRINGS, Calif. — Each

year, LabAutomation plays host to what it considers a line-up of “influential, forward thinking industry visionaries,” offering a chance for LabAutomation2011 attendees to interact with “visionaries whose work exemplifies the mission of SLAS—to advance science and education related to laboratory automation.” The three plenary speakers this year are Drs. Chad Mirkin, Daryl Lund and John Butler.

Chad A. Mirkin, Ph.D. Monday, Jan. 31, 9—10 a.m. n

Mirkin, who was asked in 2009 by President Obama to participate as a member of the President’s Council of Advisors on Science and Technology and who directs the International Institute for Nanotechnology at Northwestern University, will present “The Polyvalent Oligonucleotide Nanoparticle Conjugate: A New Frontier in In Vitro Diagnostics and Intracellular Gene Regulation.” Over the past decade, Mirkin notes, researchers have developed methods for modifying nanoparticles with oligonucleotides and explored how they can be used as designer constructs for preparing highly ordered, highly functional materials. This has led to the discovery of many unusual fundamental properties that make these materials particularly useful in biodiagnostics and intracellular gene regulation. His plenary session will focus on the rules that govern the use of these conjugates and sequence specific crystallization, high selectivity and sensitivity nucleic acid and protein detection and antisense therapy.

Daryl Lund, Ph.D. Tuesday, Feb. 1, 9—10 a.m. n

The editor-in-chief of the Journal of Food Science and an emeritus professor at the University of Wisconsin, Madison, Lund’s presentation is titled “Laboratory Sensitivity and Automation: Essential for Utilizing the Full Value of Food.” Lund notes that regulatory agencies have come to depend on the ability to measure ingredients and contaminants to assure consumers of value and safety and eliminate fraud. As we have come to the point of marketing food because of its functional properties of promoting good health, lab techniques that accurately measure chemical constituents are more crucial. As our ability to measure constituents becomes more sensitive, Lund says, it calls into question what constitutes a safe level. In his presentation, Lund will explore these issues and the relationship between food and drugs.

John M. Butler, Ph.D. Wednesday, Feb. 2, 12:45 p.m. n

“Lab Automation: A Necessary Part of the Future of Forensic DNA Testing” is the title of the plenary session to be presented by Butler, who is a fellow and group leader of the National Institute of Standards and Technology. Unlike what we see on television, real forensic DNA labs are overwhelmed with evidence that needs to be analyzed, with case backlogs growing and budgets shrinking. This presentation reviews the current state of the science and its future. ddn

For more information, visit www.DrugDiscoveryNews.com

b r i e f s

miRagen and t2cure sign licensing deal for microRNA target implicated in vascular disease BOULDER, Colo.—miRagen Therapeutics Inc., a biopharmaceutical company developing microRNA (miRNA)-based therapeutics for cardiovascular and muscle disease, and t2cure, a clinicalstage biopharmaceutical company developing progenitor cell-based regenerative therapeutics for cardiac or peripheral vascular diseases, have entered into a licensing agreement that provides miRagen Therapeutics with exclusive rights to the technology and intellectual property related to the in-vivo use of discoveries made by the University of Frankfurt and licensed by t2cure regarding microRNA 92 (miR-92). miR-92 is a key regulator of neoangiogenesis as part of ischemic disease, which may be relevant to peripheral arterial disease and other cardiovascular disorders. t2cure retains the rights to use modulators of miR-92 for ex-vivo treatment of cellular therapeutics. Financial details of the agreement were not disclosed.

GNS and Brigham and Women’s Hospital partner on asthma genetics

January 2011 • Drug Discovery News  23



Teaming up to fight Alzheimer’s GE Healthcare enters research collaboration with Janssen Pharmaceutica to identify biosignatures in Alzheimer’s disease detection

“The ability to identify the disease early and do something about it is going to be tremendous. We know that this is a very complex disease and adding one more area that we can look for early detection biosignatures makes tremendous sense for us in how we can help patients.”

By David Hutton PRINCETON, N.J.—GE

Healthcare is joining forces with Janssen Pharmaceutica NV to research methods of detecting Alzheimer’s in patients—even before they begin to exhibit symptoms of the devastating disease. The terms of the deal between Johnson & Johnson’s Janssen unit and GE Healthcare were not disclosed. The research effort is expected to combine the two companies’ expertise in data integration, informatics, genomics and imaging. According to Pascale Witz, president and CEO of medical diagnostics at GE Healthcare, the goal of the collaboration is to find a biosignature that may enable the detection of Alzheimer’s disease before the onset of clinical symptoms.

— Pascale Witz, president and CEO of medical diagnostics at GE Healthcare “GE Healthcare has a global commitment to advancing clinical knowledge and providing innovations that may accelerate diagnosis of Alzheimer’s disease and transform patient management,” says Witz. Witz also points out that finding a biosignature, essentially a collection of biomarkers, that identifies people at risk from the disease would enable physicians to make more

Promega and MS Bioworks recently announced that they will collaborate on the advancement of biological research with high-quality mass spectrometry analysis. The companies’ program will feature MS Bioworks’ knowledge of sample preparation, protein digestion, LC/MS/MS, data processing, reporting and pre- and post-data analysis consultation. These analytical services complement Promega’s sample preparation products including Trypsin Gold protease, commonly used for biomarker characterization. Researchers can review mass spectrometry services, organize one-on-one consults and submit their orders online. According to the companies, scientists worldwide will be able to access protein mass spectrometry expertise and instrumentation with fast turnaround times. Financial terms were not disclosed.

MADISON, Wis.—

ALZHEIMER’S continued on page 26

A pathway to the future

CAMBRIDGE, Mass.—GNS Healthcare Inc. (GNS) recently announced a two-year collaboration with Brigham and Women’s Hospital (BWH), a teaching affiliate of Harvard Medical School, to identify biomarkers to predict patient response to asthma therapies and to discover new biology that may lead to better treatments for asthma. The collaboration will combine the disease expertise of the BWH researchers, the computational expertise of BWH and GNS, and GNS’s supercomputer-driven Reverse Engineering Forward Simulation scientific computing platform. Financial terms of the agreement were not disclosed.

Promega, MS Bioworks in pact for advanced mass spec services for proteomics

informed decisions about patient care. “Importantly, it might also accelerate the development of successful treatments for the disease,” she says. “We strongly believe that through this research collaboration, we can bring together our competence and expertise to build this biosignature.” Moreover, the collaboration can serve to

Drs. Art Cherkasov and Paul Rennie of the Vancouver Prostate Centre are using “chemogenomics” to develop a novel class of prostate cancer drugs in order to provide new options for treatment-resistant tumors. “The impact of this project on patient survival could be tremendous if we can develop a new drug that avoids this resistance issue,” says Cherkasov.

Persistence for resistance Canadian researchers use virtual screening to target prostate cancer receptor By Lloyd Dunlap VANCOUVER, British Columbia—Two

Vancouver researchers are tackling the deadliest forms of prostate cancer, the most commonly diagnosed male cancer in Canada. Drs. Art Cherkasov and Paul Rennie of the Vancouver Prostate Centre are using “chemogenomics”—the prostate continued on page 25

Active Motif acquires Genpathway for success in next era of next-gen sequencing By Lori Lesko

CARLSBAD, Calif.—After a year spent hammering out a deal to acquire significant technical know-how, a database of antibodies and bioinformatic capabilities, Active Motif has immersed San-Diego, Calif.based Genpathway Inc. into its own operations, thus preparing for its thrust into the next era of next-generation sequencing. Active Motif, a leading provider of kits and reagents for the study of epigenetic phenomena, announced on Dec. 2 the acquisition of nine-year-

old Genpathway, a specialist in solutions for the genomewide analysis of epigenetic events, including DNA methylation, histone modification and transcriptional regulation. Active Motif develops, manufactures and delivers epigenetics-based research tools to analyze nuclear function. Its customers include life scientists from academic and government institutions; biotechnology and pharmaceutical companies; hospitals and reference laboratories. “Genome-wide analysis using high-density microarrays or next-gen sequencing has significantly broadened the ability of scientists to understand epigenetic events,” says Joseph M. Fernandez, Active Motif ’s founder and CEO. “However, antibody selection, sample preparation ngs continued on page 24

24 Drug Discovery News • January 2011

nGs

continuEd froM PAGE 23

and data analysis can create significant barriers to widespread scientific exploration, especially within biomedical research.” That’s where Genpathway comes in, with capabilities to remove all of these obstacles, Fernandez says. Genpathway describes itself as an early-stage pharmacogenomics company that provides specialized drug and biomarker discovery services and develops novel diagnostic

omics & systems biology

biomarkers that predict drug responses, enabling personalized treatments. Before merging into Active Motif, Genpathway applied its proprietary chromatin and methylated DNA immunoprecipitation sequencing (ChIP-Seq) technology to understand gene regulation and genetic pathways. Genpathway’s platform “has the capacity to develop and commercialize a broad portfolio of clinically validated molecular diagnostic products and services that will enable the accurate selection of spe-

cific drugs to efficaciously treat individuals with cancer, immune disorders and other serious diseases,” according to its website. Active Motif ’s goal is to “make cutting-edge research accessible to the wider life science community— and the combination of Genpathway’s expertise in genome-wide analysis and Active Motif’s extensive offerings in ‘off-the-shelf’ epigenetic-specific tools means that we can now provide life scientists of all capabilities with the most comprehensive portfolio of characterized

For more information, visit www.DrugDiscoveryNews.com

epigenetic products available today,” Fernandez says. Theodore DeFrank, Active Motif ’s president, calls the deal a natural extension of the nearly 10 years of expertise the company has developed in the area of epigenetics. Financial and other details were not disclosed. “Active Motif acquired essentially all of the assets of Genpathway; therefore, the former Genpathway only exists as a legal entity—not as a commercial entity,” DeFrank explains. “Active Motif acquired the

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rights to the Genpathway name, so thus, from a customer perspective, Genpathway is part of Active Motif.” Patrick Mallon, the former CEO of Genpathway, tells ddn that the acquisition should have come as a surprise to no one, as both companies have been working toward this end over the past year. “The opportunity arose during business development discussions,” DeFrank says. “Active Motif and Genpathway have had various discussions over the years exploring ways in which the two companies may be able to work together. Conversations held during the summer of 2010 led to a mechanism in which we could merge the Genpathway Epigenetics service business with Active Motif’s worldwide sales and marketing efforts.” Plus, the timing was perfect, he adds. “Genpathway’s lease was expiring at the end of the year, so it was a simple decision to integrate all aspects of their business into Active Motif ’s Carlsbad headquarters,” D e Fr a n k s ays . “Give n t h at Genpathway’s facility was only 15 miles down the road, the relocation was quick and straightforward.” The Genpathway employees responsible for performing the services and interacting with customers have been retained in order to provide the continuity and quality of service the customers have come to expect, he says. The acquisition is a “perfect fit into Active Motif ’s strategic mission, which is dedicated to developing and delivering innovative cell biology-based research tools and biocomputing resources that help researchers worldwide in their quest to elucidate the function, regulation and interactions of the genes and their encoded proteins,” DeFrank says. Active Motif, founded in 1999, is well-recognized within the academic market by life science researchers studying the underlying mechanisms involved in epigenetics, DeFrank says. At the same time, Genpathway’s service business is well-regarded with the life science research groups. The combined entity will leverage the technology and tools to develop products and services more applicable to the target identification and screening processes within the drug development process—as well developing assays for the molecular diagnostics market, he says. “In the future, we aim to integrate many of Active Motif ’s unique research tools within drug discovery and biomarker-related service offerings,” DeFrank says. Operating globally from its corporate headquarters in Carlsbad, Calif., and European headquarters in Rixensart, Belgium, Active Motif has a worldwide network of sales and support offices as well as distributors in Europe, Japan and North America. ddn eDitConneCt: e011118

For more information, visit www.DrugDiscoveryNews.com

omics & systems biology 

January 2011 • Drug Discovery News  25

Thinking and doing Quintiles, London Genetics ink pharmacogenetic deal By David Hutton RESEARCH TRIANGLE PARK, N.C.—In an effort to offer pharmacogenetic solutions and advance personalized medicine, Quintiles has signed a strategic alliance with London Genetics. Financial terms were not disclosed. Under the non-exclusive alliance, Quintiles and London Genetics will collaborate to help biopharma companies take advantage of pharmacogenetic solutions, including novel biomarker and assay development services. By providing biopharma companies strategic advice on the application of pharmacogenetics and innovative pharmacogenetics solutions, Quintiles and London Genetics believe they can help customers access additional resources and speed the delivery of targeted treatments. Quintiles develops proprietary and novel biomarker tests analyzing genes and proteins that affect

cell growth and mutation, and performs these assays at labs in the United States, Scotland and China. London Genetics works with London-based centers of excellence in genetics research to provide pharmacogenetic solutions to the biopharmaceutical industry, aiming to help companies partner with relevant academics and clinicians to apply genetic knowledge to de-risk clinical trials, design and manage projects and access patient cohorts. The companies have not worked together before, and while they are not disclosing specific terms of their pact, Thomas Wollman, senior vice president of Quintiles Global Central Laboratories, says the partnership will help biopharma companies execute a welldesigned strategy regarding pharmacogenetics, whether at the product, portfolio, pipeline or enterprise level. “London Genetics is building a business relationship network that has some of the world’s top experts in PGx strategy and implementation, and Quintiles has a

Quintiles develops proprietary and novel biomarker tests analyzing genes and proteins that affect cell growth and mutation and performs these assays at labs in the United States, Scotland and China.

globally networked infrastructure and expertise in biomarker and assay development services to deliver on those efforts,” Wollman says. “We have world-class exper-

“Through this alliance, we can offer biopharma companies a world-class blend of thinking and doing when it comes to implementing innovative pharmacogenetics solutions.” —Thomas Wollman, senior vice president of Quintiles Global Central Laboratories

prostate continued from page 23

study of genomic responses to chemical compounds—to develop a novel class of prostate cancer drugs in order to provide new treatment options. The goal is the rapid identification of novel drugs and drug targets, embracing multiple early-phase drug discovery technologies ranging from target identification and validation, through compound design and chemical synthesis, to biological testing and ADME profiling. This new approach uses computer modeling in virtual 3D to predict how different chemicals or drugs will affect cancer tumors. Currently, prostate cancer afflicts about one in six men in Canada, notes Rennie, and about one in eight in the United States, or about 5,000 cases reported annually in Canada and 50,000 here. Since 1946, the disease has been treated by targeting the androgen receptor with drugs that either block or bind the male hormone receptor thereby effectively shrinking the tumor. Unfor­ tunately, for many men, the effectiveness of this type of treatment is temporary and the cancer cells become treatment-resistant. With no alternative curative treatment options available, the average life expectancy for men

whose bodies resist this type of treatment is less than 18 months. “The impact of this project on patient survival could be tremendous if we can develop a new drug that avoids this resistance issue,” says Cherkasov. To achieve this goal, the Vancouver researchers have “moved upstream,” Rennie explains, “from the ligand binding site to the BF3 region.” The goal is to target a different region of the androgen receptor. X-ray crystallography is used to determine the structure of the binding site, Cherkasov explains. The team will then use virtual screening, with docking being used as one tool, to narrow a set of more than 10 million compounds or chemicals looking for potential new drugs, and then use computational chemogenomics to screen the compounds to gauge their potential effectiveness in targeting prostate tumors. “This type of ‘virtual screening’ is expected to shave years off the typical discovery process for new drug candidates and will allow us to identify and test the most promising chemical compounds more rapidly,” says Dr. Rennie. “Presently, it can take 10 years or more to bring a compound to the stage of testing in humans. This new high-tech approach could significantly shorten the wait for novel prostate cancer treatments.”

tise to help early adopters of personalized medicine use genomic technologies to improve drug discovery and development, and a networked infrastructure to support those efforts virtually anywhere in the world. Through this alliance, we can offer biopharma companies a world-class blend of thinking and doing when it comes to implementing innovative pharmacogenetics solutions.” Dominique Kleyn, CEO of London Genetics, notes that the London-based company’s expertise in pharmacogenetic strategy development, combined with Quintiles’ expertise and infrastructure in bio-

“This type of ‘virtual screening’ is expected to shave years off the typical discovery process for new drug candidates and will allow us to identify and test the most promising chemical compounds more rapidly.” —Dr. paul rennie of the vancouver prostate centre Initially, Cherkasov estimates that the process will narrow the candidate molecules to a few hundred for testing in the wet lab. “High-throughput screening is very laborintensive. What we are seeing is that with virtual screening, we are able to narrow down what drugs we should be taking through to testing in the laboratory or the clinical trial stage,” says Cherkasov. “When trying to create new drugs in the past, you’d make your best guess on what compound you thought might work, test and get a success rate of about 0.01 percent. The use of virtual screening offers the potential for a much higher success rate—from 10 to 60 percent—which

marker development, gives biopharma companies a powerful ally in harnessing the value of genomic data for drug development. “Ultimately, our alliance will support biopharma in their interactions with academic partners and in the development of personalized medicines,” she says. “Together, our approach combines world-class expertise and global infrastructure to support the development of personalized medicines.” According to Klyen, the alliance offers mutual clients the best of both worlds. Quintiles supports a joint approach that provides PGX continued on page 26

would be an enormous improvement in the field.” In addition, the much faster process, which utilizes software Cherkasov developed and 500 processors at the Centre—with access to thousands more—is expected to generate clinic-ready candidates in as little as two years. “In this type of work, getting funding is difficult,” Rennie states, “and Genome BC jumped in.” The organization funded the project as part of its Strategic Opportunities Fund (SOF), which provides funding to key life sciences initiatives in British Columbia. The project, has received $324,000 in funding, with $161,500 from Genome BC and the rest from other partners including the Canadian Institutes of Health Research and the Vancouver Prostate Centre. “Chemogenomics is becoming an accepted part of drug discovery and promises to revolutionize the field in a manner comparable to how bioinformatics transformed biology research 10 years ago,” says Dr. Alan Winter, president and CEO of Genome BC. “This project is groundbreaking, and we are excited by the potential impact it could have on prostate cancer research.” ddn EDITCONNECT: E011119

26 Drug Discovery News • January 2011

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strategic advice on the application of pharmacogenetics and the ability to access additional resources to deliver meaningful results within the tight timeframes of clinical development programs. The alliance is non-exclusive and can be extended by agreement. “The focus of the alliance with Quintiles for London Genetics is to develop new business for the company in line with the mission of using its knowledge, experience and extensive networks to increase success in

omics & systems biology

clinical development for new drugs and diagnostics,” Klyen says. “As a result of this alliance, we expect customers will become more aware of the opportunity to increase efficiency in clinical development and benefit from increased availability of the tools available within academic and commercial partners to achieve this.” London Genetics will also participate in briefing meetings and client visits, and will develop proposals for client projects. Quintiles and London Genetics have also established an operational steering committee to evaluate client targeting opportunities. “When clients undertake collaborative

aLzHeiMer’s continuEd froM PAGE 23

enhance GE Healthcare’s existing portfolio for Alzheimer’s. The company currently has Phase III trials underway for its amyloid PET imaging compound Flutemetamol. “We have a global commitment to advance the clinical knowledge, and we believe this collaboration is one more investment we are making in a large portfolio we have already to try to accelerate the diagnostics of Alzheimer’s disease, and therefore trans-

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implementation projects, London Genetics will coordinate access to the clinical and genetic expertise and resource of its partner institutions,” Klyen notes. “This expertise and resource spans all therapeutic areas and includes a wide range of technologies. “This is evidenced by the increasingly frequent collection of DNA samples in clinical trials, the reorganization of larger companies around translational or stratified medicine teams and the appointment by mid-size firms of clinical development directors with pharmacogenetic or stratified medicine experience,” she adds. “We are aware of this clear and growing need from the increased interest

shown by biopharma in developing more personalized treatments and a growing realization that patients with the same diseases respond differently to drugs based on their genetic makeup.” The deal is latest by Quintiles, which in November inked two other deals: one with Biomoda to help the cancer diagnostics company refine its image recognition system for detecting early-stage lung cancer; and another with Dako for integrated drug-diagnostic development services and companion diagnostic products, Dako’s area of expertise. ddn

another weapon in early detection. “The underlying pathologies associated with Alzheimer’s disease, such as the formation of amyloid plaques and tau tangles in the tissues of the brain, can precede the onset of memory loss and other clinical symptoms by decades,” Dr. Husseini Manji, J&J’s global head of neuroscience research and development, says in a statement. Witz also notes that statistics indicate that there will be a growing need in coming years to battle Alzheimer’s disease.

Janssen in oncology deal with Precos

“The underlying PaThologies associated with Alzheimer’s disease, such as the formation of amyloid plaques and tau tangles in the tissues of the brain, can precede the onset of memory loss and other clinical symptoms by decades.” —Dr. HUsseini ManJi, J&J’s GLoBaL HeaD of neUroscience researcH & DeveLoPMent form patient management,” Witz points out. “The ability to identify the disease early and do something about it is going to be tremendous. We know that this is a very complex disease and adding one more area that we can look for early detection biosignatures makes tremendous sense for us in how we can help patients.” Researchers think amyloid—a protein that forms clumps in the brains of people with Alzheimer’s—may begin to accumulate in the brain decades before Alzheimer’s patients show symptoms. Having PET scanners identifying beta amyloid, experts say, could be

According to the Alzheimer’s Association, deaths attributed to the disease have increased by more than 46 percent between 2000 and 2006. In the United States alone, 5.3 million people have Alzheimer’s, at an annual cost of $172 billion. It is the sixth leading cause of death, and its mortality rates are expected to rise as the baby boomers age. In the 2009 World Alzheimer Report, Alzheimer’s Disease International estimated that there are 35.6 million people living with dementia worldwide in 2010, increasing to 65.7 million by 2030 and 115.4 million by 2050. ddn eDitConneCt: e011117

eDitConneCt: e011120

NOTTINGHAM, U.K.— Janssen also recently announced a service agreement with Preclinical Oncology Services Ltd. (PRECOS), a preclinical research and development service provider with a focus on oncology. The global contract will see PRECOS provide clinical tumor material, tumor model development, target validation and drug efficacy work to support Janssen’s oncology drug discovery, development and biomarker programs. PRECOS was launched as a spin-off from the University of Nottingham in August 2010. The master services agreement is a consolidation of a working relationship between the two companies that was first established with the university more than five years ago. “This global contract further strengthens the long-term relationship between PRECOS and Janssen and consolidates PRECOS’ evolution from a primarily academic background into an ambitious commercial entity, offering significant scientific expertise and delivering highly specialist services in the development of new anti-cancer drugs,” says PRECOS Chief Scientific Officer Prof. Sue Watson. ddn

For more information, visit www.DrugDiscoveryNews.com

b r i e f s

Plasticell and Sigma-Aldrich to produce turnkey solution for stem cell research LONDON—Plasticell and Sigma-Aldrich recently announced that they are collaborating on the creation of a novel turkey solution for stem cell research. Sigma-Aldrich will use its CompoZr Zinc Finger Nuclease Technology to engineer various human stem cell lines that enable tracking of differentiation to specific mature cell types via fluorescent reporters, integrated into developmentally expressed genes. Plasticell will use these cell lines in its CombiCult high-throughput screening system to develop novel stem cell differentiation protocols. Plasticell will own resulting protocols for high efficiency, directed differentiation of stem cells, with Sigma-Aldrich marketing the reporter stem cell lines. Cells and media may be commercialized together in kits, while reporter cell lines can be linked to specific CombiCult screens for optimised differentiation of human embryonic stem cells or induced pluripotent cells. Financial terms were not disclosed.

January 2011 • Drug Discovery News  27



Breaking through the barrier Geron licenses peptide from Angiochem to help get cancer therapeutics past the blood-brain barrier By Jeffrey Bouley MENLO PARK, Calif.—Seeking to enable better treatment of primary brain cancers and cancers that have metastasized to the brain, Geron Corp. has entered into a worldwide exclusive license agreement with Montreal, Canada-based Angiochem Inc. for peptide technology to facilitate the transfer of anticancer compounds across the blood-brain barrier (BBB). In addition, the companies have entered into a research and collaboration agreement to put these receptor-targeting peptides to work transporting telomerase inhibitors into

the central nervous system (CNS). The license covers proprietary receptortargeting peptides conjugated to tubulin disassembly inhibitors, including GRN1005, which was formerly known as ANG1005. GRN1005 is a novel taxane derivative that has completed two Phase I clinical trials in patients with primary brain tumors and in patients with brain metastases from breast and lung cancer. Angiochem will receive an upfront license fee from Geron for the exclusive license rights. Angiochem is also entitled to receive milestone payments, royalties on product sales and a share of sublicensing revenues. Specific terms were not announced. “This in-licensing augments our oncology clinical pipeline to address metastatic brain cancer, a large global unmet medical need,” says Dr. Thomas B. Okarma, president and

HUDSON, N.Y.—Taconic and BioPontis Alliance

Eisai and FORMA Therapeutics enter into broad drug discovery collaboration WOODCLIFF LAKE, N.J.—Eisai

Inc., the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co. Ltd., and FORMA Therapeutics have signed a strategic drug discovery collaboration. Under the terms of the agreement, Eisai will have access to FORMA’s Diversity Oriented Synthesis (DOS) chemistry-generated compound library and cell-based screening platforms to support the discovery of novel compounds for Eisai’s pipeline. Eisai has an option for technology transfer of FORMA’s cell-based screening platform. FORMA will receive upfront payments and committed funding of $20 million over three years and is eligible to receive additional milestones plus royalties on future products that Eisai may commercialize as a result of this collaboration. Further details were not disclosed.

bbb continued on page 28

Extending its reach

BioPontis Alliance and Taconic partner on genetically modified models for translational research LLC recently signed an agreement around the development of genetically modified models and scientific services for translational research. Taconic will serve as BioPontis Alliance’s exclusive provider of genetically modified models used in oncology applications. Taconic is also the company’s preferred provider for in vivo clinical studies in the areas of oncology, neurology and infectious disease; compound profiling services; phenotyping services; and customgenerated models.

CEO of Geron. “With GRN1005, we now have an additional compound tracked to provide Phase II human proof-of-concept in 2012. The results of the completed Phase I trial in brain metastases from common cancers showed that GRN1005 is highly active as a single agent. If these results are confirmed in our Phase II study, we anticipate rapid marketing approval.” He adds that he and the rest of his company also look forward to collaborating with Angiochem in combining the CNS-targeting peptide technology with Geron’s telomerase inhibitor technology “to enable clinical delivery of its demonstrated preclinical activity against brain cancer stem cells.” “Primary brain tumors and brain metastases present a significant unmet medical need because drugs that might be effective against

EHSI acquires stem cell biotech firm Celulas Genetica By David Hutton

Baxter International Inc. has purchased all of the hemophilia-related assets of Archemix, a privately held biopharma firm, including Archemix’s lead product ARC19499, a synthetic hemophilia therapy that is injected under the skin and is currently in a Phase I clinical trial in the United Kingdom.

philia therapy that is injected under the skin and is currently in a Phase I clinical trial in the United Kingdom. The therapy blocks Tissue Factor Pathway Inhibitor (TFPI) activity, thereby augmenting and improving blood clotting, potentially reducing replacement factor therapy for patients with hemophilia A and B. The move is a strong indication of Baxter’s interest in bolstering its presence in the fight against hemophilia, a rare genetic blood clotting disorder that primarily affects males.

footprint, Emerging Healthcare Solutions Inc. recently announced its acquisition of Celulas Genetica, a biotechnology firm based in Panama. Financial terms of the deal have not been released. Houstonbased EHSI initially signed a profit participation agreement with the company in March. Headquartered in Panama City, Panama, Celulas Genetica is a Central American leader in stem cell technology acquisition and development. In early December, Celulas Genetica purchased a license to develop and market the revolutionary Rutherford Procedure, a groundbreaking organ regeneration treatment designed to use proton-beam technology to destroy diseased organ tissue for regeneration using adult stem cells. “Celulas Genetica’s license to develop and market the Rutherford Procedure was our main motivator to complete this acquisition,” points out EHSI President and CEO Cindy Morrissey. “We intend to test this innovative procedure thoroughly and develop it into a viable treatment for deadly illnesses such as liver disease. The worldwide demand for stem cell therapies of this kind is extraordinary.” Celulas Genetica is currently exploring the possibility of working with a Chinese proton therapy facility to develop the new treatment for use around the globe.

baxter continued on page 29

ehsi continued on page 29

Baxter’s buying After dropping generic injectables, company adds hemophilia-related assets of Archemix to product stable By Kimberley Sirk DEERFIELD, Ill.— Baxter

Inter­ national Inc. announced in late November that it is in the process of buying all of the hemophiliarelated assets of Archemix, a privately held biopharma firm, and has also entered into an exclusive license agreement for related intellectual property assets. The lead product associated w it h t h e a r r a n ge m e nt i s ARC19499, a synthetic hemo-

HOUSTON—In an effort to expand its research and development

28  Drug Discovery News • January 2011

RESEARCH & DEVELOPMENT 

For more information, visit www.DrugDiscoveryNews.com

Optivia builds on UCSF work to predict liver toxicity of drugs in development NIH awards Phase I SBIR grant for new transporterbased system By Lloyd Dunlap MENLO PARK, Calif.—In a collaboration that could represent an important step forward toward ensuring drug safety and increasing drug efficacy by building the first transporter-based assay system capable of predicting ADME (absorption, distribution, metabolism and excretion) and reducing druginduced liver toxicity, Optivia Biotechnology Inc. a provider of in-vitro transporter assay services, will collaborate with the University of California, San Francisco (UCSF) to develop an innovative system for characterizing the role transporter proteins play in the disposition of drugs by the liver. The partners have received a $430,000 Phase I grant to leverage the expertise of Dr. Leslie Z. Benet, an internationally recognized drug development expert and professor and chairman emeritus in UCSF’s department of bioengineering and therapeutic sciences, along with Optivia’s novel transporter technology platform to study the effects of transporters on drug disposition and the interplay of transporters and metabolizing enzymes in the liver. The goal is to develop a transporter-based assay system capable of predicting the ADME characteristics of drug candidates. To do so, Optivia will screen 40 compounds against 10 transporters and work with UCSF to build a

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those tumors are not able to efficiently enter the brain,” adds Dr. Stephen M. Kelsey, Geron’s executive vice president and chief medical officer for oncology. “GRN1005 has a demonstrated ability to penetrate brain tissue and, more importantly, brain tumors in nonclinical models and in patients. Furthermore, patient data from the Phase I clinical study in brain metastases showed compelling preliminary evidence of anti-tumor activity.” The deal is important for Angiochem in part to demonstrate and facilitate its continued progress. As Angiochem’s chairman, president and CEO, Dr. Jean-Paul Castaigne, tells ddn, his company has already shown proof-of-concept for small-molecule formulations, and one of the next steps for Angiochem is to move into more work with peptides, proteins, enzymes and the like. In addition to its concern with developing therapeutics for brain disorders and diseases that migrate to the brain, Castaigne notes that Angiochem also has a promising

model based on the results. Dr. Yong Huang, Optivia’s president and CEO, says no specific indications will be studied, but notes that the liver is the major loci for metabolism of most drugs. The Phase I study will also address the interplay between transporters and drug metabolizing enzymes. The team will use the Biopharmaceutics Classification System (BCS), a guidance for predicting the intestinal drug absorption, to select 10 drugs from each of the four BCS categories. The Phase I program is a one year project. Phase II, Huang says, will extend to other organs—kidney, GI tract and blood-brain barrier—and extend the scope to study additional drugs. “This collaboration reflects our response to the specific call from the pharmaceutical industry and regulatory agencies for systematic data, both in vitro and in vivo, with respect to how drugs interact with multiple transporters expressed in various human organs, and how such interactions alter drug pharmacokinetics in the human body,” Huang states. “Integrating analysis of drug transporters is increasingly becoming a core requirement in ADME assessments and is anticipated to become a regulatory standard for new drug applications.” ADME models are increasingly influential in determining whether a new molecular entity should advance through R&D, and one of the fastest growing ADME research areas of the last decade is transporter proteins. It is estimated that more than 86 percent of all compounds and about 40 percent of clinical-stage drugs fail due to unsatisfactory ADME, toxicity and clinical safety properties. Drug-induced hepatotoxicity is

“GRN1005 has a demonstrated ability to penetrate brain tissue and, more importantly, brain tumors in nonclinical models and in patients.” —Dr. Stephen M. Kelsey, Geron’s executive vice president and chief medical officer for oncology peptide for pain management. “Also, for obesity we have a modified leptin able to cross the BBB,” he says. “Leptin is produced by the fat cells and then is transported to the brain by the leptin transporters at the surface of the blood-brain barrier. Unfortunately in obese patients those transporters are impaired and the more you are obese, the less leptin is transported to the brain.” Also on deck is a possible treatment for Parkinson’s disease, and a desire to further develop the oncology platform, with plans already

estimated to be responsible for as many as 5 percent of all hospital admissions and 50 percent of all acute liver failures. Druginduced liver toxicity is also one of the most common reasons for previously approved drugs to be withdrawn from the market, translating into increasing costs of drug discovery and development. For example, according to the U.S. Food and Drug Administration’s 2004 Critical Path Initiative white paper, it is estimated that

filing of a large number of drugs against a panel of key human transporters as the first step toward building transporterbased predictive models for the assessment of ADME and drug-drug interactions (DDIs). A model that correlates in-vitro data to in-vivo results would be of incalculable value to the pharmaceutical industry, since it will allow drug developers to make better decisions on the ADME properties of drug candidates prior to performing in-

“This grant will allow us to build on UCSF’s previous work suggesting that we can predict how drugs will behave in the body, specifically the liver, based on transporter biology.” — Dr. Leslie Z. Benet, professor and chairman emeritus in UCSF’s department of bioengineering and therapeutic sciences clinical failures based on liver toxicity have cost one major pharmaceutical company more than $2 billion in the last decade. “This grant will allow us to build on UCSF’s previous work suggesting that we can predict how drugs will behave in the body, specifically the liver, based on transporter biology,” says Benet, who is a member of the International Transporter Consortium. “We intend to provide a body of systematic data based on the in-vitro pro-

forming to do more work with Geron on that front. Castaigne says the two companies had not worked together before but found that they connected well after face-to-face meetings and found they had similar aims and outlooks. “We are very pleased to enter into the license and the collaboration agreements with Geron, whose clinical oncology team is highly experienced in taking anticancer drugs through clinical development,” Castaigne noted in the news release about the deal. “We look forward to further clinical development of ANG1005, now GRN1005, and to collaborating on combining our proprietary BBBpenetrating peptides with Geron’s telomerase inhibitor technology for clinical development.” Telomerase is a critical and broadly applicable tumor target, the two companies note. The enzyme is expressed in a wide range of malignant tumors, and its activity is essential for the indefinite replicative capacity of cancer that enables malignant cell growth. Telomerase has now also been shown to be a target for cancer stem cells. ddn EDITCONNECT: E011121

vivo studies, most likely reducing development costs and decreasing the number of failures related to the ADME properties of drugs.” Another next step, Huang says, may well be an FDA collaboration to determine how nutraceuticals interact in the liver with prescription and over-the-counter drugs to provide data that could be important to proposing regulations. ddn EDITCONNECT: E011124

The ‘why’ and ‘how’ of GRN1005

T

By Jeffrey Bouley

he blood-brain barrier (BBB) prevents foreign substances, including more than 95 percent of drugs, from entering the brain. This presents a practical challenge to the treatment of brain cancer, including primary tumors as well as brain metastases, which represent a substantial global unmet medical need. The United States alone sees approximately 200,000 cases of metastatic cancers in the brain annually and as many as half of patients die as a direct result of intra-cerebral disease. There are currently no drugs approved for brain metastases. GRN1005 is designed to exploit a natural mechanism by which essential substances, such as lipids and hormones, successfully enter the brain through receptors in the BBB. GRN1005 is comprised of three molecules of paclitaxel, a drug with proven anti-tumor activity outside of the brain, linked to a proprietary peptide that targets the lipoprotein receptor-related protein-1 (LRP-1), one of the most highly expressed receptors on the surface of the BBB. Binding to LRP-1 facilitates receptor-mediated transcytosis across the BBB into the brain tissue. Importantly, LRP-1 is also upregulated in many tumors, including malignant glioma and metastatic cancers both in the brain and visceral organs, enabling efficient entry to tumor cells in the brain and in the periphery using the same receptor-mediated pathway. Geron’s clinical development plan for GRN1005 includes a Phase II clinical trial to be initiated in the second half of 2011 in patients with brain metastases arising from non-small cell lung cancer and breast cancer. Geron also plans to initiate a Phase II clinical trial in patients with glioblastoma multiforme in the first half of 2012. ddn

For more information, visit www.DrugDiscoveryNews.com

baxter continued from page 27

Current estimates are that more than 400,000 people in the world have hemophilia. All races and economic groups are affected equally by the disorder. “Baxter is committed to optimizing hemophilia care and improving the lives of people living with hemophilia around the world,” says Dr. Hartmut Ehrlich, vice president of global research and development and medical affairs for Baxter’s BioScience business, in a prepared statement. “This anti-TFPI program is an important addition to other Baxter hemophilia development programs focusing on longeracting rFVIII and rFIX and nonintravenous therapies.” ARC19499 is part of a new therapeutic class referred to as “aptamers.” Aptamers are smaller than a protein or biologic, so the theory is that these molecules have the potential to be further developed for subcutaneous administration. They are short, synthetically derived oligonucleotides that form three-dimensional structures that bind with high specificity and affinity to protein and non-protein targets. Currently there is one aptamer approved by the U.S. Food and Drug Administration and available to patients today: Macugen, for the treatment of age-related macular degeneration. The Phase I clinical trial for ARC19499 was initiated by Archemix in the United Kingdom in

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Your key to additional story content At the end of every bylined story in ddn, you’ll find an Editconnect code, like the one in the story above: E011122. Simply click the Editconnect button on our home page, enter the code and access our story archives.

RESEARCH & DEVELOPMENT

August 2010 and continues to enroll patients. People living with hemophilia do not have enough of, or are missing, one of the blood clotting proteins naturally found in blood. Two of the most common forms of hemophilia are known as type A and type B. In about 30 percent of cases, there is no family history of hemophilia, and the condition is the result of a spontaneous gene mutation.



to as “Christmas disease”) do not have sufficient amounts of clotting factor IX. Baxter expects to record a special pre-tax, in-process research and development charge of approximately $30 million in the fourth quarter of 2010 relating to an upfront payment associated with the transaction. In the future, Baxter may also make milestonerelated payments to Archemix of

“Baxter is committed to optimizing hemophilia care and improving the lives of people living with hemophilia around the world. This anti-TFPI program is an important addition to other Baxter hemophilia development programs focusing on longer-acting rFVIII and rFIX and non-intravenous therapies.” — Dr. Hartmut Ehrlich, vice president of global research and development and medical affairs for Baxter’s BioScience business In people with hemophilia A, clotting factor VIII is not present in sufficient amounts or is absent. Without enough FVIII, people with hemophilia can experience spontaneous, uncontrolled internal bleeding that is painful, debilitating, damaging to joints and potentially fatal. People with hemophilia B (which is sometimes also referred

up to $285 million. Subject to regulatory approvals and other conditions, the companies expected to complete the transaction by the end of 2010. In late October, Hikma Pharma­ ceuticals, a multinational pharmaceutical group based in London, purchased Baxter’s U.S. generic injectables business for $112 million

January 2011 • Drug Discovery News  29

in cash. The deal involved products currently on the market and in the pipeline, as well as employees and real estate in New Jersey and Tennessee. “Baxter’s growth strategy is to focus more on differentiated offerings derived from the company’s expertise in enhanced packaging and formulation technologies, resulting in higher-margin products,” explained company officials at the time. Baxter officials refused to comment for this story. Archemix representatives did not respond to requests for comment. Baxter develops, manufactures and markets products that treat hemophilia, immune disorders, cancer, infectious diseases, kidney disease, trauma and other chronic and acute medical conditions. Archemix is a privately held biopharmaceutical company based in Cambridge, Mass. The company is leading the development of aptamers as a new class of directed therapeutics for the prevention and treatment of chronic and acute diseases. With their unique properties, aptamers offer an alternative to biologics and small molecules in numerous applications and hold extraordinary potential to address unmet medical needs. The company’s website states that Archemix’s business strategy is to build and advance a pipeline of proprietary aptamer products in the core areas of cardiovascular disease, hematology and oncology. ddn EDITCONNECT: E011122

Baxter licenses autoimmune disease therapy to Accentia TAMPA, Fla.—Baxter

also recently signed an agreement with Accentia Biopharmaceuticals Inc. to provide Accentia with the exclusive, worldwide right to purchase Baxter’s cyclophosphamide, which is marketed under the brand name Cytoxan, for the treatment of designated autoimmune diseases including multiple sclerosis. Cyclophosphamide is the active drug used in Revimmune therapy, Accentia’s proprietary systemof-care being developed for the treatment of a broad range of autoimmune diseases. According to the companies, further investigation of cyclophosphamide may identify a potentially valuable treatment option for patients with devastating autoimmune diseases, including multiple sclerosis, with high unmet medical need. The agreement also grants Accentia the exclusive right for designated indications to reference Baxter’s proprietary, historical data related to cyclophosphamide as part of Accentia’s planned clinical and regulatory development of Revimmune. The agree-

ment designates Baxter as Accentia’s sole source of cyclophosphamide for Revimmune. “We are pleased that, through this agreement, we will be able to support Accentia Biopharmaceuticals in the ongoing development of Revimmune,” says Dr. Debasis Chakrabarti, Baxter’s therapeutic area leader for oncology. “Further investigation of cyclophosphamide may identify a potentially valuable treatment option for patients with devastating autoimmune diseases, including multiple sclerosis, with high unmet medical need.” “With this agreement in place, we are planning a robust clinical and regulatory development strategy to advance our mission to establish Revimmune as a new standard-of-care treatment for patients suffering from autoimmune diseases, including orphan indications with potential accelerated regulatory pathways, as well as major indications such as multiple sclerosis,” says Accentia President Samuel S. Duffey. Financial terms of the deal were not released. ddn

All the news we can’t fit in print Check out the ddn Blog at http://ddnonline.wordpress.com/

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continued from page 27

In the wake of the acquisition, EHSI announced that Celulas Genetica would submit an international patent application for the Rutherford Procedure. Celulas Genetica has engaged a patent specialist to file the Patent Cooperation Treaty (PTC) application with a receiving office in China, the company noted. The biotech company licensed the procedure from a Chinese firm, BBFITCL, and plans to conduct the treatment’s clinical trials in China as well.

“Celulas Genetica’s license to develop and market the Rutherford Procedure was our main motivator to complete this acquisition. We intend to test this innovative procedure thoroughly and develop it into a viable treatment for deadly illnesses such as liver disease. The worldwide demand for stem cell therapies of this kind is extraordinary.” — Cindy Morrissey, president of EHSI “We believe that the Rutherford Procedure could very well revolutionize the treatment of liver disease worldwide,” Morrissey notes. “Filing a PTC application is a necessary step to protect the value of this crucial asset.” Morrissey says that she plans to travel to China soon to meet with stem-cell researchers and potentially help open a Celulas Genetica business office there. According to Morrissey, extending its reach into the R&D hotbed of China would build on EHSI’s expanding global footprint. Celulas Genetica will be only the latest outpost in EHSI’s global footprint. In addition to its Houston headquarters, the company also maintains business offices in Frankfurt, Germany and Warsaw, Poland. “Much of the top stem cell research being conducted today takes place outside the United States,” Morrissey points out. “To be an industry leader in this field, you have to be international, and we fully intend to fund and produce industry-leading innovations.” ddn EDITCONNECT: E011123

30 Drug Discovery News • January 2011

SmArt continuEd from pAGE 1

SmartCell’s board of directors has unanimously approved the transaction, which is subject to regulatory approval. Both companies declined to comment beyond what was stated in their Dec. 2 press release. Merck has identified diabetes and obesity as one of its development priorities, among such other commercially important disease areas as cardiovascular, oncology, infectious dis-

RESEARCH & DEVELOPMENT

ease, immunology, endocrinology and women’s health. As of Merck’s third-quarter earnings statement, the company has two diabetes programs in development: MK-3102, a treatment for diabetes mellitus in Phase II development, and MK-0431C, a diabetes treatment in Phase III development. Merck sells Januvia and Janumet, which treat type 2 diabetes by inhibiting the body’s DPP-4 enzyme. SmartCells’ SmartInsulin, a oncedaily insulin injection that aims to automatically adjust to fluctuating

levels of blood glucose, represents Merck’s foray into insulin therapies. SmartInsulin deploys an insulin therapeutic only in the presence of a specific glucose concentration range. According to SmartCells, if this approach is successful in the clinic, it has the potential to produce insulin analogs that may result in a lower risk of hypoglycemia, compared with standard insulin analogs, and improve control over both fasting and post-meal glucose levels. “Maintaining control of blood glucose levels represents a daily

challenge for people living with diabetes,” said Nancy Thornberry, senior vice president and head of Merck’s diabetes and obesity franchise, in a statement. “Through the acquisition of SmartCells, we have obtained innovative technology that may enable us to develop glucose-responsive insulins. If this investigational technology is ultimately approved for use with patients, it could provide an important new therapy for the treatment of diabetes. This holds the potential to significantly impact the

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treatment of this disease.” SmartInsulin was originally developed as part of SmartCells’ technolog y platform at the Massachusetts Institute of Technology by its president, co-founder and CEO, Dr. Todd Zion, who said in a statement that Merck’s acquisition “positions our novel technology for success in the hands of a leading pharmaceutical company with proven expertise and exceptional resources to deliver breakthrough diabetes products to patients.” “At SmartCells, we have made important progress in rapidly advancing from early concept towards clinical development,” Zion stated. That advancement has in large part been supported by grants from the National Institutes of Health and equity investments from members of Boston Harbor Angels, Angel Healthcare Investors, Beacon Angels and Cherrystone Angel Group. At least one analyst has been critical of SmartCells’ path of growth. The In Vivo Blog points out, “in its seven-year lifespan, SmartCells has raised less than $20 million, relying heavily on grants from the Juvenile Diabetes Research Association, National Institutes of Health and angels … without traditional VCs in the picture, the company’s founders seem likely to make a pretty penny even if the upfront is in the tens of millions.” Indeed, Zion told The Boston Globe that SmartCells wanted to avoid raising more money than necessary so its team could retain a significant ownership share. “We’ve always had a philosophy here that we let our operating plan dictate our financing plan, and not the other way around,” he told the newspaper. Still, the In Vivo Blog approves of the structure of Merck’s agreement, adding, “The medicine presumably overcomes some of the stigmas associated with insulin therapy— the potential risks of either hyper- or hypoglycemia and the frequent daily monitoring required to maintain appropriate blood glucose levels. Being preclinical, the company will have to show the compound has the commercial chops to survive the rise of long-acting GLP-1s, another reason an earn-out deal was a smart move on the part of the Merckies.” The Motley Fool agreed, calling Merck’s acquisition “a smart move—assuming it didn’t overpay.” “SmartInsulin is rather risky, since it uses an unproven technology, but it’s a potential blockbuster if it works,” The Motley Fool noted. “The SmartCells technology could extend beyond insulin. It could be used to sense any molecule and then release a drug. Drugs with a tight therapeutic window—where too much is bad and too little doesn’t do enough—would be good candidates. If SmartCells succeeds, its purchase will make Merck look like a downright genius no matter how much it paid upfront to buy the company.” ddn eDitConneCt: e011102

For more information, visit www.DrugDiscoveryNews.com

b r i e f s

European regulators conduct antitrust raids on several pharmas BRUSSELS—In its ongoing effort to crack down

on antitrust practices, the European Commission (EC) last month announced that it carried out “surprise inspections” at several pharmaceutical companies. “The Commission has reason to believe that the companies concerned may have acted individually or jointly, notably to delay generic entry for a particular medicine,” said the regulatory agency in a statement, but an EC spokeswoman said it is against policy to name any companies that were investigated. AstraZeneca has acknowledged that it was one of the companies inspected, but Bayer, GlaxoSmithKline, Lundbeck, Novo Nordisk, Pfizer and sanofi-aventis said they weren’t involved in the probe. In recent years, EC inspectors have said they believe that some companies have used patent filings to stop generic medicines from hitting the market, or tying up potential competitors for years in legal disputes.

FDA drug approvals slipped in 2010

Wherever you go (online), Throw there the sales pitches are the biotech Healthcare marketing on the Internet draws interest from privacy groups By Kimberley Sirk WASHINGTON, D.C.—In a year that saw vigorous activity in attempts to regulate and merely explain the role of the Internet in commerce, privacy groups and other advocates have stepped further into the debate by asking the U.S. Federal Trade Commission (FTC) to investigate ad targeting practices engaged in by online health marketers. The 144-page complaint was filed in November by the Center for Digital Democracy, Consumer Watchdog, the World Privacy Forum and the U.S. Public Interest Research Group. The groups allege via the complaint that health marketers are violating the privacy of individuals searching the Internet for potentially sensitive information by secretly track-

WASHINGTON— The U.S. Food and Drug Administration (FDA) approved about 21 drugs in 2010, down from 25 in 2009 and 24 in 2008, but higher from a recent low of 18 in 2007. Most analysts believe the drop reflects a tougher environment at the FDA, with regulators stepping up their scrutiny of safety issues in drugs for many key disease areas. Although the 2010 figures are a bit lower than previous years, FDA spokeswoman Sandy Walsh told The Wall Street Journal that there’s “no systemic change in how the FDA is approaching drug approvals.” The FDA approved a few potential blockbusters, but some of the most highly anticipated new products were delayed until this year or beyond.

Mylan’s Dey Pharma unit settles DOJ suit over reimbursements BASKING RIDGE, N.J.—Mylan

Inc. announced in December that its Dey Pharma unit has settled a 2006 lawsuit brought by the U.S. Department of Justice over Medicare and Medicaid reimbursements to pharmacists and other healthcare providers. In exchange for a release of claims, Dey agreed to pay $280 million. The settlement agreement does not constitute an admission, finding or evidence of fault, liability or wrongdoing by Dey. Pursuant to the 2007 acquisition agreement between Mylan, Dey’s parent company, and Merck KGaA, Dey’s former parent company, Merck KGaA is responsible for paying the full amount of this settlement as well as all costs and other expenses associated with pending and future-related Medicare and Medicaid reimbursement lawsuits involving Dey.

January 2011 • Drug Discovery News  31



ing them, and “gathering details on their interests and activities (and now including offline databases and employing psychographic and demographic analysis), and then plying them with marketing messages precisely honed to a particular illness or condition.” This unauthorized tracking, known as behavioral targeting, has been in the sights of privacy groups for several years. With the exponential growth of the Internet into every facet of consumers’ daily lives, the potential for sharpening advertising messages based on online behavior is irresistible to marketers. Anyone who uses Facebook or Google’s Gmail feature, as only two examples, sees targeted pitches with every click. This recent filing comes on the heels of these groups last year beseeching the U.S. Food and Drug Administration (FDA) to work with other governmental bodies to urgently deal with the sensitive matter of

WASHINGTON, D.C.—The contentious lawsuit seeking to end federal funding for embryonic stem cell (eSC) research, Sherley, et. al., v. Sebelius, et al., continues to make its way through the courts, as attorneys for those opposed to eSC research and the U.S. govern-

By Lori Lesko

ment argued before an appeals court. The case, being heard by the U.S. District Court for the District of Columbia, alleges that an order signed last year by President Barack Obama which lifted a ban on federal funding for eSC research violates the DickeyWicker Amendment, a law that prohibits the U.S. Department of Health and Human Services (HHS) from using appropriated funds for the creation of human embryos for research purposes, or for research in which human embryos are destroyed. The suit’s stem cell continued on page 33

patent continued on page 32

online continued on page 33

Stem cell case makes its way through courts By Amy Swinderman

U.S. Department of Justice files precedentsetting amicus curiae brief in landmark DNA patent case the landmark lawsuit, Association of Molecular Pathology v. U.S. Patent and Trademark Office, winds its way towards the U.S. Federal Circuit Court on appeal, a flurry of amicus curiae briefs have flown in for both sides—including a precedent-setting filing by the U.S. Department of Justice (DOJ) “in support of neither party.” The DOJ’s brief—in contending that the human genes linked to breast and ovarian cancer, BRCA1 and BRCA2, should not be eligible for patents because they are “part of nature”— appear to be more on the side of the American Civil Liberties Union (ACLU) rather than Utah-based Myriad Genetics. A three-judge federal district court panel is likely to hear the district court appeal by Spring, and could take up to one year to issue its ruling, according to Jackie Wright Bonilla, partner in Washington D.C.-based Foley & Lardner LLP, who has filed an amicus curiae brief for Myriad. The highly publicized case is expected to ultimately land in the hands of the U.S. Supreme Court. The final decision will have wideranging ramifications for the future of human gene patents and the biotech industry. The case began when several women with histories of breast cancer in their families wanted the diagnostic tests at Myriad, but could not afford the $3,000 cost and did not have insurance coverage. Several doctors’ groups, the ACLU and the Public Patent Foundation then filed a lawsuit in 2009, seeking to invalidate patents on two genes related to breast cancer and owned by Myriad.

The Sherley v. Sebelius case is expected to play out for some time, and could wind up being heard by the U.S. Supreme Court, which could ultimately have the last word on whether federal dollars should fund embryonic stem cell research.

Contentious case could be in for long haul as attorneys for both sides make arguments to appellate court

baby out with the bath water?

WASHINGTON D.C.—As

32  Drug Discovery News • January 2011

government watch

For more information, visit www.DrugDiscoveryNews.com



Compare and contrast As U.S. regulators look to implement a regulatory pathway for biosimilars, Brookings Institute panel shares lessons learned from other countries’ experience By Amy Swinderman WASHINGTON, D.C.—With the U.S. healthcare

reform law giving U.S. regulators a legal framework and authority to develop an abbreviated approval pathway for biosimilars—off-brand versions of biotech drugs— the U.S. Food and Drug Administration (FDA) is still navigating these as-yet unchartered regulatory waters. To answer some of the FDA’s nagging questions, the Brookings Institution, a nonprofit public policy organization, held a hearing Dec. 1 to discuss key implementation issues associated with biosimilar entry in the United States and what the government’s role should be in regulating the process. The hearing, called “Biosimilars in the United States: Implementation Challenges and Lessons Learned from the European Union,” addressed regulatory and implementation challenges and opportunities and provided a comparative analysis of the European Union’s experience in creating a biosimilars approval pathway. The European Union, as well as several countries around the globe, has already implemented an approval pathway for biosimilars, but it wasn’t until the passage of last year’s

patent continued from page 31

On March 29, 2010, Judge Robert W. Sweet of the Southern District of New York granted partial summary judgment, ruling that the claims of several patents on BRCA1 were invalid. Three months later, Myriad appealed, and more than a dozen amicus curiae briefs followed. The ACLU also has about a dozen amicus curiae briefs in support of its position. Now that the DOJ has weighed in with its amicus curiae brief, legal pundits are predicting a patent Armageddon, of sorts. The brief posits that the district court erroneously cast doubt on the patent eligibility of a broad range of manmade compositions of matter whose value derives from the information encoding capacity of DNA. “ S u ch c o mp o s it i o n s— e.g. , cDNAs, vectors, recombinant plasmids and chimeric proteins, as well as countless industrial products, such as vaccines and genetically modified crops, created with the aid of such molecules—are in every meaningful sense the fruits of human ingenuity and thus qualify as ‘human-made inventions’ eligible for patent protection under Section 101,” the brief states. The DOJ acknowledges its amicus curiae brief has stirred up a pot of

Patient Protection and Affordable Care Act that U.S. regulators began taking a serious look at implementing a process by which to approve the development of biosimilars here. Among the questions facing the FDA are how to identify and monitor adverse events, what kinds of clinical data are required for approval and how to involve the various relevant stakeholders in these decisions. The panel of experts was moderated by Brookings Vice President and Director of Governance Studies Darrell West. Speakers included Anthony Ridgway, a senior regulatory scientist at Health Canada; Mary Pendergast, president of Pendergast Consulting, which provides strategic and tactical advise to biotech and pharmaceutical corporations, governments, professional and patient groups and institutions on regulatory issues relating to compliance and drug development; and Henry Grabowski, professor of economics and director of the program in pharmaceuticals at Health Economics at Duke University. Ridway said that in Canada, biosimilar products are examined “on a case-by-case basis.” “Full chemistry and manufacturing data is required, plus the comparability study with the referenced biologic. Clinical data is required. The amount of that data is negotiable and is influenced by several factors. And one should use the same reference product throughout the development of the program,” Ridway explained. “On the Canadian side, we started with a new drug submission approach and said, okay, what concessions, what relaxations can be made. And I think it’s interesting that both the European Union and Canada have ended up around the same place,

controversy, but places much of the blame on the district court. “We acknowledge that this conclusion is contrary to the longstanding practice of the Patent and Trademark Office, as well as the practice of the National Institutes of Health and other government agencies that have in the past sought and obtained patents for isolated genomic DNA,” the DOJ brief states. “The district court’s judgment in this case, however, prompted the United States to reevaluate the relationship between such patents and the settled principle under Supreme Court precedent that the patent laws do not extend to products of nature.” Edward Reines, a patent attorney who represents biotechnology companies, says, “It’s major when the United States, in a filing, reverses decades of policies on an issue that everyone has been focused on for so long.” The U.S. Patent and Trademark Office has sided with the proponents and has issued thousands of patents on genes of various organisms, including on an estimated 20 percent of human genes. But in its brief, the government says it now believes the mere isolation of a gene, without further alteration or manipulation, does not change its nature.

even though we perhaps approached it from different directions.” Grabowski said there are many lessons to be learned from Europe. “Germany is the kind of leading edge of usage of biosimilars, and basically they have had biosimilars for erythropoietin now for two years and for the G-CSF’s products like Neupogen for one year,” he said. “And the penetration against the reference product, Eprex in the EPO area is now at 60 percent. We’re seeing price changes. The price discounting of the biosimilar relevant to the reference product, that introduction is now around 40 percent. And we also see the refer-

often the drug candidates, the good drug candidates, good therapeutic candidates may not have good patent protection. It may take a long time so that the core patent time is eroded.” Speaking candidly about the motivations behind defining an approval pathway for biosimilars, Pendergast said, “I think the one thing you can say about the United States is that the biosimilar legislation was definitely economically motivated, and there certainly has been enough politics in it for everyone to have a share. Should we envy our Canadian neighbors to the north, where this was not either politically nor economically motivated?” In the United States, Pendergast said, ques-

Similar or not similar: That is the question

Marie Rock, vice president of the Protein Bioanalysis group of Midwest BioResearch, summarizes the scientific hurdles facing approval of biosimilars versus generics See guest commentary on page 11

ence product dropping its price, not the full 40 percent, but a significant amount, part of the way towards the biosimilar in Europe, and that’s all without any kind of substitution or interchangeability.” Data exclusivity, one of the main points of debate in legislators’ ongoing discussion about approving biosimilars, remains an issue, Grabowksi added. “People say, well, if we have patents, why do we need some period before the data exclusivity, it’s the period before a biosimilar can rely on some of the initial safety and efficacy data to get an abbreviated approval,” he said. “Congress eventually settled on 12 years after a lot of debate. Should it be 5 years? Should it be 14? Some say we don’t need it. I think the reason you need some kind of exclusivity is

tions about the regulation of biosimilars remain across multiple government entities. “So talking about the implementation of biosimilars, I was at the FDA, worked on the Hatch-Waxman legislation before it was passed, and then helped implement it. I litigated the first case under that legislation and have watched it over the last 26 years. And one of the things I would like to point out is that 26 years later, there are still court cases, there are still guidance documents coming out, there are still areas of that law that we don’t understand or where courts have taken contrary positions,” she said. “You have a seminar next year at this time, do not expect everything to be decided, because it won’t have been.” ddn EDITCONNECT: E011128

“We acknowledge that this conclusion is contrary to the longstanding practice of the Patent and Trademark Office, as well as the practice of the National Institutes of Health and other government agencies that have in the past sought and obtained patents for isolated genomic DNA. The district court’s judgment in this case, however, prompted the United States to reevaluate the relationship between such patents and the settled principle under Supreme Court precedent that the patent laws do not extend to products of nature.” —U.S. Department of Justice’s amicus curiae brief Dr. James P. Evans, a professor of genetics and medicine at the University of North Carolina, refers to the government’s brief as “a bit of a landmark, kind of a line in the sand.” According to Bonilla, “some have accused the DOJ of misreading the law entirely and attempting to eviscerate biotechnology innovation altogether. Such viewpoints misread the point of the DOJ brief.” The DOJ argues that the district court got it wrong in certain important respects, she says.

“As part of this discussion, the DOJ likewise agrees with our position that claims directed to recombinant vectors comprising any isolated DNA—even DNA having a sequence exactly as it exists in nature—constitutes patentable subject matter,” Bonilla states. “Thus, unlike the district court opinion, the DOJ proposal does not throw the entire biotech baby out with the bath water.” That said, the DOJ “may cut off a hand of the biotech baby, with its contention that ‘isolated DNA,’

comprising a sequence from genomic DNA as it exists in a body, does not constitute patentable subject matter,” Bonilla says. The DOJ brief also argues that the “chemical structure of native human genes is a product of nature,” even when that structure is “isolated” from its natural environment. “This position presents a slippery slope of considerable concern to those involved in biotech innovation,” Bonilla says. “For example, the DOJ sidesteps an important scientific fact: all isolated nucleotide compositions—regardless of sequence—are, in fact, engineered DNA molecules.” Such DNA molecules are by definition of their existence in an isolated form, “human-made” inventions that simply do not exist without human intervention, Bonilla argues. “Then how does one successfully distinguish what is really ‘humanmade?’” Bonilla asks. “The DOJ’s position has sweeping implications, even if they’re not as debilitating as the district court opinion.” The Federal Circuit and/or Supreme Court may ultimately decide the outcome of this case based on policy and social or economic considerations, she says. ddn EDITCONNECT: E011127

For more information, visit www.DrugDiscoveryNews.com

government watch 

January 2011 • Drug Discovery News  33

online

“Pharma and other health marketers need to embrace a code of conduct that ensures they operate in a ethically responsible manner,” says Chester. “But the Federal Trade Commission, working closely with the FDA and HHS, should develop new safeguards for this marketplace. We know the FDA and HHS has taken our comments and work seriously. So far, no pharma group has responded to our complaint—which the FTC is expected to address soon.” Consumer Watchdog, World Privacy Forum and the FTC did not respond to requests for comment for this story. ddn

continued from page 31

maintaining a shroud of privacy over individuals’ medical concerns. “Consumer advocates have told both the FTC and the Department of Commerce that they must create special consumer safeguards for online pharma and health marketing,” says Jeffrey Chester of the Center for Digital Democracy (CDD). The CDD is a nonprofit group that promotes consumer protection in the digital era, especially in the health, financial and youth new media areas. “Online marketing, including the collection of user data through so-called behavioral targeting, is a new unregulated digital frontier,” says Chester. “Many of the practices used in digital marketing raise privacy and consumer protection issues, especially when deployed for sensitive matters as health, finance and (those) involving children.” Government and other media have taken a broad interest in protecting the consumer in this realm, both in attempts to explain and to educate the public about the need to protect their privacy while on the Internet. Social media behemoth Facebook has been struggling with privacy revisions to its vast network for years. The Wall Street Journal recently began an ongoing series about Internet privacy and tracking of consumer behavior; the Obama administration, through the Department of Commerce, has proposed an Internet “privacy bill of rights” and the FTC is working toward a “Do Not Track” registry. The FDA is likewise working toward issuance of social media rules for ad placement, another regulatory arena in which Chester’s group has been vocal. In late December, that body, through its Division of Drug Marketing, Advertising and Communications, issued a statement indicating that a draft guidance on that topic would not be issued until at least the first quarter of 2011. “The use of these technologies by pharmaceutical, health product, and medical information providers that directly affect the public health and welfare of consumers requires immediate action,” the groups say in the complaint. And, in a USA Today/Gallup poll released in December, survey respondents indicated that they are for the most part cognizant of the fact that their online travels are tracked to allow advertisers to pitch their wares most effectively. But this same audience says they are opposed to those tactics, even if the result

stem cell continued from page 31

lead plaintiffs, adult stem cell researchers Dr. James L. Sherley, a biological engineer at Boston Biomedical Research Institute, and Dr. Theresa Deisher, research and development director at AVM Biotechnology LLC in Seattle, also argue that Obama’s order has intensified competition for the limited government dollars, making it more difficult for them to get funding for their own work. A federal appellate panel is reviewing a surprise preliminary injunction issued Aug. 2 by federal district judge Royce Lamberth that found merit in the plaintiffs’ arguments and temporary brought federal funding for embryo-destructive research to a halt. The U.S. Court of Appeals temporarily suspended the injunction on Sept. 28 while the case is still pending.

EDITCONNECT: E011125

“Online marketing, including the collection of user data through so-called behavioral targeting, is a new unregulated digital frontier. Many of the practices used in digital marketing raise privacy and consumer protection issues, especially when deployed for sensitive matters as health, finance and (those) involving children.” — Jeffrey Chester, Center for Digital Democracy is to help keep websites free. The poll also found that, of people who used the Internet for more than an hour per day, more than six in 10 say they have noticed that some ads are targeted specifically to them based on websites they have previously visited. On the other hand, nine in 10 say they pay little or no attention to online ads. These assessments vary little by age and income. Another important finding of the Gallup poll was that, if given the choice, Internet users would allow ads from companies they select to be targeted to them. This finding had an inverse relationship to age, with younger people agreeing to the ads targeting more than those 55 and over. “If the FTC moves forward with a ‘Do Not

Track’ measure that is voluntary for advertisers, Internet users’ clear desire is for online advertisers to sign up—and leave decisions about who can track them squarely in users’ hands,” says the survey results. The groups which filed the complaint suggest that the FDA and FTC work together to address what they describe as the special privacy needs of the healthcare consumer, and that messages targeted to consumers based on where they have traveled around the Web are vastly different than virtual marketing pitches for cars or candy. Potential solutions for the advocates’ concerns include an agreement across the industry on advertising standards and disclosure about when private information is collected.

In early December, Judge Thomas Griffith said the government’s argument “rises or falls” on whether stem-cell research is intertwined with deriving stem cells. Plaintiffs’ attorney Thomas Hunger argued that federal grants for eSC research induce the private sector to create more of the cells—“there is now an incentive for the future destruction of human embryos,” he said—while U.S. Department of Justice lawyer Beth Brinkmann, representing the Obama administration, said Congress intended to make a distinction between promoting the study of eSCs and paying for their creation. Currently, NIH guidelines allow research on cells derived from embryos that would otherwise be disposed of after in-vitro fertilization procedures. The case is expected to play out for some time, and could wind up being heard by the U.S. Supreme Court. The Economist has noted

that whatever the outcome of the case, it has cast such a shadow on eSC research in the United States that researchers abroad “will be keen to take up any slack in work using embryonic stem cells.” “In November, a group at Glasgow University implanted stem cells into the brain of a stroke victim. Israel and Singapore have ambitious plans. Even South Korea, which suspended research after a scandal in 2005, is testing the water again,” The Economist points out. “Private money can fill the gap to a certain extent, as Geron and Advanced Cell Technology demonstrate. But it is unlikely to pay for fundamental research in what is still an imperfectly understood field. If the courts eventually find for the plaintiffs in Sherley v. Sebelius, and Congress does not act, the caravan of embryonic stem cell research will surely move on elsewhere.” ddn EDITCONNECT: E011126

34  Drug Discovery News • January 2011

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Screening Technology Trends First part of a multi-part series

Research at the speed of light High-throughput screening technology leads to advances in drug discovery

O

By David Hutton ne of the more recent

innovations in drug discovery, high-throughput screening (HTS), is made feasible through advances in robotics and high-speed computer technology. For scientists working in HTS laboratories, there are myriad challenges, including pressure to find increasing numbers of drug leads while containing costs. As a result, many are seeking larger compound sets, more automated systems to screen them faster, and an integrated set of equipment and consumables. High-throughput screening requires the miniaturization and automation of in-vitro bioassays so that millions of variables can be tested. HTS is often an important step in the discovery of new medicines. In this first installment of a multipart series in ddn, we focus on some of the key developments in recent years with regard to screening technology and look ahead to see what the future holds.

Today’s trends J. Fraser Glickman, director and research assistant professor of the High-Throughput Screening Resource Center at Rockefeller University, points out that there have been several key developments in HTS in recent years. “Among them, I would place the improved throughput and analysis of high-content technologies based on image analysis of cell samples, and so-called ‘fragment-based’ approaches for measuring binding

of compound fragments,” he says. “Also, we have seen a vast improvement in the automation of microtiter plate processing and the associated scheduling software. Chemin­ formatic software has also become phenomenally more effective.” Houston, Texas-based Selleck Chemicals is a worldwide supplier of high-performance kinase inhibitors and antibodies for cell signaling and oncology research. Sales director Sunny Xu notes that functional genomics with their RNAi and cDNA technologies are wellknown recent applications of HTS. “They are called siRNA highthroughput screening and cDNA library high-throughput screening,” Xu says. “Particularly, the former will help scientists to understand the molecular basis of tumorigenesis, identification of therapeutic targets and so on. Capillary electrophoresis (CE) or HPLC-based HTS systems could be applicable to complex and even unpurified chemical mixtures.” Dr. Rathnam Chaguturu is the director of HTS laboratories and courtesy research professor of molecular biosciences and medicinal chemistry at the University of Kansas. He sees an increased awareness of label-free, HCS/HCA and multiplexed assays for screening and profiling.

Label-free: The way to be? Chaguturu points out that there is a growing tendency now to adopt label-free platforms. “Currently, most assays for the detection of biologically relevant binding events use either radioactive or fluorescent dyes to tag one or more molecules, overexpression of the biological target of interest or reporter proteins,” he says. Simply put, Chaguturu explains that this is quite an unnatural set-

“Technological advancements will revolutionize the market,” says Sunny Xu, sales director for Selleck Chemicals, a supplier of high-performance life-science reagents and reference compounds for the non-clinical research fields based in Houston, Texas. “Technological advancements such as the use of robotics and cell-based assays have had a significant impact on the HTS market. HTS reagents and assays are experiencing increasing demand, leading to intense competition among reagent manufacturers, much more than among instrument manufacturers.”

up. Furthermore, researchers are restricted to a simplistic biology assessment with just point-ofcontact measures and one signaling pathway per ligand-receptor complex. “We know that the therapeutic targets do not function in isolation, but operate in a systems biology context involving a complex set of integrated biochemical pathways, and we need to find a way to quantitate these processes,” he says. “This is where label-free technologies come in to play, as 99.5 percent of human genome has not yet been fully exploited for drug discovery.” The main reason, according to Chaguturu, is because the pharmaceutical industry has operated mainly in low-risk territory with potential for greater return on investment. “Academia is the one that feeds new therapeutic targets for the pharmaceutical industry to pursue,” he says. “Academia, by the

“The oft-quoted myth that high-throughput screening has not been the panacea for drug discovery, as one was led to believe at first, has now been squashed as the origins of many of the drug candidates in pharma’s pipeline can now be traced back to in-house HTS campaigns.” — Dr. Rathnam Chaguturu, director of HTS laboratories and professor at the University of Kansas

nature of its mission, works in this unchartered territory of high risk and low reward, but for it to make headway, it is limited by the availability of easily adaptable technology formats to deorphanize the highly refractory targets. The labelfree assay technology is widely applicable for many classes of targets and cellular processes.” Chaguturu explains this is especially useful in a systems biology context in charting metabolic pathways. “Label-free technology is the way to go in deorphanizing these refractory targets, and that can be done without long and costly assay development process,” he says. “Next, this technology allows us to generate biologically relevant data in a systems biology context. It is useful as an alternate readout technology for use in the hit-to-lead optimization process, and you can work with primary cell lines and without the need for engineered cell lines.”

Growing pains Glickman points out that over the last 15 years, the field of HTS has gone from infancy into a mature and robust approach, as evidenced by the growing number of labs throughout the world and in various sectors, which no longer view it as an experimental new technology, but rather as a requirement in order to have a healthy and competitive

research program. “We always keep a certain capacity for scanning the horizon for new screening technologies, and for being creative in the way we improve our efficiency,” he notes. “Many of the pitfalls associated with HTS have now become transparent, and the community have actively presented resolutions to these issues.” As with any developing technology, change can be rapid, and in recent years, acoustic technology has been playing a large role in HTS. With so much technology changing so rapidly, there remain plenty of challenges facing scientists in HTS laboratories. Xu notes that examples of key changes are robotics, miniaturization, sophisticated assay chemistry to sophisticated software and database. According to Glickman, the main challenge “is keeping costs down and efficiency up. This does not only apply to HTS but to drug discovery in general, which is facing and will continue to face sustainability issues related to the cost burden on society.” According to Chaguturu, assay development is the most critical component leading up to a screening campaign. “For assay development work, robotics is not a deciding factor, but for screening campaigns, liquid handling robotics is a must without which no amount of FTE could measure up to the throughput needed, and do the tasks in a timely manner,” he says. Adapting to changes can be analogous to trying to turn a battleship, and Chaguturu contends that pharma greatly underestimates the significance of toxicobiology, and doesn’t understand it well enough to pick the right drug targets. “Pharma is not set up to do this sort of research,” he said, noting it “warrants collaboration between industry and academia.” The trend he views is pharma developing partnerships with academia in an open-platform paradigm to advance drug discovery endeavors. He points out several examples, including Novartis and Institutes for Biomedical Research; speed continued on page 35

For more information, visit www.DrugDiscoveryNews.com

speed

continued from page 34

GlaxoSmithKline (GSK) and Centers for Excellence for Drug Discovery; Pfizer and the Biotherapeutics and Bioinnovation Center; Lilly and Phenotypic Drug Discovery (PD2) Initiative; and Merck and Sage Bionetworks. Moreover, a dozen competing drug companies have agreed to share data on thousands of Alzheimer’s patients in hopes that the extra information will spark new ideas for treatments. Called the Coalition Against Major Diseases, the collaboration pairs patientadvocacy groups with such phar-

ddn special report

January 2011 • Drug Discovery News  35



challenge is finding talented, classically trained medicinal chemists to improve the properties of hits, which can be a long, unpredictable and arduous task.” Chaguturu points out that with the flow of top pharmaceutical drug discovery scientific talent in to academia and the industrialization of small-molecule library synthesis, academia is poised to take drug discovery to new heights. “There is also a much-needed collaborative spirit between pharma and academia in closing the risk-

reward gap as exemplified by a number of industry-academia collaborative agreements that are being put in place,” he says. “The technology transfer offices are now generally charged in guiding the researcher in IP disclosures, patenting decisions and commercialization of research results. This has transformed the faculty in to entrepreneurs in managing their inventions. So, the long-term future is quite bright.” Xu concludes that HTS technologies will be more widely accepted by

pharmaceutical and biotechnology companies as an integral part of their drug discovery processes and the HTS market will continue to grow. “Technological advancements will revolutionize the market,” Xu says. “Technological advancements such as the use of robotics and cellbased assays have had a significant impact on the HTS market. HTS reagents and assays are experiencing increasing demand, leading to intense competition among reagent manufacturers, much more than among instrument manufacturers.”

Glickman is very positive about the future of HTS, in the sense that as an approach to identify chemical lead compounds, it has become a “proven performer.” “I also feel that many of the technological innovations that have been designed for HTS drug discovery purposes, are starting to bleed over into other fields, such as RNAi screening, and in addressing basic scientific issues using the analytical techniques performed in microtiter plates,” he says. ddn EDITCONNECT: E011129

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Follow the Because high-throughput screening (HTS) technologies have been widely accepted by pharmaceutical and biotechnology companies as an integral part of their drug discovery processes, the HTS market is likely to continue its rapid pace of growth.

maceutical giants as GSK, Pfizer and AstraZeneca. It is led by the Critical Path Institute, a nonprofit partnership associated with the U.S. Food and Drug Administration (FDA) that aims to speed discovery of new drugs.

A new decade, a new mantra Even with the ever-changing technologies, Chaguturu notes that the drug discovery landscape is at a crossroads with profound changes looming in the horizon, and open innovation becoming the new mantra for reinvigorating the pharmaceutical R&D’s lackluster drug candidate pipeline. “To fill this void, academia has now ventured from its traditional role of exploring the fundamental aspects of disease biology into the high-throughput screening arena in a big way, thanks to the NIH Roadmap Initiative and the EuOpen Screen program for facilitating this transition,” he says. “The oft-quoted myth that high-throughput screening has not been the panacea for drug discovery, as one was led to believe at first, has now been squashed as the origins of many of the drug candidates in pharma’s pipeline can now be traced back to in-house HTS campaigns. HTS has found its niche in academia with research priorities in drug discovery endeavors.” Researchers, Glickman points out, are continually looking ways to improve their processes and striking the right “economy of scale.” “Scientifically, the main question for us is how we can improve the predictive value of the in-vitro tests we perform to translate well into in-vivo results,” he says. “Another

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36  Drug Discovery News • January 2011

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Billions of screens have produced … what? Critics of high-throughput screening ask: Is the approach of building a bigger haystack really the best way to find more needles?

N

By Lloyd Dunlap anoliter acoustic

compound dispensing technology; custommade benchtop enclosures with automated liquid handling vortexers and mixers; chemical libraries that have grown to include more than 1 million small molecules and grow by 20 percent every year; ministores that have the capacity to store millions of compound in 384-well microplates at -20º C that can be cherry-picked from the same or different collections—and that’s just a brief look at the advanced equipment side. Elsewhere, there’s induced fit docking; rational drug design; structurebased lead optimization; integration of experimental and in-silico data by cross-functional expert teams and dozens of other approaches. It’s all subsumed under the single rubric of high-throughput screening (HTS), which is used in one form or another in hundreds, if not thousands, of labs around the globe. HTS is defined as a method for scientific experimentation especially used in drug discovery and relevant to the fields of biology and chemistry. Using robotics, data processing and control software, liquid handling devices and sensitive detectors, HTS allows a researcher to quickly conduct millions of biochemical, genetic or pharmacological tests. Through this process, one can rapidly identify active compounds, antibodies or genes which modulate a particular bimolecular pathway. The results of these experiments provide starting points for drug design and for understanding the interaction or role of a particular biochemical process in biology. Yet after 25 years of HTS, we have little by way of NMEs that have contributed to the curing of disease or alleviation of debilitating symptoms. Several years ago, a respected U.K. researcher, Dr. David Horrobin, vented his frustration by decrying the process altogether. He noted that estimates of the ratios of compounds synthesized to marketed drugs at the time of peak success of Nobel Laureates Black, Bovet, Elion and Hitchings was about 100:1; most of the industry from about 1960 to about 1990 saw about 10,000:1 to 30,000:1; Big Pharma since the introduction of combinatorial chemistry and HTS, well over 1,000,000:1.

Horrobin asked the question, “Is the approach of building a bigger haystack really the best way to find more needles? Dr. Stephan Heyse, head of Genedata’s Screener business unit, doesn’t care for the haystack analogy because he says HTS has changed. He thinks the “more needles” approach has been supplanted by a “sharper needles” goal. “It’s more like a well-tended field where you already know a lot about what’s in each row,” he says. “We’re evolving toward biology-rich information that goes beyond simple endpoint assays and uses better detection technologies, such as optical assays and ion channel readers, to make results more trustworthy. The problem has always been that what you saw at the first filter will always be out there and can affect basic business decisions. You can’t always afford to reproduce scans to get to the next level. High-content screening, for example, provides a much broader basis for decisionmaking. You can generate active plus toxicology information, for example. Maybe weak actives that have a good tox profile are more important than just strong hits.” Summarizing the current stateof-the-art technology, Heyse notes that classical primary screens continue to be performed in high throughput—i.e., millions of wells. As new technologies such as highcontent screening and timeresolved fluorescence, label-free and electrophysiology methods deliver more information per well and screened compound, data management and analysis become more complex. Mastering these challenges yields more precise information at the HTS stage on compound mode-of-action and potential therapeutic window. Complete bioactivity profiles of compounds are compiled from sets of high-throughput primary and secondary screens, enabling optimized decisions on compound progression into the hitto-lead phase. At Schrödinger Inc., screening can vary from ligand-based similarity searches where thousands or tens of thousands of molecules are screened per second to much more refined and specific studies such as induced fit docking, explains Dr. Woody Sherman, vice president of applications science. In May 2010, his group

Dr. Stephan Heyse, head of Genedata’s Screener business unit, doesn’t care for the haystack analogy because he says HTS has changed. He thinks the “more needles” approach has been supplanted by a “sharper needles” goal. “It’s more like a well-tended field where you already know a lot about what’s in each row,” he says. “We’re evolving toward biology-rich information that goes beyond simple endpoint assays and uses better detection technologies … to make results more trustworthy. The problem has always been that what you saw at the first filter will always be out there and can affect basic business decisions. You can’t always afford to reproduce scans to get to the next level.”

reported the results of a large-scale, ligand-based virtual screening study, with the goal of improving database enrichments. The study involved 11 pharmaceutically relevant targets to investigate the interrelation between eight two-dimensional fingerprinting methods, 13 atom-typing schemes, 13 bit scaling rules and 12 similarity metrics using the new cheminformatics package Canvas. In total, 157, 872 virtual screens were performed to assess the ability of each combination of parameters to identify actives in a database screen. In general, fingerprint methods such as MOLPRINT2D, Radial and Dendritic that encode information about the local environment beyond simple linear paths outperformed other fingerprint methods. Atomtyping schemes with more specific information, such as Daylight, Mol2 and Carhart were generally superior to more generic atom-typing schemes. Enrichment factors across all targets were improved considerably with the best settings, although no single set of parameters performed optimally on all targets. Kinases remain an important drug target class within the pharmaceutical industry, Sherman notes, but he adds that the rational design of kinase inhibitors is plagued by the complexity of gaining selectivity for a small number of proteins within a family of more than 500 related enzymes. He and his team have developed a computational screening method for identifying the location and thermodynamic properties of water molecules within a protein binding site that can yield insight into previously inexplicable selectivity and structure-activity relationships. Four kinase systems (Src family, Abl/c-Kit, Syk/ZAP-70, and CDK2/4) were investigated, and differences in predicted water molecule locations and energetics were able to explain the experimentally observed binding selectivity profiles. The successful predictions across the range of kinases suggest that this screening methodology could be generally applicable for predicting selectivity profiles in related targets. “Understanding kinase selectivity is key to developing effective therapies that don’t have side effects,” he concludes. As Sherman’s work reveals, screening that predicts or confirms experimental observations can answer, in silico, fundamental questions about molecular interactions and be used as an important part of the drug development process. ddn EDITCONNECT: E011130

For For more more information, information, visit visit www.DrugDiscoveryNews.com www.DrugDiscoveryNews.com

Microscope with modular design for rapid automation development Applied Scientific Instrumentation Inc. The RAMM system’s modular design allows a custom system to be easily developed. The microscope is configurable with infinity-corrected optics, filter cubes, filterwheels and detectors. Automated features include highspeed XY stages, piezo and motorized focusing, auto-focus and a robotic specimen loader. The system provides a solid platform, and has been designed for flexible costeffective OEM development using high-quality high MTBF components to reduce cost and increase customer satisfaction. Applied Scientific Instrumentation Inc. www.ASIimaging.com (541) 461-8181 Visit us at LabAutomation booth #106

Hybrid multi-mode microplate reader BioTek Instruments Inc. BioTek Instruments Inc. recently introduced Synergy H1, a cost-effective hybrid multi-mode microplate reader featuring a highperformance filter system and flexible monochromator system. The reader is compatible with Take3 plate with 2 µL microspots for lowvolume assays and advanced quadruple monochromator optics. Dichroic-based filter optics enables fluorescence polarization and TR-FRET. BioTek Instruments Inc. www.biotek.com (802) 655-4740 Visit us at LabAutomation booth #151

System integrates automated liquid handling system within genomics worfkflow Eppendorf North America Inc. Eppendorf’s recently launched epMotion 5075 TMX PC system automates the manual steps within the next-generation sequencing (NGS) workflow, including end repair, A-tailing, adaptor ligation,

size separation, bead-based cleanup steps and PCR setup, among other applications. The epMotion 5075 TMX PC version with epBlue software is a convenient way to use an automated liquid handling system within the genomics workflow. With Eppendorf’s Thermomixer (TMX) technology integrated inside and a flexible and open platform capable of adapting to the varying needs of each NGS platform, the epMotion 5075 TMX is an ideal tool for increasing laboratory productivity and efficiencies where NGS is employed. Eppendorf North America Inc. www.eppendorf.com (800) 645-3050 Visit us at LabAutomation booth #251

Liquid handling workstation Caliper Life Sciences Inc. The Sciclone G3, the latest iteration of Caliper’s plate-prep workhorse, features a 96- or 384-channel pipetting head, optional eight-channel pipettor

new products

and/or bulk reagent dispenser as well as Caliper’s new “PING!” non-contact liquid level detection technology to ensure that all samples are processed during vacuum or pressure filtration. Sciclone also supports mag bead-based separations along with a large variety of on-deck shaking, heating and cooling options. The Sciclone G3T version with point-and-click capability supports up to 96 sample tubes with “smart” racks that ensure proper sample loading and identification prior to assay runs. Caliper Life Sciences Inc. www.caliperls.com (508) 435-9500 Visit us at LabAutomation booth #439

Compact, automated pipetting workstation Hamilton Robotics MicroLab NIMBUS is Hamilton’s compact, automated pipetting workstation, offering a high-density deck in a small footprint. Available in fourindependent channel or 96 multi-channel head platfor ms, NIMBUS provides speed, flexibility and high-performance air displacement pipetting at an affordable price, even for small, budget-challenged labs. An optional gripper with extended reach allows for easy labware transport and seamless integration to peripheral devices. Hamilton Robotics www.hamiltonrobotics.com (800) 648-5950 Visit us at LabAutomation booth #405

January 2005 2011 • Drug Discovery News   37 NOVEMBER



a dvertiser ’ s inde x Advanced Chemistry Development, Inc (ACD Labs).........26. Applied Scientific Instruments........................................19. Beckman Coulter Genomics, Inc.......................................5. BioTek Instruments, Inc...................................................15. Caliper Life Sciences........................................................3. Cambridge Healthtech Institute........................................9. Chembridge Corporation.................................................33. Eppendorf North America................................................39. Hamilton Robotics............................................................2. INDIGO Biosciences, Inc.................................................35. Invitrogen, Part of Life Technologies................................40. Molecular Devices, Inc......................................................7. Seahorse Bioscience......................................................24. Society for Laboratory Automation and Screening.....14, 30. Trevigen, Inc....................................................................21. for assay development, lead identification and lead optimization. Molecular Devices Inc. www.MolecularDevices.com (800) 635-5577 Visit us at LabAutomation booth #615

Cell sorter enables multi-color flow cytometry studies Beckman Coulter Inc. The Astrios next-generation cell sorter from Beckman Coulter Inc. leverages the stable fluidic design of the original MoFlo and the electronic processing of the MoFlo XDP, while expanding

Kit measures cell response to stress Seahorse Bioscience Inc. The XF Cell Mito Stress Test Kit, recently introduced by Seahorse Bioscience Inc., makes it easy to quantify cellular bioenergetics, identify mitochondrial dysfunction and measure cells response to stress, enabling the user to gain a greater understanding of cancer, aging, and metabolic, cardiovascular and neurodegenerative diseases. The kit measures the four key parameters of mitochondrial dysfunction in a microplate—basal respiration, ATP turnover, proton leak and reserve capacity— in real time. Seahorse Bioscience Inc. www.seahorsebio.com (978) 671-1600 Visit us at LabAutomation booths #244 & #245

Multi-mode microplate reader Molecular Devices Inc. The patent-pending SpectraMax Paradigm Platform allows users to upgrade the functionality of their instrument directly with no service call or factory shipment. Upgrading can be done in less than two minutes. This unmatched flexibility provides a platform that can be easily adapted to meet constantly evolving application needs and ever-advancing detection technologies while accommodating a range of budgets. With multiple detection modes, including AlphaScreen and HTRF, as well as 1536-well microplate compatibility to support high-throughput screening, the SpectraMax Paradigm Reader is also ideal

www.acdlabs.com www.asiimaging www.beckmangenomics.com www.biotek.com www.caliperLS.com www.healthtech.com www.chembridge.com www.eppendorf.com www.hamiltonrobotics.com www.indigobiosciences.com www.invitrogen.com www.moleculardevices.com www.seahorsebio.com www.slas.org www.trevigen.com

Print-and-apply labeling system Computype Inc. Computype Inc. and Nautilus Systems have announced the launch of the PR100i, an advanced print-and-apply system designed specifically for challenging labeling requirements in the laboratory environment. The PR100i is a desktop label applicator that can print and apply up to 12 labels in tandem with precision and accuracy. The system features a high-quality thermal transfer printing system with 600 dpi resolution, and a patentpending retracting peel edge technology, making it ideal for small labels. Computype Inc. www.computype.com (800) 328-0852

Bar-coded storage tubes for automated sample management Corning Inc. sorting capabilities with an array of laser options. A range of unique software components further enhances instrument functionality. Complex, multicolor sorting is enabled by seven pinholes that spatially separate each of the seven lasers. Auto start-up allows the researcher to define when lasers and fluidics turn on, saving valuable time. The multi-fiber Beam Shaping Optic creates flat-top beam profiles, providing short alignment times and high-level optic stability. Two stages control the alignment for all seven lasers to simplify sorter preparation. Beckman Coulter Inc. www.beckmancoulter.com (800) 232-3828

Corning Inc. has unveiled the Corning Bar Coded Storage Tubes to streamline the throughput needs of laboratories. This latest offering broadens Corning’s automation product line and provides researchers with a superior solution for enhanced sample storage, identification and retrieval. The tubes offer the market a storage solution that synchronizes two codes to the same ID, limiting the risk of confusion or duplication. Corning Inc. www.corning.com (978) 442-2200

System for live cell imaging Fluxion Biosciences Inc.

Biotage has announced the addition of ChemMatrix resins to its offering of peptide synthesis and purification products. ChemMatrix is a patented, 100-percent PEG resin from Matrix Innovation that offers substantial advantages over traditional PS- and PEG-based resins for solid phase peptide synthesis. The ChemMatrix resin is a technological tool that enables synthesis of complex molecules from biological origin, peptides, oligionucleeotides and small proteins typically used for therapeutic products. This resin is supplied as classical spherical beads.

Fluxion Biosciences Inc. has announced the new BioFlux 1000Z system for live cell imaging, the latest addition to the BioFlux product family of instruments for cellular analysis under controlled shear flow. The BioFlux 1000Z provides an integrated solution for running live cell assays under flow using Fluxion’s Well Plate Microfluidic devices. It features a fully automated imaging workstation built around the ZEISS AxioObserver microscope.

Biotage www.biotage.com +46 18 56 59 00

Fluxion Biosciences Inc. www.fluxionbio.com (866) 266-8380

PEG resins for solid phase peptide synthesis Biotage

facts & Figures

38  Drug Discovery News • January 2011

For more information, visit www.DrugDiscoveryNews.com



Report details emerging clinical operations in European markets emerging markets offer hope to an industry struggling with patent cliffs, price cuts and an uncertain economy. According to a recent report by market research firm Cutting Information Inc. (CEI), compared to other emerging regions, Central/Eastern Europe presents unique advantages, such as convenient locations, a long history of clinical trials and balanced time and cost estimates. The report, “Emerging Markets Clinical Development Series: Central and Eastern Europe,” is part of a five-part series on clinical development in emerging markets. In addition to Central/Eastern Europe, the series also examines Africa, Asia, Latin America and Brazil/Russia/India/China, also known as BRIC. According to CEI’s report, access to patients—more than any other reason—convinces companies to extend their trials outside developed countries’ borders. Top

markets such as the United States and Europe’s top five companies house hundreds of millions of potential trial subjects, but at the same time, the clinical trial market has been saturated with tens of thousands of trial protocols targeting similar patients. As a result, CEI says, many companies choose to globalize their trials in an effort to recruit more patients and avoid saturated markets. “For European companies, especially, looking to keep their trials closer to home, countries in Eastern Europe offer easy and close access to more patients,” says CEI. “Though no single country houses an enormous number of patients, and the region will never compete with India or China in population, countries such as Poland, the Czech Republic and their neighbors combine for a significant population of potential patients.” The report takes a close look at the gen-

Central/East European Population Compared to U.S. and 5 EU Countries

eral environment within Russia, Poland, Bulgaria, Romania, Turkey and the Ukraine, including demographics, political and economic landscape, healthcare system and pharmaceutical industry. It then delves into

More Expensive 90%

6-10%

11-25%

20%

20%

19%

70% 60%

40%

50% 40%

69%

80%

30%

20%

20% 10%

401.9

Russia n=5

20%

6% 6%

Poland n=5

Central/East Europe n=16

Country / Region

350

307.2

300

306.5

Average Percentage of Time Saved by Running a Site in Central/East Europe

250 200

140

150

More Time-Consuming

100

Russia

6-10%

11-25%

90%

Poland

United States

Central and Eastern Europe

80%

5 EU

Percent of Respondents

0

0-5%

Country / Region

Number of Studies Registered in Select Central/ Eastern European Countries

19% 40%

40%

70% 60% 50%

44% 20%

40% 30%

40% 20%

19%

20% 10%

2,500

2,000

0%

1,997

1,000

834 684

500

0

Poland

Russia

20%

20%

13%

Russia n=5

Poland n=5

Central/East Europe n=16

6% Country / Region

1,457 1,364

1,500

26-50%

100%

38.5

50

Number of Registered Studies

26-50%

80%

450

Population (in Millions)

0-5%

100%

0% 400

clinical development strategy within each country. The third and final section of the report presents different perspectives, drawn from surveys and interviews, on clinical development in each country. ddn

Average Percentage of Budget Saved by Running a Site in Central/Eastern Europe

Percent of Respondents

DURHAM, N.C.—The

635

564

ABOUT CUTTING EDGE INFORMATION 492

355

350

334

310

Czech Romania Turkey Slovakia Ukraine Bulgaria Croatia Estonia Lithuania Latvia Republic

Country

264

194

Serbia Slovenia

Cutting Edge Information is a business intelligence firm providing primary and secondary research on a wide range of business subjects, with a specialization on the pharmaceutical research industry. For more information about this report, or other CEI reports, visit www.cuttingedgeinfo.com. ALL information and graphics copyright © CUTTING EDGE INFORMATION

Drug Discovery News (USPS 024-504) is published monthly by Old River Publications LLC, 19035 Old Detroit Road, Suite 203, Rocky River, OH 44116; 440-331-6600. Periodical postage paid at Cleveland, Ohio and additional mailing offices. Publisher assumes no responsibility for unsolicited material or prices quoted in the magazine. Contributors are responsible for proprietary classified information. ©2011 by Old River Publications. All rights reserved. Reproduction, in whole or in part, without written permission of the publisher is expressly prohibited. Back issues, when available, cost $7 each within the past 12 months; $12 each prior to the past 12 months. Back orders must be paid in advance by check. Drug Discovery News is distributed without charge in North America to qualified drug discovery research professionals. Paid subscriptions to those not qualified cost $65 annually to the U.S. and Canada and $150 to all other countries. All payments must be made in U.S. funds drawn on a U.S. bank. Publications mail agreement no. 41401058 return undeliverable Canadian addresses to PO Box 503, RPO West Beaver Creek, Richmond Hill, ON L4B 4R6. For subscription services, including subscription information, please call 215-785-5196. POSTMASTER: Send address changes to Drug Discovery News, PO Box 3100, Langhorne, PA 19047-8800.

031.A1.0120.A © 2011 Eppendorf AG

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