ProMetic Corporate Presentation April 2016
The Biology of Healing We are the company that can effectively address the entire healing process in a groundbreaking way using both small molecule drugs and plasma protein therapies. We are continuously discovering new innovations to regulate the cycle of healing. We do it, not because we have to, but because we are compelled to. It’s at the heart of our culture to provide a pathway to hope.
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Safe Harbour Forward Looking Statement This presentation contains forward‐looking statements about ProMetic’s objectives, strategies and businesses that involve risks and uncertainties. These statements are “forward‐looking” because they are based on our current expectations about the markets we operate in and on various estimates and assumptions. Actual events or results may differ materially from those anticipated in these forward‐looking statements if known or unknown risks affect our business, or if our estimates or assumptions turn out to be inaccurate. Such risks and assumptions include, but are not limited to, ProMetic’s ability to develop, manufacture, and successfully commercialize value‐added pharmaceutical products, the availability of funds and resources to pursue R&D projects, the successful and timely completion of clinical studies, the ability of ProMetic to take advantage of business opportunities in the pharmaceutical industry, uncertainties related to the regulatory process and general changes in economic conditions. You will find a more detailed assessment of the risks that could cause actual events or results to materially differ from our current expectations in the Annual Information Form for the year ended December 31, 2015, under the heading “Risk Factors”. As a result, we cannot guarantee that any forward‐looking statement will materialize. We assume no obligation to update any forward‐looking statement even if new information becomes available, as a result of future events or for any other reason, unless required by applicable securities laws and regulations. All amounts are in Canadian dollars unless indicated otherwise.
Copyright notice The information contained in this presentation (including names, images, logos and descriptions portraying ProMetic's products and/or services) is the property of ProMetic Life Sciences Inc., of its divisions and / or of its subsidiaries (“ProMetic”) and is protected by copyright, patent and trademark law and / or other intellectual property rights. Neither this presentation nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including printing and photocopying, or by any information storage or retrieval system without prior permission in writing from ProMetic.
Disclaimer ProMetic reserves the right to make improvements, corrections and/or changes to this presentation at any time.
© ProMetic Life Sciences Inc 2016
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ProMetic Overview Fully integrated biopharmaceutical company: 290 employees. HQ in Montreal with R&D and operations in Rockville (USA), Cambridge (UK) and Canada.
Market Cap ∾C$ 2.0 Billion. Cash position ∾C$29 M (end of Q4 2015). Strategic alliances / licensing agreements with > 35 companies worldwide. 17 biopharmaceuticals of licensees relying on ProMetic’s proprietary manufacturing platforms approved by FDA / EMEA: > 30 under development. ProMetic’s drug candidates in clinical phases:
Phase II/III – Plasminogen (ODD secured from FDA / EMA) Phase II – PBI‐4050 – 3 clinical programs (ODD secured from FDA / EMA for IPF) Phase III‐ IVIG Phase III‐ for 3 other Rx expected in 2016 © ProMetic Life Sciences Inc 2016
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Business Overview
Supplier of choice of proprietary affinity chromatography to major pharmaceutical companies
Integration of ProMetic proprietary manufacturing technologies & plasma proteomics (PPPS™=Plasma Protein purification System)
© ProMetic Life Sciences Inc 2016
Orally active small molecules (e.g. PBI‐4050)
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Cohn Process Developed / Optimized for Albumin Typically, other more valuable proteins are extracted from waste streams of albumin process Or have their yield reduced by cryodepletion step ~ 3 g of fibrinogen per liter of plasma ~1.8 g or 60% in “Cryo‐poor plasma” ~30% Recovery from cryo‐poor plasma or 0.9 g per liter of plasma
II+III
IV ~1.2 g of AAT per liter of plasma ~0.4 g of Aat in paste IV Recovery of AAT from paste IV ~18% recovery ~0.22 g
~18%
~30%
Albumin V
Albumin ~80% recovery ~25g ‐ 27 g
~18%
~ 7.5 g of IgG per liter of source plasma ~ 5 g of IgG in paste II+III Recovery of IgG from Paste II+III From ~40% ‐ ~50% ~3 g ‐ ~4 g
~40%‐ ~50%
~80%‐
© ProMetic Life Sciences Inc 2015
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COHN vs. PPPS™ Only producer of plasminogen and InterAlpha in the world
PROMETIC PROCESS
>10 # proteins / Liter
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COHN PROCESS
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20%
30%
40%
50%
60%
70%
80%
Yield Extraction
Note: Excluding Albumin © ProMetic Life Sciences Inc 2015
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Proprietary platform generating high yield & purity – high value Rx Plasma
Est. value per liter of plasma Processed PROMETIC INDUSTRY Plasminogen Orphan Rx # 1 IVIG
Fibrinogen
Alpha1-antitrypsin
C1-INH
Orphan Rx # 3, 4, 5…
>> $ 500…
N.A.…
~ $ 400
~ $ 250
~ $ 150
~ $ 80
~ $ 300
~ $ 80
>> $ 500… > $ ++++ © ProMetic Life Sciences Inc 2016
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Greater Revenues (USD) per Litre of Plasma Processed $2 000 $1 800 $1 600 $1 400
Superior Production Yield on commodity products + High Value Orphan Rx Enables much higher value per liter of plasma processed
$1 200 $1 000 $800 $600 $400 $200
540
530
380
320
230
Grifols
Biotest
BPL
$0 CSL
Baxter
© ProMetic Life Sciences Inc 2016
ProMetic
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Plasma Proteins: Revenue per Litre Processed
$ sales / L of plasma
$ 3000
Product sales output per Liter of plasma processed
400,000 Liter of plasma processing capacity Winnipeg + Laval (excludes capacity contribution from Hematech & Generium expected by 2018)
$ 2000
$ 1000 Plasminogen Fibrinogen API
2016 / 2017
Plasminogen Fibrinogen IVIG AAT Orphan Rx
2018 / 2019
© ProMetic Life Sciences Inc 2016
Plasminogen Fibrinogen IVIG AAT C1‐INH Orphan Rx +
2020 +
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Existing Facilities: cGMP Pilot Plant
© ProMetic Life Sciences Inc 2016
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ProMetic plasminogen – in Phase 2/3 clinical trial Congenital Plasminogen Deficiency The phase 1 pharmacokinetic and safety study demonstrated that ProMetic plasminogen: has a prolonged half‐life as compared to previously described plasminogen concentrate; this longer half‐life will be beneficial to patients and enable for the replacement of plasminogen at home in a manner similar to hemophilia; was well tolerated by patients with no reports of drug‐related serious adverse events Plasminogen infusion in patients with lesions also provided evidence of clinical efficacy: The plasminogen and the protocol for its use enabled the German Team of physicians to quickly reach an efficacious concentration of plasminogen in the blood of a critically ill 20 month old infant, followed within a few days by a reduction of the lesions and the patient able to breathe without ventilatory support. As part of the phase 1 trial, a second case of dramatic and rapid improvement was observed, this time in a severely affected patient, a 36 year‐old woman with a plasminogen level of 4% with involvement of multiple organ systems, including the lungs, nasal passages, eyes, gums and urinary tract. Within minutes of completing the plasminogen infusion, she noted improvement in her breathing, and within 2 hours blew a piece of tissue from her nose and coughed up soft tissue lesions previously blocking her airway. This improvement in the lung was coupled with a reduction in the size of her conjunctival lesions and improvement in her prominent gum lesions. On the day following infusion, her respiratory status continued substantially improved and she did not require her typical nebulizer treatment in the morning.
X‐Ray showing left lung collapse due to airway blockage by fibrous lesions
Normal X‐Ray post plasminogen treatment
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Plasminogen in congenital deficiency ‐ LA Expanded Access Patient • December 19: Minor accident – puncture wound on front of right middle finger • December 24: In ER with infected hand (Staph aureus) – multiple surgical incisions to drain infection • Antibiotics through PIC line for 4 weeks, followed by oral Bactrim for 2 weeks. • Surgical wounds did not heal • First Plg infusion: April 13
© ProMetic Life Sciences Inc 2015
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Plasminogen in congenital deficiency ‐ LA Expanded Access Patient April 14 / 24 hours after first infusion Surgical wounds middle, index & ring fingers:
April 20 / 7 days after first infusion
April 22 / 9 days after first infusion
April 26 / 13 days after first infusion
Middle and ring fingers:
Right middle & index fingers:
Right middle, index & ring fingers: Scab fell off and new skin growth sealing the wound
© ProMetic Life Sciences Inc 2015
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Plasminogen Deficiency Program – Next steps FDA has agreed to an accelerated regulatory approval pathway • Plasminogen clinical program currently in phase II-III trial where most of the same plasminogen deficient patients (~12-15 patients) are administered multiple doses to confirm the optimal treatment regimen to achieve the targeted blood concentration of plasminogen. • BLA filing in H2 2016 & Market launch H1 2017 For the plasminogen deficiency indication, the FDA has agreed to an accelerated regulatory approval pathway given the rarity of the condition and the unmet medical need. To secure an accelerated pathway approval, a drug must treat a serious condition, provide a meaningful advantage over available therapies and demonstrate an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit.
• Expansion the Plasminogen program to other indications • Wound Care Management – Global IP position from partnership with • Other indications to come
© ProMetic Life Sciences Inc 2016
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Expansion of the Plasminogen Clinical Program to other indications ProMetic intends to expand the use of Plasminogen in other clinical indications. The agreement with Omnio AB provides ProMetic with a unique and competitive intellectual property license as well as a comprehensive proprietary understanding of the use of plasminogen in the field of hard-to-treat wounds.
Next steps & Milestones for 2016: Disclosing new therapeutic indications for plasminogen Finalizing manufacturing dossier with new and proprietary formulation for wound healing Completing the clinical trial design for wound healing Expected to initiate the wound healing clinical trial in H2 2016 in Europe 15
Plasminogen Used in a Compassionate Use (Name Patient Basis) Being Considered for Bilateral Below‐the‐Knee Amputation – Patient 77yrs old, 3 yrs with chronic ulcers in both feet Before Plasminogen Treatment
Left foot
Right foot
• Distal, partial amputation performed on left foot • Right foot had an X‐ ray verified osteomyelitis • Had been treated with antibiotics for long period • Walking mainly on his heels
Diabetic Foot Ulcer Before Plasminogen Treatment • Patient could walk and balance on the front of his feet • Osteomyelitis was completely cured No additional use of antibiotics • No side effect of plasminogen
© ProMetic Life Sciences Inc 2016
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Plasminogen Used in a Compassionate Use (Name Patient Basis) (2) 80 year old female with arteriosclerosis Postoperative wounds in both legs Before Plasminogen Treatment
Left leg
Right leg
• Bilateral neuropathy in both legs • Coronary bypass with vein grafts harvested from her left leg 3 month earlier • Painful wound treatments with debridements • No improvement
Post‐Operative Wounds After Plasminogen Treatment • Patient’s wounds were completely closed • No side effects from plasminogen
© ProMetic Life Sciences Inc 2016
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Plasminogen Used in a Compassionate Use (Named Patient Basis) (3) 66 year old female with a 9 year old wound on the lateral malleal region on her left foot On Going Plasminogen Treatment
Time point A
Time point B
• Wound is almost healed • Vitality and social life has improved successfully • No side effect of plasminogen
Chronic Wounds Time point C
Time point D
10 Kronor: 3.3cm2
© ProMetic Life Sciences Inc 2016
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Cost of Diabetic Foot Ulcers
5 Year Mortality Rates
% 120
97
100 86 80 64 55
60 45
47
48
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US$13bn ANNUAL EXTRA COST + WORK LOSS + AMPUTATIONS
US$45,000 Per amputation
© ProMetic Life Sciences Inc 2016
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ProMetic IVIG in Phase 3 Clinical Trial The Corporation received clearance by the US FDA for its Investigational New Drug (“IND”) application for its Intravenous Immunoglobulin (IVIG) biological drug product for the treatment of primary immunodeficiency diseases (“PIDD”) and has initiated its Phase 3 clinical trial.
Next steps & milestones for 2016: Completing the enrolment of adult patient cohort Initiating the pediatric patient cohort
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Plasma‐Derived Drug Candidates under Development Alpha‐1 Antitrypsin (AAT) Manufacturing scale up and IND filing in 2016 C1 esterase Inhibitor (C1‐INH) Manufacturing scale up and IND filing in 2016 Fibrinogen (Fg) Clinical program in preparation in 2016 earmarked for clinical trials in H1 2017 Inter‐alpha inhibitor protein (IAIP) Orphan indications to be disclosed in 2016 Clinical program in preparation in 2016 earmarked for clinical trials in H1 2017
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In Summary – key milestones for 2016 • Plasminogen Further confirmation of safety profile and dose regimen Initiation and completion of phase II/III Initiation of clinical trial in Europe Filing of Plasminogen wound healing IND for the upcoming clinical trial set to start in H2 2016
• IVIG Enrolment of PID patients on IVIG in the US and in Russia
• Successful Tech transfer to Emergent – Winnipeg facility Completion of scale up of manufacturing process for Alpha1‐Antitrypsin to enable IND in 2016 Completion of scale up of manufacturing process for C1‐INH to enable IND in 2016 Completion of scale up of manufacturing process for Fibrinogen to enable IND in 2016
• Disclosure of new orphan products and/or clinical indications for existing products • Business development and partnering activities © ProMetic Life Sciences Inc 2016
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ProMetic Therapeutics ‐ Update
The Biology of Healing We are the company that can effectively address the entire healing process in a groundbreaking way using both small molecule drugs and plasma protein therapies. We are continuously discovering new innovations to regulate the cycle of healing. We do it, not because we have to, but because we are compelled to. It’s at the heart of our culture to provide a pathway to hope.
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PBI‐4050 ‐ A Novel First‐in‐Class Multi Organ Anti‐Fibrotic Clinical Drug Candidate Preclinical data demonstrating reduction of fibrosis in the lungs, kidneys, heart, and liver Pancreas
Lungs
Heart
Liver
Skin
Kidneys
Non‐treated
Non‐treated
PBI‐4050 treated
PBI‐4050 treated
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PBI‐4050, a Novel First‐in‐Class Anti‐Diabetic and Anti‐Fibrotic Compound, Protects Against Diabetic Nephropathy in Type II Diabetes (db/db eNOS‐/‐ mouse model) db/db eNOS knockout Mouse model: Dramatic albuminuria, Glomerular filtration Rate , Serum Creatinine and Hypertension (vs. db/db)
Albumin/Creatinine Ratio
Masson’s Trichrome
Collagen I
Collagen IV
Nitrotyrosine
α‐SMA
F4/80
LC3A
Oxidative Stress
Myofibroblasts
Macrophages
Autophagy
Early PBI‐4050
Vehicle
H&E
Surviving Animal (Number)
Glomerular filtration Rate
Ming‐Zhi Zhang and Raymond C. Harris Vanderbilt University School of Medicine, Nashville, Tn
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PBI‐4050 Restores Pancreatic Function in db/db eNOS‐/‐ mice Late treatment restores pancreas function and insulin plasma level to that seen at 8 weeks of age . Untreated Mice Plasma Insulin Levels (ng/ml)
Early Treated Mice (8 to 20 weeks) Plasma Insulin Levels (ng/ml)
Plasma insulin levels decrease gradually
Early treatment prevents the decline of plasma insulin concentration.
*p 8%
Lungs
Heart
Liver
Kidneys
↓ Resistin (p = 0.01) ↓ Pentraxin‐3 (p = 0.01) ↓ Lep n (p = 0.06)
↓ IL‐18 (p = 0.05)
Biomarkers elevated in patients with Metabolic Syndrome and correlated with High risk of cardiovascular events
Biomarker elevated in patients with Metabolic Syndrome and correlated with Kidney Injury
Skin
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Scleroderma: Additional Indication for PBI‐4050 PBI‐4050 Significantly Reduces Fibrosis in Scleroderma Mice
Normal Mice
Scleroderma Mice treated with PBI‐4050
Scleroderma Mice
Skin
Fibrosis formation in the skin of Scleroderma Mice Treatment with PBI‐4050 totally blocked the formation of fibrosis in the Scleroderma Mice Sirius Red staining: Transdermal cut x 25. Ming‐Zhi Zhang and Raymond C. Harris Vanderbilt University School of Medicine, Nashville, TN
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Scleroderma: Additional Indication for PBI‐4050 Diffuse Scleroderma Involves More Organs – Pulmonary Hypertension Dramatically Impacts Survival
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PBI‐4050 – Phase 2 Trial in Alström Patients in the UK (Multi‐Organ Fibrosis & Type 2 Diabetes) On‐going Patients Enrolment Alström Syndrome is a rare genetic disease that affects many parts of the body. It is named for a Swedish doctor, Carl‐Henry Alström, who first described it in 1959. Alström Syndrome is caused by a mutations in a gene, called ALMS1. Many of the signs and symptoms of this condition begin in infancy or early childhood, although some appear later in life. Alström syndrome is characterized by : • a progressive loss of vision and hearing, • a form of heart disease that enlarges and weakens the heart muscle (dilated cardiomyopathy / cardiac fibrosis), • Truncal obesity, Type 2 diabetes, • Liver fibrosis • Kidney fibrosis Some individuals with Alström syndrome have a skin condition called acanthosis nigricans, which causes the skin in body folds and creases to become thick, dark, and velvety. The signs and symptoms of Alström syndrome vary in severity, and not all affected individuals have all of the characteristic features of the disorder.
Pulmonary fibrosis
Cardiomyopathy / Cardiac fibrosis
Alström Syndrome kidney Fibrosis Acanthosis nigricans
Type 2 Diabetes Hyperinsulinemia Insulin resistance
Liver fibrosis
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PBI‐4050 Clinical Program Designed to Leverage Preclinical Data and Pharmacological Activity in Patients with Metabolic Syndrome & Type 2 Diabetes
Metabolic Syndrome & Type 2 diabetes
Alström Syndrome (Multi‐organ fibrosis & T2 diabetes)
Scleroderma (systemic – diffuse is orphan indication)
Cystic Fibrosis (CF & Related Diabetes)
Chronic Kidney Disease (CKD) (CKD associated with T2 diabetes)
Idiopathic Pulmonary Fibrosis (Orphan Drug Designation USA & EU) 36
ProMetic’s Therapeutics Pipeline Therapeutics
Research
Preclin/Scale‐up
Phase 1
Phase 2
Phase 3
BLA/NDA
Market
PBI‐4050 Metabolic Syndrome & Type 2 Diabetes PBI‐4050 Alström (multi‐organ fibrosis & Type 2 Diabetes PBI‐4050 Scleroderma PBI‐4050 (Cystic fibrosis & Related Diabetes) PBI‐4050 Chronic kidney disease & Type 2 Diabetes PBI‐4050 Idiopathic pulmonary fibrosis Plasminogen Congenital plasminogen deficiency Plasminogen Wound healing IVIG Primary immune deficiency (PID) AAT Hereditary alpha 1 antitrypsin deficiency C1‐ INH Hereditary angioedema Small molecules Rx Plasma-derived Rx
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ProMetic’s Therapeutics Pipeline Therapeutics
Research
Status Preclin/Scale‐up
Phase I
Next Milestones Phase II Phase III
BLA/NDA
Market
PBI‐4050 Metabolic Syndrome & Type 2 Diabetes
Continue to monitor patients enrolled Biomarkers ‐ analysis
Initiate a placebo controlled clinical trial in Q2 2016
PBI‐4050 Alström (multi‐organ fibrosis & Type 2 Diabetes
Patients enrolment
Preliminary Readouts
PBI‐4050 Scleroderma
Clinical trial design
CTA clearance, Initiation of placebo controlled clinical trial in H2 2016
PBI‐4050 (Cystic fibrosis & Related Diabetes)
Preparation for CTA filing
CTA clearance, Initiation of placebo controlled clinical trial in Q2 2016
PBI‐4050 Chronic kidney disease & Type 2 Diabetes
Preparation for IND filing
IND clearance, Initiation of a placebo controlled clinical trial in H2 2016
PBI‐4050 Idiopathic pulmonary fibrosis
Continue to monitor patients enrolled Biomarkers ‐ analysis
Preliminary Readouts from the open label study IND clearance, Initiation of a placebo controlled clinical trial in H2 2016
Plasminogen Congenital plasminogen deficiency
Phase 2‐3 initiated Patients enrolment
Completion of patients enrolment, completion of study Filing of BLA
Plasminogen Wound healing
Clinical trial design
CTA clearance, Initiation of the clinical trial in H2 2016
IVIG Primary immune deficiency (PID)
Phase 1‐3 initiated Patients enrolment
Completion of patients enrolment (adult cohort) in Q4 2016
AAT Hereditary alpha 1 antitrypsin deficiency
Process scale up & GMP runs
IND clearance, Initiation of clinical trial in H2 2016
C1‐ INH Hereditary angioedema
Process scale up & GMP runs
IND clearance, Initiation of clinical trial in H2 2016 Small molecules Rx Plasma-derived Rx
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2016 ‐ Outlook Clinical trial milestones Plasminogen Study completion enabling BLA filing IVIG completion of enrolment enabling predictable BLA filing Clinical results (plasminogen & PBI‐4050)
Regulatory milestones Expansion of clinical trials in Europe New indications for PBI‐4050 and Plasminogen Disclosure of orphan indications for IAIP Anticipated New Orphan Drug Designations for lead drug candidates
Product pipeline growth Advancement of AAT, C1‐INH, Fg and IAIP toward the clinical stage Advancement of PBI‐4050 follow‐ons toward the clinical stage
Partnering activities for both plasma‐derived and small molecule drug candidates Corporate infrastructure Marketing organization for the launch of plasminogen in the USA cGMP Manufacturing for commercial launch and support of product pipeline development
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Q & A
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