Eligen® B12 – Human Clinical Results

Michael V. Novinski President and Chief Executive Officer July 29, 2008

Safe Harbor Safe Harbor Statement Regarding Forward-Looking Statements The statements in this presentation and oral statements made by representatives of Emisphere relating to matters that are not historical facts (including without limitation those regarding potential third party collaborations, future performance or financial results, the timing or potential outcomes of research collaborations or clinical trials, any market that might develop for any of Emisphere's product candidates and the sufficiency of Emisphere's cash and other capital resources) are forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such statements involve risks and uncertainties, including, but not limited to, the likelihood that one or more potential third party collaborations may not be consummated, that actual performance or results could materially differ, that future research will prove successful, the likelihood that any product in the research pipeline will receive regulatory approval in the United States or abroad, the ability of Emisphere and/or its partners to develop, manufacture and commercialize products using Emisphere's drug delivery technology, or Emisphere's ability to fund such efforts with or without partners. Emisphere undertakes no obligation to update any of these statements. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as to the date hereof. Accordingly any forwardlooking statements should be read in conjunction with the additional risks and uncertainties detailed in Emisphere's filings with the Securities and Exchange Commission, including those factors discussed under the caption "Risk Factors" in Emisphere's Annual Report on Form 10-K for the fiscal year ended December 31, 2007, filed on March 17, 2008. 2

Agenda ƒ Introductory Remarks ƒ B12 and Emisphere ƒ B12 Clinical Data ƒ Expert Commentary ƒ Wrap-up

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Introductory Remarks

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Emisphere Objective ƒ Commercialize the Eligen® Technology • Use B12 as a possible avenue

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Why B12? ƒ Vitamin B12 is an essential vitamin, but a poorly absorbed molecule/nutrient ƒ For those who are B12 deficient or at-risk, current options are injections (painful ), or megadoses in tablet form (poorly absorbed with high uncertainty) ƒ Currently • 5 million people in the United States are taking 40 million injections annually, with 250 million injections estimated worldwide • At least an estimated 600 million tablets are purchased annually by an additional 5 million people

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B12 Program ƒ Animal studies • High dose – one species • Physiological dose – one species • Physiological dose – second species

ƒ Human Studies • High dose – absorption and rate • Lower dose – absorption and rate versus IV and commercial tablet

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Eligen® B12 – Human Clinical Trial ƒ Study conducted in 20 healthy males, with a single administration of Eligen® B12 – well tolerated with no adverse reactions ƒ Eligen® B12 formulation bypasses normal absorption process ƒ Eligen® B12 formulation demonstrates 240% improvement in bioavailability versus standard oral tablet in healthy males ƒ Absorption time with Eligen® B12 was 30 minutes, versus 6.5 hours for standard oral tablet ƒ Eligen® B12 bioavailability of 5%

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What Does This Mean? ƒ Reduces uncertainty of megadose oral therapy and oral therapy in general • Patients at-risk • Individuals concerned about levels of this essential vitamin

ƒ Reduce dependence on injections taken by millions • Improve compliance • More convenient dosage formulation

ƒ Highly effective treatment through consistently enhanced bioavailability ƒ Moving away from injections broadens application for oral therapy as a solution or approach to the problems associated with B12 supplementation 9

Eligen® B12 – Human PK Study ƒ Pharmacokinetic study conducted in 20 healthy male subjects divided into four arms • Four patients received 1mg B12 intravenously • Four patients received 10mg Eligen® B12 • Six patients received 5mg Eligen® B12 • Six patients received commercially available 5mg B12 tablet

ƒ 10mg Eligen® group served essentially as a pilot arm to determine appropriate dose for pharmacokinetic purposes ƒ Following these results, dosage reduced by 50% to a level that is being used in certain commercially available formulations ƒ Expect to be able to reduce dose further based on the data received and the linear relationship between the two Eligen® groups 10

Eligen® B12 – Human Clinical Data ƒ Mean B12 peak blood levels were more than 10 times higher for the Eligen® B12 formulation than the 5mg commercial tablet • 12847 pg/mL and 1239 pg/mL, respectively

ƒ Time to reach peak concentration reduced by more than 90%, where mean Tmax was 0.5 hours for the 5mg Eligen® B12 and 6.8 hours for the commercial 5mg dose ƒ Mean AUC (24h) values were 54609 hr* pg/mL for Eligen® B12 and 23165 hr* pg/mL for the commercial 5mg product

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Eligen® B12 – Mean PK Data

Treatment 5 mg B12 Commercial Formulation 5 mg B12 Eligen® Formulation

Cmax

Tmax

AUC24

(pg/mL)

(hr)

(hr* pg/mL)

1239±450

6.8±3.2

23165±8382

12847±6613*

0.5±0.2 *

54609±16405 *

*p