Download 2nd Quarter Conference Call

Eligen® B12 – Human Clinical Results
Michael V. Novinski
President and Chief Executive Officer
July 29, 2008
Safe Harbor
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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
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statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act
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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
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not to place undue reliance on these forward-looking statements, which speak only as to the date hereof.
Accordingly any forward-looking 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.
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Agenda
 Introductory Remarks
 B12 and Emisphere
 B12 Clinical Data
 Expert Commentary
 Wrap-up
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Introductory Remarks
4
Emisphere Objective
 Commercialize the Eligen® Technology
• Use B12 as a possible avenue
5
Why B12?
 Vitamin B12 is an essential vitamin, but a poorly absorbed
molecule/nutrient
 For those who are B12 deficient or at-risk, current options
are injections (painful ), or megadoses in tablet form
(poorly absorbed with high uncertainty)
 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
 Animal studies
• High dose – one species
• Physiological dose – one species
• Physiological dose – second species
 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
 Study conducted in 20 healthy males, with a single
administration of Eligen® B12 – well tolerated with no
adverse reactions
 Eligen® B12 formulation bypasses normal absorption
process
 Eligen® B12 formulation demonstrates 240% improvement
in bioavailability versus standard oral tablet in healthy
males
 Absorption time with Eligen® B12 was 30 minutes, versus
6.5 hours for standard oral tablet
 Eligen® B12 bioavailability of 5%
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What Does This Mean?
 Reduces uncertainty of megadose oral therapy and oral therapy in
general
• Patients at-risk
• Individuals concerned about levels of this essential vitamin
 Reduce dependence on injections taken by millions
• Improve compliance
• More convenient dosage formulation
 Highly effective treatment through consistently enhanced
bioavailability
 Moving away from injections broadens application for oral therapy
as a solution or approach to the problems associated with B12
supplementation
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Eligen® B12 – Human PK Study
 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
 10mg Eligen® group served essentially as a pilot arm to determine
appropriate dose for pharmacokinetic purposes
 Following these results, dosage reduced by 50% to a level that is
being used in certain commercially available formulations
 Expect to be able to reduce dose further based on the data received
and the linear relationship between the two Eligen® groups
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Eligen® B12 – Human Clinical Data
 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
 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
 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<0.05, t-Test
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Eligen® B12 – Human Clinical Data
Serum Cyanocobalamin Concentration (pg/mL)
Mean (± S.D.) Serum B12 Concentrations Concentrations in Healthy Male Subjects
1000000
5 mg Eligen B12
5 mg Commerical B12
10 mg Eligen B12
100000
1 mg IV Commerical B12
10000
1000
100
0
2
4
6
8
10
12
14
16
18
20
22
24
Time (hr)
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Eligen® B12 – Human Clinical Data
Mean Serum B12 Concentrations in Healthy Male Subjects
20100
Serum Concentration (pg/mL)
18100
mg Commercial B12 5
mg Eligen B12 5
16100
14100
12100
10100
8100
6100
4100
2100
100
0
2
4
6
8
10
12
14
16
18
20
22
24
Time (hr)
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Eligen® B12 – Human Clinical Data
Mean Cmax Values Following Oral B12 Treatments
45000
40000
10 mg Eligen B12
5 mg Eligen B12
5 mg commercial B12
30000
25000
20000
15000
10000
5000
0
Mean AUC Values Following Oral B12 Treatments
225000
AUC (hr*pg/mL)
Cmax (pg/mL)
35000
200000
10 mg Eligen B12
175000
5 mg Eligen B12
5 mg commecial B12
150000
125000
100000
75000
50000
25000
0
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Eligen® B12 – Clinical Update
Conclusions

Eligen® significantly enhances B12 delivery in humans

Eligen® utilized a new mechanism of B12 delivery

B12 animal studies proved highly predictive of the observed
human response
Next steps

Clinical investigation of Eligen® B12 pharmacokinetics at
lower doses in target populations (Q3/2008)

Clinical investigation of Eligen® B12 therapeutic efficacy in
target populations (Q4/2008)
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Eligen® B12 – Why It’s Important for Patients
 This presents a potential paradigm shift in the way we
approach B12 deficiency and at-risk people
 Emisphere’s carriers reduce the potential uncertainty
associated with oral megadoses of B12
 New formulation may prevent the substantial number of
B12 injections given worldwide
 This may be an effective recourse for people who are at-risk
of B12 deficiency, are already identified as B12 deficient,
and for people who are concerned about this important
vitamin
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Eligen® B12 – Commercial Application

Food fortification

Supplementation for those individuals concerned about
B12

Supplementation for the at-risk populations

Supplementation for B12 deficient segments
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Eligen® B12 – Commercial Application

Clinical strategy to support all segments

Regulatory strategy to allow access to all segments

•
NDI
•
GRAS
Evaluate each segment to maximize the potential valuation
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Eligen® B12 – Summary
 All research indicates that Eligen® B12 presents a
significant improvement to help approach the problem of
B12 supplementation, regardless of level of
supplementation that may be required
 Emisphere is committed to commercializing Eligen® B12
as an opportunity for all defined segments
 These data only further demonstrate the value of the
Eligen® Technology as a platform to improve the
bioavailability for difficult to absorb molecules; including,
but not limited to, other essential vitamins and minerals,
prescription drug products, and even other possible
molecules
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Q&A
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