R&D Day June 18, 2008 -...

Need, Commitment, Expertise

R&D Day June 18, 2008

Alan W. Dunton, M.D.President and CEO

Safe Harbor StatementSafe Harbor Statement

Except for the historical information contained herein, the matters discussed are forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties, such as the progress of clinical development of bevirimat and the timing of results of clinical trials, the execution of the Company's financing plans, the timely availability of new products, market acceptance of the Company'sproducts, the impacts of competitive products and pricing, government regulation of the Company's products, the Company's ability to complete product development collaborations and other strategic transactions and other risks and uncertainties set forth in the Company's filings with the Securities and Exchange Commission. These risks and uncertainties could cause actual results to differ materially from any forward-looking statements made herein.

2

Advancing a pipeline of novel HIV drug candidatesAdvancing a pipeline of novel HIV drug candidates

Steady stream of near-term milestones

Highly experienced team in place

– Track record of successfully developing and commercializing drugs

Bevirimat

HIV Fusion Inhibitor

Second-generation HIV Maturation Inhibitor

Research Preclinical Phase 1 Phase 2 Phase 3

Third-generation HIV Maturation Inhibitor

3

Experienced team leading Panacos forwardExperienced team leading Panacos forwardAlan W. Dunton, M.D.President & CEO

Johnson & Johnson; Roche; Ciba-Geigy; Metaphore

Graham P. Allaway, Ph.D. Chief Operating Officer

Progenics Pharm.; Manchester Biotech; NIH; Panacos Co-founder

Jane P. HendersonChief Financial and Business Officer

HSBC; CIBC; Lehman Brothers; Citigroup

Scott McCallister, M.D. Chief Medical Officer

Bristol-Myers Squibb; BoehringerIngelheim

Frederick Schmid, D.V.M., M.B.A.SVP, Commercial Operations & Business Development Roche; GlaxoSmithKline

David E. Martin, Pharm.D., M.B.A.SVP, Drug Development

DuPont Pharma; PharmaResearch; SmithKline Beecham

Tom Lategan, D.Phil.VP, Regulatory Affairs

Actelion Pharmaceuticals; The Medicines Company; Roche

John D. Richards, D.Phil. VP, Manufacturing Operations

The Medicines Company; Immulogic; Zeneca PLC

4

Board of Directors committed to Panacos’successBoard of Directors committed to Panacos’success

Alan W. Dunton, M.D.Johnson & Johnson; Roche; Ciba-Geigy; Metaphore; Director: Adams Respiratory, MediciNova, Targacept

President & CEO, Director

Jeremy Hayward-SurryFormer President, Pall Corporation

Chairman of the Board

Laurent Fischer, M.D.CEO, Ocera Therapeutics; Dupont Pharma; Roche; Director, AIDS Healthcare Foundation

Director

R. John Fletcher, M.B.A. CEO, Fletcher Spaght; BCG; Director, AutoImmune, Spectranetics, Axcelis

Director

Irwin LernerFormer Chairman & CEO, Roche Inc.; Director & Chairman, Medarex; Director, Covance, Nektar

Director

Joseph M. LimberCEO, Prometheus Labs; ACLARA; Syntex; Ciba-Geigy; SEQUUS

Director

Robert G. SavagePharmacia; Johnson & Johnson; Director, Noven Pharma; Lead Director, The Medicines Company; Chairman, EpiCept

Director

5

Our goals for hosting this R&D DayOur goals for hosting this R&D Day

Provide detailed insight into Panacos’ pipeline– Bevirimat:

• Gag polymorphisms and bevirimat efficacy• Formulation status• Next steps for development program

– Maturation inhibitors next generations: strategy– Small molecule oral fusion inhibitors: significance

Articulate the significant market potential of bevirimat– Continued need for novel mechanism HIV drugs

Outline the short-term value-creating events for PanacosIntroduce you to the Panacos team – Express our commitment– Give confidence in our expertise

6

Key highlights from today’s meetingKey highlights from today’s meeting

Changes in patient care benefit bevirimat

Study 203 (prospective extension) results confirm predictors of response

Identification of Gag polymorphisms and their impact on bevirimat efficacy and market potential – An attractive market opportunity

– Physicians treat patients based upon viral profiling (genotyping)

– Genotyping is not expected to have a negative impact on a successful bevirimat launch

Significant upside in oral fusion program

Panacos is on the road to success

7

Our Key Opinion LeadersOur Key Opinion Leaders

Calvin J. Cohen, MD, MScDirector, Community Research, Community Research Initiative of New England Director, Research, Harvard Vanguard Medical Associates

Joseph J. Eron, MDProfessor, Division of Infectious Diseases Principal Investigator, AIDS Clinical Trials Unit Associate Director, General Clinical Research Center University Of North Carolina at Chapel Hill AIDS Clinical Trials Unit, Department of Medicine , Division of Infectious Diseases

Richard Harrigan, PhDDirector, Research Labs, BC Centre for Excellence in HIV/AIDS Vancouver BCAssociate Professor, Division of AIDS, University of British Columbia

8

HIV and AIDSThe Shifting Treatment Landscape

Calvin Cohen, MDCommunity Research Initiative New England

Harvard Medical SchoolBoston, MA

Topics

HIV: epidemiology of the pandemic

2008 treatment options

Limitations of treatment

Future of HIV treatment 2010 and beyond

Estimated global number of people living with HIV: 1990–2007

This bar indicates the rangeYear

1990 1995 1998

Mill

ions

1993 1996 20042000 2002 2006

0

10

20

30

40

1991 19991992 1994 1997 20052001 2003 2007

2007 AIDS epidemic update figure

http://www.unaids.org/en/

http://www.who.int/en/

The number of men and women living with AIDS continues to increase

The AIDS epidemic in the US disproportionately affects people of color

The HIV-1 replication cycle

Entry Inhibitors

RT Inhibitors

IntegraseInhibitors

Protease Inhibitors

Maturation Inhibitors

Fusion Inhibitors

Entry Inhibitors

Integrase Inhibitors

Protease InhibitorsNRTIs

• Zidovudine

NNRTIs

Available antiretroviral drugs 1990

Fusion Inhibitors

Entry Inhibitors


Protease Inhibitors

• Saquinavir

NRTIs• Didanosine

• Lamivudine

• Stavudine

• Zalcitabine

• Zidovudine

NNRTIs

• Nevirapine


Fusion Inhibitors

Entry Inhibitors


Protease Inhibitors• Amprenavir

• Indinavir

• Lopinavir

• Nelfinavir

• Ritonavir

• Saquinavir

NRTIs• Abacavir

• Didanosine

• Lamivudine

• Stavudine

• Zalcitabine

• Zidovudine

NNRTIs• Delavirdine

• Efavirenz

• Nevirapine


Fusion Inhibitors

• Enfuvirtide

Entry Inhibitors

• Maraviroc


• Raltegravir


• None

Protease Inhibitors• Amprenavir

• Atazanavir

• Darunavir

• Fos-Amprenavir

• Indinavir

• Lopinavir

• Nelfinavir

• Ritonavir

• Saquinavir

• Tipranavir

NRTIs• Abacavir

• Didanosine

• Emtricitabine

• Lamivudine

• Stavudine

• Tenofovir

• Zalcitabine

• Zidovudine


• Efavirenz

• Nevirapine

• Etravirine


CD4 cell count and plasma HIV-1 RNA level—the impact of HAART

150

100

50

0

-50

-100

-150

-200

CD

4+C

ell C

ount

Plasma H

IV-1 RN

A

1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997

Years MonotherapyDouble RTI CombinationsHighly Active Antiretroviral Therapy

Rates of virologic failure in patients starting triple therapy (resistance)

J. Hopkins: all patients starting 3-drug HAART 1996-2002 (n=1255)

% with <400 copies/mLat 6 mos.:- 1996 43.8- 1997-8 54.2- 1999-2000 70.3- 2001-2 72.4

Moore RD, et al, J AIDS 2005;39:195-8; Lampe F, et al. Arch Int Med 2006;166:521-8.

Virologic failure from 5 observational cohorts; % > 500 copies (n=4,143)

(p<0.001 for trend)

25%30%31%

34%39%

42%40%

0

10

20

30

40

50

1996 1997 1998 1999 2000 2001 2002

Patie

nts

(%)

2008 DHHS guidelines When to start: a shift to earlier treatment?

Available at: http://aidsinfo.nih.gov/Default.aspx. Revision January 29, 2008.

Clinical Conditions and/or CD4 Count Recommendations

CD4 count <350 cells/mm3

History of AIDS-defining IllnessPregnant womenPersons with HIV-associated nephropathyPersons coinfected with HBV, when HBV treatment is indicated

Initiate ARV Therapy

Patients with CD4 > 350 cells/mm3Optimal time to initiate ARV therapy not well defined

Consider patient scenarios and comorbidities

ARV-naïve treatment (“gold standard”) TDF / 3TC / EFV long-term follow-up

▬N=86; Longer term extension in Latin America

% HIV RNA <50 c/mL through Week 192

Enejosa J, et al. 10th EACS; November 17–20, 2005; Dublin, Ireland, Abstract PE7.3/13.

% P

atie

nts

with

H

IV R

NA

<50

c/m

L

0

20

40

60

80

100

0 24 48 72 96 120 144 168 192

ITT M = F

ITT M = Excluded

92%87%

Week

Gilead 903E

DHHS 2008 guidelinesRecommended regimens for treatment-naïve patients

Select 1 Component From Column A and 1 From Column B

Column A Column B

NNRTI or PI NRTIs

Preferred componentsEFV ATV/r

FPV/r (BID*)LPV/r (BID*)

TDF/FTC -or-

ABC/3TC

[HLA-B*5701 negative only]

Alternative components

NVP ATV FPVFPV/r (QD*)

LPV/r (QD*)SQV/r

ZDV/3TC

-or-

DDI + (FTC or 3TC)

Available at: http://aidsinfo.nih.gov/Default.aspx. Revision January 29, 2008.

*BID = Twice daily; QD = Once daily

Treatment options: key points

23 individual drug options and 6 fixed dose combinations are approved in the US—and 2 novel MOA drugs approved in last 18 months

Due to ongoing resistance and tolerability challenges, new drugs (also novel MOA) continue to be needed

Local and international therapeutic guidelines have shifted to recommend earlier start of treatment

Long-term gold standard treatment regimen for naïve or experienced patients are 2 NRTIs + NNRTI or PI (HAART)– New treatment paradigm possible?

0

0.5

1

1.50 2 4 8 12 16 20 24

Weeks

Med

ian

decr

ease

H

IVR

NA

log

copi

es/m

L

lamivudine monotherapy

Kuritzkes D, et al. AIDS. 1996;10:975-981.

(n = 14)

Resistance to individual ARV drugs can occur quickly

- Lamivudine (3TC) monotherapy linked to resistance and virologicfailure within 2 weeks

- Other NRTIs also maintain M184V (e.g. FTC)

- Single dose nevirapine(primarily used for MTCT) also leads to rapid resistance development

Virologic activity and resistance: with NRTIs(and some NNRTIs) this happens rapidly

Raltegravir: the development of resistance

Hazuda DJ, et al. 16th International HIV Drug Resistance Workshop, Barbados 2007

-100 0 100 200 300 400 500 600 700Days in study

22.5

33.5

44.5

55.5

6

Log

[vRN

A]

400cp/ml

Patient B

N155HN155H, L74L/M, T97A

+DVR

-100 0 100 200 300 400 500 600 700Days in study

22.5

33.5

44.5

55.5

6

Log

[vRN

A]

400cp/ml

Patient C

N155H

+ ENF, DRV/r

-100 0 100 200 300 400 500 600 700Days in study

22.5

33.5

44.5

55.5

6

Log

[vRN

A]

400cp/ml

Patient A

Q148HG140SE138E/K

N155H

-100 0 100 200 300 400 500 600 700Days in study

22.5

33.5

44.5

55.5

6

Log

[vRN

A]

400cp/ml

Patient DQ148H, G140S (pop)

G140G/S, Q148Q/H, N155N/H (pop)Q148H and N155H unlinked (clonal)

Short- and long-term safety and tolerability

Short-term safety/tolerability challenges

- Diarrhea, nausea/vomiting: most PIs - Hypersensitivity reactions: abacavir, nevirapine- Elevated bilirubin (+/- jaundice): atazanavir- Elevated liver function tests: NNRTIs, PIs

Long-term safety/tolerability challenges

- Lipodystrophy, body habitus changes: some PIs, some NRTIs- Increased MI risk: some PIs, some NRTIs- Reduced kidney function: tenofovir- Peripheral neuropathy: stavudine- Anemia, leukopenia: zidovudine

Recent use of ddI or ABC increased risk of MI: a limitation of chronic NRTI use?

* Recent = still using or stopped within last 6 months

Stratified by recent* abacavir use

Overall Low Moderate High Not known

Observed Rates of MI for Recent* Use of Abacavir by Predicted 10-year Coronary Heart Disease (CHD) Risk

D:A:D Study

35302520151050

Rat

e (p

er 1

000

PY

Predicted 10-year CHD risk

No recent abacavirRecent abacavir

16

32

D:A:D Study Group. Lancet. April 2 2008, Epub.

Limitations of treatment: key points

Patients need convenient, easy-to-tolerate regimens that have persistent long-term virologic suppression

All treatment regimens require lifelong adherence

Even the most potent drugs must be combined with other active agents for optimal virologic suppression

Resistance development occurs at different rates for each drug

All drugs have at least some relevant side effects: - Some just a nuisance, some may be significant

Newest ARV class: Raltegravir vs. EFV + TDF/3TC HIV RNA <50 copies/mL [NC=Failure]

Markowitz M, et al. IAS 2007; Abstract TUAB104.

0 2 4 8 12 16 24 32 40 48Week

0

20

40

60

80

100

Per

cent

of P

atie

nts

with

HIV

RN

A <5

0 co

pies

/mL

Raltegravir 100 mg b.i.d. (n=39)




Efavirenz 600 mg q.d. (n=38)

Speed to <50 copies/mL for EFV slower than RAL

Raltegravir: the W48 virologic benefit is impacted by the use of specific ARVs in OBR

0 20 40 60 80 100

34

68

57

47

20

64

89

80

69

60

443

44

45

75

191

228

22

23

47

90

Enfuvirtide Darunavir

+

+

+

+

-

-

+ : First use in OBT- : Not used in OBT

Virologic failures carried forward.

TotalSubgroup

-

-

Raltegravir + OBT Placebo + OBT

Cooper D and Steigbigel R, et al. 15th CROI; Boston, MA (2008); Absts. 788 and 789.

Add >2 (preferably 3) fully active agents to an optimized background regimen

Consider RTV-boosted PIs, new MOA drug, and optimized background

Don’t add just 1 active drug to a new regimen as resistance is likely to develop quickly

For patients with extensive prior treatment and drug resistance:- Goal: re-suppress HIV RNA to <50 copies/mL- If complete suppression not possible, preserve immune function and

prevent progression

1/08

2008 DHHS guidelines for experienced patients: general principles

Fusion Inhibitor• Enfuvirtide

CCR5 Antagonists• Maraviroc

• Vicriviroc

IntegraseInhibitors

• Raltegravir

• Elvitegravir

Maturation Inhibitors• Bevirimat

PIs - Protease Inhibitors

• Atazanavir

• Darunavir

• Fos-amprenavir

• Indinavir

• Lopinavir

• Nelfinavir

• Ritonavir

• Saquinavir

• Tipranavir

NRTIs• Abacavir

• Didanosine

• Emtricitabine

• Lamivudine

• Stavudine

• Tenofovir

• Zidovudine

• Apricitabine


• Efavirenz

• Nevirapine

• Etravirine

• Rilpivirine

Increasing ARV options: five late-stage clinical drug candidates, four in existing classes, one novel MOA

*In Phase III development: the final stage of evaluation prior to possible FDA drug approval

The future of treatment: key points

Nearly all new agents in development will not be oral or are from existing classes

Despite great advances in HIV treatment, the population of patients with resistance or intolerance to existing treatment options increases, new drugs continue to be needed

Long term treatment may be linked to long term toxicities

In 2010 and beyond:- More people around the world will be on treatment than ever before- Resistance to the newest classes of approved drugs may increase- New classes of drugs will be important components of regimens for

experienced patients (and possibly naïve patients)

HIV and AIDSThe Shifting Treatment Landscape

Calvin Cohen, MDCommunity Research Initiative New England

Harvard Medical SchoolBoston, MA

Bevirimat Bevirimat Novel AntiNovel Anti--HIV HIV

Maturation InhibitorMaturation Inhibitor

36

Joseph Eron, MDUniversity of North Carolina

Bevirimat Clinical Data TopicsBevirimat Clinical Data Topics

Continued need for new oral anti-HIV agents with novel mechanism of action to partner with existing potent drugs

Study 201: 10 days monotherapy in naïve and experienced patients

Study 203: 14 days functional monotherapy in highly experienced patients

Predictors of bevirimat treatment response– Retrospective analysis discovers importance of Gag polymorphisms

– Prospective trial confirms Gag polymorphisms as predictors

Genotype is a simple, common assay to test of Gag sequence

Clinical resistance data 37

Bevirimat Targets Gag at the CA-SP1 Cleavage SiteBevirimat Targets Gag at the CA-SP1 Cleavage Site

38

P6

GAG polyprotein

CA MA NC

P6 CA MA NC

protease

protease

Untreated

BEVIRIMATbudding HIV particle

Treated

SP-1

CD4cell

CA‐SP1 cleavage site between Gag codons 363‐364

Bevirimat Study 201:10D Monotherapy in Naïve/Experienced PatientsBevirimat Study 201:10D Monotherapy in Naïve/Experienced Patients

o Tested doses up to 200mg

oMean VL reduction ~1 log through 10 days (top dose only)

o Target blood level for optimal response not yet established

o Placebo‐like safety profile through 10 days

o Based on these data, modeling suggested Emax90 was 360mg QD

39

-1.2

-1.0

-0.8

-0.6

-0.4

-0.2

0.0

0.2

0.4

0 5 10 15 20 25

Placebo25 mg50 mg100 mg200 mg

1/3 ARV‐experienced; 2/3 ARV‐naïve

QD for 10 days

Liquid bevirimat solution

Primary endpoint: VL reduction at D11

Treatment Day

Viral Load Re

duction

Bevirimat Study 203 DesignBevirimat Study 203 Design

Bevirimat Study 203 DemographicsBevirimat Study 203 Demographics

41

BEVIRIMAT-TREATED PATIENTS

PLACEBO-TREATED PATIENTS

N 46 13

Age 48.0 (27-70) 47.1 (34-63)

Gender 45M, 1F 12M, 1F

Symptomatic HIV or AIDS

74% 67%

Mean Baseline CD4 (copies/mm3)

277 (30-562) 393 (172-859)

Baseline Viral Load (log10 copies/mL)

4.2 (2.7-5.3) 4.1 (3.7-5.2)

Bevirimat Study 203 Safety Data:Adverse Events (all grades)Bevirimat Study 203 Safety Data:Adverse Events (all grades)

BEVIRIMAT-TREATED PLACEBO-TREATED# % # %

N 46 13TOTAL WITH ANY ADVERSE EVENTS

32 70% 10 77%

GI-RELATEDDIARRHEA 10 22% 5 39%NAUSEA 9 20% 4 31%FLATULENCE 4 9% 1 8%VOMITING 3 7% 2 15%

CNS-RELATEDHEADACHE 9 20% 3 23%DIZZINESS 3 7% 1 8%ABNORMAL DREAMS 5 11% 0 0%

RASH 3 7% 3 23%42

Bevirimat Study 203 Safety Data:Lab Abnormalities (grades 2-4)Bevirimat Study 203 Safety Data:Lab Abnormalities (grades 2-4)

43

Patients with baseline abnormalities excluded unless worsened on treatment.

‐2‐1.8‐1.6‐1.4‐1.2‐1

‐0.8‐0.6‐0.4‐0.2

00.20.4

0 10 20 30 40 50 60 70 80 90 100 110 120

Bevirimat Trough Level (ug/mL)

Viral Loa

d Red

uction

(lo

g copies/m

L)

44

RespondersNon-responders

Bevirimat Study 203: Viral Load Reduction and Trough Data Clearly Demonstrate 2 Patient GroupsBevirimat Study 203: Viral Load Reduction and Trough Data Clearly Demonstrate 2 Patient Groups

NON‐RESPONDERS

RESPONDERS

Bevirimat Study 203: Bi-Modal Efficacy DistributionBevirimat Study 203: Bi-Modal Efficacy Distribution

Responders (definition: > 0.5 log viral load reduction)– N=20– 19 had bevirimat plasma level > 20ug/mL– Mean 1.26 log VLR at Day 14

Non-responders (definition: < 0.5 log viral load reduction)– N=24– 19 had bevirimat plasma level > 20µg/mL– Mean 0.05 log VLR at Day 14

While responders had clinically meaningful VL changes, particularly for such heavily experienced patients,

why don’t all patients respond?45

Bevirimat Study 203: Responder Non-Responder ComparisonBevirimat Study 203: Responder Non-Responder Comparison

Non-Responders Responders Sig.

N 24 20 --

Mean Baseline VL (log copies/mL)

4.23 3.99 NS

Mean Day 15 VLR -0.05 -1.26 <0.0001

Mean Baseline CD4 (copies/mm3)

233 342 <0.01

Mean No. Primary PR mutations

3.7 2.8 NS

Mean No. Gag Polymorphisms (positions 320-400)

7.3 5.9 NS

369 21% 5%

370 54% 15%

371 33% 20%46

Optimal Bevirimat Treatment Response Requires:Optimal Bevirimat Treatment Response Requires:

Bevirimat plasma trough levels > 20 µg/mL– Achieved in all patients in Study 203 at liquid doses ≥ 250 mg

– Twice daily tablet dose now being studied

and

The baseline Gag genotype sequence must be free of changes at positions 369, 370 or 371– Gag amino acid sequence tested easily with a genotype: the most

commonly used resistance test

Registration studies likely will focus on this Phase 3 Profile patient population

47

Bevirimat Study 203: Overall Viral Load Reduction DataBevirimat Study 203: Overall Viral Load Reduction Data

‐0.6

‐1.26

All Patients Phase 3 Profile Patients

1344

48

% patients with >0.5 log VLR45% 92%

All Patients on Bevirimat: ‐‐With/without 369‐371 polymorphisms‐‐Any trough level

Phase 3 Profile Patients on Bevirimat:‐‐No 369‐371 polymorphisms‐‐All with trough level >20 µg/mL

Bevirimat Study 203: VLR Reduced in Patients with Gag Polymorphisms at 369, 370 or 371Bevirimat Study 203: VLR Reduced in Patients with Gag Polymorphisms at 369, 370 or 371

‐0.16‐0.24

‐0.32

‐1.08

‐1.26

369 370 371 No 369‐371 No PM & Cmin>20

49

7 patients had 2 Gag polymorphisms (none had 3):‐‐3 with 369 + 370: mean VLR: ‐0.31 log‐‐4 with 370 + 371: mean VLR: +0.04 log

131712166

Bevirimat Study 203:Specific Amino Acid Changes at 369, 370 or 371Bevirimat Study 203:Specific Amino Acid Changes at 369, 370 or 371

50

GAG POSITION POLYMORPHISM

NUMBER HAVING (OUT OF 59 TOTAL

PATIENTS)Q369 H 9

V370 AM

DELETION

1543

T371 ASN

DELETION

4214

‐‐ Baseline Gag polymorphisms in 59 patients on either bevirimat or placebo

‐‐ 29 (49.2%) had at least one polymorphism at 369, 370 or 371

Bevirimat: Key Gag Polymorphisms at 369, 370 or 371 are Different than in vitro Selected MutationsBevirimat: Key Gag Polymorphisms at 369, 370 or 371 are Different than in vitro Selected Mutations

…G H K A R V L A E A M S Q V T N S A T I M

RED: in vitro resistance mutations1,2

GREEN: key polymorphisms3

*References:

1.Li et al. 2003, PNAS 100:13555–13560

2.Adamson et al. 2006, J. Virol. 80:10957-10971

3.Sitges abstracts

358 363 364 366 369 370 371

CA SP1

51

Gag and Protease Changes Rarely Observed During Bevirimat TreatmentGag and Protease Changes Rarely Observed During Bevirimat Treatment

Gag-related mutations or polymorphismsStudy 201 (true monotherapy)– Through 10 days of bevirimat treatment, 0 patients developed

bevirimat-related resistance mutations or polymorphisms at Gag positions 369, 370 or 371

Study 203 (functional monotherapy)– 2/46 patients on bevirimat had a resistance mutation at A364V

• 1 during extended tablet dosing (transient) likely related to non-adherence

• 1 developed A364A/V mixture; no virologic rebound occurred – 5/46 (11%) of patients on bevirimat and 1/13 (8%) on placebo

developed a new polymorphism at Gag positions 369, 370 or 371

PR-related mutationsStudy 203 (functional monotherapy)– 2 patients developed a new primary PR mutation that was not

present at baseline (both mixed populations likely present at baseline)

52

‹#›

Gag Genotype Fits into Existing Practice and Reimbursement Patterns (www.vircolab.com)

Gag Genotype Fits into Existing Practice and Reimbursement Patterns (www.vircolab.com)

Bevirimat:Prospective Trial of Gag PolymorphismsBevirimat:Prospective Trial of Gag Polymorphisms

Summary of Bevirimat Clinical DataSummary of Bevirimat Clinical Data

Mean VLR of 1.26 log through 14 days in experienced patients with no 369-371 PMs and trough >20 µg/ML– Same population likely to be studied in Phase 3

Predictors of treatment response (baseline Gag sequence) are established

Bevirimat trough level needed for response is known and achievable with both current formulations

Placebo-like safety profile through 14 days

2 ongoing studies: prospective trial to confirm key Gag polymorphisms (now complete) and controlled trial of twice daily tablets (enrolling)

55

Bevirimat Bevirimat Novel AntiNovel Anti--HIV HIV

Maturation InhibitorMaturation Inhibitor

56

Joseph Eron, MDUniversity of North Carolina

Prospective Study of Gag PolymorphismsProspective Study of Prospective Study of Gag PolymorphismsGag Polymorphisms

Scott McCallister, MDChief Medical Officer

57

Bevirimat Prospective Study of Gag PolymorphismsBevirimat Prospective Study of Gag Polymorphisms

Prospective trial design

Data– Safety– Pharmacokinetics– Viral Load Reduction– Gag Polymorphisms Present

Aggregate data (original Study 203 combined with Prospective Study)– All patients with Gag polymorphisms at 369, 370 or 371 vs.

all patients without Gag polymorphisms

Implications for Phase 3 registration studies

58

Bevirimat Prospective Study of Gag PolymorphismsBevirimat Prospective Study of Gag Polymorphisms

Bevirimat Prospective Study of Gag Polymorphisms:DemographicsBevirimat Prospective Study of Gag Polymorphisms:Demographics

60

NAÏVE PATIENTS

EXPERIENCED PATIENTSWITHOUT

POLYMORPHISMS

EXPERIENCED PATIENTS WITH

POLYMORPHISMS

N 9* 10 8

MEAN AGE (RANGE) 40.3 (25‐54) 43.2 (28‐54) 45.1 (31‐60)

GENDER (M, F) 9M 8M, 2F 7M, 1F

MEAN BASELINE CD4 (CELLS/MM3)

366 (132‐708) 380 (156‐962) 341 (190‐612)

MEAN BASELINE VIRAL LOAD (LOG10 COPIES/ML)

4.5 (4.1‐5.1) 4.4 (3.3‐5.1) 4.0 (3.1‐5.2)

*A total of 9 naïve patients completed 14 days of BVM treatment; 2 additional patients received BVM for only 2 days.

Bevirimat Prospective Study of Gag Polymorphisms:Treatment-related Adverse EventsBevirimat Prospective Study of Gag Polymorphisms:Treatment-related Adverse Events

61

NAÏVE PATIENTS


POLYMORPHISMS

EXPERIENCED PATIENTSWITH

POLYMORPHISMS

All events of mild intensity (Grade 1)

N 11 10 8

GI EVENTS

DIARRHEA 2 (18%) 6* (60%) 2 (25%)

NAUSEA 2 (18%) 1 (10%) 0 (0%)

STOMACH DISCOMFORT 0 (0%) 2 (20%) 1 (13%)

VOMITING 1 (9%) 1 (10%) 0 (0%)

CNS EVENTS

HEADACHE 0 (0%) 1 (10%) 0 (0%)

* Overall diarrhea rate for 100 bevirimat‐treated HIV+ patients = 26%

Bevirimat Prospective Study of Gag Polymorphisms:Lab Abnormalities* (> Grade 2)Bevirimat Prospective Study of Gag Polymorphisms:Lab Abnormalities* (> Grade 2)

62

* Patients with baseline abnormalities excluded, unless worsened on treatment.

NAÏVE PATIENTS


POLYMORPHISMS

EXPERIENCED PATIENTS WITH

POLYMORPHISMS

LIPIDS

TOTAL CHOLESTEROL 0 0 1 (G2)

TRIGLYCERIDES 0 0 1 (G3)

LDL 0 1 (G3) 0

HEPATIC

ALT 0 1 (G2) 0

AST 0 1 (G3) 0

PANCREAS

GLUCOSE 2 (G2) 0 1 (G2)

LIPASE 0 0 1 (G2)

HEMATOLOGY

NEUTROPENIA 0 1 (G2) 0

PLATELETS 0 1 (G2) 0

PTT 0 0 2 (G2)

Bevirimat Prospective Study of Gag Polymorphisms:PharmacokineticsBevirimat Prospective Study of Gag Polymorphisms:Pharmacokinetics

63

Bevirimat Trough Level

67

Bevirimat Prospective Study of Gag Polymorphisms:Baseline Gag Positions 369, 370 or 371Bevirimat Prospective Study of Gag Polymorphisms:Baseline Gag Positions 369, 370 or 371

9 ARV-naïve patients– 8/9 had no baseline Gag changes– 1/9 had V370M

10 ARV-experienced patients without Gag polymorphisms– 10/10 had no baseline Gag changes

8 ARV-experienced with Gag polymorphisms– 8/8 had baseline Gag changes– 3/8 had mixed populations– 1/8 had V370M– 0/8 had Q369H and 0/8 had V370A

64

Bevirimat Prospective Study:VLR in Patients With/Without Gag PolymorphismsBevirimat Prospective Study:VLR in Patients With/Without Gag Polymorphisms

PATIENTS WITH RESPONSE PREDICTORS

(NO POLYMORPHISMS AT GAG CODONS 369, 370 OR 371)

PATIENTS WITHOUT RESPONSE PREDICTORS

(ANY POLYMORPHISM AT GAG CODONS369, 370 OR 371) SIGNIFICANCE

N 18 9 ‐‐

MEAN VIRAL LOAD REDUCTION (LOG10 COPIES/ML)

‐1.13 ‐0.59 P < 0.04

65

Bevirimat Prospective StudyVLR in Naïve vs. Experienced PatientsBevirimat Prospective StudyVLR in Naïve vs. Experienced Patients

NAÏVE PATIENTS

EXPERIENCED PATIENTS WITHOUT

POLYMORPHISMS

EXPERIENCED PATIENTSWITH

POLYMORPHISMS

N 9 10 8

MEAN VIRAL LOAD REDUCTION (LOG10 COPIES/ML) ON DAY 15

‐1.04 ‐1.10 ‐0.65

66

– For the 8 naïve patients without baseline polymorphisms, mean VLR was ‐1.16 log copies/mL.

Bevirimat Prospective Study of Gag Polymorphisms:ConclusionsBevirimat Prospective Study of Gag Polymorphisms:Conclusions

Efficacy data confirm the retrospective analysis

Patients free of Gag polymorphisms at positions 369, 370 or 371 are likely to have an optimal treatment response to bevirimat

– The -1.13 VLR for patients without baseline polymorphisms was statistically significant relative to those with polymorphisms

100% of patients in this prospective study had bevirimat plasma levels above the 20 µg/mL trough threshold

Bevirimat continued to have an encouraging safety profile

67

Bevirimat Aggregate DataOriginal Study 203 Combined with Prospective TrialBevirimat Aggregate DataOriginal Study 203 Combined with Prospective Trial

ALL PATIENTSWITH NO

POLYMORPHISMS

ALL PATIENTS WITH ANY

POLYMORPHISM AT 369, 370 OR 371

All patients with available baseline Gag data and with bevirimat trough level >20 µg/mL

N 32 30

NO. PATIENTS (%) WITH > 0.5 VLR (LOG10 COPIES/ML)

28 (88%) 11 (37%)

MEAN VIRAL LOAD REDUCTION (LOG10 COPIES/ML)

‐1.16 ‐0.45

68

Bevirimat Aggregate DataPhase 3 Registration Study PlansBevirimat Aggregate DataPhase 3 Registration Study Plans

Phase 3 Registration Studies (subject to regulatory concurrence)

– All patients to be screened with genotype for Gag, RT and PR

– Patients without polymorphisms at Gag positions 369, 370 or 371 will be randomized to BVM or comparator arms

– Patients with polymorphisms who otherwise qualify will be offered BVM treatment in a separate investigative arm for 7 days

• Patients with > 0.5 VLR by Day 7 continue BVM with an optimized background regimen

• Patients with < 0.5 VLR by Day 7 discontinue BVM

69

Prospective Study of Gag PolymorphismsProspective Study of Prospective Study of Gag PolymorphismsGag Polymorphisms


70


Bevirimat Bevirimat Development ProgramDevelopment Program

Bevirimat Development ProgramPhase 2 ProgramBevirimat Development ProgramPhase 2 Program

72

Bevirimat Development ProgramPhase 2 and 3 ProgramBevirimat Development ProgramPhase 2 and 3 Program

73

Study 203 extension (prospective test of Gag)Study 203 extension (prospective test of Gag)

Objective: – Prospective assessment of Gag polymorphisms at positions 369,

370, 371 in patients with and without treatment experienceDesign:– Gag genotype tested at screening visit– Bevirimat 300mg QD (liquid formulation)– Viral load reduction on Day 14– 24 patients planned

• ARV-naïve patients• ARV-experienced patients without Gag polymorphisms• ARV-experienced patients with Gag polymorphisms

– 12 sites in U.S.Status:– Fully enrolled 15 May – Data available June 2008

74

Study 204 (trial of twice-daily tablets)Study 204 (trial of twice-daily tablets)Objective:– Study tablet formulation BID with extension phase for those with

virologic benefitDesign:– Gag genotype not used to filter patients at screening visit– Bevirimat 200 or 300mg BID (tablet formulation)– Viral load reduction on Day 14– 32 patients

• ARV-naïve patients• ARV-experienced patients

– Patients with > 0.5 log VLR by Week 2 may continue to Week 24 (beyond?)

– Multiple sites in Australia, New Zealand, Belgium, PolandStatus:– Screening began April 08 – 14-day data expected 2H08

75

Study 205 (extended duration trial with Phase 3 dose)Study 205 (extended duration trial with Phase 3 dose)

Objective: – Controlled Phase 2b definitive dose confirmation in Phase 3 Profile

patients with extended duration• Safety and persistence of virologic benefit

Design:– Gag genotype tested at screening visit– Proportion with VL <50 copies/mL at Week 16– 120 ARV-experienced patients (GSS 2-4 only)

• 80 receive bevirimat + 2-3 drug OBR• 40 receive placebo + 2-3 drug OBR

– Patients continue treatment after Week 16 to ~3 years– Sites in North America and Australia

Status:– Patient screening begins 4Q08/1Q09

76

Phase 3 regulatory changes: EMEA and FDAPhase 3 regulatory changes: EMEA and FDA

1. All primary endpoints must be < 50 copies/mL

2. All comparative studies must have 2+ active drugs in comparator arm.

3. Can divide experienced patients into those with GSS of 2+ or GSS of 0, 1

a) Low GSS patients (0, 1) must not be studied in a 2-arm comparative design, since they might randomize to an arm with 0-1 active agents

b) Low GSS patients may be studied in a 1-arm activity trial of less than 24W

c) Such 1-arm designs are inadequate to demonstrate safety

4. Traditional 2-arm design for high GSS patients unlikely to show a superiority at 24W, so should use a non-inferiority endpoint at 48W

5. For naïve studies: 48W minimum for a superiority design (and against SOC comparator) and 96W minimum for a non-inferiority design

77

Phase 3 registration studies: 301 and 302Phase 3 registration studies: 301 and 302Objective: – Demonstrate safety and efficacy of bevirimat against standard of

care in treatment-experienced patients

Design:– 48-week non-inferiority comparison of bevirimat vs. standard of care– Primary endpoint: <50 copies/mL– All patients screened for Gag polymorphisms at baseline

• Those without polymorphisms at 369, 370 or 371 may randomize• Those with polymorphisms may enter 3rd arm with bevirimat for 7 days

before reassessment– Final dose to be decided– N=800-1000 across 2 studies (2:1 bevirimat: SOC)– Multinational study

Status:– Patient screening to begin 2009

78

79

Phase 1 Phase 2 Phase 3

Clinical Studies in HIV+ Patients

PediatricsEAP

ARV‐experienced (X 2)ARV‐naïve

Regulatory Requirements

QTc Prolongation, Hepatic Insufficiency, ADME

ARV Drug‐Drug Interactions

Raltegravir*Tenofovir

Non‐ARV Drug‐Drug Interactions

RifampinOral contraceptiveMethadoneProton Pump Inhibitor

Bevirimat: Longer-term study plansBevirimat: Longer-term study plans

* In vitro drug-drug interactions unremarkable

‹#›

Gag genotype fits into existing practice and reimbursement patterns (www.vircolab.com)

Gag genotype fits into existing practice and reimbursement patterns (www.vircolab.com)

Genotype assays: most common resistance testGenotype assays: most common resistance test

Patients have a resistance test before starting treatment for the first time and whenever changing treatment

Individual patient genotype testing is the most common resistance test used by clinicians

Genotypes are simple to perform, widely available, and fully reimbursed

Genotype testing: cost $200-400; results in 7-14 days

Interpretation of results differ by testing company but are evidence-based simplifications for clinicians

Test development at resistance companies currently in discussions

81


Bevirimat Bevirimat Development ProgramDevelopment Program

Graham P. Allaway, Ph.D.Chief Operating Officer

Bevirimat: Bevirimat: Understanding Understanding PolymorphismsPolymorphisms

Presentation highlightsPresentation highlights

Laboratory studies confirm effect of polymorphisms at Gag 369, 370, 371 on bevirimat activity

Polymorphisms are distinct from resistance mutations

How do the polymorphisms affect bevirimat activity?

84

Laboratory studies confirm importance of polymorphisms at Gag 369, 370, 371Laboratory studies confirm importance of polymorphisms at Gag 369, 370, 371

Effect of polymorphisms confirmed in different assay formats using:– Patient isolates

– Site-directed mutants

Studies conducted by several groups: InPheno, Virco, Southern Research, and Panacos – Data presented by InPheno, Virco, and Panacos at

Sitges

Patent filing around polymorphism analysis

85

Viruses with “wild-type” 369-371 are more sensitive to bevirimat (InPheno assay)Viruses with “wild-type” 369-371 are more sensitive to bevirimat (InPheno assay)

86

More sensitive (<2X wild-type)

Less sensitive(>3X wild-type)

In vitro sensitivity to bevirimat(IC50 relative to wild-type )

CA-SP1 Sequence

0.57 GHKARVL-AEAMSQVTKSATMM0.84 GHKARVL-AEAMSQVTNPPTIM0.87 GHKARVL-AEAMSQVTNSATIM1.00 (wild-type control) GHKARVL-AEAMSQVTNPATIM1.02 GHKARVL-AEAMSQVTGSAAVM1.14 GHKARVL-AEAMSQVTNSATVM1.16 GHKARVL-AEAMSQVTNPATIM1.51 GHKARVL-AEAMSQVTPSATVM1.69 GHKARVL-AEAMSQVTNPSNIM1.79 SHKARIL-AEAMSQVTGPANIM

3.60 GHKARVL-AEAMSQMTNSAAIM4.25 GHKARVL-AEAMSQMTNSAAIM4.60 GHKARVL-AEAMSQMTNPATIM4.61 SHKARVL-AEAMSQV-NPTNIM4.85 NHKARIL-AEAMCHVTNSATVM12.8 GHKARVL-AEAMSQMTNSATTM14.5 SHKARVL-AEAMCQA-NSTTVM15.3 GHKARVL-AEAMSQATASNVIM

17.4 GHKARVL-AEAMSQA-NSSSIM22.2 GHKARVL-AEAMSQATASNVIM32.3 GHKARVL-AEAMSQATNSAAIM

Bevirimat blocks CA-SP1 processing in “wild-type” but not in polymorphic virusBevirimat blocks CA-SP1 processing in “wild-type” but not in polymorphic virus

369 370 371

…G H K A R V L A E A M S Q V T N S A T I M…G H K A R V L A E A M S Q A T A S N V I M…G H K A R V L A E A M S Q V T G S A A V M…G H K A R V L A E A M S Q M T N S A A I M

CA SP1Wild-type

Patient #125Patient #126Patient #127

Wild-type#125

V370A#126None

#127V370M

─ + ─ + ─ + ─ +Bevirimat:CA-SP1CA

87

Isabelle Malet, Marc Wirden, Anne Derache, Anne Simon, Christine Katlama, Vincent Calvez and Anne-Genevie`ve Marcelin

88

Study of PI-treated patients: > 68% had wild-type QVT at 369-371; changes at 370 most frequent

Each patient may have multiple polymorphisms, so the % of patients with polymorphisms may be less than

the frequency of polymorphisms

357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377

↓

Determinants of bevirimat clinical response: polymorphisms in SP1, not resistance mutationsDeterminants of bevirimat clinical response: polymorphisms in SP1, not resistance mutations

…G H K A R V L A E A M S Q V T N S A T I M

RED: location of in vitro resistance mutations1,2

GREEN: location of key polymorphisms3

*References:

1. Li et al. 2003, PNAS 100:13555–13560

2. Adamson et al. 2006, J. Virol. 80:10957-10971

3. Sitges abstracts

358 363 364 366 369 370 371

CA SP1

89

Polymorphisms behave differently than resistance mutationsPolymorphisms behave differently than resistance mutations

Polymorphisms have not appeared in extensive in vitro resistance selection experiments by several independent groups– Perhaps because bevirimat is active against polymorphic viruses

at low levels of viral replication

– Will this translate to lack of in vivo selection of polymorphisms by bevirimat?

• Further studies necessary

Why do the polymorphisms exist in some patients and not others?– Treatment experience/immune response?

90

How do polymorphisms affect bevirimat activity?How do polymorphisms affect bevirimat activity?Bevirimat competes with protease for binding to the CA-SP1 cleavage site:

91

Bevirimat

Bevirimat targets CA-SP1, not proteaseBevirimat targets CA-SP1, not proteaseBevirimat has no effect on protease activity in cell-free systems1,2

Bevirimat resistance mutations generated in cell culture experiments occur only near the CA-SP1 cleavage site, not in protease or elsewhere in the genome1,2,3

SIV is insensitive to bevirimat – Its CA-SP1 sequence differs from that of HIV-1– SIV acquires bevirimat sensitivity when its CA-SP1 sequence is

replaced by the HIV-1 sequence4

All PI-resistant viruses tested to date are sensitive to bevirimat1,2

Bevirimat is synergistic with protease inhibitors5

References:1. Li et al. (2003) PNAS 100:13555-135602. Zhou et al. (2004) J. Virol. 78:922-93. Adamson et al. 2006, J. Virol. 80:10957-109714 Zhou et al. (2004), Retrovirology 1:15 5. Kilgore et al. (2006), CROI, Denver, Co.

Predicted structure of CA-SP1 cleavage site indicates bevirimat binds to a helical region in Gag Predicted structure of CA-SP1 cleavage site indicates bevirimat binds to a helical region in Gag

… G H K A R V L A E A M S Q V T N S A T I M …

SP1CA NC

93

Model suggests bevirimat binding site forms helical bundle structure: this may be perturbed by SP1 polymorphisms Model suggests bevirimat binding site forms helical bundle structure: this may be perturbed by SP1 polymorphisms

94Wright et al. EMBO J. (2007) 26:2218-26

SP1

CA

Panacos confirms polymorphisms affecting bevirimatPanacos confirms polymorphisms affecting bevirimat

Laboratory studies confirm effect of polymorphisms at Gag 369, 370, 371 on bevirimat activity

Polymorphisms are distinct from resistance mutations

Polymorphisms likely affect bevirimat activity by altering the CA-SP1 helix conformation

95

Graham P. Allaway, Ph.D.Chief Operating Officer

Bevirimat: Bevirimat: Understanding Understanding PolymorphismsPolymorphisms

Richard Harrigan, PhDBC Centre for Excellence in HIV/AIDS

University of British Columbia

97

Gag: A Structural Protein of HIVGag: A Structural Protein of HIVThe Viral Target for BevirimatThe Viral Target for Bevirimat

Presentation topicsPresentation topics

Structure and function of Gag

Development of polymorphisms

Prevalence of polymorphisms at 369, 370 or 371

Genotypic testing for Gag

98

The HIV genome: function and ARV drug targetThe HIV genome: function and ARV drug target

HIV Component Function ARV Drug

GagSynthesizes major structural and core proteinsCapsid-SP1 cleavage site is the target of bevirimat Bevirimat

Pol Yields viral enzymes RT, PR, and integrase

PIs: ATV, RTV, LPV, DRV, othersNRTIs: ZDV, ABC, DDI, othersNNRTIs: EFV, NVP, ETVNTRTI: TDFInt Inh: RAL, ELV

Env Synthesizes surface protein subunits of the virus Fusion Inh: T20R5 Antag: MVC, VCVPA-161

Others Nef, Rev, Tat, VIF, VPR, VPU Discovery stages

99

The HIV-1 replication cycleThe HIV-1 replication cycle

Entry Inhibitors

RT Inhibitors

IntegraseInhibitors

Protease Inhibitors


100

Bevirimat targets Gag at the CA-SP1 cleavage siteBevirimat targets Gag at the CA-SP1 cleavage site

101

P6

GAG polyprotein

CA MA NC

P6 CA MA NC

protease

protease

Untreated

BEVIRIMAT

budding HIV particle

Treated

SP-1

CD4cell

CA‐SP1 cleavage site between Gag codons 363‐364

SP1MA CA p6 PR INTSP2NC

LTRgag pol env

PROTEASE

P51 (RT) P66 (RT)

LTR

NEF

HIV-1 genome: proximity of Gag and Pol and capsid-SP1 cleavage siteHIV-1 genome: proximity of Gag and Pol and capsid-SP1 cleavage site

Key Points:1. Gag and Pol are adjacent genes2. Gag has 6 component subunits and 500 amino acids3. Protease mutations may lead to compensatory changes on Gag

(at cleavage sites)

102

Gag: the development of polymorphismsGag: the development of polymorphisms

Gag polymorphisms– Compensatory change to evade immune pressure – Compensatory change to allow cleavage by protease that has mutations

due to protease inhibitor use

Gag polymorphisms due to CTL-based immune pressure often have an association with an HLA epitopeIn a review of heavily treatment-experienced patients at UBC, compensatory Gag polymorphisms occurred at multiple Gag locations:– NC-SP1 cleavage site: 52% of patients– SP2-P6 cleavage site: 43%– SP2-NC cleavage site: 39%–– CA-SP1 cleavage site: 4%

103

…

% of treatment experienced patients with cleavage site mutations

**50%**36%

21%14%

7%

4%PITreated

SP1MA CA p6 PR P51(RT) INTSP2NC

4%

NRTI 11% 11% 4%

P66(RT) NEF

4%19% 16%

11%

7%

** = p <0.05

HIV-1 genome: locations of compensatory Gag polymorphisms that follow protease mutationsHIV-1 genome: locations of compensatory Gag polymorphisms that follow protease mutations

Most common sites of Gag compensatory changes due to protease mutations

(from database of experienced patients)

104

Gag positions near CA-SP1 cleavageHLA epitope associationGag positions near CA-SP1 cleavageHLA epitope association

Gag is a common target of the immune system (CTL: cytotoxic T-lymphocytes) in trying to control HIV infection, even in the absence of anti-HIV drugs

Multiple HLA epitopes are known that map to specific positions on Gag

HLA epitopes near the CA-SP1 cleavage site on Gag are known– None yet identified that specifically target Gag positions 369, 370

or 371

105

0

20

40

60

80

0 50 100 150 200 250 300 350 400 450 500HIV GAG Codon

% a

a va

riatio

n

p17 p2/p7/p1/p6p24

Selection pressure from the human immune system results in Gag polymorphisms

• HIV-HLA associations observed at 51/500 (10%) Gag codons

Brumme et al., PLoS Pathogens July 2007

Prevalence of Gag polymorphisms in patients at academic databasePrevalence of Gag polymorphisms in patients at academic database

At UBC cohort of J. Montaner and colleagues, HIV-positive adults had samples collected for genotype assay 1996-2005

Samples not part of a clinical trial

567 ARV-naïve patients were assessed with Gag genotype– Standard DNA primers used to determine amino acid sequence

– Mean CD4: 280 copies/mm3

– Mean Viral Load: 5.0 log copies/mL

114 ARV-experienced patients were assessed with Gag genotype (standard primers)

107

Prevalence of Gag polymorphisms at 369, 370 or 371 (UBC patient database)Prevalence of Gag polymorphisms at 369, 370 or 371 (UBC patient database)

Patient Population N

Proportion without polymorphisms at 369, 370 or 371

ARV‐naïve 567 60.2%

ARV‐experienced 114 59.7%

108

Malet et al: 68.3% of PI‐experienced patients were free of polymorphisms at 369, 370 or 371 (AIDS 2007, 21[7]:783)

Prevalence in ARV-naïve vs. experienced patients (UBC patient database)Prevalence in ARV-naïve vs. experienced patients (UBC patient database)

Patients free of polymorphisms at individual positions 369, 370 or 371 in two clinical databases at UBC

109

ARV‐naïve Patients (N=567)

ARV‐experienced Patients(N=114)

Q369 95.4% 93.8%

V370 72.3% 75.4%

T371 92.0% 90.4%

Individual amino acid changes at 369, 370 or 371 (UBC ARV-naïve patient database)Individual amino acid changes at 369, 370 or 371 (UBC ARV-naïve patient database)

110

Gag codon with Clade B consensus

amino acidAmino acid

polymorphismProportion of patients without polymorphism

V370 AV/A

DeletionMIL

81.4%96.8%97.9%98.6%98.8%98.8%

T371 DeletionAN

94.8%98.4%98.8%

Q369 HQ/H

97.7%97.7%

0.00

10.00

20.00

30.00

40.00

50.00

60.00

<25 25-49 50-99 100-199 200-499 >=500

CD4

%

No Mutation Mutation

CD4 count distribution is similar for patients with and without mutations

Source: 2008 UBC patient clinical database (Harrigan)

Gag polymorphisms: summary conclusionGag polymorphisms: summary conclusionCA-SP1 cleavage site on Gag is the target of bevirimat

Gag polymorphisms are compensatory, due either to immune pressure or protease mutations

Patients free of 369-371 polymorphisms in external databases

– 60.2% in 567 ARV-naïve patients (Harrigan, UBC)

– 59.7% in 114 ARV-experienced patients (Harrigan, UBC)

– 68.3% in 82 PI-experienced patients (Malet, Paris)

Amino acid changes at individual codons are variable, and some may not have an impact on bevirimat activity

Gag genotype can be assessed with a well-standardized and widely used assay that is rapid and relatively simple to perform

112

Richard Harrigan, PhDBC Centre for Excellence in HIV/AIDS

University of British Columbia

113

Gag: A Structural Protein of HIVGag: A Structural Protein of HIVThe Viral Target for BevirimatThe Viral Target for Bevirimat

114

David E. Martin, Pharm.D., MBASenior Vice President

Drug Development

PK/PD Profile andPK/PD Profile andFormulation ProgressFormulation Progress

Bevirimat PK/PD and formulation highlightsBevirimat PK/PD and formulation highlights

Predictable pharmacokinetics

Limited potential for drug-drug interactions

Achieved top of the dose-response curve

Identified target plasma concentration

Developing tablet and liquid formulations

115

Bevirimat demonstrates predictable human pharmacokineticsBevirimat demonstrates predictable human pharmacokinetics

Long terminal elimination half-life: ~60 hours

Linear and predictable pharmacokinetics

Glucuronidated and excreted through the bile

No renal clearance, and no circulating glucuronidemetabolites

No significant gender differences

No significant differences between HIV-infected patients and uninfected patients

Well absorbed throughout the small intestine

116

Bevirimat demonstrates lack of clinically relevant interactionsBevirimat demonstrates lack of clinically relevant interactions

No metabolically based interaction with raltegravir

– In vitro drug-drug interaction study

No effect on atazanavir pharmacokinetics or atazanavir-induced hyperbilirubinemia– Atazanavir is a substrate for CYP3A

– Indicates no clinically relevant interactions with other CYP3A substrates

Minimal effect of ritonavir on bevirimat pharmacokinetics– Ritonavir 100mg BID: ~17% decrease in bevirimat exposure

• Most commonly used boosting dose

117

Maximal viral load reduction achieved in Study 203Maximal viral load reduction achieved in Study 203

118

PK/PD Response in Patients without Polymorphisms*

0.0

0.4

0.8

1.2

1.6

2.0

0 10 20 30 40 50 60 70 80 90 100Average Cmin on Day 14 and Day 15 (μg/mL)

Mea

n H

IV R

NA

Red

uctio

n fr

om B

asel

ine

on D

ay 1

5(L

og10

/mL)

PredictedObserved

EC50 = 21.2 μg/mL

Emax = 1.27 Log10/mL

EC90 = 27.0 mg/mL

*Excludes patients 106 and 47

Bevirimat target trough concentration identifiedBevirimat target trough concentration identified

119

100% of responders had trough concentrations > 20 µg/mL

60% of non-responders had trough concentrations < 20 µg/mL

* Excludes patients 106 and 47

PK/PD Response in Patients without Polymorphisms*

0.0

0.4

0.8

1.2

1.6

2.0

0 10 20 30 40 50 60 70 80 90 100

Average Cmin on Day 14 and Day 15 (µg/mL)

Mea

n H

IV R

NA

Red

uctio

n fr

om B

asel

ine

on D

ay 1

5(L

og10

/mL)

PredictedObserved

EC50 = 21.2 µg/mL

Emax = 1.27 Log10/mL

EC90 = 27.0 mg/mL

PK/PD highlightsPK/PD highlights

120

Observed maximal antiviral effect in Study 203– No further dose escalation required

Identified minimal trough concentration of 20 µg/mL

Target trough concentration achievable with doses > 250 mg/day

Solid and liquid formulations in developmentSolid and liquid formulations in development

Tablets– 100mg tablets developed: 2 distinct formulations

– Manufacturing for clinical use in 3Q08

– Expected for use in Study 205

Liquid– Multi-component formulation under development

• Key issue: long-term stability

– Powder for dispersion under development• Patients disperse stable powder in water prior to administration

• Combines the advantages of a solid (stability) with the advantages of a liquid (bioavailability)

– Proof-of-concept demonstrated for both formulations

121

Tablet formulation: monkeyTablet formulation: monkey

122

* Administered dose of 100 mg (n=3-6/dose)

AUC values are normalized (mg/kg) and converted to percent with the reference 50 mg tablet representing 100%

Tim e (hr)

0 4 8 12 16 20 24

BVM

Con

cent

ratio

n (u

g/m

L)

0

10

20

30

40

10% H P B C D Form ula tionA lcohol Form ula tionTween-80 Form ula tionW ater Form ula tion

Bioequivalence of liquid formulations vs. cyclodextrin reference in humansBioequivalence of liquid formulations vs. cyclodextrin reference in humans

10% HPBCDFormulation #1Formulation #2 Powder for Dispersion

Bevirimat PK/PD and formulation highlightsBevirimat PK/PD and formulation highlights

Predictable pharmacokinetics

Limited potential for drug-drug interactions

Top of the dose-response curve achieved

Target plasma concentration identified

Tablet and liquid formulations in development– 100 mg tablet available in 3Q08

– Proof-of-concept demonstrated for both liquid and powder for dispersion formulations. Currently optimizing both approaches

124

125

David E. Martin, Pharm.D., MBASenior Vice President

Drug Development

PK/PD Profile andPK/PD Profile andFormulation ProgressFormulation Progress

Graham P. Allaway, PhDChief Operating Officer

22ndnd and 3and 3rdrd Generation Generation Maturation InhibitorsMaturation Inhibitors


Panacos discovered maturation inhibition – Broad franchise of 2nd- and 3rd-generation maturation

inhibitors

2nd-generation: analogs of bevirimat with distinct properties– Several promising compounds identified

3rd-generation: proprietary assay to identify maturation inhibitors based on novel chemical scaffolds– Recent success: hits obtained and confirmed in follow-

up assays127

128

Panacos’ maturation inhibitor franchisePanacos’ maturation inhibitor franchise

Bevirimat

Second-generation HIV Maturation Inhibitor

Discovery Preclinical Phase 1 Phase 2 Phase 3

Third-generation HIV Maturation Inhibitor

Novel target discovered by Panacos and collaboratorsBroad IP position around compounds and targetStrong competitive position

Goals for 2nd-generation maturation inhibitor programGoals for 2nd-generation maturation inhibitor program

Develop bevirimat analogs to expand maturation inhibitor market – Distinct activity against polymorphic viruses, compared to bevirimat

– Reduced serum protein binding: potential for greater potency (bevirimat ~ 99.5% HSA bound)

• Potential for QD tablet co-formulations

• Maintain bevirimat metabolic profile (long half-life, lack of drug interactions)

PA-040 first to be tested in Phase 1 – 8 X lower protein binding compared to bevirimat, yet retained long

half-life suitable for QD dosing

– Did not reach target oral bioavailability

129

Additional 2nd-generation compounds identified with improved oral bioavailabilityAdditional 2nd-generation compounds identified with improved oral bioavailability

Select additional 2nd-generation compounds for clinical testing during 2008 based on:– Activity against polymorphic viruses

and/or

– Potential for lower dose, ideally single QD tablet

2nd-generation Lead CompoundIn vitro anti-HIV potency Similar to bevirimat and PA-040

Plasma-free fraction 13-fold greater than bevirimat

Oral bioavailability in rats 6-fold greater than PA-040

130

Goals for 3rd-generation maturation inhibitor programGoals for 3rd-generation maturation inhibitor program

Identify compounds, chemically unrelated to bevirimat, that inhibit CA-SP1 cleavage

Proprietary HTS assay developed

– Currently screening diverse drug-like small molecule libraries

Active compounds identified

– 2 active compounds confirmed in Gag processing assay

131

3rd-generation hits show specific, dose-dependent inhibition of CA-SP1 processing3rd-generation hits show specific, dose-dependent inhibition of CA-SP1 processing

bevirimat (µM)DM

SO 20 10 5 2.5

CA-SP1CA

Hit # 1 (µM)

80 40 20 10 5 2.5 80 40 20 10 5 2.5

Hit # 2 (µM)

Steady-state Gag Processing in Virions

132

Compounds are structurally distinct; tractable chemistry

Additional hits currently being followed up

3rd-gen. compounds will be selected for optimization based on:– Activity against polymorphic viruses– Potential for improved formulation or other characteristics

Panacos has a broad franchise of 2nd- and 3rd-generation maturation inhibitorsPanacos has a broad franchise of 2nd- and 3rd-generation maturation inhibitors

2nd-generation: poised to select next preclinical lead candidate based on:

– Activity against polymorphic viruses (screening ongoing)

and/or

– Potential for lower dose, ideally single QD tablet (compound identified)

3rd-generation: Panacos recently identified the first maturation inhibitors with novel scaffolds, compared to bevirimat

– Current goal: analyze multiple hits and select compounds for optimization and potential future clinical development

133

Graham P. Allaway, PhDChief Operating Officer

22ndnd and 3and 3rdrd Generation Generation Maturation InhibitorsMaturation Inhibitors

Karl Salzwedel, Ph.D.Senior Director

Virology and Drug Discovery

135

Oral HIV Fusion InhibitorsOral HIV Fusion Inhibitors

136


Identified small-molecule oral HIV fusion inhibitors– Panacos has succeeded where others have been

unsuccessful

Novel approach used in developing a proprietary high-throughput screening assayIdentified several families of oral HIV fusion inhibitorsFirst preclinical candidate selected: PA-161Continuing to optimize additional lead compounds

Panacos targets both ends of HIV-1 lifecyclePanacos targets both ends of HIV-1 lifecycle

OralFusion

Inhibitors


137

138

3 distinct classes of HIV entry inhibitors3 distinct classes of HIV entry inhibitors

Attachment inhibitors– BMS-806 (development terminated)

– TNX-355 CD4 antibody (Genentech)

Coreceptor antagonists (CCR5)– maraviroc (Pfizer, approved)

– vicriviroc (Schering-Plough, in development)

Fusion inhibitors– enfuvirtide (Trimeris/Roche)

139

HIV fusion inhibitor pipelineHIV fusion inhibitor pipeline

Enfuvirtide (FUZEON, T-20): only approved fusion inhibitor– 36-aa peptide

– 106-step synthesis

– BID subcutaneous injection (90 mg)

– Most expensive HIV drug (>$20,000/yr, >$55/day)

– $266.8 million worldwide sales in 2007

No other fusion inhibitors currently in the clinic

HIV fusion: complex conformational changes = multiple drug targetsHIV fusion: complex conformational changes = multiple drug targets

140

gp41

gp120

gp120 comes

off

CD4binds

Coreceptorbinds

6-HelixBundle(6HB)

141

Enfuvirtide target is not amenable to small molecule inhibitionEnfuvirtide target is not amenable to small molecule inhibition

142

Panacos takes a unique approach to identify oral fusion inhibitorsPanacos takes a unique approach to identify oral fusion inhibitors

Unsuccessful efforts by other groups– Peptide-based biochemical screening for compounds

that work at the same molecular target as enfuvirtide– Computer-aided drug design focused exclusively on

enfuvirtide target

Panacos develops proprietary cell-based assay– Captures multiple targets in the cascade of molecular

changes that drive fusion and culminate in 6-helix bundle formation

143

Panacos’ proprietary fusion inhibitor screening assayPanacos’ proprietary fusion inhibitor screening assay

Panacos discovered novel class of orally bioavailable HIV-1 fusion inhibitorsPanacos discovered novel class of orally bioavailable HIV-1 fusion inhibitors

144

Potency (IC50; µM) PK

SeriesScreening

AssayInfection

AssayOral

Bioavailability

A 0.0005 0.004 19% (mouse)

B 0.3 1 30% (rat)

C 0.05 0.04 ND

>0.5 million compounds screened8 distinct, chemically tractable series identified for optimizationFocused on 3 series with greatest potencyExtensive laboratory studies confirm mechanism of action– Molecular target upstream of enfuvirtide target

145

PA-161 selected as preclinical leadPA-161 selected as preclinical lead

Nanomolar activity against diverse primary HIV-1 isolates in the presence of human serum

Good oral bioavailability, potential for BID or QD dosing

No significant off-target receptor binding, including functional hERG testing

Optimization ongoing of additional lead compounds

146

Panacos’ inhibitors retain activity against most enfuvirtide-resistant mutantsPanacos’ inhibitors retain activity against most enfuvirtide-resistant mutants

Series A Peptide-based Inhibitor

Fold Resistance

L33SV38EI37KN42T/N43KV38A/N42TV38E/N42SV38A

11.70.54.81.20.90.52.0

3.060.56.39.37.323.39.5

(Red = >2-Fold Resistance)

Mutant

147

Oral fusion inhibitor program highlightsOral fusion inhibitor program highlights

Developed & validated proprietary screening approach for oral fusion inhibitor discovery

Potent fusion inhibitors identified – Orally bioavailable, unlike enfuvirtide

– Active against both X4 & R5 strains, unlike maraviroc

– Novel target site and mechanism of action

– Distinct determinants of resistance

Preclinical lead candidate selected: PA-161

Continuing to optimize additional lead compounds

Karl Salzwedel, Ph.D.Senior Director

Virology and Drug Discovery

148

Oral HIV Fusion InhibitorsOral HIV Fusion Inhibitors

Bevirimat Market Potential Bevirimat Market Potential andand

HIV Marketplace DynamicsHIV Marketplace Dynamics

149

Frederick Schmid, DVM, MBASenior Vice President

Commercial Operations and Business Development

Questions we ask ourselvesQuestions we ask ourselves

How robust is the antiretroviral market going forward?

Isn't the market largely satisfied already?

Where will bevirimat business come from?

How will bevirimat fit into the treatment scheme?

Will polymorphism testing be a limiting burden?

150

What a difference 5 years can make…… In 2002, Combivir and Sustiva had locked up the marketWhat a difference 5 years can make…… In 2002, Combivir and Sustiva had locked up the market

151

TRx

mar

ket s

hare

How robust is the ARV market?How robust is the ARV market?

DataMonitor projects a $6B market growing to $11B by 2015

What factors will sustain that growth?– Only ~75% of people with HIV know their status

• Aggressive testing policies being implemented to expand that number

– Only 55% - 65% of people with HIV are on ARVs• Having more agents available will tips the scales toward starting earlier vs.

conserving

– Growing bolus of experienced patients still need new options• People living longer with HIV• Existing classes are compromised and of little use to long-time patients

Novel MOA is lynch pin for competitive advantageBevirimat is the only novel, oral ARV in late-stage development

152

There is significant room for growthThere is significant room for growth

2007 US HIV Market (Patients 000’s)

1,000 – 1,2001

1. CDC 20052. Synovate Healthcare US HIV Monitor 1Q07

HIV Infected Diagnosed On Anti-retroviralTreatment

750 – 9001

5002

153

Fusion Inhibitors

• Enfuvirtide

Entry Inhibitors

• Maraviroc

IntegraseInhibitors

• Raltegravir

Protease Inhibitors• Atazanavir

• Darunavir

• Fos-Amprenavir

• Indinavir

• Lopinavir

• Nelfinavir

• Ritonavir

• Saquinavir

• Tipranavir

NRTIs• Abacavir

• Didanosine

• Emtricitabine

• Lamivudine

• Stavudine

• Tenofovir

• Zidovudine


• Efavirenz

• Nevirapine

• Etravirine

Long list of drugs but in older classes, and Long list of drugs but in older classes, and intraintra--class crossclass cross--resistance reduces options resistance reduces options dramaticallydramatically

Of all the HIV drugs in development, there is just one novel, oral ARV drug

in late‐stage development

2007 201020092008 201320122011 2014 2015

BevirimatRaltegravir

Etravirine HIV Vaccine

Vicriviroc

PRO 140

TNX 355 Elvitegravir

Elvucitabine

Racivir Amdoxivir

Apricitabine

Incyte CCR5

HGS CCR5 MAb

Tai Med anti‐CD4 MAbTobira CCR5

Idenix NNRTI

Ardea NNRTI

Pfizer NNRTI

Koronis NRTI

Gilead NRTI

Entry Inhibitors

NNRTIs

NRTIs


Maraviroc

PPL‐100

PIs

Maturation Inhibitor

As many switches onto 3rd+ lines as in first two lines even though patient prevalence is much higher in first two linesAs many switches onto 3rd+ lines as in first two lines even though patient prevalence is much higher in first two lines

Sources: CDC, Plan A HIV Alert- Lines of Therapy, 2006-2016156

Bevirimat captures substantial value at launch by penetrating later lines of therapy…Bevirimat captures substantial value at launch by penetrating later lines of therapy…

Volume: 115K patients will start new regimen in 3rd+ linesExisting major drug classes will be compromised– 75% of patients likely will have only 1-2 fully active and tolerable drugs

leftConservatively, 60% will not have Gag PMs– In such a highly tailored situation, bevirimat should reach 75% of these

patients

Price: “3rd-agent” pricing reference (boosted PIs) estimated to have average daily price of ~$45 by bevirimat launch

$13,500/patient-year (assuming 80% adherence)

115k pts x .75 x .60 x .75 = ~ 39k patients39k x $13.5k x 80% adherence ~ $420M

(at 2% penetration in first and second lines, >$500M)*U.S. only projections

157

…and builds into earlier lines, based on patient-friendly profile and formulation choice…and builds into earlier lines, based on patient-friendly profile and formulation choice

Current domination by Atripla is not fait acompli– One pill QD hailed as "Holy Grail"– But there are soft spots in the armor

• Component toxicitieso Efavirenzo Tenofovir

• Large pillso Sizeable niche of patients prefer “non-solid” formulations

Gaps in Atripla value proposition leaves room for Panacos to take share in early lines

158

No surprise, physicians focus on efficacy and toxicity, not pills vs. liquidsNo surprise, physicians focus on efficacy and toxicity, not pills vs. liquids

159 Panacos 3rd-party market research

But many patients have issues with pills, especially women and people of colorBut many patients have issues with pills, especially women and people of color

160

%

•26% of all patients report problems swallowing pills•2007 research by Harris Interactive supports this (40%)

Panacos 3rd-party market research

41

60

69

80

89

RAL (GSS = 0)

RAL

RAL + DAR

RAL + ENF

RAL + DAR + ENF

% C

opie

s <5

0

161Pooled data from BENCHMRK1 & 2 trials

Novel MOA and tailored fit offers advantages for including bevirimat in

compromised regimens

The more active agents the better: Where will bevirimat fit?The more active agents the better: Where will bevirimat fit?

Testing for polymorphisms will be nearly invisible to key constituents: doctors and payorsTesting for polymorphisms will be nearly invisible to key constituents: doctors and payors

Gag test will be based upon simple genotype test already in use

Patients receive genotyping before starting first treatment and whenever changing treatment– Most common resistance test used by clinicians

– Simple to perform, widely available, and fully reimbursed

– Cost $200-400…Results in 7-14 days…simple report to doctors

Simple bolt-on modifications routinely added to current assay by commercial testing companies– Not an entirely new phenotypic assay like TROPHILE™

– Each testing company adds new genotypes to stay relevant

– Engaged in advanced discussions with major players in HIV testing

162

Answers to our marketing questionsAnswers to our marketing questionsHIV market continues to be robust

More patients takings ARVsMore moving into later lines

The market is not satisfiedBurgeoning experienced patient population needs novel MOAsNext novel MOA to market will shore up regimen durability

Bevirimat will penetrate later lines, based upon its novel MOA, potency and tolerability

Penetrate earlier lines with patient-friendly formulations vs. "pill fatigue"

Bevirimat fits into future HIV treatment schemes Tailored fit and novel MOA adds certainty vs. archived mutationsLike Fuzeon, bevirimat is potent and novel, but in an oral form

Polymorphism testing will not be a burden

163

Bevirimat Market Potential Bevirimat Market Potential andand

HIV Marketplace DynamicsHIV Marketplace Dynamics

164

Frederick Schmid, DVM, MBASenior Vice President

Commercial Operations and Business Development

Partnership Strategy and Financial Review

Jane Pritchett HendersonChief Financial and Business Officer

166

Partnership strategies to build shareholder valuePartnership strategies to build shareholder value

Partnership opportunities for all programs– Retained worldwide rights to date– Interest from pharma/large biotech– Value-enhancing events increases interest

Panacos seeks to maintain co-marketing rights in N. America– Small sales force sufficient for HIV – Expertise to implement this strategy– Partner will be responsible for ROW– Retain significant economic upside

Potential for future pipeline expansion – In-house programs – Strategic alliances

Bevirimat is a commercially attractive drug candidateBevirimat is a commercially attractive drug candidate

Patients’ need for new options grows every year

Competitive profile– Potent, first-in-class, novel-mechanism drug– Side effects comparable to placebo– Simple, convenient dosing, forgiving– No clinically relevant drug interactions

• Use in any HAART regimen

– Tablet and liquid formulations under development• Maximizes potential market

Solid intellectual property position in maturation inhibition– Patent family gives protection through 2026 and beyond

Worldwide market potential: $500 - $750M167

Lead small molecule compound identified: PA-161Blocks conformational changes in gp41– Target distinct from FUZEON’s– Activity against FUZEON-resistant HIV

Leading position for oral product– Patented, innovative drug discovery platform

Market potential $500M - $1BAdditional partnership opportunity

Significant potential upside for an oral HIV fusion inhibitor Significant potential upside for an oral HIV fusion inhibitor

{gp41

HIV

Human cell

Panacos is in a sound financial position to negotiate optimal deal Panacos is in a sound financial position to negotiate optimal deal

Selected Financial Data (millions) 3/31/08

Cash, cash equivalents & marketable securities $43.6

Total debt $18.9

Shares outstanding 53.5

169

170

Significant accomplishments over the past 6 monthsSignificant accomplishments over the past 6 monthsBevirimat

Completed bevirimat Phase 2b functional monotherapy studies –no further dose escalation required

Identified predictors of response

Approximately 60-70% of HIV patients have responder Gag profile

Confirmed responder population prospectively

Identified commercializable tablet and liquid formulation

Initiated multinational studies with tablet dose

Oral FusionSelected an oral HIV fusion inhibitor lead

CorporateAppointed CFO

Need, Commitment, Expertise

The Future of PanacosAlan W. Dunton, M.D.President and CEO

Panacos is in a very strong position to deliver shareholder valuePanacos is in a very strong position to deliver shareholder value

Bevirimat– Commercially attractive drug candidate – Addresses continued market need for novel, potent, safe and

oral HIV therapeutics● Steady flow of clinical milestones expected in near-term

Second- and third-generation maturation inhibition programs are progressingSignificant upside from oral fusion inhibitor – Expect to be first to enter the clinic – Strong interest from potential partners

New management team in place – Proven track record of drug development, approval, launch and

commercialization

173

Milestones that build shareholder value over next 12 monthsMilestones that build shareholder value over next 12 months

Bevirimat:Confirm 100mg tablet bioavailability in the clinic Complete multinational Phase 2b studiesInitiate registration studies for marketing approvalConduct discussions with FDA and EMEACollaborate with partner for registration and commercialization

Oral Fusion Inhibitor:Complete preclinical safety studiesFile INDEstablish development partnership

2nd/3rd-generation Maturation Inhibitor:Select lead compound for further development

174

Panacos in 2013, our 5-year goals Panacos in 2013, our 5-year goals

A fully integrated biotech company with U.S. sales force– Bevirimat is 1st commercial product

– Generating revenue

– Building brand awareness with physicians

– Strong support for Company from HIV community

Oral fusion inhibitor product candidate in Phase 3

Strong antiviral pipeline with multiple candidates in development to fuel commercial growth

At or nearing financial independence

Pharmaceutical collaborations to expand access to Panacos’drug candidates

Name recognition globally for positive impact on HIV therapy

175

Antiviral Drugs for Major Human Disease

Nasdaq:[email protected]

R&D Day June 18, 2008 -...

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