1. International Partnership for Microbicides ARV-Based Microbicides - Cause for Optimism Dr. Zeda Rosenberg, CEO Mexico City, 4 August 2008

2. 9.5 trials completed or stopped N9, Savvy – surfactants CS, Carraguard, PRO 2000 (2%) – polyanions 2 trials ongoing BufferGel, PRO 2000 (0.5%) – polyanions Early Generation Efficacy Trials

3. The Next Generation  Highly potent and HIV-specific (ARV-based)  Established safety & efficacy in AIDS treatment  Multiple mechanisms of action against HIV  Developed as single drugs and in combination  Can be formulated for sustained protection  Once a day / once a month Gel applicator Ring Tablet, capsule, film

4. Why Vaginal Dosing? Protection specifically for women High drug levels where virus enters the body Low systemic exposure Reduced chance of systemic side effects Precedent in contraception Theoretically, less chance of selection for resistance No one prevention option will satisfy all Microbicides, PrEP, vaccines, etc.

5. Topical Tenofovir NRTI Most advanced ARV microbicide in the pipeline Preclinical development began in late 1990s Proof-of-concept efficacy trials ongoing/planned Gilead license to CONRAD and IPM Viread® marketed as AIDS therapeutic

6. Topical Tenofovir Trials StudyPhaseSponsor/DeveloperCountriesResults/Status HPTN 0501NIAID / HPTNUSACOMPLETED in 2004 Well tolerated, HIV-/+ women CONRAD A04-099 1CONRAD, IPMUSACOMPLETED in 2006 Male tolerance study HPTN 0592NIH / MTNUSA, IndiaCOMPLETED in 2007 Good safety and acceptability profile CONRAD A04-095 1CONRAD, IPMUSA, Dominican R. DATA ANALYSIS PK results expected 2008 CAPRISA 004 2BUSAID, SA DST / CONRAD, CAPRISA SAONGOING since May 2007 Results expected 2010 MTN 0021NIH / MTNUSAONGOING since June 2008 PK study, pregnant women MTN 0012NIH / MTNUSA, Uganda, SA ONGOING since July 2008 Topical and oral tenofovir MTN 003 (VOICE) 2BNIH / MTNMalawi, Uganda, SA, Zambia, Zimbabwe PLANNED for Q1 2009 Topical tenofovir, oral tenofovir, oral Truvada

7. Dapivirine (TMC120)  Highly potent NNRTI  Developed by Tibotec, licensed to IPM  Originally tested as oral therapeutic (11 studies) N CH 3 CH 3 H 3 C H N N N H CN  Multiple vaginal dosage forms in development (gels, rings, films, tablets, other)  Phase 1/2 studies completed and ongoing; Phase 3 planned 2010

8. Dapivirine Ring & Gel - Completed Trials StudyDesignCountriesStudy Results IPM 001, IPM 008 7 days 25 or 200 mg N=25 Belgium Good safety profile and well tolerated High drug levels (> 1000 x EC50) well distributed in vaginal tissues & fluids Low levels in plasma (<50 pg/mL) IPM 018 28 days 25 mg N=24 Belgium Reservoir & matrix rings have good safety profile and are well tolerated High drug levels (> 4 logs x EC50), significantly more drug with matrix Low levels in plasma (<2 ng/mL) StudyDesignCountriesStudy Results IPM 003, IPM 005B 42 days 2.5 ml N=148 Rwanda South Africa Tanzania Good safety profile and well tolerated No drug-related SAEs IPM 00410 days 2.5 ml N=18 South Africa Good safety profile and well tolerated No drug-related SAEs PK data supports once-daily use

9. UC-781UC-781 Highly potent NNRTI Cellegy license to CONRAD 4 Phase 1 studies completed or in data analysis (Thailand, US) – vaginal and rectal 2 Phase 1 studies ongoing – vaginal and male tolerance 2 studies planned: Single agent PK and expanded safety – planned early 2009 Combination UC-781/tenofovir safety – planned early 2010 Source: CONRAD

10. UC-781 Trials - Completed/Ongoing Trials StudyPhaseSponsor/DeveloperCountriesResults/Status CONRAD A02-033 1CONRADUSACOMPLETED Tolerance, abstinent women CDC-47441CDC, MoH Thailand / CONRAD ThailandDATA ANALYSIS Safety/acceptability women, acceptability male partners U19 AI0516611NIH, CONRAD / Univ of Pittsburg USADATA ANALYSIS Safety/persistence, abstinent women U19 AI0606141NIH, CONRAD, UCLA USADATA ANALYSIS Rectal safety/acceptability, men and women CONRAD A06-104 1CONRAD, CFHCUSAONGOING Male tolerance HC 1011CDC, CONRAD / Emory Univ USAONGOING Safety/acceptability, HIV-/+ women

11. PC-815PC-815 MIV-150 (NNRTI) + Carraguard Medivir license to Population Council In vitro activity EC50 of PC-815 is ~10X stronger than Carraguard PC-815 is active against wide variety of HIV isolates Seminal fluid does not impede activity HIV prevention studies ongoing in primate model Phase 1 clinical trials being planned Source: Population Council

12. Topical Maraviroc CCR5 blocker Pre-formulation ongoing Pfizer license to IPM Combination dapivirine/maraviroc Silicone & EVA ring feasibility initiated Gel initiated Film to be initiated Virology ongoing Preclinical assessment 28-day vaginal rabbit dosing study ongoing PK and safety studies planned 2009-10 Selzentry™ marketed as AIDS therapeutic

13. PipelinePipeline  BMS 793  Pyrimidinediones  S-DABO  M167  RANTES analogs  L’644 peptide Important to add back-up drugs, especially drugs in late stage development or marketed therapeutics  NCp7’s  GM Biotics  Cyanovirin-N  Others?  Integrase inhibitors  Small molecule fusion inhibitors

14. Lessons Learned from Prior Trials Lessons learnedWhat can be done going forward Prioritization Advance best-in-class product only into Phase 3 Safety Continue early looks for harm Adherence Longer acting formulations Product acceptability studies Explore novel adherence strategies/technologies Incidence Epi studies conducted in advance Futility Early stop if unlikely to show efficacy Pregnancy Contraceptives and counseling provided on site where feasible Regulatory Obtain feedback/input in advance of trial Locations Address co-enrollment concerns

15. Why Optimism? New generation of microbicides with highly potent ARVs Multiple mechanisms of action against HIV Single drugs or combinations Longer duration of protection Multiple formulations to give women more options Increased focus on adherence Novel trial designs Increased support from donors, pharma, scientific, advocacy and local communities

16. Women Urgently Need Microbicides “A microbicide could mean the difference between life and death for millions of women. Let us do everything in our power to accelerate its development.” Mrs. Graça Machel, March 2008