Phase 2 of new ARVs  Fostemsavir, prodrug of temsavir (attachment inhibitor) –AI Study  TAF (TFV prodrug) –Study –Study  Doravirine (non nucleoside reverse transcriptase inhibitor) –MK Study  Cabotegravir (integrase inhibitor) –LATTE Study  BMS (maturation inhibitor) –AI Study

MK Study: doravirine (DOR) + TDF/FTC vs EFV + TDF/FTC DOR 25 mg qd + TDF/FTC DOR 50 mg qd + TDF/FTC DOR 100 mg qd + TDF/FTC DOR 200 mg qd + TDF/FTC EFV 600 mg qd + TDF/FTC  Phase IIb, part 1  Design Randomisation* 1 : 1 : 1 : 1 : 1 Double-blind ARV-naïve HIV RNA > 1,000 c/mL CD4 ≥ 100/mm 3 W24W96 Open-label W36 DOR 100 mg + TDF/FTC  Objective –Primary endpoints % HIV-1 RNA < 40 c/mL at W24 (estimation comparisons for DOR dose selection), ITT, NC=F Safety : general at W24, pre-specified CNS AEs by W8 and W24 * Randomisation stratified on HIV RNA (> or ≤ 100,000 c/mL) Morales-Ramirez JO, CROI 2014, Abs. 92LB DOR 100 mg + TDF/FTC MK Study Double blind

MK Study: doravirine (DOR) + TDF/FTC vs EFV + TDF/FTC DOR 100 mg qd + TDF/FTC EFV 600 mg qd + TDF/FTC  Phase IIb, part 2  Design Randomisation 1 : 1 Double-blind ARV-naïve HIV RNA > 1,000 c/mL CD4 ≥ 100/mm 3 W96  Objective –CNS adverse events analysis, W8 Parts 1 and 2 combined (DOR 100 mg vs EFV) –Efficacy and safety analyses, W48 : part 1 only, W96 : parts 1 and 2 % with HIV RNA < 40 c/mL, < 200 c/mL, NC=F approach for missing data Change from baseline in CD4 cell count, observed failure approach Safety endpoints : adverse events, laboratory parameters N = 66 MK Study Gatell JM. HIV Drug Therapy 2014, Abs. O434

DOR qdEFV 600 mg 25 mg N = mg N = mg N = mg N = 41 N = 42 Median ageOverall : 35 years HIV RNA (log 10 c/mL), median HIV RNA > 100,000 c/mL28%30%29% 31% CD4 cell count/mm 3, median B subtype88%79%81%88%86% Discontinuation by W249.8%9.3%4.8%7.3%16.3% For adverse event*12102 Lost to follow-up00113 Withdrew consent21011 Medical decision11011 Discontinuation by W489.8%18.6%14.3%12.2%23.3% For AE / lack of efficacy1 / 03 / 12 / 00 / 12 / 1 LTFU / withdrew consent / other0 / 2 / 1 1 / 1 / 22 / 1 /13 / 2 /1 Baseline characteristics and patient disposition (Part 1) * DOR 25 mg : stupor (n = 1), DOR 50 mg: abdominal pain/nausea/insomnia (n = 1), sleep disorder (n = 1), DOR 100 mg : hallucinations (n = 1), EFV : right-sided dysesthesia (n = 1), hallucinations (n = 1) Morales-Ramirez JO, CROI 2014, Abs. 92LB, Gatell JM. HIV Drug Therapy 2014, Abs. O434 MK Study: doravirine (DOR) + TDF/FTC vs EFV + TDF/FTC MK Study

MK Study: doravirine (DOR) + TDF/FTC vs EFV + TDF/FTC DOR 100 mg, N = 108EFV 600 mg, N = 108 Median age, years ; female, %35 ; 8%34 ; 6% HIV RNA (log 10 c/mL), median4.6 HIV RNA > 100,000 c/mL35%37% CD4 cell count/mm 3, median CNS events at W8, all causality (Parts 1 and 2) Baseline characteristics (Parts 1 and 2) DOR 100 mgEFV 600 mg Dizziness9.3%27.8% Insomnia2.8%6.5% Abnormal dreams / Nightmares16.7% / 8.3%5.6% / 5.6% Hallucinations2.8%0.9% Depression1.9%0.9% Somnolence00.9% Attention disturbance2.8%0 Suicidal ideation0.9%0 % patients with ≥ 1 CNS event DOR 100 mg N = 108 EFV 600 mg N = %43.5%  (95% CI) : ( to - 8.8) MK Study Gatell JM. HIV Drug Therapy 2014, Abs. O434

Response to treatment, HIV RNA < 40 c/mL (ITT, NC = F)  Mean change in CD4/mm 3 at W48 – DOR all doses : – EFV : Morales-Ramirez JO, CROI 2014, Abs. 92LB, Gatell JM. HIV Drug Therapy 2014, Abs. O434 MK Study MK Study: doravirine (DOR) + TDF/FTC vs EFV + TDF/FTC /4032/4127/42 32/4230/ /4034/4130/42 31/4332/42 W24 W48 DOR 25 mg DOR 50 mg DOR 100 mg DOR 200 mg EFV DOR 25 mg DOR 50 mg DOR 100 mg DOR 200 mg EFV %

HIV RNA < 40 c/mL (ITT, NC = F) at W48 by screening HIV RNA MK Study MK Study: doravirine (DOR) + TDF/FTC vs EFV + TDF/FTC Gatell JM. HIV Drug Therapy 2014, Abs. O434 %

 Virologic failure definition –Non-response : HIV RNA never < 40 c/mL by Week 24, or –Rebound : after initial response of HIV RNA < 40 c/mL, 2 consecutive HIV RNA ≥ 40 c/mL at least 1 week apart, at or after Week 24  Criteria for resistance testing –HIV RNA > 500 c/mL DOR all doses, N = 166EFV, N = 42 Virologic failure ≥ 40 c/mL27 (16.3%)6 (14.3%) Resistance testing performed61 Emergent NNRTI mutations1*0 Emergent NRTI mutations00 * K101K/E Resistance data at virologic failure, W48 MK Study MK Study: doravirine (DOR) + TDF/FTC vs EFV + TDF/FTC Gatell JM. HIV Drug Therapy 2014, Abs. O434

MK Study: doravirine (DOR) + TDF/FTC vs EFV + TDF/FTC DOR qd EFV 600 mg N = mg N = mg N = mg N = mg N = 41 Serious AE (none drug-related)10%2.3%4.8%2.4%9.5% Discontinued due to AE, n14202 Drug-related AE40%46.5%16.7%43.9%57.1% Dizziness, n Abnormal dreams, n39234 Diarrhea, n41124 Nausea, n Fatigue, n24152 Clinical adverse events at W48 (Part 1) MK Study Gatell JM. HIV Drug Therapy 2014, Abs. O434

DOR qd EFV 600 mg N = mg N = mg N = mg N = mg N = 41 Platelet count, Grade 2 / Grade 30 / 0 1 / 00 / 10 / 0 LDL-cholesterol, Grade 1 / Grade 22 / 11 / 02 / 13 / 07 / 1 Total cholesterol, Grade 1 / Grade 23 / 01 / 12 / 04 / 010 / 3 Glucose, Grade 1 / Grade 22 / 15 / 21 / 12 / 15 / 1 Creatinine Grade AST, Grade 1 / Grade 2 / Grade 35 / 0 / 11 / 2 / 13 / 0 / 03 / 2 / 06 / 2 / 0 ALT, Grade 1 / Grade 24 / 04 / 31 / 02 / 16 / 0 Alkaline phosphatase Grade Lipase, Grade 1 / Grade 2 / Grade 3-43 / 5 / 12 / 2 / 17 / 2 / 22 / 4 / 07 / 5 / 0 Laboratory abnormalities at W48 (Part 1), N MK Study MK Study: doravirine (DOR) + TDF/FTC vs EFV + TDF/FTC Gatell JM. HIV Drug Therapy 2014, Abs. O434

MK Study: doravirine (DOR) + TDF/FTC vs EFV + TDF/FTC  Conclusion –In antiretroviral-naïve, HIV-1 infected subjects, DOR 100 mg qd + TDF/FTC had a lower rate of treatment-emergent CNS events by week 8 than EFV + TDF/FTC –DOR 25 to 200 mg qd for 48 weeks had simialr virologic and immunologic efficacy to EFV with low rate of resistance mutation development and good safety and tolerability profile –DOR 100 mg qd dose was selected for further development Gatell JM. HIV Drug Therapy 2014, Abs. O434 MK Study