Phase 2 of new ARVs BMS-955176 (maturation inhibitor) - AI468002 Study

AI468002 Study: BMS-955176 Phase II Design Phase IIa, randomised, double-blind, dose-escalating study ARV-naïve (≤ 1 week of treatment) or experienced (PI and maturation inhibitor naïve) patients, > 18 years, HIV RNA > 5,000 c/mL, CD4 cell count > 200/mm3 For all dose groups : 8 patients on BMS-176 qd and 2 on placebo HIV RNA evaluated at Day 1 to 14, Day 17-19 and Day 24 BMS-176 5 mg qd or placebo BMS-176 10 mg qd or placebo BMS-176 20 mg qd or placebo BMS-176 40 mg qd or placebo BMS-176 80 mg qd or placebo BMS-176 120 mg qd or placebo AI468002 Study Hwang C. CROI 2015, Abs. 114LB

Baseline characteristics AI468002 Study: BMS-955176 Phase II Baseline characteristics Placebo N = 12 BMS-176 5 mg N = 8 10 mg 20 mg 40 mg 80 mg 120 mg Median age, years 36 43.5 39 33 38 31.5 37.5 Female 12.5% HIV RNA (log10 c/mL), median 4.0 4.1 3.6 3.8 CD4 cell count/mm3, median 458 437 539 512 536 504 498 ARV-naïve : 92% ; ARV-experienced : 8% AI468002 Study Hwang C. CROI 2015, Abs. 114LB

Maximum median reduction in HIV RNA from baseline, log10 c/mL AI468002 Study: BMS-955176 Phase II Maximum median reduction in HIV RNA from baseline, log10 c/mL Placebo N = 12 5 mg qd N = 8 10 mg qd 20 mg qd 0.0 -0.2 -0.4 -0.6 -0.8 40 mg qd 80 mg qd 120 mg qd -1.2 -1.4 -1.6 -1.8 -1.0 - 0.381 - 0.498 - 0.976 - 1.115 - 1.555 - 1.654 - 1.701 Median change in HIV RNA from baseline to day 11 was – 1.4 log10 c/mL BMS-955176 exposure-response relationship is consistent with dose-response antiviral activity AI468002 Study Hwang C. CROI 2015, Abs. 114LB

AI468002 Study: BMS-955176 Phase II Maximum median reduction in HIV RNA, log10 c/mL by baseline Gag polymorphisms Placebo N = 12 5 mg qd N = 8 10 mg qd 20 mg qd 0.0 -0.2 -0.4 -0.6 -0.8 40 mg qd 80 mg qd 120 mg qd -1.2 -1.4 -1.6 -1.8 -1.0 -0.55 -0.48 -1.05 - 1.66 - 1.55 - 1.57 - 1.75 -0.33 -0.52 -0.97 - 0.93 - 1.43 - 1.98 - 1.71 6 5 3 4 2 -2.0 No polymorphisms With polymorphisms (V362, Q369, V370) AI468002 Study Hwang C. CROI 2015, Abs. 114LB

AI468002 Study: BMS-955176 Phase II Adverse events Placebo N = 12 5 mg N = 8 10 mg 20 mg 40 mg 80 mg 120 mg Discontinuation due to adverse event Serious AEs Grade 3-4 related AEs Death Laboratory abnormalities (Grade 2-4) 1* * Transient grade 3 neutropenia reported as related to study drug AI468002 Study Hwang C. CROI 2015, Abs. 114LB

AI468002 Study: BMS-955176 Phase II Conclusion BMS-955176 is a potent, once-daily, second-generation maturation inhibitor with a maximum median decrease of 1.7 log10 copies/mL in plasma HIV RNA with 10 days of monotherapy at the 40 mg dose Doses of 20-120 mg qd resulted in decreases > 1 log10 c/mL Plateau of ≈ - 1.6 log10 c/ml at 40-120 mg qd Similar antiviral activity against both wild-type HIV-1 and HIV-1 with Gag polymorphisms not responsive to a first-generation maturation inhibitor Well tolerated No serious adverse events, No adverse events leading to discontinuation, No grade 3-4 adverse events, No significant laboratory abnormalities AI468002 Study Hwang C. CROI 2015, Abs. 114LB