1. Phase 2 of new ARVs BMS-955176 (maturation inhibitor)
- AI Study

2. 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 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
AI Study
Hwang C. CROI 2015, Abs. 114LB

3. Baseline characteristics
AI Study: BMS 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%
AI Study
Hwang C. CROI 2015, Abs. 114LB

4. Maximum median reduction in HIV RNA from baseline, log10 c/mL
AI Study: BMS 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
Median change in HIV RNA from baseline to day 11 was – 1.4 log10 c/mL
BMS exposure-response relationship is consistent with dose-response antiviral activity
AI Study
Hwang C. CROI 2015, Abs. 114LB

5. AI Study: BMS 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)
AI Study
Hwang C. CROI 2015, Abs. 114LB

6. 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
AI Study
Hwang C. CROI 2015, Abs. 114LB

7. AI468002 Study: BMS-955176 Phase II Conclusion
BMS 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 mg qd resulted in decreases > 1 log10 c/mL
Plateau of ≈ log10 c/ml at 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
AI Study
Hwang C. CROI 2015, Abs. 114LB