Braveheart Bio, Inc. · NASDAQ:BRVE
Braveheart Bio — Technical Presentation
15 slides from Braveheart Bio's technical presentation
Slide 1: Efficacy and Safety of BHB/HRS-1893 in Symptomatic Obstructive Hypertrophic Cardiomyopathy
Efficacy and Safety of BHB/HRS-1893 In Symptomatic Obstructive Hypertrophic Cardiomyopathy: Results From a 12-Week Phase 2 Study Limei Wang, Mo Zhang, Lianjun Xu, Dong Wang, Xiangyu Zhang, Zijuan Wang, Zhenhui Zhu, Xin Quan, Qing Wei, Xue Feng, Shiqin Wei, Lei Song, Wen Jiang, Lianming Kang* *Princi
Slide 2: Disclosures
Disclosures Limei Wang, M.D. – Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China This study and presentation was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd. and Braveheart
Slide 3: Background
Background • BHB/HRS-1893 is a selective, reversible, small-molecule cardiac myosin inhibitor (CMI) engineered for rapid onset of action, shallow LVEF, and ease of use. • By inhibiting cardiac myosin ATPase activity, BHB/HRS- 1893 reduces actin-myosin crossbridge formation and normalizes cardiac con
Slide 4: Study design
Study design Adult patients with symptomatic oHCM who had resting LVOT-G ≥50 mmHg (or resting LVOT-G ≥30 mmHg and Valsalva LVOT-G ≥50 mmHg), LVEF ≥60%, and NYHA Class II-III were enrolled. Option for dose titration to occur weekly if Valsalva LVOT-G > 30 mmHg and LVEF > 55% Drug discontinuation BHB/
Slide 5: Study endpoints
Study endpoints Primary endpoint • Change in Valsalva LVOT-G from baseline to Week 12 Key secondary endpoints • Change from baseline in: • Peak oxygen uptake (pVO2) • KCCQ-CSS • Resting LVOT-G • NT-proBNP • Proportion with NYHA class improvement of ≥1 LVOT-G, left ventricular outflow tract gradient;
Slide 6: Baseline characteristics
Baseline characteristics 20-40-60 BID 40-60-80 BID 40-80-120 QD (N = 14) (N = 14) (N = 14) Age, years, mean(SD) 48.4 (12.5) 51.5 (10.4) 54.8 (11.2) Male, n (%) 10 (71.4) 9 (64.3) 7 (50.0) Background therapy, n (%) Beta blockers 13 (92.9) 12 (85.7) 12 (85.7) Calcium channel blockers 0 1 (7.1) 1 (7.1)
Slide 7: Rapid, deep, and reversible gradient reduction
Rapid, deep, and reversible gradient reduction Resting Valsalva washout washout Day 2 Data are shown as mean, SEM. LVOT-G, left ventricular outflow tract gradient.
Slide 8: 86% of patients in 40-60-80 BID cohort achieved Valsalva <30 mmHg gradient response
86% of patients in 40-60-80 BID cohort achieved Valsalva <30 mmHg gradient response 42 of 42 patients in the 12 week core treatment rolled into the OLE Resting LVOTG < 30 mmHg + Valsalva LVOTG < 50 mmHg Valsalva LVOTG < 30 mmHg At week 39 of OLE treatment Resting LVOTG < 30 mmHg period, 88% had Vals
Slide 9: Functional capacity and symptom improvement displayed across clinical endpoints
Functional capacity and symptom improvement displayed across clinical endpoints Peak VO2 NYHA Class Improvement 1 100 1.0 1.0 80 % of patients 0.7 mL/kg/min 0.6 60 0.5 40 20 0.0 0 20-40-60 40-60-80 40-80-120 20-40-60 40-60-80 40-80-120 BID BID QD BID BID QD 100% cycle based CPET Peak VO2, peak oxyg
Slide 10: NT-proBNP rapidly normalized in >80% of patients
NT-proBNP, key biomarker of heart failure, rapidly normalized in >80% of patients 2000 washout NT-proBNP NT-proBNP 20-40-60 40-60-80 40-80-120 NT-proBNP (pg/mL) 1000 (pg/mL) mg BID mg BID mg QD 1000 Baseline 622.8 701.9 549.2 (Geometric Mean) Post - Treatment 73.9 84.1 48.0 (Geometric Mean) 500 Post
Slide 11: BHB/HRS-1893 drove deep and rapid reductions in LVOT-G with low impact to LVEF
BHB/HRS-1893 drove deep and rapid reductions in LVOT-G with low impact to LVEF 0 0 washout LVEF events Dose reductions below 55% Dose (mg) LVEF, change Schedule (D84) 20-40-60 -2.7% BID 40-60-80 -2.1% BID 40-80-120 -1.8% QD Data are shown as mean, SD. LVEF, left ventricular ejection fraction
Slide 12: Potential for highly simplified dose regimen
Potential for highly simplified dose regimen Dose distribution at Week 12 20 mg 40 mg 60 mg 80 mg BID BID BID BID 100% of doses selected by 20-40-60 mg BID 2 8 4 LVOT-G < 30 mmHg 40-60-80 mg BID 9 4 1 89% of patients received 40 or 60 mg BID at last dose 1 2
Slide 13: Adverse events
Adverse events • AEs were mild or moderate in severity. • There were no serious AEs or AEs leading to treatment interruption, discontinuation, or death. BHB/HRS-1893 BHB/HRS-1893 BHB/HRS-1893 Total Group 1 Group 2 Group 3 (N = 42) (N = 14) (N = 14) (N = 14) Any TEAEs 12 (85.7) 10 (71.4) 14 (100) 36
Slide 14: Conclusions
Conclusions • Best-in-class potential across efficacy, safety, and ease-of-use • BHB/HRS-1893 treatment resulted in rapid, deep, and durable reductions in LVOT obstruction at rest and after Valsalva • In the twice-daily setting, most patients start and end at the same dose, 40 mg BID; 89% served by
Slide 15: Acknowledgement
Acknowledgement • All patients and their families • All investigators and research personnel who conducted this trial • Study sponsor: Jiangsu Hengrui Pharmaceuticals Co., Ltd., China • Braveheart Bio, Inc.