Braveheart Bio spends $185 million on drug to rival Bristol-Myers Squibb's Cardio Med
Bristol-Myers Squibb currently has the only drug approved to treat obstructive hypertrophic cardiomyopathy, a debilitating disease that can progress to heart failure. But the drug's safety risks and limitations still fall short of patient demand, a demand a growing number of biotech companies are racing to meet.
Braveheart Bio is developing a drug that clinical data to date shows potential advantages in terms of safety and greater patient and physician convenience. San Francisco-based Braveheart is preparing to advance its licensed molecule into Phase 3 testing, and on Wednesday the startup unveiled $185 million in funding for the global clinical trial, which is expected to begin in 2026.
In obstructive hypertrophic cardiomyopathy (oHCM), the heart muscle thickens, making it harder for the organ to pump blood. Standard treatments include older drugs not developed for oHCM, such as blood pressure-lowering beta-blockers and calcium channel blockers. These drugs do not address the underlying cause of the thickening, which is caused by excessive contractions driven by a mutant form of the heart muscle protein called myosin.
Braveheart's drug, BHB-1893, is an oral, small molecule myosin inhibitor. Blocking this target has been clinically and regulatoryly validated by BMS's Camzyos, which in 2022 became the first myosin inhibitor approved by the FDA for the treatment of oHCM. But the drug, expected to be a blockbuster, also has the effect of lowering left ventricular ejection fraction (LVEF), which is the amount of blood pumped out by the left ventricle with each contraction. Reduced LVEF may lead to heart failure, a risk noted in a boxed warning on the Camzyos label. Because of this risk, Camzyos can only be used through a Risk Evaluation and Mitigation Strategy (REMS), a program used to monitor and manage potential complications.
Braveheart CEO Travis Murdoch said BHB-1893 may have safety advantages. oObstruction of blood flow in HCM results in a high gradient, which is a measure of the force required to pump blood. A high gradient means the heart has to work harder. As a class, myosin inhibitors reduce gradients. But Murdoch said the data for BHB-1893 showed the potential to become best-in-class.
“We see a sharp drop in the gradient,” Murdoch said. “Based on the phase 1 data, all patients achieved what is considered a full gradient response within days. So we think this does show the potential for greater efficacy that needs to be translated and observed in further clinical studies.”
Phase 1 data were presented at the European Society of Cardiology Congress in September. Soon after, Hengrui Pharmaceuticals, the Shanghai company that discovered and developed the molecule, announced that Braveheart had acquired global rights to the drug, excluding China, Hong Kong, Macau and Taiwan. Murdoch said his company also saw encouraging Phase 2 results, but the data remains confidential. Hengrui is currently evaluating the drug, known as HRS-1893, in a Phase 3 trial in China.
Murdoch said data so far for BHB-1893 suggests it has a greater safety margin before adverse effects occur. This margin avoids the security risks posed by Camzyos and the REMS program. Camzyos' REMS requires echocardiographic assessment of LVEF before and during treatment. Murdoch, a gastroenterologist, said that patients taking BHB-1893 reached a stable state in about a week, and the drug concentration in the body was always within the therapeutic range. Reaching steady state more quickly could simplify dose titration, making BHB-1893 a potentially more tunable drug, he said.
“This is important from the perspective of how and when physicians use such drugs because the more complex titrations, along with the high number of echocardiograms, are quite onerous for physicians. [healthcare] system,” Murdoch said.
Murdoch declined to reveal the molecular properties of BHB-1893 that make it a potentially better drug, saying those details had not been made public. But he said the pharmacology of BHB-1893 appears to be different, and clinical trial results so far support that. Braveheart is also developing the molecule for the less common form of non-obstructive HCM, which may further differentiate it from BMS drugs. In April, Camzyos failed Phase 3 testing for this indication despite positive trends in many biomarkers. Murdock said these results suggest that different molecules with different characteristics may be successful.
Murdoch most recently served as CEO of Human Immunology Biosciences (HI-Bio), a developer of drugs for autoimmune diseases. Last year, Biogen spent more than $1.1 billion to acquire the clinical-stage startup as part of its pipeline diversification strategy. Murdoch continued to lead Biogen's HI-Bio team, but this summer the investment firm that formed Braveheart persuaded him to join. Murdoch said the companies spent a year scouring the world for cardiovascular assets, and BHB-1893 came out on top.
Investors in Braveheart's Series A financing include Andreessen Horowitz, Forbion, OrbiMed, Enavate Sciences and Frazier Life Sciences. Biogen CEO Chris Viehbacher is chairman of Braveheart's board of directors. Braveheart paid $75 million to license BHB-1893; Hengrui may receive up to $1 billion in milestone payments related to the drug's progress.
Startups developing non-obstructive HCM drugs include Haya Therapeutics and Imbria Pharmaceuticals. oHCM drugs can reach patients quickly. The FDA is expected to rule on aficamten, a cardiac myosin inhibitor developed by Cytokinetics, on December 26. The drug was originally expected to receive a regulatory decision in May, but the FDA told Cytokinetics it needed more time to review the drug's proposed REMS. Like Braveheart, Cytokinetics views safety as key to differentiating its drug from BMS's obstructive HCM products.
Cytokinetics said in its latest quarterly report: “We believe aficamten's commercial prospects are highly dependent on FDA approval of aficamten with labeling and REMS, which would be less challenging for prescribers and patients than REMS for Camzyos.”
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