Bitterroot Bio has announced positive results from its Phase 1 clinical trial of BRB-002, a novel protein therapy targeting CD47 for the treatment of atherosclerotic cardiovascular disease. The first-in-human study, conducted in healthy volunteers, demonstrated the safety, tolerability, and target engagement of BRB-002, paving the way for a Phase 2 proof-of-concept trial in patients with established atherosclerosis.
The Phase 1 study was a randomized, placebo-controlled, double-blinded, single ascending dose trial involving 36 healthy volunteers. Participants were divided into five cohorts, receiving single subcutaneous doses of BRB-002 ranging from 0.1 mg/kg to 5.0 mg/kg. The primary objective was to assess the safety and tolerability of BRB-002, as well as its pharmacokinetic properties and target engagement profile.
Safety and Tolerability
The results indicated that BRB-002 was safe at all doses tested, with no serious adverse events reported. The rates of treatment-emergent adverse events were similar between the active and placebo groups, with the most common adverse events being headaches and injection site reactions. Importantly, the study found no clinically significant impact on hematologic parameters, and no instances of anemia, thrombocytopenia, or febrile neutropenia were observed.
Target Engagement
BRB-002 demonstrated robust target engagement, with CD47 receptor occupancy increasing in a dose-dependent manner. At the highest doses tested, receptor occupancy reached up to 100%. Preclinical models of atherosclerosis have shown that CD47 receptor occupancy of 6-26% correlated with meaningful reductions in aortic plaque burden compared to controls.
Clinical Significance
Atherosclerosis remains a significant global health challenge, with current treatment options, such as lipid-lowering therapies, often leaving patients at substantial residual risk for cardiovascular events. BRB-002 represents a novel approach to addressing this unmet need by modulating the immune response within inflamed atherosclerotic plaque.
"We are thrilled to share these results from our Phase 1 study that demonstrated the remarkable safety of BRB-002," said Craig T. Basson, MD, PhD, Chief Medical Officer at Bitterroot Bio. "We are also pleased that this profile is accompanied by robust and long-lasting receptor occupancy to allow us to identify potentially therapeutic doses for our Phase 2 proof-of-concept study that is planned to start in the first half of this year."
Future Directions
Bitterroot Bio plans to present detailed data from the Phase 1 study at the American College of Cardiology Scientific Session in March 2025. The company is also preparing to initiate a Phase 2 proof-of-concept trial of BRB-002 in patients with established atherosclerosis in the first half of 2025. This trial will assess the potential of BRB-002 to reduce cardiovascular risk by modulating the macrophage response within inflamed atherosclerotic plaque.
"This is an important milestone for Bitterroot Bio in our journey to advance BRB-002, a first-in-class, immune-modulating molecule that targets the biology of atherosclerotic plaque," said Pavan Cheruvu, MD, Chief Executive Officer at Bitterroot Bio.
