Bitterroot Bio Begins Dosing in Phase 2a Study of BRB-002 for Cardiovascular Disease

Bitterroot Bio, a leading innovator in cardio-immunology treatments, has begun dosing the first participant in the MATADOR Phase 2a study for its novel therapy, BRB-002, in Australia. The study is a randomized, double-blind, and placebo-controlled trial aiming to assess BRB-002's effect on patients suffering from atherosclerosis. This investigational protein therapy specifically targets the CD47 receptor, offering a potentially groundbreaking treatment option for atherosclerotic cardiovascular disease (ASCVD).

BRB-002 operates through immunomodulation, particularly affecting macrophages, which distinguishes it from existing therapies. Its unique mechanism is designed to reduce vascular inflammation—a primary cause of plaque rupture—and to lower plaque burden, both critical factors in preventing major adverse cardiovascular events (MACE).

The dosing follows positive results from a Phase 1 study. During this earlier trial, presented at the American College of Cardiology Scientific Sessions, BRB-002 demonstrated safety across all dosage levels without any serious adverse events. Importantly, the therapy showed no notable impact on blood parameters such as anemia, thrombocytopenia, or febrile neutropenia. The data also indicated strong dose-dependent engagement with the target receptor, achieving up to full CD47 receptor occupancy at higher doses.

The ongoing Phase 2a study aims to further explore safety and tolerability of BRB-002 over a 13-week treatment period in ASCVD patients. Researchers will also assess pharmacokinetics and pharmacodynamics, alongside changes in carotid artery plaque inflammation using 18F-FDG-PET/CT imaging. The trial will commence with patients who have documented imaging of carotid atherosclerosis, organized into various dose exploration groups, followed by a larger expansion cohort.

Bitterroot Bio anticipates sharing the initial findings of this study by the end of 2026. Craig Basson, MD, PhD, the company's Chief Medical Officer, emphasized the importance of this milestone, noting that while lipid-lowering therapies have advanced treatment outcomes, a substantial residual risk remains for many patients. There is a pressing need for innovative approaches that tackle different underlying pathways of the disease.

Dr. Basson expressed optimism that BRB-002's direct targeting of atherosclerotic plaques could significantly reduce vascular inflammation and residual risk, thereby enhancing long-term cardiovascular health for patients with ASCVD. He highlighted the study's role in offering valuable insights into the safety, tolerability, and biological effects of this novel method.

BRB-002 represents a pioneering protein therapy being tested as a potential treatment for ASCVD. It functions by inhibiting the CD47 receptor, known as the "don't eat me" signal, to mitigate the root causes of atherosclerosis and lessen inflammatory plaque burdens. The Phase 1 clinical study of BRB-002 was completed in Australia by Bitterroot Australia Pty Ltd, a subsidiary of Bitterroot Bio, Inc.

Bitterroot Bio has established itself as a leader in cardio-immunology, focusing on the interaction between the immune system and cardiovascular health. The company is dedicated to understanding how immune modulators influence the progression of cardiovascular diseases, with the ultimate goal of enhancing the lives of those affected by these conditions.