The start-up’s lead program, BRB-002, is designed to target the CD47/SIRPα pathway and the underlying causes of vascular inflammation and atherosclerosis.
Pictured: Jar of money / Adobe Stock, juliasudnitskaya
Wednesday, California start-up Bitterroot Bio launched from stealth and closed a $145 million Series A funding round to develop innovative immunotherapies for cardiovascular diseases.
Founded in 2021, Bitterroot is built on the research of its cofounders and directors, Irving Weissman and Nicholas Leeper, both from the Stanford University School of Medicine. Their work has focused on the emerging field of cardio-immunology, which seeks to understand the connections and interplay between the immune system and cardiovascular health.
In a 2016 study published in Nature, Leeper and Weissman detailed the role of CD47, a surface protein that protects cells from macrophages, in atherosclerosis. CD47 appears to be present in high amounts in atherosclerotic plaques, which weakens phagocytosis in the vicinity and impairs the clearance of these plaques.
The 2016 study also demonstrated that delivering antibodies that block CD47 could restore the function of macrophages in mice and facilitate the clearance of plaques and reversal of atherosclerosis.
Bitterroot is leveraging Leeper’s and Weissman’s CD47 scholarship to develop novel therapies for heart conditions. The start-up’s lead program, BRB-002, is designed to target the CD47/SIRPα pathway and the underlying causes of vascular inflammation and atherosclerosis.
The anti-CD47 approach to cardiovascular pathology has yet to be tested in humans.
Joining Leeper and Weissman at Bitterroot is Pavan Cheruvu, who will serve as its president and CEO. Most recently, Cheruvu was an executive team member at Roivant Sciences and had been the chief executive of Sio Gene Therapies prior to that. Cheruvu’s experience spans both the private and public sectors and across various areas such as oncology, neurology, cardiology and infectious diseases.
Serving as Bitterroot’s chief medical officer is Crag Basson, who had previously spent 10 years at Novartis, where he worked as the company’s global head of translational medicine for the cardiovascular and metabolic therapeutic areas. Basson was also previously chief medical officer of Boston Pharmaceuticals.
Aside from its experienced leadership, Bitterroot is supported by a strong syndicate of backers, including ARCH Venture Partners, which co-led the Series A with Deerfield Management, as well as Kock Disruptive Technologies and Alexandria Venture Investments.
From Cancer to Cardio
Beyond cardiovascular disease, CD47 is also a known player in cancer and its over-expression has been shown to help tumor cells evade not only the cancer-killing action of macrophages but also the body’s immune surveillance mechanisms.
In 2016, Weissman co-founded Forty Seven Inc., an immuno-oncology company focused on developing anti-CD47 therapies. Its lead candidate, magrolimab, is an IgG4 monoclonal antibody being trialed in several solid and hematologic cancers alone or in combination with other antibodies or T-cell checkpoint inhibitors.
Gilead gained access to magrolimab in March 2020, when it acquired Forty Seven for $4.9 billion. The CD47 cancer program has since hit several roadblocks. In January 2022, the FDA placed a partial clinical hold on all studies of magrolimab combined with azacitidine due to safety issues.
This was followed by even more clinical holds in February and April 2022.
Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
