Bitterroot joins the biotechs hoping to put novel CVD therapeutics on the front page.
Developments in cancer research and new oncology therapies often grab the headlines, but cardiovascular disease remains the leading cause of mortality worldwide, claiming nearly 18 million lives annually [1]. While significant advancements have been made in the field of oncology, the development of innovative treatments for heart disease has been limited – one American still has a heart attack approximately every 40 seconds [2].
Biotech Bitterroot Bio aims to change this narrative by leveraging insights from the fields of immunology and cardiology. Recently emerging from stealth, the Palo Alto-based company secured an impressive $145 million series A funding round, the largest-ever investment for a preclinical cardiovascular disease (CVD)-focused biotech. Led by ARCH Venture Partners and Deerfield Management, with participation from Google Ventures, Koch Disruptive Technologies and others, Bitterroot Bio is on a mission to revolutionize cardiovascular therapeutics and tackle the global burden of heart disease.
Longevity.Technology: CVD remains a significant global health burden, causing nearly twice as many deaths as cancer each year [1]. Despite this, there has been a limited pace of innovation in the field over the past two decades, and the standard approaches to heart disease treatment, such as lowering LDL cholesterol and administering antiplatelet agents, have persisted without substantial breakthroughs. Bitterroot, along with companies such as Cyclarity and Kate Therapeutics, has decided that it’s time for a change of heart.
Announcing Bitterroot Bio’s emergence from stealth and whopping $145 million raise, its CEO, Dr Pavan Cheruvu, noted that there is an urgent need for fresh and innovative therapeutic strategies in the cardiovascular domain.
“Cardiovascular disease represents an enormous global health burden, and there is a pressing need for safe and effective therapies,” he said. “Our team is excited to leverage our deep expertise in immunology and cardiology to develop transformative therapies that have the potential to improve outcomes for patients with atherosclerosis and other serious cardiovascular disorders [3].”
Bitterroot Bio aims to revolutionize cardiovascular therapeutics by leveraging insights from oncology and autoimmune diseases. Drs Nicholas Leeper and Irving Weissman, the company’s founders, recognized the potential of immunotherapies in targeting inflammation and the immune response.
The Don’t eat me/Eat me adventure
Cancer cells protect themselves from the immune system with proteins, such as CD47, that tell immune cells not to engulf them. Blocking the ‘don’t eat me’ signal means the immune cells sense an ‘eat me’ signal instead and move in for the kill. Antibodies that block CD47 are in clinical trials.
Bitterroot’s flagship asset, BRB-002, focuses on atherosclerosis, a condition characterized by arterial plaque buildup. This protein biologic targets CD47 and blocks its signaling with the aim of restore macrophagic function, effectively eliminating plaques. Notably, BRB-002 not only halts plaque progression but also dissolves existing plaques.
Unlike CD47-targeting drugs being developed for cancer, BRB-002 doesn’t need to get inside a tumor; because it specifically targets the vascular wall, lower doses are needed and this, coupled with its purified formulation, has resulted in a drug that exhibits strong affinity for CD47 targets, but reduces the likelihood of adverse effects commonly associated with CD47-targeting therapies.
With substantial funding now in the bag, Bitterroot Bio aims to advance BRB-002 through Phase 1 and likely proof-of-concept Phase 2a clinical trials, and plans to get BRB-002 into the clinic during 2024 [4]. within the next calendar year. First-in-human trials are planned to evaluate the drug’s safety, tolerability and efficacy in patients with atherosclerosis and other cardiovascular conditions. Bitterroot Bio’s approach holds the potential to reshape the treatment landscape for cardiovascular diseases, but it is not the only biotech hoping to transform the way cardiovascular diseases are treated.
Other ones to watch
Cyclarity, a pioneering company based at the prestigious Buck Institute for Research on Aging in California is another biotech with its sights firmly fixed on atherosclerosis. Its platform uses custom-engineered cyclodextrins to capture and remove oxidized cholesterol derivatives from cells, effectively removing plaque from arterial walls and rehabilitating toxic foam cells into healthy macrophages. Cyclarity’s lead candidate is a proprietary, non-toxic cyclodextrin designed for high affinity and specificity in targeting oxidized cholesterol.
Eko is leveraging digital health technology to enhance the detection and management of cardiovascular conditions. Their AI-powered stethoscopes and handheld ECG devices enable healthcare providers to remotely monitor and diagnose heart conditions with greater accuracy and efficiency, improving patient outcomes and reducing healthcare costs.
Ventrix is pioneering a groundbreaking approach for treating heart attacks. They have developed an injectable hydrogel that, when administered to the site of a heart attack, can scaffold the regeneration of damaged cardiac tissue, potentially restoring heart function and improving patient recovery.
Verve Therapeutics has embarked on a research collaboration with Eli Lilly that focuses on advancing Verve’s preclinical stage in vivo gene editing program targeting lipoprotein(a) (Lp(a)). Elevated Lp(a) is an established and genetically validated, independent risk factor for atherosclerotic cardiovascular disease (ASCVD), ischemic stroke, thrombosis and aortic stenosis, and Verve hopes its therapy will lower of Lp(a) and reduce ASCVD events.
Kate Therapeutics is developed next-gen genetic medicines for muscle and heart diseases. By applying applying novel capsid and cargo technology platforms, KateTx’s platform can target cardiac muscle, tackling genetically defined and complex heart diseases that cannot currently be addressed due to a lack of specific and effective delivery to these tissues.
Heartseed, a Tokyo-based biotech, is developing iPSC-derived cardiomyocytes for heart failure. Its lead asset, HS-001 , is an allogeneic iPSC-derived, highly purified ventricular cardiomyocyte spheroid. Once transplanted, the cardiomyocytes electrically couple with the patient’s myocardium to improve cardiac output by remuscularization and secretion factors that encourage vascularization.
The University of Cambridge has created a novel AI algorithm that could help personalize the prevention of cardiovascular disease. The algorithm can accurately estimate the risk of heart disease caused by cumulative exposure to cholesterol and blood pressure levels and the benefits of lowering both – this provides essential information that can be used to make hyper-personalized treatment decisions, including optimal timing, intensity and duration of therapies that most effectively prevent atherosclerotic cardiovascular events.
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277211/
[2] https://www.cdc.gov/heartdisease/facts.htm
[3] https://bit.ly/3Xugxih
[4] https://bit.ly/3NDfycf
