With new startup Bitterroot, Forty Seven founder takes aim at heart disease

Venture firms have historically hesitated to invest in heart drugs. They’re expensive to develop and test and, in recent years, have taken a backseat to research areas like cancer and rare diseases, which can have shorter development timelines.

Yet heart disease remains the world's leading cause of death and a big opportunity for biotech companies. MyoKardia and The Medicines Co., for instance, were both acquired for billions of dollars after heart medicines they developed succeeded in clinical testing. Verve Therapeutics successfully raised hundreds of millions of dollars privately and publicly to test a gene editing treatment for heart disease.

More recently, pharmaceutical companies and smaller biotechs have begun investing heavily in a class of diabetes and weight-loss drugs that are being tested for their potential to lower the risk of heart problems.

Now Bitterroot is emerging with a large investment round of its own. The startup is building on Weissman's research into CD47, a protein associated with a "don't eat me" signal that enables tumors to go undetected by the immune system. Those features have led drugmakers to view antibodies targeting CD47 as key pieces for cancer immunotherapy combinations. But recent research has suggested the protein plays a role in heart disease, too.

Elevated levels of CD47 are found in the blood vessels of people with thickened arteries, where the protein helps harmful cells form plaques. Higher CD47 levels are also associated with a higher risk of heart attacks and strokes. A paper published by Weissman and others last year indicated that blocking CD47 might help the immune system destroy those damaging cells, reduce plaque formation and provide a benefit "independent of traditional cardiovascular risk factors."

The approach hasn't been tested in humans. Additionally, CD47 drugs, including the one invented by Weissman's Forty Seven and now owned by Gilead, have had a bumpy ride in clinical testing for cancer. Several human studies of that drug, magrolimab, were halted because of safety concerns. Other large players, such as Bristol Myers Squibb and AbbVie, have dialed back investment in recent years too.