Biotech targeting rare heart mutation with gene therapy scores $11M in Series A haul
While cardiovascular disease is the leading cause of death globally — it is cancer that has benefited most from strides in precision medicine. Now that cardiovascular-specific genetic mutations are being discovered — they are prime targets for genetic therapy. A biotechnology company carved out of research conducted at Temple University is focusing on a mutant gene that is understood to cause a rare heart condition, which can eventually lead to a heart transplant or the use of implanted cardiac assist devices.
The condition, dilated cardiomyopathy, affects more than 3 million patients in the United States — and in about 35,000 patients, its etiology can be traced to mutations in the BAG3 gene. It is a disease of the heart muscle, usually starting in the heart’s main pumping chamber, the left ventricle. The ventricle stretches and dilates, precluding its ability to pump blood efficiently.
So far, patients are typically treated with a cocktail of treatments including ACE inhibitors, beta-blockers, water pills and blood thinners. The company, christened Renovacor, is developing a gene-therapy designed to treat the BAG3 subpopulation using viral vector. In this population, the mutation prevents the gene from functioning properly — and the therapy is engineered to replace the gene to restore function.
“Gene therapy is…coming into its own and becoming a more a more practical modality for therapeutic intervention. So as those things come together I think…we’re on the cusp of cardiovascular disease moving into a new phase where precision medicine is going to become one of the approaches we have,” chief Maggie Cook noted in an interview with Endpoints News.
In some ways, cardiomyopathies appear to be more amenable to precision medicine than cancer — failing hearts are thought to be generally homogenous; many signaling pathways responsible for regulating cardiac function have been identified; mutations in at least forty genes have been shown to cause familial dilated cardiomyopathy, and the various forms of heart muscle disease have been well characterized phenotypically, Renovacor co-founder Arthur Feldman wrote in a paper published in 2017.
“A principal difference between the translational sciences in HF (heart failure) and in cancer biology that might explain in part the relative lack of precision therapy in the treatment of HF is that HF research has been driven in large part by discoveries in investigational models of HF, whereas drug discovery in cancer has been driven by the elucidation of altered biology of human tumors,” he noted.
Renovacor is expected to be ready for early-stage studies within three years — for now, it is putting together an application to take the drug into the clinic. On Wednesday, it unveiled an $11 million Series A round of financing co-led by Novartis Venture Fund, Broadview Ventures, and BioAdvance, and included the participation of New Leaf Venture Partners and Innogest Capital.
Existing rare disease gene therapies — while considered revolutionary in terms of potency — threaten to wreak havoc on the US healthcare system with their million-dollar price tags. For preclinical Renovacor, it is too early to discuss pricing.
However, the disease the company is targeting carries a heavy burden of hospitalization and morbidity. “The disease comes on in their early 40s, and these are otherwise healthy young adults, so they can live with the disease, and have a huge cost of care over time, then progress to meeting heart transplant, or implanted cardiac assist devices. So…based on different methodologies that you could consider the overall market opportunity…is an attractive one in many different pricing models,” Cook said.
“I think there will always be… cardiovascular disease that’s due to lifestyle choices. And that can’t always necessarily be parsed out genetically…some of that lifestyle intervention will always be necessary,” she added. “However, there are probably groups like the one we’ve identified, where a genetic cause is the primary cause of disease and we can approach that with a more precise therapy.”
The startup is not ruling out a partnership in the future. “You can certainly see it (the therapy) fitting into the portfolio of a larger company,” Cook said.
In May, the head of the Center for Human Genetic Research at Massachusetts General Hospital and the Broad’s Cardiovascular Disease Initiative, Sekar Kathiresan, set up his own shop to tweak genes, such as APOC3 or ANGPTL3, which carry mutations that can rapidly clear triglyceride-rich lipoproteins — which raise individuals’ risk of heart attack — from circulation.