BEAT BioTherapeutics Corp. (BEATBio) is developing BB-R12, a novel biological therapy with the potential to revolutionize the treatment of heart failure. Heart failure is a large and growing epidemic. The World Health Organization reports that 29% of deaths worldwide are due to cardiovascular disease. Approximately 6 million Americans are living with heart failure today.
BEATBio’s founders made the fundamental discovery that deoxy-ATP (dATP), a natural variant of the more prevalent ATP, and a building block for DNA is a superior “fuel” for heart muscle contraction. Our cardiac gene therapy, BB-R12, uses an AAV viral vector (AAV6) to deliver a gene that increases the production of dATP in the heart. dATP triggers enhanced myosin filament cross-bridge formation causing the heart to beat more powerfully and pump blood more efficiently. More oxygenated blood is supplied to distal organs and tissues correcting the primary disease effects of heart failure. Simple delivery of BB-R12 to the heart through a standard catheter allows it to move through the arterial walls to deliver its transgene directly to heart muscle cells. Once the transgene enters the cardiac muscle cells it produces a natural protein enzyme that converts small amounts of ATP to dATP. Cell-to-cell diffusion of dATP to adjacent heart muscle cells occurs via gap junctions, so only a minority of “factory cells” needs to express and “export” the enzyme to produce increased overall cardiac performance. The company’s advisory teams are recognized experts in cardiovascular biology, cardiovascular medicine, heart failure and gene therapy technology. The technology was developed using $50MM in NIH funding over the past 15 years and BEATBio has an exclusive, worldwide license.
Accomplishments to Date:
- Discovery: Demonstrated that increased dATP dramatically restores ejection fraction and overall cardiac performance in multiple small animal models of heart failure and restores contraction and relaxation function to depressed cardiac muscle cells following injury
- Validation: Recently published on our mechanism of action using tissue samples from 15 patients with severe heart failure undergoing cardiac transplant or LVAD implantation and showed that dATP significantly increased contraction of these cardiomyocytes
- Manufacturing: Created, scaled up and filed patents on a human construct, BB-R12, using an experienced contract manufacturer and the NIH’s proven manufacturing system
- Validation: Successfully repeated prior small animal safety and efficacy data with the human drug candidate
- Validation: Successfully completed a large animal study using the “gold standard” swine infarction-heart failure model with BB-R12 and demonstrated statistically and clinically significant improvements in cardiovascular performance. (This study has now been published in the European Journal of Heart Failure)
- Safety: In the swine study and in small animal studies, there were no observed safety issues
- Durability: Shown that a single administration of BB-R12 to animals is long-lasting and that animals expressing the transgenes from birth live normal life spans and have increased cardiac performance for life
- Development: Held a successful, formal, Pre IND meeting with the FDA that confirmed our proposed forward development plan through IND and Phase I human trials
- Advisory: Assembled an expert team of advisors and consultants to optimally develop the portfolio
- Financial: Raised a $4MM seed round to scale up and pursue IND enabling activities