Today, the South San Francisco–based start-up Tenaya Therapeutics announced that it raised $92 million in series B financing to take a bold and broad approach to treating cardiac diseases.
The start-up is developing small molecules and gene therapies to treat multiple rare, genetic heart diseases that have been overlooked by larger companies. At the same time, Tenaya is developing gene therapies that program connective tissue cells to morph into heart muscle cells in people who have suffered a heart attack.
Tenaya is the brainchild of five academic cofounders from the Gladstone Institutes, a sixth academic cofounder from the University of Texas Southwestern Medical Center, and David Goeddel from the venture capital firm The Column Group, which launched the start-up with $50 million in series A financing in 2016.
So far, most gene therapies under development are intended to treat rare genetic disorders. Manufacturing the therapies is difficult and expensive, and the first two approved in the US have price tags of $850,000 and $2.1 million. The Centers for Disease Control and Prevention estimate that 790,000 people in the US have a heart attack every year. If Tenaya is successful in its gene therapy ambitions, it will raise many questions about how to bring gene therapy to the masses.
Many gene therapy companies are using adeno-associated viruses (AAVs) to deliver therapeutic genes into cells. Different variants of AAVs are best for getting genes into different organs, such as the eye, liver, or muscles. But the most popular AAVs are not great at making their way into heart tissue. Because of that, Tenaya invested in making new AAVs and screening them for uptake into specific heart cells. “Everything so far has been home grown,” CEO Faraz Ali says.
The start-up is using those AAVs to develop therapies for rare genetic cardiomyopathies—diseases where the heart has a hard time pumping blood. When the mutation that causes the disease is known, it could be fixed by using AAVs to deliver a healthy copy of the gene.
Tenaya is also shooting for a larger market with gene therapies that may help people recover after a heart attack. Ali calls this the company’s cellular regeneration platform. In 2012, Deepak Srivastava, a Tenaya cofounder from the Gladstone Institute of Cardiovascular Disease, showed that it is possible to convert connective tissue cells called cardiac fibroblasts into active heart muscle cells known as cardiomyocytes. That work, done in mice, used a cocktail of proteins called transcription factors to reprogram cells (Nature 2012, DOI: 10.1038/nature11044).
Ali says Tenaya has expanded upon Srivastava’s work to find a combination of transcription factors that it can encode into a single AAV for its experimental human gene therapy. He emphasizes that Tenaya’s approach won’t convert the scar tissue that forms after a heart attack back into muscle. But depending on how soon after a heart attack the gene therapy is given, the therapy might prevent the formation of additional scar tissue, and it should encourage the formation of new muscle.
The start-up has a third research program that uses cardiomyocytes derived from people with rare heart diseases to screen for small molecules that can boost the health of heart cells. “A typical biotech has a single platform,” Ali says. “We are turning the biotech playbook a little bit on its head.”
Ali says the new financing will help Tenaya move multiple programs towards the clinic and scale up its in-house gene therapy production in South San Francisco. He hopes to start clinical testing for at least one program by the end of 2021.