Startups, Venture

Third Rock sinks $59M into Casma’s ‘recycling’ tech, with neuro on the mind

It feels like launch season, and Third Rock is on a roll. The venture fund and startup incubator is unveiling yet another biotech — its third public launch in a number of weeks. This one is stepping out with a $58.5 million Series A, and a locked and loaded staff of autophagy experts.

Beth Levine

The company, called Casma Therapeutics, has quietly been working on technology that it hopes will arrest — or even reverse — the progression of both rare and broad genetic diseases, including the failure-ridden space of neurodegeneration.

To do this, Cambridge, MA-based Casma is using new strategies to boost the body’s ability to break down material it no longer needs, like misfolded proteins, invading pathogens, or spare organelles. Think of it as the cell’s recycling system. When this slaughter and salvage process (called autophagy) isn’t working — or when it’s overwhelmed by disease — all sorts of things can go awry.

Casma’s CEO Keith Dionne tells me the company is looking at using small molecules to drug various proteins involved in triggering autophagy. The idea is to intervene at strategic points in the autophagy process to boost the recycling system. And they’ve got preclinical data that suggest turning the dial up on autophagy could lead to treatments for a wide range of disease, including lysosomal storage disorders, liver and muscle diseases, inflammatory disorders, and neurodegeneration.

Andrea Ballabio

“In preclinical models, we’re seeing a major effect in a number of diseases,” Dionne said. “And it’s proven to be quite safe. If you genetically induce autophagy in mice, they live healthier, longer lives — freer of disease.”

Casma already has “4 to 5” programs in the pipeline, Dionne said.

James Hurley

Interest in this field has been warming up since 2016, when the discovery of key mechanisms in autophagy earned the Nobel Prize for Physiology or Medicine. Since then, the science has moved rapidly. Many companies are now pursuing the idea of autophagy’s impact on disease.

“There are a number of drugs known to enhance autophagy as a side effect,” Dionne said. “The key thing we want to do is go after the specific mechanism, without a lot of other side effects.”

Herbert “Skip” Virgin

Casma’s scientific founders certainly have loads of combined experience in autophagy. Among them is Beth Levine, director of the Center for Autophagy Research, who’s recognized as a worldwide expert in autophagy for her discovery of the mammalian autophagy gene, BECN1, and other components of the autophagy pathway. Then there’s Andrea Ballabio, a leader in the field of transcriptional regulation of lysosomal biogenesis and autophagy; James Hurley, who performed groundbreaking studies to determine the structure and activity of autophagy core complexes; and Herbert “Skip” Virgin, who forged new ground in the understanding of autophagy’s role in inflammation and immunity.

Dionne said the company’s Series A should get them 2 to 3 years of runway, giving the company the chance to develop specific enhancers of autophagy and validate if they’re working.

Image: Keith Dionne. Casma


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