Casma Therapeutics is taking aim at a range of conditions through a "long-neglected" cell process: its garbage disposal. Armed with $58.5 million in series A cash from Third Rock, the biotech is working on a platform that could lay the groundwork for disease-modifying therapies for inflammatory and neurodegenerative diseases, among others.
Autophagy, the process by which cells clear out unwanted material—such as proteins, organelles and pathogens—has been implicated in a number of disease areas. In neurodegenerative disease, says Casma CEO Keith Dionne, cells' ability to induce autophagy slows down over time and dysfunctional material starts to accumulate. Cellular function starts to decline and then the cells die.
“This is an exciting time to launch Casma, as new discoveries have shed light on just how vital the process of autophagy is to maintain cellular health and prevent disease,” Dionne said in a statement. “We are driven to expand our understanding of this fundamental cellular process—and to translate those insights into breakthroughs for patients.”
Casma has not disclosed specific indications but said it is looking broadly at lysosomal storage disorders and liver and muscle diseases, as well as inflammatory and neurodegenerative diseases. First up, Dionne said, is company building. With its office and lab space up and running, the 10-person biotech is looking to double the number of its employees by the end of the year.
It will develop its product engine, which is designed to identify and validate targets that induce autophagy at various stages of the process and connect them to various diseases. From there, the plan is to advance four or five lead programs to identify small molecules that interact with validated targets, with the goal of bringing them into preclinical and clinical work, Dionne said.
“Understanding autophagy has opened up a vast new set of targets for drug discovery and development,” said Beth Levine, M.D., a scientific co-founder of Casma who discovered the first known mammalian autophagy gene, BECN1. “We see a tremendous opportunity to make a difference for patients who have few other options.”
Blocking autophagy is one strategy to bring about cell death, which can be useful in cancer treatment. But in certain conditions, boosting the process can promote cell death. Casma thinks that enhancing autophagy will have broader applications than inhibiting it, Dionne said.
It's not the only one. Novartis' blood cancer drug nilotinib, marketed as Tasigna, works by forcing cancer cells into autophagy. It showed promise in a small phase 1 study in patients with Parkinson's disease, though the study was not set up to demonstrate efficacy and was not placebo-controlled. A phase 2 Parkinson's trial is now enrolling patients. And the amyotrophic lateral sclerosis-focused startup, QurAlis, is taking a three-pronged approach to the disease, one of which aims to restore autophagy.