Coda Biotherapeutics launched with a $19 million series A to push its chemogenetic gene therapy platform toward the clinic. Its goal is to create a gene therapy that can be switched on and off, and dialed up and down, to overcome limitations in current technology and open up more diseases to gene therapy.
“Most applications of gene therapy are transferring a gene for constitutive expression of the protein product. That works in a lot of situations, but in many situations, you may need more control than that,” said CEO Michael Narachi, an Amgen veteran who then served as CEO of Orexigen.
For example, Sarepta’s gene therapy for Duchenne muscular dystrophy focuses on boosting levels of micro-dystrophin, a shortened version of dystrophin, a protein that patients with DMD do not produce. Instead of restoring protein expression by replacing a faulty gene with a healthy one, Coda’s approach uses gene therapy to get cells to produce “switch” proteins that have “little to no effect” on the cells until a small-molecule drug is delivered. And because the proteins have been engineered for sensitivity to the small molecule, doses are low, which can limit off-target effects of the drug on other tissues.
MPM Capital and Versant Ventures led the financing, while Astellas Venture Management and Novartis also participated.
Coda’s first focus is neurological diseases, but thinks its platform can be applied in “almost any therapeutic area or disease condition,” Narachi said. At the moment, the company is developing engineered neurotransmitter receptors that are activated by oral drugs to calm down hyperexcitable neurons responsible for chronic neuropathic pain. The gene that codes for the receptors will be delivered via viral vector.
The company’s next steps will be to build out and get its design ready for gene transfer, Narachi said. It’s currently a virtual outfit with a team of around 10 staffers that are mostly focused on research in South San Francisco. The short-term plan is to double that number, he said.
Adding switches to gene therapies is not new—there is a concern that these treatments may stay switched on even after they’ve had their intended effect and cause unwanted side effects. Multiple research groups are working to control gene therapies, but current approaches still have some kinks that need to be worked out before they can be used in humans.
Scientists from the University of Bath and the University of Cardiff used an amino acid to switch on protein expression in mice that had been genetically engineered to glow under ultraviolet light. And a team from King’s College used a dual-vector system that enables an on-off switch for their gene therapy that is triggered by the antibiotic doxycyline. But this system has proven "leaky" so far—even after the gene was switched off, a small part of it remained active. Both approaches target how proteins are expressed, while Coda's platform is designed to control gene therapy at the level of protein activity.
Editor's note: This article has been updated to correct how Coda's technology was characterized. It uses gene therapy to cause cells to express "switch" proteins/receptors, not gene editing.