Roche schizophrenia drug that failed PhIII gets a new life in rare disorder as OrbiMed leads $90M for startup
Until a few years ago, GlyT1, a glycine transporter, seemed like a promising target for an add-on therapy to treat negative symptoms of schizophrenia.
But scientists were thrusted back to the drawing board in 2014, when Roche reported that its GlyT1 inhibitor, bitopertin, had failed two Phase III trials. A few months later, they scrapped the program altogether.
The drug sat on the shelves for seven years. Then Disc Medicine came along.
The biotech, which had licensed bitopertin from Roche in a $200 million deal with an undisclosed upfront, has now nabbed $90 million in Series B cash to take the drug in a completely different direction: rare genetic disorders known as erythropoietic porphyrias.
Disc Medicine had a lead program on its own: DISC-0974, an anemia drug that works by controlling iron metabolism and is already in the clinic. The hematology-focused company, though, had been researching other ways to treat diseases by going after “fundamental components” of pathways related to red blood cells, said CEO John Quisel, so as to fully take advantage of the expert network and capabilities it’s built.
One of those pathways is heme synthesis. In erythropoietic porphyrias, a buildup of porphyrins lead to toxic reactions to sunlight — 30 minutes under the sun could cause severe pain and a burning sensation.
Across a series of cellular and mouse experiments, researchers found that targeting a heme metabolite called protoporphyrin IX could fix the defect that results in porphyrin accumulation.
Because Roche had been looking at glycine control as a way to treat schizophrenia patients, investigators had measured those metrics and showed that’s exactly what the drug did in patients — even though they were “hematologically normal.” Clinical data from thousands of patients also suggest a clean safety profile.
While a host of GlyT1 inhibitors had been created, many had failed in earlier stages for safety or other reasons. Roche offered the best molecule with a solid clinical package.
“It’s very rare to be able to move into a Phase II program with this kind of information already established by Roche,” Quisel said.
“The task left for us at Disc is to demonstrate how much we are addressing the unmet need in EPP patients,” added Will Savage, who was promoted to CMO last week as part of a quartet of leadership changes.
With the new cash infusion, the team — now standing at 20 — expects to have multiple Phase II trials for bitopertin and DISC-0974 up and running, then secure proof-of-concept data in 2023. Then there are the early-stage discovery programs lining behind.
OrbiMed led the new round, joined by new investors Arix Bioscience, Janus Henderson Investors, 5AM Ventures, Rock Springs Capital, Nantahala Capital Management, Willett Advisors, and Alexandria Venture Investments. Existing backers, including Atlas Venture, Novo Holdings and Access Biotechnology, also participated.