Exclusive: Maze unveils their $191M pipeline, taking on Vertex and two long-sought conditions
More than two years after emerging from stealth mode with $191 million, a guild of prestigious scientific founders and support from some top-flight VCs, Maze Therapeutics is finally ready to unveil what they’ve been up to.
Maze CEO Jason Coloma walked Endpoints News through their de-stealthed pipeline Monday, showcasing three programs that are still early stage but progressed since the company’s 2019 launch. They include a new small molecule approach for the rare lysosomal disorder Pompe disease, a chronic kidney disease target that will put them in square competition with Vertex, and an ALS gene therapy that theoretically could be marketed for the entire patient population.
The targets all come from the initial batch of programs the Maze’s founders seeded the company with at the start, but they also announced new directions for their earlier stage research, with plans to broadly focus on cardio/renal, cardiovascular, neurology, eye and metabolic diseases and use a number of technologies. Eventually, that could give them 10 to 15 programs between themselves and their partners.
To plan for that expansion, they’ve hired Atul Dandekar, who led ophthalmology at Roche and Genentech, as chief strategy officer.
“In order to execute on that strategy, of course, it’s not trivial,” Coloma said of the 10-15 program plan. “For a small company to try to be indication agnostic and modality agnostic, how do you make those trade-offs between different levels of investments? And to have someone who has seen programs not only get into the clinic but into the marketplace I think is important.”
Although Maze launched with a stated goal of finding new so-called genetic modifiers — underappreciated genes that can change the severity of a monogenetic disease like sickle cell — all of the company’s initial programs go after genes that have been studied previously, including, in one case, to the extent that a rival company put a drug for it in Phase II last year. But Coloma said that each relies on techniques Maze collected and developed to turn those genes into drugs.
“Some of these targets have been known for a while,” he said. “But it took many, many years to figure out how do we utilize all the different technologies at our disposal to actually turn that into a drugging program.”
The Pompe disease program, for instance, goes after a gene called Gys1 that is responsible for making glycogen in cells. The rare muscle-wasting condition arises when glycogen builds up in the cells of patients who don’t have a functioning copy of the enzyme for disposing the sugary molecule, and drug programs have largely either infused artificial copies of that enzyme or sought to deliver a gene for a healthy one. For years, though, researchers theorized you could also inhibit Gys1 and prevent glycogen from building up in the first place.
Maze figured out two pieces of the puzzle to make such a program possible. First, Coloma claimed, Maze became the first company to crack the crystal structure of the enzyme Gys1 codes for. Second, he said, they used tissue and genetic data from thousands of patients at the UK biobank to find that people who happen to have mutated Gys1 genes functional normally, meaning that it should be safe to knock out.
Maze is now developing a daily pill for patients with late-onset stage of the disease. It would be the first oral therapy in a field dominated by infused proteins and experimental gene therapies.
“That would be paradigm-changing,” Coloma said.
The second program is for APOL1, a gene that has long been linked to a greatly increased risk of kidney disease. Vertex now has a molecule in Phase II for the APOL1-linked kidney conditions. Coloma argued that the company’s functional genomics platform could give them new insights and give them a best-in-class drug, but he didn’t offer specifics on what those insights were or might be.
He noted that Vertex has yet to publish their animal data.
“I think you see that quite a bit in cardio-renal,” Coloma said. “It’s not an area where you want to be necessarily first-in-class.”
Lastly, they’ll develop a gene therapy for ALS that targets a gene called ATXN2. Biotechs developing ALS gene therapies have understandably largely focused on single genes that drive ALS, but those genes only account for a small subset of patients. Developing an approach pioneered by co-founder Aaron Gitler, Maze will look to knock out a gene whose absence can help protect against the buildup of dangerous plaques.
The first program, for pompe disease, is slated for the clinic in 2022.