Trying to deliver compact CRISPR-based gene-editing packages to new places in the body, Regeneron Pharmaceuticals Inc. and a Peninsula company co-founded by Nobel laureate Jennifer Doudna signed a deal valued at $100 million, the companies said Thursday.
It is the third big deal signed by Mammoth Biosciences Inc., a Brisbane company founded seven years ago by the University of California, Berkeley chemist Doudna, two Berkeley doctoral students and two Stanford University Ph.D. students. Mammoth got a $40 million upfront payment in a 2022 deal with Bayer AG and an initial $41 million from a 2021 agreement with Vertex Pharmaceuticals Inc.
Regeneron (NASDAQ: REGN) and Mammoth aren't disclosing their disease targets. But Mammoth could receive up to $370 million per target from Regeneron in development, regulatory and commercial milestone payments plus royalties, and it has an option to ditch the milestones and royalties to cofund and share profits on a majority of its programs.
Some $95 million of the upfront from Regeneron is in the form of an equity investment in Mammoth.
Nobel Laureate in Chemistry Jennifer Doudna poses for a photo outside the Innovative Genomics Institute at UC Berkeley in Berkeley, Ca. on Wednesday, Nov. 23, 2022.
Beyond the payouts, Mammoth's deal could be significant for the field of medicines using CRISPR, or clustered regularly interspaced short palindromic repeats, that is used to selectively fix stretches of DNA.
The first generation of CRISPR medicines, like Vertex's one-time sickle cell treatment Casgevy, is an ex vivo therapy, meaning a patient's cells are modified in a lab then transplanted back into the patient. In vivo therapies like those that are the focus of the Mammoth's deals with Regeneron, Bayer and Vertex aim to land all gene-editing tools to the exact place in the body where the therapy is needed, eliminating the lengthy process of re-engineering cells outside the body.
What's more, the deal gives Mammoth another chance to show how the DNA cutting tools it develops — so-called Cas proteins — can be reduced to fit snugly with other tools inside delivery vehicles such as shelled out adeno-associated viruses, or AAVs, that Regeneron is using.
Mammoth's Cas proteins are a third of the size of the original CRISPR-Cas9 that Doudna originally explored, said Lucas Harrington, who serves as chief science officer and co-founded Mammoth with Janice Chen, Trevor Martin, Ashley Tehranchi and Doudna.
Chen is chief technology officer and Martin is CEO of Mammoth. Tehranchi is no longer with the company.
Size is everything as corporate and academic researchers try to find ways to move the delivery of CRISPR beyond the liver into muscle and the brain, for example.
Mammoth Bio founders Janice Chen, Lucas Harrington (center) and Trevor Martin
"Most genetic diseases are not in the liver," Harrington said. "The challenge is, how do we get into these other tissues."
Regeneron, the 35-year-old developer of the dermatitis drug Dupixent, the eye drug Eylea and other therapies, is working on the next generation of AAVs that are big improvements for safely and specifically landing CRISPR packages in the body, Harrington said.
Regeneron, which will lead development and commercialization, for five-and-a-half years will largely have access to Mammoth's editing technologies and an option to extend that access for an additional two years for an undisclosed fee.
The two companies for years had been talking and getting to know each other scientifically, Martin said. The fact that Tarrytown, New York-based Regeneron, like 150-employee Mammoth, is a founder-led company went a long way, with neurologist Leonard Schleifer as board co-chair and CEO and molecular immunologist George Yancopoulos still leading it as board co-chair, president and chief scientific officer.
"We have the same ambition to be a longtime biotech," Martin said.