Mammoth Biosciences

Mammoth Biosciences is a biotechnology company headquartered at 1000 Marina Blvd., Brisbane, California, that develops therapeutics and diagnostics based on CRISPR technology. Its core scientific asset is a portfolio of proprietary ultracompact CRISPR-Cas systems — including NanoCas and CasPhi (CasΦ) and the Cas14 family — discovered through a metagenomics-based protein discovery and engineering platform. These enzymes are described as a third or less the size of Cas9, which the company states allows all-in-one packaging into adeno-associated virus (AAV) vectors and more efficient packaging into lipid nanoparticles (LNP), addressing delivery constraints for in vivo editing in tissues beyond the liver. The company also reports less restrictive or shorter protospacer adjacent motif (PAM) requirements and allele-specific editing capability relative to Cas9.

Beyond nuclease knockouts, Mammoth is developing additional editing modalities including base editing, reverse transcriptase editing (gene writing), and epigenetic editing, positioned as compatible with single-AAV delivery. Its disclosed pipeline includes MB-111, a wholly owned liver program using an ultracompact nuclease knockout delivered by LNP to inactivate the APOC3 gene and lower apoC-III protein and plasma triglycerides, targeting familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (sHTG). Additional undisclosed programs span neuromuscular and CNS targets (AAV delivery) and other tissues, run internally or with partners.

Historically, Mammoth also built a CRISPR-Cas12a-based molecular diagnostics platform (DETECTR, and DETECTR BOOST), which received FDA emergency use authorization for a COVID-19 test and was pursued with partners including GlaxoSmithKline, MilliporeSigma, Hamilton Company, Agilent Technologies, Horizon Discovery and Merck & Co., plus DARPA and NIH RADx funding. In 2023 the company announced it would refocus on CRISPR-based therapeutics, with reported layoffs of 35 staff on the testing team.

Founding story

Mammoth Biosciences was founded in 2017 by Trevor Martin, a recent Stanford PhD, together with UC Berkeley scientists Janice Chen and Lucas Harrington and their advisor, CRISPR co-inventor and Nobel laureate Jennifer Doudna. According to Mayfield, Martin initially incorporated the company as Apheleia Diagnostics around a CRISPR diagnostic technology licensed from UC Berkeley; Mayfield partner Ursheet Parikh, who met Martin through managing partner Navin Chaddha in 2017, invested at seed stage and helped bring Doudna and her students Chen and Harrington into the company, after which the four co-founded Mammoth Biosciences around the concept of a broad CRISPR platform (described internally as "Mammoth Inside").

Business model

Mammoth combines a wholly owned therapeutic pipeline with platform licensing and partnership deals. Partnership economics disclosed for Regeneron include $100 million in upfront payment and equity investment, $370 million per target in development, regulatory and commercial milestones, royalties from single digits to mid-teens on net sales, and an option to co-fund and share profits on a majority of collaboration programs. The Vertex agreement covers two in vivo indications with $40 million in upfront payments and investments, up to $650 million in potential future payments, and tiered royalties on net sales.

Reported revenue sources are collaboration-derived: upfront payments, equity investments, development/regulatory/commercial milestone payments and tiered royalties on future net sales from pharma partnerships (Regeneron, Vertex), plus historical government contracts and diagnostics partnerships. No product sales revenue is disclosed in the sources.

Traction

Mammoth reports raising over $465 million from investors in the US and internationally, including $195 million announced in September 2021 at a valuation above $1 billion. Headcount grew from 35 in 2020 to more than 100 in 2021, with one secondary source citing 190 employees. Pipeline traction includes nomination of MB-111 as first development candidate, non-human primate skeletal muscle editing data with AAV-delivered NanoCas presented at ASGCT 2025, and MB-111 preclinical data at the ESGCT 32nd Annual Congress. Commercial traction includes multi-hundred-million-dollar partnership frameworks with Regeneron and Vertex and, historically, FDA emergency use authorization for its COVID-19 DETECTR test and DARPA/NIH/DoD awards.

Latest developments

Recent announcements include the nomination of MB-111 as Mammoth's first development candidate and the appointment of genetic medicines veteran Bob D. Brown (former EVP of R&D and President at Dicerna) to the board of directors; new results on NanoCas described as the first efficient ultracompact extrahepatic gene editor; presentation of non-human primate skeletal muscle in vivo editing data at ASGCT 2025; MB-111 preclinical data at the ESGCT 32nd Annual Congress; a Regeneron collaboration on next-generation CRISPR-based gene editing across multiple diseases; a California Life Sciences Pantheon Award; and scheduled presentations at the 41st, 43rd and 44th Annual J.P. Morgan Healthcare Conferences.