Charles Chiu
Charles Chiu, MD, PhD

Mammoth Biosciences has raised $45 million in an oversubscribed Series B financing with the goal of expanding beyond CRISPR-based disease detection—including a collaboration targeting 2019-nCoV coronavirus—towards offerings that apply the company’s platform to gene editing and next-generation therapeutics.

Mammoth is partnering with infectious disease specialist Charles Chiu, MD, PhD, a professor at University of California, San Francisco and director of the UCSF-Abbott Viral Diagnostics and Discovery Center—and a member of the company’s Scientific Advisory Board—to create a prototype of a rapid point-of-care molecular test for 2019-nCoV that can quickly and accurately distinguish the recently-discovered coronavirus strain from all other infectious diseases.

“The current tests can take up to 24 hours to return results. The key idea is: is it possible to create a test that has a much more rapid turnaround, and is also very rapidly developed, and that also has that really intense accuracy that you need from the test?” Mammoth Biosciences CEO and co-founder Trevor Martin, PhD, told GEN Edge.

“We’re aiming for as short a time frame as possible. You definitely want something less than an hour, ideally.”

Mammoth’s new Series B financing, Martin said, will fuel development of Mammoth’s CRISPR platform, with a focus on an enzyme discovered by the company, Cas14. In a 2018 study published in Science, a research team led by Mammoth co-founder and CRISPR pioneer Jennifer Doudna, PhD, (HHMI/University of California, Berkeley) detailed how the compact effector protein appeared to target single-stranded DNA without the usual sequence restrictions of class 2 CRISPR systems such as Cas9 and Cas12.

Mammoth reasons that Cas14’s higher fidelity and smaller footprint—one-third that of class 2 CRISPR systems—will enable its use in a broader range of next-gen editing targets in both ex vivo and in vivo applications. Cas14 could enable targeted gene regulation, precision editing, and other advanced CRISPR modalities.

Opening up delivery options

Trevor Martin, PhD, CEO and co-founder of Mammoth Biosciences

“You can actually open up tons of different delivery options, and also the efficacy of that delivery,” Martin said. Whether using an AAV (adeno-associated virus) or an LNP (lipid-based nanoparticle), “these can all benefit hugely from having a nano-sized protein. That’s one of the novel properties of these enzymes that we’re excited about all that can be leveraged in the therapeutic space.”

“Cas9 is a great protein,” Martin insists, adding there’s a reason why it’s being driven forward into the clinic and actually curing people, “which is really awesome. But it has real limitations.”

One of those limitations, according to Martin, include the requirement of a short Protospacer Adjacent Motif (PAM) sequence adjacent to the cleavage site, which limits the areas of the genome where it be used. “This can be OK if you’re taking a sledgehammer approach and you just want to put [the edit] anywhere in the gene. But for next-generation therapies, where you want more of a scalpel than a sledgehammer, you really want to have increased targeting ability.”

Another Cas9 limitation is that it favors ex vivo applications—although the first in vivo test of CRISPR-Cas9-based genome editing in humans, the Phase I/II Brilliance trial (NCT03872479) was launched last year by Allergan and Editas Medicine.

“There’s not necessarily one protein that’s going to be perfect for everything,” Martin explained. “In some cases, maybe you want a small enzyme. In other cases, maybe you don’t necessarily need a small or large, for example in diagnostics. In other cases, it’s really all about the off-target vs. on-target.”

“At Mammoth, we have the largest toolbox of proteins, so for whatever problem we’re tackling—and we’re very product-focused in that sense—we want to have the right tool in the toolbox that we can pull out to tackle that product.”

Besides expanding the CRISPR toolbox, Mammoth has been expanding its staff and adding experience to its C-suite. In recent weeks, the company has appointed Ted Tisch (ex-Synthego and Bio-Rad Laboratories) as COO, and named Peter Nell, a co-founder of Casebia (a joint venture between Bayer and CRISPR Therapeutics) as chief business officer. The Dean of the Stanford University School of Medicine, Lloyd B. Minor, MD, has joined the Mammoth advisory board.

Gene editing partnership

Last summer, Mammoth completed its move into larger labs dubbed “Mammoth 2.0” in South San Francisco, CA. [Mammoth Biosciences]
Mammoth also recently announced its first gene-editing partnership, licensing its platform to Horizon Discovery to develop a new generation of genetically engineered CHO cells for producing biotherapeutics such as therapeutic antibodies. The value of that partnership was not disclosed.

Mammoth also plans to expand into CRISPR-based therapeutics through partnerships with biotech and pharmaceutical companies.

The Series B financing brings Mammoth to more than $70 million in total capital raised since it was established in 2017 by Doudna and Martin along with CSO Lucas Harrington, PhD, and CTO Janice Chen, PhD.

Mammoth’s co-founders brought the company from stealth mode in April 2018, disclosing plans to develop an easy-to-use and affordable point-of-care test enabling fast, simultaneous detection of multiple conditions, in real-time, both in the hospital and at home, through a single credit card-sized strip form factor.

Last year, Mammoth exclusively licensed patents granted by the U.S. Patent and Trademark Office to the regents of the University of California that cover CRISPR collateral cleavage diagnostic systems—a key milestone, according to the company, in its effort to be the first to market a CRISPR-based disease detection platform.

Decheng Capital led the Series B financing, with participation by Doudna as well as Mayfield, NFX, Brook Byers—and Verily Life Sciences, the life sciences research organization of Google parent, Alphabet Inc.

Last summer, Mammoth completed its move into larger labs dubbed “dubbed Mammoth 2.0” in South San Francisco, CA, within Verily’s campus, from a shared incubator space in San Francisco’s Dogpatch neighborhood.

Martin said Mammoth connected with Verily through individual investors that included Jeff Huber, founding CEO and vice chairman of liquid biopsy pioneer GRAIL, as well as an independent director on Mammoth’s board. Huber is a former Google executive who led development for Google Ads, Google Apps, and Google Maps. “Our current investors have been really awesome in terms of connecting us with people that can help us out,” Martin said.

Mayfield led Mammoth’s $23 million Series A financing in 2018, with participation from NFX as well as 8VC.

“Mammoth is now in this amazing position to really be the foundation for what’s next in CRISPR. That’s what we’re excited about!” Martin said.

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