NEW YORK – CRISPR technology startup Mammoth Biosciences said on Thursday that it has raised a combined $195 million through Series C and Series D financing rounds, making it a so-called unicorn company — startups that are valued at more than $1 billion.
The financing included a $45 million Series C round, which was completed in late 2020, and was led by Redmile Group and Foresite Capital. That round also included participation from previous investors, as well as Amazon. The financing also included a $150 million Series D round, which was led by Redmile Group, with participation from Foresite Capital, Senator Investment Group, Sixth Street, Greenspring Associates, Mayfield, Decheng Capital, NFX, and Plum Alley.
The firm's most recent fundraising round before this was an oversubscribed $45 million Series B in January 2020, led by Decheng Capital, with participation from Mayfield, NFX, Verily, and Brook Byers.
Mammoth said it will use the funds to broaden its toolkit of next-generation CRISPR systems, with a focus on building a pipeline of in vivo gene-editing therapeutics, specifically using a set of ultra-small Cas proteins the firm has exclusively licensed from the University of California, Berkeley. It will also continue to develop its CRISPR-based diagnostics platform.
"[Achieving unicorn status] really helps us deliver on the promise of CRISPR and our excitement about these new proteins," Mammoth CEO Trevor Martin said. "In particular, one of the main things we're excited about is these ultra-small [Cas proteins] that we pioneered. People didn't really realize at all that CRISPR systems could be so small and compact, and that unlocks a huge area of different in vivo applications."
In general, Martin added, the company's "North Star" in therapeutics is the field of permanent genetic cures and in vivo applications, where CRISPR-based therapeutics are delivered directly into the body to edit cells, rather than in vitro therapeutics, where patients' cells are taken out of the body, edited in a dish, and then reinjected.
"I think what's been most public about the company is [that] the pandemic has really accelerated our diagnostic work," Martin said. "But also, we've been pedal to the metal on our therapeutic applications and we've made huge technical strides there. So definitely this money [from the financing round] is going to enable taking our therapeutic programs to the next level, both in terms of building out internal programs … and working with partners on these ultra-small systems."
In particular, Mammoth is focused on developing the properties of the Cas14 and Casɸ nucleases, which were both discovered in the lab of company cofounder and Berkeley researcher Jennifer Doudna. These Cas families are the smallest known CRISPR systems, and Mammoth believes they can help therapeutics developers overcome some of the challenges faced by using more well-known enzymes such as Cas9 and Cas12, such as advanced and expanded delivery for in vivo genome editing in a variety of diseases.
Although research remains to be done on their capabilities, Cas14 nucleases have already been shown to be exceptionally small at only 400 to 700 amino acids in length. The nuclease also doesn't seem to need a specific protospacer adjacent motif (PAM) in order to bind or cleave a target DNA sequence.
As for Casɸ, it was shown to comprise a single protein of about 70 kilodaltons and a CRISPR array. But aside from its small size, the researchers who discovered it also found that the protein was able to develop its own guide RNA and cut the target DNA within the same site at the same time. That means it doesn't need to outsource gRNA production to other enzymes like Cas9 or Cas14 do. And unlike Cas12, it doesn't need to carry additional domains for gRNA development. The protein's small size in combination with its minimal PAM requirement would be particularly advantageous for both vector-based delivery into cells and a wider range of targetable genomic sequences.
For diagnostics, the company said it will continue to build decentralized, on-demand diagnostics for patients and consumers, such as the SARS-CoV-2 tests that it developed during the COVID-19 pandemic on its DETECTR platform. The biotech company first described its DETECTR-based SARS-CoV-2 test in April 2020, and then Mammoth partnered with the consumer healthcare arm of pharmaceutical company GlaxoSmithKline to develop a CRISPR-based SARS-CoV-2 diagnostic test for use by consumers at home and healthcare providers in clinics.
The company also took a lead role earlier this year in a US government-funded, public-private effort to develop multi-pathogen detection platforms based on CRISPR technology. The project, funded through a $36.7 million contract from the Defense Advanced Research Projects Agency's (DARPA) Detect It with Gene Editing Technologies (DIGET) program, aims to create a disposable point-of-care device for the detection of at least 10 pathogens, and a massively multiplexed device for the detection of at least 1,000 targets.
Martin also noted that the company is working on a platform he referred to as CRISPR Plus — a type of system that would combine CRISPR with various functionalities such as CRISPR activating, CRISPR inhibiting, base editing or others. The ability to combine all these functions into one platform would be enabled by the ultra-small systems, he said. Mammoth is currently experimenting with what such a platform could do, both internally and with potential partners.