The COVID pandemic was a make or break moment for many a biotech. At Mammoth Biosciences, it may have been a little of both. For Janice Chen, Ph.D., the CRISPR biotech's chief technology officer and co-founder who ventured out of her lab and into the C-suite in 2018, the whole journey has been wild.
“Sometimes I feel like riding a tiger,” Chen said in an interview with Fierce Biotech. “It's incredibly thrilling to be able to be an inventor on these technologies and then be a part of mapping out how that ultimately will get to patients.”
Chen got her start in the University of California, Berkeley lab of Jennifer Doudna, Ph.D., which is where Mammoth was born, co-founded as well by CEO Trevor Martin, Chief Scientific Officer Lucas Harrington and Doudna. Chen was one of the main authors on a paper describing the DETECTR system to use CRISPR-CAS12 to detect the SARS-CoV-2 virus. After making discoveries at the bench, Chen decided to make the jump to biotech leadership.
“We started this company because we recognize just how powerful this CRISPR technology platform is and how expansive it can be,” Chen said. “It's sometimes hard to imagine that we've been able to bring Mammoth to where we are today.”
It doesn’t hurt, of course, to have a world-renowned CRISPR pioneer behind your company. But even that couldn’t shield Mammoth completely from the brutal market churn that has been devouring biotechs as the pandemic slides into the rearview mirror. Mammoth just announced a pivot away from the testing technology—one of Chen’s early triumphs. Thirty-five staffers were let go in the transition in March as the focus moves to therapeutics.
“We had to make some difficult strategic decisions at the end of the year, but, in terms of being able to get through a difficult market environment, I think we're very well positioned,” she said.
Chen attributes the industry's challenges to the "ripple effects" of the pandemic—when money poured in for startups and the hope of riding the wave of goodwill as companies scrambled to provide vaccines, therapeutics and diagnostics.
Post-pandemic Mammoth
The company came into the public consciousness in the early days of the pandemic by developing a CRISPR-based COVID-19 test that was eventually granted an emergency use authorization by the FDA. The authorization was revoked this February at Mammoth’s request when the biotech decided against commercializing it.
“We really stepped up to the challenge during COVID in terms of getting our diagnostics platform and pushing that forward,” Chen said. Mammoth partnered with private and government collaborators to make the EUA happen. The resulting technology showcased what CRISPR can do for testing in a very short time frame.
Mammoth is putting COVID testing for the masses behind it, and the remaining diagnostics team will instead consider ways to use CRISPR for genotyping or helping other companies better their products.
“What we're finding is that many of the platforms that are on the market now are struggling to kind of meet this post pandemic world and what that means for being able to provide meaningful results when we're not in emergency situations,” Chen said. “So that's kind of where we're focused on for CRISPR diagnostics, is to fit that specific need, which is still a tremendous opportunity for Mammoth.”
Mammoth will not be “focusing on battling it out in the commercial world, but really enabling those technologies so that we can work with partners to actually fill that gap in their portfolios.”
Chen is proud of the diagnostics work, but as Mammoth’s focus shifts, she says the company’s other discoveries, a portfolio of enzymes including the ultra-compact CRISPR enzymes to be showcased at the American Society for Gene and Cell Therapy annual meeting this month, are just as important.
“At this time, we really pared back our diagnostic effort and really just focused on what we do best, which is discovering and developing CRISPR CAS enzymes that have new and unique capabilities,” Chen said. Those enzymes could be used for diagnostics, but Mammoth is more focused on the opportunities in therapeutics now, she confirmed. “Ultimately, we're really excited about kind of the full spectrum of where CRISPR can play a role. And having these different use cases is something that is also very unique to Mammoth [that] other different companies are not pursuing.”
That means Chen is not going anywhere, even if she’s best known for the DETECTR work.
“There's been a lot of evolution for myself personally, and of course for the company, but embracing that change is something that I've become very comfortable with over the years,” Chen said. It was at grad school where she learned how to focus on a big problem but still follow the science where it leads. “Those are the lessons that translate really well into starting a company.”
The ultra-small enzymes are designed to fit within the constraints of a single adeno-associated virus capsid to be used with in vivo gene editing. The goal is to open up indications beyond the liver, which is where other leading gene editing companies have been confined with the currently dominant technology that’s already in the clinic. Mammoth has yet to disclose specific indications, but Chen highlighted muscle or the central nervous system as potential targets.
Mammoth has partnerships with Vertex Pharmaceuticals and Bayer in addition to a wholly owned pipeline. Right now, the biotech is working through de-risking the ultra-compact enzymes, Chen said. While she could not say definitively when Mammoth might enter the clinic, she promised “it won't be more than five years.”
Chen says that Mammoth has “a couple years of cash runway” and is “in a good situation,” so there’s no urgent need to fundraise or add more partnerships to the two Big Pharma collaborations.
“When it comes to partnering, we're extremely thoughtful about it,” Chen said. A good partner for Mammoth would “help us move faster” and add some complementary technology—both qualities that were found with the Vertex and Bayer tie-ups, she noted. “So as we think about partnering in the future, that's the mindset and the lens that we look through.”
Wherever Mammoth takes its therapeutics, it's a good time to be in gene editing; the industry is poised to have its first regulatory approval from the FDA for Vertex and CRISPR Therapeutics' sickle cell treatment. Chen reflected on the 10 years since Doudna and her collaborator Emmanuelle Charpentier, Ph.D., published their CRISPR-CAS9 paper and the incredible work happening at peer companies like Intellia Therapeutics (another Doudna-founded biotech).
"It's a huge milestone for the field and really exciting to be witnessing it at this point in the history of CRISPR," Chen said.