The field of genetic medicine is working on therapies that can do their editing work in the body, reaching many different tissue and cell types. Regeneron Pharmaceuticals and Mammoth Biosciences are joining forces to see if their respective technologies can deliver on that promise.
Regeneron is providing $100 million to Mammoth to make the deal announced Thursday a reality.
Delivery to specific tissues has long been a challenge for genetic drugs. Lipid nanoparticles are one delivery method, but these preferentially reach the liver. Adeno-associated viruses (AAV) offer an alternative, but these delivery vehicles have limited capacity for genetic cargo.
Tarrytown, New York-based Regeneron’s research involves developing AAVs that use antibodies to target their delivery to specific tissues and cell types. Brisbane, California-based Mammoth brings its experience with CRISPR, particularly ultra-compact gene editing systems, to the alliance. Early CRISPR research in the biopharmaceutical industry used the relatively large cutting enzyme Cas9, said Janice Chen, co-founder and chief technology officer of Mammoth. The startup is based on research by Jennifer Doudna, who won a Nobel Prize for her work in CRISPR. Doudna’s research also included other CRISPR proteins that are much smaller than Cas9. That’s key to Mammoth’s approach, whose CRISPR enzymes fit AAV and make room for more genetic cargo.
“We believe in the incredible power of gene editing, which we leverage in our diverse preclinical and clinical genetic medicine pipeline,” said Christos Kyratsous, senior vice president and co-head of Regeneron Genetic Medicines at Regeneron, in a prepared statement. “After years of working to develop our next-generation delivery approaches, we are eager to combine them with Mammoth’s gene editing systems to better match payload, delivery system and disease type.”
Regeneron was already looking for in vivo CRISPR therapies through its alliance with Intellia Therapeutics. In 2016, the partners began collaborating on NTLA-2001, a CRISPR/Cas9 gene editing therapy in clinical development for transthyretin amyloidosis, a rare disease caused by abnormal versions of a liver protein. In 2020, the alliance was expanded to include hemophilia A and B. Last year, the companies expanded their partnership again to include neurological and muscular diseases.
Mammoth co-founder and CEO Trevor Martin declined to say what diseases his company and Regeneron will fight. In general, however, he said these are genetic diseases where in vivo editing can provide patients with a one-time treatment.
“A single injection can potentially lead to a permanent cure for the disease,” he said.
The financials of the agreement consist of Regeneron paying Mammoth $5 million upfront and making a capital investment of $95 million. Regeneron will have access to Mammoth’s processing technologies, except for certain excluded targets. Regeneron may pay a renewal fee to extend its access to these technologies for an additional two years.
The agreement stipulates that the two companies will jointly select targets and investigate them. Regeneron will lead the development and commercialization of potential therapies. The number of targets covered by the agreement was not disclosed, but Mammoth is eligible to receive up to $370 million in development, regulatory and commercial milestone payments for each target, as well as royalties from sales of approved products. The deal also gives Mammoth the opportunity to co-finance most collaboration programs and participate in their commercialization instead of receiving milestone payments and royalties.
Mammoth’s initial focus was on developing CRISPR-based diagnostics. During the Covid-19 pandemic, Mammoth has intensified its work in both diagnostics and therapy. Diagnostic applications of CRISPR are still part of Mammoth’s broader strategy, but the company is starting to focus more on therapeutics, Chen said. The company’s most advanced internal program is in preclinical development for two liver diseases. This therapeutic candidate is delivered by a lipid nanoparticle.
Regeneron is the third biopharmaceutical industry partner for Mammoth, following alliances with Bayer and Vertex Pharmaceuticals. Martin said Regeneron’s capital puts Mammoth in a strong financial position and the company doesn’t need to raise more money immediately.
Photo by Mammoth Biosciences