The genetic medicines field is working toward therapies capable of doing their editing work inside the body by reaching many different types of 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 committing $100 million to Mammoth to kick off the agreement, which was announced Thursday.
Delivery to particular tissues is a long-standing challenge for genetic medicines. Lipid nanoparticles are one delivery method, but these particles preferentially go to the liver. Adeno-associated viruses (AAV) offer an alternative, but these delivery vehicles have limited capacity for genetic cargo.
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The research of Tarrytown, New York-based Regeneron includes the development of AAVs that use antibodies to target their delivery to specific tissues and cell types. Brisbane, California-based Mammoth brings to the alliance its experience with CRISPR, particularly ultracompact gene-editing systems. Early biopharmaceutical industry CRISPR research used the Cas9 cutting enzyme, which is relatively large in size, said Janice Chen, a co-founder and chief technology officer of Mammoth. The startup is based on research from Jennifer Doudna, who won a Nobel Prize for her work in CRISPR. Doudna’s research also spanned other CRISPR proteins that are much smaller than Cas9. That’s key to the approach of Mammoth, whose CRISPR enzymes can fit on AAV with room to spare for more genetic cargo.
“We believe in the incredible power of gene editing, which we are utilizing in our diverse preclinical and clinical genetic medicines pipeline,” Christos Kyratsous, senior vice president and co-head of Regeneron Genetic Medicines at Regeneron, said in a prepared statement. “After years spent developing 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 in the chase 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 the transthyretin amyloidosis, a rare disease driven by abnormal versions of a liver protein. In 2020, the alliance expanded to hemophilia A and B. Last year, the companies expanded their partnership yet again to add neurological and muscular diseases.
Trevor Martin, co-founder CEO of Mammoth, declined to say which diseases his company and Regeneron will pursue. But speaking generally, he said they are genetic diseases in which in vivo editing could offer patients a one-time treatment.
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“A single injection can potentially result in a permanent cure for the disease,” he said.
The financials of the agreement break down to Regeneron paying Mammoth $5 million upfront and making a $95 million equity investment. Regeneron gains access to Mammoth’s editing technologies, other than for certain excluded targets. Regeneron may pay an extension fee to extend its access to those technologies for two more years.
The agreement calls for the two companies to jointly select targets and research them. Regeneron will lead development and commercialization of potential therapies. The number of targets covered by the agreement was not disclosed, but Mammoth is eligible for up to $370 million in development, regulatory, and commercial milestone payments for each target, plus royalties from sales of approved products. The deal also gives Mammoth the option of co-funding and sharing in the commercialization of most of the collaboration programs in lieu of receiving milestone payments and royalties.
Mammoth’s initial focus was the development of CRISPR-based diagnostics. During the Covid-19 pandemic, Mammoth ramped up work in both diagnostics and therapeutics. 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. That 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 the capital from Regeneron puts Mammoth in a strong financial position and the company does not have to immediately raise more money.
Photo by Mammoth Biosciences
