Regeneron is expanding its genetic medicine efforts and will work with California startup Mammoth Biosciences on gene-editing programs reaching parts of the human body beyond the liver, the companies announced Thursday.
While CRISPR/Cas9 gene-editing technology has won a Nobel Prize, biopharma companies have struggled to turn the tool into therapies that can reach many of the body’s tissues and organs. Instead, drug developers have crowded into disease targets in the liver, the clearinghouse organ where delivery systems like lipid nanoparticles or viral vectors typically wind up.
Lucas HarringtonRegeneron, however, has been researching ways to use its antibody expertise to effectively guide a hollowed-out virus to new parts of the body — and delivering a payload with it. While standard Cas9 systems are comparatively large — about 1,300 to 1,400 amino acids — Mammoth has systems as small as about 500 amino acids, CSO Lucas Harrington said in an interview. Those systems are small enough to be more easily packaged inside delivery viruses like Regeneron’s.
“Maybe we can do something great together that neither company can do as well by ourselves,” Regeneron SVP of research Christos Kyratsous said in an interview. “This is one of those cases where we hope that one-plus-one is greater than two.”
Under the deal terms, Regeneron will pay $5 million and make a $95 million upfront equity investment in Mammoth, with the startup eligible for up to $370 million in milestone payments and potential royalties for each target.
Drugs heading into clinic, but with no firm timeline
Mammoth launched in 2018, with CRISPR pioneer Jennifer Doudna as a co-founder and Apple CEO Tim Cook as an early investor. It raised a $150 million Series D in 2021 at a valuation of over $1 billion. CEO Trevor Martin said Tarrytown, NY-based Regeneron’s equity investment is at a valuation “not down from our last round.”
A big biotech partner provides some validation to Mammoth, which pivoted away from its diagnostics research with layoffs last year. Its lead internal program is a gene-editing technology that aims to knock down the APOC3 gene in the liver, Martin said. He declined to give a timeline for when that may enter the clinic, but described initial non-human primate results as exciting.
That drug is targeting a rare liver disease called familial chylomicronemia syndrome as well as severe hypertriglyceridemia, or higher-than-usual levels of a type of fat in the blood. Mammoth is starting with a liver-focused program to first de-risk its editing technology before moving beyond the liver, Martin said.
“We are driving it forward on a very rapid timescale,” Martin said.
Christos KyratsousOn Regeneron’s side, Kyratsous said his team is preparing to present new research at next month’s American Society of Gene & Cell Therapy annual meeting, with a focus on data for delivering to the central nervous system in mice and non-human primates. He, too, declined to say when the first program using these antibody-directed viral vectors could enter the clinic, but added it probably wouldn’t be in 2024.
“Over the next couple of years, I think it’s realistic to say, some of these things are either going to be in the clinic or much closer to the clinic,” he said.
Broadly, Kyratsous said he’s further encouraged by recent research on this concept, which includes targeting additional, as-of-now undisclosed tissues beyond muscle and the central nervous system.
“This dream we had when we first started talking about this about a year ago seems to be holding true for multiple different tissues and different applications,” he said. “We’re becoming more and more optimistic about the use of this technology and the translatability of these findings as we are heading towards the clinic.”