Precision BioSciences is leaving the annual meeting of cell and gene therapy stakeholders with confidence, touting two preclinical studies suggesting that its Arcus platform can go toe-to-toe against CRISPR.
Presentation of the data at the American Society of Gene and Cell Therapy annual meeting was, above all, an opportunity to showcase the company’s platform, which was derived from I-CreI, a naturally occurring gene editing enzyme that comes from algae. According to Precision Chief Scientific Officer Derek Jantz, Ph.D., Arcus' X-factor is its ability to make insertions to the genome as opposed to only eliminating gene function.
When it comes to leveraging gene editing for rare genetic disease, this ability to make insertions is significant, because "the vast majority of genetic disorders are caused by the absence of something that is supposed to be there,” Jantz told Fierce Biotech.
One of the two early programs Precision highlighted detailed this exact mechanism among infant nonhuman primates to treat ornithine transcarbamylase deficiency (OTCD). To accomplish this, Precision targeted the PCSK9 gene, which via accumulated data from a later-stage high cholesterol program was shown to be able to be wiped out without issue. Once it settled on PCSK9, the company used two adeno-associated viral (AAV) vectors to actually tweak the genes: one that knocked out PCSK9 and another that delivered an ornithine transcarbamylase minigene.
The study authors found that the treatment resulted in a higher transduction efficiency in liver cells than the threshold seen in patients who are benefiting from treatment.
But that wasn’t all the company shared. Precision is also working on a lipid nanoparticle to deliver gene therapy that it touts as potentially curative for chronic hepatitis B. Whereas most treatments look to stop the hepatitis virus from replicating, Precision’s intends to kill off the viral DNA entirely.
To test it, the company used both a mouse and nonhuman primate model, which found a "significant decrease" in total AAV copy number as well as high indel frequency, a measure of gene editing precision. Treatment in the mouse model specifically resulted in a 96% reduction in circulating surface antigen of the virus. Study author Cassandra Gorsuch, Ph.D., director of gene therapy discovery at Precision, said this was promising.
Evidently, the hype that Precision has accrued through its early development has been noticed by others. The OTCD program has been picked up by iECURE, one of the multiple companies that spun out of the lab of Jim Wilson, M.D., Ph.D., at the University of Pennsylvania. The chronic hepatitis B program, on the other hand, was first snagged by Gilead Sciences in 2018 before being axed in 2020. That’s no problem for Jantz, who said the company is happy to have it back.
“The plan is we're gonna take this forward ourselves, at least until there is clinical data,” he said. “And then at that point, if a partnership makes sense, then we'll probably explore that.”