Why RNA Is Good For Business

By Matthew Pillar, Editor, Bioprocess Online

This article originally appeared in the March, 2023 issue of Life Science Leader magazine.

Early last year, Nutcracker Therapeutics landed a $170 million Series C to further its work developing an RNA drug development platform. That’s pretty noteworthy, considering how easy it is for biopharmaceutical companies to get lost in the cacophony of their peer companies rallying around the therapeutic potential of RNA. Hundreds of biotechs around the globe can count at least one RNA-based therapeutic in their development arsenal, if not because the science is promising, almost certainly because the acronym attracts attention from the investment community.

The operative words in Nutcracker’s case, however, aren’t “RNA therapeutic.” They’re “RNA platform.” The company’s preclinical lineup consists of a multimodal RNA therapeutic for HPV-driven tumors, a patient- specific multimodal RNA therapeutic aimed at T cell lymphoma, and a multimodal RNA therapeutic for genitourinary tumors. That’s an uncommonly wide swath of big swings, and it’s all born of the same internal platform that allows the company to design and manufacture its candidates in-house. On episode 124 of the Business of Biotech podcast, Nutcracker Chief Business Officer Geoff Nosrati, Ph.D., shared why RNA is both good science and good for business.

ELIMINATING RESEARCH & MANUFACTURING BOTTLENECKS

There isn’t much that hasn’t already been said about the clinical-stage stability and versatility advantages of RNA-based therapeutics. What’s not as often discussed are its drug discovery attributes. “Even before you get into the clinic, it’s a very efficient platform for screening a lot of different protein constructs,” explains Nosrati. “You can make RNAs that encode several different proteins that you want to evaluate therapeutically, and you can do it very quickly.” To that end, Nutcracker has an advantage in its in-house RNA production capability, which Nosrati says eliminates common bottlenecks at the research and discovery stages. He says it’s not uncommon for Nutcracker to build 100 or more constructs at once for evaluation in a single indication, all under its own roof. At the manufacturing stage, he says the company’s in-house capabilities remove both general and RNA-specific bottlenecks. “If you reserve a slot with one of the big CDMOs right now, there’s an 18-to-24-month lead time to have your product made, and it’s very expensive. It will be two years before your protein is in vials and ready to be administered to patients.”

That in-house control enables another efficiency advantage at Nutcracker. “I’m going to make the CMC people cry a little bit by saying this,” says Nosrati, “but with RNA, you’re always generally making the same thing, ribonucleotide polymers. Whether it encodes drug A or drug B, it’s still RNA.” That, he says, affords the advantage of many CMC commonalities among production runs.

Those advantages add up to a low incremental cost of production in a low-dose therapeutic development arena that doesn’t require thousands of square feet of manufacturing capacity. “Having our own facility where we can control production allows us to do more in the clinic than a company without its own manufacturing capabilities,” says Nosrati. “That’s appealing because in drug development, it’s always better to have more good shots on goal due to the inherent unpredictability of drug efficacy in the clinic.” At present, Nutcracker is gearing that facility up for GLP tox studies in advance of its foray into the clinic this year. Learn more about the business efficiencies of RNA from this scientist-turned-chief business officer on episode 124 of the Business of Biotech podcast, available anywhere you listen to podcasts.