Biogen taps start-up for RNAi collaboration

A start-up that launched only 8 months ago has attracted the attention of Biogen, a major developer of neurological drugs.

City Therapeutics will develop its namesake cityRNAs—short for cleavage-inducing tiny guide RNAs—for Biogen, with the goal of reaching a single, unnamed target that mediates multiple central nervous system (CNS) diseases. Biogen has agreed to pay the young start-up $16 million up front and invest $30 million in the firm, with the promise of adding up to $1 billion in potential milestone payments. Biogen also has the option to choose another target later on.

The collaboration is City’s second since launching publicly in October. The company inked a deal with the ophthalmological drug developer Bausch + Lomb in January to develop RNA-interference (RNAi) drugs for retinal diseases including geographic atrophy. Bausch + Lomb agreed to pay City an undisclosed amount up front and a potential $485 million in milestone payments.

City’s technology is based on work by chemist Kotaro Nakanishi at the Ohio State University, who found that cityRNAs could activate the protein argonaute-3 to slice through other proteins (Proc. Natl. Acad. Sci. U.S.A. 2020, DOI: 10.1073/pnas.2015026117). CityRNAs are also well positioned to get to multiple types of tissues, including CNS, eye, muscle, fat, and lung tissues, because they are so small—even smaller than the small interfering RNAs (siRNAs) that form the backbone of most RNAi therapies to date.

City is building on that work by engineering new delivery vehicles for its cityRNAs, according to CEO Andy Orth.

“In the RNAi space right now, one of the more exciting things that is happening are these novel delivery ligands,” Orth tells C&EN. “For each differing tissue type one is aiming to target—be it ocular, as we are with our Bausch + Lomb partnership, or CNS, as we’ve just announced with the Biogen deal—each one of those is likely requiring its own novel targeting ligand. So the work that we’re doing here at City, but also the work that’s going on, frankly, all over the world right now, is really exciting.”

Orth joined the company in January after holding senior positions at Biogen and siRNA pioneer Alnylam Pharmaceuticals. (Alnylam’s founding CEO, John Maraganore, is a founder and chairman of the board of City.) Orth is among several new C-suite executives at City: chief medical officer Baisong Mei, another Biogen veteran, joined the company in March, as did chief human resources officer Anna O’Driscoll, who’d previously spent 5 years at Alnylam.

All told, City has around 50 full-time employees, nearly twice as many as it did when it launched.

Orth expects that City will start testing its first in-house drug candidate in human trials by the end of this year, but he declines to disclose any specifics about that compound’s target or disease area yet. Partnerships will also continue to be part of the start-up's business strategy, he says.

“We’re in a very fortunate position in that the amount of very high-quality development candidates that we’re able to generate outstrips our ability to develop them,” Orth says. “That allows us to be discerning on what it is that we, as a company of 50 people with the resources we have, take forward into the clinic and what might be a great opportunity to partner.”