City Therapeutics has launched with $135 million and Alnylam’s former CEO leading the charge as it develops a pipeline of next-generation RNAi therapies that could act on tissues apart from the liver, which is a challenge faced by many similar candidates.
John Maraganore’s role as executive chair and one of many co-founders at the Cambridge, MA-based biotech represents a noteworthy return to the drug development space.
Maraganore left Alnylam in 2021 after spending nearly two decades helping build that company from scratch. Since the departure, he has been appointed to numerous advisory roles and worked for venture capital firms such as ARCH Venture Partners and Atlas Venture.
City plans to advance its lead program into the clinic by the end of next year and file one to two INDs every year starting from 2026, according to a Tuesday release. While the company has not yet disclosed its targets or indications, it has already selected a development candidate for the lead program, Maraganore told Endpoints News in an interview.
At City, “we’re very focused on engineering the RNAi trigger molecule, the siRNA. Or in some aspects of the IP that we’ve in-licensed, the so-called cleavage-inducing tiny RNAs,” Maraganore said. The company is focusing on engineering RNAi molecules to have better potency, selectivity, durability and have a smaller size, he added.
All these improvements could help the company address the challenge of extrahepatic delivery. FDA-approved siRNA drugs target the liver because that’s where RNA-carrying particles tend to accumulate, but this limits the types of diseases the approach can be used to treat.
City will also “work on novel ligands” so that it can “achieve targeted, cell-specific uptake of these RNAi triggers into specific cell types and tissues” as well as using human genetics to guide target selection, Maraganore said.
The company’s $135 million Series A should give it a runway “well into 2026,” supporting the IND filing and initial clinical data for its lead program, Maraganore said. The fundraise was led by ARCH with contributions from other investors, including Slate Path Capital, Rock Springs Capital and Regeneron Ventures.
There’s “no question” that City will go public in the future, and that could happen “as early as 2026” depending on the market environment and the company’s progress, Maraganore said. Deals with pharma could also form an important part of the biotech’s strategy. “There’s way too many opportunities than what we can do alone as a company,” he said.