Startup led by John Maraganore raises $135M to build ‘future of RNAi’

Since stepping down as CEO of Alnylam Pharmaceuticals three years ago, John Maraganore has lent his talents widely, joining the boards of up-and-coming biotechnology companies, advising them on strategy and allying with some of the venture firms that back those young drugmakers.

His latest role returns him to his Alnylam roots. On Tuesday, City Therapeutics launched with a plan to build the next generation of the “RNA interference” medicines Alnylam pioneered. Maraganore, who co-founded City with a group of venture capitalists, scientists and other Alnylam veterans, will serve as the biotech’s executive chair.

“At Alnylam, we launched the birth of RNAi therapeutics as a new class of medicines,” Maraganore said in a statement announcing City’s debut. “We see the potential for RNAi to emerge as the next major category of high-impact medicines, rivaling if not exceeding the success of monoclonal antibodies.”

“New innovation is needed to realize this future, and we believe City Therapeutics can lead this next chapter,” he added.

City plans to innovate in several ways, including by tweaking the components of the biological process by which RNA interference, or RNAi, works. Typically, RNAi is described as a technique to “silence” genes. It does so via small, interfering strands of RNA that trigger cleavage of the messenger RNA instructions cells use to produce proteins.

City aims to design new kinds of RNAi triggers that similarly spark mRNA cutting, but are smaller and more potent. One example is what City terms “cleavage-inducing tiny RNAs,” the acronym for which led to the biotech’s name.

The startup also aims to design targeting molecules, or ligands, that enable the delivery of these engineered RNA strands to more types of cells and tissues. (The approved RNAi medicines that Alnylam and rival Dicerna Pharmaceuticals have to date developed are all aimed at the liver.)

To get started, City has $135 million in funding from a large syndicate of investors that includes Arch Venture Partners, an early investor in Alnylam. Also backing City are Fidelity Management & Research, Invus and Regeneron Ventures, along with several other firms.

“The time to re-enter the RNAi revolution is now, and our investment in City Therapeutics is based on our conviction that RNAi therapeutics will expand as a major category of breakthrough medicines,” said Robert Nelsen, a managing director and co-founder of Arch, in a statement.

City didn’t disclose which diseases it will target, but expects to begin clinical testing for its first program “at or around” the end of next year. The company hopes to advance one or two new drugs into the clinic each year after that.

It’s not the only biotech startup setting out to improve on RNAi medicines. On Monday, Judo Bio launched with plans to bring RNAi drugs to the kidney by using what it calls ligand-siRNA conjugates. Maraganore is also on Judo’s advisory board.