In New York, Gotham Starts Up With $54M for RNA-Modifying Drugs

Xconomy New York — 

A new company has emerged from New York City’s growing startup biotech scene. Gotham Therapeutics launched today with a $54 million Series A round, becoming the second startup since May to form with a plan to alter RNA molecules with chemical drugs.

The funding was co-led by Versant Ventures, a venture firm that formed an outpost in New York in 2015 and has since started multiple Manhattan-based biotechs. Gotham doesn’t hail from Versant’s Big Apple biotech incubator, Highline Therapeutics. But it is nonetheless based in New York City, whose life sciences startup ecosystem has historically lagged behind more established hubs elsewhere.

Gotham being based in New York is noteworthy. Over the last several years, the city has made a concerted effort to bolster its startup biotech scene. City and state governments have committed more than $1 billion to growing New York’s biotech industry. Several startup incubators have sprouted up, and startup creators like Versant and Flagship Pioneering have arrived.

But the effort is still early, and New York currently has nowhere near the number of high-profile biotech startups that Boston and San Francisco regularly churn out. Case in point: Gotham’s $54 million round is the largest Series A for a New York biotech startup this year, eclipsing the $48 million haul Quentis Therapeutics, another Versant-backed startup, announced in February.

Gotham is capitalizing on new insights into the myriad ways the cell controls gene activity. As these methods are revealed, more potential drug targets may be within reach. Gotham is specifically focused on messenger RNA (mRNA), molecules that carry the genetic instructions encoded in DNA to the cell’s protein-making factories. The startup wants to design drugs that change how the cell chemically modifies mRNA.

The cell tweaks mRNA in several ways to control what proteins are made and how much. One way the cell does this is to attach or remove certain chemical groups from the mRNA. These changes affect gene activity and some may promote diseases like cancer. Gotham’s drugs would block the enzymes that make disease-related changes to mRNA.

Research into the nature of these chemical modifications to RNA, a field called epitranscriptomics, took off in 2012, when biologists published genome-wide maps of a specific kind of chemical tag on RNA. One of those scientists, Samie Jaffrey, from Weill Cornell Medicine, is a cofounder of Gotham.

Gotham is aiming its drugs at enzymes that alter mRNA in the most commonly known and well-studied way—by either adding or removing a certain type of chemical group at a specific site on mRNA molecules. These modifications are known as m6A. The company is also targeting molecules that simply latch onto these same sites to control the fate of the mRNA.

Lee Babiss, Gotham’s CEO and cofounder, says his team’s first drugs will likely be targeted at cancer, but Gotham will also pursue treatments for autoimmune and neurodegenerative diseases.

Gotham isn’t alone. Accent Therapeutics, which launched in May with a $40 million financing, is also targeting RNA-modifying enzymes involved in cancer.

Both will have to be careful. Side effects associated with drugging the enzymes involved in RNA modification will be a concern, says Hongchuan Jin of Zhejiang University Medical School in Hangzhou, China and a cancer biologist who has written about the links between m6A and cancer.

“RNA modification is a general program to regulate gene expression” that both healthy and diseased cells use, Jin says. So it will be critical for drug developers to precisely target cancer-causing RNAs while sparing others, he adds. Epitranscriptomic drugs “in general lack the specificity in molecular targeting” compared to other more proven gene-silencing methods, like RNA interference, he says. (The FDA approved the first-ever RNAi medicine, from Alnylam Pharmaceuticals, in August.)

But Jin adds that investing in such drugs is still worthwhile, given the numerous experimental treatments that target chemical changes to DNA, known as epigenetic drugs, that have made it to clinical testing for various types of cancers.

Babiss says his team, working over the last year and a half, has so far shown that knocking out whole proteins involved in modifying mRNA seems to kill cancer cells in the lab. Now they are seeing if small molecules can have the same effect. He says the new funding should get Gotham to early stage clinical testing.

Forbion and SR One co-led the round, and Celgene and Alexandria Venture Investments also took part.