Ribometrix Inc., a Durham, N.C.-based startup developing small-molecule drugs to modulate RNA activity, has raised $30 million in a series A financing. The round, led by Merck KGaA's M Ventures, will help the company advance its discovery platform and its internal pipeline, it said.
Amgen Ventures, Pappas Capital and Illumina Ventures also supported the financing.
The company expects to focus on applications of RNA targeting in cancer and neurodegeneration, CEO Mike Solomon told BioWorld.
Several RNA-targeted drugs have already gained FDA approval, including the antisense therapies Tegsedi (inotersen, Akcea Therapeutics Inc.) and the RNAi therapy Onpattro (patisiran, Alnylam Pharmaceuticals Inc.). But while each can be powerful, such injectable treatments can also be limited due to the physiochemical characteristics of oligonucleotides, Solomon said. The prospect of developing small-molecule drugs that can be taken orally, get into the brain and achieve better tissue distribution is where Ribometrix is focused.
Initially founded with grants by University of North Carolina at Chapel Hill chemistry professor Kevin Weeks and his collaborator Katie Warner, now senior director of research at the company, Ribometrix was started to develop applications of the Weeks-invented SHAPE (Selective 2′ Hydroxyl Acylation analyzed by Primer Extension) technology. Solomon said it's considered "the gold standard for determining the three-dimensional structure of RNA at the single nucleotide level." But when he first saw it, a different opportunity was apparent: its potential as a screening platform to find small molecules that bind to RNA.
"There are compounds reported in the literature that bind to RNA, but they generally target the secondary structures of RNA and are not very drug-like," Solomon said. "By targeting the three-dimensional structure of the RNA, you can think about it as much more analogous to a protein, where you're able to get selectivity and better drug-like properties," he said.
Ribometrix's 15-person team has been fine-tuning the platform for screening applications ever since a $7.5 million seed financing, led in October 2017 by SV Health Investors and Hatteras Venture Partners. With the new $30 million round, its team will now be able to build its staff to about 30 employees next year, adding drug discovery experts, a chief scientific officer, heads of biology and chemistry and others. Together, they'll work to move the company's discovery-stage programs to new inflection points, Solomon said, though he declined to provide a timeline for that work.
Solomon, a venture partner at SV Health Investors, has held executive operational roles at Decibel Therapeutics Inc., Link Medicine Corp. and Hypnion Inc. and was a founder of Epizyme Inc.
Beyond oncology and neurodegeneration, the Ribometrix team will also work to take advantage of the agnostic nature of its screening technology, by pursuing partnerships built around new targets and indications.
Ribometrix, a moniker invented by Warner, gets its name from a combination of "ribo" from ribonucleic acid and "metrix," as in the quantitative measurements derived from the SHAPE technology. It joins several other companies seeking to develop RNA-targeted small-molecule therapies. Like Ribometrix, Waltham, Mass.-based Arrakis Therapeutics Inc. has developed its own discovery platform that includes the SHAPE technology. It has a quartet of candidates in development for cancer, neurological disease, a genetic disorder and a yet-to-be revealed indication, according to Cortellis. Skyhawk Therapeutics Inc., also of Waltham, is also developing small-molecule candidates using its SkySTAR platform (Skyhawk Small molecule Therapeutics for Alternative splicing in RNA). So far, it has revealed an oncology-targeted program and three neurology-focused programs.
Another company, Expansion Therapeutics Inc., of San Diego and Jupiter, Fla., is building on work out of Matthew Disney's Scripps Research Institute lab. It has disclosed discovery-stage programs focused on treating two types of myotonic dystrophy as well as two additional programs for an expansion repeat disorder and a non-expansion repeat disorder.
But Solomon isn't sweating the competition. RNA-targeting is an enormous space, he said. "I think there's room for multiple successful companies. Success for any of us is good for all of us."