By Conor Hale, Nov 13, 2018

The company plans to go after several undruggable targets in Huntington’s and c-Myc transcription factor-related cancers.

Ribometrix has raked in $30 million to push its platform into full drug discovery mode, aimed at fitting small molecules into the three-dimensional folds and pockets of RNA structures to modulate their activity.

The series A round was led by Merck KGaA’s M Ventures, with Amgen Ventures, Pappas Capital and Illumina Ventures also backing the effort.

Additionally, Ribometrix’s founding investors—including SV Health Investors, AbbVie Ventures, Hatteras Venture Partners, MP Healthcare Venture Management, the Dementia Discovery Fund and Alexandria Venture Investments—returned from a $7.5 million seed round completed one year ago.

Based on the work of the company’s scientific co-founder, Kevin Weeks, a distinguished professor at the University of North Carolina at Chapel Hill, Ribometrix’s drug compound screening engine is based on mapping out the larger shapes of RNA molecules.

“When the team initially showed me what a tertiary structure of an RNA looked like, it looked like a protein,” Ribometrix CEO Michael Solomon told FierceBiotech. “You could see pockets and clefts and places that you could stick small molecules into. And I was pretty amazed by that.”

By developing small molecules that bind to the folded shape of messenger RNA and micro RNA, the company hopes to interrupt their downstream translation into disease-causing proteins, including many that had previously been considered undruggable.

“The nice thing about a platform like this, and going against undruggable targets, is that you can go across all sorts of indications,” said Solomon, who helped found Epizyme and served as its VP of discovery. “We’re largely focusing right now on oncology and neurodegeneration, however, we plan on partnering with companies on other indications.”

This includes diseases such as Huntington’s and the c-Myc transcription factor, which has been linked to drivers of different cancers. “Transcription factors are good example because they're just hard to drug with traditional modalities,” he said, with some completely lacking small molecule binding sites, and with biologics having difficulty getting inside a cell.

But by moving upstream to the RNA, you can find a targetable structure that inhibits its translation to begin with, turning the treatment into a more-typical medicinal chemistry problem.

“What we’re trying to do is similar to antisense or RNA interference, but with a small molecule—and therefore having all the inherent advantages of a small molecule, like oral activity, wide tissue distribution and brain penetration,” he said.

With the new funding, the Durham, North Carolina-based company plans to nearly double its staff, from 15 to about 30, while bringing on a chief scientific officer and chemistry and biology heads. It also plans to advance its multiple discovery-stage programs into preclinical testing.

“The idea of being able to drug RNA and go after currently undruggable targets has been widely resonating with strategic investors and pharma companies,” Solomon said.

Source: https://www.fiercebiotech.com/biotech/ribometrix-raises-30m-to-drug-upstream-rna-small-molecules