Resalis takes aim at ‘master regulator of metabolism’

Since the advent of the Moderna and Pfizer-BioNTech COVID-19 vaccines, RNA-based drug and vaccine candidates have garnered significant cash and attention. RNA is a hot topic. According to the team at Resalis Therapeutics, it’s also a hot target.

Italy-based Resalis launched today with €10 million ($10.7 million) to develop therapies targeting non-coding RNA to treat metabolic diseases. Non-coding RNA is RNA that does not get translated into a protein. One such type, called microRNA, gloms onto a strand of messenger RNA (mRNA), blocking a portion of that strand from being translated. As the name suggests, microRNA are very small—usually around 20–24 nucleotides, says Riccardo Panella, Resalis’s chief scientific officer and cofounder—and they can bind to several different mRNAs.

With their lead candidate, Resalis is targeting a specific microRNA called microRNA-22 (miR-22). “We say it’s the master regulator of metabolism,” Sakari Kauppinen, Resalis’s chief technology officer and cofounder. miR-22 has targets in multiple different pathways, including lipid biosynthesis and inflammation, which are central to obesity and nonalcoholic fatty liver disease, Panella says. Resalis intends to go after both conditions with a mir-22 inhibitor.

Their lead candidate, RES-010, is an antisense oligonucleotide, with acomplementary sequence to mir-22’s, allowing it to bind to the microRNA target. This should prevent mir-22 from binding to mRNA strands and blocking translation.

Inhibiting miR-22 should allow the team to control multiple pathways while only inhibiting one target, an approach that Panella says gives them a leg up on competitors. Other companies’ approaches mostly take aim at targets that don’t have the same master-regulator role, like proteins. “We have to acknowledge that this particular disease is very complex,” he says, referring to obesity. “And finding a single protein that can control everything is kind of a dream—but we don’t live in dreams.”

Drugs that induce weight loss have received significant attention in recent years. In May of last year, the US Food and Drug Administration approved Eli Lilly and Company’s Mounjaro (tirzepatide) for type 2 diabetes, and the FDA has given Lilly fast track designation for the evaluation of the drug for the treatment of adults with “obesity” or who are “overweight” with weight-related comorbidities. Novo Nordisk’s type 2 diabetes drug Ozempic (semaglutide), which acts on one of the same receptors as Mounjaro, was approved for chronic weight management in 2021 under the name Wegovy.