Aiming to rewire metabolism, Resalis raises €10M to launch first-in-human study of obesity treatment
05 Jan 2024
OligonucleotidePhase 1
While GLP-1 receptor agonists continue to post impressive weight loss data – and attract a slew of high-priced deals – the drugs face several shortcomings in obesity, including the duration of effect after treatment ends. Resalis is aiming to fill those holes with a complementary therapy: an antisense oligonucleotide (ASO) that targets miR-22, which controls multiple pathways associated with the metabolic root of obesity.
The round, which comes a year after Resalis’ initial €10 million seed funding, was led by Sunstone Life Science Ventures with participation from existing investors including Claris Ventures and angel investors.
One target, many pathways
Resalis’ strategy for a disease-modifying obesity therapeutic hinges on one microRNA (miRNA).
Riccardo Panella began investigating miR-22 as a postdoc at Harvard Medical School and discovered its importance in multiple metabolic pathways – and its potential as a therapeutic target for obesity. Soon after, he started collaborating with Sakari Kauppinen to further explore the biology of miR-22, thanks to a grant from the Novo Nordisk Foundation, and they designed ASOs that could inhibit the target. After settling on a lead compound and amassing pharmacological and animal model data, the pair founded Resalis in 2021. Panella serves as chief scientific officer; Kauppinen is the company’s chief technology officer.
“Because they’re very short, one miRNA can interact with a lot of different targets, depending on what is expressed at that moment in a cell or tissue,” Panella told FirstWord. Some of the key targets of miR-22 the Resalis team has identified include FGF21, ACLY, PGC-1α, and SIRT1 – all which have key roles in metabolic pathways.
The ability to affect multiple targets is especially attractive in obesity because it’s a complex, multi-tissue, multi-pathway disease. With RES-010, “We found a way to hit multiple birds with one stone,” Panella said. “By silencing miR-22, we can deregulate multiple players at the same time that are important for driving the obesity phenotype.”
Getting at the metabolic root
The end goal is to rewire our cellular metabolism – making it harder for the body to store fat, and promoting energy consumption, Resalis CEO Alessandro Toniolo said.
Mice data hints at what the result of such rewiring could look like in humans. In a study published last year in the International Journal of Molecular Sciences, Panella and Kauppinen found that when two groups of mice were fed high-fat diets, those with a miR-22 knockout gained significantly less weight than those with the target intact.
Plus, another mice study showed that miR-22 inhibition only triggered fat loss, not muscle – another drawback to GLP-1 receptor agonism.
Toniolo said the team found that, unless the mice had an excess of fat, they did not lose body weight. Because GLP-1 receptor agonists are appetite suppressors, patients often lose both fat and muscle mass, which can be unhealthy for the elderly.
Another shortcoming facing the modality is that when patients stop taking the drugs, they often regain weight.
However, Toniology believes pairing a GLP-1 receptor agonistGLP-1 receptor agonist with RES-010 for a course of treatment could resolve these issues. He doesn’t see the ASO replacing GLP-1s, but rather as a complementary therapy.
Resalis plans to start a Phase I dose-ascending study of RES-010 in Europe this half.
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