Sanofi Invests in Resalis Therapeutics' miRNA-22 Inhibitor for Obesity Treatment
核心洞察
Sanofi SA makes a strategic equity investment in Resalis Therapeutics (搜索) to advance the clinical development of RES-010, an antisense oligonucleotide targeting microRNA-22 (搜索).
RES-010 aims to convert white fat cells into brown fat cells, reverse fibrosis, and restore lipid and energy homeostasis by inhibiting microRNA-22 (搜索).
Resalis Therapeutics (搜索) is preparing to enroll patients in a Phase I clinical trial to assess the safety and therapeutic window of RES-010.
Sanofi SA has made a strategic equity investment in Resalis Therapeutics (搜索) srl, an Italian antisense oligonucleotide specialist, to support the clinical development of RES-010, a therapy targeting obesity (搜索) and related metabolic disorders. This investment follows Resalis' initial €10 million Series A financing aimed at advancing its obesity program, RES-10, into clinical trials.
The investment will support the development of RES-010, an antisense nucleotide designed to inhibit microRNA-22 (搜索) (miR-22). The therapy aims to catalyze the conversion of white, fat-storing fat cells into brown, fat-burning fat cells, reverse fibrosis, and restore lipid and energy homeostasis. The financial details of the transaction and its potential impact on future M&A or drug licensing agreements were not disclosed. However, the investment is expected to be in the range of €50 million to €150 million, which is the average cost for R&D, GMP-compliant lot production, patient recruitment, and data evaluation up to Phase II proof-of-concept.
RES-010: Targeting miR-22 for Metabolic Rewiring
RES-010 is a locked nucleic acid (LNA) targeting miR-22(-3p), a non-coding RNA that plays a crucial role in the molecular pathways underlying obesity (搜索), obesity-related metastasis, metabolic associated fatty liver disease (搜索) (MAFLD), and its progressive state, metabolic associated steatohepatitis (搜索) (MASH). It functions through an antisense mechanism. miR-22 orchestrates multiple pro-lipogenic programs by modulating both direct and indirect gene targets. Genetic ablation of miR-22 has demonstrated a shift towards higher energy expenditure and browning of white adipose tissue.
Data comparing obese and normal-weight individuals revealed that miR-22-3p was significantly overexpressed in obese human adipose tissue (p-value: 0.0078; q-value: 0.0373). Its expression also correlated positively with anthropometric and metabolic characteristics, including waist–hip ratio, body-mass index, serum triglycerides, serum ApoB, HOMAIR, serum alanine aminotransferase, and serum C-reactive protein. Conversely, miR-22-3p levels correlated negatively with muscle mass, serum adiponectin, and serum HDL cholesterol. Predictive analysis indicated that several metabolic pathways are under the control of miR-22, suggesting that its role in metabolic homeostasis is conserved across mice and humans.
Potential Advantages over Existing Therapies
Compared to current peptidic GLP-1 modulators and second- and third-generation appetite modulators marketed by companies like Novo Nordisk and Eli Lilly, and those in development by Roche, AstraZeneca, and Boehringer Ingelheim, LNA-based miRNA-22 blockers may offer distinct advantages. These include not affecting muscle mass decrease, a common side effect of unspecific central regulators of appetite. Furthermore, they may not require lifelong administration and could provide a more causal treatment for metabolic diseases. Additionally, the programmable and potentially cost-effective nature of RNA synthesis may reduce the cost of current biological therapies.
Clinical Development Plans
According to Alessandro Toniolo, CEO of Resalis Therapeutics (搜索), the company is preparing to enroll patients in a Phase I clinical trial to assess the safety and therapeutic window of RES-010. Toniolo expressed confidence that robust data could allow rapid progression to Phase II development, assuming RES-010 successfully completes Phase I studies. Resalis also has a GalNac-modified miRNA-22 backup program, RES-20, in early preclinical development.