Axovia Therapeutics Unveils New Preclinical Data for AXV-201, for Treatment of Genetic Obesity Caused by MC4R Mutations, at ASGCT

Yahoo

15-05-2025

Positive preclinical POC data show that novel gene therapy, AXV-201, prevented obesity and metabolic disease in a monogenic model
LONDON, May 15, 2025 (GLOBE NEWSWIRE) -- Axovia Therapeutics Ltd., a biotechnology company developing therapies to address the genetic causes of blindness and obesity, announced that today it will unveil new preclinical proof-of-concept data for novelly designed, AXV-201, to treat individuals with severe obesity and very high BMIs resulting from MC4R mutations, in a poster presentation at the American Society of Gene and Cell Therapy (ASGCT) 28th Annual Meeting, which is being held from May 13-17, 2025 in New Orleans, LA.
'Today's presentation highlights how a new human sequence and AAV9 vector, AXV-201, can rescue the weight gain phenotype and could prove to be a powerful treatment for individuals with severe obesity and very high BMIs resulting from MC4R mutations,' said Dr. Victor Hernandez, Co-Founder and Chief Scientific Officer. 'MC4R is a key regulator of body weight and is the most common cause of genetic early-onset monogenic obesity. A gene replacement therapy could be transformative for those suffering across the globe.'
Preclinical proof-of-concept data highlights include:
New codon-optimized self-complementary human cMC4R sequence was able to express the MC4R transgene activity greater than five times more efficiently than the wild-type cDNA
In vivo administration of AXV-201 in Mc4r-null mice prevented the development of obesity in males and females, restoring a normal weight trajectory comparable to wild-type controls and showed normalization of neurometabolic markers
No safety concerns were observed when wild-types cohorts were dosed with AXV-201
'Genetic forms of obesity, such as those linked to MC4R mutations, represent a significant and often overlooked challenge for patients and clinicians alike,' said Dr. Jesse Richards, OU Health. 'Despite advances in obesity research, there remains a critical unmet need for effective therapies that address the underlying genetic causes. These data lay the groundwork for bringing new hope to individuals and families affected by MC4R-related obesity, offering the possibility of a targeted intervention that aims to normalize weight and have a better effect than currently available options.'
About Melanocortin 4 Receptor () MutationsMelanocortin 4 receptor (MC4R) mutations are the most common cause of human monogenic obesity. Individuals with MC4R loss of function mutations suffer from hyperphagia, severe obesity and hyperinsulinemia. Impact of the different type of MC4R mutation depends on how they reduce MC4R expression and the impact they have on the production of cyclic AMP (cAMP). Mutations in heterozygosity, with partial MC4R functionality are the most frequent, but homozygous mutations and double heterozygotes account for 25% of MC4R mutations. There are approximately 50,000 patients with complete MC4R loss of function (LoF) and BMI>40 in the United States, European Union and Middle East.
About Axovia Therapeutics Ltd.Axovia Therapeutics is leading the development of therapies that address the genetic causes of blindness and obesity syndromes that are driven by cilia dysfunction. Ciliopathies are a group of more than 55 rare inherited genetic diseases linked to more than 950 genes that impact the function of cilia which are critical for protein transport and cellular signaling. The company plans to initiate a clinical study to treat retinal degeneration for its lead program for Bardet-Biedl Syndrome (BBS), AXV-101, in mid-2025, based on robust preclinical efficacy and toxicological data with established scaled GMP manufacturing and patient registries. AXV-101 has achieved U.S. Food and Drug Administration Orphan Drug Designation and Rare Pediatric Disease Designation. The company is developing its second program, AXV-201, for genetic obesity caused by MC4R mutations. Axovia is backed by ALSA Ventures and was formed following decades of work on ciliopathies at University College London by co-founders Professor Phil Beales and Dr. Victor Hernandez. For further information, please visit https://axoviatherapeutics.com.
Contact:Professor Phil BealesChief Executive [e-mail]