Axovia Therapeutics has presented new preclinical data supporting its novel gene therapy approach for treating blindness associated with Bardet-Biedl Syndrome (BBS) at the American Society of Gene and Cell Therapy (ASGCT) 28th Annual Meeting in New Orleans.
The biotechnology company showcased results from two poster presentations that validate the planned dosing regimen and protocol for their upcoming Phase 1/2 first-in-human study of AXV-101, scheduled to begin in mid-2025.
"As we draw closer to the initiation of our Phase 1/2 first-in-human study mid-year, these presentations at ASCGT highlight critical data supporting our planned dosing regimen and trial protocol," said Dr. Victor Hernandez, Co-Founder and Chief Scientific Officer of Axovia. "We believe that our novel gene therapy, AXV-101, can modify the underlying disease of BBS, including prevention of vision loss by halting retinal degeneration."
Enhanced Efficacy with Multi-Bleb Dosing Strategy
The first poster presented data on a new dosing regimen for AXV-101 (AAV9-BBS1) that demonstrated significant improvements in both histological and functional photoreceptor survival in Bbs1 M390R mice. The research highlighted the benefits of a multi-bleb strategy, which uses lower viral titer per bleb but higher total titer per eye.
Key findings showed that a double bleb approach with AXV-101 effectively halted retinal degeneration and preserved outer nuclear layer (ONL) thickness while maintaining safety at higher doses per retina. Longitudinal analysis revealed enhanced functional rescue of photoreceptors, with the double bleb approach achieving up to 70% of wild-type retinal function.
Additionally, AXV-101 demonstrated the ability to restore photoreceptor numbers and arrestin-C localization for up to six months post-treatment, indicating durable therapeutic effects.
Favorable Biodistribution Profile
The second poster detailed the development of a droplet digital PCR (ddPCR) assay to quantify AXV-101 levels in a mouse biodistribution study. Results showed that AXV-101's distribution was largely restricted to the dosing tissue (eye), with minimal transfer to nearby neuronal tissues and no distribution to organs outside the central nervous system or into the germline.
The data revealed a clear dose-dependent distribution in the eye, with the high dose group averaging 6,344 copies, the medium dose group 2,220 copies, and the low dose group 235 copies. In the high dose group, a small, expected distribution was observed in the optic nerve and brain tissues, while the medium dose showed limited distribution in the optic nerve and frontal cortex.
Importantly, biodistribution throughout the rest of the analyzed organs was minimal and comparable to controls, demonstrating no spread of the AXV-101 vector outside neuronal tissue.
Expert Perspective and Clinical Implications
Dr. Shehla Mohammed, Clinical Lead for the BBS specialized service at St Thomas' Hospital in London, commented on the findings: "These preclinical results are very encouraging and provide important support for the planned dosing regimen and protocol for the Phase 1/2 study. These results represent a critical step forward as Axovia advances this therapy into clinical development, with the ultimate goal of offering the BBS community a much-needed treatment that can address retinal degeneration."
Understanding Bardet-Biedl Syndrome
Bardet-Biedl Syndrome is an autosomal recessive disorder associated with primary cilia dysfunction. The condition presents with multiple clinical features, most notably retinal degeneration and morbid obesity. Currently, there is no curative treatment for BBS.
The disease affects between one in 70,000 to one in 100,000 people in Europe and North America, with up to ten times higher prevalence in certain populations in the Middle East. In Europe and North America, BBS1 is the most commonly mutated gene found in BBS patients, with the missense BBS1 M390R mutation being the most common allele.
About Axovia Therapeutics
Axovia Therapeutics is focused on developing therapies that address the genetic causes of blindness and obesity syndromes driven by cilia dysfunction. Ciliopathies encompass more than 55 rare inherited genetic diseases linked to over 950 genes that impact the function of cilia, which are critical for protein transport and cellular signaling.
The company's lead program, AXV-101 for Bardet-Biedl Syndrome, has received U.S. Food and Drug Administration Orphan Drug Designation and Rare Pediatric Disease Designation. Axovia is also developing a second program, AXV-201, for genetic obesity caused by MC4R mutations.
Backed by ALSA Ventures, Axovia was formed following decades of work on ciliopathies at University College London by co-founders Professor Phil Beales and Dr. Victor Hernandez. The company's planned Phase 1/2 clinical trial for AXV-101 represents a significant milestone in their mission to develop effective treatments for patients with BBS and related conditions.
