Q32 Bio has announced a delay in the planned Phase 2 clinical trial of ADX-097 for the treatment of ANCA-associated vasculitis (AAV). The trial, which was anticipated to commence in 2025, is now postponed indefinitely as the company shifts its focus to other clinical programs.
The company's decision is driven by a strategic prioritization of bempikibart, a therapy candidate for alopecia areata, and an ongoing basket study evaluating ADX-097 in kidney damage resulting from autoimmune and immune-related conditions. This change in focus was detailed in a recent company press release.
ADX-097: Targeting Complement Overactivation in AAV
ANCA-associated vasculitis is a group of autoimmune diseases characterized by inflammation and damage to small blood vessels, often driven by self-reactive antibodies called ANCAs. Excessive activation of the complement system, a crucial part of the immune response, is also implicated in the pathogenesis of AAV, leading to tissue damage across various organs.
ADX-097 is a novel antibody designed to target C3d and factor H, two key proteins within the complement pathway. Unlike conventional complement inhibitors, ADX-097 is engineered to selectively act on tissues exhibiting high levels of C3d, indicative of complement overactivation, while sparing tissues with normal complement activity. This targeted approach aims to minimize the risk of widespread immune suppression.
Promising Phase 1 Data
In a Phase 1 first-in-human trial, ADX-097 was administered to healthy volunteers via intravenous and subcutaneous routes. The study assessed the safety, pharmacokinetics (drug movement within the body), and pharmacodynamics (drug effects on the body) of ADX-097.
The results indicated that ADX-097 was well-tolerated across various doses, with no serious adverse events or immune reactions reported. Notably, weekly subcutaneous injections of 450 mg achieved blood concentrations expected to effectively suppress the complement system in damaged tissues without causing systemic complement inhibition. This suggests that ADX-097 could selectively block complement overactivation in target tissues, avoiding broad immunosuppression.
Implications for AAV Treatment
While the delay in the Phase 2 trial is a setback for the AAV program, the ongoing basket trial (NCT06419205) continues to evaluate ADX-097 in adults with autoimmune or immune-related conditions causing kidney damage. The future of ADX-097 as a potential treatment for AAV remains uncertain pending further updates from Q32 Bio.
