REGENXBIO Inc. announced additional interim safety data and initial efficacy data from the Phase I/II AFFINITY DUCHENNE?? trial of RGX-202 for the treatment of Duchenne Muscular Dystrophy (Duchenne). Results were shared at the 28th Annual International Congress of the World Muscle Society.

RGX-202 is an investigational one-time AAV therapeutic for Duchenne, using the NAV® AAV8 vector to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal (CT) domain as well as a muscle-specific promoter to support a targeted therapy for improved resistance to muscle damage associated with Duchenne. Data were presented from dose level 1 (1x1014 genome copies (GC)/kg body weight) of the ongoing Phase I/II AFFINITY DUCHENNE? trial, which continues to recruit ambulatory patients (aged 4 to 11 years) and is using commercial-ready cGMP material from the REGENXBIO Manufacturing Innovation Center.

Safety Update: As of September 28, 2023, RGX-202 was reported to be well tolerated with no drug-related serious adverse events in three patients, aged 4.4, 10.6 and 6.3 years, dosed to date at dose level 1. Time of post-administration follow up ranges from three weeks to more than five months. The two patients who reached three-month follow-up have completed the immunosuppression regimen per study protocol. Biomarker Data: Initial biomarker data from two patients who completed three-month trial assessments indicate encouraging increases in expression of RGX-202 microdystrophin from bicep muscle biopsies taken at three months following one-time administration of RGX-202.

In addition, RGX-202 microdystrophin was detectable by immunofluorescence staining throughout muscle tissue at three months, with RGX-202 microdystrophin protein localized to the sarcolemma. RGX-202 microdystrophin levels were measured using an automated and precise western blot method (Jess), and comparable results were confirmed with a proprietary liquid chromatography-mass spectrometry (LC-MS) method. In the patient aged 4.4 years old, RGX-202 microdystrophin expression was measured to be 38.8% compared to control.

A reduction from baseline in serum creatinine kinase (CK) levels of 43% was observed at ten weeks, supporting evidence of clinical improvement. Elevated CK levels are associated with muscle injury and are uniformly elevated in patients with Duchenne. In the patient aged 10.6 years old, RGX-202 microdystrophin expression was measured to be 11.1% compared to control and a reduction from baseline in serum CK levels of 44% was observed at ten weeks.

Clinical Program Updates: REGENXBIO expects to dose patients at dose level 2 (2x1014 genome copies (GC)/kg body weight) in the Phase I/II AFFINITY DUCHENNE trial by the end of 2023. In addition, the trial protocol has been amended to accelerate the development of RGX-202, updating the dose expansion phase of the trial to begin after two patients, from the previous three patients. REGENXBIO also provided an update on a newly completed preclinical efficacy study evaluating RGX-202 manufactured using REGENXBIO's NAVXpress?

commercial-ready process at both dose levels. RGX-202 at dose level 2 showed improvement in functional performance, compared to dose level 1, as determined by forelimb muscle strength and treadmill exhaustion in mdx mice. This data further supports plans to immediately initiate dose escalation to dose level 2. The Company expects to share initial strength and functional assessment data for both dose levels in 2024.

Additionally, REGENXBIO expects to make a pivotal dose determination and initiate a pivotal program for RGX-202 in 2024.