Trial to Assess Selecta’s Gene Therapy/Immunomodulatory Combo in Patients With MMA

Selecta Biosciences’ first-in-human clinical trial is assessing the safety and efficacy of MMA-101 gene therapy in combination with ImmTOR, the company’s investigational immunomodulatory agent, in patients with methylmalonic acidemia (MMA) due to methylmalonyl-CoA mutase (MMUT) deficiency.

The clinical trial was presented at the 2023 American Society of Gene and Cell Therapy (ASGCT) Annual Meeting, taking place May 16-20 in Los Angeles, California, by Rehan Azeem, MD, MPH, vice president, clinical development, Selecta Biosciences.

“Therapeutic goal of a single intravenous administration of MMA-101 is to induce constitutive expression of the wild type MMUT gene in the livers of patients and provide long-term correction of the metabolic defect,” Azeem and colleagues wrote in their poster.

The trial will have a cohort of 3 adolescents and a cohort of 3 children that will receive 1.0E13 vg/kg MMA-101 and 0.15 or up to 0.3 mg/kg of ImmTOR. The trial consists of a prescreening period of 2 remote visits 80 and 60 days before dosing, a screening period up to 45 days before dosing, a pre-dose baseline period of 1 to 14 days, and then the treatment period, which will begin with the dosing of the first adolescent patient with MMA-101. All other participants will receive MMA-101 and ImmTOR on day 1 and ImmTOR alone on days 28 and 56. Study follow-up will continue for 1 year, and then another 4 years as part of long-term follow-up.

ImmTOR consists of biodegradable polymeric nanoparticles encapsulating sirolimus. It is designed to address challenges with immunogenicity of adeno-associated virus (AAV) gene therapy by inducing immune tolerance and may reduce or eliminate AAV8 neutralizing antibody formation and therefore allow potential redosing of gene therapy in the future. MMA-101 is a liver-targeted, recombinant AAV gene therapy that expresses the MMUT transgene

“ImmTOR has the potential to increase safety of AAV gene therapy in pediatric MMA patients by mitigating acute hepatic inflammation, inhibiting AAV-specific T cell responses, and stabilizing the defect in hepatic mitophagy associated with MMA,” Azeem and colleagues concluded. “ImmTOR may enhance efficacy when used at the first dose AAV gene therapy by enhancing transgene expression and durability. Treatment with MMA-101 gene therapy can potentially provide an early in patients when maximum clinical benefit may be expected by preventing acute-on-chronic neurological injury, other long-term systemic complications, and permanent severe disability.”