Selecta Biosciences, Inc. Announces Top Line Data from the Phase I SEL-399 AAV Empty Capsid Study, Highlighting Potential Benefits of ImmTOR? in Gene Therapy
November 08, 2021 at 08:12 am EST
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Selecta Biosciences, Inc. announced top-line results from a joint Selecta and AskBio Phase I randomized, placebo controlled, double blind, dose-escalation study to evaluate the potential of its ImmTOR??platform in mitigating the formation of neutralizing antibodies against an adeno-associated viral serotype 8 (AAV8) serotype capsid used in gene therapies. At day 30, in those subjects administered a single 0.3 mg/kg dose of ImmTOR, Selecta observed a median anti-AAV8 neutralizing antibody titer of 1:5, a 250-fold lower level than that observed in subjects dosed with AAV8 capsid alone. In the Phase I study, researchers evaluated the administration of a single intravenous (IV) dose of a AAV8 empty capsid containing no DNA with and without a single dose of ImmTOR. Healthy subjects (n=23) were enrolled in a randomized 3:1 ratio of AAV8 dose of 2e12 vector genomes (vg)/kilogram (kg) alone (n=8) or in combination with either 0.15 mg/kg (n=9) or 0.3 mg/kg (n=6) of ImmTOR. The primary endpoints evaluated were safety and neutralizing anti-AAV8 antibody titers. Key findings include: No Serious Adverse Events were reported. All treatment-related adverse events were expected for ImmTOR, readily monitorable, and transient; AAV8 empty capsids elicited a strong immune response with peak median anti-AAV8 neutralizing antibody (NAb) titers of 1:6875; Median day 30 titers of neutralizing anti-AAV8 antibodies were 1:25 and 1:5 in the 0.15 mg/kg and 0.3 mg/kg ImmTOR cohorts, respectively; Median day 30 titers of neutralizing anti-AAV8 antibodies were 50-fold and 250-fold lower in the 0.15 mg/kg and 0.3 mg/kg ImmTOR cohorts, respectively, compared to the median titer of control subjects dosed with AAV8 empty capsid alone; At 30 days, of subjects who received 0.3 mg/kg of ImmTOR, 6 of 6, or 100%, exhibited an anti-AAV8 neutralizing antibody titer of 1:25 or less, and 4 of 6 or 67% had a titer of 1:5 or less; At 30 days, of subjects that received 0.15 mg/kg of ImmTOR, 6 of 9, or 67%, exhibited an anti-AAV8 neutralizing antibody titer of 1:25 or less, and 2 of 9, or 22% had a titer of 1:5 or less; By comparison, of subjects that received AAV8 empty capsid alone, only 1 of 8, or 12.5%, had a neutralizing antibody titer of 1:25 or less at 30 days, and no subjects (0/8) had a titer of 1:5 or less; At 90 days 2 of 6 subjects in the 0.3 mg/kg cohort were observed to have sustained control of neutralizing antibodies with titers of 1:25 or less; and Consistent with preclinical data, company observed that the single dose ImmTOR cohorts saw delayed formation of neutralizing antibodies eventually reaching similar median levels of neutralizing antibodies to the control group by day 90.
Cartesian Therapeutics, Inc. is a clinical-stage company. The Company is engaged in developing messenger ribonucleic acids (mRNA) cell therapies for the treatment of autoimmune diseases. It is leveraging its proprietary technology and manufacturing platform, RNA Armory, to develop mRNA cell therapies for autoimmune diseases. Its lead asset e, Descartes-08, is an autologous mRNA chimeric antigen receptor T-cell therapy (CAR-T) directed against the B cell maturation antigen (BCMA), that the Company is developing for the treatment of autoimmune diseases. Descartes-08 is in Phase II clinical development. Descartes-15 is a next-generation, autologous anti-BCMA mRNA CAR-T. Using its proprietary technology and manufacturing platform, it designed Descartes-15 to be more resistant than Descartes-08 to recycling of the CAR upon multiple antigen exposures. It is developing Descartes-33 to deliver a combination of therapeutic proteins that target key drivers in the pathogenesis of autoimmunity.
Selecta Biosciences, Inc. Announces Top Line Data from the Phase I SEL-399 AAV Empty Capsid Study, Highlighting Potential Benefits of ImmTOR? in Gene Therapy