Inozyme Pharma, Inc. announced positive topline pharmacokinetic (PK), pharmacodynamic (PD), and safety data from the ongoing Phase 1/2 clinical trials of INZ-701 in ENPP1 Deficiency and ABCC6 Deficiency (PXE). The Company also reported encouraging patient reported outcome data as measured by global impression of change (GIC) in the ENPP1 Deficiency trial. Phase 1/2 Clinical Trial in Adults with ENPP1 Deficiency: Nine patients were initially enrolled in the ongoing Phase 1/2 clinical trial across three dose cohorts of INZ-701 (0.2 mg/kg (n=3), 0.6 mg/kg (n=3), and 1.8 mg/kg (n=3)). Pharmacodynamic Data: Mean baseline PPi across all three cohorts was 426±407 nM. Rapid, significant, and sustained increase in PPi was observed in all patients, with a target PPi threshold observed from the lowest dose of 0.2 mg/kg. PPi increased in all patients to levels comparable to those observed in a study of healthy subjects (n=10), which showed PPi levels between 1002 nM and 2169 nM. Pharmacokinetic Data: INZ-701 activity in a dose proportional manner was observed. Long half-life of approximately 126 hours and drug accumulation as shown by a greater than dose proportional exposure suggests the potential for once weekly dosing. Safety Data: INZ-701 was generally well-tolerated and exhibited a favorable safety profile, with no serious or severe adverse events attributed to INZ-701 and no adverse events leading to study withdrawal. 3/9 patients experienced mild adverse events related to INZ-701. Injection site reactions (bruising or pain) occurred in 2/9 patients. Other related adverse events included decreased appetite and fatigue. There were two serious adverse events not related to INZ-701. All nine patients enrolled in Phase 2, one of whom subsequently withdrew from the study following week 12 due to travel reasons. Eight patients continue on INZ-701 treatment. Anti-Drug Antibody (ADA) Data: INZ-701 exhibited a favorable immunogenicity profile with low titers of non-neutralizing ADAs observed in 7/9 patients. Emerging Exploratory Clinical Data: GIC is a patient reported outcome measure (PRO) in the ongoing Phase 1/2 clinical trial of INZ-701 in ENPP1 Deficiency. The measurement is performed by the clinician (C-GIC) and the patient (P-GIC) and assesses overall change in health from baseline on a 7-point scale as measured from “very much worse” (-3) to “very much improved” (+3). GIC is an exploratory endpoint and an early indicator of potential clinical outcomes. 6/8 patients showed concordant improvements on overall health on C-GIC and P-GIC. 5/8 patients showed “much improved” (+2) or “very much improved” (+3) on P-GIC. No patients showed a deterioration in overall health from baseline on C-GIC or P-GIC. Phase 1/2 Clinical Trial in Adults with ABCC6 Deficiency: Nine patients were initially enrolled in the ongoing Phase 1/2 trial across three dose cohorts of INZ-701 (0.2 mg/kg (n=3), 0.6 mg/kg (n=3), and 1.8 mg/kg (n=3)). Pharmacodynamic Data: Mean baseline PPi across all three cohorts was 947±193 nM. Rapid and significant increase in PPi was observed in all cohorts with a dose response observed. PPi showed sustained increase in the higher dose cohort to levels comparable to those observed in a study of healthy subjects (n=10), which showed PPi levels between 1002 nM and 2169 nM. Pharmacokinetic Data: INZ-701 activity in a greater than dose proportional manner was observed. Long half-life of approximately 126 hours and drug accumulation as shown by a greater than dose proportional exposure suggests the potential for once weekly dosing. Safety Data: INZ-701 was generally well-tolerated and exhibited a favorable safety profile, with no serious or severe adverse events. All adverse events were mild to moderate in severity. Anti-Drug Antibody (ADA) Data: INZ-701 exhibited a favorable immunogenicity profile with low titers of non-neutralizing ADAs observed in 6/9 patients. ENPP1 Deficiency
Start of FDA pivotal trial meetings— first quarter of 2023. Initiation of ENERGY-1 - Phase 1b clinical trial of INZ-701 to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of INZ-701 in infants— second quarter of 2023. Interim clinical data from ongoing Phase 1/2 trial in adults—third quarter of 2023. Initiation of pivotal trial in pediatric patients, subject to regulatory approval— third quarter of 2023. Start of EMA protocol assistance meetings— fourth quarter of 2023. ABCC6 Deficiency: Interim clinical data from ongoing Phase 1/2 trial in adults— fourth quarter of 2023.
Initiation of Phase 2/3 clinical trial, subject to regulatory approval—2024.