Positive Phase 1/2 Results for INZ-701 in Adults with PXE and ENPP1 Deficiencies

In a recent announcement, Inozyme Pharma, a biopharmaceutical firm focused on treating rare diseases, shared promising results from their Phase 1/2 clinical trials of INZ-701. The trials involved adult patients suffering from ABCC6 Deficiency and ENPP1 Deficiency, conditions characterized by abnormal mineralization and intimal proliferation.

The study on ABCC6 Deficiency enrolled ten adults with severe manifestations of the disease, including cardiovascular and retinal issues. Participants were divided into three cohorts, each receiving different doses of INZ-701: 0.2 mg/kg, 0.6 mg/kg, and 1.8 mg/kg. The preliminary findings indicated a favorable safety profile for INZ-701, with no serious adverse events reported.

Significant observations from the ABCC6 Deficiency trial include the stabilization and reduction of carotid intima-media thickness (cIMT), a risk factor for cardiovascular disease and stroke. Additionally, an increase in choroidal thickness, which is associated with retinal health, was noted across all dose cohorts. The Global Visual Function Questionnaire (VFQ-25) scores showed preservation and improvement in visual function over 48 weeks for patients with initial scores below normal.

In the ENPP1 Deficiency trial, thirteen adults were enrolled across different dosing cohorts. The biomarker data collected suggested a potential for disease modification with INZ-701 treatment. Key changes included a significant reduction in fibroblast growth factor-23 (FGF-23) levels and an increase in bone-specific alkaline phosphatase (BSAP), alongside a decrease in c-telopeptide (CTX), indicating improved bone mineralization.

Both trials demonstrated that INZ-701 was well-tolerated, with a favorable safety profile and low titers of non-neutralizing anti-drug antibodies (ADAs) observed in the majority of patients.

Inozyme Pharma also conducted natural history studies to understand the progression of early-onset ABCC6 Deficiency. The findings underscored the substantial disease burden in pediatric patients, with a high incidence of stroke and severe neurological and cardiovascular diseases occurring early in life.

Given the high risk of cerebrovascular disease in children with ABCC6 Deficiency, Inozyme Pharma is planning to work with regulatory authorities on a pivotal trial design for INZ-701 in pediatric patients. The company aims to initiate this pivotal trial in the first quarter of 2025, subject to regulatory review and funding.

INZ-701, a recombinant Fc fusion protein, is an enzyme replacement therapy being developed to address diseases affecting the vasculature, soft tissue, and skeleton. The therapy works by metabolizing ATP to produce pyrophosphate (PPi), a natural inhibitor of mineralization, and AMP, which can be processed to yield phosphate and adenosine, both of which are natural inhibitors of intimal proliferation.

Inozyme Pharma is committed to advancing INZ-701 as a potential treatment for ENPP1 Deficiency, ABCC6 Deficiency, and calciphylaxis, with ongoing clinical trials aimed at evaluating the safety, tolerability, and efficacy of the therapy. The company's mission is to develop novel therapeutics to improve the lives of patients suffering from these rare and debilitating conditions.