Inozyme Pharma Reports Positive Interim Data from Phase 1 SEAPORT 1 Trial of INZ-701

Inozyme Pharma, Inc., a biopharmaceutical company specializing in therapeutics for rare diseases affecting bone health and blood vessels, has revealed positive interim data from its Phase 1 SEAPORT 1 trial of INZ-701. This trial involved patients with end-stage kidney disease (ESKD) who are undergoing hemodialysis. The findings will be presented at the American Society of Nephrology’s Kidney Week 2024 in San Diego.

The SEAPORT 1 trial, an open-label study, aimed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of INZ-701. This enzyme replacement therapy, an ENPP1-Fc fusion protein, is designed to elevate plasma pyrophosphate (PPi) and adenosine levels. Patients with ESKD typically have lower PPi levels, and those suffering from calciphylaxis - a severe complication of ESKD - show even more critically low levels.

The trial included 11 patients who were administered 1.8 mg/kg of INZ-701 subcutaneously each week over a four-week period. Data from eight patients who completed the study showed significant increases in PPi levels. By the third week, PPi levels reached the normal range, particularly in those with the lowest baseline levels.

Key findings demonstrated that INZ-701 notably raised PPi levels from a baseline mean of 619nM to 1551nM by the 24th day. This increase is significant, considering healthy subjects’ PPi levels range between 1002nM and 2169nM. Additionally, the therapy resulted in decreased biomarkers of mineral metabolism, such as serum phosphate and fibroblast growth factor-23, which are involved in vascular calcification in ESKD.

The safety profile of INZ-701 was positive, with no drug-related adverse events reported. Most treatment-emergent adverse events were mild to moderate, except for one instance of hyperkalemia that required urgent dialysis. Pharmacokinetic profiles were consistent with previous studies, indicating stable drug exposure in dialysis patients. Anti-drug antibodies were detected in three patients but were not linked to any adverse events.

This interim data supports the potential of INZ-701 to modify the progression of calciphylaxis by addressing the underlying PPi deficiency. Calciphylaxis, characterized by abnormal mineralization and blood vessel proliferation in the skin and fatty tissues, leads to severe complications and a high mortality rate. Currently, there are no approved treatments for this condition, making INZ-701 a promising candidate.

Inozyme Pharma plans to initiate a registrational trial for INZ-701 in calciphylaxis in 2025, contingent upon regulatory approval and sufficient funding. This trial aims to provide a therapeutic option for a patient population that currently lacks effective treatments.

Inozyme Pharma continues to focus on developing therapies for rare diseases that impact bone health and vascular function. The positive interim results from the SEAPORT 1 trial of INZ-701 highlight the potential of this therapy to bring significant benefits to patients suffering from ESKD and calciphylaxis.

The company remains dedicated to advancing its understanding and treatment of diseases related to the PPi-Adenosine Pathway, which plays a crucial role in regulating pathological mineralization and intimal proliferation. By addressing disruptions in this pathway, Inozyme aims to alleviate the severe outcomes associated with these conditions, providing hope for patients with limited treatment options.