SEAPORT 1: An Open-label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of INZ-701 in Participants with ESKD Undergoing Hemodialysis: Interim Analysis

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Background: Calciphylaxis is a dire complication of end-stage kidney disease (ESKD) with high mortality and no approved therapies. It is characterized by calcification and occlusion of arterioles in the skin leading to painful lesions, ulceration, and infection. Plasma pyrophosphate (PPi), a critical inhibitor of ectopic vascular calcification, is low in chronic kidney disease (CKD) patients and even lower in ESKD patients, who are at highest risk of developing calciphylaxis. Moreover, lower PPi is associated with worse survival in calciphylaxis patients. The ectonucleotide pyrophosphatase/phosphodiesterase type 1 (ENPP1) enzyme is responsible for generating most of the body’s PPi via catalysis of extracellular ATP. INZ-701 is a novel fusion protein comprised of functional ENPP1 enzyme fused to the Fc portion of human immunoglobulin 1. Treatment of a CKD rat model with INZ-701 prevented or reduced vascular calcification. Objective: To evaluate the safety, pharmacokinetics and pharmacodynamics of INZ-701 in patients with ESKD receiving hemodialysis. The primary endpoint is change from baseline in plasma PPi. Methods: Open-label phase 1 trial of INZ-701 in individuals aged 18 – 69 years with ESKD receiving hemodialysis thrice weekly and who had low PPi (< 700 nM) at screening. Participants were administered 1.8 mg/kg of INZ-701 subcutaneously once weekly for four weeks. Results: Thirteen participants were screened and 8 have been entered into the study to date. Median baseline age for entered participants was 67 years (range 28-69) and 5 participants (63%) were male. Six participants (75%) had type 2 diabetes. The majority of participants were Black or African American (n=5, 63%). Median (IQR) plasma PPi at baseline in the 8 entered participants was 281 nM (322). Median PPi for all screened patients was 502 nM (422). Conclusion: Median PPi at screening in 13 patients with ESKD on hemodialysis was substantially lower than what is reported in healthy volunteers (1002-2169 nM; n=10), which supports previous findings implicating PPi in the pathophysiology of ESKD. INZ-701 safety, tolerability, pharmacokinetics, and pharmacodynamics results will be presented. Funding: Commercial Support - Inozyme Pharma

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