Inozyme Pharma has reported encouraging interim data from its ENERGY 3 pivotal trial evaluating INZ-701 in pediatric patients with ENPP1 Deficiency, showing the drug's potential to address the underlying disease pathophysiology through sustained increases in serum phosphate levels and a favorable safety profile.
The company announced that mean serum phosphate levels increased over time in patients receiving INZ-701, while declining in the conventional therapy arm despite ongoing vitamin D3 and phosphate supplementation. By Week 13, mean serum phosphate levels increased 8.2% from baseline in the INZ-701 arm compared to a 0.04% decrease in the conventional treatment arm. This separation between treatment groups widened over time, with the INZ-701 arm showing a 12.1% increase by Week 39 versus a 9.0% decrease in the control arm.
"The consistency we have observed across safety, immunogenicity, and increases in phosphate levels reinforces our conviction in INZ-701's ability to address the underlying biology of ENPP1 Deficiency," said Douglas A. Treco, Ph.D., CEO and Chairman of Inozyme Pharma. "With no dropouts or dose modifications to date, the emerging profile in pediatric patients is highly encouraging."
Promising Safety and Immunogenicity Profile
The ENERGY 3 trial completed enrollment in January 2025 and is on track to deliver topline data in the first quarter of 2026. To date, there have been no patient discontinuations, dose adjustments, or dosing holidays due to safety or tolerability concerns, and the Data Safety Monitoring Board has identified no new safety signals.
Preliminary anti-drug antibody (ADA) data from 17 patients who had completed at least 13 weeks of dosing showed that 15 patients had either no detectable ADAs or low titer responses. The highest titer among these patients was 1,280, comparable to levels previously observed in adult trials that had no effect on drug exposure or patient safety.
Two patients exhibited higher-titer ADA responses (5,120 and 40,960), similar to levels observed in some infants. The median ADA titer at Week 13 was 80 across all 17 patients, and no ADAs have been associated with any impact on patient tolerability or adverse events.
Clinical Significance for Skeletal Health
Low serum phosphate (hypophosphatemia) is a key driver of rickets and osteomalacia in patients with ENPP1 Deficiency. The interim data demonstrated that 35% of patients treated with INZ-701 achieved normal serum phosphate levels at least once, while no patients in the conventional treatment arm reached the normal range.
"These emerging data on serum phosphate levels suggest that INZ-701 may have a meaningful impact on the severity of rickets and other skeletal complications in children with ENPP1 Deficiency," said Thomas Carpenter, M.D., Professor of Pediatrics and Orthopaedics at Yale School of Medicine. "The consistency of the safety profile and biomarker responses to date is encouraging and supports further clinical development."
Leadership Transition and Regulatory Progress
Inozyme announced the appointment of Petra Duda, M.D., Ph.D., as Chief Medical Officer, effective May 15, 2025. Dr. Duda brings more than two decades of global clinical development, medical affairs, and regulatory leadership experience, with deep expertise in rare and ultra-rare diseases. She succeeds Kurt Gunter, M.D., who will retire and transition to an advisory role.
The company also reported significant regulatory progress, including the acceptance of new ICD-10 diagnosis codes for disorders of pyrophosphate metabolism, including ENPP1 Deficiency, by the U.S. Centers for Medicare & Medicaid Services. These codes will go into effect in October 2025.
Additionally, Inozyme reached an agreement with Japan's Pharmaceuticals and Medical Devices Agenda (PMDA) on a regulatory filing strategy for INZ-701 in ENPP1 Deficiency. The PMDA has agreed to accept data generated from clinical trials conducted outside of Japan without requiring the inclusion of Japanese patients for filing.
About ENPP1 Deficiency and INZ-701
ENPP1 Deficiency is a serious and progressive rare disease affecting blood vessels, soft tissues, and bones. Infants with the condition are typically diagnosed with generalized arterial calcification of infancy (GACI Type 1), with approximately 50% mortality within six months. Children with this condition typically develop autosomal-recessive hypophosphatemic rickets type 2 (ARHR2), while adolescents and adults may develop osteomalacia.
INZ-701 is an ENPP1 Fc fusion protein enzyme replacement therapy designed to address the underlying cause of ENPP1 Deficiency by restoring pyrophosphate (PPi) and adenosine levels. The ENERGY 3 trial is a pivotal, multicenter, randomized controlled study evaluating the efficacy and safety of INZ-701 in children aged 1 to under 13 years with ENPP1 Deficiency.
Financial Position
As of March 31, 2025, Inozyme reported cash, cash equivalents, and short-term investments of $84.8 million, which the company anticipates will fund operations into the first quarter of 2026. Research and development expenses were $20.4 million for the quarter, compared to $19.1 million for the prior-year period, primarily due to increased INZ-701-related research and development expenses.
The company reported a net loss of $28.0 million, or $0.44 loss per share, for the quarter ended March 31, 2025, compared to $23.3 million or $0.38 loss per share for the prior-year period.
