Inozyme Pharma (INZY) Stifel 2024 Healthcare Conference summary

Program overview and scientific rationale

• INZ-701 is an enzyme replacement therapy designed to increase pyrophosphate and adenosine, targeting blood vessel health and bone formation in three rare diseases: ENPP1 deficiency, ABCC6 deficiency, and calciphylaxis.

• ENPP1 deficiency leads to severe vascular calcification in infants and abnormal bone growth (rickets) in children, with a significant unmet need in the pediatric population.

• ABCC6 deficiency involves a substrate defect affecting PPi production, with animal and human data supporting INZ-701's potential efficacy.

• Calciphylaxis, an acquired disease in dialysis patients, is linked to low pyrophosphate and may be treatable with INZ-701.

Clinical development and trial design

• Phase 1/2 studies in adults showed safety, tolerability, and biomarker improvements; pediatric pivotal study (ENERGY-3) is the core of the regulatory strategy.

• ENERGY-3 is a randomized, controlled trial in children with rickets, using 2.4 mg/kg weekly dosing, powered at 80% to detect improvement in rickets score (RGI-C) and PPi levels.

• Single-arm studies in infants (ENERGY-1 in the US, ENERGY-2 ex-US) and adults will support the regulatory package, with infant data updates expected in Q4.

• Regulatory endpoints focus on PPi increase and rickets score improvement, with US and EU agencies aligned on primary/co-primary endpoints.

Regulatory and strategic considerations

• Regulatory strategy aims for approval across all age groups, leveraging data from adults, children, and infants, similar to precedents set by Strensiq and Crysvita.

• For ABCC6, discussions with regulators are ongoing, with a likely path involving a randomized controlled trial using composite clinical endpoints.

• Calciphylaxis program is building a biological rationale, focusing on early diagnosis and intervention based on pyrophosphate levels.