Inozyme Pharma (INZY) 24th Annual Needham Virtual Healthcare Conference summary

Program overview and disease background

• INZ-701 is an enzyme replacement therapy targeting rare diseases, primarily ENPP1 deficiency, which causes abnormal tissue and bone mineralization due to low pyrophosphate levels.

• ENPP1 deficiency is autosomal recessive, with biallelic patients experiencing a spectrum of severity, from infant mortality to lifelong rickets and mobility issues.

• Prevalence is estimated at 1 in 64,000 pregnancies, with about 10,000 addressable patients in North America, Brazil, Japan, and Europe.

• Diagnosis rates are very low, likely under 10%, due to limited physician awareness and genetic testing.

• The initial commercial focus is on pediatric patients, especially infants and children with severe disease, aiming for a broad label across all ages.

Clinical development and trial design

• The pivotal ENERGY-3 phase 3 trial in children (ages 1–13) is randomized 2:1 against standard of care, with primary endpoints of pyrophosphate increase and rickets improvement.

• U.S. regulators require a primary endpoint of pyrophosphate and a trend in rickets score; Europe uses both as co-primary endpoints, with a relaxed statistical threshold for rickets improvement.

• The RGI-C (rickets improvement) is measured by a seven-point X-ray scale, with the trial powered to detect a 0.7 difference between groups at 90% power and p=0.2.

• Secondary endpoints include RSS (rickets severity score) and growth Z-score, with primary analysis at week 52 and crossover to treatment for control patients after one year.

• Long-term safety exposure is robust, with most patients self-administering at home and strong safety data across age groups.

Clinical data and efficacy insights

• Adult studies showed rapid normalization of pyrophosphate, improved mobility, and positive patient- and clinician-reported outcomes.

• In infants, four out of five treated survived, with improved heart function and stabilization of phosphate levels, reducing risk of rickets.

• Some infants developed high antibody titers (ADA), which can reduce drug exposure but are considered manageable through dose adjustment or immunosuppression.

• Antibody issues are not expected to impede commercial success, as seen in other enzyme replacement therapies.

• The company is optimistic that efficacy in adults will translate to even greater benefit in children due to higher bone turnover.