Homology Medicines announces initial data from pheEDIT trial

Homology Medicines announced initial clinical data from the first dose cohort in the pheEDIT Phase 1, dose-escalation trial evaluating gene editing candidate HMI-103 in adults with classical phenylketonuria, or PKU, the most prevalent and severe form of the disease. As of the data cut-off date of July 26, HMI-103 has been generally well-tolerated in all three participants. Participant 1 experienced a reduction in plasma phenylalanine levels to below the U.S. American College of Medical Genetics and Genomics PKU treatment guideline threshold of less than 360 micromol/L*, and the majority of Phe levels have been below 360 micromol/L through 31 weeks post-dose, including after the initiation of dietary protein supplementation. Participant 2 has experienced a meaningful plasma Phe reduction of 49% at 17 weeks post-dose. Participant 3 was recently dosed. HMI-103 is a nuclease-free gene editing candidate for PKU designed to harness the body’s natural DNA repair process of homologous recombination to insert a functional gene and liver-specific promoter, and to increase PAH with episomal expression in all transduced liver cells. HMI-103 was administered to participants via a one-time intravenous infusion at a dose of 6E13 vg/kg. As of the data cut-off date of July 26, HMI-103 has been generally well-tolerated by all three participants with no serious adverse events, or SAEs, and the majority of treatment-related adverse events, or AEs, have been mild. All liver function tests have remained in the normal range during the prophylactic immunosuppression regimen incorporating the T-cell inhibitor tacrolimus in combination with corticosteroid. At baseline, Participant 1’s plasma Phe level was 781 +/- 145 micromol/L, an average of five readings during the Screening and Run-in period while on a stable, Phe-restricted diet. Following HMI-103 administration, and while on a Phe-restricted diet, the participant experienced a rapid and clinically meaningful plasma Phe reduction of 55% change from baseline and below the ACMG PKU treatment guideline threshold of 360 micromol/L. At 14 weeks post-dose, Participant 1 achieved a plasma Phe reduction of 98% change from baseline and, at that time, supplemental protein was added to the diet per protocol, based on plasma Phe levels of less than30 micromol/L. After dietary protein supplementation, the majority of Participant 1’s plasma Phe levels have remained below 360 micromol/L, with a plasma Phe reduction of 59% change from baseline at 31 weeks post-dose. Participant 2’s baseline plasma Phe level was 1,506 +/- 173 micromol/L. Following HMI-103 administration, the participant experienced variable plasma Phe levels, potentially due to self-liberalized and variable protein intake, including above baseline diet, and has achieved a meaningful plasma Phe reduction of 49% from baseline at 17 weeks post-dose. Participant 3’s baseline plasma Phe level was 1,492 +/- 93 micromol/L. Participant 3 was recently dosed, and plasma Phe values are currently above baseline; however, the company believes additional data are needed to make a meaningful conclusion given the timeframe and the participant’s self-liberalized and variable dietary protein intake to above baseline diet.