Homology Medicines, Inc. (NASDAQ:FIXX), a genetic medicines company, announced today the peer-reviewed publication of preclinical data that supports Homology’s HMI-102 investigational gene therapy program for the treatment of adults with phenylketonuria (PKU). HMI-102 is currently being evaluated in the pheNIX Phase 1/2 clinical trial, and the Company plans to provide an update on the trial when selecting the dose for the expansion part, which is currently anticipated in mid-2020.
The published data shows that a single administration of HMI-102 (AAVHSC15-PAH) produced a sustained reduction in phenylalanine (Phe), the key biomarker in the diagnosis and management of PKU, for the lifespan of the established murine model for PKU. The data also demonstrated a concomitant increase in tyrosine (Tyr), a metabolite of Phe and precursor to neurotransmitters, indicating enzymatic activity. Additionally, brain levels of Phe, 5-HIAA (downstream serotonin metabolite) and coat color were normalized, further indicating restoration of the Phe metabolic pathway.
“We developed a robust preclinical data package for our investigational HMI-102 gene therapy, which supported the initiation of our ongoing Phase 1/2 pheNIX clinical trial for adults with PKU,” stated Albert Seymour, Ph.D., Chief Scientific Officer of Homology Medicines. “These published data demonstrated that a single dose of HMI-102 was able to restore the normal biochemical pathway in the established PKU model on normal protein diet. Initial data from the pheNIX trial suggests that the increased PAH enzymatic activity after administration of HMI-102 seen in the preclinical model was also observed in the clinical study.”
Key data in the publication include:
- A single IV administration of HMI-102 reduced serum Phe concentrations to normal levels within one week in the PKU murine model, and mean levels remained below 120 µM (the normal range) over the course of the 48-week study.
- A corresponding increase in Tyr concentration was also observed, indicating restoration of the Phe/Tyr metabolic pathway.
- HMI-102 administration was also associated with an increase in 5-HIAA and a decrease in Phe in the brain to normal levels.
The publication, “Sustained Correction of a Murine Model of Phenylketonuria Following a Single Intravenous Administration of AAVHSC15-PAH,” was peer-reviewed and published in the journal Molecular Therapy: Methods & Clinical Development. For more information, please visit www.homologymedicines.com/publications.