Homology Medicines Announces Encouraging Initial Data from First Dose Level in the pheEDIT Trial Evaluating Gene Editing Candidate HMI-103 in Adults with Classical PKU
Participant 1 Achieved Clinically Meaningful Reduction in Plasma Phe of Up to 99% Change from Baseline and Below the
Participant 2 Plasma Phe Level Reduction of 49% Change from Baseline at 17 Weeks Post-Dose
HMI-103 Has Been Generally Well-Tolerated
Webcast Scheduled for Today,
“We are pleased to report today that the first dose level in the pheEDIT gene editing trial for PKU was generally well-tolerated by all three participants, with Participant 1 achieving Phe levels below the
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 (I.V.) infusion at a dose of 6E13 vg/kg**. As of the data cut-off date of
At baseline, Participant 1’s plasma Phe level was 781 ± 145 (SD) μmol/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 μmol/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 <30 μmol/L. After dietary protein supplementation, the majority of Participant 1’s plasma Phe levels have remained below 360 μmol/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 (SD) μmol/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 (SD) μmol/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.
“These initial data show that a one-time dose of HMI-103 meaningfully reduced Phe in two participants, including when protein intake was increased for Participant 1, which is not otherwise expected for people living with PKU,” said
Conference Call and Webcast Information
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*Vockley J., et al., Genet Med. 2014
**Weight-based dosing up to 100 kilograms
HMI-103 is a one-time, in vivo, nuclease-free gene editing candidate for PKU designed to harness the body's natural DNA repair process of homologous recombination to replace the disease-causing gene with a functional gene and liver-specific promoter and to maximize PAH in all transduced liver cells with episomal expression. HMI-103 has the potential to treat adults and children whose livers are still rapidly growing. HMI-103 was granted Fast Track designation by the
About the pheEDIT Clinical Trial for PKU
Homology is conducting the pheEDIT Phase 1, open-label, dose-escalation clinical trial, which is evaluating a single I.V. administration of gene editing candidate HMI-103 in adults with uncontrolled classical PKU due to PAH deficiency. The trial is designed to evaluate up to three sequential doses of HMI-103. The trial includes a targeted, prophylactic immunosuppression regimen that consists of a T-cell inhibitor, tacrolimus, and a tapering course of corticosteroids.
PKU is a rare inborn error of metabolism caused by a mutation in the PAH gene. PKU results in a loss of function of the enzyme phenylalanine hydroxylase, which is responsible for the metabolism of Phe, an amino acid obtained exclusively from the diet. If left untreated, toxic levels of Phe can accumulate in the blood and result in progressive and severe neurological impairment. Currently, there are no treatment options for PKU that target the underlying genetic cause of the disease. According to the
This press release contains forward-looking statements. We intend such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding: our expectations surrounding the potential, safety, efficacy, and regulatory and clinical progress of our product candidates, including HMI-103 for the treatment of PKU; the potential of our gene therapy and gene editing platforms, including our GTx-mAb platform; our plans and timing for the release of additional preclinical and clinical data; our plans to progress our pipeline of genetic medicine candidates and the anticipated timing for these milestones; our position as a leader in the development of genetic medicines; and our participation in upcoming presentations and conferences. The words “believe,” “may,” “will,” “estimate,” “potential,” “continue,” “anticipate,” “intend,” “expect,” “could,” “would,” “project,” “plan,” “target,” and similar expressions are intended to identify forward-looking statements, though not all forward-looking statements use these words or expressions. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; failure to identify additional product candidates and develop or commercialize marketable products; the early stage of our development efforts; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process; interim, topline and preliminary data may change as more patient data become available, and are subject to audit and verification procedures that could result in material changes in the final data; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties, including for the manufacture of materials for our research programs, preclinical and clinical studies; failure to obtain
Source: Homology Medicines, Inc.