Homology Medicines is focused on advancing our genetic medicines platform as one-time treatments and potential cures for patients with rare diseases

Homology Medicines is focused on advancing our genetic medicines platform as one-time treatments and potential cures for patients with rare diseases

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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

July 27, 2023

Participant 1 Achieved Clinically Meaningful Reduction in Plasma Phe of Up to 99% Change from Baseline and Below the U.S. PKU Treatment Guideline Threshold (<360 μmol/L)*; At 31 Weeks Post-Dose, Phe Level 319 μmol/L With a 59% Reduction from Baseline, Even After Dietary Protein Supplementation

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, July 27, 2023 at 4:30 p.m. ET

BEDFORD, Mass., July 27, 2023 (GLOBE NEWSWIRE) -- Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today encouraging 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 (PKU), the most prevalent and severe form of the disease. As of the data cut-off date of July 26, 2023, HMI-103 has been generally well-tolerated in all three participants. Participant 1 experienced a reduction in plasma phenylalanine (Phe) levels to below the U.S. American College of Medical Genetics and Genomics (ACMG) PKU treatment guideline threshold of <360 μmol/L*, and the majority of Phe levels have been below 360 μmol/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.

“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 U.S. PKU treatment guideline threshold even after the addition of dietary protein, and Participant 2 experiencing meaningful reductions in plasma Phe,” said Albert Seymour, Ph.D., President and Chief Executive Officer of Homology Medicines. “We believe these initial clinical data from the first cohort suggest that our one-time gene editing approach has the potential to restore the normal biochemical pathway and support our recommendation to dose-escalate to identify an optimal dose.”

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 July 26, 2023, HMI-103 has been generally well-tolerated by all three participants with no serious adverse events (SAEs), and the majority of treatment-related adverse events (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 (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 Julie Jordan, M.D., Chief Medical Officer of Homology Medicines. “It is noteworthy to see this magnitude of plasma Phe reduction in classical PKU, a population who generally cannot bring their levels below the U.S. PKU treatment guideline threshold even while restricting Phe intake, let alone after the addition of protein to the diet. We are also pleased that the targeted immunosuppression regimen has been effective in the first dose cohort. I would like to thank the PKU community, especially the participants and care teams at the clinical sites, who have made it possible to evaluate this new genetic medicine approach.”

Conference Call and Webcast Information
Homology will host a live webcast presentation and conference call today, July 27, 2023, at 4:30 p.m. ET. The webcast will be available on Homology’s website in the Investors section, and a replay of the webcast will be available on the website for 90 days following the presentation. To access using the conference call line, register here to obtain dial-in and passcode details.

*Vockley J., et al., Genet Med. 2014
**Weight-based dosing up to 100 kilograms

About HMI-103
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 U.S. Food and Drug Administration for the treatment of neurocognitive and neuropsychiatric manifestations of PKU secondary to phenylalanine hydroxylase deficiency.

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.

About PKU
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 National PKU Alliance, PKU affects nearly 16,500 people in the U.S. with approximately 350 newborns diagnosed each year. The worldwide prevalence of PKU is estimated to be 50,000 people.

About Homology Medicines, Inc. 
Homology Medicines, Inc. is a clinical-stage genetic medicines company dedicated to transforming the lives of patients suffering from rare diseases by addressing the underlying cause of the disease. The Company’s clinical programs include HMI-103, a gene editing candidate for phenylketonuria (PKU); HMI-203, an investigational gene therapy for Hunter syndrome; and HMI-102, an investigational gene therapy for adults with PKU. Additional programs focus on paroxysmal nocturnal hemoglobinuria (PNH), metachromatic leukodystrophy (MLD) and other diseases. Homology’s proprietary platform is designed to utilize its family of 15 human hematopoietic stem cell-derived adeno-associated virus (AAVHSCs) vectors to precisely and efficiently deliver genetic medicines in vivo through a nuclease-free gene editing modality, gene therapy, or GTx-mAb, which is designed to produce antibodies throughout the body. Homology established an AAV manufacturing and innovation business in partnership with Oxford Biomedica, which was based on Homology’s internal process development and manufacturing platform. Homology has a management team with a successful track record of discovering, developing and commercializing therapeutics with a focus on rare diseases. Homology believes its initial clinical data and compelling preclinical data, scientific and product development expertise and broad intellectual property position the Company as a leader in genetic medicines. For more information, visit

Forward-Looking Statements
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 U.S. or international marketing approval; ongoing regulatory obligations; effects of significant competition; unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives; product liability lawsuits; securities class action litigation; the impact of the COVID-19 pandemic and general economic conditions on our business and operations, including our preclinical studies and clinical trials; failure to attract, retain and motivate qualified personnel; the possibility of system failures or security breaches; risks relating to intellectual property; and significant costs incurred as a result of operating as a public company. These and other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the quarter ended March 31, 2023 and our other filings with the Securities and Exchange Commission could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.

Company Contact:
Brad Smith
Chief Financial and Business Officer

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Source: Homology Medicines, Inc.