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Homology Medicines Announces Peer-Reviewed Publication of HMI-102 Investigational Gene Therapy Demonstrating Restoration of Normal Metabolic Pathway in PKU Disease Model

- Data Package Supported Initiation of Ongoing pheNIX Clinical Trial for Adults with PKU -

BEDFORD, Mass., March 16, 2020 – 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

About the Phase 1/2 pheNIX Clinical Trial in Phenylketonuria (PKU)
The pheNIX trial is the first gene therapy clinical trial ever conducted for people with PKU. pheNIX is designed to evaluate the safety and efficacy of a single intravenous administration of HMI-102 in adult patients with PKU aged 18-55. The study design allows for expansion of the number of patients in any dose cohort pending review by the Data Monitoring Committee and the Homology Internal Data Review Team. A decision to expand would trigger the addition of the randomized, concurrently controlled Part B of the trial, which has the potential to be converted to a registrational trial. The primary efficacy endpoint of the expansion part is incidence of sustained plasma Phe concentration ≤360 μmol/L as demonstrated by two measurements ≤360 μmol/L between 16 and 24 weeks.

About Homology Medicines, Inc.
Homology Medicines, Inc. is a genetic medicines company dedicated to transforming the lives of patients suffering from rare genetic diseases with significant unmet medical needs by curing the underlying cause of the disease. Homology’s proprietary platform is designed to utilize its human hematopoietic stem cell-derived adeno-associated virus vectors (AAVHSCs) to precisely and efficiently deliver genetic medicines in vivo either through a gene therapy or nuclease-free gene editing modality across a broad range of genetic disorders. Homology has a management team with a successful track record of discovering, developing and commercializing therapeutics with a particular focus on rare diseases, and intellectual property covering its suite of 15 AAVHSCs. Homology believes that its compelling preclinical data, scientific expertise, product development strategy, manufacturing capabilities and intellectual property position it as a leader in the development of genetic medicines. For more information, please visit

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. 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; plans and timing for the release of clinical data from the Phase 1/2 pheNIX trial, including the Part B expansion; plans and timing for the release of clinical data; our beliefs regarding our manufacturing capabilities; advancing our novel platform and pipeline; our goal of delivering potential cures to patients; beliefs about preclinical data; our position as a leader in the development of genetic medicines; the sufficiency of our cash, cash equivalents and short-term investments; and our participation in upcoming presentations and conferences. 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 capabilities and potential expansion of our manufacturing facility; risks relating to the regulatory approval process; 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; 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; failure to attract, retain and motivate qualified personnel; the possibility of system failures or security breaches; risks relating to intellectual property and significant costs as a result of operating as a public company. These and other important factors discussed under the caption “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2019 and our other filings with the SEC 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 Contacts:
Theresa McNeely
Chief Communications Officer and Patient Advocate

Media Contact:
Cara Mayfield
Senior Director, Patient Advocacy and Corporate Communications