Homology Medicines Announces FDA Clearance of Investigational New Drug Application for HMI-102 Gene Therapy Candidate for PKU

April 4, 2019 at 7:00 AM EDT

- Phase 1/2 pheNIX Trial Would Represent First PKU Gene Therapy to Enter the Clinic -

- Initial Clinical Data Expected by the End of 2019 -

BEDFORD, Mass., April 04, 2019 (GLOBE NEWSWIRE) -- Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today that the U.S. Food and Drug Administration (FDA) has provided clearance for Homology to begin its Phase 1/2 pheNIX clinical trial with HMI-102, a one-time gene therapy candidate for adults with the rare genetic disease phenylketonuria (PKU), an inborn error of metabolism. Homology has been working closely with multiple clinical sites in the U.S. to prepare for potential initiation of the pheNIX trial, which is designed to evaluate the safety and efficacy of the investigational gene therapy in a randomized, concurrently-controlled, dose-escalation study in adult patients with classic PKU.

“Our progress into the clinic with a one-time gene therapy candidate that is designed to address the underlying cause of the disease for adults with PKU will be an important milestone for Homology, as well as the patients and families who need new treatment options for this rare genetic disorder of metabolism,” said Albert Seymour, Ph.D., Chief Scientific Officer of Homology Medicines. “Our IND package included compelling data showing that administration of HMI-102 restored the phenylalanine metabolic pathway, resulting in normalization of blood phenylalanine levels and an increase in neurotransmitter production in a well-established PKU model. In addition, we provided comprehensive pharmacology, toxicology and CMC data that supported our application. We look forward to our continued work with multiple centers in the U.S. to initiate the trial as soon as possible and report initial clinical data this year.”

HMI-102 is designed to use one of Homology’s proprietary human hematopoietic stem-cell derived adeno-associated virus vectors (AAVHSCs) to deliver a functional copy of the phenylalanine hydroxylase (PAH) gene to the liver cells, where there is a missing or mutated PAH gene. This in vivo gene therapy approach is intended to enable the production of the PAH enzyme responsible for metabolizing phenylalanine (Phe). People with PKU are not able to metabolize Phe properly resulting in significantly elevated levels of Phe, and if left untreated, can lead to severe neurological impairment. Phe reduction is an established clinical endpoint for PKU registrational trials.

“A potentially curative gene therapy that provides the functional gene and relieves the burden of PKU would be a major advance for patients and their families,” stated Arthur Tzianabos, Ph.D., President and Chief Executive Officer of Homology Medicines.

Homology’s IND package contained preclinical data demonstrating that HMI-102 restored the normal biochemical pathway, including data showing that treatment with HMI-102:

  • Lowered serum Phe to normal levels within one week, which was durable for the lifespan of the murine model, and lowered brain Phe to normal levels;
  • Increased tyrosine, which is responsible for the production of neurotransmitters, and increased brain 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of serotonin; and
  • Changed coat color, indicating production of melanin.

The IND package also included data demonstrating that direct weight-based dosing translated between the murine model and non-human primates. Data also indicated that HMI-102 was well-tolerated at or exceeding the planned clinical dose range.

The GMP manufacturing campaign is well underway and the Company expects to have ample supply of HMI-102 for the pheNIX trial. Homology anticipates the first patient to be dosed following requisite Institutional Biosafety Committee and Institutional Review Board approvals at the clinical sites.

About the pheNIX Phase 1/2 PKU Clinical Trial
The Phase 1/2 pheNIX trial is an open-label, randomized, concurrently controlled, dose-escalation study designed to evaluate the safety and efficacy of HMI-102 in adults with classic PKU, defined as patients with Phe levels greater than 1,200 umol/L, due to phenylalanine hydroxylase (PAH) deficiency. In addition to safety measures, the trial is also designed to evaluate reduction in serum Phe levels.

The first cohort of patients, aged 18 – 55 years old, will receive a single intravenous administration of HMI-102, a gene therapy designed to deliver a functional copy of the PAH gene to liver cells. Safety data from the initial cohort of patients will inform the dose-escalation plan for additional patient cohorts and/or expansion of the clinical trial.

About Phenylketonuria (PKU)
PKU is a rare, inherited inborn error of metabolism caused by a mutation in the PAH gene. The current standard of care is a highly restrictive diet, but it is not always effective, and there are currently no treatments available that address the genetic defect in PKU. If left untreated, PKU can result in progressive and severe neurological impairment. PKU affects approximately 15,000 people in the U.S., and an estimated 300 newborns are diagnosed each year.

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 www.homologymedicines.com.

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 statements regarding the potential for HMI-102 to address the underlying genetic cause of PKU; advancing our novel gene therapy and gene editing technology platform and pipeline; our expectations surrounding initiation and timing of clinical trials for our PKU gene therapy program; our beliefs regarding our supply and manufacturing capabilities; our goal of improving the lives of patients with rare genetic diseases; the anticipated timing of the release of clinical data for the Phase 1/2 clinical trial; beliefs about preclinical data; and our position as a leader in the development of genetic medicines. 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: the fact that 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 marketable products; the early stage of our development efforts; our failure or the failure of our collaborators to successfully develop and commercialize drug candidates; 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; the inability to obtain orphan drug exclusivity; 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; the price of our common stock may be volatile; significant costs as a result of operating as a public company; and any securities class action litigation. 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, 2018 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.

Investor Contact: Media Contact:
Theresa McNeely Cara Mayfield
SVP, Corporate Communications & Patient Advocacy Senior Director, Patient Advocacy and Corporate Communications


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Source: Homology Medicines, Inc.