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Homology Medicines Achieves 2018 Goals and Prepares PKU Gene Therapy Program for the Clinic with Initial Data Expected in 2019

- Two Additional Programs Advance to IND-Enabling Studies, Including First Gene Editing Program and a CNS Gene Therapy -

- Homology’s New GMP Manufacturing Facility Preparing for Production at 500 Liter Scale -

- Orphan Drug Designation Granted for HMI-102 PKU Gene Therapy in the U.S. and E.U. -

BEDFORD, Mass., January 7, 2019 – Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced that it achieved all corporate goals for 2018, positioning the Company to start a Phase 1/2 clinical trial of the Company’s first gene therapy program in adults with phenylketonuria (PKU), with initial data expected in 2019.

Homology closed out the year by nominating development candidates for two additional programs focused on pediatric rare genetic diseases, both of which have entered into IND-enabling studies. These candidates comprise a nuclease-free in vivo gene editing approach for PKU and a gene therapy approach for metachromatic leukodystrophy (MLD), Homology’s lead central nervous system (CNS) program and a fatal pediatric lysosomal storage disorder. Pipeline advancements are expected to be supported by Homology’s newly completed GMP gene therapy and gene editing manufacturing facility.

“We entered 2018 with aggressive goals to translate our technology into development programs that have the potential to cure people living with rare genetic diseases,” said Arthur Tzianabos, Ph.D., President and Chief Executive Officer of Homology Medicines. “Through the hard work of our team and the rapid progression of our dual gene therapy and gene editing platform, we are pleased that we met all of our 2018 goals and enter 2019 with strong momentum to move our pipeline forward.”

Dr. Tzianabos continued, “We begin this year on track to start and report initial data from our Phase 1/2 gene therapy trial for adults with PKU, and we have begun IND-enabling studies with our first gene editing program for children with PKU. Our approach with PKU exemplifies the duality and flexibility of our technology platform where we choose the best genetic medicines approach based on human biology and the underlying cause of disease. Since our naturally derived AAVs cross the blood-brain-barrier, we are also targeting diseases of the central and peripheral nervous system, beginning with our lead CNS gene therapy program for MLD. With two additional programs now in IND-enabling studies, we expect that our new GMP manufacturing facility will provide us with control over the pace of development for these and future pipeline programs.”

Key 2018 Accomplishments and 2019 Priorities HMI-102 In Vivo Gene Therapy for Adults with PKU

  • Progressed through IND-enabling studies to support a Phase 1/2 clinical trial in adults with PKU in 2019, with initial data expected by year-end.
  • Presented long-term durability data demonstrating that a single intravenous dose of HMI-102 restored the natural biochemical pathway in the standard ENU2 murine model of human PKU:
    • Restored phenylalanine (Phe) to normal levels and was sustainable for 48 weeks, consistent with the lifespan of this model.
    • Increased tyrosine levels, which are required for production of neurotransmitters, and changed coat color, a phenotypic correction indicating melanin production. Tyrosine and melanin are byproducts of Phe metabolism and signal restoration of the natural biochemical pathway.
  • Reported top-line data from first-of-its-kind, five-year retrospective chart review of PKU patients, which confirmed key elements of Homology’s proposed Phase 1/2 trial design. Consistent findings from two PKU academic centers of excellence in the U.S. showed that actively monitored patients, including those on restrictive low Phe diet, had Phe levels well-above the generally accepted threshold, underscoring the need for treatments that restore the normal biochemical pathway.
  • Established GMP processes and scale to support the Phase 1/2 trial.
  • Received Orphan Drug Designation in the U.S. and the E.U.

HMI-103 In Vivo Gene Editing Treatment for Pediatric Patients with PKU

  • As reported earlier today, data demonstrated that a single intravenous dose of Homology’s human gene editing candidate led to efficient and selective editing in a humanized murine model. This led to selection of the HMI-103 gene editing development candidate with IND-enabling studies now underway.
  • Presented data in the standard murine model of PKU showing that a single intravenous dose of Homology’s murine gene editing construct led to a durable and statistically significant reduction in Phe levels compared to baseline and to untreated controls; these data also showed phenotypic coat color change, which indicates melanin production through the restoration of the normal biochemical pathway.

HMI-202 In Vivo Gene Therapy Treatment for Lead CNS Program, MLD

  • Generated positive data demonstrating ability to achieve the therapeutic threshold for enzyme activity in the MLD disease model, which led to selection of the HMI-202 gene therapy development candidate with IND-enabling studies now underway.
  • Presented data at Society for Neuroscience showing a single intravenous dose crossed the blood-brain-barrier and had broad tissue tropism and physiological relevance for neuronal pathways, resulting in increased human enzyme activity to levels well-above the therapeutic threshold when compared to average adult human enzyme activity.

Manufacturing Capabilities

  • Established GMP processes and capacity to support Phase 1/2 PKU gene therapy clinical trial.
  • Constructed 25,000 square foot GMP manufacturing facility at Homology that can accommodate both gene therapy and gene editing pipeline programs, leveraging initial bioreactor scale of 500 liters and preparing for GMP production.

Dual Technology Platform

  • Published and presented data supporting broad applicability of Homology’s AAVHSC platform for gene editing and gene therapy, including:
    • Publication in the Proceedings of the National Academy of Sciences demonstrating efficient and precise nuclease-free in vivo gene editing capabilities.
    • Publication in Human Gene Therapy Clinical Development indicating majority of the human population may be suitable for treatments delivered by Homology’s human-derived AAVs due to low levels of pre-existing neutralizing antibodies.
    • Data showing Homology’s AAVHSCs crossing the blood-brain-barrier and targeting central and peripheral nervous systems as well as other disease-relevant tissues (e.g., retina).
  • Efforts continue to advance the scientific understanding and potential of the Company’s AAVHSC gene therapy and gene editing platform, with additional presentations and publications expected in 2019 and beyond.

Financial Position

  • Completed successful IPO in March 2018, which provided at least two years of cash to advance programs through key milestones, including reporting initial data from the PKU Phase 1/2 gene therapy trial, and construction of the new GMP manufacturing facility that supports both gene therapy and gene editing.

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 statements regarding upcoming events and presentations; advancing our novel gene therapy and gene editing technology platform and pipeline; our expectations surrounding initiation of clinical trials for our PKU gene therapy program, release of clinical data, and timing thereof; the progress of IND-enabling studies for our PKU gene editing and MLD gene therapy programs; our beliefs regarding our manufacturing capabilities and ability to accommodate both gene therapy and gene editing pipeline programs; our goal of improving the lives of patients with rare genetic diseases; beliefs about our position as a leader in the development of genetic medicines; and the sufficiency of our cash position. 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 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 international marketing approval; failure to obtain U.S. marketing approval; ongoing regulatory obligations; effects of significant competition; 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 Quarterly Report on Form 10-Q for the quarter ended September 30, 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.

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