– Well-Tolerated in First-in-Human AAVHSC Gene Therapy Trial –

– Preliminary Data from First Patient in Second Cohort Showed Dose-Response with Observed Reductions from Baseline in Phe and Phe/Tyr Ratio and Increased Tyr –

BEDFORD, MA, USA I December 17, 2019 I Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today promising initial clinical data from the first gene therapy clinical trial in phenylketonuria (PKU). The pheNIX trial is a Phase 1/2 randomized, concurrently controlled, dose-escalation study for adults with PKU. As of December 2, 2019, two patients had received investigational HMI-102 gene therapy in Cohort 1 (low-dose) and one patient in Cohort 2 (mid-dose). Preliminary safety data from Cohorts 1 and 2 showed HMI-102 was well-tolerated. Efficacy data from the first patient in Cohort 2 indicated a dose-response effect with an observed reduction in phenylalanine (Phe) levels from baseline, increase in tyrosine (Tyr), and reduction in the Phe/Tyr ratio, suggestive of increased enzymatic activity. Phe is a registrable endpoint in PKU, Tyr is a product of Phe metabolism and a precursor to neurotransmitters, and the Phe/Tyr ratio is a clinically relevant diagnostic measurement for PKU.

“We believe that the initial efficacy from Cohort 2 suggest HMI-102 is delivering the PAH gene that produces the functional PAH enzyme and restores the biochemical pathway that converts Phe to Tyr,” stated Albert Seymour, Ph.D., Chief Scientific Officer of Homology Medicines. “We are pleased with the data with HMI-102, as this trial represents the first time one of our novel, human-derived AAVHSCs has been administered to patients, and provides initial evidence supporting our vector platform. The safety results observed and trial design allowed us to quickly execute on our plan to dose-escalate, and our wide safety margin provides potential for further dose-escalation.”

The dataset encompasses two patients from Cohort 1 and one patient from Cohort 2. A second patient was dosed in Cohort 2 after the cutoff date, and therefore not included in this analysis.

Initial Safety Observations
There were no treatment-emergent adverse events (TEAEs) or serious TEAEs. All patients’ ALT (alanine aminotransferase) and AST (aspartate aminotransferase) levels remained within the normal range.

Initial Efficacy Observations
The first patient dosed in Cohort 2 experienced a reduction in Phe of 35% and 48% from baseline at Weeks 1 and Week 4, respectively, as compared to Cohort 1, which generally did not show a reduction in Phe through Weeks 10 and 12. This is consistent with a dose-response. Per protocol, patient baseline is defined as one day prior to dosing. The first patient dosed in Cohort 2 also showed increases in Tyr levels of 72% and 85% at Weeks 1 and Week 4, respectively, suggesting increased PAH enzyme activity. In addition, the patient experienced a 62% and 72% reduction in the Phe/Tyr ratio from baseline to Weeks 1 and 4, respectively.

All patients reported maintaining consistent protein intake pre- and post-treatment.

The pheNIX trial 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 phase is incidence of sustained plasma Phe concentration ≤360 μmol/L as demonstrated by two measurements ≤360 μmol/L between 16 and 24 weeks.

“Over a year-and-a-half ago as a preclinical company, we made a commitment to report initial clinical data from the pheNIX trial by the end of 2019. Today, we provide more data than we promised, which I believe is a testament to our team’s ability to execute as well as the strong interest from patients and physicians,” stated Arthur Tzianabos, Ph.D., President and Chief Executive Officer of Homology Medicines. “This progress would not be possible without the patients, physicians and clinical staff who have enabled this first PKU gene therapy trial, and we thank them for their participation and support.”

Conference Call and Webcast Information
Homology will host a live webcast presentation and conference call today, December 17, 2019, at 4:30 p.m ET. The webcast will be accessible on Homology’s website in the Investors section, and the webcast replay will be available on the website for 90 days following the presentation. To access using the conference call line, dial 1-866-244-8091 (U.S./Canada toll-free) or 1-602-563-8623, with Conference ID 8777521.

About HMI-102
HMI-102 is an investigational gene therapy in development for the treatment of phenylketonuria (PKU) in adults. HMI-102 is designed to encode the PAH gene, which is mutated in people with PKU, in the liver-tropic AAVHSC15 vector. Homology has received Fast Track Designation and orphan drug designation for HMI-102 from the U.S. Food and Drug Administration (FDA), and orphan drug designation from the European Medicines Agency (EMA).

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 16,500 people in the U.S. and 50,000 people globally, with an estimated 350 newborns diagnosed in the U.S. and 1,000 to 1,500 newborns diagnosed globally 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.

SOURCE: Homology Medicines