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Homology Medicines Announces Presentation of Positive Data from the Dose-Escalation Phase of the pheNIX Gene Therapy Trial for Adults with PKU

 - Marked Reductions in Phe Observed at Two Doses -  

- Achieved Goal with Plans to Advance to Randomized, Concurrently Controlled Expansion Phase of Trial -    

- Webcast / Conference Call Today, November 6 at 4:30 p.m. ET -  

BEDFORD, Mass., November 6, 2020 – Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today the presentation of positive data from the dose-escalation portion of the Phase 1/2 gene therapy pheNIX clinical trial for adults with phenylketonuria (PKU). The results showed that product candidate HMI-102 was generally well-tolerated, and resulted in marked reductions in phenylalanine (Phe) and the Phe-to-tyrosine (Tyr) ratio (Phe/Tyr ratio) at two doses. Phe is a registrable endpoint in PKU, and the Phe/Tyr ratio is a clinically relevant diagnostic measurement for PKU. With these positive results, Homology is progressing to the randomized, concurrently controlled expansion phase of the trial, which has the potential to be converted to a registrational trial.

The data were presented today in an oral presentation by Olaf Bodamer, M.D., Ph.D., FACMG, FAAP, Park Gerald Chair in Genetics & Genomics and Associate Chief of Genetics & Genomics at Boston Children’s Hospital, and principal investigator of the pheNIX trial, during the New England Consortium of Metabolic Programs (NECMP) annual meeting, which is focused on new research in metabolic disorders. NECMP includes metabolic clinics, healthcare providers, patient organizations and others dedicated to increasing knowledge of metabolic disorders and improving delivery of healthcare to patients. 

“This is the first-ever PKU gene therapy clinical trial, and I am excited to share these data with the PKU community as I believe they demonstrate the potential of HMI-102 to treat the underlying genetic cause and reduce the therapeutic burden for patients and their families,” stated Dr. Bodamer. “PKU is a challenging condition, and a treatment that establishes normal metabolism could change the prognosis for patients with this rare genetic disorder. We look forward to participating in the next phase of the study.”

“We are pleased to have met the goals of the dose-escalation portion of the trial, which were evaluation of safety and efficacy of a single I.V. administration of HMI-102 and dose determination for the expansion phase of the trial,” stated Gabe Cohn, M.D., Chief Medical Officer of Homology Medicines. “Even as many patients self-liberalized their diets, there were patients at the mid- and high-doses with plasma Phe values below 360 μmol/L and/or 600 μmol/L, and one of these patients achieved a Phe level within the normal range. This is the first time a genetic medicines approach has achieved these results in patients with PKU. We have learned a tremendous amount in the dose-escalation phase and are applying these learnings to the expansion phase of the trial, which we anticipate initiating in early 2021.”

Dr. Cohn continued, “We greatly appreciate the PKU community of patients, clinicians and caregivers who have participated in this first phase of the pheNIX trial, and we look forward to working together during the next phase.”

As of the data cutoff date of October 19, 2020, six patients in the dose-escalation phase of the pheNIX trial had received gene therapy product candidate HMI-102 across three dose cohorts (low-dose Cohort 1, n=2; mid-dose Cohort 2, n=2; high-dose Cohort 3, n=2). Cohorts included males and females, with an age range of 21-49 and time in study ranging from 13 weeks to 52 weeks (end of study).

Safety Observations HMI-102 was generally well-tolerated, and there were no treatment-related serious adverse events (SAEs). There were no clinically significant changes in ECG or vital signs and no clinical signs of complement activation. The Grade 1 and 3* alanine aminotransferases (ALTs) observed in Cohorts 2 and 3, which is common in AAV-based gene therapy, were managed with increased steroids when necessary. The patients who experienced Grade 3 ALTs had pre-existing underlying immune conditions.

An independent data monitoring committee, which provided guidance throughout the pheNIX trial, concluded that there were no safety concerns related to bilirubin, and that ALT elevations may be associated with reduced efficacy. Updates to the expansion phase of the pheNIX trial, including key learnings related to patient selection, monitoring and steroid regimen, are being incorporated.

Efficacy Observations  

Cohort 1 (Low-Dose)

Through 52 weeks, patients in Cohort 1 continued to show no meaningful reductions in Phe.  

Cohorts 2 and 3 (Mid- and High-Dose)

The mean percent change from baseline in Phe observed in patients in Cohorts 2 and 3 were significant, compared to Cohort 1**. These Phe reductions occurred while patients self-liberalized their diets.

Through 48 weeks, one patient in Cohort 2 had Phe levels of <360 μmol/L and/or <600 μmol/L*** at multiple timepoints and had reached a minimum Phe level of 42 μmol/L, compared with a baseline level of 1,010 μmol/L.

Through 13 weeks, one patient in Cohort 3 had a Phe level <360 μmol/L and several Phe levels <600 μmol/L at multiple timepoints and had reached a minimum Phe level of 303 μmol/L, compared with a baseline level of 1,060 μmol/L.

In Cohorts 2 and 3, Phe reductions were greater among patients with Grade 1 ALTs compared to patients with Grade 3 ALTs****; ALT elevations were managed with increased steroids when necessary. It appears higher ALT elevations may limit therapeutic activity, but can be managed with a modified steroid regimen, which is being incorporated into the expansion phase.

Expansion Phase

Based on the safety and efficacy results observed in the dose-escalation phase, Homology is advancing to the randomized, concurrently controlled, dose expansion phase of the pheNIX trial, which has the potential to be converted to a registrational trial. All cohorts in the dose-escalation phase showed an acceptable safety profile and certain patients in Cohorts 2 and 3 showed marked Phe reductions.

Based on these collective data, Homology has selected two doses for the expansion phase: the mid-dose from Cohort 2 and a dose between the doses in Cohorts 2 and 3. The Company believes the latter dose has the potential to improve Phe reductions while reducing steroid exposure that was required at the high-dose. The Company believes that advancing two doses in parallel provides the potential to convert to a registrational trial quickly with the optimal dose as the expansion phase does not include staggered dosing between patients.  

Webcast/Conference Call

Homology management and Dr. Bodamer will host a conference call and webcast today, Friday, November 6 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 (866) 244-8091 (U.S./Canada toll-free) or (602) 563-8623, with Conference ID 7394503.

About HMI-102

HMI-102 is an investigational gene therapy in clinical 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, delivered via 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 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 phenylalanine (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 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 surrounding the Phase 1/2 pheNIX trial, including the expansion phase and the potential for conversion to a registrational trial; our position as a leader in the development of genetic medicines; 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: the impact of the COVID-19 pandemic on our business and operations, including our preclinical studies and clinical trials, and on general economic conditions; 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 of our manufacturing facility; 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; 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 Quarterly Report on Form 10-Q for the quarterly period ended June 30, 2020 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.

*ALT Grades based on Common Terminology Criteria for Adverse Events (CTCAE) Version 5

**P<0.004; Post-hoc comparison of Cohort 1 vs Cohorts 2&3 using repeated measures MANOVA/regression analysis

***U.S. and EU PKU treatment guidelines described in: Vockley J et al. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genetics in Medicine 2014;16: 188-200. van Spronsen FJ et al. Key European guidelines for the diagnosis and management of patients with phenylketonuria. Lancet Diabetes Endocrinol 2017; 5: 743–56.

****P<0.05; Post-hoc comparison of Patients 3&6 vs Patients 4&5 using repeated measures MANOVA/regression analysis

Company Contacts:
Theresa McNeely
Chief Communications Officer and Patient Advocate 

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