Homology Medicines Initiates Clinical Trial for HMI-203, a One-Time Investigational Gene Therapy Candidate for Adults with MPS II (Hunter Syndrome)

- juMPStart Trial to Evaluate First Systemic Gene Therapy Candidate for Patients with Hunter Syndrome - 

BEDFORD, Mass., October 18, 2021 – Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today that it has initiated the Phase 1 trial for HMI-203, a one-time, in vivo gene therapy candidate for the treatment of adults with mucopolysaccharidosis type II (MPS II), or Hunter syndrome. The juMPStart trial is an open-label, dose-escalation study evaluating the safety and efficacy of a single intravenous (I.V.) administration of HMI-203. Hunter syndrome is a lysosomal storage disorder caused by mutations in the iduronate 2-sulfatase (IDS) gene leading to absent or deficient I2S enzymatic activity, which causes toxic lysosomal accumulation of glycosaminoglycans (GAGs). There are no treatments currently available that address both the peripheral organ and cognitive manifestations of the disease, and there remains a high unmet medical need for patients despite the availability of enzyme replacement therapy (ERT). 

“We are excited to start the Phase 1 trial for HMI-203, our investigational gene therapy for Hunter syndrome, as our team remains dedicated to improving outcomes for the patient community since our prior work developing ERT,” said Arthur Tzianabos, Ph.D., President and Chief Executive Officer of Homology Medicines. “With today’s milestone, we have also accomplished our goal of having three clinical programs by the end of 2021, with our gene therapy and gene editing clinical trials for PKU and the initiation of the juMPStart trial for Hunter syndrome. We are executing on this and our other programs, and we look forward to our continued collaboration with the MPS II community.”

The juMPStart trial is expected to enroll up to 9 male patients ages 18-30 years old who have been diagnosed with Hunter syndrome and are currently receiving ERT. In addition to safety endpoints, the trial plans to measure plasma I2S activity, urinary GAG levels and other peripheral disease manifestations. The Phase 1 dose-escalation portion of the trial is designed to evaluate three doses of HMI-203 to potentially determine the optimal dose(s) for a future trial. 

“I am pleased to work with the Homology team, as we both have a long-held and shared commitment to the MPS II community and a focus on bringing forward a one-time gene therapy to address the underlying cause of this disease,” said Joseph Muenzer, M.D., Ph.D., Bryson Distinguished Professor in Pediatric Genetics at the University of North Carolina at Chapel Hill. “While weekly intravenous ERT has made a huge difference for the MPS II community, it is very time-consuming and there remains the need to address the brain disease in the severe or neuronopathic form of MPS II. I am optimistic that Homology’s gene therapy approach for MPS II could make a significant impact on all aspects of the disease, including the peripheral manifestations, as well as the day-to-day lives of patients and their families, and I look forward to working with the Homology team and all of the investigators in the HMI-203 clinical trial to evaluate this approach.”

Albert Seymour, Ph.D., Chief Scientific Officer of Homology Medicines, added, “We are pleased to be transitioning HMI-203 into the clinic for patients, building on the positive preclinical data we presented at scientific conferences, including the upcoming ASHG meeting. These data showed long-term expression of I2S in multiple organs, sustained secretion in the serum, reduced GAGs in all tissues tested as well as the cerebrospinal fluid, and phenotypic correction in the Hunter disease murine model following a one-time administration. We appreciated the insights from the Hunter syndrome community as we designed our clinical program, and we look forward to continuing our work together as we advance juMPStart.”

In October 2021, the U.S. Food and Drug Administration (FDA) cleared the Investigational New Drug (IND) application for HMI-203 for the treatment of Hunter syndrome to proceed. 

About HMI-203
HMI-203 is a one-time in vivo gene therapy candidate in development for the  treatment of Hunter syndrome and designed to use one of Homology’s human hematopoietic stem cell-derived adeno-associated virus vectors (AAVHSCs) to deliver functional copies of the IDS gene to multiple organs where there are missing or mutated copies of the gene. HMI-203 is developed to enable the production of the I2S enzyme that is responsible for breaking down glycosaminoglycans (GAGs), which accumulate and cause progressive debilitation and shortened life expectancy in people with Hunter syndrome. 

About Mucopolysaccharidosis Type II (MPS II), Hunter Syndrome
MPS II, or Hunter syndrome, is a rare, X-linked lysosomal storage disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene, which is responsible for producing the I2S enzyme that breaks down large sugar molecules, or cellular waste, called glycosaminoglycans (GAGs). Severe Hunter syndrome results in toxic lysosomal accumulation of GAGs that causes progressive debilitation and decline in intellectual function. Hunter syndrome occurs in approximately 1 in 100,000 to 1 in 170,000 males, and the severe form leads to life expectancy of 10 to 20 years.

About Homology Medicines, Inc. 
Homology Medicines, Inc. is a clinical-stage genetic medicines company dedicated to transforming the lives of patients suffering from rare diseases by addressing the underlying cause of the disease. The Company’s lead clinical program, HMI-102, is an investigational gene therapy for adults with phenylketonuria (PKU) and additional programs focus on lysosomal storage disorders including Hunter syndrome, paroxysmal nocturnal hemoglobinuria (PNH) and other diseases. Homology’s proprietary platform is designed to utilize its family of 15 human hematopoietic stem cell-derived adeno-associated virus vectors (AAVHSCs) to precisely and efficiently deliver genetic medicines in vivo through a gene therapy or nuclease-free gene editing modality, as well as to deliver one-time gene therapy to produce antibodies throughout the body through the GTx-mAb platform. Homology has a management team with a successful track record of discovering, developing and commercializing therapeutics with a focus on rare diseases. Homology believes its initial clinical data and compelling preclinical data, scientific and product development expertise, internal manufacturing capabilities and broad intellectual property position the Company as a leader in genetic medicines. For more information, 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 without limitation statements regarding our expectations surrounding the potential, safety, efficacy, and regulatory and clinical progress of our product candidates; the potential of our gene therapy and gene editing platforms, including our GTx-mAb platform; our plans to name a development candidate and potential thereof; our plans and timing for the release of additional preclinical and clinical data; our beliefs regarding our manufacturing capabilities; 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; difficulties or delays enrolling patients in clinical trials; 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 quarter ended June 30, 2021 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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