Homology Medicines Anticipating Gene Therapy Data Updates in PKU, Hunter Syndrome


Initial data from the trials of HMI-103 and HMI-203 are expected in 2023.

Homology Medicines has announced new progress regarding the phase 1 pheEDIT clinical trial (NCT05222178) for HMI-103 and the phase 1 juMPStart clinical trial (NCT05238324) for HMI-203 in a corporate update.1

HMI-103 is an investigational AAVHSC15 vector-based, nuclease-free gene-editing product intended to treat phenylketonuria (PKU) by replacing the disease-targeted phenylalanine hydroxylase (PAH) gene with a functional copy and a liver-specific promoter via the use of homologous recombination. In August of last year, Homology Medicines announced intention to prioritize further development of HMI-103, while deprioritizing its development of HMI-102, its other investigational genetic medicine for the treatment of PKU.2 Homology Medicines has noted that in preclinical research using a PKU mouse model, HMI-103's murine surrogate was 10 times more potent than the HMI-102 gene therapy vector.1 The open-label, dose-escalation pheEDIT study now has several participants in screening, and recently dosed the first patient. Nine clinical sites are currently active. The company expects that more sites will be activated as the year goes on, and that initial data from the trial will be announced by the middle of 2023.

“We believe HMI-103 has the potential to treat both children and adults with PKU by maximizing PAH through genome integration and episomal expression,” Albert Seymour, PhD, president and chief executive officer, Homology Medicines, stated in the corporate update.1 “Optimizing HMI-103, including vector design, integration of a strong liver-specific promoter, and enhanced packaging, resulted in increased potency, which is what you strive for with one-time genetic medicines."

HMI-203 is an investigational gene therapy intended to treat mucopolysaccharidosis II (MPS II; Hunter syndrome). It uses one of the company’s AAVHSC vectors to deliver functional copies of iduronate-2-sulfatase (IDS), the disease-targeted gene, to multiple organs. The design of the open-label, dose-escalation juMPStart trial was previously presented at the 18th Annual WORLDSymposium, February 7-11, 2022, in San Diego, California.3 Five sites in the United States and Canada have now been initiated, and Homology Medicines expects that more will be initiated later on.1 The company has additionally announced that it expects to provide initial data from the trial in the second half of this year.

“With a solid financial position, our focus is and will continue to be centered on clinical trial execution,” Seymour added to the statement.1 “HMI-103 and HMI-203 represent differentiated one-time approaches to PKU and MPS II, respectively, designed to address key unmet medical needs. Building on the interest from the physician and patient communities, we look forward to progressing these programs. Importantly, we plan to share initial clinical data from both trials in 2023, including the first data from our nuclease-free gene editing technology in humans.”

The company has additionally announced that preclinical data from non-human primates (NHPs) related to the immunosuppression regimen utilized in the pheEDIT and juMPStart studies will be presented at a future conference. The data was reported to show that a decreased neutralizing antibody response to the AAVHSC vector and increased mRNA expression was effected by the use of a prophylactic T-cell inhibitor in combination with steroids, as opposed to the use of either the T-cell inhibitor or steroids alone and the use of neither.

In addition to HMI-103 and HMI-203, Homology Medicines has announced intention to focus on investigational new drug (IND)-enabling studies for HMI-104, a candidate based on the company’s Gene Therapy-mAb (GTx-mAb) platform, which is intended to treat paroxysmal nocturnal hemoglobinuria. Furthermore, the company is also expecting a near-term announcement of preclinical data related to HMI-204, an in vivo, single-dose gene therapy candidate intended for the treatment of metachromatic leukodystrophy (MLD), the details of which were first unveiled in August of last year.1,4

1. Homology Medicines provides update on pheEDIT and juMPStart clinical trials and announces expected 2023 milestones, including initial data read-outs from both programs. News release. Homology Medicines. January 4, 2023. https://www.homologymedicines.com/news-story/homology-medicines-provides-update-on-pheedit-and-jumpstart-clinical-trials-and-announces-expected-2023-milestones-including-initial-data-read-outs-from-both-programs 
2. Homology Medicines reports second quarter 2022 financial results, recent highlights and provides business update. News release. Homology Medicines. August 15, 2022. https://www.globenewswire.com/news-release/2022/08/15/2498571/0/en/Homology-Medicines-Reports-Second-Quarter-2022-Financial-Results-Recent-Highlights-and-Provides-Business-Update.html 
3. Gingras J, Haroldson J, Smith LJ, et al. Clinical trial design for HMI-203 investigational gene therapy for mucopolysaccharidosis type II (MPS II) informed by cross-correction potential and KOL input. Presented at: 18th Annual WORLDSymposium, February 7-11, 2022; San Diego, CA. Poster #93
4. Homology Medicines announces optimized, in vivo gene therapy candidate for the treatment of metachromatic leukodystrophy. News release. Homology Medicines, Inc. August 11, 2022. https://www.homologymedicines.com/news-story/homology-medicines-announces-optimized-in-vivo-gene-therapy-candidate-for-the-treatment-of-metachromatic-leukodystrophy
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