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Patient-Informed Study to Evaluate Hunter Syndrome Gene Therapy

The trial design was informed by both patient and physician perspectives.

Homology Medicines is assessing their gene therapy candidate HMI-203 for the treatment of Hunter syndrome (mucopolysaccharidosis type 2; MPS II) in the open-label phase 1 juMPStart trial (NCT05238324).1

The juMPStart trial design was presented atthe 18th Annual WORLDSymposium, February 7-11, 2022, in San Diego, California, by Jacinthe Gingras, PhD, senior director, ophthalmology and neurology, Homology Medicines.2

“These presentations highlight how Homology’s gene therapy approach to Hunter syndrome and other lysosomal storage diseases is developed to target both the peripheral as well as the central nervous system manifestations of these multi-organ disorders,” Albert Seymour, PhD, chief scientific officer, Homology Medicines, said in a statement.1 “We designed the juMPStart clinical trial with our 1-time, systemic gene therapy candidate by incorporating data and feedback we generated from our investigational new drug-enabling studies, as well as patient, caregiver and physician feedback. We believe that HMI-203 has the potential to address the peripheral and CNS challenges of Hunter syndrome that are not addressed by standard of care enzyme replacement therapy (ERT), and that a one-time intravenous (IV) administration would be a major advance for patients and their families.”

The juMPStart trial will evaluate 3 dose levels of a 1-time, intravenous administration of HMI-203 in adult men with MPSII, with up to 3 participants in each cohort.2 The primary endpointissafety, determinedby adverse events (AEs) and serious AEs.

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Gingras outlined additional endpoints during her presentation, stating that “the selected endpoints include weekly plasma I2S activity and urinary glycosaminoglycan (GAG) levels will also be assessed. The effects of HMI-203 will be evaluated on peripheral disease manifestations including ambulation, liver and spleen volume, cardiac, and pulmonary function. In addition, evaluation of range of motion, sleep apnea and quality of life, as well as cerebrospinal fluid enzyme activity and GAG levels, will be evaluated to better understand the crossing of HMI-203 through the [blood-brain barrier].”2

The trial design was informed by patient and physician perspectives, collected in interviews, and these perspectives were also presented at the symposium by Jeffrey Haroldson, senior director, global medical affairs, Homology Medicines.3

Investigators interviewed 9 adults with MPSII and 6 physicians with significant clinical and research experience with the disease to further understand the disease burden of MPSII, the perspective of the current treatment landscape, and to understand expectations for gene therapy treatments.

“When we were asking the patients what were some of the symptoms not being treated [with enzyme replacement therapy (ERT)] that were really impacting their life, the top 3 answers were limited range of motion, pain, and heating loss. We also learned along the way that the patients report anxiety related to the uncertainty of the disease progression in addition to life expectancy,” Gingras noted in her presentation.2

Patients reported a desire for a 1-time gene therapy that would address these symptoms more effectively than ERT. Physician input on clinical trial endpoints also lined up with these needs and informed the selected endpoints previously noted, including mobility tests and pulmonary and cardiac function tests. Physicians also agreed that a large unmet need with ERT is addressing fatigue and effects on the skeletal system.

Physician and patient perspectives on disease burden did differ, as physicians regarded surgical procedures and complications as the biggest burdens of disease while patients stressed constant pain as a more burdensome symptom.

REFERENCES
1. Homology Medicines announcespresentations on HMI-203 investigationalgenetherapy for Hunter syndrome and broad applicability of AAVHSC platform for lysosomalstoragedisorders at the 18th Annual WORLDSymposium™ meeting. News release. Homology Medicines. February 10, 2022. https://www.globenewswire.com/news-release/2022/02/10/2383122/0/en/Homology-Medicines-Announces-Presentations-on-HMI-203-Investigational-Gene-Therapy-for-Hunter-Syndrome-and-Broad-Applicability-of-AAVHSC-Platform-for-Lysosomal-Storage-Disorders-at.html
2. 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
3. Haroldson J, Witalisz C, Mayfield C, et al. Patient and physician perspectives inform clinical trial design for a single intravenous dose of HMI-203, a gene therapy candidate for adults with mucopolysaccharidosis type II (MPS II, Hunter syndrome). Presented at: 18th Annual WORLDSymposium, February 7-11, 2022; San Diego, CA. Poster #118