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Homology Prioritizes Pipeline to Extend Runway, Moves Focus to PKU Gene Editing Trial

August 17, 2022

Homology Medicines, in its second quarter earnings report and business update, said it was prioritizing its pipeline and shifting its resources to the clinical trial evaluating its gene editing candidate HMI-103 for the treatment of adults with PKU.

Photo: Arthur Tzianabos, CEO of Homology Medicines

The prioritization, which it said includes a modest workforce reduction, will extend its cash runway into the fourth quarter of 2024.

“Homology has a strong cash position that is now expected to take us into the fourth quarter of 2024. The extended cash runway is, in part, based on our recent strategic decision to divert our resources to the ongoing pheEDIT clinical trial evaluating gene editing candidate HMI-103 in adults with PKU, while pausing enrollment in our HMI-102 pheNIX gene therapy trial that was recruiting for the same patient population,” said Arthur Tzianabos, CEO of Homology Medicines. “We believe this, together with additional steps that we are taking, including plans to partner our optimized MLD gene therapy program, will position the Company well to move select programs forward to near-term catalysts while focusing our resources and conserving cash. We continue to expect to provide program updates on pheEDIT and our Hunter syndrome gene therapy trial, juMPStart, at the end of the year.”

PKU, or phenylalanine hydroxylase (PAH) deficiency, is a rare genetic disorder caused by a deficiency of the enzyme PAH. This enzyme is required for the metabolism of Phe, an essential amino acid found in most protein-containing foods. If the active enzyme is not present in sufficient quantities, Phe accumulates to abnormally high levels in the blood and becomes toxic to the brain, resulting in a variety of complications including severe intellectual disability, seizures, tremors, behavioral problems, and psychiatric symptoms. As a result of newborn screening efforts implemented in the 1960s and early 1970s, virtually all individuals with PKU under the age of 40 in countries with newborn screening programs are diagnosed at birth and treatment is implemented soon after.

PKU can be managed with a severe Phe-restricted diet, which is supplemented by low-protein modified foods and Phe-free medical foods; however, it is difficult for most patients to adhere to the life-long strict diet to the extent needed to achieve adequate control of blood Phe levels. Dietary control of Phe in childhood can prevent major developmental neurological toxicities, but poor control of Phe in adolescence and adulthood is associated with a range of neurocognitive disabilities with significant functional impact.

The U.S. Food and Drug Administration had recently lifted the hold it had placed on Homology’s pheNIX gene therapy trial that had been in place since February, allowing enrollment to continue.

But the company says the prioritization of PKU clinical programs to focus on the pheEDIT trial evaluating gene editing candidate HMI-103 is part of its effort to extend Homology’s cash runway while continuing to move closer to the goal of offering solutions for both adults and pediatric patients with PKU. As a result, it has paused enrollment in the pheNIX gene therapy trial evaluating HMI-102.

Homology says prioritization offers potential to generate data, which includes a new immunosuppression regimen with a shorter course of steroids and a T-cell inhibitor as part of the pheEDIT protocol, sooner than would be possible to resume enrollment at pheNIX trial sites.

“While we continued to see biologic activity in our pheNIX gene therapy trial for PKU, we believe focusing our efforts on the gene editing program for PKU is the best approach for the Company at this time,” said Albert Seymour, president and chief scientific officer of Homology Medicines. “This was confirmed at the recent ASGCT Meeting where we shared the unique mechanism of action of HMI-103, including data showing durability and increased expression in preclinical models, coupled with the potential to treat adults and ultimately younger patients. With several sites currently active and open for enrollment, we believe we can more rapidly progress recruitment for the pheEDIT trial, which will evaluate a steroid-sparing immunosuppressive regimen, including a T-cell inhibitor, versus the time it would take to resume enrollment of the pheNIX trial. We also continued to advance HMI-104, which uses our GTx-mAb technology, into IND-enabling studies. This program represents a third part of Homology’s platform, and we believe it provides the opportunity to address potentially larger market indications.”

Homology plans to provide program updates by the end of the year, including enrollment and site status, from the phase 1 pheEDIT trial evaluating in vivo gene editing candidate HMI-103 for PKU and for its in vivo gene therapy candidate for Hunter syndrome, currently in the phase 1 juMPStart gene therapy trial.

Author: Rare Daily Staff

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