ONL Signals a Neuroprotective Shift in the Fight Against Blindness

ANN ARBOR, MI – December 09, 2025 – In the high-stakes world of biopharmaceutical development, progress is measured in data points, clinical milestones, and peer-reviewed validation. This week, Ann Arbor-based ONL Therapeutics sent a clear growth signal to the ophthalmology sector, announcing the publication of promising Phase 1b data for its lead drug candidate, xelafaslatide. The study, now available in the prestigious journal Ophthalmology Science, offers the first validated glimpse into a potential new weapon against geographic atrophy (GA), an advanced form of dry age-related macular degeneration (AMD) and a leading cause of irreversible blindness.

For a clinical-stage company like ONL, publication in a journal from the American Academy of Ophthalmology is more than a simple announcement; it is a critical stamp of scientific credibility. The data confirms that xelafaslatide was generally safe and well-tolerated in early human trials. More importantly, it revealed early efficacy signals suggesting the drug could slow the growth of GA lesions—the dead zones in the retina that steal a patient's central vision. This milestone propels ONL forward as it advances its global Phase 2 GALAXY trial, positioning the company as a serious contender in a rapidly evolving market.

A New Mechanism for a Devastating Disease

Geographic atrophy is a relentless disease. It slowly erodes the macula, the part of the retina responsible for sharp, detailed vision needed for reading, recognizing faces, and driving. Until recently, patients had no therapeutic options. The market changed with the arrival of two major drugs: Apellis Pharmaceuticals' Syfovre and Astellas' Izervay. Both therapies have offered hope by slowing the progression of GA lesions, but they do so by targeting the complement system, an inflammatory pathway implicated in the disease.

ONL Therapeutics is taking a fundamentally different approach. Xelafaslatide is not a complement inhibitor; it's a first-in-class Fas inhibitor. This mechanism targets a different biological process: apoptosis, or programmed cell death. The Fas pathway is a key signaling route that tells retinal cells, including vital photoreceptors, to self-destruct. By blocking this signal, xelafaslatide is designed to be directly neuroprotective—its goal is to keep the cells alive rather than just mitigating the inflammatory environment around them.

“Geographic atrophy remains one of the most devastating challenges in ophthalmology,” said David N. Zacks, M.D., Ph.D., chief scientific officer of ONL Therapeutics, in the company's official statement. “With its unique mechanism of action targeting the Fas pathway... xelafaslatide has the potential to protect vision.”

This distinction is a powerful growth signal. While current treatments have proven the value of slowing GA, the market is eager for next-generation therapies that could offer more. A neuroprotective agent that preserves retinal architecture could, in theory, lead to better long-term visual outcomes. It represents a strategic shift from a defensive posture against the disease to an offensive one, actively safeguarding the very cells responsible for sight.

Reducing the Burden on Patients

Beyond the novel science, xelafaslatide carries another significant signal: the potential to dramatically reduce the treatment burden for patients. Current GA therapies require intravitreal injections administered as frequently as every month. This regimen of regular, invasive procedures can be a significant physical and logistical challenge for the elderly patient population most affected by AMD.

ONL Therapeutics is exploring dosing schedules of every three or even six months for xelafaslatide. As Dr. Zacks noted, this could “ease the treatment burden for patients.” For an individual living with a chronic, progressive disease, cutting the number of required clinic visits and injections by two-thirds or more would represent a profound improvement in quality of life. This practical advantage, if proven in later-stage trials, could become a key competitive differentiator and a major driver of adoption, even in a market with established incumbents.

The Phase 1b study, while small, provided the foundational safety data needed to explore these longer-duration treatment intervals. The trial included a dose-escalation component and a randomized, sham-controlled component, which together supported the continued development of the drug and its progression into a much larger study.

The Road Ahead: The GALAXY Trial

With the Phase 1b data now validated and published, all eyes turn to the GALAXY trial (NCT06659445), ONL's global Phase 2 study. The company began randomizing patients in October 2025, signaling its confidence and operational momentum. This trial is designed to provide definitive answers about xelafaslatide's efficacy. It will enroll approximately 324 patients across North America and Europe, comparing two different doses of the drug against a sham injection.

The trial's primary endpoint is the rate of GA lesion growth at 48 weeks, a standard benchmark in the field. Success in the GALAXY trial would not only confirm the promise seen in early studies but also provide the robust data package needed to design a pivotal Phase 3 program and engage in regulatory discussions. Furthermore, ONL's strategy extends beyond GA. The company has already completed studies of xelafaslatide in macula-off retinal detachment—a condition for which it has received Orphan Drug Designation from the FDA—and progressing open-angle glaucoma. This suggests a broader platform potential for Fas inhibition, turning xelafaslatide into a potential “pipeline-in-a-product” and diversifying the company's risk.

For ONL Therapeutics, the publication of its Phase 1b data is a crucial inflection point. It provides the scientific validation needed to build investor confidence and partner interest. Now, the company must execute on the much larger and more complex GALAXY trial, a challenge that will test its clinical and operational capabilities. The ophthalmology community will be watching closely as this small biopharmaceutical company attempts to redefine what is possible for patients losing their sight to this unforgiving disease.