As Optigo Biotherapeutics recently announced the expansion to its leadership by appointing Andreas Wallnöfer, PhD, MBA, to the Board of Directors, the company also noted that its lead anti-VEGF asset, designed for extended duration, is advancing toward pre-Investigational New Drug (IND) and Good Laboratory Practice (GLP) toxicology studies targeting wet age-related macular degeneration.^1,2

To learn more, the Eye Care Network caught up with David S. Boyer, MD, of Retina-Vitreous Associates Medical Group in Los Angeles, CA, and Arshad M. Khanani MD, MA, FASRS, Sierra Eye Associates in Reno, NV, for an overview of the preclinical pharmacology and toxicology studies that underpin the program’s novel platform, the IND‑enabling package these studies support, and how preclinical data may guide the company’s clinical development plans.

MORE Q&A: Advancing a long-acting anti-VEGF candidate: What it means for retinal disease

Note: Transcript edited for clarity and length.

Can you elaborate on the preclinical pharmacology and toxicology studies for the company’s platform, and how these data support the IND-enabling package?

Boyer: The pharmacokinetic (PK) studies on nonhuman primate (NHP) cynomolgus monkeys demonstrated that XPK-640 extended the half-life of drug in the aqueous humor 10-fold. There were no systemic or ocular adverse events. Based on these findings, [the company] is moving ahead to a pre-IND meeting with the FDA.

Khanani: Preclinical studies in cynomolgus NHP show that [the] lead candidate, XPK-640, could significantly extend the durability of anti-VEGF therapy. The drug maintained therapeutic levels in the eye for 29 to 50 days, over 10 times longer than aflibercept and was well tolerated, with no detectable systemic exposure following intravitreal injection. These findings support the advancement of XPK-640 into IND-enabling GLP toxicology studies and point to the potential for longer-lasting vision protection with fewer injections, reducing treatment burden for patients with chronic retinal diseases.

How does the vitreous-anchoring mechanism of the bispecific anti-VEGF molecules influence ocular pharmacokinetics and tissue retention compared with current standard-of-care therapies?

Boyer: Current standard of care involves intravitreal injections of anti-VEGF medications monthly and then on a treat-and-extend basis. Many patients (10% to 20%) require less than 8 week dosing, although some may go 16 to 20 weeks. Based on the cynomologus NHP trial, an intravitreal injection of 2 mg aflibercept may be able to be extend drug for 1 year without a device.

Khanani: Preclinical PK data from cynomolgus NHP, the most clinically relevant model, indicate that Optigo’s vitreous-anchoring platform could sustain therapeutic drug levels for up to 12 months with the equivalent of a 2 mg aflibercept dose. By comparison, current standard-of-care intravitreal injections are typically limited to a maximum of 16-week dosing intervals, and even with a surgical implant device such as [ranibizumab injection] [Susvimo; Genentech] durability extends only to every 6 months. By anchoring the bifunctional anti-VEGF molecule within the vitreous, Optigo’s technology enhances ocular tissue retention and markedly prolongs drug exposure. For patients, this could translate to fewer injections, more consistent vision outcomes, and a meaningful reduction in the treatment burden.

What were the critical efficacy endpoints observed in the VEGF challenge models, and how do these findings inform projected dosing intervals in humans?

Boyer: Using the molar equivalent of 2 mg aflibercept the time to leakage was extended 3.5 times compared with a single aflibercept injection. This, coupled with rabbit PK experiments, indicate that the dosing interval could be as least 1 year.

Khanani: In VEGF challenge models, XPK-640 extended the time to vascular leakage in rabbits by 4 times compared with aflibercept, consistent with a 5-fold increase in ocular half-life observed in PK studies. Combined with NHP data, these findings suggest the potential for dosing intervals of up to 12 months or longer in humans, offering the promise of fewer injections and more sustained vision protection for patients with chronic retinal diseases.

From a translational perspective, how do the preclinical results guide your strategy for clinical development, including anticipated benefits in treatment durability and patient adherence?

Boyer: The clinical trial will assess safety, best-corrected visual acuity (BCVA), optical coherence tomography drying effect, and time to first rescue XPK-640 after 1 intravitreal injection. This study will guide the Phase 3 studies. The reduction in treatment burden to the patients, caretakers, and physicians can be huge, increasing compliance.

Khanani: The extended intravitreal PK of XPK-640 will be guiding the clinical development strategy. The first-in-human trial in patients with treatment-naïve wet AMD will likely be conducted without loading doses, aiming to lessen the initial treatment burden and evaluate whether a single injection can achieve meaningful disease control. The study will assess anatomical and functional outcomes, including retinal drying, improvements in BCVA, time to rescue injection, and total number of injections over a 48-week period. Based on preclinical data, it is anticipated that many patients have the potential to remain rescue-free for 6 months or longer following a single dose. Together, these elements reflect a strategy designed to maximize durability, improve compliance, and reduce the treatment burden for patients with chronic retinal disease.

David S. Boyer, MD
E: [email protected]
Boyer is in private practice with Retina-Vitreous Associates Medical Group in Los Angeles, California. Boyer serves on the scientific advisory board for Optigo Biotherapeutics.

Arshad M. Khanani MD, MA, FASRS
E: [email protected]
Khanani specializes in vitreoretinal diseases and surgery, and is managing partner, director of clinical research, director of fellowship with Sierra Eye Associates, as well as clinical professor at the University of Nevada, Reno School of Medicine in Reno. Khanani is a consultant for Optigo Biotherapeutics.

REFERENCES

1. Renowned pharma and biotech development leader, Dr. Andreas Wallnöfer, is named to Optigo Biotherapeutics’ Board of Directors as the company advances to IND-enabling studies. News release. November 4, 2025. Accessed November 5, 2025. https://www.optigobio.com/press-release-2025-11-04

2. Optigo Biotherapeutics wins People’s Choice Award at Eyecelerator and presents compelling preclinical data on long-acting intravitreal biologics at the ARVO 2025 conference. News release. May 6, 2025. Accessed November 5, 2025. https://www.optigobio.com/press-release-2025-05-06