PYC Therapeutics Shows Lasting OPA1 Gene Expression in Primates and Vision Improvement in ADOA Patients with PYC-001

PYC Therapeutics’ Commitment to Rare Genetic Disease Treatments

Headquartered in Perth, Australia, with operations in San Francisco, PYC Therapeutics focuses on developing precision medicines for genetic diseases without approved therapies. Its pipeline includes three clinical-stage programs, with PYC-001 as the lead candidate targeting the root cause of Autosomal Dominant Optic Atrophy (ADOA). This rare inherited eye disease results from approximately a 50% reduction in OPA1 protein expression in retinal ganglion cells, leading to progressive vision loss and eventual blindness.

PYC’s therapeutic strategy aims to address disease mechanisms directly by increasing OPA1 protein levels in the retina to halt or reverse neurodegeneration associated with ADOA. This approach aligns with a broader pharmaceutical trend toward targeting fundamental genetic or molecular drivers, especially in rare diseases with significant unmet needs and limited treatment options.

Durable Gene Expression Confirmed in Non-Human Primate Studies

Recent preclinical data showed that non-human primates receiving a single 15 microgram dose of PYC-001 per eye experienced a statistically significant and sustained increase in OPA1 protein expression within retinal ganglion cells lasting at least four months post-administration (Day 113). OPA1 levels were quantified using immunofluorescence intensity comparisons between treated and untreated animals. The 15 microgram dose in primates corresponds to an estimated 30 microgram human equivalent dose based on volumetric eye scaling with a factor of approximately 2.2.

This prolonged elevation of OPA1 supports extending dosing intervals in clinical trials beyond the current every 2-3 months schedule. Extending to once every four months or longer could improve patient convenience and reduce the frequency of invasive intravitreal injections. PYC plans to review and potentially amend its clinical trial protocols to incorporate these extended dosing intervals.

Clinical Trial Results Demonstrate Sustained Vision Gains and Reduced Retinal Stress

Complementing preclinical findings, updated Phase 1/2 trial data from ADOA patients indicate clinically meaningful improvements in visual acuity and reductions in retinal stress following repeated PYC-001 dosing. Visual acuity was assessed using Low Contrast Visual Acuity (LCVA) tests, relevant for detecting vision loss severity in ADOA. The analysis included 11 of 15 MYRTLE trial participants who received at least 10 micrograms of PYC-001, had baseline LCVA scores below 50 in the treated eye, and had follow-up LCVA measurements as of 30 June 2026.

Retinal stress was evaluated using Flavoprotein Fluorescence (FPF) imaging with the OcuMet Beacon device, measuring mitochondrial dysfunction as a biomarker of retinal cell stress. Treated patients showed decreased FPF levels, indicating reduced mitochondrial impairment. These efficacy outcomes were observed alongside a favorable safety profile, with no treatment-related serious adverse events reported in any patient, including those receiving multiple doses.

Protocol Amendments to Explore Longer Dosing Intervals Based on Translational Evidence

The plan to amend clinical protocols to test extended dosing intervals is driven by the successful translation of sustained OPA1 expression in primates to durable clinical benefits in patients. Longer intervals between doses would enhance patient experience by reducing injection frequency and associated risks such as infection or retinal detachment. PYC will conduct a thorough review to implement these changes while ensuring scientific rigor and regulatory compliance.

Expanding Therapeutic Potential to Other Blinding Eye Conditions Including Glaucoma

Beyond ADOA, PYC is advancing preclinical investigations of PYC-001 in glaucoma models, a major cause of irreversible blindness characterized by retinal ganglion cell death and optic nerve damage linked to mitochondrial dysfunction. Since increased OPA1 expression may modulate disease progression, this research could broaden PYC-001’s clinical applications and market reach. While still early-stage, these efforts leverage PYC’s expertise and the mechanistic foundation established through ADOA clinical success.

Strong Safety Profile Supports Ongoing Development and Patient Enrollment

PYC-001 continues to demonstrate an excellent safety and tolerability profile, with no serious adverse events related to treatment reported across all patients to date, including those receiving multiple doses. This is particularly critical in ophthalmology, where adverse effects impacting vision could be devastating. Intravitreal administration targets the retina directly while minimizing systemic exposure, contributing to the favorable safety outcomes.

This safety record underpins ongoing patient enrollment in Phase 1/2 trials and builds confidence among clinicians and participants. It also lays the groundwork for progression to larger Phase 2b and Phase 3 trials involving broader patient populations and extended follow-up, facilitating regulatory discussions on approval pathways.

Targeting Mitochondrial Dysfunction Reflects Advances in Retinal Disease Understanding

PYC’s focus on OPA1 and mitochondrial health aligns with emerging insights into genetic and degenerative retinal diseases. OPA1 is vital for mitochondrial structure and function in energy-demanding retinal ganglion cells. Reduced OPA1 in ADOA impairs oxidative phosphorylation, lowers ATP production, and increases oxidative stress, leading to cell death and vision loss. By boosting OPA1, PYC-001 aims to restore mitochondrial function and prevent neurodegeneration.

Flavoprotein Fluorescence biomarker measurements provide objective evidence of improved mitochondrial function in treated patients, reinforcing the drug’s biological activity. The combined clinical improvements in vision, decreased retinal stress, and sustained OPA1 expression present a compelling case for disease modification that is likely to resonate with regulators and the scientific community.

Clinical Trials and Patient Cohorts in ADOA Development

PYC’s ongoing Phase 1/2 trials for ADOA, registered under NCT06970106 and NCT06461286, include the MYRTLE study which enrolled 15 patients. Eleven patients met criteria for efficacy analysis based on dosing and visual acuity parameters. These modest sample sizes are appropriate for early-stage trials focused on safety and preliminary efficacy rather than definitive proof.

Multiple dosing cohorts (10 and 30 micrograms) enable dose-response assessment and optimization. Data reflect effects of repeated dosing and durability of response. The June 30, 2026 data snapshot indicates some patients are still completing follow-up, with outcomes expected to evolve. PYC’s transparency in sharing detailed clinical data demonstrates confidence and commitment to stakeholders.

Regulatory and Development Considerations for Gene Expression Enhancement Therapy

PYC-001 employs gene expression enhancement by increasing endogenous OPA1 protein levels rather than gene replacement or editing. This approach may offer regulatory and safety advantages due to its transient effect and intravitreal delivery. Protocol amendments to extend dosing intervals will require institutional and regulatory approvals before implementation.

Regulatory submissions will likely include a Biologics License Application (BLA) to the U.S. FDA and filings with agencies such as the EMA and Australia’s TGA. Approval pathways for novel ophthalmic therapies vary by indication and patient population. PYC’s ASX disclosures from 2 February 2026 outline risks inherent to clinical development and regulatory review.

Market Potential and Commercial Strategy for Rare Blinding Eye Disease

ADOA’s rarity limits patient numbers compared to common retinal diseases, but the lack of approved treatments creates significant unmet needs and potential for orphan drug designation with associated incentives and market exclusivity. PYC’s exploration of PYC-001 in glaucoma aims to expand commercial opportunities beyond the smaller ADOA population.

Intravitreal administration requires specialized healthcare infrastructure and trained ophthalmologists, which may limit access in some regions but allows controlled distribution and patient monitoring. Extending dosing intervals to every four months or longer would reduce treatment burden compared to therapies requiring monthly or bimonthly injections, offering a competitive advantage in convenience and adherence.