PYC Therapeutics (ASX:PYC) used its first-quarter investor webinar to outline how it plans to advance four drug candidates toward human safety and efficacy readouts over the next 24 months, while also addressing investor concerns about shifting development timelines. Host Rohan Hockings reiterated that the company’s approach is aimed at increasing gene expression back toward “wild type” levels in diseases caused by loss-of-function mutations, and said the company uses patient-derived cellular models to generate what it views as an early “human efficacy readout” before entering clinical development.
Financing and balance sheet “strength”
Hockings said feedback after the company’s prior financing centered on two perceived weaknesses: a mismatch between the ambition of advancing four programs and the company’s balance sheet, and a lack of “validation from industry,” including the absence of large pharma partnerships and Tier 1 specialist investors.
Near-term milestones: FDA meeting and PKD dose escalation
Hockings highlighted two near-term events. First, the company planned to meet the U.S. FDA in a Type D meeting for its retinitis pigmentosa type 11 (RP11) program to align on registrational outcomes. He cautioned that the company would not be able to communicate details until official meeting minutes are received in writing, which he said could take several weeks.
Second, he said PYC completed dosing in Cohort B2 of its polycystic kidney disease (PKD) program (single dose in patients at 1.2 mg/kg) and planned a Safety Review Committee meeting to seek permission to escalate to Cohort B3. Management expected to update the market on the SRC outcome before market open the following Friday, assuming the review was favorable.
Pipeline updates: PKD, Phelan-McDermid, and two ophthalmology programs
PKD: Management said that, if cleared to proceed, it expected to complete dosing in Cohort B3 in March and then begin the repeat-dose (Part C/Phase 1b) study in the second quarter. The company described three key clinical measures it will follow: urinary PC1 (a protein excreted in urine that management views as a proxy for increased kidney expression), MRI-based total kidney volume, and kidney function (eGFR). Hockings stressed that the program is “moving at speed” toward biomarker and anatomical surrogate endpoints, which the company expects will inform later registrational trial design.
Phelan-McDermid syndrome (PMS): PYC said it has an “elegant” preclinical package and is targeting an IND submission in Q1 next year, but acknowledged this program has experienced a timeline delay. Hockings attributed the delay to the company’s decision to target patients aged two to 18 in its Phase I/II study, which in turn requires additional non-human primate toxicology work in adult and juvenile monkeys. He described the availability of juvenile monkeys as the gating factor and said the decision carried an approximate 12-month cost penalty. The company plans to add further functional assays (including electrical activity measures) and rodent-model work to complement existing patient-derived neuronal data.
RP11 and autosomal dominant optic atrophy (ADOA): In the two eye disease programs, management said near-term focus is on building longer-term efficacy data and regulatory clarity for Phase III design. For ADOA, PYC reported it has completed dosing in a single-dose 60 microgram cohort and has initiated repeat-dose dosing at 10 and 30 micrograms, aiming to build on “encouraging early efficacy” and “clean” safety/tolerability observations discussed on the call.
Why timelines moved: “interpretation,” not trial execution
A central theme of the webinar was management’s explanation for changing timelines. Hockings said the company accepts responsibility for “too much movement” in guidance and said it intends to apply more conservatism in future expectations, especially around the transition from Phase I/II studies to registrational trials.
He emphasized that the primary changes are related to when registrational studies start and how long they must run, rather than delays in executing ongoing Phase I/II trials. For PKD, he said earlier assumptions that the Phase 1b study could be scaled directly into a registrational format were “overly bullish,” and that the company now believes it is better to extract more information from Phase 1b—particularly around dose and dosing interval—before launching a separate registrational trial.
Management also warned investors to expect substantial variability in PKD endpoints such as total kidney volume and urinary PC1, citing the large spread seen in historical datasets and noting that smaller cohort sizes (the company described two initial multiple-dose cohorts of 12 patients each at 1.2 and 2.4 mg/kg) may make early timepoints harder to interpret. While PYC still expects to generate urinary PC1 and total kidney volume data this year, Hockings said the company expects stronger conviction at later readouts, such as nine to 12 months or beyond.
Regulatory perspective in RP11: accelerated approval, endpoints, and regional differences
In Q&A, management said an accelerated approval pathway is “not in the mix” for RP11 at present because it has not seen FDA flexibility around an endpoint that could support accelerated approval. Hockings said the FDA is not willing to accept a smaller delta (such as five or 10 letters) as a leading indicator in lieu of the clinical meaningfulness bar the company expects the agency to apply.
He also discussed how the FDA’s expectations differ from Europe’s in visual acuity measures, stating that Europe adopts a 10-letter delta standard while the FDA’s expected bar is 15 letters. He said this difference could allow for divergent regulatory outcomes between regions.
Management described multiple ways to construct low-luminance visual acuity endpoints (including proportions of patients achieving gains, proportions losing a threshold amount, or mean differences between arms) and said the company is working to improve confidence in Phase III design by incorporating longer-term Phase II open-label extension data and continued regulator engagement. The company also said it expects to pursue breakthrough therapy designation for RP11 later this year, noting the process is more efficient with compelling human efficacy data.
Other Q&A points included comments that PYC is still open to partnering discussions—particularly for the ophthalmology programs—while U.S. specialist investor attention is “very much” focused on PKD and PMS. Management also said the board is considering a potential U.S. listing and would evaluate a Nasdaq move if needed to align valuation and liquidity with U.S. peers. Finally, Hockings said PYC’s partnership work with Google has not materially progressed and is not a core priority at present.
About PYC Therapeutics (ASX:PYC)
PYC Therapeutics Limited, a drug-development company, engages in the discovery and development of drug solutions in the areas of RNA therapeutics in Australia. The company's preclinical development programs include VP-001, a drug program for retinitis pigmentosa type 11; PYC-001, a drug program for the treatment of autosomal dominant optic atrophy; and PYC-002 a drug program for the treatment of a severe neurodevelopmental disorder. It also focuses on the development of programs for kidney, neurodevelopmental, retinal, and central nervous system diseases.
