Pyc Therapeutics Limited · ASX:PYC
Pyc Therapeutics — Retinal Therapeutics Innovation Summit (May 2025)
23 slides from Pyc Therapeutics's conference presentation, May 2, 2025
Slide 1: Advancing PRPF31-Related Retinitis Pigmentosa Treatment: Key Insights from the VP-001 Phase 1B Study
Advancing PRPF31-Related Retinitis Pigmentosa Treatment: Key Insights from the VP-001 Phase 1B Study Retinal Therapeutics Innovation Summit May 2, 2025 Lesley Everett, MD, PhD Paul H. Casey Ophthalmic Genetics Division Casey Eye Institute Oregon Health & Science University Portland, OR
Slide 2: Co-Investigators and Co-Authors
Co-Investigators and Co-Authors Dr. David Birch Dr. Thiran Jayasundera Dr. John Chancellor Retina Foundation Dr. Sandeep Grover Kellogg Eye Center Alkek Eye Center Dr. Byron Lam of the Southwest University of Florida University of Michigan Baylor College of Medicine Bascom Palmer Eye Institute Dept
Slide 3: Disclosures
Disclosures Investigator or Co-Investigator for Clinical Trials (no financial disclosures): 4D Molecular Therapeutics Ocugen Ascidian Therapeutics SepulBio Atsena Therapeutics Sparing Vision Beacon Therapeutics Spark Therapeutics Biogen SpliceBio Editas Medicine Sanofi Foundation Fighting Blindness
Slide 4: RP11 is a progressive blinding eye disease with no treatment options
Retinitis Pigmentosa type 11 (RP11) is a progressive blinding eye disease for which there are no treatment options (PRPF31) Degenerative sight of an RP11 patient Retinitis Pigmentosa (RP)1,2 6 YEARS OLD • A severe and progressive blinding eye disease that begins in childhood • Affects 1 in every 3,5
Slide 5: RP11 is caused by insufficient expression of PRPF31 in the retina and RPE
RP11 is caused by insufficient expression of PRPF31 in the retina and RPE PRPF31 expression Unaffected individual RP11 patient PRPF31 PRPF31 PRPF31 PRPF31 PRPF31 PRPF31 DNA RNA Protein DNA RNA Protein Functional PRPF31 expression = 100% Functional PRPF31 expression = ~50% https://plae.nei.nih.gov/ P
Slide 6: VP-001 is designed to address the underlying cause of RP11
VP-001 is designed to address the underlying cause of RP11 • Cell-penetrating peptide conjugated to an oligonucleotide to modulate CNOT3 expression • Intravitreal injection (50 µl) Without VP-001 With VP-001 ASO CNOT3 Exon 15 Intron Exon 16 Intron Exon 17 Intron Exon 18 Exon 15 Intron Exon 16 Intron
Slide 7: VP-001's Robust Preclinical Proof of Concept
VP-001’s Robust Preclinical Proof of Concept VP-001 shows the ability to rescue PRPF31 haploinsufficiency in patient-derived models PRPF31 mRNA Expression in Patient iPSC-RPE 6 days post VP-001 treatment Unaffected RP11 RP11 + VP-001 Scrambled control oligo 3) Rescues morphology of Dose-dependent ta
Slide 8: Overview of VP-001 Clinical Trials
Overview of VP-001 Clinical Trials Current stage Data from the extension study Completed Enrollment Phase 1/2 will inform the final design and Phase 1/2 studies Open-Label Extension Study duration of the registrational trial PLATYPUS: Single Ascending Dose Study and Part B Extension (12 participants
Slide 9: Overview of the Phase 1/2 studies of VP-001 in RP11
Overview of the Phase 1/2 studies of VP-001 in RP11 Overview of PLATYPUS Overview of WALLABY Primary Outcome: Safety & Tolerability Primary Outcome: Safety & Tolerability Single Ascending Dose (SAD) study SAD ‘Part B’ Multiple Ascending Dose (MAD) study Extension study • n = 3 patients per cohort •
Slide 10: Inclusion criteria progressively refined to seek an accelerated efficacy signal
The inclusion criteria was progressively refined to seek an accelerated efficacy signal in the ongoing studies of VP-001 Study Cohorts Inclusion criteria • PRPF31 mutation 3, 10, 30 mcg PLATYPUS • Light perception SAD Study 75 mcg • PRPF31 mutation • At least one of the below: • Kinetic perimetry: >
Slide 11: Key outcomes from ongoing clinical studies of VP-001 in RP11
Key outcomes from ongoing clinical studies of VP-001 in RP11
Slide 12: Overview of patient exposure to VP-001 in the Phase 1/2 trials
Overview of patient exposure to VP-001 in the Phase 1/2 trials Study Cohort Patient ID Received repeat doses of > 30 µg VP-001 Number of doses > 30 µg VP-001 patient has received SAD 3 µg Patient 1 Yes – patient was eligible for Part B study 2 (first dose was < 30 µg) SAD 3 µg Patient 2 Yes – patien
Slide 13: No treatment emergent-serious adverse events (TE-SAEs)
No treatment emergent-serious adverse events (TE-SAEs) • No Treatment Emergent-Serious Adverse events observed in any subjects dosed with VP-001 to date • Including subjects who received repeat doses of VP-001 • Treatment-Emergent Adverse Events were mostly mild and/or Safety procedure related outco
Slide 14: Dose-dependent improvement in low-luminance visual acuity
A dose-dependent improvement in low-luminance visual acuity was observed in the first study of VP-001 for Retinitis Pigmentosa type 11 20 Change from baseline in Low-Luminance 3µg treated eyes (n=3) 10µg treated eyes (n=2)3 Visual Acuity (ET-DRS letters) 15 30µg treated eyes (n=3) Mean + SEM 10 30 µ
Slide 15: Transition to therapeutically relevant repeat doses
Transition to therapeutically relevant repeat doses (subsequent data shown will reflect patients treated with multiple 30 or 75 µg doses) Overview of PLATYPUS Overview of WALLABY Primary Outcome: Safety & Tolerability Primary Outcome: Safety & Tolerability Single Ascending Dose (SAD) study SAD ‘Part
Slide 16: Improved vision on two registrational endpoints
Improved vision after VP-001 treatment on two registrational endpoints with high impact for patients with RP11 I 1 LLVA is a more sensitive marker of M P Low-Luminance impaired central vision than BCVA R O Baseline Visual Acuity and has been linked to higher V E Week 16 (+4 letters in treated eye, n
Slide 17: Improvements in low-luminance visual acuity within 12 months
RP11 patients treated with VP-001 have shown improvements in low- luminance visual acuity within 12 months VP-001 treated eyes1 show improvement in LLVA compared to the disease progression observed in the Natural History Study (NHS) of patients with RP112,3 20 1 LLVA 15 Mean VP-001 Treated Eyes (+SE
Slide 18: Greater proportion of treated eyes improve in LLVA versus untreated eyes
A greater proportion of RP11 eyes treated with VP-001 show improvement in LLVA compared to untreated eyes RP11 patients treated with VP-001 have shown improvements in LLVA relative to untreated RP11 Natural History Study subjects 100 Data from 56-weeks 1 LLVA onwards will be assessed % of eyes with
Slide 19: Microperimetry improvements observed in VP-001 treated eyes
Microperimetry improvements have been observed in VP-001 treated eyes VP-001 treatment Baseline Week 32 12.5 dB 15.1 dB 7 loci improved by >7dB Patient 1 2 MP 0.2 dB 6.3 dB 23 loci improved by >7dB Patient 2 4.6 dB 4.9 dB Patient 3 12 loci improved by >7dB PYC THERAPEUTICS Mean macular sensitivity (
Slide 20: Bilateral improvements in retinal sensitivity following unilateral injection
Bilateral improvements in retinal sensitivity following unilateral injection VP-001 treatment UNTREATED Baseline Week 32 Baseline Week 32 12.5 dB 15.1 dB 8.1 dB 10.2 dB Patient 1 2 MP 0.2 dB 6.3 dB 0.3 dB 4.7 dB Patient 2 4.6 dB 4.9 dB 4.5 dB 4.6 dB Patient 3 The phenomenon of improved visual acuity
Slide 21: Clinically meaningful improvements in microperimetry
Clinically meaningful improvements in microperimetry have been observed in RP11 patients treated with VP-0011 There is a high degree of confidence that it is likely attributable to a genuine treatment effect rather than random chance2 60 10 VP-001 treated eyes 2 MP % of eyes with >7dB change in >7 l
Slide 22: Patients report improved vision and quality of life after VP-001
Multiple RP11 patients have reported improved vision and quality of life after treatment with VP-001 - “For the first time, I’ve seen airplanes in the sky- it was amazing! When we travel to the national parks and stay in our camper van, now I can get around at dusk by myself in unfamiliar places lik
Slide 23: Acknowledgements
Acknowledgements OHSU Ophthalmic Genetics Clinical Trials Funding & Support Paul Yang, MD, PhD Hardew Mahto Foundation Fighting Blindness Career Development Mark Pennesi, MD, PhD Alexis Mooney Award (2022-2027) CD-GE-0822-0831-OHSU Andreas Lauer, MD Andrew Lamborn Steven Bailey, MD Ednah Louie Casey
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