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Investor Presentation September 2026 Life-changing science
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PYC THERAPEUTICS The purpose of this presentation is to provide an update of the business of PYC Therapeutics Limited (ASX:PYC) [‘PYC’]. These slides have been prepared as a presentation aid only and the information they contain may require further explanation and/or clarification. Accordingly, these slides and the information they contain should be read in conjunction with past and future announcements made by PYC Therapeutics and should not be relied upon as an independent source of information. Please contact PYC and/or refer to the Company's website for further information. The views expressed in this presentation contain information derived from publicly available sources that have not been independently verified. No representation or warranty is made as to the accuracy, completeness or reliability of the information. Any forward looking statements in this presentation have been prepared on the basis of a number of assumptions which may prove incorrect and the current intentions, plans, expectations and beliefs about future events are subject to risks, uncertainties and other factors, many of which are outside PYC’s control. Important factors that could cause actual results to differ materially from assumptions or expectations expressed or implied in this presentation include known and unknown risks. Because actual results could differ materially to assumptions made and PYC’s current intentions, plans, expectations and beliefs about the future, you are urged to view all forward looking statements contained in this presentation with caution. This presentation includes information about PYC’s drug development pipeline. PYC’s drug candidates are investigational or under development and not approved by any regulatory authority in any jurisdiction. The safety, efficacy or other desirable attributes of our unapproved drug candidates have not been established in patients or determined by any regulatory authority. This presentation is for corporate communication purposes only and is not intended as promotion or advertising to any audience in any jurisdiction. This presentation may also contain statistical data and drug information based on independent sources, industry publications or other publicly available information. We have not independently verified the accuracy or completeness of such data and information. Accordingly, we make no representations as to the accuracy or completeness of such data or information. You are cautioned not to give undue weight to such data. This presentation should not be relied on as a recommendation or forecast by PYC. Nothing in this presentation should be construed as either an offer to sell or a solicitation of an offer to buy or sell shares in any jurisdiction. 2PYC THERAPEUTICS Disclaimer
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PYC THERAPEUTICS 3PYC THERAPEUTICS Agenda for today • Introduction to PYC • Review of organisational build-out • Overview of the forward development plan for the company’s pipeline programs • Polycystic Kidney Disease program review and forward view of milestones • Q&A
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PYC THERAPEUTICS PYC’s mission is to create life-changing RNA therapies that address the root cause of diseases resulting from insufficient gene expression The Company’s work is dedicated to patients who currently have no treatment options available PYC THERAPEUTICS 4 Sierra – living with Phelan- McDermid Syndrome1 1. PMS Foundation – Sierra’s story
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PYC THERAPEUTICS 5PYC THERAPEUTICS There are two copies of every gene in humans One copy of a gene is non-functional in a haploinsufficiency PYC’s drug candidates leverage the ‘good’ copy of the gene to restore expression1 Unaffected Individual Haploinsufficiency Haploinsufficency + PYC drug candidate 0.0 0.5 1.0 1.5 2.0 Functional Protein Expression Under-expression Over-expression 1. Illustrative change in gene expression following administration of PYC’s RNA therapy – detailed data for each drug development program in the Company’s pipeline is available via the ASX platform and the Company’s website. PYC designs RNA therapies to increase gene expression in diseases caused by haploinsufficiency Physiological expression
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PYC THERAPEUTICS 61. See disease prevalence references of the Company’s 2026 Annual Report released to the ASX on 28 August 2026 for additional details on prevalence by indication 2. PYC owns 97.1% of VP-001 (2.9% ownership by Lions Eye Institute, Australia) and 100% ownership of all other pipeline programs Pre-clinical Prevalence1Clinical Progress expected in 20251 PYC THERAPEUTICS VP-0012 PYC-001 Phase 1/2 PYC-002 1 in 100,000 1 in 1,000 1 in 35,000 1 in 7,300 Program Platform and discovery programs Registrational PYC-003 Historical progress Polycystic Kidney Disease Phelan-McDermid Syndrome Retinitis Pigmentosa Type 11 Autosomal Dominant Optic Atrophy PYC has created a pipeline of clinical-stage drug candidates in areas of major unmet need
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PYC THERAPEUTICS 7PYC THERAPEUTICS PYC continues its organisational build-out ahead of the progression into late-stage studies • In Q2, the Company appointed a CFO and General Counsel/Co-Company Secretary • In Q3, PYC has added a Chief Clinical Development Officer and Phelan-McDermid Syndrome Program Lead • Near-term recruitment will focus on a Head of Regulatory Affairs and Ophthalmology Program Lead
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PYC THERAPEUTICS PYC has multiple human safety and efficacy read-outs expected within the next 18 months1 8PYC THERAPEUTICS 20272026Program 2028 2029 2030 Registrational trialsPYC-003 Polycystic Kidney Disease (PKD) Phase 1a/1b Studies 12-month data on registrational endpoint (TKV) Registrational efficacy outcome (12-month TKV) Registrational trialsPhase 1/2 Repeat Dose Study PYC-001 Autosomal Dominant Optic Atrophy (ADOA) Clinical proof of concept Registrational trialsPhase 1/2 studiesPYC-002 Phelan-McDermid Syndrome (PMS) Clinical proof of concept IND-enabling studies IND VP-001 Retinitis Pigmentosa type 11 (RP11) Registrational trialsPhase 1/2 Open-Label Extension Study 12-month OLE data Registrational efficacy outcome 1. Management forecast accurate as at the date of this announcement. Subject to the risks and uncertainties outlined in the Company’s ASX disclosures of 2 February 2026. Subject to change based on outcomes and strategic priorities.
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PYC THERAPEUTICS 9PYC THERAPEUTICS PKD program deep dive Discussion topics • An overview of the program – current progress • An ‘outside in’ perspective – why safety is key • The expected timeline for exploratory efficacy data • What should we expect on these endpoints?
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PYC THERAPEUTICS 10PYC THERAPEUTICS Overview of the clinical development pathway for PYC-0031 New Drug Application (NDA) 12-month TKV readout 4 12-month TKV read-out Clinical proof of concept Confirmatory 24-month eGFR readout Commercialisation 1. Subject to regulatory approval and the risks and uncertainties outlined in the Company’s ASX disclosures of 2 February 2026 2. Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) studies in patients with PKD1 gene mutation associated autosomal dominant polycystic kidney disease (PKD) 3. Gradzik M, et al. Diagnostic Imaging of Autosomal Dominant Polycystic Kidney Disease. Pol J Radiol. 2016 Sep 17;81:441-453. doi: 10.12659/PJR.894482 4. FDA. Development and Approval Process | Drugs. 2022. https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program - Accelerated approval allows for the earlier approval of drugs that treat serious conditions, and fill an unmet medical need based on a surrogate endpoint. There is an established accelerated approval path in PKD, which allows for Phase 3 trial to be conducted post approval. FDA has designated TKV as a reasonably likely surrogate endpoint (U.S. Food and Drug Administration, 2020) https://www.fda.gov/drugs/development-resources/table-surrogate-endpoints-were-basis-drug-approval-or-licensure Registrational study Total Kidney Volume (TKV) MRI3 eGFR Blood test PYC’s immediate objective Phase 2/3 Study Part A - SAD in healthy volunteers Part B – SAD in ADPKD Patients Confirmatory extension Combined Phase 1a/1b Study 2 Part C and D – MAD + OLE in PKD Patients Progress to date
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PYC THERAPEUTICS 11PYC THERAPEUTICS An ‘outside in’ perspective on the PYC-003 program • [Placeholder for the Yale video at the clinical development landscape section from 0:37 to 2:45] 1. Yale Ventures. PKD1 uORF-blocking ASOs as therapy for ADPKD Source: Yale Ventures. PKD1 uORF-blocking ASOs as therapy for ADPKD Available from: https://vimeo.com/1153969046 0:37 to 2:45
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PYC THERAPEUTICS Modelled peak target tissue concentration is similar after single and repeat dosing1 SAD MAD Dose % of AUC above minimum effective concentration1 at Month 4 0.4 mg/kg ~40% 1.2 mg/kg ~70% 2.4 mg/kg ~90% 0.1 10 100 Time (days) 1.2 mg/kg 2.4 mg/kg 28 42 56 0.4 mg/kg 3 0.3 30 7 14 21 35 49 Minimum effective concentration1 of PYC-003 in patient-derived models Part B Dose Cohort (Single) Predicted concentration of PYC-003 in kidney (μM) 0 1 63 70 77 84 91 98 105 112 7 14 21 28 35 42 49 56 63 70 77 84 91 98 105 112 0.1 10 100 Time (days) 0 1 3 Predicted concentration of PYC-003 in kidney (μM) Part C/D Dose Cohort Minimum effective concentration1 of PYC-003 in patient-derived models 30 0.3 2.4 mg/kg Q6W 1.2 mg/kg Q6W Dose % of AUC above minimum effective concentration1 at Month 4 1.2 mg/kg Q6W 100% 2.4 mg/kg Q6W 100% 1. The predicted human kidney concentration is modelled on the observed Non-Human Primate plasma:kidneyPK data and the observed human plasma PK data 2. The Minimum Effective Concentration (MEC) in patient-derived models is ~300nM, however, the MEC has been set at 1uM for the purposes of this modelling to predict the duration of exposure above a 1.2-fold increase in PC1 expression
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PYC THERAPEUTICS 13PYC THERAPEUTICS Expected timelines for the Phase 1b exploratory efficacy data1 Q4Q3Q2Q1Q4 1. Subject to the risks and uncertainties outlined in the Company’s ASX disclosures of 2 February 2026 CY2026 CY2027 Single Ascending Dose (SAD) study data through 4 months of follow- up Multiple Ascending Dose (MAD) study data through 12 months of follow- up Timing Anticipated data Progression to registrational study in CY20281
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PYC THERAPEUTICS 14PYC THERAPEUTICS Fast-progressing patients have been prioritised for the MAD study to maximise potential for early signal detection 0 2 4 6 81 3 5 7 0 1 2 3 4 5 TKV growth rate (%/year) eGFR rate of decline (ml/min/1.73m2/year) Observed annual rate of change on TKV and eGFR by Mayo Class1 1A 1B 1C 1D 1E Patients in Mayo Class 1C to 1E are expected to show >5% growth in Total Kidney Volume (TKV) per year This maximizes the potential for detecting an early treatment effect with PYC-003 1. Bais et al. 2024. Validation of the Mayo Imaging Classification System for Predicting Kidney Outcomes in ADPKD. Mar 2024. Population (n) for each Mayo Class (1A = 34, 1B = 138, 1C = 234, 1D = 131 and 1E = 81)
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PYC THERAPEUTICS 15PYC THERAPEUTICS >6 months of data is required for meaningful insight on TKV following treatment with PYC-0031 This is to allow for signal detection above the ‘noise’ of the data set, driven by: • Variability observed on this endpoint in natural history studies; • Small group size (total n=24, n=12 per cohort); and • Natural variability associated with MRI measurements. A treatment that halts disease progression in ADPKD will show significant divergence from published placebo control progression (STAGED-PKD) after ~27 weeks Combines both 1.2 mg/kg and 2.4 mg/kg and assumes equal efficacy for both (n=24) Assumption: arrest of TKV growth 1. With an input assumption that both 1.2 mg/kg and 2.4 mg/kg are effective doses
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PYC THERAPEUTICS 16PYC THERAPEUTICS Commandment #10 - “The world belongs to finishers” Finishing requires focus: pick a few things and deliver on them. In drug discovery, it’s always easier to “turn over new rocks than to concentrate your attention and resources to meet expectations and deadlines”. While it’s exciting to push new discoveries, it takes “discipline, management, people skills, encouragement, toughness to finish” and bring a drug through to PoC and eventually to market. PYC is focused on delivering near-term human Proof of Concept (PoC) read-outs for its pipeline of drug candidates 1. Phil Needleman’s ten commandments of drug development – courtesy of Bruce Booth at LifeSciVC
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Q&A September 2026 Life-changing science