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pyctx.com | ACN 098 391 961 2 expectations, and beliefs about future events are subject to risks, uncertainties and other factors, many of which are outside the Company’s control. Important factors that could cause actual results to differ materially from assumptions or expectations expressed or implied in this ASX announcement include known and unknown risks. Because actual results could differ materially to assumptions made and the Company’s current intentions, plans, expectations, and beliefs about the future, you are urged to view all forward-looking statements contained in this ASX announcement with caution. The Company undertakes no obligation to publicly update any forward-looking statement whether as a result of new information, future events or otherwise. This ASX announcement should not be relied on as a recommendation or forecast by the Company. Nothing in this ASX announcement should be construed as either an offer to sell or a solicitation of an offer to buy or sell shares in any jurisdiction. This ASX announcement was approved and authorised for release by the Board of PYC Therapeutics Limited CONTACT US Investor relations and media contact investor@pyctx.com
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ASN KIDNEY WEEK • 22 OCTOBER 2026 PYC-003 in ADPKD A peptide-oligonucleotide conjugate designed to increase PC1 expression Phase 1a/1b (PINACLE-1) Part B: single ascending dose in patients with autosomal dominant polycystic disease (ADPKD) Safety, tolerability and exploratory efficacy read-outs Jagadeesh Kurtkoti, MBBS, FRACP. Renal Medicine, South Coast Renal, Southport, Queensland, Australia Abstract TH-OR060
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Disclosures No relevant financial relationships with ineligible companies.
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ADPKD: a progressive disease with no disease-modifying therapy Healthy kidney Polycystic kidney Age 20 Age 40 Age 60 Progressive cyst growth enlarges the kidneys and reduces kidney function 12.5 million people affected worldwide 1 in 1,000 PKD1 mutation-driven PC1 deficiency is the main cause of ADPKD ~80% progress to end-stage kidney disease by age 60 ~50% Images generated using BioRender.com.
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PYC-003 addresses the root cause of ADPKD PYC-003 selectively blocks miR-17 binding to PKD1 mRNA, restoring PC1 expression UNAFFECTED INDIVIDUAL ADPKD Two functional PKD1 mRNA transcripts Normal PC1 protein levels Normal kidney miR-17 suppresses PKD1 mRNA translation Reduced PC1 protein levels Cyst growth and progressive dysfunction PYC-003 blocks miR-17 binding site on functional transcript Other miR-17 target mRNAs unaffected Increased PC1 protein levels Slowed cyst growth, preserved function PYC-003 restores PC1 toward disease-modifying levels while preserving miR-17 regulation of other RNAs miR-17 One functional PKD1 mRNA transcript PYC-003 PYC-003 Treatment PKD1 mRNA protected
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PYC-003 Global Phase 1a/1b Study (NCT06714006) Placebo controlled SAD in healthy volunteers and open-label SAD/MAD in participants with ADPKD plus open-label extension Key ADPKD Eligibility Criteria • Aged 18-65 years • Genetic confirmation of ADPKD • Mayo imaging classification (MIC) 1C, 1D, 1E • eGFR ≥ 30 mL/min/1.73 m2 • BMI ≥ 18.0 and ≤ 35.0 kg/m2, weight ≥ 50 kg Key Endpoints STUDY DESIGN PART A, n=32 Placebo-controlled SAD |healthy volunteers (HVs) PART B, n=18 - 24 Open-label single ascending dose (SAD) | ADPKD Optional 4 mg/kg cohort PART C and D – ONGOING, n=24 - 48 Open-label multiple ascending dose (MAD) + OLE | ADPKD Optional 0.4 mg/kg (Q6W) or 4.0 mg/kg (Q8W) cohorts 0.4, 1.2, 2.4 and 4.0 mg/kg PYC-003 or placebo 0.4 mg/kg PYC-003 (n=6) 1.2 mg/kg PYC-003 (n=6) 2.4 mg/kg PYC-003 (n=6) 1.2 mg/kg PYC-003 Q6W 1.2 mg/kg PYC-003 Q6W 2.4 mg/kg PYC-003 Q6W 2.4 mg/kg PYC-003 Q6W Dosing (IV infusion) Open-label extension (OLE) COMPLETE Primary: Safety and tolerability Secondary and Exploratory: • Plasma and urinary PK • PD biomarkers (uPC1), disease progression markers (total kidney volume (TKV), eGFR) Regions Australia: 10 sites New Zealand: 1 site Hong Kong: 1 site MAD
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Baseline characteristics were broadly comparable, with expected variability across small cohorts Characteristic B1 n = 6 B2 n = 6 B3 n = 6 Age (years) median (min/max) 41 (33/46) 44 (34/59) 45 (31/56) Female n (%) 4 (67%) 3 (50%) 2 (33%) BMI at screening (kg/m²) median (min/max) 25 (21/27) 28 (23/32) 29 (22/31) eGFR at baseline (mL/min/1.73m²) median (min/max) 53 (42/106) 74 (50/108) 49 (30/90) TKV at baseline (mL) median (min/max) 1802 (1185/3808) 1832 (923/4242) 2204 (1317/3567) Mayo Imaging Classification n (%) 1C 1 (17%) 3 (50%) 3 (50%) 1D 4 (67%) 3 (50%) 2 (33%) 1E 1 (17%) 0 (0%) 1 (17%) Descriptive baseline data only. No formal assessment of between-cohort balance was performed.
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Single-dose PYC-003 was well tolerated No treatment-related serious adverse events or discontinuations SAFETY OVERSIGHT • Safety evaluated through Day 28 • Independent safety review before each dose escalation • No protocol-defined stopping rule triggered Safety Outcomes for SAD Cohorts A (Healthy Volunteers) and B (ADPKD Participants) B1 0.4 mg/kg n = 6 B2 1.2 mg/kg n = 6 B3 2.4 mg/kg n = 6 Part A (HV) n = 32 Total TEAEs 9 8 12 33 Participants with ≥1 related TEAE 0 1 1 3 Total TESAEs 1 0 0 0 Treatment-related TESAEs 0 0 0 0 TEAEs leading to discontinuation 0 0 0 0 • All AEs were mild to moderate • The single SAE of mild transient amnesia in B1 was considered unrelated to study drug and has resolved
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No clinically meaningful treatment-related changes in hepatic, renal or electrolyte safety markers through Day 28 # The Day 14 elevation in one B3 participant occurred with flu-like symptoms and was assessed as unrelated to study treatment. HEPATIC RENAL / TUBULAR ELECTROLYTES B3 (2.4 mg/kg) Reference range B1 (0.4 mg/kg) B2 (1.2 mg/kg) Creatinine Potassium MagnesiumUrea KIM-1 NGAL Screening Day -1 Day 2 Day 3 Day 14 Day 28 0 5 10 15mmol/L Screening Day -1 Day 2 Day 3 Day 14 Day 28 0 50 100 150 200 250umol/L Day -1 Day 2 Day 3 Day 14 Day 28 -1 0 1 2 3 4 5 ng/mL Day -1 Day 2 Day 3 Day 14 Day 28 0 20 40 60 80ng/mL Screening Day -1 Day 2 Day 3 Day 14 Day 28 0.0 0.5 1.0 1.5mmol/L Screening Day -1 Day 2 Day 3 Day 14 Day 28 0 2 4 6mmol/L ALT AST Screening Day -1 Day 2 Day 3 Day 14 Day 28 0 20 40 60 80Units / Liter Screening Day -1 Day 2 Day 3 Day 14 Day 28 0 50 100Units / Liter # #
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Single-dose PYC-003 showed a directional increase in urinary PC1, an exploratory read-out of renal PC1 expression Earlier SAD cohorts' samples were collected under different conditions and are not included; 1.2 mg/kg data are from samples collected after a first dose in MAD. PYC-003 dosed 1.0 1.5 2.0 2.5 -1 3 14 28 42 Study day Normalized uPC1:CD133 fold change (log) from Day -1 0.75 Individual values Geometric mean, combined dose groups Participants (n) by scheduled visit Study day 1.2 mg/kg 2.4 mg/kg Combined -1 3 5 8 3 2 3 5 14 3 4 7 28 3 4 7 42 2 1 3
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Early TKV change after a single dose is directionally encouraging but requires confirmation in repeat-dose cohorts PYC-003: B2/B3 pooled (n=12 at Month 3; n=11 at Month 4) and B1 separately (n=6 at both visits); mean ± 95% CI. Illustrative Natural Progression of Untreated PKD: weighted mean annual % change in TKV from CRISP natural history, HALT-PKD A placebo (Perrone RD, et al. Kidney Med. 2022) and TEMPO 3:4 placebo (Irazabal MV, et al. Kidney Int Rep. 2016) illustrating the natural progression of untreated PKD. −5.0% −2.5% 0% +2.5% +5.0% +7.5% 0 1 2 3 4 Change in TKV (%) Month PYC-003 SAD PKD (B1 n=6, B2/B3 n=12 at M3; n=11 at M4)# Illustrative Natural Progression of Untreated PKD (n = 925) Mayo Imaging Class C/D/E Combined TEMPO 3:4, CRISP , HALT-PKD A) Mean: +6.2% annually Mean TKV change: B1 and pooled B2/B3 Mayo Imaging Class C/D/E Pooled B2/B3 (doses taken forward to MAD) B1 (only assessed in SAD) Mean ± 95% Confidence Interval # 4-month data pending for one B3 patient #
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Conclusions: Part B single-dose PYC-003 1 Safe and well tolerated: no treatment-related serious adverse events or discontinuations 2 No safety biomarker signal: no evidence of renal or liver injury, and no clinically meaningful treatment- related changes through Day 28 3 Target engagement: directional increase of exosomal PC1, an exploratory read-out of renal PC1 expression 4 Early TKV: directionally encouraging, but requires confirmation in repeat-dose cohorts Next: repeat-dose MAD and OLE studies are ongoing, with data expected in 2027
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Acknowledgements PARTICIPANTS AND FAMILIES We thank the participants who volunteered for this study, and their families and carers for their support. INVESTIGATORS AND SITE TEAMS We thank the investigators, study coordinators, and the nursing, pharmacy, imaging and laboratory staff at all participating sites, as well as referring nephrologists and PKD Australia for their support. This study was sponsored by PYC Therapeutics. Participating sites Hong Kong