Kidney Week

Abstract: TH-OR060

A Phase 1 Study of PYC-003, a Peptide-Oligonucleotide Conjugate That Increases PC1 Expression in Patients with ADPKD

Session Information

• Genetic Diseases with a Focus on ADPKD Mechanisms, Models, and Medicines
  October 22, 2026 | Location: Mile High Ballroom 4D, Convention Center
  Abstract Time: 05:20 PM - 05:30 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)

Authors

• Kurtkoti, Jagadeesh, Brockway House Medical Services, Gold Coast, Queensland, Australia

Jagadeesh Kurtkoti, MD, MBBS

• Flis, Bridget, PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Bridget Flis

• Chakera, Aron, PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Aron Chakera, MBBS, PhD

• Stevenson, Jessica, PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Jessica Stevenson

• Neve, Vanessa C., PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Vanessa C. Neve, MPhil

• Syn, Genevieve, PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Genevieve Syn, PhD

• Moses, Colette, PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Colette Moses, PhD

• Mcdonagh, Clarissa, PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Clarissa Mcdonagh

• Richworth, Caitlyn, PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Caitlyn Richworth

• Cumming, Hayley, PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Hayley Cumming

• Vasilevski, Natali, PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Natali Vasilevski, PhD

• Bautista, Angelo Patrick Rivera, PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Angelo Patrick Rivera Bautista, MSc

• Chamberlain, Audrey E., PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Audrey E. Chamberlain

• Hurst, Jan, PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Jan Hurst

• Rauschert, Sebastian, PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Sebastian Rauschert, PhD

• Kerfoot, Maria, PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Maria Kerfoot, MHS

• Martin, Adam D., PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Adam D. Martin, PhD

• Das, Subrata, PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Subrata Das, PhD

• Mitchell, George, PYC Therapeutics Limited, Nedlands, Western Australia, Australia

George Mitchell

• Hockings, Rohan, PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Rohan Hockings, MBBS

• Stirnweiss, Anja, PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Anja Stirnweiss, PhD

• Cunningham, Paula, PYC Therapeutics Limited, Nedlands, Western Australia, Australia

Paula Cunningham, PhD

Background

Autosomal dominant polycystic kidney disease (ADPKD) is caused by haploinsufficiency of the PKD1 gene, resulting in reduced expression of polycystin-1 (PC1) and progressive renal cyst development resulting in renal failure. PYC-003 is a phosphorodiamidate morpholino oligomer conjugated to a cell-penetrating peptide, designed to bind and stabilise PKD1 messenger RNA, increasing levels of functional PC1. This approach has shown efficacy in reducing cystic phenotypes in three-dimensional cyst models derived from ADPKD patient cells.

Methods

This ongoing Phase 1, first-in-human clinical trial (NCT06714006) comprises Part A, a randomised, double-blind, placebo-controlled single ascending dose (SAD) study in healthy volunteers (N=8 per cohort), and Parts B and C, open-label studies in ADPKD patients evaluating single and multiple ascending doses (N=6 per cohort) of PYC-003. Patients were pre-screened for eligibility, including estimated glomerular filtration rate >30 mL/min/1.73 m², Mayo imaging classification C-E, and genetically confirmed PKD1 mutations. Safety, tolerability, pharmacokinetics (PK), and immunogenicity were assessed across escalating dose cohorts, with dose escalation guided by a Safety Review Committee (SRC).

Results

Across SAD cohorts in healthy volunteers and ADPKD patients, SRC-reviewed safety data indicated that PYC-003 was well tolerated, with no treatment-related serious adverse events, no clinically meaningful changes in serum or urinary safety biomarkers, and no clinically meaningful liver function test abnormalities. PK profiles were characterised in healthy volunteers at doses up to 4 mg/kg and in ADPKD patients at doses up to 2.4 mg/kg. Integrated PK/PD modelling predicts that PYC-003 achieves therapeutic kidney tissue concentrations at safe and well tolerated doses.

Conclusion

These early-phase clinical data demonstrate favourable safety and pharmacokinetic properties of PYC-003 in healthy volunteers and ADPKD patients, supporting further clinical development as a potentially disease-modifying therapeutic approach targeting the underlying molecular pathology of ADPKD.