ARON CHAKERA1,2, ANJA STIRNWEISS2, JESSICA STEVENSON2, MARIA KERFOOT2, ADAM MARTIN2, SUBRATA DAS2, GENEVIEVE SYN2, AISHWARYA KUNDU2, SRI MUDUMBA2, PAULA CUNNINGHAM2
1Sir Charles Gairdner Hospital, Perth, Australia, 2PYC Therapeutics, Perth, Australia
Biography:
Dr Aron Chakera is a consultant renal and transplant physician at Sir Charles Gairdner Hospital and Head of the Translational Renal Research Group at the Harry Perkins Institute of Medical Research. His research focuses on chronic kidney disease progression, renal genetics, and the integration of diagnostics into clinical care. He is the state lead for the KidGen national kidney genetics collaborative, custodian of the Western Australian Renal Biobank and on the scientific advisory board of the PKD Australia.
Aim:
To evaluate the safety, tolerability, and pharmacokinetics of PYC-003 in healthy volunteers (HVs) and ADPKD patients.
Background:
ADPKD is caused by the haploinsufficiency of the PKD1 gene and a resulting reduction in PC1 protein. Loss of PC1 results in the development and progressive enlargement of fluid-filled renal cysts. PYC-003 was designed as a disease modifying therapy for ADPKD patients. PYC-003 is a cell penetrating peptide conjugated phosphorodiamidate morpholino oligomer which binds to PKD1 messenger RNA and upregulates PC1 protein production. This could lead to slowing down or cessation of cyst formation and cyst growth.
Methods:
This is a two-part Phase 1, single ascending dose (SAD) study to evaluate the safety, tolerability, and pharmacokinetics (PK) of PYC-003 following a single intravenous infusion. Part A is in healthy adult participants and Part B is in adult participants with confirmed PKD1 mutation-associated ADPKD.
Results:
In Part A (HVs) the first cohort’s dosing showed no clinically observed adverse effects during the D0-D3 period. Blood chemistry analysis for samples collected between D0-D14 for this group also indicated minimal changes in key safety markers.
Additional findings – including safety data, dose escalation decisions, and preliminary PK outcomes – from Part A (HVs) and preliminary data from Part B (ADPKD patients) will be presented.
Conclusions:
Preliminary data suggest that PYC-003 is well tolerated in healthy volunteers, with no significant safety concerns identified to date. Successful completion and SRC approval of Part A Cohort 2 will serve as a critical milestone for progressing to Part B Cohort 1, marking the transition to patient dosing. These early-phase results will provide valuable insights into the clinical development of PYC-003 for the treatment of ADPKD.
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