Perth-based company PYC Therapeutics will take early human data on its polycystic kidney disease drug to the American Society of Nephrology conference in Denver on 22 October.
The company, which also has offices in San Francisco, is testing candidate PYC-003 in patients whose polycystic kidney disease is caused by a mutation in the PKD1 gene. The disease causes cysts to grow in the kidneys, and it is driven by too little of a protein known as PC1. PYC says its drug "is designed to increase PC1 protein levels and address the disease process at its root cause."
The first set of results looks at urinary PC1, a measure of whether the drug is reaching its target in the kidney. Seven patients from the company's Phase 1a/1b studies had usable samples both before treatment and 14 days after a single dose. Three received 1.2 mg/kg, and four received 2.4 mg/kg. Pooled together, their urinary PC1 levels rose 46 per cent from baseline, with a 95 per cent confidence interval of 1.11 to 1.92 and a p-value below 0.05.
The company says the result "is consistent with the proposed mechanism of action of the drug candidate". It also concedes that the groups were too small to show whether a higher dose worked better, which is why the data were pooled.
The second set of results track total kidney volume, which PYC describes as "an accepted surrogate marker of disease progression in PKD". The US Food and Drug Administration lists this measure as an endpoint that can support accelerated approval. PYC measured kidney volume in 18 patients three months after a single dose and compared the change with a historical benchmark. That benchmark comes from 925 untreated patients across the TEMPO 3:4, CRISP and HALT PKD A trials, whose kidneys grew by an average of 6.2 per cent a year.
PYC's trials enrol only patients with PKD1 mutations. The company notes that "Patients with a PKD1 mutation progress faster toward end-stage kidney disease (and are consequently expected to have accelerated rates of TKV growth over time) than patients with mutations in other genes that cause PKD." The benchmark may understate how fast PYC's own patients' kidneys would have grown without treatment.
The company said the data "has been generated in a small number of patients over a short period of time and on endpoints that are variable by nature". It adds that the result "needs to be reproduced in repeat dose studies of PYC-003 in a larger number of PKD patients treated over a longer period of time before any conclusions regarding the likely impact of the drug candidate on the disease process can be drawn."
PYC is running a Phase 1b multiple ascending dose study and an associated open-label extension, and expects to present data from both in 2027. The company says progress in those studies is expected to be accompanied by talks with regulators about starting a registrational combined Phase 2/3 trial "aimed at supporting a New Drug Application for PYC-003 in PKD."
