Actually, the drug candidate PYC has chosen for PMS doesn’t use its peptide conjugate delivery technology.
Back in June 2023, PYC announced that it had optimised two different chemistries in parallel for the PMS asset, allowing optionality in the development path. One was the PPMO RNA chemistry that is used in PYC’s first three drug candidates and the other was 2′MOE RNA chemistry, a naked RNA drug chemistry which has already been clinically validated. It was explained that the 2’MOE chemistry already has an established path through non-clinical species studies to clinical validation and commercial success.
In June this year, PYC announced that it had been able to restore the deficient protein that causes PMS in the brain cells in which the disorder occurs (neurons), derived from a patient with PMS. While it was possible to achieve this using both chemistries, it was pointed out that the 2’MOE chemistry had already demonstrated clinical benefit in patients with disorders occurring in neurons.
Today it was announced that the clinical candidate for PMS has been finally decided. Pre-clinical studies have demonstrated that this candidate not only reaches the critical areas of the brain implicated in PMS but also corrects the underlying cause of PMS in neuron brain cells derived from PMS patients.
Rohan Hockings commented that “the read-through benefits from other clinically-validated drug candidates within this class in different diseases occurring in the same target cell and organ provide a clear path to the patient-impact that we are striving for.”
Earlier this year, Stoke Therapeutics announced successful Phase 1/2a results in Dravet syndrome, a monogenic neurodevelopmental disorder of haploisufficiency.* This drug candidate has since received Breakthrough Therapy Designation from the FDA. Stoke’s drug, which also targets neurons in the brain, uses a naked RNA chemistry.
Consequently, PYC has chosen to run with the 2’MOE chemistry for its PMS drug candidate.
Having an established pre-clinical and clinical pathway, successful clinical results in the same target cell and organ, and prior approval of drugs which use this chemistry, means there is the potential for less risk and a speedier path to commercialisation for PYC’s PMS asset.
In addition, it is my view that opting for an already proven chemistry makes pharma interest in partnering this asset from an earlier stage more likely, should PYC be interested in this option.
*
https://hotcopper.com.au/threads/pyc-general-discussion.7711168/page-179?post_id=73080893
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