PYC Therapeutics (PYC) investor relations material

Disease background and therapeutic rationale

• Phelan-McDermid syndrome (PMS) is caused by SHANK3 gene deficiency, leading to impaired neuronal communication and neurodevelopmental symptoms.

• SHANK3 protein is essential for synaptic structure and function, with expression in brain regions critical for cognition and behavior.

• Deficient SHANK3 disrupts neuronal connections in regions like the hippocampus and prefrontal cortex, contributing to PMS symptoms.

PYC-002 mechanism and delivery

• PYC-002 is an antisense oligonucleotide (ASO) designed to upregulate SHANK3 protein by targeting its RNA, without altering DNA.

• The drug is administered via intrathecal (IT) injection, enabling delivery to key brain regions.

• ASO technology is clinically validated and allows for precise, durable, and safe modulation of target proteins.

• Dosing is expected a few times per year, with safety supported by over 10 years of clinical use for similar ASOs.

Preclinical evidence and safety

• In PMS patient-derived cells, PYC-002 restored SHANK3 protein to healthy levels, improving neuronal connections and communication.

• Animal studies showed broad brain distribution and increased SHANK3 protein at well-tolerated doses.

• Single IT doses in rats and monkeys upregulated multiple SHANK3 isoforms and enhanced neuronal activity.

• No adverse findings were observed in exploratory safety studies in juvenile rats and monkeys.