We are so grateful to PYC Therapeutics for their informative webinar on PYC-002, an RNA-based gene therapy, held on March 13, 2025, and co-hosted by the Phelan-McDermid Syndrome Foundation and CureSHANK. We encourage you to watch the full webinar and review the Q&A document (both linked below). We also want to provide our PMSF community with a clear breakdown of the key takeaways and next steps!
Important Links
- PYC Webinar Recording from 3/13/25
- PYC Q&A to the PMSF community from 3/25/24
- PYC Press Release from December 2024
- PYC website with additional figures and data
- SHANK3 in Phelan-McDermid syndrome
- Podcast with Dr. Kate on RNA therapeutics/ASOs
- Video with Dr. Kate explaining ASOs
Gene Therapy: “ASO” vs “AAV”?
- ASO (Antisense Oligonucleotide) Therapy
- ASOs are synthetic (man-made) form of RNA molecules used in RNA-based gene therapy.
- ASO therapy targets RNA, making changes reversible—repeat dosing is required to maintain therapeutic benefits.
- PYC’s approach uses ASOs to help increase production of SHANK3 in the healthy copy of chromosome 22, this is called “SHANK3 upregulation”
- Injection site: (for PYC-002) Intrathecal (lower spine into the cerebrospinal fluid, or CSF).
- AAV (Adeno-Associated Virus) Therapy
- AAV therapy is a gene addition approach that permanently modifies DNA.
- Only one dose is required for lasting effects.
- Jaguar Gene Therapy is using AAVs to insert a functional SHANK3 gene into target brain cells.
- Injection site: (for Jaguar-201) is unilateral intracerebroventricular (ICV), through the skull into the cerebral ventricles, reaching the cerebrospinal fluid (CSF).
What Has PYC Already Done?
- Conducted initial studies using Phelan-Mcdermid syndrome patient-derived neurons.
- Demonstrated an increase in SHANK3 protein production.
What’s Next?
Current Focus: Preclinical Studies
- Nominating of clinical candidate(s) (an objective marker of ‘success’).
- Estimated 9-10 months for pre-clinical studies in mouse models and non-human primate models.
Future Plans: Phase 1/2 Clinical Trial in Humans with Phelan-McDermid Syndrome
- Regulatory submission: Estimated mid-2026.
- Human Trials: Estimated to begin late 2026/early 2027 (always subject to change).
- Phase 1: Establish safety.
- Phase 2: Assess initial efficacy.
- Trail Design: Initial human trial will be a single-dose trial.
Outstanding Questions
- Trial Location: Where will initial human clinical trial will occur (Australia vs. United States vs. UK/Europe)?
- Participant Age Range: What age groups will be included?
- Trial Size: How many participants will be enrolled?
- Genetic Inclusion Criteria: Will Class I and Class II deletions be included in the initial trial (PYC indicated it will likely be Class I first, but not definitive)?
- Treatment Goals: Will the trial target language, cognition, psychiatric/behavior symptoms, etc.?
- Dosing Plan: How many doses will be needed? What will be the interval between doses?
- Potential Side Effects: What are the possible risks of treatment?
- Further Eligibility Criteria: What are the full exclusion/inclusion criteria?
If you have any additional questions, feel free to reach out to PYC at info@pyctx.com or contact Dr. Lauren at lauren@pmsf.org.
Thank you to everyone that participated in this exciting and informative session!