CAMP4 Therapeutics has begun GLP toxicology studies for CMP-SYNGAP-01, an intrathecally delivered antisense oligonucleotide designed to upregulate SYNGAP1 expression for SYNGAP1-related neurodevelopmental disorders. Preclinical work has shown dose-dependent increases in SYNGAP1 mRNA and protein, phenotype improvement in a SYNGAP1 mouse model, and increased SYNGAP1 protein in non-human primate brain regions relevant to human disease. The GLP package is intended to support a clinical trial application and a first-in-human Phase 1/2 start as early as the second half of 2026.
The core development move is the shift from platform validation to translational readiness: CAMP4 is committing to a full preclinical safety package for a CNS ASO with pediatric relevance and repeat intrathecal dosing. The choice of a CTA pathway signals a likely ex-US initiation, aligning with sponsors that first test intrathecal agents in European or UK centers familiar with pediatric rare neurologic trials. The two-year runway telegraphs the scope of work ahead—GLP tox across species, potential juvenile studies given pediatric onset, CSF exposure, and PD assays, and CMC scale-up for a formulation suitable for repeated lumbar puncture.
Strategically, CAMP4 is positioning regulatory RNA upregulation as an alternative to gene replacement and editing in haploinsufficient disease. The thesis is operationally pragmatic: a titratable, redosable modality that can be dialed for safety and effect, in contrast to one-time AAV or CRISPRa approaches that face durability and immunogenicity constraints. The tension is familiar to CNS ASOs—demonstrating target engagement and functional benefit in a heterogeneous, developmentally evolving population, while managing procedure burden and safety signals such as dorsal root ganglion findings and neuroinflammation that have complicated other programs.
For sites, a SYNGAP1 Phase 1/2 would concentrate activity at specialized pediatric neurology centers with established intrathecal infrastructure, EEG capabilities, and experience with caregiver-reported and performance-based cognitive assessments. Expect tight genotype confirmation workflows and centralized oversight of seizure metrics, sleep, and behavioral endpoints, with digital and EEG analytics vendors playing a larger role than in typical rare disease trials. CROs will need to prioritize caregiver engagement, sedation logistics, and visit consolidation to offset procedure burden. Regulators have raised the bar on pediatric CNS programs to include clear PD markers; sponsors will be pressed to show evidence of SYNGAP1 upregulation in accessible compartments, correlate with functional readouts, and justify age-banding to capture developmental windows. Patient registries and natural history datasets, where available, will be pivotal in endpoint selection and powering assumptions.
Near-term, the readouts to watch are the breadth of the tox package, any juvenile data, and clarity on dosing cadence, which will drive site workflow and caregiver willingness. The initial CTA geography will be telling, as will the Phase 1/2 design choices around age cohorts, open-label vs. controlled components, and incorporation of CSF or electrophysiologic PD endpoints. Manufacturing readiness and device compatibility for repeat intrathecal administration are execution risks that can delay startup. Competitive pressure is emerging from multiple modalities pursuing SYNGAP1 restoration, and the field’s recent experience in Dravet and other haploinsufficiencies shows that translational fidelity from preclinical protein upregulation to clinical benefit is not assured. If CAMP4 can align PD evidence with practical, caregiver-acceptable procedures and demonstrate early signals on seizure or neurocognitive function, the program could define an operational template for transcriptional upregulation in pediatric CNS rare disease.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
