CAMP4 Therapeutics (NASDAQ:CAMP) said it expects to dose the first patient in its Phase I/II ASCEND trial of CMP-002 for SYNGAP1-related disorder during the fourth quarter, with top-line results targeted for the first half of 2028.
The company’s analyst event focused on CMP-002, an antisense oligonucleotide, or ASO, designed to increase expression of the SYNGAP1 gene. SYNGAP1-related disorder is caused by mutations that reduce functional SynGAP protein and is associated with intellectual disability, epilepsy, communication impairment, sleep problems and behavioral symptoms.
Preclinical findings
Chief Scientific Officer Dan Tardiff said CAMP4’s platform targets non-coding regulatory RNAs in an effort to increase gene expression. In the SYNGAP1 program, the company is seeking to restore protein levels toward normal levels in patients with haploinsufficiency, in which one functioning gene copy does not produce enough protein.
Tardiff said CMP-002 increased SYNGAP1 expression in patient-derived neurons and in a humanized mouse model containing the human SYNGAP1 gene. In mice with a single copy of the gene, a single intracerebroventricular dose increased SynGAP protein levels by approximately twofold, according to the presentation.
The company also reported improvements in learning and memory, motor function and hyperactivity measures in the mouse model after treatment. In a chemically induced seizure model, CMP-002 reduced seizure susceptibility relative to untreated haploinsufficient mice, Tardiff said.
In non-human primates, intrathecal administration produced dose-dependent drug concentrations across brain regions including the cortex and hippocampus, along with dose-dependent increases in SYNGAP1 protein, according to CAMP4. The company plans to administer CMP-002 intrathecally in the clinical study.
ASCEND trial design
Chief Medical Officer Yuri Maricich said ASCEND is a randomized, double-blind, controlled multiple-ascending-dose study intended to evaluate safety, tolerability, pharmacokinetics and an optimal biological dose, while seeking signals across multiple disease domains.
The trial will enroll participants ages 2 through under 18 with genetically confirmed SYNGAP1-related disorder involving protein-truncating variants in exons 5 through 19. Participants must have intellectual disability, inability to speak in phrases, sleep disturbance and refractory epilepsy with daily seizures despite treatment.
Each cohort will include at least eight participants, randomized three-to-one to receive CMP-002 or a sham pinprick control. The treatment period includes three doses over three months, followed by a six-month follow-up period. Eligible participants may enter an open-label extension after completing the study.
CAMP4 plans to assess seizures, sleep, motor function, communication, behavior, development and cognition. Methods will include seizure diaries, video EEG, caregiver and clinician assessments, actigraphy and validated scales used in neurodevelopmental disease studies. Maricich said the company is not preselecting a single efficacy endpoint because ASCEND is the first potential disease-modifying randomized study in SYNGAP1 and is intended to identify the most relevant measures for future development.
Maricich said natural-history resources, including patient registries and observational studies, have collectively characterized more than 2,500 patients and will help inform comparisons. He added that CAMP4 does not expect to routinely disclose unblinded efficacy data before the planned 2028 readout, although the study design could potentially support safety or pharmacodynamic updates before then.
Patient and clinical perspective
Beata Tarasiuk, a CURE SYNGAP1 state ambassador and mother of a 9-year-old child with the disorder, described the daily caregiving burden associated with seizures, inability to communicate verbally, sleep disruption and dependence on others for daily activities.
Mike Graglia, chief executive officer of CURE SYNGAP1, said the patient advocacy organization has worked with CAMP4 on natural-history data, trial design and family support. He said there is substantial patient-community interest in trial participation and emphasized the need for rigorous evaluation of CMP-002.
Stéphane Auvin, a professor of pediatric neurology at Paris-Cité Université, said treatments that target underlying disease mechanisms could potentially affect both seizures and non-seizure symptoms such as cognition, behavior and sleep. He noted that SYNGAP1 has a comparatively extensive natural-history record for a rare disorder, which could aid trial design and interpretation.
Pipeline expansion
Separately, CAMP4 announced SHANK3 as a new preclinical program. The company said it intends to advance a candidate for Phelan-McDermid syndrome, a neurodevelopmental disorder associated with SHANK3 mutations or deletions, toward development-candidate nomination in 2027.
Mandel-Brehm said CAMP4 also has two additional haploinsufficient developmental and epileptic encephalopathy programs that it expects to discuss in the coming year.
About CAMP4 Therapeutics (NASDAQ:CAMP)
CAMP4 Therapeutics Corporation is a clinical-stage biotechnology company developing RNA-based medicines for genetic diseases caused by insufficient expression of essential proteins. The company’s approach is designed to increase the body’s production of naturally occurring proteins by activating the transcription of specific genes, potentially addressing the underlying cause of disease rather than only treating symptoms.
CAMP4’s technology platform uses RNA-based gene-activation therapeutics intended to target regulatory regions associated with disease-relevant genes.
