CAMP4 Therapeutics Unveils Gene-Upregulation ASO Platform, Targets SYNGAP1 Clinic Entry in 2H

Key Points

• Camp4's platform uses antisense oligonucleotides to bind "regulatory RNA" and upregulate haploinsufficient genes, a strategy the company says could potentially address roughly 1,200 diseases with current emphasis on CNS indications.
• Its lead program, SYNGAP1, produced dose-dependent increases in mRNA and SynGAP protein and functional restoration in preclinical models, and Camp4 expects to enter the clinic "as early as the second half of this year" using intrathecal dosing of a naked ASO with a Spinraza-style backbone.
• Camp4 plans a Phase I/II multiple-ascending-dose study enrolling more severe (including pediatric) patients and will measure seizures plus broader endpoints (sleep, behavior, motor, communication) to inform a potential registrational strategy.

CAMP4 Therapeutics NASDAQ: CAMP outlined its approach to upregulating gene expression using antisense oligonucleotides (ASOs) and provided an update on its lead central nervous system (CNS) program targeting SYNGAP1-related disorder during a presentation at the 25th Annual Needham Healthcare Conference. The presentation was delivered by CFO Kelly Gold in a session moderated by Needham biotech analyst Joey Stringer.

Platform focused on upregulating haploinsufficient genes

Gold said Camp4 is targeting what it calls “regulatory RNA,” short non-coding RNAs transcribed from enhancers or promoters during active transcription. According to Gold, these RNAs play a role in controlling transcription by recruiting positive and negative factors. Camp4’s approach uses an ASO to bind a key site on the regulatory RNA, alter its structure, and “interrupt the binding of a repressor element,” which Gold described as “taking the brakes off” transcription to produce more mRNA.

Camp4 is focusing on haploinsufficient diseases—conditions where one allele is healthy and one is mutated or unproductive—leaving patients with about 50% of normal protein levels. Gold said the company believes its platform could potentially address roughly “1,200 or so diseases” within this category, with current emphasis on CNS indications.

SYNGAP1 program positioned for clinic entry in 2H

Camp4’s lead program targets SYNGAP1-related disorder, a rare genetic epilepsy and developmental disorder. Gold said the program remains in discovery but the company believes it could enter the clinic “as early as the second half of this year,” with plans to dose patients directly in a Phase I/II study. She also noted the company has completed the in-life portion of GLP toxicology studies and is planning to initiate a clinical study “going directly into patients in the latter half of this year.”

The company is focused on intrathecal administration of an unconjugated (“naked”) oligonucleotide for CNS delivery. In the Q&A, Gold said Camp4 is using “the same backbone chemistry as Spinraza” and expects a similar dosing regimen: a loading period of three doses followed by quarterly dosing.

Disease overview: high unmet need and complex symptom burden

Gold described SYNGAP1-related disorder as a “true haploinsufficiency,” in which mutation of one of two SYNGAP alleles results in about half the normal SynGAP protein level. She said the disease presents with intellectual disability and seizures, but also includes significant behavioral and sleep challenges that can intensify caregiver burden as patients age. She emphasized there are “no approved disease-modifying therapies,” and patients are often managed with multiple medications to address seizures, sleep, mood, and behavior.

On prevalence, Gold said Camp4 believes there are “over 10,000 patients” in the U.S. and “about an equal amount through the rest of the world,” adding that diagnosis rates may rise as awareness and genetic testing expand. She noted the condition was cloned in 2009 and has had an ICD-10 code since 2021. Gold also discussed how diagnostic timelines have shortened with broader access to sequencing: caregivers of older patients have reported taking three to five years or more to obtain a diagnosis, while more recent experiences suggest diagnosis can occur in about a year, often triggered by seizures or developmental delays and followed by genetic epilepsy panels and whole-genome sequencing.

Preclinical data showed dose-dependent increases in mRNA and protein

Gold presented several preclinical datasets supporting the company’s strategy of increasing SynGAP protein levels. In induced pluripotent stem cell-derived neurons from SYNGAP1 patients, Camp4 observed that patient neurons expressed SYNGAP mRNA at about 50% of control levels, and application of its clinical candidate “CMP-001” increased mRNA in a dose-dependent manner, according to Gold.

In a humanized SYNGAP1 mouse model—engineered with mouse SYNGAP1 removed and one healthy human SYNGAP1 gene introduced—Gold said the company saw dose-dependent increases in SynGAP protein after administering its candidate. She added that in functional readouts across learning and memory, cognition, motor function, and hyperactivity, treated diseased mice showed restoration to “wild-type levels,” describing those results as a key driver of enthusiasm for the program.

Gold also described intrathecal dosing studies in wild-type monkeys using the clinical route of administration. She said Camp4 observed broad distribution at low, mid, and high doses across multiple cortical regions and the hippocampus, along with dose-dependent increases in SynGAP protein in those regions.

Clinical design: beyond seizure endpoints

Gold said Camp4 is working on Phase I/II endpoint strategy that includes seizure measures as well as assessments beyond seizures. She said the company is considering endpoints related to sleep, motor function, communication, behavior, development, and other measures, and intends to leverage available natural history datasets. Gold noted multiple natural history studies in Europe, the U.S., and Australia, totaling “over 1,200 patient years of data obtainable.”

In response to questions about trial design, Gold said the company plans to enroll a more severe patient population in Phase I/II and expects to go directly into a multiple ascending dose (MAD) study. She said Camp4 is discussing pediatric starting ages with regulators across multiple jurisdictions and wants to treat “as young as possible,” citing the importance of earlier intervention while also stating the company believes patients “can be helped at any age” because the condition is viewed as “a neuroarrest disease as opposed to a neurodegenerative disease.”

On seizure burden under current management, Gold said families often report anti-seizure medications “sort of work until they don’t,” requiring ongoing adjustments. She said seizure frequency varies, but “10+ is not uncommon,” and some families report “25 or more a day.” She added that, for families, non-seizure issues—particularly sleep and behavior—are often a major priority alongside seizure control.

Gold said seizure endpoints may represent a more established regulatory path, but emphasized the company does not want to “limit the opportunity” of a potential therapy. She said Camp4 plans to incorporate exploratory measures in Phase I/II to inform the design of any future registrational study and to support the “broadest label” possible. Gold also noted that natural history data suggest seizure burden increases with age and remains high, while other measures may not improve and can worsen over time, particularly behavior and sleep.

Beyond SYNGAP1, Gold said Camp4 has early discovery efforts in other developmental epileptic encephalopathies, a deprioritized urea cycle disorder asset that completed Phase I/II studies in healthy volunteers and is seeking a partner, and a multi-target discovery-stage collaboration with GSK announced late last year.

About CAMP4 Therapeutics NASDAQ: CAMP

CalAmp Corp., a connected intelligence company, provides leverages a data-driven solutions ecosystem to people and organizations in the United States, Europe, the Middle East, Africa, Latin America, the Asia-Pacific, and internationally. The company operates in two segments, Software & Subscription Services and Telematics Products. It provides CalAmp Telematics Cloud platform, such as cloud-based application enablement and telematics service platforms that facilitate integration of its own applications, as well as those of third parties, through open application programming interfaces; and software as a service application, as well as provides tracking and monitoring services within fleet management, supply chain integrity, and international vehicle location.

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