By Melane Sampson
Closely held Casp-Aid is advancing a differentiated therapeutic strategy aimed at repairing damaged neurons responsible for cognitive impairment by targeting the root cause of neuronal damage in Alzheimer disease (AD). The company’s lead asset, Cognitive Impairment Modulator 765 (CIM765), is positioned as a first-in-class, symptom- and disease-modifying small molecule designed not only to slow cognitive decline, but also to potentially restore and hopefully sustain memory.
“Our goal is to move beyond simply slowing symptoms to modifying the underlying disease mechanism by safely repairing neuronal structure and function in the hope of restoring and sustaining cognition,” Andréa LeBlanc, founder, president, and interim CEO of Casp-Aid, says in an interview with BioTuesdays.
Dr. LeBlanc, a retired full professor from the Department of Neurology and Neurosurgery at McGill University, has dedicated more than 30 years to studying the molecular drivers of neurodegeneration. She is recognized for discovering the Caspase-1—Caspase-6 pathway as a key driver of cognitive decline in AD and for developing the preclinical evidence supporting CIM765’s potential to restore memory.
Despite decades-long intensive industry research, Dr. LeBlanc says progress in Alzheimer therapeutics has been limited. Currently, the approved classes of drugs include acetylcholinesterase inhibitors introduced between 1996 and 2003, which temporarily increase acetylcholine levels to enhance neurotransmission, and NMDA receptor antagonists, which modulate glutamatergic signaling. More recently, anti-amyloid beta monoclonal antibodies were introduced in 2021 with the aim of clearing amyloid plaques from the brain.
Dr. LeBlanc notes that while anti-amyloid therapies have demonstrated plaque reduction, their clinical impact on cognition remains modest. “These therapies modestly slow cognitive decline by six months, but they do not restore memory. Acetylcholinesterase inhibitors provide a short-term—three- to six-month—improvement in memory, after which they only slightly slow cognitive decline.” She indicates that safety concerns have limited adoption. “Cholinesterase inhibitors have been known to cause gastrointestinal issues, leading to about 50% of patients discontinuing use. Anti-amyloid antibodies carry risks of brain bleeding and swelling, which in rare cases have been associated with deaths in clinical trials.”
Also speaking with BioTuesdays is Rahul Sarugaser, PhD, chief financial officer of Casp-Aid, who adds, “While anti-amyloid drugs are approved in several jurisdictions, reimbursement has been inconsistent. In Europe and Canada, for example, payers have flatly rejected coverage of these therapies due to cost-benefit considerations.” He points out that with more than 55 million people worldwide living with dementia—60% to 80% of whom have AD—the need for safer, more effective therapies that focus specifically on slowing or improving cognition is urgent.
Dr. LeBlanc says that Casp-Aid is pursuing a fundamentally different hypothesis. Rather than targeting amyloid or tau—proteins known to be primary biomarkers of AD—or inflammation individually, the company is focused further upstream on repairing neuronal structure itself, regardless of the initiating stressor. She explains that neuronal damage in AD may arise from multiple causes, including genetic mutations, vascular disease, oxidative stress, inflammation, environmental exposures, or other age-dependent stressors.
“Neurons actually don’t die early in Alzheimer disease—they lose structural integrity and function. It is the loss of structure that leads to cognitive impairment. If we can inhibit neurodegeneration within the neuron, we may restore neuronal function even if initial stressors remain present.”
Over decades of research, Dr. LeBlanc identified Caspase-6 as a critical mediator of stress-induced neuronal damage. Although Caspase-6 belongs to the programmed cell death family of enzymes, its activated form in neurons does not directly induce cell death. Instead, it cleaves cytoskeletal and synaptic proteins, as well as proteins involved in removing misfolded proteins from cells, disrupting neuronal architecture and impairing the brain’s communication system.
Working with post-mortem brain tissue from patients whose memory and thinking abilities had been evaluated, Dr. LeBlanc identified that Caspase-6 levels were elevated not only in AD but also in mild cognitive impairment—an early stage of the disease. Importantly, she notes that higher Caspase-6 activity correlated inversely with global cognitive scores, including episodic and semantic memory—both of which are impaired early in AD.
“Caspase-6 activation closely aligns with cognitive dysfunction, so the pathway is a promising therapeutic target,” she says.
Since direct inhibitors of Caspase-6 were not available, Dr. LeBlanc investigated Caspase-1, a key enzyme responsible for activating Caspase-6 and known to be elevated in AD pathology. She discovered that a small-molecule Caspase-1 inhibitor—VX765, also known as belnacasan—had previously completed four FDA-authorized Phase 2 trials in inflammatory conditions, including psoriasis, Muckle-Wells syndrome, epilepsy, and COVID-19. Although these trials didn’t demonstrate efficacy in their respective indications, the molecule demonstrated an excellent safety and tolerability profile.
The compound had been shelved by its original developer, so in 2024 Casp-Aid licensed the full clinical, toxicology, and chemistry package and renamed the molecule CIM765. “For us, it was an ideal asset,” Dr. LeBlanc asserts. “It crosses the blood-brain barrier—a critical consideration in central nervous system drug development, it is highly selective and potent against Caspase-1, and has already demonstrated safety in humans.”
In longitudinal studies conducted by Dr. LeBlanc and her team, one week of VX765/CIM765 treatment normalized cognition in five- and twelve-month-old-transgenic Alzheimer mouse models carrying mutations in the amyloid precursor protein gene that show cognitive impairment at four months of age. Continued treatment maintained normal memory performance, while discontinuation led to loss of effect. Re-treatment restored cognition, confirming that the effect on cognition is directly related to VX765/CIM765.
Further studies demonstrated that even older mice with advanced pathology showed normalization of memory following treatment. Dr. LeBlanc emphasizes that transient pre-symptomatic treatment delayed the onset of cognitive impairment by four to five months in mice, which corresponds to roughly 10 to 15 years in humans. “The magnitude and speed of the effect were notable. We were not just slowing decline, we were restoring function, and this compelled us to continue efforts to assess this drug in AD.”
Casp-Aid is now preparing a Phase 2b clinical trial evaluating approximately 180 patients across the U.S. and Canada. The company plans to leverage C5 Research (C5R), a Canadian not-for-profit CRO co-founded by its interim chief medical officer, Serge Gauthier, MD, which provides access to a broad network of memory clinics and investigators.
The company already holds ample cGMP-manufactured active pharmaceutical ingredient for its clinical trials and has licensed the full preclinical, chemistry, manufacturing, controls, and toxicology package. An independent data safety monitoring board is being established, and the primary endpoint is expected at six months. From first patient dosing to data readout, the projected timeline is approximately 18 to 24 months.
“From an investor standpoint, that timeline is very attractive,” Dr. Sarugaser says. “Rather than waiting three to four years, investors could see clear proof-of-concept data in under two years.”
He emphasizes that although the original composition-of-matter patent expired in 2021, given that CIM765 remains a new chemical entity, Casp-Aid anticipates regulatory exclusivity under the Hatch-Waxman Act. “Upon regulatory approval we expect at least seven and a half years of exclusivity in the U.S. and ten years in Europe,” Dr. Sarugaser says. “This provides a commercially attractive window, particularly for a first-in-class drug that has potential to be a first-line therapy.”
He points out that neurology is a strategic priority for large pharmaceutical companies, with several recent billion-dollar transactions occurring at the Phase 1 and Phase 2 stages based largely on amyloid-related data. “In many of these cases, the acquired companies are demonstrating amyloid plaque clearance. We are aiming to demonstrate impact on cognition, which is what we believe truly matters to patients.”
Dr. Sarugaser says that comparable publicly traded Phase 2 AD companies cluster around valuations of $200 million. Casp-Aid views this as a benchmark and sees a pathway toward substantially higher valuation contingent on proof of concept.
The company is currently raising approximately $5 million in seed financing to refine product formulation, complete FDA and Health Canada regulatory submissions, and initiate clinical operations. A subsequent $20 million in Series A financing is planned to fund the Phase 2b trial.
By targeting the Caspase-1—Caspase-6 pathway, Casp-Aid is advancing a mechanism independent of the standard of care, focused instead on restoring neuronal structure and function.
“We are dedicated to getting a clean, definitive answer,” Dr. Sarugaser clarifies. “If the data confirm what we’ve seen preclinically, CIM765 could represent a fundamentally new way of treating cognitive impairment—a compelling opportunity for investors, strategic partners, and most importantly, patients.”
Dr. LeBlanc concludes, “We are advancing a breakthrough program that seeks not just to slow Alzheimer disease, but to reverse its most devastating consequence to patients and their families—memory loss.”
Editor’s Note: This article does not constitute an offer to sell or the solicitation of an offer to buy any securities of Casp-Aid, and shall not constitute an offer, solicitation or sale of any security in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.
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