Cognitive impairments are a common consequence of traumatic brain injury (TBI). Disruptions in acetylcholine neurotransmission after TBI contribute to many of the cognitive impairments reported and numerous studies show injury-related reduction in Acetylcholine (Ach) turnover and release, and decreased expression of nicotinic ACh receptors. In addition, the hippocampus, a region in the brain that plays a key role in the formation of memories, is highly vulnerable to TBI. The alpha-7 nicotinic acetylcholine receptor is highly active in this region and reduced function of the receptor is linked with cognitive impairment.
Benzgalantamine and galantamine, unlike other AChEIs, have been shown to improve function in the hippocampus, improve cognition, learning and memory in animal models of concussion. Preclinical studies suggest the dual mechanism of action of benzgalantamine, combining acetylcholinesterase inhibition and positive modulation of alpha-7 nicotinic receptor function may contribute to observed improvements in cognition, learning, and memory.
ALPHA-1062, benzgalantamine, sublingual formulation for treatment of Cognitive Impairment with mTBI
Alpha Cognition is advancing a sublingual formulation of benzgalantamine for the treatment of Cognitive Impairment with mTBI. ALPHA-1062 utilizes the same active pharmaceutical ingredient (benzgalantamine) as ZUNVEYL®, Alpha Cognition's FDA-approved treatment for mild-to-moderate Alzheimer's disease, but is being developed in a differentiated sublingual formulation optimized for rapid systemic absorption and treatment of cognitive impairment associated with mTBI.
Prior intranasal studies demonstrated substantially greater brain exposure to galantamine compared with oral administration, supporting investigation of alternative delivery approaches for CNS indications. The program leverages extensive preclinical experience, completed human safety studies, and the regulatory experience accumulated through the development and commercialization of benzgalantamine.
ALPHA-1062 has completed a pre-clinical efficacy study in mTBI. In a rodent model, ALPHA-1062 administration significantly reduced the extent of functional deficit and improved functional recovery compared to untreated animals, with performance on four of five functional recovery measures statistically indistinguishable from an uninjured cohort.
The Company expects to complete its TBI toxicity study in Q4 2026 and anticipates filing a sublingual IND for Cognitive Impairment with mTBI in the first half of 2027.
Cognitive Impairment with mTBI represents a significant market opportunity, estimated at $10.8 billion in the U.S. (approximately 1.2 million patients per year at an estimated $9,000 per treatment course), with roughly 1.4 million patients per year affected by cognitive impairment following TBI and currently no approved treatment for the condition.
In March 2026, the U.S. Patent and Trademark Office issued U.S. Patent No. 12,589,099, “ALPHA-1062 for Treating Traumatic Brain Injury,” covering methods of treating both confirmed and suspected TBI with ALPHA-1062, with protection extending to 2045.
