The Potential of AD101 for Managing Symptoms of Alzheimer Disease

Sharon L. Rogers, PhD

AD101 (AmyriAD) is an innovative small molecule influencing the flow of calcium into the presynaptic neuron, which results in an enhanced release of the neurotransmitter acetylcholine. This unique mechanism leads to an upregulation of neurotransmission, ultimately benefiting learning and memory in animal models. AD101 has been evaluated extensively thus far, with 7 clinical trials involving over 500 participants with mild to moderate Alzheimer disease (AD). Encouragingly, data from these trials indicate that AD101 is well-tolerated and can be conveniently administered orally once daily (NCT00842816 and NCT00842673).¹

In a recent randomized, double-blind, placebo-controlled phase 2 study, AD101 displayed significant and statistically validated enhancements in global function and cognition when added to a stable dose of 10mg/day donepezil, as compared with donepezil alone. For context, donepezil has been part of the global standard of care for AD since 1996 and functions as an inhibitor of the enzyme acetylcholinesterase, safeguarding acetylcholine from degradation once it is released into the synapse.¹ Overall, AD101's innovative approach of modulating calcium influx and acetylcholine release shows promise in improving cognitive function in patients with AD, offering new possibilities for treatment alongside existing medications like donepezil. AD101 has completed phase 2 clinical trials and is ready for phase 3, however the phase 3 trial has not been initiated.

In a recent interview with NeurologyLive®, Sharon L. Rogers, PhD, chief executive officer at AmyriAD Therapeutics, talked about the potential of AD101. She discussed how the therapy differs from the other drugs in the AD pipeline in its approach to treating the disease. Rogers, who previously served as a research chief at Eisai, also shared her reaction to the recent news on the traditional approval of lecanemab (Leqembi), the first traditionally approved agent in more than 20 years. In addition, she explained the ways that AD101 could potentially offer hope and benefits to patients with AD, their caregivers, and their providers.

NeurologyLive: Can you provide an overview of your therapeutic in development?

Sharon L. Rogers, PhD: Our lead compound is AD101, a drug that improves both of the core symptoms of Alzheimer disease, cognition and global function.

How is this new therapy different from the others in the AD pipeline?

AD101 is the only agent directed toward treating the core symptoms with a unique, first-in-class mechanism of action that enhances neurotransmission without unwanted peripheral effects. It is not a disease modifying agent (like the beta-amyloid monoclonals) and it is not directed toward late-stage psychiatric symptoms.

Where do you think the field of AD therapies is moving toward?

I believe AD is bringing itself more in line with the treatment practices of other chronic diseases like diabetes, high blood pressure and Parkinson disease. Virtually all chronic diseases are managed using multiple drug therapies, each contributing to improved patient symptoms via differing mechanisms of action.

What was your reaction to the lecanemab news?

I was very happy for my former colleagues at Eisai and believe they conducted an impeccable phase 3 program with unequivocal positive results.

Does the approval of lecanemab impact your therapy in any way?

Yes. Drugs like lecanemab will slow the progression of AD but will not halt or reverse it.Patients will continue to have the disease and symptoms will worsen over time. That makes symptom management strategies like AD101, that improve cognition and function, even more important for patients, caregivers and health care providers.

Transcript edited for clarity.

REFERENCES
1. AmyriAD to Present Clinical and Preclinical Data at the 15th Clinical Trials on Alzheimer's Disease (CTAD) Conference. News Release. AmyriAD. Published November 29, 2022. Accessed August 1, 2023. https://amyriadtherapeutics.com/amyriad-to-present-clinical-and-preclinical-data-at-the-15th-clinical-trials-on-alzheimers-disease-ctad-conference/