Athira Pharma Announces Completion of Enrollment in Phase 2 ACT-AD Trial Evaluating ATH-1017 for Mild-to-Moderate Alzheimer’s Disease

Athira Pharma, Inc. recently announced it has completed enrollment in ACT-AD, a Phase 2 randomized, placebo-controlled study of ATH-1017 in patients with mild-to-moderate Alzheimer’s disease. ATH-1017 is a small molecule designed to enhance the activity of Hepatocyte Growth Factor (HGF) at its receptor, MET, which are expressed in the central nervous system to promote brain health and function. Athira expects to report topline results from the trial in the first half of 2022.

“The completion of enrollment in our ACT-AD trial is an important step forward in advancing ATH-1017 as a potential new treatment option for patients suffering from Alzheimer’s and other dementias,” said Mark Litton, PhD, MBA, President and Chief Executive Officer at Athira. “We look forward to building on this momentum and sharing topline results from this Phase 2 trial in the first half of 2022. As part of our overall clinical development program to maximize the full potential of ATH-1017, we plan to initiate a clinical trial in Parkinson’s disease dementia later this year. At Athira, we are committed to improving the lives of patients and their caregivers, and we are proud of our progress towards this goal to date.”

“The completion of enrollment in ACT-AD is an important clinical milestone for Athira. Results from this trial may provide Athira with supportive information that can help optimize our ongoing potentially pivotal LIFT-AD trial and confirm the statistically significant improvement in P300 latency, a functional measure of working memory processing speed, demonstrated in our early trial. We are thankful to have reached this milestone and for the combined efforts of our researchers, partners and the patient and caregiver community,” said Hans Moebius, MD, PhD, Chief Medical Officer at Athira. “The pathophysiology of Alzheimer’s disease is complex and includes not only the hallmarks of beta-amyloid deposits and neurofibrillary tangles, but neuroinflammation, vascular dysfunction, and neurodegeneration. By focusing on neuronal network recovery, ATH-1017’s novel mechanism of action is agnostic to the underlying disease pathology of Alzheimer’s and other dementias.”

The ACT-AD study (www.act-adtrial.com, NCT04491006) is a randomized, double-blind, placebo-controlled, 26-week Phase 2 clinical trial. Participants were randomized across two dose groups and one placebo group on a 1:1:1 basis to receive a daily subcutaneous injection of ATH-1017 or placebo over a treatment course of 26 weeks. The study has enrolled 77 patients with mild-to-moderate Alzheimer’s disease across 14 sites in the United States and Australia. Patients will be evaluated for improvement in cognition, global, and functional assessments comparing treatment arms to placebo. ACT-AD will also use electroencephalogram (EEG), to measure quantitative electroencephalogram (qEEG), and Event-Related-Potential (ERP P300), a functional measure of working memory processing speed. Following completion of the 26-week treatment period during the LIFT-AD or ACT-AD trials, patients may elect to continue on the open label extension and receive treatment with ATH-1017 at the high dose (70 mg/day) for up to an additional 26 weeks.

ATH-1017, Athira’s lead therapeutic candidate, is a positive modulator of HGF/MET. ATH-1017 is a prodrug that is administered via subcutaneous injection in its inactive form and rapidly converted in plasma to an active tyrosine metabolite (dihexa). Since 2018, ATH-1017 has been assessed in multiple preclinical and clinical studies by Athira and by its third-party contractors. Studies performed by third parties sponsored by Athira regarding ATH-1017’s safety profile and treatment potential include the following:

• A non-clinical study in an Alzheimer’s disease (AD) animal model (APP1/PS1), which showed that ATH-1017 treatment increased the qEEG gamma power that is associated with cognitive processing and memory.
• IND enabling studies including nonclinical GLP long-term toxicology and safety pharmacology studies performed by independent contract research organizations with validated methods and audited reports.
• A Phase 1a/b clinical trial in healthy young, healthy elderly, and AD subjects, in which ATH-1017 was shown to be well-tolerated with no serious adverse events and demonstrated statistically significant improvement in Event-Related Potential, or ERP. ERP P300 latency, an objective measure of working memory processing speed, was noted in patients with AD following multiple dose treatments with ATH-1017 compared with those receiving placebo (P<0.05). Recently, an independent auditing firm affirmed the GCP compliance and data management quality of the Phase 1a/b clinical trial.

Athira, headquartered in the Seattle area, is a late clinical-stage biopharmaceutical company focused on developing small molecules to restore neuronal health and stop neurodegeneration. Athira aims to provide rapid cognitive improvement and alter the course of neurological diseases with our novel mechanism of action. Athira is currently advancing its lead therapeutic candidate, ATH-1017, a novel small molecule for Alzheimer’s and Parkinson’s disease dementia. For more information, visit www.athira.com.