Athira Pharma, Inc. announced its drug development pipeline consists of potential first-in-class (fosgonimeton) and next-generation small molecule therapeutic candidates (ATH-1105 and ATH-1020) designed to promote the neurotrophic HGF system, which activates neuroprotective, neurotrophic and anti-inflammatory pathways in the central nervous system. Athira?s therapeutic candidates have distinct properties, which the Company believes may be applicable to a broad range of neurodegenerative diseases. Fosgonimeton (ATH-1017) ?

A potentially first-in-class, once daily, subcutaneously administered drug candidate initially targeted for the potential treatment of Alzheimer?s disease. LIFT-AD Phase 2/3 clinical trial of fosgonimeton in mild-to-moderate Alzheimer?s disease: The LIFT-AD study is investigating the effects of fosgonimeton 40 mg compared with placebo in mild-to-moderate AD patients who are not receiving background therapy. In October 2022, following an unblinded interim efficacy and futility analysis, an independent data monitoring committee recommended continuation of the LIFT-AD study in patients with mild-to-moderate AD who are not receiving background therapy.

The committee also determined that the study would be well powered to achieve the primary endpoint with approximately 300 patients given the preliminary effect size observed in the unblinded interim analysis of approximately 100 patients treated. In May 2023, Athira selected the 40 mg dose for further development and potential regulatory approval. In January 2024, Athira announced completion of enrollment in the LIFT-AD study, ultimately randomizing approximately 315 patients in the primary analysis population.

The Company expects to report topline data in the second half of 2024. Open Label Extension (OLEX) fosgonimeton trial: Eligible participants who complete the LIFT-AD or ACT-AD trials and elect to participate in the ongoing OLEX are able to receive up to 30 months of open-label treatment. Greater than 85% of participants who completed either study have elected to enroll in OLEX to date.

Currently more than 60 patients are continuing fosgonimeton treatment beyond 18 months, which is unexpected in a progressive mild-to-moderate Alzheimer?s disease population. Athira believes OLEX will complement its long-term safety database and provide insights into fosgonimeton?s long-term effects for up to three years of investigational treatment. SHAPE Phase 2 clinical trial of fosgonimeton in mild-to-moderate Parkinson?s disease dementia and Dementia with Lewy bodies: In December 2023, Athira announced encouraging results from the exploratory SHAPE Phase 2 clinical trial of fosgonimeton for the potential treatment of Parkinson's disease dementia and Dementia with Lewy bodies.

Treatment with fosgonimeton 40 mg (n=5) compared to placebo (n=7) showed positive effects in cognitive measures including ADAS-Cog13, MMSE, and COWAT over the 6-month double-blind treatment period. The primary endpoint, a composite score of the change in Event-Related-Potential (ERP) P300 latency and cognitive assessment (ADAS-Cog13), was not met compared with placebo. Fosgonimeton was generally well tolerated, with a favorable safety profile.

There were no treatment-related serious adverse events observed in the study. The most common adverse event in the treatment groups was injection site reactions. ATH-1105 ?

A next-generation, orally administered drug candidate developed for the potential treatment of amyotrophic lateral sclerosis as the Company?s initial indication. ATH-1105?s potential as a treatment for ALS is supported by a growing body of preclinical evidence demonstrating statistically significant improvements on nerve and motor function, biomarkers of inflammation and neurodegeneration, and survival in various ALS animal models. These data were presented throughout 2023 at a variety of key scientific and medical meetings including the American Association of Neurology (AAN), the Alzheimer?s Association International Congress (AAIC), the Northeast Amyotrophic Lateral Sclerosis Consortium® (NEALS), and the Motor Neurone Disease Association (MNDA).

The initiation of first-in-human studies of ATH-1105 is targeted for the first half of 2024 to evaluate this promising drug candidate as a treatment for ALS.