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Annovis Bio Planning New Drug Trial in Biomarker-Defined Alzheimer's Group After Mixed Study Readout

NEW YORK – Annovis Bio is planning a pivotal Phase III trial to test its investigational drug buntanetap in a biomarker-defined group of early Alzheimer's disease patients, despite mixed results from a Phase II/III data readout.

Malvern, Pennsylvania-based Annovis said it will report the Phase II/III trial data to the US Food and Drug Administration and request an end-of-Phase II meeting. In a planned Phase III trial to confirm positive findings from a subgroup analysis of the Phase II/III data, the company said it will focus on patients with confirmed early Alzheimer's based on tau levels and evaluate the drug during an 18-month period, longer than the previous study's 12 months.

Investigators enrolled more than 300 patients with mild-to-moderate Alzheimer's into the randomized-controlled Phase II/III trial. In that trial, patients received either one of three doses of buntanetap or a placebo, in addition to continuing their standard care, for 12 weeks. Buntanetap is a daily oral medication that binds to an iron-responsive element in the mRNA of neurotoxic proteins, including beta-amyloid, tau, and alpha-synuclein, to inhibit their translation, which the company believes can reverse neurodegeneration in multiple neurodegenerative diseases.

The company on Monday reported data on a subgroup analysis of patients from the Phase II/III trial with early Alzheimer's defined based on Mini Mental State Examination score and elevated levels of tau at baseline. In this subgroup, investigators observed significantly higher improvement on Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11) scores, one of two co-primary endpoints in the trial, in each of the treatment groups compared to placebo and compared to baseline.

However, the drug was not statistically significant on its other co-primary endpoint, assessments based on the Alzheimer's Disease Cooperative Study Clinician's Global Impression of Change (ADCS-CGIC), as scores on that scale "barely changed" across all treated and placebo groups. Scores slightly improved in the two higher-dose groups, but the changes were not statistically significant, according to the company.

Annovis' share price, which closed at $18.01 on Friday, dropped more than 60 percent on the news Monday. Shares opened at $6.89 on Tuesday.

The company noted that total plasma tau levels decreased for all treatment groups, suggesting a disease-modifying effect. The drug was well tolerated, with a comparable number of adverse events between treatment and placebo groups and with the majority of events mild to moderate in severity. There were no serious adverse events related to the drug.

"This Phase II/III Alzheimer study builds and expands on the understanding we collected in the Phase II studies," Melissa Gaines, Annovis' senior VP of clinical operations, and Cheng Fang, Annovis' senior VP of R&D, said in a statement. "We are preparing the data to discuss with the FDA on how to proceed to show disease-modification."