Annovis Bio Reports Major Phase II/III Alzheimer's Trial Success

Annovis Bio, Inc., a clinical-stage company focused on neurodegenerative diseases, has revealed promising results from its Phase II/III study of buntanetap, an oral drug designed to combat Alzheimer's Disease (AD) and Parkinson's Disease (PD). The medication works by binding to an iron-responsive element in the mRNA of neurotoxic proteins, thereby inhibiting their production and reducing amyloid beta, tau, alpha-synuclein, and TDP43.

In a randomized, double-blind, placebo-controlled trial, buntanetap demonstrated a statistically significant improvement in cognitive function, as measured by the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11), in mild AD patients. The study involved over 700 screened patients, with 353 enrolled and 325 completing the 12-week trial across 54 sites in the US. The patients had mild to moderate AD, with baseline Mini Mental State Examination (MMSE) scores ranging from 14 to 24.

The treatment's efficacy was highly correlated with the MMSE score at baseline, indicating that patients with milder AD responded better to buntanetap. Notably, the 30mg dose group showed a three-fold increase in the number of responders compared to the placebo group. Furthermore, the drug was well-tolerated, with a safety profile consistent with previous trials and no serious adverse events attributed to buntanetap.

The study also observed a reduction in plasma total Tau (tTau) levels post-treatment, aligning with earlier Phase IIa findings and supporting the drug's proposed disease-modifying effect. However, the study did not yield significant results for the Alzheimer’s Disease Cooperative Study Clinician’s Global Impression of Change (ADCS-CGIC) or the ADCS-ADL, likely due to the placebo's subjective nature and the trial's short duration.

Based on these findings, Annovis plans to conduct a pivotal Phase III trial focusing on biomarker-positive early AD patients. The company intends to engage with the FDA to discuss the next steps and will present the data at the AAIC2024 conference, aiming for publication in a peer-reviewed journal.

Buntanetap's potential as a safe and convenient oral therapy that could provide symptomatic relief while slowing disease progression is a significant milestone for Alzheimer's patients. The drug's novel mechanism of action targets multiple neurotoxic proteins, offering a unique approach to treating neurodegeneration. Annovis Bio, headquartered in Malvern, Pennsylvania, is dedicated to developing therapies that can restore axonal and synaptic activity, with the ultimate goal of treating memory loss and dementia associated with AD and PD.

The study's success underscores the rapid advancements in the AD biomarker field. The use of plasma biomarkers, which became commercially available in 2024, has been shown to be as effective as traditional methods like CSF and PET scans, providing a more accessible means of diagnosis and tracking treatment efficacy.

In summary, the Phase II/III study of buntanetap has shown positive results in improving cognition and reducing neurotoxic proteins in mild AD patients, setting the stage for a more extensive and longer-term Phase III trial to further validate these findings and explore the drug's potential as a disease-modifying therapy.