Annovis’s Buntanetap Shows Dose-Dependent Cognitive Gains, Biomarker Reductions; Phase 3 80% Enrolled
Annovis’s Phase 2/3 study in 351 mild to moderate AD patients showed dose-dependent, statistically significant ADAS-Cog11 gains in pTau217-positive subjects alongside reductions in tau, TDP-43, neuroinflammation markers and NfL, with no safety issues in ApoE4 carriers. These results support its pivotal Phase 3 trial, now 80% enrolled.
1. Phase 2/3 Study Design and Enrollment
The randomized, double-blind, placebo-controlled trial enrolled 351 patients with mild to moderate Alzheimer’s disease for 12 weeks, testing 7.5 mg, 15 mg and 30 mg daily doses of buntanetap. Participants included pTau217 biomarker–positive subjects and allowed continuation of existing symptomatic therapies.
2. Cognitive Efficacy Outcomes
In pTau217-positive mild AD patients (MMSE 21–24), buntanetap demonstrated dose-dependent, statistically significant ADAS-Cog11 improvements versus placebo, with the 30 mg dose delivering the strongest and most consistent benefits across age, BMI, sex, ethnicity and ApoE4 status.
3. Biomarker and Safety Findings
Buntanetap treatment led to reductions in neurotoxic proteins tau and TDP-43, decreased levels of IL-5, IL-6, S100A12, IFN-γ and IGF1R, and lowered neurofilament light chain. Safety was favorable at all doses and stages, with no increased adverse events in ApoE4 carriers and compatibility with concurrent AD medications.
4. Pivotal Phase 3 Trial Advancement
The ongoing pivotal Phase 3 study in pTau217 biomarker–positive early AD (MMSE 20–28) is nearing full enrollment at 80% and will assess symptomatic effects at 6 months and potential disease-modifying benefits at 18 months to confirm Phase 2/3 findings.