Annovis Bio, Inc.

Our Company is a late-stage clinical drug platform company focused on neurodegeneration, specifically Alzheimer's disease (AD) and Parkinson's disease (PD). The company is developing its main product candidate, buntanetap, which is designed to treat AD, PD, and potentially other chronic neurodegenerative diseases. Buntanetap is a synthetically produced small molecule that is taken orally and can penetrate the brain. Studies have shown that buntanetap inhibits the creation of neurotoxic proteins—APP/Aβ (APP), tau/phospho-tau (tau), α-Synuclein (αSYN), and TDP43—which are major causes of neurodegeneration. High levels of these proteins impair axonal transport, which is vital for communication within and between nerve cells. When this communication is disrupted, the immune system attacks and eventually kills nerve cells. In completed clinical studies with AD and PD patients, and pre-clinical studies in mice and rats, buntanetap was observed to lower neurotoxic protein levels, leading to improved axonal transport, reduced inflammation, less nerve cell death, and improved affected function. Currently, the company is conducting two clinical studies: a pivotal Phase 3 study in early AD (NCT06709014) and an open-label extension (OLE) study in PD (NCT07284784). A third study for Parkinson's disease dementia (PDD) is planned. In February 2025, the FDA-cleared pivotal Phase 3 AD Trial began. This is a randomized, double-blind, placebo-controlled, multicenter Phase 3 study involving 760 early AD patients. The trial has two parts: a 6-month treatment period to confirm buntanetap's symptomatic efficacy, followed by an additional 12 months of treatment to demonstrate potential disease-modifying efficacy at 18 months. Patients remain blinded for the additional 12 months after the initial 6-month period. The symptomatic portion of the trial, if well-designed and executed, may support a New Drug Application (NDA) filing, potentially within one year of the 6-month treatment period's completion. A similar pathway for a second NDA for disease modification may be possible after 18 months, supported by a well-designed and executed long-term portion of the trial.