Posiphen (buntanetap) / Annovis Bio - LARVOL DELTA

Annovis Announces Partnership with Weave Bio, AI Regulatory Platform, in Preparation of NDA for Buntanetap in Alzheimer’s Disease (The Manila Times) - "Under the collaboration, Annovis will use Weave for drafting, reviewing and managing the NDA documents as the Company heads toward a 6-month top-line data readout from the pivotal Phase 3 AD trial - the data that will form the basis of the submission. Annovis’ regulatory and clinical teams will retain full responsibility for content, verification and final approval of every document submitted to the U.S. Food and Drug Administration (FDA)...The collaboration follows the completion of enrollment in Annovis’ pivotal Phase 3 AD study (NCT06709014), which enrolled 862 biomarker-confirmed patients, exceeding the original target of 760. The Company aims to reach the database lock for the 6-month treatment period in December 2026, followed by the top-line symptomatic data announcement in March 2027."

Licensing / partnership • P3 data: top line • Trial status • Alzheimer's Disease

Annovis to Host Corporate Update Webinar on September 2, 2026 (The Manila Times) - "The webinar will provide an overview of the Company’s recent progress, ongoing clinical programs, and upcoming milestones...'Several key milestones have been reached: our pivotal Phase 3 AD trial is fully enrolled, and preparations are already underway for the top-line data readout and regulatory submissions, both expected in 2027. We also plan to continue our AD program into an open-label study to generate long-term safety data for buntanetap, with first patients joining in October 2026. On the PD side, the open-label study is well underway, and discussions with Key Opinion Leaders and the FDA are ongoing to initiate the Parkinson's disease dementia program.'"

Clinical • FDA filing • New trial • Alzheimer's Disease • Parkinson's Disease

Annovis Provides Corporate Updates and Second Quarter 2026 Financial Results (The Manila Times) - "Enrollment: The trial is fully enrolled with 850 patients, exceeding the original target enrollment number of 760 patients...Timeline: The Company plans a database lock for the 6-month analysis in Q1 2027, with the top-line symptomatic data readout anticipated in the same quarter. The disease-modifying data readout is expected a year later....Alzheimer’s disease - OLE study: Start: The AD OLE study is expected to initiate in October 2026....Aim and patients: The AD OLE study will allow patients who are currently in the pivotal Phase 3 trial to receive buntanetap after completing their 18-month treatment period. Patients from both arms - buntanetap and placebo - will be allowed to join."

Enrollment closed • P3 data: top line • Trial status • Alzheimer's Disease

Parkinson’s disease - OLE study (The Manila Times) - "Enrollment: The study has so far enrolled 266 patients toward its estimated enrollment goal of 500. It accepts participants who were in prior Annovis’ clinical trials as well as new patients who have deep brain stimulation (DBS); Site activation: 26 clinical sites have been activated across the US."

Trial status • Parkinson's Disease

An Open-label Long-term Safety Study of Buntanetap in Participants With AD (clinicaltrials.gov) - P2/3 | N=400 | Not yet recruiting | Sponsor: Annovis Bio Inc.

New P2/3 trial • Alzheimer's Disease • CNS Disorders • Dementia

Clinical trial design and baseline characteristics of buntanetap's pivotal study in treating early Alzheimer's patients (CTAD 2026) - No abstract available

Clinical • Alzheimer's Disease • CNS Disorders

Analysis of the Efficacy of Acetylcholinesterase Inhibitors in the Treatment of Alzheimer's Disease, Literature Review. (PubMed, Int J Mol Sci) - "Evidence from key trials indicates that standard AChEIs induce significant cognitive stabilization compared to placebo, with rivastigmine maximizing daily living parameters via transdermal delivery...Conversely, emerging agents like huperzine A and the translation-blocker Posiphen demonstrate disease-modifying potential by modulating CSF biomarkers associated with amyloid and tau proteins. Clinically, while traditional regimens are limited by gastrointestinal toxicities, transitioning toward innovative multi-target structures represents a necessary shift to address both cognitive decline and neurodegeneration."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • Pain

Annovis Reaches Full Enrollment in Pivotal Phase 3 Trial of Buntanetap for Early Alzheimer’s Disease (The Manila Times) - "With the last patient expected to complete the 6-month treatment period in January 2027, followed by data cleaning and analysis, Annovis anticipates the following near-term milestones: Q1 2027: 6-month symptomatic top-line data readout; Q1 2028: 18-month disease-modifying top-line data readout; Regulatory submissions: The Company has already begun preparations for NDA submissions to the U.S. Food and Drug Administration (FDA), building on guidance received during prior FDA interactions, to position Annovis for submission shortly after each respective readout."

Enrollment closed • P3 data: top line • Trial completion date • Alzheimer's Disease

Efficacy and Safety of phenserine and its enantiomer, buntanetap (Posiphen) in treatment of Alzheimer's disease, a systematic review and meta-analysis (EAN 2026) - No abstract available

Retrospective data • Review • Alzheimer's Disease • CNS Disorders

A Conjugate of Aminoadamantane and Tetrahydro-γ-Carboline Inhibits Accumulation of Mutant α-Synuclein A53T in the Cellular Model of Proteinopathy. (PubMed, Biochemistry (Mosc)) - "This study evaluates the anti-aggregation properties of EC3222x, a conjugate of pharmacophoric fragments of amantadine and a fluorinated derivative of tetrahydro-γ-carboline...Its efficacy was comparable to that of SynuClean-D and Buntanetap, known inhibitors of α-synuclein aggregation...Importantly, EC3222x did not affect the accumulation of another aggregation-prone protein, TDP-43, in a similar cellular model, indicating its specificity for α-synuclein. These findings suggest that EC3222x may represent a promising candidate for the development of therapeutic agents targeting synucleinopathies."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease • Movement Disorders • Neuroblastoma • Oncology • Parkinson's Disease • Proteinopathy • Solid Tumor • TARDBP

Annovis Announces Pricing of $15.0 Million Public Offering of Common Stock and Accompanying Warrants (The Manila Times) - "Annovis intends to use the net proceeds from the offering for the continued clinical development of its lead compound buntanetap in clinical studies for Alzheimer’s disease (AD) and Parkinson’s Disease (PD) and for working capital and general corporate purposes."

Financing • Alzheimer's Disease • Parkinson's Disease

A Double-blind Dual Study Assessing Safety and Efficacy of Buntanetap in Participants With Early AD (clinicaltrials.gov) - P3 | N=760 | Active, not recruiting | Sponsor: Annovis Bio Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders

Alzheimer’s disease – pivotal Phase 3 trial (NCT06709014) (GlobeNewswire) - "Enrollment: 85% of patients enrolled; Screening: On May 15, 2026, Annovis closed enrollment to new participants after reaching a sufficient number of patients in screening to meet the trial's enrollment goal....Phase 3 AD study: Annovis expects to reach full enrollment in summer 2026. The symptomatic data readout is anticipated approximately 6 months after the last patient is dosed. The disease-modifying data readout is anticipated 18 months after the last patient is dosed."

Enrollment status • P3 data • Alzheimer's Disease

Upcoming milestones (GlobeNewswire) - "NDA pathway: Based on the Phase 3 AD study outcomes, Annovis plans to engage with the FDA regarding a regulatory NDA submission for buntanetap as a symptomatic treatment for AD in early 2027 and as a disease-modifying treatment in early 2028."

FDA filing • Alzheimer's Disease

Parkinson’s disease – OLE study (NCT07284784) (GlobeNewswire) - "Enrollment: 40% of patients enrolled....Annovis expects to complete enrollment for the PD OLE study in the fourth quarter of 2026."

Enrollment status • P2/3 data • Parkinson's Disease

Buntanetap is currently being investigated in a pivotal Phase 3 clinical trial enrolling pTau217 biomarker-positive patients with early AD (MMSE 20–28) (NCT06709014). (GlobeNewswire) - "The trial is designed to replicate and extend the findings of the Phase 2/3 study, evaluating the efficacy of buntanetap at 6 and 18 months, measuring symptomatic and potential disease-modifying benefits, respectively. The study is nearing full enrollment, with 80% of patients already enrolled."

Trial status • Alzheimer's Disease

Annovis Publishes Phase 2/3 Alzheimer's Trial Results in Nature Portfolio (GlobeNewswire) - "The study demonstrated that buntanetap was safe and well-tolerated across all disease stages and dose levels. Notably, safety was also assessed in ApoE4 carriers, the most genetically at-risk population for AD, with no increase in adverse events compared to non-carriers and to placebo...Biomarker analyses further revealed reductions in neurotoxic proteins TDP-43 and tau, in the markers of neuroinflammation, including IL-5, IL-6, S100A12, IFN-γ, and IGF1R, as well as in the marker of neurodegeneration, neurofilament light chain (NfL), pointing to potential disease-modifying activity."

P2/3 data • Alzheimer's Disease

Annovis Closes $10 Million Offering, Extending Cash Runway Through Phase 3 Alzheimer's Disease 6-Month NDA Submission (The Manila Times) - "Financing secures path to first NDA submission for buntanetap; 6-Month symptomatic data readout anticipated Q1 2027...Proceeds from this offering will primarily support the advancement of buntanetap through the pivotal Phase 3 AD trial (NCT06709014), which is approaching full enrollment with 75% of participants already enrolled...In parallel, Annovis is conducting an open-label extension (OLE) study in PD patients (NCT07284784), which has enrolled 28% of participants since its inception in February 2026."

FDA filing • Financing • P3 data • Trial status • Alzheimer's Disease • Parkinson's Disease

Annovis Announces $10 Million Underwritten Offering of Common Stock and Accompanying Warrants (The Manila Times) - "Annovis intends to use the net proceeds from the offering for the continued clinical development of its lead compound buntanetap in a Phase 3 study for Alzheimer’s disease, and for working capital and general corporate purposes."

Financing • Alzheimer's Disease

Annovis Secures U.S. Patent for Buntanetap in the Prevention and Treatment of Neurological Injuries Caused by Brain Infections (Yahoo Finance) - "...Patent No. 12,582,632 B2, covering prevention and treatment of neurological injuries arising from brain infections through the administration of buntanetap or related compounds...The newly issued patent covers administration of buntanetap and related compounds across the full spectrum of infectious agents implicated in neurological injury, reflecting the breadth of microbial threats the brain may encounter. The patent includes claims for preventive use of buntanetap in healthy individuals who are at risk of exposure as well as for reversal of neurological damage in individuals already affected by these infections. The current patent protection extends through 2044."

Patent • Alzheimer's Disease

Annovis Publishes Historical Review of Buntanetap in The Scientist (GlobeNewswire) - "As Annovis advances its clinical pipeline with both AD and PD trials actively enrolling patients, this historical review offers important context for understanding buntanetap's scientific journey and its significance in the neurodegenerative disease space. The article traces the compound's development from its 19th-century origins and the identification of its mechanism of action to the search for the correct chemical form and its progression through clinical trials...Buntanetap is currently being evaluated in a pivotal Phase 3 study in early AD (NCT06709014), with 70% patients enrolled, and in an open-label extension study in PD (NCT07284784), with 20% patients enrolled."

Enrollment status • Review • Alzheimer's Disease • Parkinson's Disease

BUNTANETAP TREATMENT IN PARKINSON'S DISEASE PATIENTS WITH MCI OR MILD DEMENTIA (ADPD 2026) - "Distinct patterns of cognitive decline were demonstrated between PD patients with and without amyloid co-pathology. Buntanetap treatment significantly improved cognitive function in participants with amyloid co-pathology and improved MDS-UPDRS Part III regardless of amyloid burden. Further biomarker data supports buntanetap's mechanism of action."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Huntington's Disease • Movement Disorders • Parkinson's Disease • APP

A DUAL 6-MONTH & 18-MONTH RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND, CLINICAL TRIAL INVESTIGATING EFFICACY AND SAFETY OF BUNTANETAP IN EARLY ALZHEIMER'S PARTICIPANTS (ADPD 2026) - P2/3, P3 | "In summary, the Phase 3 study in early AD is ongoing. We will share our progress to date, along with key insights and lessons learned throughout the conduct of the trial."

Clinical • Alzheimer's Disease • CNS Disorders • Inflammation

CAN WE PREVENT PARKINSON'S DISEASE? (ADPD 2026) - "Promising results come from the prasinezumab and buntanetap trials and other drugs are coming to reduce alfa syn toxicity but also for genetic forms and enzyme iperactivity. However today it is possible to reduce the risk of PD , increasing and encouraging physical exercise, curing pre-diabetes, reduce the exposition to pesticides and pollution, reduce the intake of ultra processed food."

CNS Disorders • Melanoma • Metabolic Disorders • Movement Disorders • Parkinson's Disease • Solid Tumor • Type 2 Diabetes Mellitus • Vascular Neurology

Annovis Partners with NeuroRPM to Deploy AI-Powered Digital Biomarker Technology in Parkinson's Disease Study (GlobeNewswire) - "Annovis Partners with NeuroRPM to Deploy AI-Powered Digital Biomarker Technology in Parkinson's Disease StudyAnnovis’ recently launched open-label study in PD patients (ANVS-25002) is currently enrolling participants across the 25 sites in the United States to test buntanetap for the duration of 36 months. As part of the initiative to advance management, monitoring, and data collection, the Company has entered into a partnership with NeuroRPM to introduce the first FDA-cleared AI-enabled medical device that allows to monitor the primary PD symptoms – bradykinesia, tremor, and dyskinesia. This information will serve as a digital biomarker, capturing real-time evidence of how disease symptoms change during the course of the study....The ANVS-25002 study has currently enrolled 90 out of the estimated total 500 patients."

Trial status • Parkinson's Disease