Posiphen (buntanetap) / Annovis Bio - LARVOL DELTA

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

Annovis Provides Corporate Updates and Reports Fiscal Year 2025 Financial Results (GlobeNewswire) - "As of March 2026, Annovis has enrolled 65% of the target participant population for its pivotal Phase 3 AD clinical trial across 83 clinical sites in the United States."

Enrollment status • Alzheimer's Disease

Annovis Announces Two Presentations at the AD/PD 2026 International Conference (GlobeNewswire) - "The presentations will highlight clinical data supporting buntanetap's treatment effect in PD with a particular focus on cognition and biomarker findings, and provide an update on the ongoing pivotal Phase 3 trial in early AD."

Biomarker • Clinical data • Trial status • Alzheimer's Disease • Dementia • Parkinson's Disease

Annovis Secures DSMB Approval to Advance Pivotal Phase 3 Trial of Buntanetap in Alzheimer’s Disease (Businesswire) - "During the open session, Annovis presented an overview of the trial status, including enrollment progress, adverse events, and study timelines...Moreover, the 6-month safety data in Alzheimer’s patients were consistent with those observed in Parkinson’s patients at the same time point. Subsequent safety evaluations are planned at 12 and 18 months....The pivotal Phase 3 AD clinical trial of buntanetap (NCT06709014) is currently recruiting patients across the United States and is now 40% complete. The first symptomatic efficacy readout is anticipated in early 2027, followed by a disease-modifying readout expected in early 2028."

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

A Study of Buntanetap in Participants With PD (clinicaltrials.gov) - P2/3 | N=500 | Recruiting | Sponsor: Annovis Bio Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Movement Disorders • Parkinson's Disease

Drug Development. (PubMed, Alzheimers Dement) - "The reviewed studies suggest that Phenserine and Posiphen may improve cognitive function and reduce Alzheimer's disease biomarkers and markers of neuroinflammation present in cerebrospinal fluid. However, small sample sizes and variability in dosages limit the generalizability of these findings. Future trials with larger cohorts and standardized protocols are needed to validate these results."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dermatology • Inflammation • Movement Disorders • Pain • Parkinson's Disease • APP

Developing Topics. (PubMed, Alzheimers Dement) - "These findings support the continued development of Form B for future clinical use, as it combines enhanced solid-state stability with a preserved PK profile essential for buntanetap's therapeutic efficacy. Form B has also been approved by the FDA for all future clinical studies including the ongoing pivotal Phase 3 Early AD trial."

Journal • Alzheimer's Disease • CNS Disorders • Movement Disorders

Developing Topics. (PubMed, Alzheimers Dement) - "This Phase III trial is being conducted to determine whether buntanetap, which inhibits the translation of neurotoxic aggregating proteins, is able to a) duplicate the efficacy seen in our phase IIb study and improve symptomatic effects and b) show potential disease-modifying effects...Tables will be featured on the poster showing the status of the following per July 2025: • An update of the recruiting sites and locations • A US map with all site locations shown as pins, to highlight regional study access • pTau217 selection inclusion/exclusion figures • Current enrollment versus Target enrollment of 760 participants • Actual monthly participant accrual versus projected monthly accrual • Estimated timelines for the 6-month and 18-month end of study data readouts • Screen failure rate with breakdown of screen failure reasons In summary, we will show the ease of using plasma biomarkers to determine the presence of AD."

Biomarker • Journal • Alzheimer's Disease • CNS Disorders

Developing Topics. (PubMed, Alzheimers Dement) - "Based on clinical and biomarker data from our previous studies, we designed a novel Phase 3 study to validate symptomatic improvement and potentially show disease-modification effects of buntanetap in treating early AD patients."

Biomarker • Journal • Alzheimer's Disease • CNS Disorders • Inflammation • APP • TARDBP

Developing Topics. (PubMed, Alzheimers Dement) - P2/3, P3 | "Analyses from two RCTs confirmed similar mean Cmax, Tmax, and AUC0-t across doses of 7.5mg-30mg buntanetap in both patients with early AD and PD. These data confirm fast plasma peak, as seen in all of our previous studies, and dose-dependent exposure to drug, supporting buntanetap's PK uniformity across AD and PD indications."

Journal • Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease

Annovis Announces Open-Label Extension Study for Parkinson's Disease Patients (Annovis Bio Press Release) - "Enrollment will begin in January 2026; Participants will be treated with buntanetap for 36 months; The study aims to enroll 500 patients...The OLE PD study represents an important step toward a future New Drug Application (NDA) submission by helping Annovis meet the FDA’s patient exposure requirements."

Trial status • Parkinson's Disease

A Study of Buntanetap in Participants With PD (clinicaltrials.gov) - P2/3 | N=500 | Not yet recruiting | Sponsor: Annovis Bio Inc.

New P2/3 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

Double 6/18-month Phase III study to reproduce symptomatic and potentially show disease-modifying efficacy of buntanetap in treating Alzheimer's disease (CTAD 2025) - No abstract available

Clinical • P3 data • Alzheimer's Disease • CNS Disorders

Amyloid Co-Pathology and Cognitive Decline in Buntanetap Treated Parkinson's Disease Dementia Patients (CTAD 2025) - No abstract available

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

Annovis To Present at the 2025 Annual Meeting of the Parkinson Study Group (Annovis Bio Press Release) - "The presentation will also debut a cross-study comparison of the completed trials, providing the most comprehensive look yet at cognitive outcomes across all tested indications by Annovis and highlighting the population that benefits most – patients with amyloid pathology."

Clinical data • Parkinson's Disease

Annovis Announces Two Presentations at the CTAD 2025 Conference (GlobeNewswire) - "The presentations will highlight progress across the Alzheimer’s and Parkinson’s programs, with a particular focus on recent biomarker data supporting the potential disease-modifying activity of buntanetap."

Biomarker • Clinical data • Alzheimer's Disease • Parkinson's Disease

Annovis Bio, Inc…announced that the U.S. Food and Drug Administration (FDA) has scheduled a Type C meeting in January 2026 to discuss the Company’s pathway for Parkinson’s disease dementia (PDD). (Annovis Bio Press Release) - "The upcoming meeting will focus on the clinical development pathway for buntanetap in PDD, a debilitating condition affecting approximately 30% of PD patients, with some reports suggesting that up to 80% develop dementia over the long term....The meeting agenda will include discussions on clinical trial design, patient population, and a potential approval route....Annovis also confirmed that its Phase 3 clinical trial in early AD continues to enroll patients according to plan, with full FDA agreement on all critical study parameters."

FDA event • Trial status • Dementia • Parkinson's Disease

Annovis Reports New Biomarker Data Linking Amyloid Co-Pathology to Accelerated Cognitive Decline in Parkinson's Patients (GlobeNewswire) - "Further analysis revealed that approximately 25% of them exhibited amyloid co-pathology and experienced more pronounced cognitive decline over the course of the study, which was counteracted and reversed by buntanetap...As anticipated, buntanetap treatment led to significant cognitive improvement in Parkinson’s patients with amyloid co-pathology. This response was further supported by measurable reductions in pTau217, total tau, and brain-derived (BD) tau – well-established biomarkers of neurodegeneration used in AD....The full biomarker data will be presented at the Clinical Trials on Alzheimer's Disease (CTAD) conference in San Diego, December 1-4, 2025. Additional details regarding the presentation will be announced closer to the conference date via a separate news release."

P3 data • Parkinson's Disease

Annovis Achieves Significant Milestones and Sustains Strong Progress in Phase 3 Alzheimer’s Program (GlobeNewswire) - "All 84 clinical sites across the U.S. are fully activated, enrolling, and treating patients...This milestone is complemented by another achievement: the first group of patients has completed the 6-month treatment period, keeping the Company on track to deliver symptomatic data in the second half of 2026...The pivotal Phase 3 study (NCT06709014) aims to enroll a total of 760 patients with early AD and biomarker-confirmed amyloid pathology....Participants who have completed the initial 6-month period seamlessly continue blinded treatment for additional 12 months toward the study completion."

P3 data • Trial status • Alzheimer's Disease

Annovis Announces Novel Biomarker Data in Alzheimer’s Patients Supporting Buntanetap’s Potential as a Disease-Modifying Treatment (GlobeNewswire) - "The analysis of patient samples from the Phase 2/3 AD study (NCT05686044) revealed that buntanetap targets key biomarkers of neuroinflammation and neurodegeneration. The following inflammatory markers were reduced in the treatment group vs placebo: IL-5, IL-6, S100A12, IFN-γ, and IGF1R. These molecules are known to drive pro-inflammatory responses in AD and have been associated with elevated amyloid-β burden. By modulating these pathways, buntanetap may reduce chronic inflammation and attenuate amyloid accumulation. Equally compelling was the observation that buntanetap decreased levels of NFL, a protein fragment released from damaged neurons, indicating improved cellular integrity and neuronal health....The full biomarker data will be presented during the Clinical Trials on Alzheimer's Disease (CTAD) conference in San Diego, taking place December 1-4, 2025."

Biomarker • P2/3 data • Alzheimer's Disease

Pharmacokinetics of Novel Crystalline Buntanetap in Mice, Dogs, and Humans. (PubMed, Biomolecules) - "Consistent with previous reports, Form A and Form B alike reached fast peak plasma concentrations (<2 h), demonstrated efficient partitioning into brain tissue, and were fully cleared by 12 h post-dose. Furthermore, metabolic profiling showed that both forms produced identical PK profiles for the primary metabolites, N1- and N8-norbuntanetap, confirming that Form B retains the established metabolic characteristics of Form A. These findings support the continued development of Form B for future clinical use, as it combines enhanced solid-state stability with a preserved PK profile essential for buntanetap's therapeutic efficacy."

Journal • PK/PD data • Preclinical • Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease

Annovis Reports Peer-Reviewed Publication Highlighting Pharmacokinetics of Novel Crystal Buntanetap (GlobeNewswire) - "Recently, the Annovis team identified a new dihydrate crystal, which incorporates two moles of water in its structure and offers greater stability. This publication examines how the new crystal form behaves in the body following oral administration, focusing on absorption and clearance. The findings confirm that crystal buntanetap preserves the PK profile and metabolism of the original form, which are essential for the drug’s therapeutic efficacy....The new crystal buntanetap is currently being used in the pivotal Phase 3 clinical trial (NCT06709014) in patients with early AD, which is actively enrolling participants across the U.S. The study is designed to deliver two key readouts: symptomatic (Fall 2026) and disease-modifying (Fall 2027)."

Enrollment status • P3 data • Preclinical • Alzheimer's Disease