Posiphen (buntanetap) / Annovis Bio - LARVOL DELTA

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

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

Clinical highlights (GlobeNewswire) - "Annovis’ pivotal Phase 3 study in early AD (NCT06709014) is advancing rapidly, with 76 U.S. sites secured and 46 currently enrolling patients. The remaining sites are expected to begin enrollment shortly...The pivotal Phase 3 trial has attracted strong participation, with 38 patients already receiving buntanetap or placebo and nearly 200 more in screening – a number that continues to grow each day – with screen failure rate being as expected at 50%."

Trial status • Alzheimer's Disease

Annovis to Attend the AAIC 2025 with Four Poster Presentations (GlobeNewswire) - "Annovis Bio, Inc...announced its senior management will attend the Alzheimer’s Association International Conference (AAIC), taking place July 27–31, 2025, in Toronto, Canada. The Company will present four scientific posters highlighting advances of Alzheimer’s clinical program and pharmacokinetic characterization of its lead drug candidate, buntanetap."

Clinical protocol • P3 data • Alzheimer's Disease • Parkinson's Disease

Annovis Bio Launches Phase 3 Alzheimer’s Trial, Expands Research Efforts (City Buzz) - "Annovis Bio Inc. has advanced its Alzheimer’s disease research by launching a comprehensive Phase 3 clinical trial targeting early-stage patients. The trial, which began in the first quarter of 2025, will enroll up to 760 participants to evaluate the effectiveness of buntanetap over an 18-month period."

Trial status • Alzheimer's Disease

HOW THE THERAPEUTIC APPROACH TO EARLY PARKINSON'S DISEASE WILL CHANGE IN THE NEXT FUTURE (ADPD 2025) - "Levodopa remains the most efficacious drug, a better preparation of levodopa like IPX 203 can ensure more stable plasma levels of Levodopa...Tavapadon is a new dopamine agonist stimulating D1-D5 receptors which concluded the phase III. Other compounds such as CVN424 (Cerevance) orally active and selective GPR6 inverse agonist, piperamat (IRLAB 752) a cortical enhancer to improve balance, Clenbuterol/Nadolol for cognition, mesdopetam a D3 antagonist are under investigation...These include the monoclonal antibody prasinezumab, UCB0599 and buntanetap small-molecules α-synuclein aggregation inhibitor, the vaccine ACI-7104.056 by AC immune...The LRKK2 kinase inhibitor BIIB122/DNL151 is in phase IIb in PD. BIAL BIA 28-6156 activator of the GCase enzyme is under investigation in patients with GBA mutation. The combination of symptomatic and disease modifying therapy, the use of accurate biomarkers and more precise treatment will be the future in the treatment of PD."

CNS Disorders • Movement Disorders • Parkinson's Disease • GBA

APOE4 AND BUNTANETAP IN PHASE II/III ALZHEIMER'S PATIENTS (ADPD 2025) - "We will conduct an additional phase III study in biomarker-positive mild AD patients for 6-month to confirm the safety, efficacy, and symptomatic efficacy of buntanetap and an 18-month study to show potential disease-modification. We further want to evaluate the relation of buntanetap with APOE4 carriers and non-carriers."

Clinical • P2/3 data • Alzheimer's Disease • CNS Disorders • Inflammation • APOE • APP • TARDBP

BUNTANETAP IMPROVES EARLY PARKINSON'S PATIENTS' COGNITION AND MOTOR FUNCTIONS IN A PHASE 3 STUDY (ADPD 2025) - P1/2, P3 | "Buntanetap promises to be the first drug to improve both cognitive and motor functions in PD patients and improve cognition in AD patients. The company plans to submit the data to the FDA to agree on a path forward to NDA."

Clinical • P3 data • Alzheimer's Disease • CNS Disorders • Dementia • Movement Disorders • Parkinson's Disease