Posiphen (buntanetap) / Annovis Bio - LARVOL DELTA

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

Annovis to Attend AD/PD 2025 with Extensive Scientific Program (GlobeNewswire) - "'At this meeting, we will present comprehensive data from our latest Phase 3 PD and Phase 2/3 AD studies. For Parkinson’s, we will take a deeper look into the cognitive response, while for Alzheimer’s, we will dive into the advantages of buntanetap for APOE4 carriers, addressing a pressing challenge in existing AD therapies'."

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

Annovis Joins Experts at Drug Development Summit to Redefine Parkinson's Treatment (GlobeNewswire) - "Annovis Bio Inc...will participate at the 13th Alzheimer’s & Parkinson’s Drug Development Summit happening on March 18-20 in Boston, MA....'We will present the lessons learned from our AD and PD clinical trials, delve into buntanetap’s mechanism of targeting alpha-synuclein, and discuss ways to usher in a new era for Parkinson’s treatment'."

Clinical data • Parkinson's Disease

Annovis to Present at Oppenheimer’s 35th Annual Healthcare Life Sciences Conference (GlobeNewswire) - "Annovis Bio Inc...today announced that its CEO, Maria Maccecchini, Ph.D., will present at the Oppenheimer's 35th Annual Healthcare Life Sciences Conference...Dr. Maccecchini will discuss the Company’s latest advancements, highlighting the progress of the pivotal Phase 3 trial in early AD and strategic initiatives toward a New Drug Application (NDA) for buntanetap as both a symptomatic and potentially disease-modifying treatment."

Trial status • Alzheimer's Disease

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

Enrollment open • Alzheimer's Disease • CNS Disorders

Annovis Announces First Patients Entered into Pivotal Phase 3 Study of Buntanetap for Early Alzheimer’s Disease (GlobeNewswire) - "Annovis Bio Inc...today announced that the first two patients have been entered into the pivotal Phase 3 study evaluating buntanetap in early AD....Annovis anticipates enrolling over 750 participants across ~100 sites in the United States."

Trial status • Alzheimer's Disease

Annovis Bio, Inc. Announces Proposed Public Offering (GlobeNewswire) - "Annovis Bio, Inc...today announced that it intends to offer to sell common stock and warrants in an underwritten public offering. All of the common stock and warrants are to be sold by the Company....The Company intends to use the net proceeds from the offering primarily for working capital and general corporate purposes, including the continued clinical development of the Company’s lead compound, Buntanetap."

Financing • Alzheimer's Disease • CNS Disorders

Annovis Granted U.S. Patent for Treatment and Prevention of Acute Brain or Nerve Injuries Securing Global Protection (GlobeNewswire) - "Annovis Bio Inc...today announced it was granted the U.S. patent covering methods for the treatment and prevention of acute brain or nerve injuries using buntanetap. This newly issued patent is based on buntanetap’s ability to reduce neurotoxicity and mitigate neurodegenerative processes, which can be applicable to such conditions as stroke, ischemia, traumatic brain injury, micro infarcts, and other forms of acute injuries. The patent has already been granted in the EU, Japan, and worldwide."

Patent • CNS Disorders

FDA Accepts Final Protocol for Pivotal Phase 3 Alzheimer’s Disease Study, Streamlining Development Pathway (GlobeNewswire) - "Annovis Bio Inc...today announced that the FDA has accepted an updated protocol for the pivotal Phase 3 AD study, which is slated to begin in January 2025."

FDA event • New P3 trial • Alzheimer's Disease

Developing Topics. (PubMed, Alzheimers Dement) - "This short study shows a symptomatic effect with a possible disease-modification trend according to the tau data. The next study will have a longer duration, improved design and be statistically powered to validate symptomatic improvement and disease-modification."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Inflammation • APP

A 6-month & 18-month Randomized Dual Study Assessing Safety and Efficacy of Buntanetap in Participants with Early AD (clinicaltrials.gov) - P3 | N=760 | Not yet recruiting | Sponsor: Annovis Bio Inc.

New P3 trial • Alzheimer's Disease • CNS Disorders

Annovis Bio Reports Third Quarter Financial Results and Provides Business Update (GlobeNewswire) - "Clinical Updates...The 6-month symptomatic study is expected to begin in Q1 2025...The company has an adequate runway for all Phase 3 preparatory studies and for entering the pivotal Phase 3 AD study in Q1 2025."

Commercial • New P3 trial • Alzheimer's Disease • CNS Disorders