NYSE: ANVS

This pivotal Phase 3 AD Trial will utilize standard clinical outcome measures including Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (“ADAS-Cog13”) and Alzheimer’s Disease Cooperative Study-Instrumental Activities of Daily Living Scale (“ADCS-iADL”). Volumetric MRI imaging and certain plasma biomarkers will also be assessed, including p-tau217 levels, leveraging recent biomarker assay advances in AD to better diagnose Alzheimer’s patients and disease progression.

In January of 2026, we began an OLE study to evaluate the long-term safety and efficacy of buntanetap in PD patients. The study aims to enroll 500 patients, who will be treated with buntanetap for 36 months or until buntanetap is on the market. The patient population consists of two cohorts: cohort 1 with invited participants from prior clinical studies and cohort 2 with patients who did not take part in earlier trials but have been receiving deep brain stimulation (“DBS”) for at least 12 months following successful surgery. The OLE PD study represents an important step toward a future NDA submission by helping meet the FDA patient exposure requirements.

In 2025, we further discussed a study in PDD with the FDA. After showing that the amyloid-positive PD population with the Mini Mental State Examination (“MMSE”) score above 20 responds exceptionally well to our drug, buntanetap, we received approval to proceed. We are refining the proposed protocol for the PDD program and will initiate the study contingent on additional funding.

To date, we have concluded 12 clinical studies, most of which were in healthy volunteers to assess safety, food effect, pharmacokinetics (“PK”), distribution, etc. The most important clinical studies are described below:

In 2021, we completed two Phase 1/2 clinical studies: one in 14 early AD patients and one in 54 early PD patients (together, the “AD/PD Trials”). In the AD/PD Trials, early AD patients were defined as those with a MMSE score between 19 and 28 and early PD patients as those at Hoehn & Yahr stages 1, 2 or 3. MMSE is a brief screening instrument used to assess cognitive function, with total scores ranging from 0 to 30 and a lower score indicating greater disease severity, while the Hoehn & Yahr scale is a medical assessment used to measure staging of the functional disability associated with PD where a higher stage indicates greater disease severity. In collaboration with the Alzheimer’s Disease Cooperative Study (“ADCS”), we also conducted a trial in 16 early AD

patients (the “ADCS Trial”). In the ADCS Trial, early AD patients were defined as those patients with a MMSE score between 19 and 28. At the completion of the ADCS Trial, the data showed that buntanetap acts as a translational inhibitor in humans just like in animals, and we further observed that there was statistical improvement in cognition in early AD patients, just like in the AD/PD Trials.

All three clinical trials above were double-blind and placebo-controlled. We designed the studies by applying our understanding of the underlying neurodegenerative disease states and measured both target and pathway validation in the spinal fluid of patients to determine whether patients’ underlying disease condition improved following treatment. In addition to meeting their primary endpoints of safety and tolerability and secondary endpoint of PK of buntanetap, our AD/PD Trials also met exploratory endpoints of measures of biomarkers and improvements in cognition in AD patients as well as function in PD patients. We believe that the AD/PD Trials represent the first double-blind, placebo-controlled study that showed improvements in AD patients, as measured by ADAS-Cog and in PD patients, as measured by Unified Parkinson’s Disease Rating Scale (“MDS-UPDRS” or “UPDRS”). ADAS-Cog is an assessment scale that measures cognitive functions and non-cognitive functions such as mood and behavior. More specifically, ADAS-Cog11 is the cognitive assessment scale used to measure areas commonly seen to decline in AD patients. It consists of 11 specific tasks such as word recall, comprehension, object-naming, etc., in order to produce a scale measurement. UPDRS Part II and III are composed of a 42-item rating scale designed to assess PD-related disability and impairment and also evaluate the activities of daily living and motor function.

Following completion of the AD/PD Trials, we submitted our data to the FDA and requested direction to further pursue the development of buntanetap in early PD patients. With the FDA’s guidance, we initiated a Phase 3 study in early PD patients in August 2022 (the “Phase 3 PD Trial”). In the Phase 3 PD Trial, early PD patients were defined as those at Hoehn & Yahr stages 1, 2 or 3 and OFF times of less than two hours per day. OFF time refers to periods when PD motor and/or non-motor symptoms occur between medication doses. We also submitted a proposed protocol for the treatment of moderate AD to the FDA, and after receiving permission to proceed, we initiated a Phase 2/3 study in mild to moderate AD patients in February 2023 (“Phase 2/3 AD Trial”). In the Phase 2/3 AD Trial, mild to moderate AD patients were defined as those with a MMSE score between 14 and 24. Our Phase 3 PD Trial and Phase 2/3 AD Trial each had built-in interim analyses.

Our Phase 3 PD Trial was completed on December 4, 2023, and we released the topline PD study efficacy data on July 2, 2024. The study data showed that in two subgroups, buntanetap improved UPDRS Part II, III, II+III and total. It also showed that in the entire intent to treat (“ITT”) population, buntanetap stopped the loss of cognition and that in the 12% of patients that already had cognitive issues, buntanetap improved cognition in a dose-dependent, statistically significant way. We asked the FDA for a Type C meeting to discuss the data and the continued development of buntanetap for Lewy body dementia. In response, we received a letter from the FDA saying that because Lewy body dementia is a challenging disease to treat and because there are no accepted end-points, they would like to discuss the two conditions — dementia with Lewy bodies and PDD — separately and independently. However, the FDA did approve a protocol for an OLE study in PD patients, consisting of two cohorts: cohort 1 with invited participants from prior clinical studies and cohort 2 with patients who did not take part in earlier trials but have been receiving DBS for at least 12 months following successful surgery.

Our Phase 2/3 AD Trial was completed on February 13, 2024, and on April 29, 2024, we announced topline efficacy data. The data showed that in early AD patients, buntanetap improved ADAS-Cog11 in a dose-dependent fashion and was statistically significant from placebo and from baseline.

On October 10, 2024, we met with the FDA in an end-of-phase 2 meeting to discuss the Phase 2/3 AD data and to agree on a regulatory path forward. Annovis and the FDA have aligned on a development path for buntanetap towards the filing of NDAs, one for short-term and one for long-term efficacy. During the end-of-phase 2 meeting for AD, the FDA raised no concerns with our data on buntanetap’s safety, including impact on liver enzymes, drug interactions, dose selection, PK and population PK. Further, the FDA confirmed that future development can proceed using the new crystal form of buntanetap.

We believe that we are the only company developing a drug for AD and PD that inhibits more than one neurotoxic protein and has a mechanism of action designed to restore nerve cell axonal and synaptic activity. By improving brain function, our goal is to treat memory loss and dementia associated with AD, as well as body and brain function issues associated with PD. Based on preclinical and clinical data collected to date, we believe that buntanetap has the potential to be the first drug to interfere with the underlying mechanism of neurodegeneration, potentially enabling buntanetap to be the only drug to improve cognition in AD and motor function in PD. The industry has historically encountered challenges in specifically targeting one neurotoxic protein, be it APP,

tau or αSYN, indicating that doing so does not change the underlying course of neurodegeneration. Our ultimate goal is to develop a disease modifying drug (“DMD”) for patients with neurodegeneration by leveraging our clinical and preclinical data, which shows inhibition of the most relevant neurotoxic proteins. Studies have found that AD and PD are the most common neurodegenerative diseases in the United States, and accordingly these diseases present two unmet needs of the aging population and two potentially large U.S. markets, when DMD is developed and approved.

Our leadership team has substantial experience and extensive industry knowledge and has been successful with respect to meeting clinical timelines, enrollment progression and data readouts.

Company Leadership

Maria L. Maccecchini, Founder, President and Chief Executive Officer, founded Annovis in May 2008 to develop improved therapeutics for neurodegeneration. She was previously the Founder and Chief Executive Officer of Symphony Pharmaceuticals, a biotech company that was sold to Transgenomic in 2001. Prior, she was the General Manager of Bachem Bioscience, the U.S. subsidiary of Bachem AG, Switzerland. Dr. Maccecchini completed one postdoc at Caltech and another at the Roche Institute of Immunology. Her Ph.D. in biochemistry is from the Biocenter of Basel with a two-year visiting fellowship at The Rockefeller University.

Mark Guerin, Chief Financial Officer, is a financial executive and leader with demonstrated expertise leading accounting, finance, human resources and IT activities in publicly-traded and venture-backed companies. He effectively directed, managed and performed a full scope of finance functions including public offerings, rights offering, registered direct offerings and more. Most recently, he worked as Chief Financial Officer at Onconova Therapeutics, now known as Traws Pharma, Inc. (Nasdaq: TRAW), where he supported several critical financing transactions, including a rights offering, public offerings, registered direct offerings and at-the-market offerings. Prior, he served as Vice President of Finance and Chief Financing Officer at Cardiokine, Inc. and as Director, Financial Reporting and Internal Controls at Barrier Therapeutics, Inc.

Cheng Fang, Senior Vice President, Research and Development, has broad scientific knowledge and over a decade of experience working in the field of neurodegenerative diseases. She previously worked at Clarivate Analytics and the Cornell Institute for Medical Research. As a Research Assistant Professor at Boston University, she designed projects that addressed prion diseases and AD. Dr. Fang has a Ph.D. in biology and neuroscience from Pennsylvania State University. She also holds a B.S. in biopharmaceutics from Nanjing University.

Eve Damiano, Senior Vice President, Regulatory, has spent over 35 years in the biotechnology sector, focusing on the definition and execution of regulatory strategies. Ms. Damiano has held various senior management positions throughout her career, with experience garnered at companies including Centocor, MedImmune, OraSure Technologies and Vicuron Pharmaceuticals. Ms. Damiano holds a track record in the definition and execution of regulatory strategies. She holds an M.S. from the Drexel University College of Medicine.

Sarah MacCallum joined the Company as Senior Clinical Project Manager in 2023. She was promoted to Director of Clinical Operations in 2024 and currently supports all clinical trial activities. She is an experienced Clinical Project Manager and Registered Nurse, who has spent over a decade building skills in clinical research on a foundation of direct patient care. Her clinical trial background includes neuro-oncology, breast and bowel cancer, cardiology, pediatric organ transplant and neuromuscular disorders. She has worked at the site, contract research organizations (“CRO”) and sponsor levels in various roles before joining the team as Senior Clinical Project Manager for Clinical Operations. Sarah received her B.S. in Nursing from Saint Louis University and a B.A. in English from The Ohio State University.

Mike Christie, Vice President, Process Chemistry, has spent over 40 years working in the pharmaceutical industry, with a focus on process chemistry research and development, pilot plant production and good manufacturing practice (“cGMP”) operations. He has held senior management positions in both large (SmithKline, Rhodia, Teva) and mid-size (Cephalon) companies, as well as being the founder of a company providing contract process research and development services (later acquired by ChiRex). Dr. Christie is co-author or co-inventor on several publications and patents. He earned his B.S. in chemistry from the University of Michigan and his Ph.D. from MIT.

Mechanism of Action

Our lead drug candidate, buntanetap, is designed as an oral translational inhibitor of neurotoxic aggregating proteins such as APP, tau and αSYN. To understand how buntanetap can potentially inhibit translation, we undertook two complementary approaches: a macro approach to examine all proteins in the cell whose translation is affected by buntanetap and a micro approach to study the mechanism of action using molecular biology, to understand and validate the binding and function.

First, a non-biased proteomics approach was applied to explore what proteins in the total protein universe were specifically downregulated by buntanetap. We have observed that, in addition to the proteins already known to be reduced by buntanetap, other neurotoxic aggregating proteins - huntingtin protein (“HTT”) and TDP43 - were downregulated as well.

A detailed analysis of the reduction of these protein levels was conducted in five different laboratories using multiple methodologies. The results observed in the analysis revealed that the mRNAs of these proteins have a special region, an atypical stem loop, which is preserved and responsible for their translation. When this region is bound to an RNA binding protein, the mRNA is not translated. When this region is free, the mRNA is translated. In neurodegenerative conditions, the mRNA coding for these neurotoxic proteins is over-translated, produces high levels of these proteins and causes them to become toxic. Buntanetap was observed to specifically increase the affinity between this special region and the RNA binding protein, preventing the mRNA from being released and translated.

The process outlined above leads to lower translation, lower levels of neurotoxic proteins and less toxicity in the brain. By preventing the overexpression of these neurotoxic proteins, buntanetap is designed to reverse the downstream toxic cascade that leads to neurodegeneration and reinstates homeostasis.

The following illustration visually depicts the mechanism of action of buntanetap:

MOA; Chen XQ et al. Pharmaceutics 09-2021 Iron and Neurodegeneration; Wong f. et al. Frontiers Aging Neuroscience; 03-2022

The special region in the mRNA is a 5’UTR iron responsive element (“IRE”) present in all mRNAs of neurotoxic aggregating proteins. The RNA binding protein is the Iron Regulatory Protein-1 (“IRP1”) that specifically binds the IREs of neurotoxic aggregating proteins.

The Toxic Cascade Leading to Nerve Cell Death and Loss of Function

The toxic cascade in neurodegeneration begins with high levels of neurotoxic proteins, which lead to impaired axonal transport, inflammation, death of nerve cells and loss of cognition and motor function. Buntanetap and ANVS405, our product candidates designed to treat acute neurodegeneration, including traumatic brain injury (“TBI”), have a mechanism of action we believe to be unique. The mechanism of action is designed to inhibit the over-translation of and ultimately reduce the levels of APP, tau and αSYN, which play a central role in the pathogenesis of both AD and PD. This leads us to believe that buntanetap has the potential to be a promising drug for the treatment of both AD and PD. Our approach is innovative in that we do not have a single therapeutic target for a single disease; instead, we are developing a technology platform that has the potential to target the mRNAs of multiple neurotoxic proteins, which are potentially impactful for multiple diseases.

In our AD/PD Trials in human AD and PD patients, we observed that buntanetap reduced levels of neurotoxic proteins, improved axonal transport and synaptic function, reduced inflammation, improved the health of nerve cells and improved cognition and function in mild to moderate AD and PD patients. Further, we have also observed that buntanetap reduced the levels of multiple neurotoxic proteins in animals, reversed the entire toxic cascade and recovered the affected function, be it in the brain, the body, or the eyes.

Pipeline

Our pipeline consists of: buntanetap for chronic neurodegeneration - including AD, PD and PDD - as well as within certain combination therapies summarized below; ANVS405 for acute neurodegeneration; and ANVS301 for advanced AD.

Buntanetap

Our lead product candidate, buntanetap, is an orally administered drug being developed for chronic indications such as AD and PD. Buntanetap has been observed to improve axonal transport in these diseases in preclinical studies by inhibiting the overproduction of neurotoxic proteins that kill nerve cells. In Phase 2/3 early AD patients, we have seen a statistically significant improvement in ADAS-Cog. In Phase 3 PD patients, we have seen statistically significant improvement in cognition in the ITT population, as well as in UPDRS scores for a per protocol population. The drug has further demonstrated improvements of cognition, including memory and learning, in AD mice, as well as movement, including colonic motility and grip strength, in PD mice. Buntanetap was tested in three Phase 1 clinical studies that showed it to be well tolerated. This safety data is applicable to the clinical development of buntanetap for AD, PD, and potentially other chronic neurodegenerative diseases.

Below is a summary depiction of our previously completed clinical studies of buntanetap. To date, over 1,200 human patients have been treated in the clinic and the drug has consistently shown to be well tolerated with minimal side effects:

We believe that buntanetap has the potential to be the only drug to improve both cognition in AD patients and motor function in PD patients.

ANVS405

ANVS405 is an intravenous drug being developed for acute indications and focused on protecting the brain after TBI and/or stroke. ANVS405 is the same compound as buntanetap, given in cases of acute head and brain trauma. In prior animal studies, ANVS405 was given to rats intravenously after TBI to determine whether ANVS405 would reach the brain in less than 15 minutes, as opposed to 1.5 hours if given orally. TBI rats that were treated with ANVS405 after the injury exhibited enhanced memory and learning and lower microglia activation, a measure of inflammation. The program has previously been funded by a grant from the U.S. Army and has since been completed. We therefore plan to seek additional grant funding to further the development of ANVS405 for acute indications of brain and nerve trauma. If and when we receive such sufficient funding, we plan to conduct a follow-on study to evaluate the effect of ANVS405 administered to TBI rats at various intervals post-injury to determine how long after a TBI a patient can effectively be treated. Our plan is to seek further funding to conduct the toxicology and PK studies in animals, file the Investigational New Drug application (“IND”), conduct the safety and PK studies in humans and later, continue with Phase 2 and Phase 3 efficacy studies.

ANVS301

ANVS301 is an orally administered drug being developed to increase cognitive capability in later stages of AD and dementia. ANVS301 was observed to improve memory and learning in rats of an advanced age by lowering the number of errors from six to three and shortening run times from approximately 75 to approximately 28 seconds. ANVS301 previously finished a single ascending dose Phase 1 clinical trial that was conducted and financed by the National Institute of Health (“NIH”).

Ongoing and Planned Clinical Trials of Buntanetap

Ongoing Pivotal Study for AD

Development of buntanetap for AD includes the recently initiated pivotal Phase 3 study in 760 early AD patients. This study was designed to include both a 6-month treatment window to demonstrate symptomatic efficacy, followed by a 12-month extension that will allow the study to achieve an 18-month treatment window that may demonstrate disease-modifying effects. We also expect future development to include an OLE study for AD.

In February of 2025, we initiated the Phase 3 AD Trial of buntanetap in 760 early AD patients with 380 dosed and 380 placebo patients. The Phase 3 AD Trial is a double-blind, placebo-controlled efficacy study which treats early AD patients. The inclusion criteria for early AD is the MMSE score of 20 to 28 and the disease diagnosis according to National Institute on Aging (“NIA”) and NIA and the Alzheimer’s Association (“NIA-AA”) criteria. Patients participating in the trial are aged 55-85, have a study partner, are of non-child-bearing age or agree to effective contraception, and have no evidence of suicidal ideation. Additionally, for the Phase 3 AD Trial we are incorporating a new biomarker-based inclusion criteria for a positive reading of p-tau217 levels in plasma.

The p-tau217, a phosphorylated form of the tau protein, has been recognized by the FDA as an acceptable early detection biomarker for AD. The trial is conducted at 83 sites in the United States.

Patients participating in the trial can remain on any drugs they regularly take, whether for AD or for other conditions, as long as they are stable on such medication, with the exception of approved monoclonal antibodies lecanemab (Leqembi®) and donanemab (KisunlaTM). Patients with uncontrolled diabetes, cardiovascular issues or seizures, patients with clinically significant abnormal laboratory values, patients with cancer within the last year and patients suffering from alcohol or substance abuse are excluded from participating.

Patients are randomly assigned to receive either 30 mg of buntanetap or placebo, once per day. Patients visit the clinic for first-time dosing, followed by an at home dosing period of 24/72 weeks. As described above, the study plan calls for opening the blind to a select group of individuals who will analyze the data after the 24-week treatment window, in order to evaluate 6-month efficacy of buntanetap. Study participants will remain blinded and will continue participation for an additional 48 weeks so that buntanetap’s disease-modifying efficacy can be evaluated over a total of 18 months.

Below is a visual depiction of the development path and study design for the active Phase 3 AD program:

We expect the 6-month symptomatic component of the combined AD trial to read-out in the second half of 2026. The 18-month disease modifying component is expected to read out in the second half of 2027.

Ongoing Open Label Extension for PD

After receiving permission from the FDA to conduct a 3-year OLE in PD patients, we initiated the study in November 2025. The OLE is designed to evaluate the long-term safety and efficacy of buntanetap and to measure its sustained benefits on both motor and cognitive functions. Furthermore, during the study we will collect biomarker data that will help us deepen our understanding of buntanetap’s potential as a disease-modifying treatment.

Planned Pivotal Study for PDD

As mentioned above, we proposed a pivotal Phase 3 trial for PDD to the FDA. In the previous Phase 3 PD Trial, buntanetap showed statistically significant improvement in MDS-UPDRS Part II, III, IV, total and MMSE in a per protocol subgroup population. Interestingly, it prevented worsening of cognition in the entire ITT population and showed highly statistical improvement in cognition in the cognitively impaired PD patients. Given the strong cognition data, we asked the FDA for approval to conduct a study in PDD, which was approved. We are refining the proposed protocol for the PDD program and will initiate the study contingent on additional funding.

Summary of All Performed Clinical Studies

Phase 3 PD Trial

In August 2022, we initiated a Phase 3 PD Trial of buntanetap in 450 early PD patients, which were separated into three cohorts of 150 patients. The Phase 3 PD Trial was conducted at 53 sites in the United States and 49 sites in the EU. The Phase 3 PD Trial was a double-blind, placebo-controlled efficacy study which treated participants with early PD over the duration of 6 months. The inclusion criteria for early PD included: stages of Hoehn & Yahr 1, 2 and 3 with less than 2 hours of OFF time; MMSE score of 22 to 30. Patients participating in the trial were age 40-85, were of non-child-bearing age or agreed to effective contraception and had no evidence of suicidal ideation. Patients participating in the trial were permitted to remain on any drugs they regularly took, whether for PD or for other conditions, as long as were stable on such medication. Patients with uncontrolled diabetes, cardiovascular issues or seizures, patients with clinically significant abnormal laboratory values, patients with cancer within the last year and patients suffering from alcohol or substance abuse were excluded from the trial. Patients were randomly assigned to receive either 10 or 20 mg of buntanetap or placebo, once per day. Patients visit the clinic for the first-time dosing in clinic, followed by an at home dosing period of 6 months. The study plan incorporated an interim analysis at two months, the results of which were disclosed by the Company on March 31, 2023. Based on the results of the interim analysis, we proceeded with the Phase 3 PD Trial as planned in accordance with the previously established protocol.

The Phase 3 PD Trial’s primary endpoints were evaluated using MDS-UPDRS Part II and III. Specifically, the FDA requested two co-primary endpoints to have an objective primary endpoint (MDS-UPDRS Part III, motor function) and a subjective primary endpoint (MDS-UPDRS Part II, activities of daily living). Together, these co-primary endpoints were intended to provide a more complete picture of the study and treatment results. The secondary endpoints were evaluated using the following measures: the MDS-UPDRS total score, which included the Part II and III measures as well as mentation, behavior, mood symptoms and complications of dopaminergic therapy; the participant global impression of change (“PGIC”), a participant-reported outcome, which reported how a patient’s condition has changed compared to their condition at the beginning of treatment; and the Change on Clinical Global Impression of Severity (“CGIS”), which measured the severity of movement impairment as assessed by a site rater.

The study was completed on December 4, 2023, and the topline Phase 3 PD Trial efficacy data were released on July 2, 2024. The data showed that in two subgroups buntanetap improved UPDRS Part II, III, II+III and total score. It also showed that in the entire ITT population, buntanetap stopped the loss of cognition and that in the 12% of patients with cognitive impairments, buntanetap improved cognition in a dose-dependent, statistically significant manner.

Phase 2/3 AD Trial

In February 2023, we initiated a Phase 2/3 AD Trial of buntanetap in 320 mild to moderate AD patients, which were separated into four cohorts of 80 patients. The Phase 2/3 AD Trial was conducted at 64 sites in the United States. The Phase 2/3 AD Trial was a double-blind, placebo-controlled efficacy study which treated patients with mild to moderate AD over the duration of 3 months. The inclusion criteria for mild to moderate AD was the MMSE score of 14 to 24. Patients participating in the trial were age 55-85, had a study partner, were of non-child-bearing age or agreed to effective contraception, and had no evidence of suicidal ideation. Patients participating in the trial were permitted to remain on any drugs they took regularly, whether for AD or for other conditions, as long as they were stable on such medication. Patients with uncontrolled diabetes, cardiovascular issues or seizures, clinically significant abnormal laboratory values, cancer within the last year and those suffering from alcohol or substance abuse were excluded from participating.

Patients were randomly assigned to receive either 7.5, 15 or 30 mg of buntanetap or placebo, once per day. Patients visited the clinic for the first-time dosing in clinic, followed by an at home dosing period of 3 months. The study plan incorporated an interim analysis at six weeks, the results of which were disclosed on October 23, 2023. Similar to above for the Phase 3 PD Trial, we proceeded with the remaining part of the AD study as planned after the interim analysis.

The co-primary endpoints of the Phase 2/3 AD Trial were evaluated using the following measures: ADAS-Cog11 and ADCS-Clinical Global Impression of Change (“ADCS-CGIC”), which focuses on clinicians’ observations of change in the patient’s cognitive, functional and behavioral performance since the beginning of a trial. The FDA requested the inclusion of two co-primary endpoints to have an objective primary endpoint (ADAS-Cog, cognition) and a subjective primary endpoint (ADCS-CGIC, activities of daily living). Together, these co-primary endpoints were intended to provide a more complete picture of the study and treatment

results. The secondary endpoints were evaluated using the following measures: the ADCS-ADL, which measures 6 basic activities of daily living items, including basic self-care tasks such as feeding, mobility and bathing, and 17 instrumental activities of daily living items, which include a broad range of activities based on cultural norms and gender roles; MMSE; and the digital symbol substitution test (“DSST”), which asks individuals to record associations between different symbols and numbers within time limits to assess cognition.

The Phase 2/3 AD Trial was completed on February 13, 2024, and on April 29, 2024, we announced topline efficacy data. The data showed that in a subgroup of early AD patients, buntanetap improved ADAS-Cog11 in a dose-dependent fashion and was statistically significant from placebo and from baseline.

On October 10, 2024, the Company met with the FDA in an end-of-phase 2 meeting to discuss its Phase 2/3 AD data and to agree on a regulatory path forward. Annovis and the FDA have now aligned on a development path for buntanetap towards the filing of NDAs, one for short-term and one for long-term efficacy. The Phase 3 program investigates buntanetap in patients with early AD and will consist of one study that first incorporates a 6-month study period aimed at confirming buntanetap’s symptomatic effects and later moving into an 18-month study period designed to demonstrate potential disease-modifying effects. While the overall study will last for the entire 18 months, the completion of the first 6-month treatment period, if well-designed and well-executed, may be sufficient to support an NDA filing, potentially within one year of the study’s initiation.

During the end-of-phase 2 meeting, the FDA raised no concerns with the Company’s data on buntanetap’s safety, including liver enzymes, drug interactions, dose selection, PK, population PK, and confirmed that development can proceed using the new crystal form of buntanetap.

Phase 1/2 AD/PD Trials

In 2021, we completed a Phase 1/2 clinical trial of buntanetap in 14 early AD and 54 early PD patients (the “AD/PD Trials”) which were conducted at 12 clinical sites in the United States. The AD/PD Trials were double-blind, placebo-controlled studies which treated mild to moderate AD and early PD patients for 25 +/- 2 days. The inclusion criteria for the AD portion of the AD/PD Trials were MMSE 18-28 and age 45 and older. For the PD portion of the AD/PD Trials, inclusion criteria were MMSE 18-30, age 45 and older and Hoehn & Yahr 1, 2 or 3. Patients participating in the trial were of non-child-bearing age or agreed to effective contraception and had no evidence of suicidal ideation. Patients participating in the trial could remain on any drugs they regularly took, whether for PD, for AD or for other conditions, as long as they were stable on such medication. Patients with uncontrolled diabetes, cardiovascular issues or seizures, patients with clinically significant abnormal laboratory values, patients who had cancer within the prior year and patients who suffered from alcohol or substance abuse were excluded from the trial.

The AD/PD Trials were designed to assess the safety, tolerability and PK of buntanetap. The studies met their primary endpoints of safety and tolerability, as measured by the percentage of patients with treatment-emergent adverse events in the buntanetap treatment arms as compared to the placebo groups, and secondary endpoint of PK of buntanetap, as measured by the concentration of buntanetap in plasma. The studies also met exploratory endpoints of measures of biomarkers related to neurotoxic protein cascade, and improvements in cognition in AD patients and function in PD patients. We believe the AD/PD Trials were the first double-blind, placebo-controlled studies that showed improvements in AD patients as measured by ADAS-Cog and in PD patients as measured by UPDRS.

The studies were conducted in two parts. The first part of the AD/PD Trials was in 14 early AD patients and 14 early PD patients. Patients were randomly assigned to receive either 80 mg of buntanetap or placebo, once per day. The second part of the AD/PD Trials was a dose response analysis performed in 40 early PD patients in which patients were randomly assigned to receive 5 mg, 10 mg, 20 mg, or 40 mg of buntanetap, once per day. In both parts of the AD/PD Trials, patients visited the clinic for the first-time dosing in clinic, followed by an at home dosing period of 25 +/- 2 days. We measured levels of neurotoxic proteins, neurotransmitters, neurotrophic factors, inflammation, and nerve cell death in all patients, as well as cognitive and functional improvements.

Safety results showed that buntanetap was well-tolerated in all dose groups. No serious adverse events were reported. The adverse events seen included problems related to CNS sampling: headaches, back and leg pain. PK parameters for buntanetap in plasma of AD and PD patients were similar to those seen in Phase 1 in our single ascending dose (“SAD”) and multiple ascending dose (“MAD”) studies in healthy volunteers, and in a proof-of-concept study in mild-cognitive impaired (“MCI”) patients.

We observed that buntanetap administration for 25 days lowered secreted APP α and β as well as total-tau and phosphorylated-tau levels in AD patients, and αSYN levels in PD patients. APP and its downstream products and tau are the neurotoxic proteins involved in AD, while αSYN is the primary neurotoxic culprit of PD.

Cerebrospinal fluid (“CSF”) was extracted before starting the study at baseline and at time 0 to 6 hours at the end of the study in both placebo and buntanetap treated patients. The values from time 0 to 6 hours were pooled to lower variability and the placebo values were deducted from the treated values. In all but one case, Aβ42, we saw that the levels in buntanetap treated patients were lower than in placebo patients. With respect to Ab42, we observed that levels were slightly higher, which is consistent with our hypothesis that Aβ42 levels are lower in advanced AD and higher in early AD. We believe that higher Aβ42 levels we observed suggest that the course of AD was reversed and the patients improved. Again, CSF was extracted at baseline and for 6 hours after the study and the values of the placebo patients were subtracted from the buntanetap treated patients. We observed that inflammatory markers were generally reduced in both patient populations.

We observed that buntanetap reduced neurofilament light (“NFL”) levels in both AD and PD patients, suggesting a potential improvement in axonal integrity. We also observed that buntanetap reduced neurogranin (“NG”) levels in both AD and PD, potentially suggesting more intact synaptic functions. The same CSF as above was used to measure neurofilament light and neurogranin before and after treatment and to compare buntanetap patients to placebo. In both patient populations, neurofilament light and neurogranin are lower in treated than in placebo patients.

These results suggest that buntanetap has the potential to reduce neurotoxic proteins, rescue axonal transport, reduce inflammation, and protect synaptic functions.

We performed ADAS-Cogs and WAIS coding tests to evaluate buntanetap’s effects on AD patients’ cognition. ADAS-Cog11 was performed at the beginning of the study at baseline and at the end at 25 days in the buntanetap-treated and the placebo groups. Although the study was not powered for efficacy, ADAS-Cog11 improved by 4.4 points, a statistically significant improvement of 28.57%. An improvement in ADAS-Cog11, which is reflected by a lower ADAS-Cog11 result, indicates increased cognitive performance. At 25 days, the treated group’s improvement from baseline was 3.3 points, or 20.71%, better than the placebo group’s improvement from baseline.

The WAIS coding test measures speed in movement and thinking. Treated AD patients showed a 6.6 point, or 16.17%, statistically significant improvement from baseline. Furthermore, the treated group’s improvement from baseline was 3.1 points, or 8.8%, better than the placebo group’s improvement from baseline.

In PD, we pooled the original 14 PD patients with the additional 40 PD patients and looked at the MDS-UPDRS and WAIS coding tests to evaluate buntanetap’s effects on PD patients’ mobility and functionality. The 54 PD patients received doses of either 5, 10, 20, 40 or 80 mg buntanetap treatment or placebo, once per day. We observed a statistically significant improvement in UPDRS Part II, III and IV individually. Specifically, Part III of the MDS-UPDRS measures the motor functions and has long been used as a standard to assess drugs’ effects on patients’ mobility.

We combined the two best doses, 10 and 20 mgs, and all doses, and saw an improvement of 3.6 (16.4%) for 10 and 20 mg, and of 2.4 (13.3%) for all doses combined compared to baseline. In the WAIS coding test, PD patients showed a statistically significant improvement both from baseline (17.1% for 10+20 mg; 13.3% for all doses combined) and from placebo (27.1% for 10+20 mg; 23.3% for all doses combined).

Axonal Transport in Human Nerve Cells

When the information highway of a nerve cell slows down, the nerve cell is unable to properly communicate with other nerve cells, internal organs and the periphery and it gets sick and dies.

The transfer of information in a nerve cell is called axonal transport. Axonal transport is responsible for:

● neurotransmitters GABA (anxiety), ACh (cognition), dopamine (movement), serotonin (mood);

● neurotrophic factors NGF, BDNF; and

● all communication within and between nerve cells.

When transport and synaptic transmission are impaired, the cell releases lower levels of neurotransmitters, leading to impaired nerve cell health. The diseased cell is then attacked by the immune system, which is activated when it detects a diseased cell, and it eventually kills the cell. Impairment in axonal transport, therefore, leads to inflammation and eventually to nerve cell death. This is visually illustrated below.

TBI Study in Rats

TBI causes severe cognitive and neurological impairment, which can incapacitate the patient, reduce quality of life, and increase the risk of morbidity and mortality. TBI is known to increase the risk for neurodegenerative disorders such as AD and PD. Several studies have analyzed changes in the brain after TBI and identified up-regulation of neurotoxic proteins, such as APP, tau and αSYN.

In our study, rats were subjected to either fluid percussion injury (“FPI”) or sham operation to one side of the brain. Three different ANVS405 doses or saline were given intraperitoneally to rats subjected to FPI for four weeks, with the first dose administered one-hour post-injury. At the termination of the treatment, all of the rats were first tested for their performance in a water maze, and then they were sacrificed for brain staining of living cells and determination of microglia activation. 10 mg/kg ANVS405 was shown to improve memory and learning as measured by water maze performance. Furthermore, sections of the brain were stained with tyrosine hydroxylase (“TH”), wherein TH stains only live cells. The amounts of TH immunoreactivity in the whole striatum of the brain slices were measured. The rats treated with all three doses of ANVS405 showed higher TH staining in the ipsilateral area of the brain than the vehicle treated animals. Thus, ANVS405 demonstrated the ability to protect the striatum following FPI in rats.

Because FPI can induce microglial activation, we next checked whether ANVS405 would reverse this pathology. In our study, we found that ANVS405 increased the number of resting microglia and reduced the number of activated microglia.

Stroke Mice Model

Buntanetap was also tested in a stroke model, in which mice were challenged with MCAo-induced stroke (middle carotid artery occlusion induced stoke) and after four weeks, the number of surviving neurons was quantified. After four weeks the locomotor function, behavior, and cognition of these mice were also evaluated.

Buntanetap, in combination with pifithrin-α (“PFT-α”) given to mice after the induced stroke improved mice locomotor activity and cognitive function. While both treatments yielded improvements in locomotor and cognitive function, the combined buntanetap/PFT-α treatment proved able to enhance stroke-induced endogenous neurogenesis and improve the functional recovery in stroke animals. The combined treatment also significantly improved cognitive function more than the single treatment with PFT-α.

Potential Markets for our Lead Drug Candidate

With there being a very large potential market for neurodegenerative diseases, most pharma companies have a program studying some aspects of nerve and brain degeneration. Some newer approaches target tau, whose expression is more closely associated with cognitive decline. Similarly, for PD, several companies are trying to inhibit αSYN. So far, we believe that generally, neither drugs attacking tau nor αSYN have shown positive results. Hence there is a substantial need for a new and different disease-modifying strategy. There is more than one neurotoxic protein in the brain of AD and of PD patients, and the same neurotoxic proteins are involved in the pathogenesis of AD and PD.

A significant portion of AD patients’ brains display mixed PD pathology and vice versa. Therefore, just attacking one of these proteins may result in no or lower efficacy than attacking them all. To prove that this approach is possible, we are studying the effects of buntanetap on the levels of several neurotoxic proteins and other surrogate markers, in parallel, in both AD and PD patients.

Alzheimer’s Disease Market

AD is a neurodegenerative disorder with cognitive, functional, and behavioral alterations. AD is age-related, and its incidence is increasing with the aging of the population. It is estimated that currently 55 million victims of AD or some form of dementia exist in the world and by 2050, the number will grow to nearly 140 million people worldwide. In the United States, it is estimated that there are nearly seven million patients with AD currently and that by 2060, the number of people aged 65 and older with AD is projected to reach nearly 14 million people. Nearly eightfold as many people have preclinical AD as have symptomatic AD and are at risk for progressing to full manifestation of the disease. Disease-modifying treatments (“DMTs”) that will prevent or delay the onset or slow the progression of AD are urgently needed. Similarly, medications to effectively improve cognition or ameliorate neuropsychiatric symptoms of patients in the symptomatic phases of AD are needed to improve memory and behavior.

The incidence rate of AD increases significantly with age. Individuals between ages 64 to 75 have an incidence rate of 0.4%, which increases to 3.2% for people between ages 75 and 84 and finally to 7.6% for people aged 85 and above. These incidence rates are cumulative as an individual ages, which means that an individual reaching 90 years of age will have a 38% chance of suffering from AD while an individual reaching the age of 95 will have a 76% chance of suffering from AD. AD is becoming increasingly common as the global population ages and as the health systems in developing countries improve. There is a significant need to identify drugs that prevent, delay the onset, slow the progression, or improve the symptoms of AD.

Parkinson’s Disease Market

PD is also a progressive neurodegenerative disorder with both movement and non-movement symptoms, functional, behavioral and cognitive alterations. PD, like AD, is age-related and is becoming markedly more common with the aging of the world’s population. PD affects about 1% of the population over the age of 60, while in individuals over the age of 85, this prevalence reaches 5%, highlighting the impact that advancing age has on the risk of developing this condition.

PD affects more than 10 million people worldwide, of which nearly one million are in the U.S. While a 2014 study estimated that the incidence in the U.S. will rise to 1.2 million by 2030, a later 2022 study found that there are nearly 90,000 new cases of PD diagnosed each year in the U.S., potentially supporting an even greater future incidence rate. By 2050, the number of worldwide PD patients is expected to grow to up to 30 million.

The National Parkinson’s Foundation estimates that the economic burden of PD is at least $25 billion a year in the United States.

To date, there are no available treatments capable of curing PD, with current therapies seeking only to ameliorate dopamine-related motor symptoms of the disease. There is a clear and unmet medical need for new DMTs that can slow or prevent PD progression.

Mixed Pathologies Market

In addition to the unmet need of AD and PD patients, approximately 50% of patients exhibit mixed pathologies, with some pathologies resembling AD and some resembling PD.

Dementia is increasingly being recognized in cases of PD; such cases are termed PD dementia (“PDD”). The spread of fibrillar αSYN pathology from the brainstem to limbic and neocortical structures seems to be the strongest neuropathological correlate of emerging dementia in PD. Up to 50% of patients with PDD develop sufficient numbers of Aβ plaques and tau-containing neurofibrillary tangles for a secondary diagnosis of AD, and these pathologies may act synergistically with αSYN pathology to confer a worse prognosis.

Another study looked at the incidence of mixed pathologies diagnosed community-dwelling older persons. Those with dementia most often have multiple brain pathologies, which greatly increases the odds of dementia. Specifically, in people with dementia, over 50% had multiple diagnoses (AD, PD/Lewy body dementia, PDD or infarcts). After accounting for age, persons with multiple diagnoses were almost three times more likely to exhibit dementia compared to those with one pathologic diagnosis.

We believe that a therapy that only addresses Aβ, tau or αSYN is less likely to help people with mixed pathologies. Since buntanetap is designed to inhibit more than one neurotoxic protein, we believe that it may have the potential to slow or eventually stop AD, PD and mixed pathology diseases.

Therapeutic Approaches and Competition

Alzheimer’s Disease Approaches

Drug development for AD has historically proven to be very difficult. Drugs which have been approved for the treatment of AD include cholinesterase inhibitors (tacrine, donepezil, rivastigmine, galantamine), an N-methyl-D-aspartate receptor antagonist (memantine) and more recently, monoclonal antibody treatments (donanemab, lecanemab). Many failures in AD drug development have occurred, with both small molecules and immunotherapies failing to show a dramatic drug/placebo difference or having unacceptable toxicity.

Most clinical trials conducted have addressed amyloid targets. Since Aβ accumulates for years before the symptoms of AD are visible, some pharmaceutical companies are testing their drugs earlier, including in cognitively normal people or those who have genetic profiles that place them at high(er) risk for developing AD.

An increasing number of agents are also directed at tau-related targets. Neurofibrillary tangles are one of two major pathological hallmarks of AD. Correlation studies conducted by Braak and Braak demonstrate that neurofibrillary tangle burden more closely correlates with cognitive decline than amyloid plaque load. Several Phase 3 studies conducted with tau approaches have failed. There are still several anti-tau approaches in the clinic.

In summary, at present there are few disease-modifying agents currently on the market and existing treatments show limited efficacy. Previous large efforts to develop a DMD for AD has targeted Aβ42, but many Aβ42 approaches to date have failed and again, have shown limited efficacy when treating AD. Further, most companies testing tau have shown negative results as well. As a result, many organizations have pulled out of AD research and are waiting to see if a new or alternative approach may have a better outcome. Since the AD brain contains several neurotoxic proteins – APP and its toxic fragments Aβ42 and IC99, as well as tau and αSYN – we believe an Aβ42-only approach is not sufficient in order to develop a DMD drug. We believe that a DMD drug needs to target more than just one toxic protein to be efficacious and we are developing buntanetap with this approach in mind. A concerning observation derived from a review of the existing industry AD pipeline is the lack of agents targeting the moderate to advanced stages of AD. With over 15 million people affected by AD dementia worldwide, there is an urgent need to develop more effective symptomatic treatments for moderate to advanced stage disease. The paucity of agents directed at this population represents a significant weakness of the AD drug development pipeline.

Parkinson’s Disease Approaches

Levodopa (“L-DOPA”) was introduced for use in treating PD more than 40 years ago and remains the mainstay of therapy for improving the symptoms of the disease. Unlike dopamine, which cannot cross the blood—brain barrier, L-DOPA is effectively absorbed into the brain, where it metabolizes into dopamine. It is typically administered five times a day and works well in controlling symptoms for one to five years. Unfortunately, the effects of L-DOPA in any patient diminish with time. There are several other drugs available to treat PD, which also seek to modulate dopamine levels. Combination drug therapy is common in PD. For instance, the use of other drug classes such as the catechol-O-methyltransferase (“COMT”) inhibitors and the monoamine oxidase (“MAO”) inhibitors allow patients to reduce L-DOPA dosing levels.

The current global market for PD drugs is estimated at $5 to $6 billion worldwide, despite high-volume generics. The most important current therapy for PD, L-DOPA, is prescribed as a generic. While volume growth in the category is expected to remain healthy, dollar growth will likely remain relatively flat as some of the category’s larger brands contend with generic inroads. The size of the current market reflects the absence of innovative branded therapies more than it does the medical need.

So far, we believe that only buntanetap and Exenatide are in the later stages of clinical development for disease-modification, and no products have yet shown efficacy in PD patients long term. Although several drugs have shown potential neuroprotective ability in preclinical studies, demonstrating these effects in clinical studies remains a challenge. Beyond drug therapies, a few cell and gene therapy approaches are also being explored. Progress across these newer technology platforms has been slow.

Intellectual Property Overview

We strive to protect and enhance the proprietary technologies, inventions and improvements that we believe are important to our business, including seeking, maintaining and defending patent rights, whether developed internally or licensed from third parties. Our policy is to seek to protect our proprietary position by, among other methods, pursuing and obtaining patent protection in the United States and in jurisdictions outside of the United States related to our proprietary technology, inventions, improvements, platforms and our product candidates that are important to the development and implementation of our business.

Annovis has filed fourteen (14) families of patents and patent applications to prolong the patent life of buntanetap. The pending patent applications invented and filed by Annovis include claims directed to:

● a method of treating neurodegenerative diseases such as AD and PD;

● a method of treating and/or preventing acute brain and nerve injuries;

● a method of prevention and treatment of disease states due to metal dis-homeostasis such as AD or PD as well as other acute or chronic neurodegenerative diseases;

● a method of treating viral and bacterial infections of the brain, including COVID-19;

● a method of inhibiting cancer metastasis;

● combinations of buntanetap with some drugs and uses of these combinations to treat neurodegenerative diseases;

● a method of treating neuropsychiatric indications;

● a new composition of matter of Posiphen, Form B or ANVS402; and

● new methods for making buntanetap and Posiphen Form B.

Solid forms of chemical compounds can exist in different crystalline structures. One crystalline structure of Posiphen is buntanetap. Annovis, through its research efforts, invented a new crystalline form of Posiphen, known as Form B (“ANVS402”). Form B, or ANVS402, has demonstrated certain improvements over buntanetap and was filed as a new composition of matter patent application. All our patents have been successfully transferred from the original form of buntanetap and rewritten to cover the new crystal form. Every patent family is now represented for both forms of our drug candidate, securing comprehensive protection, which extends to 2046. All patents are filed internationally, securing global coverage of buntanetap.

As of March 2, 2026, our patent portfolio is comprised of 40 issued patents and 48 pending patent applications in various jurisdictions.

The patents, granted and if granted based on the pending applications, have expiration dates between 2031 and 2045. The first patent application family we filed, which would be expected to expire in 2031, before any patent term adjustments or extensions, covers the use of buntanetap in the treatment of AD, PD and other neurodegenerative disorders such as Huntington’s disease, prion diseases, amyotrophic lateral sclerosis, tauopathies, frontotemporal dementia, Lewy bodies disease, and chronic traumatic encephalopathy, based on our preclinical research. In August 2019, the U.S. Patent and Trademark Office (“USPTO”) granted the first of our Annovis patents from this family covering treatment of PD and Lewy body diseases. Subsequently, the USPTO also granted patents covering treatment frontotemporal dementia and tauopathies, chronic traumatic encephalopathy, prion diseases, amyotrophic lateral sclerosis, AD and Huntington’s disease.

The second patent application family covers ANVS405’s use in acute brain and nerve trauma and would be expected to expire in 2036, before any patent term adjustments or extensions. In December 2020, the EPO approved the whole patent, and it has since been approved in most countries filed, claiming a method of treating acute nerve and brain injuries by administering ANVS405

before and after the injury. The USPTO instead has asked us to separate the application into four divisional applications covering stroke, TBI, nerve injury and spinal cord injury.

The third patent application family relates to the use of the mechanism of action of buntanetap and ANVS405 to prevent and treat neurodegenerative diseases and would be expected to expire in 2038, before any patent term adjustments or extensions. The first divisional of this application was approved in December 2022, and it covers the prevention of neurodegenerative diseases. The patent has been issued in most jurisdictions.

The fourth patent application family relates to a method of inhibiting, preventing, or treating neurological injuries due to viral, bacterial, fungal, protozoan, or parasitic infections in humans and in animals via administration of buntanetap or related compounds. In May 2020, we filed a patent application with the USPTO concerning a method of inhibiting, preventing, or treating neurological injuries due to viral, bacterial, fungal, protozoan, or parasitic infections in humans and in animals via administration of buntanetap or related compounds, which would be expected to expire in 2041, before any patent term adjustments or extensions.

The fifth patent family application is directed to a method of maintaining heavy metal homeostasis avoiding the effect of toxic levels of a heavy metal in cells in a healthy human or restoring heavy metal homeostasis in a sick human patient. The USPTO granted the first patent in this family on March 7, 2023, which is expected to expire in 2039, before any patent term adjustments or extensions.

The sixth patent application relates to treating brain metastasis via administration of buntanetap or related compounds. In September 2023, we filed a U.S. nonprovisional patent application directed to treatment of brain metastasis via administration of buntanetap or related compounds with the USPTO, which, if allowed, would be expected to expire in 2043, before any patent term adjustments or extensions. The cancer patent family has been expanded to include cancer growth and metastasis for a number of cancer types.

The seventh patent application family relates to treatment of mental illness via administration of buntanetap or related compounds. In January 2024, we filed an International (PCT) application and a U.S. nonprovisional patent application directed to treatment of mental illness via administration of buntanetap or related compounds with the USPTO, which, if allowed, would be expected to expire in 2044, before any patent term adjustments or extensions.

The eighth patent application family relates to treatment of neurodegenerative diseases and other diseases via co-administration of buntanetap or related compounds and an antidiabetic agent. In September 2024, we filed an International (PCT) application and a U.S. nonprovisional patent application directed to treatment of neurodegenerative diseases and other diseases via administration of this combination.

The ninth patent application family relates to treatment of neurodegenerative diseases and other diseases via co-administration of buntanetap or related compounds and a phosphodiesterase inhibitor. In September 2024, we filed an International (PCT) application and a U.S. nonprovisional patent application directed to treatment of neurodegenerative diseases and other diseases via administration of this combination.

The tenth patent application family relates to treatment of neurodegenerative diseases and other diseases via co-administration of buntanetap or related compounds and an antihypertensive agent. In September 2024, we filed an International (PCT) application and a U.S. nonprovisional patent application directed to treatment of neurodegenerative diseases and other diseases via administration of this combination.

The eleventh patent application family relates to treatment of neurodegenerative diseases and other diseases via co-administration of buntanetap with two additional therapeutic agents. In August 2024, we filed a provisional U.S. Patent application directed to treatment of neurodegenerative diseases and other diseases via administration of this combination.

The twelfth patent application family relates to treatment of neurodegenerative diseases and other diseases via co-administration of buntanetap or related compounds and an additional therapeutic agent. In February 2025, we filed a provisional U.S. Patent application directed to treatment of neurodegenerative diseases and other diseases via administration of this combination.

The thirteenth patent application family relates to the new Form B of Posiphen (ANVS402); it demonstrates that it can be used instead of buntanetap, including in the foregoing uses of buntanetap of the Company’s patent portfolio. Posiphen Form B may be the compound of choice in current uses of buntanetap, because it may have advantageous properties such as better stability and higher purity. In 2023, the Company filed with the USPTO two provisional patent applications as to Posiphen Form B. In 2024, the Company filed an International (PCT) application as to Posiphen Form B and uses thereof. The “International Search Report and Written Opinion” issued by the USPTO in the prosecution of the PCT application was favorable, indicating that the searched claims directed to Posiphen Form B are novel and inventive. The Company expects to further file patent applications in the U.S. and outside the U.S. as National and Regional Phase patent applications of the PCT application. As to this family of patent applications involving Posiphen Form B and uses thereof, patents would be expected to expire in 2044, before any patent term adjustments or extensions. The Company also expects to seek New Chemical Entity status for Posiphen Form B before the FDA, and to seek additional regulatory exclusivity based thereon.

The fourteenth patent application family relates to new, improved and commercially advantageous methods for preparing buntanetap and Posiphen Form B. The Company sees this patent application family as providing further protection as to methods that use buntanetap or Posiphen Form B, and for Posiphen Form B. In particular, in 2024 the Company filed with the USPTO a provisional patent application directed to these new methods of preparing buntanetap and Posiphen Form B. The Company expects in 2025 to further file at least an International (PCT) application, claiming priority from that provisional patent application, and directed to the new, improved and commercially advantageous methods for preparing buntanetap and Posiphen Form B, and thereafter patent applications in the United States and outside the United States as National and Regional Phase patent applications of the PCT application. As to this family of patent applications, patents would be expected to expire in 2045, before any patent term adjustments or extensions.

In 2025, we rewrote every patent family we had to also incorporate Posiphen Form B. To date, every invention we patented, whether the patent has been granted or is still in the application state, refers to the original Form A and to the new Form B.

It is possible that we will fail to identify further patentable aspects of our research and development output before it is too late to obtain patent protection. The patent applications that we own may fail to result in issued patents with claims that provide further coverage of buntanetap or any other product candidate in the United States or in other foreign countries.

Furthermore, we rely upon trade secrets and know-how and continuing technological innovation to develop and maintain our competitive position. We seek to protect our proprietary information, in part, using confidentiality agreements with our collaborators, employees and consultants and invention assignment agreements with our employees. We also have confidentiality agreements or invention assignment agreements with our collaborators and selected consultants.

Sales and Marketing

If buntanetap is approved for AD or PD, we plan to enter into sales and marketing agreements with one or several pharmaceutical companies to sell to neurologists, geriatric specialists and to primary care physicians. We also may explore the use of a variety of types of collaboration, co-promotion, distribution and other marketing arrangements with one or more third parties to commercialize our product candidates.

Manufacturing

Buntanetap is a small molecule that is manufactured using a patented process. We do not own, operate, and currently have no plans to establish any manufacturing facilities. We therefore rely and expect to continue to rely solely on third-party contractors for manufacturing clinical supplies for our current and future potential product candidates, and plan to do so for commercial supplies also, if any of our product candidates receive marketing approval. We also rely on these third parties for encapsulating, packaging and stabilizing clinical trial materials. Presently we are working with a U.S. supplier for the manufacture of cGMP active pharmaceutical ingredient (API) to meet our buntanetap clinical study supply demands. We have also engaged a backup API manufacturing contractor, with primary operations in China. We also have an agreement with a local U.S. supplier for the encapsulating, packaging, and stability of the clinical trial material. These arrangements will allow us to enter large and long-term advanced clinical studies. We have only limited supply agreements in place with respect to buntanetap and our product candidates, and these arrangements do not currently extend to commercial supply. We do not have long-term committed arrangements with respect to buntanetap, any of our other product candidates, or other materials.

Government Regulation

The FDA and comparable regulatory authorities in state and local jurisdictions and in other countries impose substantial and burdensome requirements upon companies involved in the clinical development, manufacturing, marketing and distribution of drugs, such as those we are developing. These agencies and other federal, state and local entities regulate, among other things, the research and development, testing, manufacturing, quality control, safety, effectiveness, labeling, storage, record-keeping, approval, advertising and promotion, distribution, post-approval monitoring and reporting, sampling and export and import of our product candidates.

U.S. Government Regulation of Drug Products

In the United States, the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act (“FDCA”) and its implementing regulations. Failure to comply with the applicable U.S. requirements at any time during the product development process, approval process or after approval, may subject an applicant to a variety of administrative or judicial sanctions, such as the FDA’s refusal to approve pending NDAs, withdrawal of an approval, imposition of a clinical hold, issuance of warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal penalties.

The process required by the FDA before a drug may be marketed in the United States generally involves the following:

● Completion of preclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s good laboratory practice regulations.

● Submission to the FDA of an IND application, which must become effective before human clinical trials may begin.

● Approval by an independent institutional review board (“IRB”), at each clinical site before each trial may be initiated.

● Performance of adequate and well-controlled human clinical trials in accordance with good clinical practice (“GCP”), requirements to establish the safety and efficacy of the proposed drug product for each indication.

● Submission to the FDA of an NDA.

● Satisfactory completion of an FDA advisory committee review, if applicable.

● Satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the product is produced to assess compliance with cGMP requirements and to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity.

● Satisfactory completion of FDA audits of clinical trial sites to assure compliance with GCPs and the integrity of the clinical data.

● Payment of user fees and securing FDA approval of the NDA.

● Compliance with any post-approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy (“REMS”) and the potential requirement to conduct post-approval studies.

Preclinical Studies

Preclinical studies include laboratory evaluation of product chemistry, toxicity and formulation, as well as animal studies to assess potential safety and efficacy. An IND sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data and any available clinical data or literature, among other things, to the FDA as part of an IND. Some preclinical testing may continue even after the IND is submitted. An IND automatically becomes effective 30 days after receipt by the FDA, unless before that time the FDA raises concerns or questions related to one or more proposed clinical trials and places the

clinical trial on a clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. As a result, submission of an IND may not result in the FDA allowing clinical trials to initiate.

Clinical Trials

Clinical trials involve the administration of the investigational new drug to human subjects under the supervision of qualified investigators in accordance with GCP requirements, which include the requirement that all research subjects provide their informed consent in writing for their participation in any clinical trial. Clinical trials are conducted under protocols detailing, among other things, the objectives of the trial, the parameters to be used in monitoring safety, and the effectiveness criteria to be evaluated. A protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of the IND. In addition, an IRB at each institution participating in the clinical trial must review and approve the plan for any clinical trial before it initiates at that institution. Information about certain clinical trials must be submitted within specific timeframes for public dissemination on www.clinicaltrials.gov.

Human clinical trials are typically conducted in three sequential phases, which may overlap or be combined:

● Phase 1: The drug is initially introduced into healthy human subjects or patients with the target disease or condition and tested for safety, dosage tolerance, absorption, metabolism, distribution, excretion and, if possible, to gain an early indication of its effectiveness.

● Phase 2: The drug is administered to a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage.

● Phase 3: The drug is administered to an expanded patient population, generally at geographically dispersed clinical trial sites, in well-controlled clinical trials to generate enough data to statistically evaluate the efficacy and safety of the product for approval, to establish the overall risk-benefit profile of the product, and to provide adequate information for the labeling of the product.

Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA and more frequently if serious adverse events occur.

Special FDA Expedited Review and Approval Programs

The FDA has various programs, including fast track designation, accelerated approval, priority review, and breakthrough therapy designation, which are intended to expedite or simplify the process for the development and FDA review of drugs that are intended for the treatment of serious or life-threatening diseases or conditions and demonstrate the potential to address unmet medical needs. The purpose of these programs is to provide important new drugs to patients earlier than under standard FDA review procedures.

To be eligible for a fast-track designation, the FDA must determine, based on the request of a sponsor, that a product is intended to treat a serious or life-threatening disease or condition and demonstrates the potential to address an unmet medical need. The FDA will determine that a product will fill an unmet medical need if it will provide a therapy where none exists or provide a therapy that may be potentially superior to existing therapy based on efficacy or safety factors. The FDA may review sections of the NDA for a fast-track product on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the NDA, the FDA agrees to accept sections of the NDA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the NDA.

The FDA may give a priority review designation to drugs that offer major advances in treatment or provide a treatment where no adequate therapy exists. A priority review means that the goal for the FDA to review an application is six months, rather than the standard review of ten months under current PDUFA guidelines. Under the current PDUFA agreement, these six- and ten-month review periods are measured from the “filing” date rather than the receipt date for NDAs for new molecular entities, which typically adds approximately two months to the timeline for review and decision from the date of submission. Most products that are eligible for fast-track designation are also likely to be considered appropriate to receive a priority review.

In addition, products tested for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may be eligible for accelerated approval and may be approved on the basis of adequate and well-controlled clinical trials establishing that the drug product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality (“IMM”) that is reasonably likely to predict an effect on IMM or other clinical benefit, taking into account the severity, rarity or prevalence of the condition and the availability or lack of alternative treatments. As a condition of approval, the FDA may require a sponsor of a drug receiving accelerated approval to perform post-marketing studies to verify and describe the predicted effect on IMM or other clinical endpoint, and the drug may be subject to accelerated withdrawal procedures.

Moreover, under the provisions of the Food and Drug Administration Safety and Innovation Act passed in July 2012, a sponsor can request designation of a product candidate as a “breakthrough therapy.” A breakthrough therapy is defined as a drug that is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. Drugs designated as breakthrough therapies are also eligible for accelerated approval. The FDA must take certain actions, such as holding timely meetings and providing advice, intended to expedite the development and review of an application for approval of a breakthrough therapy. Annovis would like to petition the FDA to classify buntanetap as a breakthrough therapy in the future.

Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened. We may explore some of these opportunities for our product candidates as appropriate.

Orphan Drug Designation and Exclusivity

Under the Orphan Drug Act, the FDA may designate a drug product as an “orphan drug” if it is intended to treat a rare disease or condition (generally meaning that it affects fewer than 200,000 individuals in the United States, or more in cases in which there is no reasonable expectation that the cost of developing and making a drug product available in the United States for treatment of the disease or condition will be recovered from sales of the product). A company must request orphan product designation before submitting an NDA. If the request is granted, the FDA will disclose the identity of the therapeutic agent and its potential use. Orphan product designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.

If a product with orphan status receives the first FDA approval for a disease or condition, the product generally will be receiving orphan product exclusivity. Orphan product exclusivity means that the FDA may not approve any other applications for the same product for the same indication for seven years, except in certain limited circumstances. If a drug or drug product designated as an orphan product ultimately receives marketing approval for an indication broader than what was designated in its orphan product application, it may not be entitled to exclusivity. Orphan exclusivity will not bar approval of another product under certain circumstances, including if a subsequent product with the same active ingredient for the same indication is shown to be clinically superior to the approved product on the basis of greater efficacy or safety, or providing a major contribution to patient care, or if the company with orphan drug exclusivity is not able to meet market demand. Further, the FDA may approve more than one product for the same orphan indication or disease if the products contain different active ingredients. Moreover, competitors may receive approval of different products for the indication for which the orphan product has exclusivity or obtain approval for the same product but for a different indication for which the orphan product has exclusivity.

Marketing Approval and Post-Approval Requirements

Assuming successful completion of the required clinical testing, the results of the preclinical and clinical studies, together with detailed information relating to the product’s chemistry, manufacture, controls and proposed labeling, among other things, are submitted to the FDA as part of an NDA requesting approval to market the product for one or more indications. In most cases, the submission of an NDA is subject to a substantial application user fee. Under the Prescription Drug User Fee Act (“PDUFA”) guidelines that are currently in effect, the FDA has a goal of ten months from the date of “filing” of a standard NDA, for a new molecular entity to review and act on the submission. This review typically takes twelve months from the date the NDA is submitted to FDA because the FDA has approximately two months to make a “filing” decision.

The FDA also may require submission of a REMS plan to ensure that the benefits of the drug outweigh its risks. The REMS plan could include medication guides, physician communication plans, assessment plans, and/or elements to assure safe use, such as restricted distribution methods, patient registries, or other risk minimization tools.

The FDA conducts a preliminary review of all NDAs within the first 60 days after submission, before accepting them for filing, to determine whether they are sufficiently complete to permit substantive review. Once the submission is accepted for filing, the FDA begins an in-depth substantive review. The FDA reviews an NDA to determine, among other things, whether the drug is safe and effective and whether the facility in which it is manufactured, processed, packaged or held meets standards designed to assure the product’s continued safety, quality and purity.

Before approving an NDA, the FDA typically will inspect the facility or facilities where the product is manufactured. Additionally, before approving an NDA, the FDA may inspect one or more clinical trial sites to assure compliance with GCP requirements.

The FDA may refer an application for a novel drug to an advisory committee. While the FDA is not bound by the recommendations of an advisory committee, it considers such recommendations carefully when making decisions.

After evaluating the NDA and all related information, including the advisory committee recommendation, if any, and inspection reports regarding the manufacturing facilities and clinical trial sites, the FDA may issue an approval letter, or, in some cases, a complete response letter. A complete response letter generally contains a statement of specific conditions that must be met in order to secure final approval of the NDA and may require additional clinical or preclinical testing for the FDA to reconsider the application. If and when those conditions have been met to the FDA’s satisfaction, the FDA will typically issue an approval letter. An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications.

Even if the FDA approves a product, it may limit the approved indications for use of the product, require that contraindications, warnings or precautions be included in the product labeling, require that post-approval studies, including Phase 4 clinical trials, be conducted to further assess a drug’s safety after approval, require testing and surveillance programs to monitor the product after commercialization, or impose other conditions, including distribution and use restrictions or other risk management mechanisms under a REMS.

Once an approval of a drug or medical device is granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in mandatory revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical trials to assess new safety risks; or imposition of distribution or other restrictions under a REMS program. Other potential consequences include, among other things:

● Restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls.

● Fines, warning letters or holds on post-approval clinical trials.

● Refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocation of product approvals.

● Product seizure or detention, or refusal to permit the import or export of products.

● Injunctions or the imposition of civil or criminal penalties.

The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market. Drugs or devices may be promoted only for the approved indications and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability.

U.S. Coverage and Reimbursement

Significant uncertainty exists as to the coverage and reimbursement status of our lead product candidate, buntanetap, or any other candidate for which we may seek regulatory approval. Sales in the U.S. will depend in part on the availability of adequate financial coverage and reimbursement from third-party payors, which include government health programs such as Medicare, Medicaid, TRICARE and the Veterans Administration, as well as managed care organizations and private health insurers. Prices at which we or our customers seek reimbursement for our product candidates can be subject to challenge, reduction or denial by payors.

The process for determining whether a payor will provide coverage for a product is typically separate from the process for setting the reimbursement rate that the payor will pay for the product. Third-party payors may limit coverage to specific products on an approved list or formulary, which might not include all the FDA-approved products for a particular indication. Also, third-party payors may refuse to include a branded drug on their formularies or otherwise restrict patient access to a branded drug when a less costly generic equivalent or another alternative is available. Medicare Part D, Medicare’s outpatient prescription drug benefit, contains protections to ensure coverage and reimbursement for oral oncology products, and all Part D prescription drug plans are required to cover substantially all oral anti-cancer agents. However, a payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be available. Private payors often rely on the lead of the governmental payors in rendering coverage and reimbursement determinations. Sales of buntanetap or any other product candidates will therefore depend substantially on the extent to which the costs of our products will be paid by third-party payors. Achieving favorable coverage and reimbursement from the Centers for Medicare and Medicaid Services (“CMS”) and/or the Medicare Administrative Contractors is typically a significant gating issue for successful introduction of a new product.

Third-party payors are increasingly challenging the price and examining the medical necessity and cost-effectiveness of medical products and services, in addition to their safety and efficacy. In order to obtain coverage and reimbursement for any product that might be approved for marketing, we may need to conduct studies in order to demonstrate the medical necessity and cost-effectiveness of any products, which would be in addition to the costs expended to obtain regulatory approvals. Third-party payors may not consider our product candidates to be medically necessary or cost-effective compared to other available therapies, or the rebate percentages required to secure favorable coverage may not yield an adequate margin over cost or may not enable us to maintain price levels sufficient to realize an appropriate return on our investment in drug development.

U.S. Healthcare Fraud and Abuse Laws and Compliance Requirements

We are subject to various federal and state laws targeting fraud and abuse in the healthcare industry. These laws may impact, among other things, our proposed sales and marketing programs. In addition, we may be subject to patient privacy regulation by both the federal government and the states in which we conduct our business. The laws that may affect our operations include:

● the federal Anti-Kickback Statute, which prohibits, among other things, persons from soliciting, receiving, offering or paying remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation of, an item or service reimbursable under a federal healthcare program, such as the Medicare and Medicaid programs. The term “remuneration” has been broadly interpreted to include anything of value;

● federal false claims and civil monetary penalties laws, including the federal civil False Claims Act, which prohibits anyone from, among other things, knowingly presenting, or causing to be presented, for payment to federal programs (including Medicare and Medicaid) claims for items or services that are false or fraudulent;

● provisions of the U.S. federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), which created new federal criminal statutes that prohibit, among other things, knowingly and willfully executing a scheme to defraud any healthcare benefit program or making false statements in connection with the delivery of or payment for healthcare benefits, items or services. In addition, HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act and its implementing regulations, impose certain requirements relating to the privacy, security and transmission of individually identifiable health information; and

● the federal Physician Payment Sunshine Act requirements, under the Patient Protection and Affordable Care Act, which require manufacturers of certain drugs and biologics to track and report to CMS payments and other transfers of value

they make to U.S. physicians and teaching hospitals as well as physician ownership and investment interests in the manufacturer.

Regulation Outside of the United States

To the extent that any of our product candidates, once approved, are sold in a foreign country, we may be subject to similar foreign laws and regulations, which may include, for instance, applicable post-marketing requirements, including safety surveillance, anti-fraud and abuse laws and implementation of corporate compliance programs and reporting of payments or other transfers of value to healthcare professionals.

To market our future products in the European Economic Area (“EEA”), which is comprised of the 27 Member States of the EU plus Norway, Iceland and Liechtenstein, and many other foreign jurisdictions, we must obtain separate regulatory approvals. More concretely, in the EEA, medicinal products can only be commercialized after obtaining a Marketing Authorization (“MA”). There are two types of MAs:

● The Community MA, which is issued by the European Commission through the Centralized Procedure, based on the opinion of the Committee for Medicinal Products for Human Use of the European Medicines Agency (“EMA”) and which is valid throughout the entire territory of the EEA. The Centralized Procedure is mandatory for certain types of products, such as biotechnology medicinal products, orphan medicinal products and medicinal products indicated for the treatment of AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune and viral diseases. The Centralized Procedure is optional for products containing a new active substance not yet authorized in the EEA, or for products that constitute a significant therapeutic, scientific or technical innovation or which are in the interest of public health in the EU; and

● National MAs, which are issued by the competent authorities of the Member States of the EEA and only cover their respective territory, are available for products not falling within the mandatory scope of the Centralized Procedure. Where a product has already been authorized for marketing in a Member State of the EEA, this National MA can be recognized in another Member State through the Mutual Recognition Procedure. If the product has not received a National MA in any Member State at the time of application, it can be approved simultaneously in various Member States through the Decentralized Procedure.

Under the above-described procedures, before granting the MA, the EMA or the competent authorities of the Member States of the EEA assess the risk-benefit balance of the product based on scientific criteria concerning its quality, safety and efficacy.

Data and Marketing Exclusivity

In the EEA, new products authorized for marketing, or reference products, qualify for eight years of data exclusivity and an additional two years of market exclusivity upon marketing authorization. The data exclusivity period prevents generic or biosimilar applicants from relying on the preclinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar marketing authorization in the EU during a period of eight years from the date on which the reference product was first authorized in the EU. The market exclusivity period prevents a successful generic or biosimilar applicant from commercializing its product in the EU until 10 years have elapsed from the initial authorization of the reference product in the EU. The 10-year market exclusivity period can be extended to a maximum of eleven years if, during the first eight years of those 10 years, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.

Orphan Drug Designation

In the EEA, a medicinal product can be designated as an orphan drug if its sponsor can establish that the product is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting not more than five in ten thousand persons in the EU when the application is made, or that the product is intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition in the EU and that without incentives it is unlikely that the marketing of the drug in the EU would generate sufficient return to justify the necessary investment in development. For either of these conditions, the applicant must demonstrate that there exists no satisfactory method of diagnosis, prevention or treatment of the

condition in question that has been authorized in the EU or, if such method exists, the drug will be of significant benefit to those affected by that condition.

In the EEA, an application for designation as an orphan product can be made any time prior to the filing of an application for approval to market the product. Marketing authorization for an orphan drug leads to a ten-year period of market exclusivity. During this market exclusivity period, the EMA or the member state competent authorities, cannot accept another application for a marketing authorization, or grant a marketing authorization, for a similar medicinal product for the same indication. The period of market exclusivity is extended by two years for medicines that have also complied with an agreed PIP.

This period may, however, be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for orphan drug designation, for example because the product is sufficiently profitable not to justify market exclusivity. Market exclusivity can be revoked only in very selected cases, such as consent from the marketing authorization holder, inability to supply sufficient quantities of the product, demonstration of “clinical superiority” by a similar medicinal product, or, after a review by the Committee for Orphan Medicinal Products, requested by a member state in the fifth year of the marketing exclusivity period (if the designation criteria are believed to no longer apply). Medicinal products designated as orphan drugs are eligible for incentives made available by the EU and its Member States to support research into, and the development and availability of, orphan drugs.

Human Capital

As of February 28, 2026, we had eight full-time employees and also utilize the services of key part-time employees or consultants. We contract with consultants and third parties for the conduct of certain clinical development, accounting and administrative activities. We anticipate hiring of additional employees as we continue to advance our clinical trial programs. None of our employees are represented by labor unions or covered by collective bargaining agreements.

Our human capital resource objectives include, as applicable, identifying, recruiting, retaining, training, incentivizing, and integrating our existing and new employees, advisors and consultants. We offer competitive compensation packages that are competitive within our industry. We incentivize high performance through an annual bonus program based on organizational performance, for which all employees are eligible. We also offer equity incentive plans, the purpose of which are to attract, retain and reward personnel through the granting of stock-based compensation awards. These awards are granted in order to align employee and consultant performance incentives with objectives that will increase stockholder value.

Corporate Information

We were incorporated in Delaware in 2008. Our principal executive offices are located at 101 Lindenwood Drive, Suite 225, Malvern, PA 19355 and our telephone number is (484) 875 3192.

Available Information

We file annual, quarterly, and current reports, proxy statements, and other documents with the Securities and Exchange Commission (“SEC”) under the Securities Exchange Act of 1934, as amended (the “Exchange Act”). The SEC maintains an internet website, www.sec.gov, that contains reports, proxy, and information statements, and other information regarding issuers, including us, that file electronically with the SEC. Copies of each of our filings with the SEC on Form 10-K, Form 10-Q, and Form 8-K and amendments to those reports, can be viewed and downloaded free of charge at our website, www.annovisbio.com, as soon as reasonably practicable after the reports and amendments are electronically filed with or furnished to the SEC. Our website and the information contained on, or that can be accessed through, our website shall not be deemed to be incorporated by reference in, and is not considered part of this Annual Report on Form 10-K.