10q10k10q10k.net

What changed in Annovis Bio, Inc.'s 10-K — 2024 vs 2025

vs

Paragraph-level year-over-year comparison of Annovis Bio, Inc.'s 2024 and 2025 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2025 report.

+411 added−403 removedSource: 10-K (2026-03-13) vs 10-K (2025-03-21)

Top changes in Annovis Bio, Inc.'s 2025 10-K

411 paragraphs added · 403 removed · 336 edited across 7 sections

Item 1. Business

Business — how the company describes what it does

134 edited+24 added−12 removed158 unchanged
Biggest changeIn 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. 26 Table of Contents 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.
Biggest changeIn 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 27 Table of Contents they make to U.S. physicians and teaching hospitals as well as physician ownership and investment interests in the manufacturer.
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, placebo-controlled.
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.
Patients will visit the clinic for the first-time dosing in clinic, 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.
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.
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 regularly took, whether for AD or for other conditions, as long as they were stable on such medication.
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.
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 family relates to treating brain metastasis via administration of buntanetap or related compounds.
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 several studies, buntanetap was observed to inhibit the synthesis of neurotoxic proteins — APP/Aβ (“APP”), tau/phospho- tau (“tau”) and α-Synuclein (“αSYN”) — that are some of the main causes of neurodegeneration. High levels of neurotoxic proteins lead to reduced axonal transport, which is responsible for the communication between and within nerve cells.
In several studies, buntanetap was observed to inhibit the synthesis of neurotoxic proteins — APP/Aβ (“APP”), tau/phospho-tau (“tau”), α-Synuclein (“αSYN”) and TDP43 — that are some of the main causes of neurodegeneration. High levels of neurotoxic proteins lead to reduced axonal transport, which is responsible for communication between and within nerve cells.
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 participating. Patients were randomly assigned to receive either 7.5, 15 or 30 mg of buntanetap or placebo, once per day.
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 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 to be randomly assigned to receive either 30 mg of buntanetap or placebo, once per day.
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.
First, the 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.
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, that is preserved and responsible for their translation.
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.
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. More in particular, in 2024 the Company filed with the USPTO a provisional patent application directed to these new methods of 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.
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.
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.
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 Investigational New Drug application (“IND”), 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.
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.
Patients participating in the trial are age 55-85, have a study partner, are of non-child-bearing age or agree to effective contraception, and have no evidence of suicidal ideation.
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.
When that communication is compromised, the immune system is activated and attacks the nerve cells, eventually killing them. We have observed in our clinical studies in early AD and early PD patients and pre-clinical studies in mice and rats that buntanetap lowered neurotoxic protein levels leading to improved axonal transport, reduced inflammation, lower nerve cell death and improved affected function.
When that communication is compromised, the immune system is activated and attacks the nerve cells, eventually killing them. We have observed in our completed clinical studies in AD and PD patients and pre-clinical studies in mice and rats that buntanetap lowered neurotoxic protein levels leading to improved axonal transport, reduced inflammation, lower nerve cell death and improved affected function.
Progress across these newer technology platforms has been slow. 18 Table of Contents 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.
Progress across these newer technology platforms has been slow. 19 Table of Contents 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.
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 Parkinson’s disease, 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.
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.
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. 16 Table of Contents Alzheimer’s Disease Market AD is a neurodegenerative disorder with cognitive, functional, and behavioral alterations.
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. 17 Table of Contents Alzheimer’s Disease Market AD is a neurodegenerative disorder with cognitive, functional, and behavioral alterations.
By preventing the overexpression of these neurotoxic proteins, buntanetap is designed to reverse the downstream toxic cascade that leads to neurodegeneration and reinstates homeostasis. 7 Table of Contents 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.
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: 8 Table of Contents MOA; Chen XQ et al. Pharmaceutics 09-2021 Iron and Neurodegeneration; Wong f. et al.
After accounting for age, persons with multiple diagnoses were almost three times more likely to exhibit dementia compared to those with one pathologic diagnosis. 17 Table of Contents We believe that a therapy that only addresses Aβ, tau or αSYN is less likely to help people with mixed pathologies.
After accounting for age, persons with multiple diagnoses were almost three times more likely to exhibit dementia compared to those with one pathologic diagnosis. 18 Table of Contents We believe that a therapy that only addresses Aβ, tau or αSYN is less likely to help people with mixed pathologies.
The Phase 3 program will investigate 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.
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.
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 aspect of nerve and brain degeneration.
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.
The Phase 2/3 AD study 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.
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.
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 received marketing approval. We also rely on these third parties for encapsulating, packaging and stabilizing clinical trial materials.
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.
Our approach is innovative in that we do not have a single 8 Table of Contents 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.
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.
More specifically, ADAS-Cog 11 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.
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.
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, pharmacokinetics, population pharmacokinetics, and confirmed that development can proceed using the new crystal form of buntanetap. .
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.
The data exclusivity period prevents generic or biosimilar applicants from relying on the pre-clinical 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 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.
Based on pre-clinical 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.
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 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 pharmacokinetics of buntanetap, as measured by the concentration of buntanetap in plasma.
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.
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 SEC under the Securities Exchange Act of 1934, as amended (the “Exchange Act”).
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 secondary endpoints were evaluated using the following measures: the ADCS-Instrumental Activities of Daily Living Scale (“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 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.
In the Phase 2/3 AD Study, mild to moderate AD patients were defined as those with a MMSE score between 14 and 24. Our Phase 3 PD Study and Phase 2/3 AD Study each had built in interim analyses.
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 ultimate goal is to develop a disease modifying drug (“DMD”) for patients with neurodegeneration by leveraging our clinical and pre-clinical data, which shows inhibition of the most relevant neurotoxic proteins.
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.
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 New Drug Applications (NDAs), one for short-term and one for long-term efficacy.
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.
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, 2025, we had eight full-time employees. We also utilize the services of seven key part-time employees or consultants.
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.
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, 6 Table of Contents with experience garnered at companies including Centocor, MedImmune, OraSure Technologies and Vicuron Pharmaceuticals. Ms.
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.
Up to 50% of patients with PDD develop sufficient numbers of Aβ plaques and tau-containing neurofibrillary tangles for a secondary diagnosis of Alzheimer’s disease, 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.
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.
At the termination of the treatment, all of the rats were first tested for their performance in a water 15 Table of Contents 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.
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.
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 Prion’s disease, tauopathies, chronic traumatic encephalopathy, prion diseases, amyotrophic lateral sclerosis, Alzheimer’s and Huntington’s disease.
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.
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. 21 Table of Contents U.S.
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.
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.
Axonal transport is responsible for: ● neurotransmitters GABA (anxiety), ACh (cognition), dopamine (movement), serotonin (mood); ● neurotrophic factors NGF, BDNF; and 15 Table of Contents ● 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.
Clinical trials are conducted under protocols detailing, among other 22 Table of Contents 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.
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.
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, 25 Table of Contents Medicaid, TRICARE and the Veterans Administration, as well as managed care organizations and private health insurers.
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.
The Phase 2/3 AD study 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.
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 .
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.
Thus, ANVS405 demonstrated the ability to protect the striatum following FPI in rats. 16 Table of Contents 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.
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 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 13 Table of Contents results.
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.
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. 25 Table of Contents The FDA also may require submission of a REMS plan to ensure that the benefits of the drug outweigh its risks.
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 R&D services (later acquired by ChiRex). Dr. Christie is co-author or co-inventor on several publications and patents.
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.
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 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.
As a condition of approval, the FDA may require a 23 Table of Contents 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.
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.
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. 14 Table of Contents The transfer of information in a nerve cell is called axonal transport.
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.
We believe that we are the only company developing a drug for AD and PD that is designed to inhibit more than one neurotoxic protein and has a mechanism of action designed to restore nerve cell axonal and synaptic activity.
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.
Patients visited the clinic for the first-time dosing in clinic, followed by an at home dosing period of 12 weeks. The study plan incorporated an interim analysis at six-weeks, the results of which were disclosed on October 23,2023.
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.
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.
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 20 Table of Contents before and after the injury.
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.
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. 26 Table of Contents U.S.
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.
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. 29 Table of Contents
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 U.S. The AD/PD Trials were double-blind, placebo-controlled studies which treated mild to moderate AD and early PD patients for 25 +/- 2 days.
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 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 U.S. and outside the U.S. as National and Regional Phase patent applications of the PCT application.
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.
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.
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 23 Table of Contents clinical trial on a clinical hold.
During the end-of-phase 2 meeting for AD, the FDA raised no concerns with the Company’s data on buntanetap’s safety, including impact on liver enzymes, drug interactions, dose selection, pharmacokinetics and population pharmacokinetics. Further, the FDA confirmed that future development can proceed using the new crystal form of buntanetap.
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 .
In addition to meeting their primary endpoints of safety and tolerability and secondary endpoint of pharmacokinetics (“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.
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.
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.
The industry has historically encountered challenges in specifically targeting one neurotoxic protein, be it APP, 6 Table of Contents tau or αSYN, indicating that doing so does not change the underlying course of neurodegeneration.
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, our Founder, President and CEO, founded Annovis in May 2008 to develop improved therapeutics for neurodegeneration.
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.
In the WAIS coding test, PD patients showed a statistically significant improvement both from baseline (17.1% for 10+20mg; 13.3% for all doses combined) and from placebo (27.1% for 10+20mg; 23.3% for all doses combined).
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).
The secondary endpoints were evaluated using the following measures: the MDS-UPDRS total score, which includes the Part II and III measures we well as mentation, behavior, and mood symptoms, and complications of dopaminergic therapy; the participant global impression of change (“PGIC”), a participant-reported outcome which asks how their condition has changed compared to their condition at the beginning of treatment; and the Change on Clinical Global Impression of Severity (“CGIS”), which measures the severity of movement impairment as assessed by a site rater.
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.
Since the AD brain contains several neurotoxic proteins—amyloid precursor protein 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.
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.
The Company also expects to seek New Chemical Entity status for Posiphen Form B before the US Food and Drug Administration (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 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.
Based on the results of the interim analysis, we proceeded with the Phase 3 PD Study as planned in accordance with the previously established protocol. The Phase 3 PD Trial’s primary endpoints were evaluated using the following measures: MDS-UPDRS Part II and III.
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.
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.
In collaboration with the Alzheimer’s Disease Cooperative Study (“ADCS”), we also conducted a trial in 16 early AD 5 Table of Contents patients (the “ADCS Trial”). In the ADCS Trial, early AD patients were defined as those patients with a MMSE score between 19 and 28.
ANVS405 ANVS405 is an intravenous drug being developed for acute indications and focused on protecting the brain after Traumatic Brain Injury (“TBI”) and/or stroke. ANVS405 is the same compound as buntanetap, given in cases of acute head and brain trauma.
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.
Our plan is to seek further funding to conduct the toxicology and pharmacokinetics (“PK”) studies in animals, file the initial new drug application (“IND”), conduct the safety and PK studies in humans and later, continue with Phase 2 and Phase 3 efficacy studies.
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.
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) as to Posiphen Form B and uses thereof.
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.
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 aligned on a development path for buntanetap towards the filing of New Drug Applications (NDAs), one for short-term and one for long-term efficacy.
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.
Studies have found that AD and PD are the most common neurodegenerative diseases in the U.S., and accordingly these diseases present two unmet needs of the aging population and two potentially large U.S. markets, if a DMD is developed and approved.
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.
She was previously the Founder and CEO of Symphony Pharmaceuticals/Annovis, a biotech company that was sold to Transgenomic in 2001. She was previously 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.
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.
To date, over 1,000 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.
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: 10 Table of Contents 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.
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.
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.
The inclusion criteria for early PD was Hoehn & Yahr 1, 2 and 3 with less than 2 hours of OFF time, as well as a MMSE score of 22 to 30. Patients participating in the trial were age 40-85, were of non-child-bearing age or agree to effective contraception and had no evidence of suicidal ideation.
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.
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.
Most products that are eligible for fast-track designation are also likely to be considered appropriate to receive a priority review. 24 Table of Contents 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.

… 90 more changes not shown on this page.

Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

144 edited+10 added−22 removed540 unchanged
Biggest changeHITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions; ● the Federal Food, Drug and Cosmetic Act (“FDCA”), which prohibits, among other things, the adulteration or misbranding of drugs, biologics and medical devices; ● the U.S. federal legislation commonly referred to as the Physician Payments Sunshine Act, enacted as part of the ACA, and its implementing regulations, which requires certain manufacturers of drugs, devices, biologics, and medical supplies that are reimbursable under Medicare, Medicaid, or the Children’s Health Insurance Program to report annually to the government information related to certain payments and other transfers of value to physicians and teaching hospitals, as well as ownership and investment interests held by the physicians described above and their immediate family members; and ● analogous U.S. state laws and regulations, including: state anti-kickback and false claims laws, which may apply to our business practices, including but not limited to, research, distribution, sales, and marketing arrangements and claims involving healthcare items or services reimbursed by any third-party payor, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the U.S. federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws and regulations that require drug manufacturers to file reports relating to pricing and marketing information, which requires tracking gifts and other remuneration and items of value provided to healthcare professionals and entities; and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
Biggest changeHITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions; ● the Federal Food, Drug and Cosmetic Act (“FDCA”), which prohibits, among other things, the adulteration or misbranding of drugs, biologics and medical devices; ● the U.S. federal legislation commonly referred to as the Physician Payments Sunshine Act, enacted as part of the ACA, and its implementing regulations, which requires certain manufacturers of drugs, devices, biologics, and medical supplies that are reimbursable under Medicare, Medicaid, or the Children’s Health Insurance Program to report annually to the government information related to certain payments and other transfers of value to physicians and teaching hospitals, as well as ownership and investment interests held by the physicians described above and their immediate family members; and ● analogous U.S. state laws and regulations, including: state anti-kickback and false claims laws, which may apply to our business practices, including but not limited to, research, distribution, sales, and marketing arrangements and claims involving healthcare items or services reimbursed by any third-party payor, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the U.S. federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws and regulations that require drug manufacturers to file reports relating to pricing and marketing information, which requires tracking gifts and other remuneration and items of value provided to healthcare professionals and entities; and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts. 56 Table of Contents Because of the breadth of these laws and the narrowness of the statutory exceptions and regulatory safe harbors available under such laws, it is possible that some of our business activities, including our consulting agreements and other relationships with physicians and other healthcare providers, some of whom receive stock or stock options as compensation for their services, could be subject to challenge under one or more of such laws.
The GDPR provides that EU member states may establish their own laws and regulations limiting the processing of personal data, including genetic, biometric or health data, which could limit our ability to use and share personal data or could cause our costs to increase.
The GDPR provides that the EU member states may establish their own laws and regulations limiting the processing of personal data, including genetic, biometric or health data, which could limit our ability to use and share personal data or could cause our costs to increase.
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.
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.
Patent applications in the United States, EU and elsewhere are published approximately 18 months after the earliest filing for which priority is claimed, with such earliest filing date being commonly referred to as the priority date. Therefore, patent applications covering our future product candidates, or their manufacture or use may currently be unpublished.
Patent applications in the United States, the EU and elsewhere are published approximately 18 months after the earliest filing for which priority is claimed, with such earliest filing date being commonly referred to as the priority date. Therefore, patent applications covering our future product candidates, or their manufacture or use may currently be unpublished.
Depending upon the timing, duration and conditions of FDA marketing approval of our product candidates, we may be able to extend the term of a patent covering each product candidate under the Drug Price Competition and Patent Term Restoration Act of 1984, referred to as the Hatch-Waxman Amendments and similar legislation in the EU.
Depending upon the timing, duration and conditions of the FDA marketing approval of our product candidates, we may be able to extend the term of a patent covering each product candidate under the Drug Price Competition and Patent Term Restoration Act of 1984, referred to as the Hatch-Waxman Amendments and similar legislation in the EU.
Even if we are successful, litigation could result in substantial cost and be a distraction to our management and other employees. Our proprietary information may be lost, or we may suffer security breaches.
Even if we are successful, litigation could result in a substantial cost and be a distraction to our management and other employees. Our proprietary information may be lost, or we may suffer security breaches.
These systems can be subject to technical system flaws; power loss; cyber attacks, including viruses, malware, phishing, ransomware, terrorism, and surveillance, unauthorized access, malicious software, intentional or inadvertent data privacy breaches by employees or others with authorized access, hacktivism, ransomware, physical or electronic break-ins, fires or natural disasters, supply chain attacks, and other cybersecurity issues.
These systems can be subject to technical system flaws; power loss; cyber attacks, including viruses, malware, phishing, ransomware, terrorism, surveillance, unauthorized access, malicious software, intentional or inadvertent data privacy breaches by employees or others with authorized access, hacktivism, ransomware, physical or electronic break-ins, fires or natural disasters, supply chain attacks and other cybersecurity issues.
Collaborations involving buntanetap or any future product candidates would pose significant risks to us, including the following: ● collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations; ● collaborators may not perform their obligations as expected or at all; ● we could grant exclusive rights to our collaborators that would prevent us from collaborating with others; ● collaborators may not pursue development and commercialization of any product candidates that achieve regulatory approval or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborators’ strategic focus or available funding, or external factors, such as an acquisition, that divert resources or create competing priorities; ● collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; ● collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; ● product candidates discovered in collaboration with us may be viewed by our collaborators as competitive with their own product candidates or drugs, which may cause collaborators to cease to devote resources to the commercialization of our product candidates; ● a collaborator with marketing and distribution rights to any product candidate that achieves regulatory approval may not commit sufficient resources to the marketing and distribution of such products; ● a collaborator’s sales and marketing activities or other operations may not be in compliance with applicable laws, resulting in civil or criminal proceedings; ● disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or the preferred course of development, might cause delays in or termination of the research, development or commercialization of product candidates, might lead to additional responsibilities for us with respect to product candidates, or might result in litigation or arbitration, any of which would be time-consuming and expensive; ● collaborators may not properly enforce, maintain or defend our or their intellectual property rights or may use our or their proprietary information in such a way as to invite litigation that could jeopardize or invalidate such intellectual property or proprietary information or expose us to potential litigation; 70 Table of Contents ● collaborators may infringe, misappropriate or otherwise violate the intellectual property rights of third parties, which may expose us to litigation and potential liability; ● collaborators may not provide us with timely and accurate information regarding development, regulatory or commercialization status or results, which could adversely impact our ability to manage our own development efforts, accurately forecast financial results or provide timely information to our stockholders regarding our out-licensed product candidates; ● we may be required to invest resources and attention into such collaboration, which could distract from other business objectives; ● disputes may arise between the collaborators and us regarding ownership of or other rights in the intellectual property generated in the course of the collaborations; ● collaboration agreements may not lead to development or commercialization of product candidates in the most efficient manner or at all; ● if a collaborator of ours were to be involved in a business combination, the continued pursuit and emphasis on our product development or commercialization program could be delayed, diminished or terminated; and ● collaborations may be terminated, including for the convenience of the collaborator, prior to or upon the expiration of the agreed upon terms and, if terminated, we may find it more difficult to enter into future collaborations or be required to raise additional capital to pursue further development or commercialization of the applicable product candidates.
Collaborations involving buntanetap or any future product candidates would pose significant risks to us, including the following: ● collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations; ● collaborators may not perform their obligations as expected, or at all; ● we could grant exclusive rights to our collaborators that would prevent us from collaborating with others; ● collaborators may not pursue development and commercialization of any product candidates that achieve regulatory approval or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborators’ strategic focus or available funding, or external factors, such as an acquisition, that divert resources or create competing priorities; ● collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; ● collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; ● product candidates discovered in collaboration with us may be viewed by our collaborators as competitive with their own product candidates or drugs, which may cause collaborators to cease to devote resources to the commercialization of our product candidates; ● a collaborator with marketing and distribution rights to any product candidate that achieves regulatory approval may not commit sufficient resources to the marketing and distribution of such products; ● a collaborator’s sales and marketing activities or other operations may not be in compliance with applicable laws, resulting in civil or criminal proceedings; ● disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or the preferred course of development, might cause delays in or termination of the research, development or commercialization of product candidates, might lead to additional responsibilities for us with respect to product candidates or might result in litigation or arbitration, any of which would be time-consuming and expensive; ● collaborators may not properly enforce, maintain or defend our or their intellectual property rights or may use our or their proprietary information in such a way as to invite litigation that could jeopardize or invalidate such intellectual property or proprietary information or expose us to potential litigation; 72 Table of Contents ● collaborators may infringe, misappropriate or otherwise violate the intellectual property rights of third parties, which may expose us to litigation and potential liability; ● collaborators may not provide us with timely and accurate information regarding development, regulatory or commercialization status or results, which could adversely impact our ability to manage our own development efforts, accurately forecast financial results or provide timely information to our stockholders regarding our out-licensed product candidates; ● we may be required to invest resources and attention into such collaboration, which could distract us from other business objectives; ● disputes may arise between the collaborators and us regarding ownership of or other rights in the intellectual property generated in the course of the collaborations; ● collaboration agreements may not lead to development or commercialization of product candidates in the most efficient manner, or at all; ● if a collaborator of ours were to be involved in a business combination, the continued pursuit and emphasis on our product development or commercialization program could be delayed, diminished or terminated; and ● collaborations may be terminated, including for the convenience of the collaborator, prior to or upon the expiration of the agreed upon terms and, if terminated, we may find it more difficult to enter into future collaborations or be required to raise additional capital to pursue further development or commercialization of the applicable product candidates.
Our future funding requirements, both near and long-term, will depend on many factors, including, but not limited to: ● the initiation, progress, timing, costs and results of preclinical studies and clinical trials, including patient enrollment in such trials, for buntanetap or any other future product candidates; ● the clinical development plans we establish for buntanetap and any other future product candidates, including any modifications to clinical development plans based on feedback that we may receive from regulatory authorities; ● the number and characteristics of product candidates that we discover or in-license and develop; ● the outcome, timing and cost of regulatory meetings and reviews by the FDA and comparable foreign regulatory authorities, including the potential for the FDA or comparable foreign regulatory authorities to require that we perform more studies than those that we currently expect; ● the requirements of regulatory authorities in any additional jurisdictions in which we may seek approval for buntanetap and any future product candidates and our anticipated timing for seeking approval in such jurisdictions; ● the costs of filing, prosecuting, defending and enforcing any patent claims and maintaining and enforcing other intellectual property and proprietary rights; ● the effects of competing technological and market developments; ● the costs associated with hiring additional personnel and consultants as our business grows, including additional executive officers and clinical development, regulatory, CMC, quality and commercial personnel; ● the costs and timing of the implementation of commercial-scale manufacturing activities, if any product candidate is approved, including as a result of inflation, any supply chain issues or component shortages; ● the costs and timing of establishing sales, marketing and distribution capabilities for any product candidates for which we may receive regulatory approval; ● our ability to achieve sufficient market acceptance, coverage and adequate reimbursement from third-party payors and adequate market share and revenue for any approved products; ● the terms and timing of establishing and maintaining collaborations, licenses and other similar arrangements; and ● the costs associated with any products or technologies that we may in-license or acquire; Conducting clinical trials and preclinical studies and potentially identifying future product candidates is a time consuming, expensive and uncertain process that takes years to complete, and we may never generate the necessary data or results required to 31 Table of Contents obtain regulatory approval and commercialize buntanetap or any future product candidates.
Our future funding requirements, both near and long-term, will depend on many factors, including, but not limited to: ● the initiation, progress, timing, costs and results of preclinical studies and clinical trials, including patient enrollment in such trials, for buntanetap or any other future product candidates; ● the clinical development plans we establish for buntanetap and any other future product candidates, including any modifications to clinical development plans based on feedback that we may receive from regulatory authorities; ● the number and characteristics of product candidates that we discover or in-license and develop; ● the outcome, timing and cost of regulatory meetings and reviews by the FDA and comparable foreign regulatory authorities, including the potential for the FDA or comparable foreign regulatory authorities to require that we perform more studies than those that we currently expect; ● the requirements of regulatory authorities in any additional jurisdictions in which we may seek approval for buntanetap and any future product candidates and our anticipated timing for seeking approval in such jurisdictions; ● the costs of filing, prosecuting, defending and enforcing any patent claims and maintaining and enforcing other intellectual property and proprietary rights; ● the effects of competing technological and market developments; ● the costs associated with hiring additional personnel and consultants as our business grows, including additional executive officers and clinical development, regulatory, CMC, quality and commercial personnel; ● the costs and timing of the implementation of commercial-scale manufacturing activities, if any product candidate is approved, including as a result of inflation, any supply chain issues or component shortages; 32 Table of Contents ● the costs and timing of establishing sales, marketing and distribution capabilities for any product candidates for which we may receive regulatory approval; ● our ability to achieve sufficient market acceptance, coverage and adequate reimbursement from third-party payors and adequate market share and revenue for any approved products; ● the terms and timing of establishing and maintaining collaborations, licenses and other similar arrangements; and ● the costs associated with any products or technologies that we may in-license or acquire; Conducting clinical trials and preclinical studies and potentially identifying future product candidates is a time-consuming, expensive and uncertain process that takes years to complete, and we may never generate the necessary data or results required to obtain regulatory approval and commercialize buntanetap or any future product candidates.
The degree of market acceptance of our product candidates, if approved, will depend on a number of factors, including but not limited to: ● the efficacy and potential advantages compared to alternative treatments; ● the indications for which our product candidates are approved; ● the limitation of our targeted patient population and other limitations or warnings contained in any FDA-approved labeling; ● effectiveness of sales and marketing efforts; ● the cost of treatment in relation to alternative treatments, including any similar generic treatments; ● our ability to offer our products for sale at competitive prices; ● the convenience and ease of administration compared to alternative treatments; ● the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; ● the strength of marketing and distribution support; 48 Table of Contents ● the availability of third-party coverage and adequate reimbursement; ● the willingness of patients to pay all, or a portion of, out-of-pocket costs associated with our products in the absence of sufficient third-party coverage and adequate reimbursement; ● the prevalence and severity of any side effects; ● any restrictions on the use of our product together with other medications; ● potential product liability claims; ● the timing of market introduction of our products as well as availability, safety and efficacy of competitive drugs; and ● unfavorable publicity relating to the product.
The degree of market acceptance of our product candidates, if approved, will depend on a number of factors, including but not limited to: ● the efficacy and potential advantages compared to alternative treatments; ● the indications for which our product candidates are approved; 49 Table of Contents ● the limitation of our targeted patient population and other limitations or warnings contained in any FDA-approved labeling; ● effectiveness of sales and marketing efforts; ● the cost of treatment in relation to alternative treatments, including any similar generic treatments; ● our ability to offer our products for sale at competitive prices; ● the convenience and ease of administration compared to alternative treatments; ● the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; ● the strength of marketing and distribution support; ● the availability of third-party coverage and adequate reimbursement; ● the willingness of patients to pay all, or a portion of, out-of-pocket costs associated with our products in the absence of sufficient third-party coverage and adequate reimbursement; ● the prevalence and severity of any side effects; ● any restrictions on the use of our product together with other medications; ● potential product liability claims; ● the timing of market introduction of our products as well as availability, safety and efficacy of competitive drugs; and ● unfavorable publicity relating to the product.
Patient enrollment and retention in clinical trials depends on many factors, including: ● the patient eligibility and exclusion criteria as defined in the protocol; ● the size of the patient population required for analysis of the trial’s primary endpoints; ● the nature and design of the trial protocol; ● the existing body of safety and efficacy data with respect to the product candidate; ● the proximity of patients to clinical sites; ● our ability to recruit clinical trial investigators with the appropriate competencies and experience; ● clinicians’ and patients’ perceptions as to the potential advantages and risks of the product candidate being studied in relation to other available therapies, including any new drugs that may be approved for the indications we are investigating; ● competing clinical trials being conducted by other companies or institutions; ● our ability to obtain and maintain patient consents; and 38 Table of Contents ● the risk that patients enrolled in clinical trials will drop out of the trials before completion.
Patient enrollment and retention in clinical trials depends on many factors, including: ● the patient eligibility and exclusion criteria as defined in the protocol; ● the size of the patient population required for analysis of the trial’s primary endpoints; ● the nature and design of the trial protocol; 39 Table of Contents ● the existing body of safety and efficacy data with respect to the product candidate; ● the proximity of patients to clinical sites; ● our ability to recruit clinical trial investigators with the appropriate competencies and experience; ● clinicians’ and patients’ perceptions as to the potential advantages and risks of the product candidate being studied in relation to other available therapies, including any new drugs that may be approved for the indications we are investigating; ● competing clinical trials being conducted by other companies or institutions; ● our ability to obtain and maintain patient consents; and ● the risk that patients enrolled in clinical trials will drop out of the trials before completion.
If approved, buntanetap and any future product candidates may not achieve commerciab success. Our commercial revenue, if any, will initially be derived from sales of buntanetap, which we do not expect to be commercially available for many years, if at all. Accordingly, we will need to continue to rely on additional financing to achieve our business objectives.
If approved, buntanetap and any future product candidates may not achieve commercial success. Our commercial revenue, if any, will initially be derived from sales of buntanetap, which we do not expect to be commercially available for many years, if at all. Accordingly, we will need to continue to rely on additional financing to achieve our business objectives.
Our operations have consumed substantial amounts of cash since inception. We expect to continue to spend substantial amounts to advance the clinical development of buntanetap. If we obtain receive regulatory approval for buntanetap or any other product candidates, we also expect to incur significant commercialization expenses related to product manufacturing, marketing, sales, and distribution.
Our operations have consumed substantial amounts of cash since inception. We expect to continue to spend substantial amounts to advance the clinical development of buntanetap. If we obtain regulatory approval for buntanetap or any other product candidates, we also expect to incur significant commercialization expenses related to product manufacturing, marketing, sales, and distribution.
If we obtain regulatory approval of product candidates and ultimately commercialize our products in foreign markets, we would be subject to additional risks and uncertainties, including: ● different regulatory requirements for approval of drugs in foreign countries; ● reduced protection for intellectual property rights; ● the existence of additional third-party patent rights of potential relevance to our business; ● unexpected changes in tariffs, trade barriers and regulatory requirements; 42 Table of Contents ● economic weakness, including inflation, or political instability in particular foreign economies and markets; ● compliance with export control and import laws and regulations; ● compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; ● foreign currency fluctuations, which could result in increased operating expenses and reduced revenue, and other obligations incident to doing business in another country; ● foreign reimbursement, pricing and insurance regimes; ● workforce uncertainty in countries where labor unrest is common; ● differing regulatory requirements with respect to manufacturing of products; ● production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and ● business interruptions resulting from geopolitical actions, including war and terrorism, or natural disasters including earthquakes, typhoons, floods and fires.
If we obtain regulatory approval of product candidates and ultimately commercialize our products in foreign markets, we would be subject to additional risks and uncertainties, including: ● different regulatory requirements for approval of drugs in foreign countries; ● reduced protection for intellectual property rights; ● the existence of additional third-party patent rights of potential relevance to our business; ● unexpected changes in tariffs, trade barriers and regulatory requirements; ● economic weakness, including inflation, or political instability in particular foreign economies and markets; ● compliance with export control and import laws and regulations; ● compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; ● foreign currency fluctuations, which could result in increased operating expenses and reduced revenue, and other obligations incident to doing business in another country; ● foreign reimbursement, pricing and insurance regimes; ● workforce uncertainty in countries where labor unrest is common; ● differing regulatory requirements with respect to manufacturing of products; ● production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and ● business interruptions resulting from geopolitical actions, including war and terrorism, or natural disasters including earthquakes, typhoons, floods and fires.
The patent applications that we own may fail to result in issued patents with claims that provide further coverage of buntanetap, Posiphen Form B, or any other product candidate in the United States or in other foreign countries. 59 Table of Contents Our patents may be challenged in courts, in patent offices or before other administrative bodies which could result in the invalidation, narrowing or unenforceability of our patents and our patent portfolio, along with the unpredictable nature of patent prosecution, may not provide us with sufficient rights to similarly challenge other parties or exclude others from commercializing products similar or identical to ours.
The patent applications that we own may fail to result in issued patents with claims that provide further coverage of buntanetap, Posiphen Form B, or any other product candidate in the United States or in other foreign countries. 61 Table of Contents Our patents may be challenged in courts, in patent offices or before other administrative bodies which could result in the invalidation, narrowing or unenforceability of our patents and our patent portfolio, along with the unpredictable nature of patent prosecution, may not provide us with sufficient rights to similarly challenge other parties or exclude others from commercializing products similar or identical to ours.
It is not possible to prevent all threats or to our information technology systems and information and those of our third-party service providers, over which we exert less control, and any controls we implement to do so may prove to be ineffective.
It is not possible to prevent all threats to our information technology systems and information and those of our third-party service providers, over which we exert less control, and any controls we implement to do so may prove to be ineffective.
In addition, regardless of merit or eventual outcome, product liability claims may result in: ● impairment of our business reputation and significant negative media attention; ● withdrawal of participants from our clinical trials; ● significant costs to defend the litigation; ● distraction of management’s attention and our resources from our primary business; ● substantial monetary awards to patients or other claimants; ● inability to commercialize buntanetap or any other product candidate; ● product recalls, withdrawals or labeling, marketing or promotional restrictions; ● decreased market demand for any product; 45 Table of Contents ● significant negative financial impact; and ● a decline in our stock price.
In addition, regardless of merit or eventual outcome, product liability claims may result in: ● impairment of our business reputation and significant negative media attention; ● withdrawal of participants from our clinical trials; 46 Table of Contents ● significant costs to defend the litigation; ● distraction of management’s attention and our resources from our primary business; ● substantial monetary awards to patients or other claimants; ● inability to commercialize buntanetap or any other product candidate; ● product recalls, withdrawals or labeling, marketing or promotional restrictions; ● decreased market demand for any product; ● significant negative financial impact; and ● a decline in our stock price.
Risks Related to Our Common Stock The market price of our common stock has been volatile and fluctuated substantially in the past and may continue to experience volatility and substantial fluctuations in the future, which could result in substantial losses for purchasers of our common stock. The market price of our common stock is highly volatile.
Risks Related to Our Common Stock The market price of our common stock has been volatile and fluctuated substantially in the past and may continue to experience volatility and substantial fluctuations in the future, which could result in substantial losses for purchasers of our common stock. The market price of our common stock is volatile.
In addition, manufacturers can be held liable under the FCA even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims; 54 Table of Contents ● Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), which imposes criminal and civil liability for, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private) and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement, in connection with the delivery of, or payment for, healthcare benefits, items or services.
In addition, manufacturers can be held liable under the FCA even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims; ● Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), which imposes criminal and civil liability for, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private) and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement, in connection with the delivery of, or payment for, healthcare benefits, items or services.
The market price of our common stock may be subject to wide fluctuations in response to a variety of factors, including the following: ● results of our clinical trials, and the results of trials of our competitors or those of other companies in our market sector; ● our ability to enroll subjects in our future clinical trials; ● delays or unanticipated developments in the completion of our planned clinical trials; ● any delay in submitting an NDA and any adverse development or perceived adverse development with respect to the FDA’s review of that NDA; ● our ability to obtain and maintain regulatory approval of buntanetap or any future product candidates or additional indications thereof, or limitations to specific label indications or patient populations for its use, or changes or delays in the regulatory review process; ● failure to successfully develop and commercialize buntanetap or any future product candidates; 72 Table of Contents ● the degree and rate of physician and market adoption of any of our current and future product candidates; ● inability to obtain additional funding or obtaining funding on unattractive terms; ● regulatory or legal developments in the United States and other countries applicable to buntanetap or any other product candidates; ● adverse regulatory decisions; ● changes in the structure of healthcare payment systems; ● manufacturing, supply or distribution delays or shortages, including our inability to obtain adequate product supply for buntanetap or any other product candidates, or the inability to do so at acceptable prices; ● the success or failure of our efforts to identify, develop, acquire or license additional product candidates; ● introduction of new products, services or technologies by our competitors; ● failure to meet or exceed financial projections we provide to the public; ● failure to meet or exceed the estimates and projections of the investment community; ● changes in the market valuations of companies similar to ours; ● market conditions in the pharmaceutical and biotechnology sectors, and the issuance of new or changed securities analysts’ reports or recommendations; ● announcements of significant acquisitions, strategic collaborations, joint ventures or capital commitments by us or our competitors; ● any changes to our relationship with any manufacturers, suppliers, collaborators or other strategic partners; ● significant lawsuits, including patent or shareholder litigation, and disputes or other developments relating to our proprietary rights, including patents, litigation matters and our ability to obtain patent protection for our technologies; ● additions or departures of key scientific or management personnel; ● sales of our common stock by us or our stockholders in the future; ● changes in our capital structure, such as future issuances of securities and the incurrence of additional debt; ● changes in accounting standards, policies, guidelines, interpretations or principles; ● trading volume of our common stock; ● actual or anticipated fluctuations in our financial condition and results of operations; ● publication of news releases by other companies in our industry, and especially direct competitors, including about adverse developments related to safety, effectiveness, accuracy and usability of their products, reputational concerns, reimbursement coverage, regulatory compliance, and product recalls; 73 Table of Contents ● announcement or progression of geopolitical events (including in relation to the conflict between Russia and Ukraine or Isreal and Hamas); and ● the other factors described in this “Risk Factors” section.
The market price of our common stock may be subject to wide fluctuations in response to a variety of factors, including the following: ● results of our clinical trials and the results of trials of our competitors or those of other companies in our market sector; ● our ability to enroll subjects in our future clinical trials; ● delays or unanticipated developments in the completion of our planned clinical trials; ● any delay in submitting an NDA and any adverse development or perceived adverse development with respect to the FDA’s review of that NDA; ● our ability to obtain and maintain regulatory approval of buntanetap or any future product candidates or additional indications thereof, or limitations to specific label indications or patient populations for its use, or changes or delays in the regulatory review process; ● failure to successfully develop and commercialize buntanetap or any future product candidates; ● the degree and rate of physician and market adoption of any of our current and future product candidates; 74 Table of Contents ● inability to obtain additional funding or obtaining funding on unattractive terms; ● regulatory or legal developments in the United States and other countries applicable to buntanetap or any other product candidates; ● adverse regulatory decisions; ● changes in the structure of healthcare payment systems; ● manufacturing, supply or distribution delays or shortages, including our inability to obtain adequate product supply for buntanetap or any other product candidates, or the inability to do so at acceptable prices; ● the success or failure of our efforts to identify, develop, acquire or license additional product candidates; ● introduction of new products, services or technologies by our competitors; ● failure to meet or exceed financial projections we provide to the public; ● failure to meet or exceed the estimates and projections of the investment community; ● changes in the market valuations of companies similar to ours; ● market conditions in the pharmaceutical and biotechnology sectors, and the issuance of new or changed securities analysts’ reports or recommendations; ● announcements of significant acquisitions, strategic collaborations, joint ventures or capital commitments by us or our competitors; ● any changes to our relationship with any manufacturers, suppliers, collaborators or other strategic partners; ● significant lawsuits, including patent or shareholder litigation, and disputes or other developments relating to our proprietary rights, including patents, litigation matters and our ability to obtain patent protection for our technologies; ● additions or departures of key scientific or management personnel; ● sales of our common stock by us or our stockholders in the future; ● changes in our capital structure, such as future issuances of securities and the incurrence of additional debt; ● changes in accounting standards, policies, guidelines, interpretations or principles; ● trading volume of our common stock; ● actual or anticipated fluctuations in our financial condition and results of operations; ● publication of news releases by other companies in our industry, and especially direct competitors, including about adverse developments related to safety, effectiveness, accuracy and usability of their products, reputational concerns, reimbursement coverage, regulatory compliance, and product recalls; ● announcement or progression of geopolitical events (including in relation to the conflict between Russia and Ukraine or in the Middle East); and 75 Table of Contents ● the other factors described in this “Risk Factors” section.
Additionally, other pharmaceutical companies targeting these same diseases are recruiting clinical trial patients from these patient populations, which may make it more difficult to fully enroll our clinical trials.
Additionally, other pharmaceutical companies targeting these same diseases are recruiting clinical trial patients from these patient populations, which may make it more difficult to fully enroll in our clinical trials.
Additionally, if one or more of our product candidates receives marketing approval, and we or others later identify undesirable side effects caused by such products, a number of potentially significant negative consequences could result, including: ● regulatory authorities may withdraw approvals of such product; 40 Table of Contents ● regulatory authorities may require additional warnings on the label, such as a “black box” warning or contraindication; ● additional restrictions may be imposed on the marketing of the particular product or the manufacturing processes for the product or any component thereof; ● we may be required to implement a REMS or create a medication guide outlining the risks of such side effects for distribution to patients; ● we could be sued and held liable for harm caused to patients; ● the product may become less competitive; and ● our reputation may suffer.
Additionally, if one or more of our product candidates receives marketing approval, and we or others later identify undesirable side effects caused by such products, a number of potentially significant negative consequences could result, including: ● regulatory authorities may withdraw approvals of such product; ● regulatory authorities may require additional warnings on the label, such as a “black box” warning or contraindication; ● additional restrictions may be imposed on the marketing of the particular product or the manufacturing processes for the product or any component thereof; ● we may be required to implement a REMS or create a medication guide outlining the risks of such side effects for distribution to patients; ● we could be sued and held liable for harm caused to patients; ● the product may become less competitive; and ● our reputation may suffer.
If our operations are found to be in violation of any of the laws described above or any other governmental laws and regulations that may apply to us, we may be subject to the imposition of civil, criminal and administrative penalties, damages, disgorgement, monetary fines, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, individual imprisonment, contractual damages, reputational harm, diminished profits and future earnings, additional reporting requirements or oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, and curtailment or restructuring of our operations, any of which could adversely affect our ability to 55 Table of Contents operate our business and our results of operations.
If our operations are found to be in violation of any of the laws described above or any other governmental laws and regulations that may apply to us, we may be subject to the imposition of civil, criminal and administrative penalties, damages, disgorgement, monetary fines, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, individual imprisonment, contractual damages, reputational harm, diminished profits and future earnings, additional reporting requirements or oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, and curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations.
However, trade secrets or confidential know-how can be difficult to maintain as confidential. 65 Table of Contents To protect this type of information against disclosure or appropriation by competitors, our policy is to require our employees, consultants, contractors and advisors to enter into confidentiality agreements and, if applicable, material transfer agreements, consulting agreements or other similar agreements with us prior to beginning research or disclosing proprietary information.
However, trade secrets or confidential know-how can be difficult to maintain as confidential. 67 Table of Contents To protect this type of information against disclosure or appropriation by competitors, our policy is to require our employees, consultants, contractors and advisors to enter into confidentiality agreements and, if applicable, material transfer agreements, consulting agreements or other similar agreements with us prior to beginning research or disclosing proprietary information.
We cannot guarantee that any of our or our licensors’ patent searches or analyses, including but not limited to the identification of relevant patents, the scope of patent claims or the expiration of relevant patents, are complete or thorough, nor can we be certain that we have identified each and every third-party patent and pending application in the United States, Europe and elsewhere that is relevant to or necessary for the commercialization of our product candidates in any jurisdiction.
We cannot guarantee that any of our or our licensors’ patent searches or analyses, including but not limited to the identification of relevant patents, the scope of patent claims or the expiration of relevant patents, are complete or thorough, nor can we be certain that we have identified each and every third-party patent and pending application in the United States, the EU and elsewhere that is relevant to or necessary for the commercialization of our product candidates in any jurisdiction.
The auditor’s opinion on our audited financial statements for the year ended December 31, 2024 includes an explanatory paragraph stating that we have incurred recurring losses from operations that raise substantial doubt about our ability to continue as a going concern for the next twelve months from the date of the financial statements included in this Annual Report on Form 10-K.
The auditor’s opinion on our audited financial statements for the year ended December 31, 2025, includes an explanatory paragraph stating that we have incurred recurring losses from operations that raise substantial doubt about our ability to continue as a going concern for the next twelve months from the date of the financial statements included in this Annual Report on Form 10-K.
In addition, later discovery of previously unknown adverse events or other problems with our products, manufacturers or manufacturing processes or failure to comply with regulatory requirements, may yield various results, including: ● restrictions on manufacturing such products; ● restrictions on the labeling or marketing of products; ● restrictions on product distribution or use; 43 Table of Contents ● requirements to conduct post-marketing studies or clinical trials; ● warning letters or untitled letters; ● withdrawal of the products from the market; ● refusal to approve pending applications or supplements to approved applications that we submit; ● recall of products; ● fines, restitution or disgorgement of profits or revenues; ● suspension or withdrawal of marketing approvals; ● refusal to permit the import or export of our products; ● product seizure; or ● injunctions or the imposition of civil or criminal penalties.
In addition, later discovery of previously unknown adverse events or other problems with our products, manufacturers or manufacturing processes or failure to comply with regulatory requirements, may yield various results, including: ● restrictions on manufacturing such products; ● restrictions on the labeling or marketing of products; ● restrictions on product distribution or use; ● requirements to conduct post-marketing studies or clinical trials; ● warning letters or untitled letters; ● withdrawal of the products from the market; ● refusal to approve pending applications or supplements to approved applications that we submit; ● recall of products; ● fines, restitution or disgorgement of profits or revenues; ● suspension or withdrawal of marketing approvals; ● refusal to permit the import or export of our products; ● product seizure; or ● injunctions or the imposition of civil or criminal penalties.
Our consultants and advisors may be engaged by entities other than us and may have commitments under consulting or advisory contracts with other entities that may limit their availability to us. 68 Table of Contents Other pharmaceutical companies with which we compete for qualified personnel have greater financial and other resources, different risk profiles, and a longer history in the industry than we do.
Our consultants and advisors may be engaged by entities other than us and may have commitments under consulting or advisory contracts with other entities that may limit their availability to us. 70 Table of Contents Other pharmaceutical companies with which we compete for qualified personnel have greater financial and other resources, different risk profiles and a longer history in the industry than we do.
Some claimants may have 60 Table of Contents substantially greater resources than we do and may be able to sustain the costs of complex intellectual property litigation to a greater degree and for longer periods of time than we could. In addition, patent holding companies that focus solely on extracting royalties and settlements by enforcing patent rights may target us.
Some claimants may have 62 Table of Contents substantially greater resources than we do and may be able to sustain the costs of complex intellectual property litigation to a greater degree and for longer periods of time than we could. In addition, patent holding companies that focus solely on extracting royalties and settlements by enforcing patent rights may target us.
Among some of the other changes introduced by the AIA are changes that limit where a patentee may file a patent infringement suit and provide opportunities for third parties to challenge any issued patent with the USPTO. This applies to all of our 62 Table of Contents U.S. patents, even those issued before March 16, 2013.
Among some of the other changes introduced by the AIA are changes that limit where a patentee may file a patent infringement suit and provide opportunities for third parties to challenge any issued patent with the USPTO. This applies to all of our 64 Table of Contents U.S. patents, even those issued before March 16, 2013.
Our expenses will also increase substantially if and as we: ● continue to progress our development in AD and PD with additional pivotal Phase 3 studies, or conduct clinical trials for any other product candidates; ● scale-up cGMP drug supply manufacturing and complete necessary work to support an NDA for buntanetap in AD or in PD; 29 Table of Contents ● are required by the FDA to complete additional toxicological/pharmacological studies to support an NDA for buntanetap in AD or in PD; ● establish a sales, marketing and distribution infrastructure to commercialize our drug, if approved, and for any other product candidates for which we may obtain marketing approval; ● maintain, expand and protect our intellectual property portfolio; ● hire additional clinical, scientific and commercial personnel; ● add operational, financial and management information systems and personnel, including personnel to support our product development and future commercialization efforts, as well as to support our requirements as a public reporting company; and ● acquire or in-license or invent other product candidates or technologies.
Our expenses will also increase substantially if and as we: ● continue to progress our development in AD and PD with additional pivotal Phase 3 studies, or conduct clinical trials for any other product candidates; ● scale-up cGMP drug supply manufacturing and complete necessary work to support an NDA for buntanetap in AD or in PD; ● are required by the FDA to complete additional toxicological/pharmacological studies to support an NDA for buntanetap in AD or in PD; ● establish a sales, marketing and distribution infrastructure to commercialize our drug, if approved, and for any other product candidates for which we may obtain marketing approval; ● maintain, expand and protect our intellectual property portfolio; ● hire additional clinical, scientific and commercial personnel; ● add operational, financial and management information systems and personnel, including personnel to support our product development and future commercialization efforts, as well as to support our requirements as a public reporting company; and ● acquire or in-license or invent other product candidates or technologies.
As a result, our financial results and the commercial prospects for any product candidate that we develop would be harmed, our costs could increase, and our ability to generate revenue could be delayed. If our relationship with any CROs terminate, we may not be able to enter into arrangements with alternative CROs or do so on commercially reasonable terms.
As a result, our financial results and the commercial prospects for any product candidate that we develop would be harmed, our costs could increase, and our ability to generate revenue could be delayed. If our relationship with any CROs terminates, we may not be able to enter into arrangements with alternative CROs or do so on commercially reasonable terms.
Accordingly, such events could cause adverse 71 Table of Contents effects and material disruptions to our operations or systems or those of our business partners; compromise the security, integrity, availability, and confidentiality of customer information, employee information, strategic projects, product formulas and other trade secrets, other business or personal sensitive data, including third party confidential information in our possession.
Accordingly, such events could cause adverse 73 Table of Contents effects and material disruptions to our operations or systems or those of our business partners; compromise the security, integrity, availability, and confidentiality of customer information, employee information, strategic projects, product formulas and other trade secrets, other business or personal sensitive data, including third-party confidential information in our possession.
Furthermore, we rely on CROs and clinical trial sites to ensure the proper and timely conduct of our clinical trials and, while we have agreements governing their committed activities, we have limited influence over their actual performance, as described in “—Risks Related to Our Dependence on Third Parties.” 35 Table of Contents The regulatory approval processes of the FDA and comparable foreign authorities are lengthy, time consuming and inherently unpredictable, and if we are ultimately unable to obtain regulatory approval for buntanetap or any other product candidates, our business will be substantially harmed.
Furthermore, we rely on CROs and clinical trial sites to ensure the proper and timely conduct of our clinical trials and, while we have agreements governing their committed activities, we have limited influence over their actual performance, as described in “—Risks Related to Our Dependence on Third Parties.” The regulatory approval processes of the FDA and comparable foreign authorities are lengthy, time-consuming and inherently unpredictable, and if we are ultimately unable to obtain regulatory approval for buntanetap or any other product candidates, our business will be substantially harmed.
If we are unable to obtain patent term extension or the term of any such extension is less than we request, the period during which we can enforce our patent rights for that product will be shortened and our competitors may 64 Table of Contents obtain approval to market competing products sooner.
If we are unable to obtain patent term extension or the term of any such extension is less than we request, the period during which we can enforce our patent rights for that product will be shortened and our competitors may 66 Table of Contents obtain approval to market competing products sooner.
Although we are given an opportunity to respond to such rejections, we may be unable to overcome them. At times, competitors may adopt trade names or trademarks similar to ours, thereby impeding our ability to build brand identity and possibly leading to market 66 Table of Contents confusion.
Although we are given an opportunity to respond to such rejections, we may be unable to overcome them. At times, competitors may adopt trade names or trademarks similar to ours, thereby impeding our ability to build brand identity and possibly leading to market 68 Table of Contents confusion.
If we were to initiate legal proceedings against a third party to enforce a patent covering one of our product candidates, the defendant could counterclaim that our patent is invalid or unenforceable. In patent litigation in the United States and in Europe, defendant counterclaims alleging invalidity or unenforceability are commonplace.
If we were to initiate legal proceedings against a third party to enforce a patent covering one of our product candidates, the defendant could counterclaim that our patent is invalid or unenforceable. In patent litigation in the United States and in the EU, defendant counterclaims alleging invalidity or unenforceability are commonplace.
We adopted this provision because we believe it makes it less likely that we will be forced to incur the expense of defending duplicative actions in multiple forums and less likely that plaintiffs’ attorneys will be able to employ such litigation to coerce us into otherwise unjustified settlements, and we believe the risk of a court declining to enforce this provision is remote, as the General Assembly of Delaware has specifically amended the Delaware General Corporation Law to authorize the adoption of such provisions.
We adopted this provision because we believe it makes it less likely that we will be forced to incur the expense of defending duplicative actions in multiple forums and less likely that plaintiffs’ attorneys will be able to employ such litigation to coerce us into otherwise unjustified settlements, and we believe the risk of a court declining to enforce this provision is remote, as the General Assembly of Delaware has specifically amended the Delaware General Corporation Law to authorize the adoption of such provisions. 78 Table of Contents
The product liability insurance coverage we carry or acquire in the future may not be sufficient to reimburse us for any expenses or losses we may suffer. In connection with all our clinical studies, we carry insurance for product liability claims in the United States and in Europe. Insurance coverage is increasingly expensive.
The product liability insurance coverage we carry or acquire in the future may not be sufficient to reimburse us for any expenses or losses we may suffer. In connection with all our clinical studies, we carry insurance for product liability claims in the United States and in the EU. Insurance coverage is increasingly expensive.
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.
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.
If our CROs do not successfully carry out their contractual duties or obligations, fail to meet expected deadlines, or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols or regulatory requirements or for any other reason, our clinical trials may be extended, delayed or terminated, and we may not be able to obtain regulatory approval for, or successfully commercialize any product candidate that we develop.
If our CROs do not successfully carry out their contractual duties or obligations, fail to meet expected deadlines, or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols or regulatory requirements or for any other reason, our clinical trials may be extended, delayed or terminated, and we may not be able to obtain regulatory approval for, or successfully 53 Table of Contents commercialize any product candidate that we develop.
The secure processing, maintenance and transmission of this information is critical to our 67 Table of Contents operations. Despite our security measures, our information technology and infrastructure may be vulnerable to attacks by hackers or breached due to employee error, malfeasance or other disruptions.
The secure processing, maintenance and transmission of this information is critical to our 69 Table of Contents operations. Despite our security measures, our information technology and infrastructure may be vulnerable to attacks by hackers or breached due to employee error, malfeasance or other disruptions.
We may not have sufficient financial or other resources to adequately conduct such litigation or proceedings. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of 61 Table of Contents their substantially greater financial resources.
We may not have sufficient financial or other resources to adequately conduct such litigation or proceedings. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of 63 Table of Contents their substantially greater financial resources.
Before obtaining regulatory approvals for the commercial sale of buntanetap for a target indication, we must demonstrate with substantial evidence gathered in preclinical studies and clinical trials, generally including two adequate and well-controlled clinical trials, and, with respect to approval in the United States, to the satisfaction of the FDA, that buntanetap is safe and effective for use for that target indication and that the manufacturing 33 Table of Contents facilities, processes and controls are adequate.
Before obtaining regulatory approvals for the commercial sale of buntanetap for a target indication, we must demonstrate with substantial evidence gathered in preclinical studies and clinical trials, generally including two adequate and well-controlled clinical trials, and, with respect to approval in the United States, to the satisfaction of the FDA, that buntanetap is safe and effective for use for that target indication and that the manufacturing facilities, processes and controls are adequate.
The FDA or any foreign regulatory bodies can delay, limit or deny approval of our product candidates or require us to conduct additional preclinical or clinical testing or abandon a program for many reasons, including: ● the FDA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials; 36 Table of Contents ● the FDA or comparable foreign regulatory authorities may disagree with our safety interpretation of our drug; ● the FDA or comparable foreign regulatory authorities may disagree with our efficacy interpretation of our drug; ● the FDA or comparable foreign regulatory authorities may regard our CMC package as inadequate.
The FDA or any foreign regulatory bodies can delay, limit or deny approval of our product candidates or require us to conduct additional preclinical or clinical testing or abandon a program for many reasons, including: ● the FDA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials; ● the FDA or comparable foreign regulatory authorities may disagree with our safety interpretation of our drug; ● the FDA or comparable foreign regulatory authorities may disagree with our efficacy interpretation of our drug; ● the FDA or comparable foreign regulatory authorities may regard our CMC package as inadequate.
The GDPR applies extraterritorially and implements stringent operational requirements for processors and controllers of personal data, including, for example, high standards for obtaining consent from individuals to process their personal data, robust disclosures to individuals, a comprehensive individual data rights regime, data export restrictions governing transfers of data from the European Union (“EU”) to other jurisdictions, short timelines for data breach notifications, limitations on retention of information, increased requirements pertaining to health data, other special categories of personal data and coded data and additional obligations if we contract third-party processors in connection with the processing of personal data.
The GDPR applies extraterritorially and implements stringent operational requirements for processors and controllers of personal data, including, for example, high standards for obtaining consent from individuals to process their personal data, robust disclosures to individuals, a comprehensive individual data rights regime, data export restrictions governing transfers of data from the EU to other jurisdictions, short timelines for data breach notifications, limitations on retention of information, increased requirements pertaining to health data, other special categories of personal data and coded data and additional obligations if we contract third-party processors in connection with the processing of personal data.
If the patent applications we own with respect to our development programs and product candidates fail to issue, if their breadth or strength of protection is threatened, or if they fail to provide meaningful exclusivity for buntanetap, Posiphen Form B, or any future product candidate, it could dissuade companies from collaborating with us to develop product candidates, and threaten our ability to commercialize future product candidates.
If the patent applications we own with respect to our development programs and product candidates fail to issue, if their breadth or strength of protection is threatened, or if they fail to provide meaningful exclusivity for buntanetap, Posiphen Form B, or any future product candidate, it could dissuade companies from collaborating with us to develop 59 Table of Contents product candidates, and threaten our ability to commercialize future product candidates.
If we license products or businesses, we may not be able to realize the benefit of such transactions if we are unable to successfully integrate 69 Table of Contents them with our existing operations and company culture.
If we license products or businesses, we may not be able to realize the benefit of such transactions if we are unable to successfully integrate 71 Table of Contents them with our existing operations and company culture.
The report of our independent registered accounting firm on our audited financial statements for the fiscal year ended December 31, 2024 contains an explanatory paragraph relating to our ability to continue as a going concern.
The report of our independent registered accounting firm on our audited financial statements for the fiscal year ended December 31, 2025, contains an explanatory paragraph relating to our ability to continue as a going concern.
Our ability to obtain clinical or, if approved, commercial, supplies of buntanetap or any future product candidates could be disrupted if the operations of these suppliers were affected by a man-made or natural disaster or other business interruption, and our ability to commence, conduct or complete our clinical trials in a timely manner could be similarly adversely affected by any of 34 Table of Contents the foregoing.
Our ability to obtain clinical or, if approved, commercial, supplies of buntanetap or any future product candidates could be disrupted if the operations of these suppliers were affected by a man-made or natural disaster or other business interruption, and our ability to commence, conduct or complete our clinical trials in a timely manner could be similarly adversely affected by any of the foregoing.
If we cannot successfully manage the promotion of buntanetap or any future product candidates, if approved, we could become subject to significant liability, which would materially adversely affect our business and financial condition. 44 Table of Contents We may seek a Breakthrough Therapy designation for buntanetap from the FDA in PD and AD.
If we cannot successfully manage the promotion of buntanetap or any future product candidates, if approved, we could become subject to significant liability, which would materially adversely affect our business and financial condition. We may seek a Breakthrough Therapy designation for buntanetap from the FDA in PD and AD.
We can be held liable for the corrupt or other illegal activities of our employees, agents, CROs, contractors and other collaborators and partners, even if we do not explicitly authorize or have actual knowledge of such activities, and any training or compliance programs or other initiatives we undertake to prevent such activities may not be effective.
We can be held liable for 57 Table of Contents the corrupt or other illegal activities of our employees, agents, CROs, contractors and other collaborators and partners, even if we do not explicitly authorize or have actual knowledge of such activities, and any training or compliance programs or other initiatives we undertake to prevent such activities may not be effective.
Clinical trials can be delayed for a variety of reasons, including delays related to: ● the FDA or comparable foreign regulatory authorities disagreeing as to the design or implementation of our clinical studies; ● obtaining regulatory approval to commence a trial; ● reaching an agreement on acceptable terms with prospective CROs, and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; ● obtaining Institutional Review Board (“IRB”) approval at each site, or Independent Ethics Committee (“IEC”) approval at sites outside the United States; ● recruiting suitable patients to participate in a trial in a timely manner and in sufficient numbers; ● patients failing to complete a trial or return for post-treatment follow-up; ● imposition of a clinical hold by regulatory authorities, including as a result of unforeseen safety issues or side effects or failure of trial sites to adhere to regulatory requirements or follow trial protocols; ● clinical sites deviating from trial protocol or dropping out of a trial; ● addressing patient safety concerns that arise during the course of a trial; ● adding a sufficient number of clinical trial sites; or ● manufacturing sufficient quantities of product candidate for use in clinical trials.
Clinical trials can be delayed for a variety of reasons, including delays related to: ● the FDA or comparable foreign regulatory authorities disagreeing as to the design or implementation of our clinical studies; ● obtaining regulatory approval to commence a trial; ● reaching an agreement on acceptable terms with prospective CROs, and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; ● obtaining IRB approval at each site, or Independent Ethics Committee (“IEC”) approval at sites outside the United States; ● recruiting suitable patients to participate in a trial in a timely manner and in sufficient numbers; ● patients failing to complete a trial or return for post-treatment follow-up; ● imposition of a clinical hold by regulatory authorities, including as a result of unforeseen safety issues or side effects or failure of trial sites to adhere to regulatory requirements or follow trial protocols; ● clinical sites deviating from trial protocol or dropping out of a trial; ● addressing patient safety concerns that arise during the course of a trial; ● adding a sufficient number of clinical trial sites; or 36 Table of Contents ● manufacturing sufficient quantities of product candidate for use in clinical trials.
Without an internal team or the support of a third party to perform marketing and sales functions, we may be unable to compete successfully against these more established companies. 49 Table of Contents A variety of risks associated with operating internationally could materially adversely affect our business.
Without an internal team or the support of a third party to perform marketing and sales functions, we may be unable to compete successfully against these more established companies. A variety of risks associated with operating internationally could materially adversely affect our business.
If any of our product candidates receive marketing approval, the accompanying label may limit the approved indicated use of the product candidate, which could limit sales of the product candidate. The FDA may also impose requirements for costly post-marketing studies or clinical trials and surveillance to monitor the safety or efficacy of a product.
If any of our product candidates receive marketing approval, the accompanying label may limit the approved indicated use of the product candidate, which could limit sales of the product candidate. The FDA may also impose requirements for costly post-marketing studies 44 Table of Contents or clinical trials and surveillance to monitor the safety or efficacy of a product.
Activities 50 Table of Contents subject to these laws could also involve the improper use or misrepresentation of information obtained in the course of clinical trials, creation of fraudulent data in preclinical studies or clinical trials or illegal misappropriation of drug product, which could result in regulatory sanctions and cause serious harm to our reputation.
Activities subject to these laws could also involve the improper use or misrepresentation of information obtained in the course of clinical trials, creation of fraudulent data in preclinical studies or clinical trials or illegal misappropriation of drug product, which could result in regulatory sanctions and cause serious harm to our reputation.
Similarly, the complexity and uncertainty of European patent laws has also increased in recent years. In addition, the European patent system is relatively stringent in the type of amendments that are allowed during prosecution.
Similarly, the complexity and uncertainty of European patent laws have also increased in recent years. In addition, the European patent system is relatively stringent in the type of amendments that are allowed during prosecution.
Because of the numerous risks and uncertainties associated with pharmaceutical product development, we are unable to accurately predict the timing or amount of increased expenses or when, or if, we will be able to begin generating revenue from the commercialization of any products or achieve or maintain profitability.
Because of the numerous risks and uncertainties associated with pharmaceutical product development, we are unable to accurately predict the timing or amount of increased expenses or when, or if, 30 Table of Contents we will be able to begin generating revenue from the commercialization of any products or achieve or maintain profitability.
Only a small number of new treatments have been approved for AD since 2003. From 2004 to 2025, phase 2 and 3 clinical trials for unique compounds with various mechanisms of action intended to combat AD had a development success rate of just 8%.
Only a small number of new treatments have been approved for AD since 2003. From 2004 to 2025, Phase 2 and 3 clinical trials for unique 38 Table of Contents compounds with various mechanisms of action intended to combat AD had a development success rate of just 8%.
Regulatory requirements can vary widely from country to country and could delay or prevent the introduction of our products in those countries. We do not have any product candidates approved for sale in any jurisdiction, including in international markets, and we do not have experience in obtaining regulatory approval in international markets.
Regulatory requirements can vary widely from country to country and could delay or prevent the introduction of our products in those countries. We do not have any product 43 Table of Contents candidates approved for sale in any jurisdiction, including in international markets, and we do not have experience in obtaining regulatory approval in international markets.
Maccecchini, PhD, as well as the other principal members of our management, scientific and clinical teams. Although we have employment agreements, offer letters or consulting agreements with our executive officers, these agreements do not prevent them from terminating their services at any time.
Maccecchini, Ph.D., as well as the other principal members of our management, scientific and clinical teams. Although we have employment agreements, offer letters or consulting agreements with our executive officers, these agreements do not prevent them from terminating their services at any time.
Moreover, if buntanetap or any future product candidates are associated with undesirable side effects in clinical trials or demonstrate characteristics that are unexpected, we may elect to abandon their development or limit their development to more narrow uses or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a risk-benefit perspective, which may limit the commercial expectations for the product candidate if approved.
Moreover, if buntanetap or any future product candidates are associated with undesirable side effects in clinical trials or demonstrate characteristics that are unexpected, we may elect to abandon their development or limit their development to more narrow uses or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less severe or more acceptable 41 Table of Contents from a risk-benefit perspective, which may limit the commercial expectations for the product candidate if approved.
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.
In September 2024, we filed an 60 Table of Contents 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.
Pursuant to Section 404 of SOX, we are required to furnish a report by our senior management on our internal control over financial reporting. While we remain an emerging growth company, we will not be required to include an attestation report on internal control over financial reporting issued by our independent registered public accounting firm.
Pursuant to Section 404 of SOX, we are required to furnish a report by our senior management on our internal control over financial reporting. While we remain a smaller reporting company, we will not be required to include an attestation report on internal control over financial reporting issued by our independent registered public accounting firm.
This choice of forum provision may limit a stockholder’s ability to bring a claim in a 76 Table of Contents judicial forum that the stockholder believes is favorable for disputes with us or our directors, which may discourage meritorious claims from being asserted against us and our directors.
This choice of forum provision may limit a stockholder’s ability to bring a claim in a judicial forum that the stockholder believes is favorable for disputes with us or our directors, which may discourage meritorious claims from being asserted against us and our directors.
For example, unlike other countries, China has a heightened requirement for patentability, and 63 Table of Contents specifically requires a detailed description of medical uses of a claimed drug.
For example, unlike other countries, China has a heightened requirement for patentability and 65 Table of Contents specifically requires a detailed description of medical uses of a claimed drug.
Change in control as defined by Section 382 occurs when there is an ownership change among stockholders owning directly or indirectly 5% or more of our common stock, as well as an aggregate ownership change with respect to such stockholders of 32 Table of Contents more than 50% of our common stock.
Change in control as defined by Section 382 occurs when there is an ownership change among stockholders owning directly or indirectly 5% or more of our common stock, as well as an aggregate ownership change with respect to such stockholders of more than 50% of our common stock.
For example, 37 Table of Contents the manufacturing process being used to produce clinical material for our planned clinical trials is different than that used in prior trials of buntanetap. There can be no assurance that such changes will achieve these intended objectives.
For example, the manufacturing process being used to produce clinical material for our planned clinical trials is different than that used in prior trials of buntanetap. There can be no assurance that such changes will achieve these intended objectives.
Our operations and the operations of our suppliers, contract research organizations (“CROs”), hospitals, clinical trial sites, regulators, consultants and other third parties with whom we conduct business could be subject to earthquakes, power shortages, telecommunications or infrastructure failures, cybersecurity incidents, physical security breaches, water shortages, floods, hurricanes, typhoons, blizzards and other extreme weather conditions, fires, and other natural or manmade disasters or business interruptions, for which we are predominantly self-insured.
Our operations and the operations of our suppliers, CROs, hospitals, clinical trial sites, regulators, consultants and other third parties with whom we conduct business could be subject to earthquakes, power shortages, telecommunications or infrastructure failures, cybersecurity incidents, physical security breaches, water shortages, floods, hurricanes, typhoons, blizzards and other extreme weather conditions, fires, and other natural or manmade disasters or business interruptions, for which we are predominantly self-insured.
If one or more of these analysts cease coverage of us or fail to 74 Table of Contents regularly publish reports on us, we could lose visibility in the financial markets, which could cause our share price or trading volume to decline.
If one or more of these analysts cease coverage of us or fail to regularly publish reports on us, we could lose visibility in the financial markets, which could cause our share price or trading volume to decline.
Because the outcome of any clinical trial or preclinical study is highly uncertain, we cannot reliably estimate the actual amount of financing necessary to successfully complete the development and commercialization of buntanetap or any other product candidates.
Because the outcome of any clinical trial or preclinical study is highly uncertain, we cannot reliably estimate the actual amount of financing necessary to successfully complete the development and commercialization of 31 Table of Contents buntanetap or any other product candidates.
If we are unsuccessful in identifying and developing additional product candidates or are unable to do so, our business, results of operations, cash flows, financial condition and/or prospects may be materially and adversely affected.
If we are unsuccessful in identifying and developing additional product 35 Table of Contents candidates or are unable to do so, our business, results of operations, cash flows, financial condition and/or prospects may be materially and adversely affected.
Based on our current operating plan, we believe that our current cash and cash equivalents will enable us to fund our operating expenses and capital expenditure requirements into the fourth quarter of 2025. We have based this estimate on assumptions that may prove to be wrong, and we could deploy our available capital resources sooner than we currently expect.
Based on our current operating plan, we believe that our current cash and cash equivalents will enable us to fund our operating expenses and capital expenditure requirements into the third quarter of 2026. We have based this estimate on assumptions that may prove to be wrong, and we could deploy our available capital resources sooner than we currently expect.
If the interim, topline or preliminary data that we report differ from actual results, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to obtain approval for, and commercialize, product candidates may be harmed, which could significantly harm our business prospects.
If the interim, topline or preliminary data that we report differ from actual results, or if others, including regulatory authorities, disagree with 40 Table of Contents the conclusions reached, our ability to obtain approval for, and commercialize, product candidates may be harmed, which could significantly harm our business prospects.
They may also terminate or refuse to renew their agreement at a time that is costly or otherwise inconvenient for us. If we were unable to find an adequate CMO or another acceptable solution in time, our clinical trials could be delayed, or our commercial activities could be harmed.
They may also 52 Table of Contents terminate or refuse to renew their agreement at a time that is costly or otherwise inconvenient for us. If we were unable to find an adequate CMO or another acceptable solution in time, our clinical trials could be delayed, or our commercial activities could be harmed.
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 U.S. and outside the U.S. as National and Regional Phase patent applications of the PCT application.
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.
In the event of a delisting, we can provide no assurance that any action taken by us to restore compliance with listing requirements would allow our common stock to become listed again, stabilize the market price or improve the liquidity of our common stock, or prevent future non-compliance with the listing requirements of the New York Stock Exchange.
In the event of a delisting, we can provide no assurance that any action taken by us to restore compliance with listing requirements would allow our common stock to become listed again, stabilize the market price or improve the liquidity of our common stock, or prevent future non-compliance with the listing requirements of the NYSE.
It is difficult to predict at this time what third-party payors will decide with respect to the coverage and reimbursement for our product candidates. 47 Table of Contents No uniform policy for coverage and reimbursement for products exists among third-party payors in the United States. Therefore, coverage and reimbursement for products can differ significantly from payor to payor.
It is difficult to predict at this time what third-party payors will decide with respect to the coverage and reimbursement for our product candidates. No uniform policy for coverage and reimbursement for products exists among third-party payors in the United States. Therefore, coverage and reimbursement for products can differ significantly from payor to payor.
We cannot be sure that coverage and reimbursement in the United States, the European Union or elsewhere will be available, or at an acceptable level, for any product that we may develop, and any reimbursement that may become available may be decreased or eliminated in the future.
We cannot be sure that coverage and reimbursement in the United States, the EU or elsewhere will be available, or at an acceptable level, for any product that we may develop, and any reimbursement that may become available may be decreased or eliminated in the future.
If our financial performance fails to meet analyst estimates or one or more of the analysts who cover us downgrade our common stock or change their opinion of our common stock, our share price would likely decline.
If our financial performance fails to meet analyst estimates or one or more of the analysts who cover us downgrade our common stock or change their 76 Table of Contents opinion of our common stock, our share price would likely decline.

… 96 more changes not shown on this page.

Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

6 edited+1 added−1 removed9 unchanged
Biggest changeThe AIMC will document findings and make them available to the Disclosure Committee, which includes cross functional senior management representation from, legal, finance, investor relations and business segments.
Biggest changeThe AIMC will document findings and make them available to the Disclosure Committee, which includes cross functional senior management representation from legal, finance, investor relations and business segments. The Disclosure Committee, in conjunction with third-party experts, including outside legal counsel, is responsible for assessing the materiality of any cybersecurity incident and coordinating external communications and disclosures, including with the SEC.
While our Board and Audit Committee oversee cybersecurity risk, management, through the AIMC, is responsible for the implementation and management of cybersecurity risk management systems and processes and for the communication of incidents to senior management and the Audit Committee. The AIMC meets with the Audit Committee on a quarterly basis and meets with the BOD at least annually.
While our Board and Audit Committee oversee cybersecurity risk, management, through the AIMC, is responsible for the implementation and management of cybersecurity risk management systems and processes and for the communication of incidents to senior management and the Audit Committee. The AIMC meets with the Audit Committee on a quarterly basis and meets with the Board at least annually.
The Board has delegated to the Audit Committee the responsibility to oversee the integrity of the Company’s information technology and cybersecurity risks and to assess the risks and incidents relating to cybersecurity threats.
The Board of Directors has delegated to the Audit Committee the responsibility to oversee the integrity of the Company’s information technology and cybersecurity risks and to assess the risks and incidents relating to cybersecurity threats.
As of December 31, 2024, we are not aware of any cybersecurity threats that have materially affected or are reasonably likely to materially affect the Company's business strategy, results of operations, or financial condition, although we may be materially affected in the future by such risks or future material incidents.
As of December 31, 2025, we are not aware of any cybersecurity threats that have materially affected or are reasonably likely to materially affect the Company's business strategy, results of operations, or financial condition, although we may be materially affected in the future by such risks or future material incidents.
We continue to invest in cybersecurity and enhance our internal controls and processes, which are designed to help protect our systems and the information they contain. Our Board is actively involved in the assessment, oversight and management of the material risks that could affect the Company.
We continue to invest in cybersecurity and enhance our internal controls and processes, which are designed to help protect our systems and the information they contain. 79 Table of Contents Our Board of Directors is actively involved in the assessment, oversight and management of the material risks that could affect the Company.
See “Risk Factors—Risks Related to Our Business Operations—Disruption, failure or cyber security breaches affecting or targeting computers and infrastructure used by us or our business partners may adversely impact our business and operations” for additional information regarding cybersecurity risks. 77 Table of Contents Governance Roles and Responsibilities Cybersecurity is an important part of our risk management processes and an area of focus for the Annovis management and Board of Directors.
See “Risk Factors—Risks Related to Our Business Operations—Disruption, failure or cyber security breaches affecting or targeting computers and infrastructure used by us or our business partners may adversely impact our business and operations” for additional information regarding cybersecurity risks.
Removed
The Disclosure Committee, in conjunction with third-party experts, including outside legal counsel, is responsible for assessing the materiality of any cybersecurity incident and coordinating external communications and disclosures, including with the Securities and Exchange Commission.
Added
Governance Roles and Responsibilities Cybersecurity is an important part of our risk management processes and an area of focus for the Annovis management and Board of Directors.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

1 edited+0 added−0 removed1 unchanged
Biggest changeWe are not currently a party to any material legal proceedings, and we are not aware of any pending or threatened legal proceedings against us that we believe could have a material adverse effect on our business, operating results or financial condition. Item 4. Mine Safety Disclosures. Not applicable. ​ 78 Table of Contents PART II
Biggest changeWe are not currently a party to any material legal proceedings, and we are not aware of any pending or threatened legal proceedings against us that we believe could have a material adverse effect on our business, operating results or financial condition. Item 4. Mine Safety Disclosures. Not applicable. ​ 80 Table of Contents PART II

Item 4. Mine Safety Disclosures

Mine Safety Disclosures — required of mining issuers

1 edited+0 added−0 removed0 unchanged
Biggest changeItem 4. Mine Safety Disclosures. 78 ​ ​ Part II. 79 ​ ​ ​ Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities. 79 ​ ​ ​ Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations. 79 ​ ​ ​
Biggest changeItem 4. Mine Safety Disclosures. 80 ​ ​ Part II. 81 ​ ​ ​ Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities. 81 ​ ​ ​ Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations. 81 ​ ​ ​

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

2 edited+0 added−0 removed3 unchanged
Biggest changeItem 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities. Market Information Our common stock is listed on the New York Stock Exchange under the symbol “ANVS”. Our common stock began trading on the New York Stock Exchange on November 18, 2021.
Biggest changeItem 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities. Market Information Our common stock is listed on the NYSE under the symbol “ANVS”. Our common stock began trading on the NYSE on November 18, 2021.
From January 29, 2020, the date of our initial public offering, to November 17, 2021, our common stock traded on the NYSE American. Prior to January 29, 2020, there was no public market for our stock. Holders of Record As of March 18, 2025, there were approximately 23 holders of record of shares of our common stock.
From January 29, 2020, the date of our IPO, to November 17, 2021, our common stock traded on the NYSE American. Prior to January 29, 2020, there was no public market for our stock. Holders of Record As of March 13, 2026, there were approximately 30 holders of record of shares of our common stock.

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

48 edited+40 added−32 removed53 unchanged
Biggest changeResults of Operations Years ended December 31, 2024 and 2023 Operating expenses and other income (expense) were comprised of the following: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ ​ ​ ​ ​ December 31, ​ ​ ​ ​ 2024 2023 ​ ​ Change ​ ​ (in thousands) Operating expenses: ​ ​ ​ ​ ​ ​ ​ ​ ​ Research and development ​ $ 19,995 ​ $ 38,791 ​ $ (18,796) General and administrative ​ ​ 6,699 ​ ​ 6,244 ​ ​ 455 Total operating expenses ​ ​ 26,694 ​ ​ 45,035 ​ ​ (18,341) Other income (expense): ​ ​ ​ ​ ​ ​ ​ ​ ​ Interest income ​ ​ 332 ​ ​ 668 ​ ​ (336) Other financing costs ​ ​ (1,853) ​ ​ - ​ ​ (1,853) Change in fair value of warrants ​ ​ 3,626 ​ ​ (11,837) ​ ​ 15,463 Other income (expense), net ​ ​ 2,105 ​ ​ (11,169) ​ ​ 13,274 Net loss ​ $ 24,589 ​ $ 56,204 ​ $ (31,615) ​ Research and Development Expenses Research and development expenses decreased by $18.8 million for the year ended December 31, 2024 compared to the year ended December 31, 2023.
Biggest changeWe have not yet conducted a comprehensive study to assess whether a change of ownership as defined by Section 382 has occurred since our inception. ​ 85 Table of Contents Results of Operations Years ended December 31, 2025 and 2024 Operating expenses and other income (expense) were comprised of the following: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ ​ ​ ​ ​ December 31, ​ ​ ​ ​ ​ ​ ​ 2025 ​ ​ ​ 2024 ​ ​ Change ​ ​ (in thousands) ​ ​ ​ Operating expenses: ​ ​ ​ ​ ​ ​ ​ ​ ​ Research and development ​ $ 25,216 ​ ​ ​ $ 19,995 ​ $ 5,221 General and administrative ​ ​ 4,480 ​ ​ 6,699 ​ ​ (2,219) Total operating expense ​ ​ 29,696 ​ ​ 26,694 ​ ​ 3,002 Other income (expense): ​ ​ ​ ​ ​ ​ ​ ​ ​ Interest income ​ ​ 699 ​ ​ 332 ​ ​ 367 Other financing costs ​ ​ — ​ ​ (1,853) ​ ​ 1,853 Change in fair value of warrants ​ ​ 142 ​ ​ 3,626 ​ ​ (3,484) Total other income, net ​ ​ 841 ​ ​ 2,105 ​ ​ (1,264) Net loss ​ $ 28,855 ​ $ 24,589 ​ $ 4,266 ​ Research and Development Expenses Research and development expenses increased by $5.2 million for the year ended December 31, 2025, compared to the year ended December 31, 2024.
Our future funding requirements, both near and long-term, will depend on many factors, including, but not limited to: ● the initiation, progress, timing, costs and results of preclinical studies and clinical trials, including patient enrollment in such trials, for buntanetap or any other future product candidates; ● the clinical development plans we establish for buntanetap and any other future product candidates, including any modifications to clinical development plans based on feedback that we may receive from regulatory authorities; ● the number and characteristics of product candidates that we discover or in-license and develop; ● the outcome, timing and cost of regulatory meetings and reviews by the FDA and comparable foreign regulatory authorities, including the potential for the FDA or comparable foreign regulatory authorities to require that we perform more studies than those that we currently expect; ● the requirements of regulatory authorities in any additional jurisdictions in which we may seek approval for buntanetap and any future product candidates and our anticipated timing for seeking approval in such jurisdictions; ● the costs of filing, prosecuting, defending and enforcing any patent claims and maintaining and enforcing other intellectual property and proprietary rights; ● the effects of competing technological and market developments; ● the costs associated with hiring additional personnel and consultants as our business grows, including additional executive officers and clinical development, regulatory, CMC, quality and commercial personnel; ● the costs and timing of the implementation of commercial-scale manufacturing activities, if any product candidate is approved, including as a result of inflation, any supply chain issues or component shortages; ● the costs and timing of establishing sales, marketing and distribution capabilities for any product candidates for which we may receive regulatory approval; 85 Table of Contents ● our ability to achieve sufficient market acceptance, coverage and adequate reimbursement from third-party payors and adequate market share and revenue for any approved products; ● the terms and timing of establishing and maintaining collaborations, licenses and other similar arrangements; and ● the costs associated with any products or technologies that we may in-license or acquire.
Our future funding requirements, both near and long-term, will depend on many factors, including, but not limited to: ● the initiation, progress, timing, costs and results of preclinical studies and clinical trials, including patient enrollment in such trials, for buntanetap or any other future product candidates; ● the clinical development plans we establish for buntanetap and any other future product candidates, including any modifications to clinical development plans based on feedback that we may receive from regulatory authorities; ● the number and characteristics of product candidates that we discover or in-license and develop; ● the outcome, timing and cost of regulatory meetings and reviews by the FDA and comparable foreign regulatory authorities, including the potential for the FDA or comparable foreign regulatory authorities to require that we perform more studies than those that we currently expect; ● the requirements of regulatory authorities in any additional jurisdictions in which we may seek approval for buntanetap and any future product candidates and our anticipated timing for seeking approval in such jurisdictions; ● the costs of filing, prosecuting, defending and enforcing any patent claims and maintaining and enforcing other intellectual property and proprietary rights; ● the effects of competing technological and market developments; ● the costs associated with hiring additional personnel and consultants as our business grows, including additional executive officers and clinical development, regulatory, CMC, quality and commercial personnel; ● the costs and timing of the implementation of commercial-scale manufacturing activities, if any product candidate is approved, including as a result of inflation, any supply chain issues or component shortages; ● the costs and timing of establishing sales, marketing and distribution capabilities for any product candidates for which we may receive regulatory approval; 88 Table of Contents ● our ability to achieve sufficient market acceptance, coverage and adequate reimbursement from third-party payors and adequate market share and revenue for any approved products; ● the terms and timing of establishing and maintaining collaborations, licenses and other similar arrangements; and ● the costs associated with any products or technologies that we may in-license or acquire.
In several studies, buntanetap was observed to inhibit the synthesis of neurotoxic proteins — APP/Aβ (“APP”), tau/phospho- tau (“tau”) and α-Synuclein (“αSYN”) — that are some of the main causes of neurodegeneration. High levels of neurotoxic proteins lead to reduced axonal transport, which is responsible for the communication between and within nerve cells.
In several studies, buntanetap was observed to inhibit the synthesis of neurotoxic proteins — APP/Aβ (“APP”), tau/phospho-tau (“tau”), α-Synuclein (“αSYN”) and TDP43 — that are some of the main causes of neurodegeneration. High levels of neurotoxic proteins lead to reduced axonal transport, which is responsible for communication between and within nerve cells.
ASU 2024-03 is effective for annual reporting periods beginning after December 15, 2026, and interim reporting periods beginning after December 15, 2027, with early adoption permitted. The Company is still evaluating the impacts of this ASU on its future financial statements and disclosures.
ASU 2024-03 is effective for annual reporting periods beginning after December 15, 2026, and interim reporting periods beginning after December 15, 2027, with early adoption permitted. The Company is evaluating the impacts of this ASU on its future financial statements and disclosures.
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.
We designed our 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.
Risk Factors of this Annual Report on Form 10-K for a discussion of important factors that could cause actual results to differ materially from the results described in or implied by the forward-looking statements contained in the following discussion and analysis. 79 Table of Contents Overview Company Overview We are a late-stage clinical drug platform company addressing neurodegeneration, such as Alzheimer’s disease (“AD”) and Parkinson’s disease (“PD”).
Risk Factors of this Annual Report on Form 10-K for a discussion of important factors that could cause actual results to differ materially from the results described in or implied by the forward-looking statements contained in the following discussion and analysis. 81 Table of Contents Overview Company Overview We are a late-stage clinical drug platform company addressing neurodegeneration, such as Alzheimer’s disease (“AD”) and Parkinson’s disease (“PD”).
Based on pre-clinical 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.
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.
In the Phase 2/3 AD Study, mild to moderate AD patients were defined as those with a MMSE score between 14 and 24. Our Phase 3 PD Study and Phase 2/3 AD Study each had built in interim analyses.
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 ultimate goal is to develop a disease modifying drug (“DMD”) for patients with neurodegeneration by leveraging our clinical and pre-clinical data, which shows inhibition of the most relevant neurotoxic proteins.
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.
General and Administrative Expenses General and administrative (“G&A”) expenses consist primarily of salaries, benefits and other related costs, including public company costs as well as stock-based compensation, for personnel serving in our executive, finance, accounting, and administrative functions.
General and Administrative Expenses General and administrative expenses consist primarily of salaries, benefits and other related costs, including public company costs as well as stock-based compensation, for personnel serving in our executive, finance, accounting, and administrative functions.
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 is designed to inhibit more than one neurotoxic protein and has a mechanism of action designed to restore nerve cell axonal and synaptic activity.
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.
Product candidates in later stage clinical development generally have higher research and development expenses than those in earlier stages of development, primarily due to increased size (e.g., patient population) and duration of the clinical trials. We track and record information regarding external research and development expenses for each study or trial that we conduct.
Product candidates in later stage clinical development generally have higher research and development expenses than those in earlier stages of development, primarily due to increased size (e.g., patient population) and duration of the clinical trials. We track and record information regarding external research and development expenses for each study 84 Table of Contents or trial that we conduct.
In November 2024, the FASB issued ASU 2024-03, Income Statement — Reporting Comprehensive Income — Expense Disaggregation Disclosures (Subtopic 220-40): Disaggregation of Income Statement Expenses (“ ASU 2024-03 ”) , which requires public entities, at annual and interim reporting periods, to disclose in a tabular format additional information about specific expense categories in the notes to the financial statements.
Recent Accounting Pronouncements In November 2024, the FASB issued ASU 2024-03, Income Statement — Reporting Comprehensive Income — Expense Disaggregation Disclosures (Subtopic 220-40): Disaggregation of Income Statement Expenses (“ ASU 2024-03 ”) , which requires public entities, at annual and interim reporting periods, to disclose in a tabular format additional information about specific expense categories in the notes to the financial statements.
This could substantially limit the amount of tax attributes that can be utilized annually to offset future taxable income or tax liabilities. The amount of the annual limitation is determined based on our value immediately prior to the ownership change. Subsequent ownership 82 Table of Contents changes may further affect the limitation in future years.
This could substantially limit the amount of tax attributes that can be utilized annually to offset future taxable income or tax liabilities. The amount of the annual limitation is determined based on our value immediately prior to the ownership change. Subsequent ownership changes may further affect the limitation in future years.
Treasury securities in effect at the time of grant for a period that is commensurate with the assumed expected term. Expected Dividends. The expected dividend yield is 0% because we have not historically paid, and do not expect for the foreseeable future to pay, a dividend on our common stock.
Treasury securities in effect at the time of grant for a period that is commensurate with the assumed expected term. 91 Table of Contents Expected Dividends. The expected dividend yield is 0% because we have not historically paid, and do not expect for the foreseeable future to pay, a dividend on our common stock.
Segment Information ​ As of December 31, 2024, we viewed our operations and managed our business as one operating segment consistent with how our chief operating decision-maker, our Chief Executive Officer, makes decisions regarding resource allocation and assessing performance. As of December 31, 2024, substantially all of our assets were located in the United States.
Segment Information ​ As of December 31, 2025, we viewed our operations and managed our business as one operating segment consistent with how our chief operating decision-maker (“CODM”), our Chief Executive Officer, makes decisions regarding resource allocation and assessing performance. As of December 31, 2025, substantially all of our assets were located in the United States.
We believe our estimates and assumptions are reasonable under the current conditions; however, actual results may differ from these estimates. Any changes to estimates will be recorded in the 87 Table of Contents period in which a circumstance causing a change in estimate becomes known and the impact of any change in estimate could be material.
We believe our estimates and assumptions are reasonable under the current conditions; however, actual results may differ from these estimates. Any changes to estimates will be recorded in the period in which a circumstance causing a change in estimate becomes known and the impact of any change in estimate could be material.
Recent Accounting Pronouncements In December 2023, the FASB issued ASU No. 2023-09, Income Taxes (Topic 740): Improvements to Income Tax Disclosures (“ASU 2023-09”), which improves income tax disclosures by requiring: (1) consistent categories and greater disaggregation of information in the rate reconciliation, and (2) income taxes paid disaggregated by jurisdiction.
Recently Adopted Accounting Pronouncements In December 2023, the FASB issued ASU No. 2023-09, Income Taxes (Topic 740): Improvements to Income Tax Disclosures (“ASU 2023-09”), which improves income tax disclosures by requiring: (1) consistent categories and greater disaggregation of information in the rate reconciliation, and (2) income taxes paid disaggregated by jurisdiction.
We measure and record stock compensation expense using the applicable accounting guidance for share-based payments using the Black-Scholes option pricing model to value option awards which requires the use of subjective assumptions, including the expected life of the option and expected share price volatility.
We measure and record stock compensation expense using the 90 Table of Contents applicable accounting guidance for share-based payments using the Black-Scholes option pricing model to value option awards which requires the use of subjective assumptions, including the expected life of the option and expected share price volatility.
When that communication is compromised, the immune system is activated and attacks the nerve cells, eventually killing them. We have observed in our clinical studies in early AD and early PD patients and pre-clinical studies in mice and rats that buntanetap lowered neurotoxic protein levels leading to improved axonal transport, reduced inflammation, lower nerve cell death and improved affected function.
When that communication is compromised, the immune system is activated and attacks the nerve cells, eventually killing them. We have observed in our completed clinical studies in AD and PD patients and preclinical studies in mice and rats that buntanetap lowered neurotoxic protein levels leading to improved axonal transport, reduced inflammation, lower nerve cell death and improved affected function.
We expect that our research and development expenses in 2025 and for the next several years will continue to remain elevated as a result of costs associated with completing our Phase 3 trial for AD, our planned Phase 3 trial for PD and other subsequent planned activities leading up to a potential NDA filing(s) with the FDA.
We expect that our research and development expenses in 2026 and for the next several years will continue to remain elevated as a result of costs associated with completing our Phase 3 trial for AD, the OLE PD study, our planned Phase 3 trial for PDD, and other subsequent planned activities leading up to a potential NDA filing(s) with the FDA.
Studies have found that AD and PD are the most common neurodegenerative diseases in the U.S., and accordingly, these diseases present two unmet needs of the aging population and two potentially large U.S. markets, if a DMD is developed and approved. We have never been profitable and have incurred net losses since inception.
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. We have never been profitable and have incurred net losses since inception.
Research and Development Expenses Our research and development (“R&D”) expenses consist of expenses incurred in development and clinical studies relating to our product candidates, including: ● expenses associated with clinical development; 81 Table of Contents ● personnel-related expenses, such as salaries, benefits, travel and other related expenses, including stock-based compensation; and ● payments to third-party contract research organizations (“CROs”), contract manufacturing organizations (“CMOs”), contractor laboratories and other independent contractors.
Research and Development Expenses Our research and development expenses consist of expenses incurred in development and clinical studies relating to our product candidates, including: ● expenses associated with clinical development; ● personnel-related expenses, such as salaries, benefits, travel and other related expenses, including stock-based compensation; and ● payments to third-party contract research organizations (“CROs”), contract manufacturing organizations (“CMOs”), contractor laboratories and other independent contractors.
Stock-based compensation expense was $3.8 million and $4.6 million for the years ended December 31, 2024 and 2023, respectively. As of December 31, 2024, we had $2.4 million of unrecognized stock-based compensation expense, related to service-based options, which will be recognized over a remaining weighted-average period of 1.0 years.
Stock-based compensation expense was $1.8 million and $3.8 million for the years ended December 31, 2025 and 2024, respectively. As of December 31, 2025, we had $1.1 million of unrecognized stock-based compensation expense, related to service-based options, which will be recognized over a remaining weighted-average period of 1.1 years.
We believe that our current cash and cash equivalents will be sufficient to fund our operating expenses and capital expenditure requirements into the fourth quarter of 2025.
We believe that our current cash and cash equivalents will be sufficient to fund our operating expenses and capital expenditure requirements into the third quarter of 2026.
In accordance with the terms of the Distribution Agreement, we may offer and sell shares of our common stock having an aggregate offering price of up to $50.0 million from time to time through or to OpCo, acting as our agent or principal.
In accordance with the terms of the 87 Table of Contents Distribution Agreement, the Company may offer and sell shares of its common stock having an aggregate offering price of up to $50.0 million from time to time through or to OpCo, acting as agent or principal.
Our accumulated deficit at December 31, 2024 was $134.8 million. We expect to incur losses for the foreseeable future, and we expect these losses to increase as we continue our development of, and seek regulatory approvals for, our product candidates.
Our accumulated deficit on December 31, 2025 was $163.7 million. We expect to incur losses for the foreseeable future, and we expect these losses to increase as we continue our development of, and seek regulatory approvals for, our product candidates.
NOL carryforwards generated beginning in 2018 are permitted to offset 80% of taxable income in future years. As of December 31, 2024, the Company also had U.S. state NOL carryforwards of $56.6 million, which may be available to offset future income tax liabilities and will expire beginning in 2028.
As of December 31, 2025, the Company also had U.S. state NOL carryforwards of $74.9 million which may be available to offset future income tax liabilities and will expire beginning in 2028.
Income Taxes As of December 31, 2024, the Company had U.S. federal net operating loss (“NOL”) carryforwards of $54.1 million, which may be available to offset future income tax liabilities. Federal NOL carryforwards generated in 2017 and prior of $2.8 million will expire beginning 2032. The remaining federal NOL carryforwards generated beginning in 2018, do not expire.
Income Taxes As of December 31, 2025, the Company had U.S. federal net operating loss (“NOL”) carryforwards of $72.4 million which may be available to offset future income tax liabilities and will expire beginning in 2032.
During the year ended December 31, 2024, we have sold 26,788 shares of common stock pursuant to the Distribution Agreement for gross proceeds of $0.2 million before commissions.
During the year-ended December 31, 2025, the Company sold 2.1 million shares of common stock pursuant to the Distribution Agreement for gross proceeds of $6.8 million before commissions.
We have irrevocably elected not to avail ourselves of this exemption from new or revised accounting standards and, therefore, we will be subject to the same new or revised accounting standards as other public companies that are not emerging growth companies. Item 7A. Quantitative and Qualitative Disclosures About Market Risk. This item is not required for smaller reporting companies.
We have irrevocably elected not to avail ourselves of this exemption from new or revised accounting standards and, therefore, we will be subject to the same new or revised accounting standards as other public companies that are not emerging growth companies. As of December 31, 2025, we no longer qualify as an emerging growth company. Item 7A.
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 (our “Phase 2/3 AD Study”).
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 3 PD Study, 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.
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.
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 UPDRS. Following completion of the AD/PD Trials, we submitted our data to the U.S.
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 UPDRS. ADAS-Cog is an assessment scale that measures cognitive functions and non-cognitive functions such as mood and behavior.
The study data showed that in two subgroups, buntanetap improved UPDRS 2, 3, 2+3 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.
It also showed that in the entire ITT Alzheimer’s 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.
Cash Flows The following table summarizes our cash flows from operating, investing and financing activities the years ended December 31, 2024 and 2023. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ ​ December 31, ​ 2024 2023 ​ ​ (in thousands) Total net cash (used in) provided by: ​ ​ Operating activities ​ $ (21,895) ​ $ (39,967) Financing activities ​ 26,692 ​ 17,344 Net increase (decrease) in cash and cash equivalents ​ $ 4,797 ​ $ (22,623) ​ Operating Activities For the year ended December 31, 2024, cash used in operations was $21.9 million compared to $40.0 million for the year ended December 31, 2023.
See the section of this Annual Report on Form 10-K titled “Risk Factors” for additional risks associated with our substantial capital requirements. ​ 89 Table of Contents Cash Flows The following table summarizes our cash flows from operating, investing and financing activities the years ended December 31, 2025 and 2024. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ ​ December 31, ​ ​ ​ ​ 2025 ​ ​ ​ 2024 ​ ​ (in thousands) Total net cash provided by (used in): ​ ​ ​ ​ Operating activities ​ $ (25,620) ​ $ (21,895) Financing activities ​ 34,600 ​ 26,692 Net increase (decrease) in cash and cash equivalents ​ $ 8,980 ​ $ 4,797 ​ Operating Activities For the year ended December 31, 2025, cash used in operations was $25.6 million compared to $21.9 million for the year ended December 31, 2024.
The Phase 2/3 AD study 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.
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. 83 Table of Contents On October 10, 2024, the Company 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.
February 2025 ThinkEquity Offering On February 3, 2025, we entered into an Underwriting Agreement with ThinkEquity LLC, acting as representative of the underwriters with respect to an underwritten public offering of 5.3 million units of the Company.
February 2025 ThinkEquity Underwritten Offering and Warrant Issuance On February 3, 2025, the Company entered into an Underwriting Agreement with ThinkEquity LLC (“ThinkEquity”), with respect to an underwritten public offering of 5.3 million units of the Company, each unit consisting of one share of common stock, par value $0.0001 per share and one warrant to purchase one share of the Company Stock (the “ThinkEquity Warrants”).
Our research and development expenses in 2023 were primarily related to the execution of our Phase 3 study in early PD patients and our Phase 2/3 study in AD patients.
Our research and development expenses in 2025 were primarily related to our Phase 3 AD Trial which started in February 2025.
Total warrant commissions payable to Canaccord for these exercises totaled $0.5 million, which was expensed in the Statements of Operations for the year ended December 31, 2024. December 2024 ATM On December 11, 2024, we entered into an Equity Distribution Agreement (“Distribution Agreement”) with Oppenheimer & Co. Inc. (“OpCo”), relating to the sale of shares of our common stock.
The shares of common stock and warrants were issued separately. No ThinkEquity Warrants were exercised during the year ended December 31, 2025. December 2024 ATM On December 11, 2024, the Company entered into an Equity Distribution Agreement (“Distribution Agreement”) with Oppenheimer & Co. Inc. (“OpCo”) relating to the sale of shares of the Company’s common stock.
Based on the results of the interim analysis, we proceeded with the Phase 3 PD Study as planned in accordance with the previously established protocol. The study was completed on December 4, 2023, and we released the topline PD Study efficacy data on July 2, 2024.
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 II, III, II+III and total.
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 aligned on a development path for buntanetap towards the filing of New Drug Applications (“NDAs”), one for short-term and one for long-term efficacy.
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.
Interest Income Interest income decreased by $0.3 million for the year ended December 31, 2024 compared to the year ended December 31, 2023. The decrease was primarily the result of lower cash and cash equivalent balances on hand year-over-year. Other Financing Costs Financing costs were $1.9 million for the year ended December 31, 2024.
The increase was driven by increased cash and cash equivalent balances, as a result of our public offering with ThinkEquity, which closed in February 2025. Other Financing Costs There were no other financing costs incurred for the year ended December 31, 2025, compared to $1.9 million incurred for the year ended December 31, 2024.
For the year ended December 31, 2023, the change in fair value was primarily attributable to issuance of the liability-classified Canaccord Warrants and the increase in our stock price during the fourth quarter. Liquidity and Capital Resources Since our inception in 2008, we have devoted most of our cash resources to research and development and general and administrative activities.
The $3.5 million difference between periods was primarily driven by increased volatility in our stock price during the first half of 2024, as compared to 2025. Liquidity and Capital Resources Since our inception in 2008, we have devoted most of our cash resources to research and development and general and administrative activities.
Change in Fair Value of Warrants Change in fair value of warrants was a gain of $3.6 million for the year ended December 31, 2024 compared to a loss of $11.8 million the year ended December 31, 2023. This change was attributable to the fair value remeasurement with respect to our liability-classified Canaccord Warrants during 2024.
The $1.9 million decrease was attributable to the 2024 Equity Line of Credit (“ELOC”) financing facility being exhausted prior to the year ended December 31, 2025, whereas during the same period during 2024 the facility was active. 86 Table of Contents Change in Fair Value of Warrants Change in fair value of warrants was a gain of $0.1 million for the year ended December 31, 2025, compared to a gain of $3.6 million the year ended December 31, 2024.
Cash provided by financing activities was $17.3 million during the year ended December 31, 2023, which was primarily attributable to proceeds from issuance of common stock and warrants for capital raises, including proceeds from our equity financing with Canaccord as well as proceeds from exercises of our Canaccord Warrants.
Financing Activities Cash provided by financing activities was $34.6 million during the year ended December 31, 2025, which primarily consisted of the $19.2 million of proceeds from our registered offering with ThinkEquity, $6.8 million of proceeds from our ATM facility with OpCo., $5.5 million of proceeds from our registered offering of shares and Pre-Funded Warrants, as well as $3.1 million of proceeds from our registered offering of shares with our two members of the Board of Directors.
General and Administrative Expenses General and administrative expenses increased by $0.5 million for the year ended December 31, 2024, compared to the year ended December 31, 2023. The increase was primarily a result of warrant exercise commissions expensed during the current year.
During the six months ended December 31, 2025, the Company incurred expenses of $10.6 million in our AD program and $1.5 million in our PD program. General and Administrative Expenses General and administrative expenses decreased by $2.2 million for the year ended December 31, 2025, compared to the year ended December 31, 2024.
Each unit sold consisted of one share 84 Table of Contents of common stock and one warrant to purchase one share of common stock (the “ThinkEquity Warrants”), at a per unit price of $4.00 (the “Offering”). Aggregate gross proceeds from the Offering were $21.0 million before deducting underwriting discounts and other estimated offering expenses.
The units were priced at $4.00 per unit and the offering resulted in gross proceeds of $21.0 million, before deducting underwriting discounts, fees and other related expenses. Net proceeds from the transaction totaled $19.3 million. The ThinkEquity Warrants have an exercise price of $5.00 per share, are immediately exercisable and expire five years from their date of issuance.
Removed
Food and Drug Administration (“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 (our “Phase 3 PD Study”).
Added
We believe that the AD/PD Trials represent the first double-blind, placebo-controlled study that showed improvements in AD patients, as measured by Alzheimer’s Disease Assessment Scale-Cognitive Subscale (“ADAS-Cog”), and in PD patients, as measured by Unified Parkinson’s Disease Rating Scale (“MDS-UPDRS” or “UPDRS”).
Removed
Our Phase 3 PD Study incorporated an interim analysis at two months, the results of which were disclosed on March 31, 2023. The pre-planned interim analysis was conducted by our data analytics provider based on 132 patients from all cohorts collectively, for which baseline and two-month data was available.
Added
Currently we are conducting two clinical studies – a pivotal Phase 3 study in early AD (“Phase 3 AD Trial”) (NCT06709014) and an open-label extension (“OLE”) study in PD (NCT07284784), and we plan for a third study in Parkinson’s disease dementia (“PDD”).
Removed
We expect to discuss the Phase 3 PD data with the FDA at an end-of-study meeting during 2025. During that meeting, we plan to propose continued development of buntanetap with an additional, pivotal Phase 3 trial.
Added
In February of 2025, we initiated the FDA-cleared pivotal Phase 3 AD Trial: a randomized, double-blind, placebo-controlled, multicenter Phase 3 study in 760 early AD patients.
Removed
With respect to the Phase 2/3 AD Study, we disclosed the results of the interim analysis on October 23, 2023, and similar to our PD study, based on the outcome of the interim analysis, we proceeded with the study as planned.
Added
The trial investigates buntanetap and consists of two parts: a 6-month treatment period aimed at confirming buntanetap’s symptomatic efficacy, followed by an additional 12 months of treatment to show potential disease-modifying efficacy at 18 months. After the 6-month treatment period has been completed, patients will continue to be blinded for an additional 12 months.
Removed
The Phase 3 AD program will investigate 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, then later transitioning into an 18-month study period, designed to demonstrate potential disease-modifying effects.
Added
If well-designed and well-executed, the symptomatic portion of the trial may be sufficient to support a New Drug Application (“NDA”) filing, potentially within one year of the 6-month treatment period completion. A similar pathway could be available after 18 months, where a second NDA for disease modification may be supportable with a well-designed and well-executed long-term portion of the trial.
Removed
While the overall study will span the combined 18-month treatment period, the completion of the first 6-month period, if well-designed and well-executed, may be sufficient to support an NDA filing, potentially within one year of the 6-month treatment period initiation. 80 Table of Contents During the end-of-phase 2 meeting for AD, the FDA raised no concerns with the Company’s data on buntanetap’s safety, including impact on liver enzymes, drug interactions, dose selection, pharmacokinetics and population pharmacokinetics.
Added
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 (“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.
Removed
Studies have found that AD and PD are the most common neurodegenerative diseases in the U.S., and accordingly these diseases present two unmet needs of the aging population and two potentially large U.S. markets, if a DMD is developed and approved.
Added
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.
Removed
We believe that we are the only company developing a drug for AD and PD that is designed to inhibit more than one neurotoxic protein and has a mechanism of action designed to restore nerve cell axonal and synaptic activity.
Added
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.
Removed
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.
Added
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.
Removed
Based on pre-clinical 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.
Added
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.
Removed
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.
Added
We are refining the proposed protocol for the PDD program and will initiate the study contingent on additional funding. 82 Table of Contents To date, we have concluded 12 clinical studies, most of which were in healthy volunteers to assess safety, food effect, PK, distribution, etc.
Removed
Our ultimate goal is to develop a disease modifying drug (“DMD”) for patients with neurodegeneration by leveraging our clinical and pre-clinical data, which shows inhibition of the most relevant neurotoxic proteins.
Added
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”).
Removed
We have not yet conducted a comprehensive study to assess whether a change of ownership as defined by Section 382 has occurred since our inception.
Added
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.
Removed
The decrease was primarily the result of our Phase 3 PD and Phase 2/3 AD studies being active during the majority of 2023, whereas 2024 study activity was minimal because the aforementioned trials had been completed.
Added
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.
Removed
This decrease related to timing of study costs was primarily offset by increases in statistics, bioanalytical and CMC costs during the year ended December 31, 2024. Year-over-year increases for these items took place as we analyzed data from our completed Phase 3 PD and Phase 2/3 AD studies and performed preparatory work for our pivotal Phase 3 AD study.
Added
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.
Removed
We did not incur any financing costs for the year ended December 31, 2023. The change was attributable to issuance costs as well as changes in derivative fair value associated with our ELOC financing with an ELOC Purchaser, described further below.
Added
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.

… 40 more changes not shown on this page.

Other ANVS 10-K year-over-year comparisons