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Vistagen Therapeutics, Inc.

Vistagen Therapeutics, Inc.VTGN财报

Nasdaq · 医疗保健 · 药物制剂

Vistagen Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing innovative treatments for mental health and central nervous system disorders including anxiety and depression. It primarily targets North American and global markets, advancing multiple drug candidates through clinical development stages to address unmet patient medical needs.

What changed in Vistagen Therapeutics, Inc.'s 10-K — 2024 vs 2025

Top changes in Vistagen Therapeutics, Inc.'s 2025 10-K

548 paragraphs added · 610 removed · 447 edited across 6 sections

Item 1. Business

Business — how the company describes what it does

119 edited+49 added−61 removed224 unchanged
In addition, we believe that our highly selective outsourcing of certain research, development, legal, manufacturing and regulatory advisory activities gives us flexible access to a broad range of capabilities and expertise at a lower overall cost than developing and maintaining certain of such capabilities and expertise internally on a full-time basis.
In addition, we believe that our highly selective outsourcing of certain research, development, legal, manufacturing and regulatory advisory activities gives us flexible access to a broad range of capabilities and expertise at a lower overall cost than developing and maintaining such capabilities and expertise internally on a full-time basis.
On September 1, 2023, we entered into an Exclusive Negotiation Agreement (the Negotiation Agreement) with Fuji Pharma Co., Ltd. (Fuji Pharma), a Tokyo Stock Exchange-listed, Japan-based pharmaceutical company.
Exclusive Negotiation Agreement with Fuji Pharma Co., LTD. On September 1, 2023, we entered into an Exclusive Negotiation Agreement (the Negotiation Agreement) with Fuji Pharma Co., Ltd. (Fuji Pharma), a Tokyo Stock Exchange-listed, Japan-based pharmaceutical company.
These laws may affect our future sales, marketing, and other promotional activities by imposing administrative and compliance burdens. 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 certain business activities could be subject to challenge under one or more of such laws.
These laws may affect our future sales, marketing, and other promotional activities by imposing administrative and compliance burdens. 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 certain business activities could be subject to challenge under one or more such laws.
As of March 31, 2024, these patent properties consist of the following: Fasedienol for the Acute Treatment of SAD The granted U.S. patents relate to the use of fasedienol for the acute treatment of SAD and nominally will expire either in 2025 or 2028 and foreign patents will nominally expire in 2026, subject to patent term extensions that may be available in the U.S. and in certain foreign countries.
As of March 31, 2025 , these patent properties consist of the following: Fasedienol for the Acute Treatment of SAD The granted U.S. patents relate to the use of fasedienol for the acute treatment of SAD and nominally will expire either in 2025 or 2028 and foreign patents will nominally expire in 2026, subject to patent term extensions that may be available in the U.S. and in certain foreign countries.
With colleagues who can contribute unique viewpoints and diverse perspectives to all aspects of the business, we believe that our culture can be more collaborative, more accepting of difference and more prepared for overall success as we seek to o develop groundbreaking therapies for psychiatric and neurological disorders.
With colleagues who can contribute unique viewpoints and diverse perspectives to all aspects of the business, we believe that our culture can be more collaborative, more accepting of difference and more prepared for overall success as we seek to develop groundbreaking therapies for psychiatric and neurological disorders.
The implementation of current and future cost containment measures or other healthcare reforms may adversely affect our operations and prevent us from being able to generate revenue, attain profitability or commercialize our drug candidates. 23 Table of Contents The Foreign Corrupt Practices Act The Foreign Corrupt Practices Act (FCPA) prohibits any U.S. individual or business from paying, offering, or authorizing payment or offering of anything of value, directly or indirectly, to any foreign official, political party, or candidate for the purpose of influencing any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business.
The implementation of current and future cost containment measures or other healthcare reforms may adversely affect our operations and prevent us from being able to generate revenue, attain profitability or commercialize our drug candidates. 24 Table of Contents The Foreign Corrupt Practices Act The Foreign Corrupt Practices Act (FCPA) prohibits any U.S. individual or business from paying, offering, or authorizing payment or offering of anything of value, directly or indirectly, to any foreign official, political party, or candidate for the purpose of influencing any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business.
We have a U.S. registration application pending for VISTAGEN in international class 10 for “human and veterinary preparations for medical uses.” Strategic Transactions and Relationships Given the depth of clinical development across our neuroscience pipeline and potential additional preclinical candidates from our pherine platform, we have the potential to pursue multiple strategic development and commercialization partnerships across our pipeline to efficiently unlock the full value of our product candidate portfolio.
We have a U.S. registration application pending for VISTAGEN in international class 10 for “human and veterinary preparations for medical uses.” Strategic Transactions and Relationships Given the depth of clinical development across our neuroscience pipeline and potential additional preclinical candidates from our pherine platform, we have the potential to pursue multiple strategic development and commercialization partnerships across our pipeline to efficiently unlock potential incremental value of our product candidate portfolio.
The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to CMS information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other healthcare professionals such as physician assistants and nurse practitioners, and teaching hospitals, and applicable manufacturers and applicable group purchasing organizations to report annually to CMS ownership and investment interests held by physicians and their immediate family members.
The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with 21 Table of Contents specific exceptions, to report annually to CMS information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other healthcare professionals such as physician assistants and nurse practitioners, and teaching hospitals, and applicable manufacturers and applicable group purchasing organizations to report annually to CMS ownership and investment interests held by physicians and their immediate family members.
In addition, we may face competition to fasedienol for treatment of anxiety in adult and adolescent patients with SAD from generic antidepressants as well as off-label use of generic benzodiazepines and generic beta blockers even though no drug in either of such generic drug classes has been systematically developed for treatment of SAD, acute or otherwise, and thus no drug in either of such generic drug classes has been FDA-approved for the acute treatment of SAD.
In addition, we may face competition to fasedienol for treatment of anxiety in adult and adolescent patients with SAD from generic antidepressants as well as off-label use of generic benzodiazepines and generic beta blockers even though no drug in either of those generic drug classes have been systematically developed for treatment of SAD, acute or otherwise, and thus no drug in either of such generic drug classes has been FDA-approved for the acute treatment of SAD.
Of the fasedienol-treated patients, 35.7% demonstrated this statistically significant and clinically meaningful improvement in SUDS score, as compared to 18.6% in the placebo-treated group (p=0.020). Fasedienol was observed to be well-tolerated with no serious adverse events (SAEs), and the treatment-emergent adverse event (TEAE) profiles were comparable between fasedienol and placebo.
Of the fasedienol-treated patients, 35.7% demonstrated this statistically significant improvement in SUDS score, as compared to 18.6% in the placebo-treated group (p=0.020). Fasedienol was observed to be well-tolerated with no serious adverse events (SAEs), and the treatment-emergent adverse event (TEAE) profiles were comparable between fasedienol and placebo.
In the previously unreported randomized, double-blind, placebo-controlled, crossover Phase 2A pilot study designed to explore the efficacy, safety, and tolerability of intranasal administration of PH15 on psychomotor performance as measured by reaction time in sleep-deprived participants, PH15 demonstrated a statistically significant improvement in reaction time compared to placebo and caffeine in the sleep-deprived study participants.
In a randomized, double-blind, placebo-controlled, crossover Phase 2A pilot study designed to explore the efficacy, safety, and tolerability of intranasal administration of PH15 on psychomotor performance as measured by reaction time in sleep-deprived participants, PH15 demonstrated a statistically significant improvement in reaction time compared to placebo and caffeine in the sleep-deprived study participants.
We do not currently own or operate, nor do we plan to own or operate, manufacturing facilities for the production of our drug substances and drug product candidates for nonclinical, clinical or commercial use. We conduct manufacturing and analytical testing activities under individual project work orders with independent CMOs to supply all of our nonclinical and clinical trial needs.
We do not currently own or operate, nor do we plan to own or operate, manufacturing facilities for the production of our drug substances and drug product candidates for nonclinical, clinical or commercial use. We conduct manufacturing and analytical testing activities under individual project work orders with independent CDMOs to supply all of our nonclinical and clinical trial needs.
PH80 for the Treatment of Vasomotor Symptoms (Hot Flashes) Due to Menopause and Other Indications The granted U.S. a nd foreign patents and corresponding pending foreign patents relate to the use of PH80 to treat vasomotor symptoms (hot flashes) due to menopause. Patents that have been or may yet be granted will expire in 2029.
PH80 for the Treatment of Vasomotor Symptoms (Hot Flashes) Due to Menopause and Other Indications The granted U.S. a nd foreign patents and corresponding pending foreign patent applications relate to the use of PH80 to treat vasomotor symptoms (hot flashes) due to menopause. Patents that have been or may yet be granted will expire in 2029.
NDA Submission, Review by the FDA, and Marketing Approval Assuming successful completion of the required clinical and preclinical testing, the results of product development, including chemistry, manufacturing, and control (CMC) information, results from non-clinical studies and clinical trial results, including negative or ambiguous results as well as positive findings, are all submitted to the FDA, along with the 15 Table of Contents proposed labeling, as part of an NDA requesting approval to market the product for one or more indications.
NDA Submission, Review by the FDA, and Marketing Approval Assuming successful completion of the required clinical and preclinical testing, the results of product development, including chemistry, manufacturing, and control (CMC) information, results from non-clinical studies and clinical trial results, including negative or ambiguous results as well as positive findings, are all submitted to the FDA, along with the proposed labeling, as part of an NDA requesting approval to market the product for one or more indications.
Certain states also require implementation of commercial compliance programs and compliance with the pharmaceutical industry’s voluntary compliance guidelines and the applicable compliance guidance promulgated by the federal government, or otherwise restrict payments or the provision of other items of value that may be made to healthcare providers and other potential referral sources; impose restrictions on marketing practices; or require drug manufacturers to track and report information related to payments, gifts, and other 21 Table of Contents items of value to physicians and other healthcare providers.
Certain states also require implementation of commercial compliance programs and compliance with the pharmaceutical industry’s voluntary compliance guidelines and the applicable compliance guidance promulgated by the federal government, or otherwise restrict payments or the provision of other items of value that may be made to healthcare providers and other potential referral sources; impose restrictions on marketing practices; or require drug manufacturers to track and report information related to payments, gifts, and other items of value to physicians and other healthcare providers.
Neither we nor Fuji Pharma is obligated to enter into the Potential Definitive Agreement, and if we and Fuji Pharma have not entered into the Potential Definitive Agreement on or before the end of the Exclusive Negotiation Period, either party may terminate any further negotiations.
Neither we nor Fuji Pharma are obligated to enter into the Potential Definitive Agreement, and if we and Fuji Pharma have not entered into the Potential Definitive Agreement on or before the end of the Exclusive Negotiation Period, either party may terminate any further negotiations.
FDA Regulation of Combination Products Certain product candidates may be comprised of components, such as drug components and device components, that would normally be regulated under different types of regulatory authorities, and frequently by different centers at the FDA. These products are known as combination products.
FDA Regulation of Combination Products Certain product candidates may be comprised of components, such as drug components and device components, which would normally be regulated under different types of regulatory authorities, and frequently by different centers at the FDA. These products are known as combination products.
In addition, we take other appropriate precautions, such as physical and technological security measures, to guard against the misappropriation of our proprietary information by third parties. 10 Table of Contents Trademarks We also own a registered trademark in the U.S. for “VISTAGEN,” for “biotechnology services” in international class 42, which was renewed in 2021.
In addition, we take other appropriate precautions, such as physical and technological security measures, to guard against the misappropriation of our proprietary information by third parties. Trademarks We also own a registered trademark in the U.S. for “VISTAGEN,” for “biotechnology services” in international class 42, which was renewed in 2021.
However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the nonclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and efficacy. Trade Secrets In addition to patents, we may rely on trade secrets to develop and maintain our competitive position.
However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the nonclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and efficacy. 10 Table of Contents Trade Secrets In addition to patents, we may rely on trade secrets to develop and maintain our competitive position.
Although currently there are no FDA-approved therapies for MDD with the neurocircuitry-focused MOA of itruvone, we are aware of numerous companies that are developing and commercializing or have commercialized therapies targeting the MDD market, including, among others, Axsome Therapeutics, Sage Therapeutics, Relmada Therapeutics, Xenon, Intra-Cellular Therapies, Johnson & Johnson, Usona Institute, Boehringer Ingelheim, and Sirtsei Pharmaceuticals.
Although currently there are no FDA-approved therapies for MDD with the neurocircuitry-focused MOA of itruvone, we are aware of numerous companies that are developing and commercializing or have commercialized therapies targeting the MDD market, including, among others, Axsome Therapeutics, Relmada Therapeutics, Xenon, Johnson & Johnson, Usona Institute, Boehringer Ingelheim, and Sirtsei Pharmaceuticals.
Changes to the manufacturing process are strictly regulated and often require prior FDA approval or notification before being implemented. FDA regulations also require investigation and correction of any deviations from cGMP and product specifications and impose reporting and documentation requirements upon the sponsor and any third‑party manufacturers 18 Table of Contents that the sponsor may decide to use.
Changes to the manufacturing process are strictly regulated and often require prior FDA approval or notification before being implemented. FDA regulations also require investigation and correction of any deviations from cGMP and product specifications and impose reporting and documentation requirements upon the sponsor and any third‑party manufacturers that the sponsor may decide to use.
As a result, the coverage determination process is often time-consuming and costly and may require the provision of scientific and clinical support for the use of new products to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.
As a result, the coverage determination process is often time-consuming and costly and may require the provision of scientific and clinical support for the use of 22 Table of Contents new products to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.
New CMOs may be added to our supply chain strategy in the future to ensure that our nonclinical, clinical and, subject to NDA approval, commercial manufacturing and testing needs are met.
New CDMOs may be added to our supply chain strategy in the future to ensure that our nonclinical, clinical and, subject to NDA approval, commercial manufacturing and testing needs are met.
An active moiety is the molecule or ion excluding those appended portions of the molecule that cause the drug to be an ester, salt, including a salt with hydrogen or coordination bonds, or other noncovalent derivatives, such as a complex, chelate, or clathrate, of the molecule, responsible for the therapeutic activity of the drug substance.
An active moiety is the molecule or ion excluding those appended portions of the molecule that cause the drug to be an ester, salt, including a salt with hydrogen or coordination bonds, or other noncovalent derivatives, such as a complex, chelate, or clathrate, of the 19 Table of Contents molecule, responsible for the therapeutic activity of the drug substance.
NCE and NCI 19 Table of Contents exclusivities will not delay the submission or approval of a full NDA; however, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well‑controlled clinical trials necessary to demonstrate safety and efficacy.
NCE and NCI exclusivities will not delay the submission or approval of a full NDA; however, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well‑controlled clinical trials necessary to demonstrate safety and efficacy.
In a randomized, double-blind, placebo-controlled parallel design exploratory Phase 2A clinical trial of itruvone in MDD, the results of which were published in the peer-reviewed British Journal of Pharmaceutical and Medical Research , at a 6.4 μg dose administered intranasally twice daily for eight weeks, itruvone significantly reduced depressive symptoms as early as one week based on the 17-item Hamilton Depression Scale (HAM-D-17) scores compared to placebo (p=0.022).
In a randomized, double-blind, placebo-controlled parallel design exploratory Phase 2A clinical trial of itruvone as a stand-alone treatment for MDD, the results of which were published in the peer-reviewed British Journal of Pharmaceutical and Medical Research, at a 6.4 microgram dose administered intranasally twice daily for eight weeks, itruvone significantly reduced depressive symptoms in as early as one week based on the 17-item Hamilton Depression Scale (HAM-D-17) scores compared to placebo (p=0.022).
Investigators must also provide certain information to the clinical trial sponsors to allow the sponsors to make certain financial disclosures to the FDA. Clinical trials are conducted under protocols detailing, among other things, the objectives of the trial, dosing procedures, subject selection and exclusion criteria and the 14 Table of Contents safety and effectiveness criteria to be evaluated.
Investigators must also provide certain information to the clinical trial sponsors to allow the sponsors to make certain financial disclosures to the FDA. Clinical trials are conducted under protocols detailing, among other things, the objectives of the trial, dosing procedures, subject selection and exclusion criteria and the safety and effectiveness criteria to be evaluated.
The key competitive factors affecting the success of all of our product 12 Table of Contents candidates, if approved, are likely to be their efficacy, safety, tolerability, convenience, price, the level of branded and generic competition, and the availability of reimbursement from government and other third‑party payers.
The key competitive factors affecting the success of all of our product candidates, if approved, are likely to be their efficacy, safety, tolerability, convenience, price, the level of branded and generic competition, and the availability of reimbursement from government and other third‑party payers.
Our PALISADE-2 trial also met an additional exploratory endpoint, the difference in the proportion of patients in each treatment group with a 20-point or greater improvement in patient-assessed SUDS score from baseline (Visit 2) to treatment (Visit 3).
Our PALISADE-2 Phase 3 trial also met an additional exploratory endpoint with a statistically significant difference in the proportion of patients in each treatment group with a 20-point or greater improvement in patient-assessed SUDS score from baseline (Visit 2) to treatment (Visit 3).
Our PALISADE-2 Phase 3 trial met its primary efficacy endpoint, which was the difference in mean SUDS scores during the public speaking challenge at baseline (Visit 2) and treatment (Visit 3) for subjects treated with fasedienol versus placebo at Visit 3.
PALISADE-2 met its primary efficacy endpoint, which was the difference in mean SUDS scores during the public speaking challenge at baseline (Visit 2) and treatment (Visit 3) for subjects treated with fasedienol versus placebo at Visit 3.
Clinical holds also may be imposed by the FDA at any time before or during trials due to safety concerns or noncompliance with applicable requirements, and in either case, the proposed trial or trials may not begin or continue until the FDA notifies the IND sponsor that the hold has been lifted.
Clinical holds also may be imposed by the FDA at any time before or during trials due to safety concerns or noncompliance with applicable requirements, and in either case, the proposed trial or trials may not begin or 14 Table of Contents continue until the FDA notifies the IND sponsor that the hold has been lifted.
The trial also met its secondary endpoint, demonstrating a statistically significant difference in the proportion of clinician-assessed responders between fasedienol and placebo as measured by the Clinical Global Impressions – Improvement (CGI-I) scale.
PALISADE-2 also met its secondary endpoint, demonstrating a statistically significant difference in the proportion of clinician-assessed responders between fasedienol and placebo as measured by the Clinical Global Impressions – Improvement (CGI-I) scale.
As a condition of approval, the FDA generally requires that a sponsor of a drug receiving accelerated approval perform adequate and well-controlled confirmatory clinical trials, and may require that such confirmatory trials be underway prior to granting accelerated approval.
As a condition of approval, the FDA generally requires that 17 Table of Contents a sponsor of a drug receiving accelerated approval perform adequate and well-controlled confirmatory clinical trials, and may require that such confirmatory trials be underway prior to granting accelerated approval.
While we believe that our employees and consultants, scientific knowledge, technology, and development experience provide us with competitive advantages, we face potential competition from many different sources, including major pharmaceutical, specialty pharmaceutical, and biotechnology companies, academic institutions and governmental agencies, and public and private research institutions.
While we believe that our employees and consultants, scientific knowledge, technology, and development experience provide us with competitive 12 Table of Contents advantages, we face potential competition from many different sources, including major pharmaceutical, specialty pharmaceutical, and biotechnology companies, academic institutions and governmental agencies, and public and private research institutions.
For that acute indication, we have aligned with the FDA that a clinic-based public speaking challenge and the Subjective Units of Distress Scale (SUDS) are the appropriate study design and primary efficacy endpoint, respectively, to measure anxiety immediately related to the specific stressor, and is the most appropriate and efficient path for our registration-directed PALISADE Phase 3 Program, which is focused on fasedienol’s potential to become the first FDA-approved acute treatment of SAD.
We have aligned with the FDA that a clinic-based public speaking challenge and the Subjective Units of Distress Scale (SUDS) are the appropriate study design and primary efficacy endpoint, respectively, to measure anxiety immediately related to the specific stressor, and is the most appropriate and efficient path for our U.S. registration-directed PALISADE Program, which is focused on fasedienol’s potential to become the first FDA-approved acute treatment of anxiety for adults with SAD.
Hence, acute treatment with fasedienol has the potential to reduce the wave of anxiety usually experienced by SAD patients before engaging in or during a feared social or performance situation.
Acute treatment with fasedienol has the potential to reduce the wave of anxiety usually experienced by SAD patients before engaging in and during a feared and anxiety-provoking social or performance situation.
By design, we do not currently have any fixed contractual arrangements in place with any CMOs, for either long-term supply or redundant supply, of drug substances or drug product for our drug product candidates.
By design, we do not currently have any fixed contractual arrangements in place with any CDMOs, for either long-term supply or redundant supply of drug substances or drug product for our pherine product candidates.
If a CRL is issued, the applicant may either resubmit the NDA, addressing all of the deficiencies identified in the letter; withdraw the 16 Table of Contents application; or request an opportunity for a hearing.
If a CRL is issued, the applicant may either resubmit the NDA, addressing all of the deficiencies identified in the letter; withdraw the application; or request an opportunity for a hearing.
Some states also have enacted fraud, 13 Table of Contents waste, and abuse laws that parallel (and in some cases apply more broadly than) federal laws, and in some cases price transparency requirements. FDA Regulation In the U.S., the FDA regulates drugs under the FDCA and its implementing regulations.
Some states also have enacted fraud, waste, and abuse laws that parallel (and in some cases apply more broadly than) federal laws, and in some cases price transparency requirements. FDA Regulation In the U.S., the FDA regulates drugs under the FDCA and its implementing regulations.
If the government decides to intervene in a qui tam action and prevails in the lawsuit, the individual will share in the proceeds from any fines or 20 Table of Contents settlement funds. If the government declines to intervene, the individual may pursue the case alone, subject to governmental review and certain approvals.
If the government decides to intervene in a qui tam action and prevails in the lawsuit, the individual will share in the proceeds from any fines or settlement funds. If the government declines to intervene, the individual may pursue the case alone, subject to governmental review and certain approvals.
Some third-party payors also require pre-approval of coverage for new or innovative devices or therapies before they will reimburse healthcare providers that use such therapies.
Some third-party payors also require pre- 23 Table of Contents approval of coverage for new or innovative devices or therapies before they will reimburse healthcare providers that use such therapies.
If our product candidates are approved for commercial distribution, we intend to execute long-term commercial supply agreement(s) with our CMOs to produce our future commercial supplies on our behalf.
If our pherine product candidates are approved for commercial distribution, we intend to execute long-term commercial supply agreement(s) with our CDMOs to produce our future commercial supplies on our behalf.
These treatments often include generic antidepressants such as: fluoxetine (Prozac), previously marketed by Eli Lilly and Company; sertraline (Zoloft) and venlaxafine (Effexor), both previously marketed by Pfizer, Inc.; and paroxetine (Paxil) and bupropion (Wellbutrin), both previously marketed by GlaxoSmithKline (now GSK).
These treatments often include generic antidepressants such as: fluoxetine (Prozac), previously marketed by Eli Lilly and Company; sertraline (Zoloft) and venlaxafine (Effexor), both previously marketed by Pfizer, Inc.; paroxetine (Paxil) and bupropion (Wellbutrin), both previously marketed by GlaxoSmithKline (now GSK), and brexpiprazole (Rexulti) previously marketed by Otsuka America.
Accordingly, our Phase 3 clinical trials in our PALISADE Phase 3 Program are randomized, double-blind, placebo-controlled, clinical trials designed to evaluate the efficacy, safety, and tolerability of a single dose of fasedienol to relieve anxiety symptoms in adult patients with SAD during a simulated, anxiety-provoking public speaking challenge conducted in a clinical setting, as measured using the patient-reported SUDS as the primary efficacy endpoint.
The Phase 3 clinical trials in our PALISADE Program are randomized, double-blind, placebo-controlled, U.S. multi-center clinical trials designed to evaluate the efficacy, safety, and tolerability of a single dose of fasedienol to relieve anxiety symptoms in adult patients with SAD during a simulated, anxiety-provoking public speaking challenge conducted in a clinical setting, as measured using the patient-rated SUDS as the primary efficacy endpoint.
Although there are three generic oral antidepressants approved by the FDA for the treatment of SAD, such drugs do not achieve rapid-onset therapeutic effects and are associated with undesirable side effects.
Although there are three generic oral antidepressants approved by the FDA for the treatment of SAD, they are not approved for the acute treatment of SAD, do not achieve rapid-onset therapeutic effects and are associated with undesirable side effects.
PH15’s proposed MOA targets nasal receptors that activate olfactory-amygdala and olfactory hippocampus neural circuits in the limbic system that are known to be associated with psychomotor activity and cognition, without requiring systemic absorption or direct action on neurons in the brain. PH15 has demonstrated an excellent safety profile in all clinical trials completed to date.
PH15’s proposed MOA targets nasal receptors that activate olfactory-to-amygdala and olfactory-to-hippocampus neural circuits in the limbic system that are known to be associated with psychomotor activity and 6 Table of Contents cognition, without requiring systemic absorption or direct action on neurons in the brain. PH15 has demonstrated excellent safety data in all clinical trials completed to date.
If coverage and reimbursement are not 22 Table of Contents available or reimbursement is available only to limited levels, we may not successfully commercialize any drug candidate for which we obtain marketing approval.
If coverage and reimbursement are not available or reimbursement is available only to limited levels, we may not successfully commercialize any drug candidate for which we obtain marketing approval.
Our PALISADE Phase 3 Program also includes open-label extension safety studies, a small Phase 2 repeat dose study (Repeat Dose Study), certain standard preclinical studies, and a small human factor study. 3 Table of Contents In early August 2023, we received and reported positive topline results from our PALISADE-2 Phase 3 trial of fasedienol for the acute treatment of SAD.
Our PALISADE Program also includes open-label extension safety studies, the ongoing small Phase 2 Repeat Dose Study, certain standard preclinical studies, and a small human factor study. In August 2023, we received and reported positive topline results from our PALISADE-2 Phase 3 trial of fasedienol for the acute treatment of anxiety in adults with SAD.
Our Other Clinical-Stage Programs Premenstrual Dysphoric Disorder (PMDD) According to the National Institutes of Health (NIH), 5% to 8% of menarcheal individuals have moderate-to-severe symptoms that can cause significant distress and functional impairment, suggestive of PMDD, a severe, sometimes disabling extension of premenstrual syndrome (PMS).
Overview of Premenstrual Dysphoric Disorder According to the National Institutes of Health (NIH), 5% to 8% of menarcheal individuals have moderate-to-severe symptoms that can cause significant distress and functional impairment, suggestive of premenstrual dysphoric disorder (PMDD), a severe, sometimes disabling extension of premenstrual syndrome (PMS).
We conduct periodic quality audits of each of the CMO’s facilities to ensure that they are fully compliant with cGMPs. We believe that all of our existing CMOs are, or will be, capable of providing sufficient quantities of both drug substance and drug product to meet our nonclinical and clinical development needs.
We conduct periodic quality audits of each of the CDMO’s facilities to ensure that they are fully compliant with cGMPs. We believe that all of our existing CDMOs are, or will be, capable of providing sufficient quantities of both drug substance and drug product to meet our nonclinical and clinical development needs, as well as our commercial needs.
Post‑Approval Requirements Any product manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, as well as other federal and state agencies, including, among other things, requirements related to manufacturing, recordkeeping, and reporting, including adverse experience reporting, drug shortage reporting, and other periodic reporting; drug supply chain security surveillance and tracking requirements; product sampling and distribution; advertising; marketing; promotion; certain electronic records and signatures; licensure in certain states for the manufacturing and distribution of drug products; and post-approval obligations imposed as a condition of approval, such as additional clinical trials, REMS, and surveillance to assess safety and effectiveness after commercialization.
Post‑Approval Requirements Any product manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, as well as other federal and state agencies, including, among other things, requirements related to manufacturing, recordkeeping, and reporting, including adverse experience reporting, drug shortage reporting, and other periodic reporting; drug supply chain security surveillance and tracking requirements; product sampling and distribution; advertising; marketing; promotion; certain electronic records and signatures; licensure in certain states for the manufacturing and distribution of drug products; and post-approval obligations imposed as a condition of approval, such as additional clinical trials, REMS, and surveillance to assess safety and effectiveness after commercialization. 18 Table of Contents After approval, most changes to the approved product, such as adding new indications or other labeling claims are subject to prior FDA review and approval.
This previously unreported Phase 2A pilot study of PH15 was sponsored by Pherin and conducted at the National Institute of Psychiatry, Sleep Disorders Clinic in Mexico City, Mexico prior to our acquisition of Pherin in February 2023.
This study of PH15 was sponsored by Pherin and conducted at the National Institute of Psychiatry, Sleep Disorders Clinic in Mexico City, Mexico prior to our acquisition of Pherin in February 2023.
Responders were identified as those who were rated ‘very much less anxious’ or ‘much less anxious’ and 37.7% of fasedienol-treated patients were rated as responders, as compared to 21.4% of those treated with placebo (p=0.033).
Responders were identified as those who were rated "very much less anxious" or "much less anxious" and 37.7% of fasedienol-treated patients were rated as responders, as compared to 21.4% of those treated with placebo (p=0.033).
Like PALISADE-2, PALISADE-3 is, and PALISADE-4 will be, multi-center, randomized, double-blind, placebo-controlled studies designed to evaluate the efficacy, safety, and tolerability of the acute administration of fasedienol to relieve anxiety symptoms in adult patients with SAD after a single dose of fasedienol during a simulated, anxiety-provoking public speaking challenge conducted in a clinical setting, as measured using the patient-reported SUDS as the primary efficacy endpoint.
Like PALISADE-2, PALISADE-3 and PALISADE-4 are U.S. multi-center, randomized, double-blind, placebo-controlled Phase 3 studies designed to evaluate the efficacy, safety, and tolerability of the acute administration of fasedienol to relieve anxiety symptoms in adults with SAD after a single dose of fasedienol during a simulated, anxiety-provoking public speaking challenge conducted in a clinical setting, as measured using the patient-reported SUDS as the primary efficacy endpoint.
When administered intranasally in microgram-level doses, odorless and tasteless fasedienol activates receptors of peripheral nasal chemosensory neurons connected to subsets of neurons in the olfactory bulbs that, in turn, connect to neurons in the limbic amygdala involved in the pathophysiology of SAD, and potentially other acute anxiety and mood disorders.
When administered intranasally in microgram-level doses, neurocircuitry-focused fasedienol activates receptors of peripheral nasal chemosensory neurons connected to subsets of neurons in the olfactory bulbs that, in turn, connect to neural circuits in the limbic amygdala involved in the pathophysiology of SAD, and potentially other acute anxiety disorders.
The trial also met an important exploratory patient-reported endpoint focused on the difference in the proportion of patient-assessed responders between fasedienol and placebo as measured by the Patient’s Global Impression of Change (PGI-C) scale.
The trial also met an important exploratory patient-reported endpoint with a statistically significant difference in the proportion of patient-assessed responders between fasedienol and placebo as measured by the Patient’s Global Impression of Change (PGI-C) scale.
This study will be a small multi-center, randomized, double-blind, placebo-controlled, three-arm Phase 2 clinical trial designed to evaluate repeated dosing (up to two doses within ten minutes) of fasedienol in adult patients with SAD during a single, simulated, anxiety-provoking public speaking challenge in a clinical setting.
This study is a small U.S. multi-center, randomized, double-blind, placebo-controlled, three-arm exploratory Phase 2 clinical trial designed to evaluate repeated dosing (up to 3 Table of Contents two doses within ten minutes) of fasedienol in adult patients with SAD during a single, simulated, anxiety-provoking public speaking challenge in a clinical setting.
Vasomotor Symptoms (hot flashes) due to Menopause We are aware of various current pharmacotherapies for vasomotor symptoms (hot flashes) due to menopause, including hormonal therapy (estrogen with or without progesterone, or a synthetic progestin), gabapentins, certain antidepressants, clonidine, as well as fezolinetant, a newly-approved non-hormonal neurokinin 3 (NK3) receptor antagonist developed and commercialized by Astellas, and a similar product candidate, elinzanetant, a non-hormonal, NK3 receptor antagonist, in late-stage development by Bayer.
Vasomotor Symptoms (hot flashes) due to Menopause We are aware of various current pharmacotherapies for vasomotor symptoms (hot flashes) due to menopause, including hormonal therapy (estrogen with or without progesterone, or a synthetic progestin), gabapentins, certain antidepressants, clonidine, as well as Veozah, marketed by Astellas Pharma, and a similar product candidate, elinzanetant, a non-hormonal, NK3 receptor antagonist, in late-stage development by Bayer.
Two of the Phase 3 trials in our PALISADE Phase 3 Program were previously concluded, PALISADE-1, concluded in 2022 and did not meet its primary endpoint, and PALISADE-2, concluded in 2023 and successfully met its primary endpoint, and as further described below, two Phase 3 trials, PALISADE-3 and PALISADE-4 are ongoing or will be initiated in 2024.
Two of the Phase 3 trials in our PALISADE Program were previously concluded; PALISADE-1, reported in 2022, did not meet its primary endpoint, and PALISADE-2, reported in 2023, successfully met its primary efficacy endpoint, and as further described below, two Phase 3 trials, PALISADE-3 and PALISADE-4, are ongoing.
Itruvone was well-tolerated and did not cause psychological side effects (such as dissociation or hallucinations), sexual side effects, weight gain, or other safety concerns that may be associated with other approved pharmacological therapies for MDD.
Itruvone was well-tolerated and did not cause psychological side effects (such as dissociation or hallucinations), sexual side effects, weight gain, or other safety concerns that may be associated with other approved pharmacological therapies for MDD. The trial was sponsored by Pherin Pharmaceuticals, Inc.
Unless earlier terminated due to certain material breaches of the contract, or otherwise, the AffaMed Agreement will expire on a jurisdiction-by-jurisdiction basis until the latest to occur of expiration of the last valid claim under a licensed patent of fasedienol in such jurisdiction, the expiration of regulatory exclusivity in such jurisdiction or ten years after the first commercial sale of fasedienol in such jurisdiction. 11 Table of Contents Exclusive Negotiation Agreement with Fuji Pharma Co., LTD.
Unless earlier terminated due to certain material breaches of the contract, or otherwise, the AffaMed Agreement will expire on a jurisdiction-by-jurisdiction basis until the latest to occur of expiration of the last valid claim under a licensed patent of fasedienol in such jurisdiction, the expiration of regulatory exclusivity in such jurisdiction or ten years after the first commercial sale of fasedienol in such jurisdiction.
The trial was sponsored by Pherin Pharmaceuticals, Inc (Pherin), now our wholly-owned subsidiary, and was conducted in Mexico prior to our acquisition of Pherin in February 2023. Positive data from our recent U.S. Investigational New Drug (IND) enabling Phase 1 trial of itruvone demonstrated that there were no reported treatment-related SAEs or discontinuations due to adverse events in the trial.
(Pherin), which is 4 Table of Contents now our wholly-owned subsidiary, and was conducted in Mexico prior to our acquisition of Pherin in February 2023. Positive data from our June 2023 U.S. Investigational New Drug (IND) enabling Phase 1 trial of itruvone demonstrated that there were no reported treatment-related SAEs or discontinuations due to adverse events in the trial.
Overall, no TEAEs, except for pyrexia in the placebo group (2.49%), was more prevalent than 2.0%. To complement our successful PALISADE-2 Phase 3 trial, we launched our PALISADE-3 Phase 3 trial in March 2024 and we are preparing to launch our PALISADE-4 Phase 3 trial in the second half of 2024.
Overall, no TEAEs, except for pyrexia in the placebo group (2.49%), was more prevalent than 2.0%. To complement our successful PALISADE-2 Phase 3 trial, we launched our PALISADE-3 and PALISADE-4 Phase 3 trials 2024.
Because of its innovative non-systemic neurocircuitry-focused MOA, we believe fasedienol has the potential to achieve these rapid-onset anxiolytic effects on an as-needed basis rather than chronic daily dosing, and with a significantly reduced risk of unwanted side effects and safety concerns, such as potential drug-drug interactions, abuse, misuse, and addiction, associated with current oral and certain other systemically absorbed neuropsychiatric pharmaceuticals that act directly on neurons in the brain and are sometimes prescribed for anxiety disorders.
Because of its innovative non-systemic neurocircuitry-focused MOA, we believe fasedienol has the potential to achieve rapid-onset anxiolytic effects for individuals with SAD on an acute, as- 2 Table of Contents needed basis, with a significantly reduced risk of unwanted side effects and safety concerns, such as potential drug-drug interactions, abuse, misuse, and addiction, associated with certain current oral and other systemically absorbed neuropsychiatric pharmaceuticals that act directly on neurons in the brain and are sometimes prescribed off-label for the acute treatment of SAD.
Because of the development timeline for this drug product candidate, it is unlikely that patent term extensions will be available in the U.S. or foreign countries. However, regulatory and data exclusivity (discussed below) should be available upon product approval in the U.S. and certain foreign countries.
Because of the development timeline for this indication, it is unlikely that patent term extensions will be available in the U.S. or foreign countries. However, w e expect regulatory and data exclusivity will be available upon product approval of PH80 in the U.S. and certain foreign countries.
We are aware of companies that are or may be developing therapies targeting acute treatment in the SAD market, including, among others, Bionomics, Vanda Pharmaceuticals, and Receptor Life Sciences, Ananda Scientific, EmpowerPharm and PureTech.
We are aware of companies that are or may be developing therapies targeting acute treatment in the SAD market, including, among others, Neuphoria, Vanda Pharmaceuticals, and PureTech.
PH15 for Cognitive and Psychomotor Improvement due to Mental Fatigue PH15 is an odorless, tasteless synthetic investigational neuroactive pherine with a novel, rapid-onset proposed MOA that is fundamentally differentiated from the MOA of all currently approved treatments to improve psychomotor or cognitive impairment caused by mental fatigue.
PH15 for Improvement of Cognitive and Psychomotor Impairment due to Mental Fatigue PH15 is our investigational pherine product candidate with a novel, rapid-onset neurocircuitry-focused proposed MOA that is differentiated from the MOA of all currently approved treatments to improve psychomotor or cognitive impairment caused by mental fatigue.
Responders were identified as those who self-rated ‘very much less anxious’ or ‘much less anxious’ and 40.6% of fasedienol-treated patients were rated as responders, as compared to 18.6% of those treated with placebo (p=0.003).
Responders were identified as those who self-rated "very much less anxious" or "much less anxious" on the PGI-C and 40.6% of fasedienol-treated patients were rated as responders, as compared to 18.6% of those treated with placebo (p=0.003).
Treatments may also include currently marketed proprietary branded medications indicated for MDD such as: Trintellix, which is marketed by Takeda Pharmaceuticals America, Inc and H. Lundbeck A/S; Viibryd and Vraylar, which are marketed by Abbvie; and Rexulti which is marketed by Otsuka America.
Treatments may also include currently marketed proprietary branded medications indicated for MDD such as: Trintellix, which is marketed by Takeda Pharmaceuticals America, Inc and H. Lundbeck A/S; Viibryd and Vraylar, which are marketed by Abbvie, Auvelity, which is marketed by Axsome Therapeutics, and Caplyta, which is marketed by Intra-Cellular Therapies, recently acquired by Johnson & Johnson.
Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened. 17 Table of Contents Orphan Drug Designation Under the Orphan Drug Act, the FDA may grant orphan designation to a drug intended to treat a rare disease or condition, which is a disease or condition that affects fewer than 200,000 individuals in the U.S. or, if it affects more than 200,000 individuals in the U.S., there is no reasonable expectation that the cost of developing and making a drug product available in the U.S. for this type of disease or condition will be recovered from sales of the product.
Orphan Drug Designation Under the Orphan Drug Act, the FDA may grant orphan designation to a drug intended to treat a rare disease or condition, which is a disease or condition that affects fewer than 200,000 individuals in the U.S. or, if it affects more than 200,000 individuals in the U.S., there is no reasonable expectation that the cost of developing and making a drug product available in the U.S. for this type of disease or condition will be recovered from sales of the product.
Symptoms of MDD also may include diminished pleasure in activities, changes in appetite that result in weight changes, insomnia or oversleeping, psychomotor agitation, loss of energy or increased fatigue, feelings of worthlessness or inappropriate guilt, difficulty thinking, concentrating or making decisions, and thoughts of death or suicide and attempts at suicide.
Symptoms of MDD can include a lack of pleasure in activities, changes in appetite resulting in weight fluctuations, insomnia or excessive sleeping, psychomotor agitation, loss of energy or increased fatigue, feelings of worthlessness or inappropriate guilt, difficulty thinking, concentrating or making decisions, and thoughts of death or suicide and attempts at suicide.
In some cases, the term of a U.S. patent may be shortened by a terminal disclaimer that reduces its term to align with that of a related patent. 9 Table of Contents Depending upon the timing, duration, and specifics of the FDA approval, if any, of our drug candidates, some of our U.S. patents may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the Hatch-Waxman Amendments.
Depending upon the timing, duration, and specifics of the FDA approval, if any, of our drug candidates, some of our U.S. patents may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the Hatch-Waxman Amendments.
We have never had a work stoppage, and none of our employees is represented by a labor organization or under any collective bargaining agreement. We consider our employee relations to be good.
We have never had a work stoppage, and none of our employees is represented by a labor organization or under any collective bargaining agreement. We consider our employee relations to be good. 25 Table of Contents Available Information We file reports and other information with the U.S.
Patents that may be granted on such patent applications nominally will expire in 2044, subject to patent term extensions that may be available in the U.S. and certain foreign countries.
Patents that may be granted on such patent applications nominally will expire in 2044, subject to patent term extensions that may be available in the U.S. and certain foreign countries. Regulatory and data exclusivity may be available upon product approval of PH15 for this indication in the U.S. and certain foreign countries.
Government Regulation and Product Approval Government authorities in the U.S., at the federal, state, and local level, and in other countries and supranational regions, extensively regulate, among other things, the research, development, testing, manufacture, quality, packaging, storage, recordkeeping, labeling, advertising, promotion, distribution, marketing, import, and export of pharmaceutical products such as those we are developing.
Other Indications We are still assessing our potential competition for PH15 to improve cognitive and/or psychomotor impairment and PH284 for cancer cachexia. 13 Table of Contents Government Regulation and Product Approval Government authorities in the U.S., at the federal, state, and local level, and in other countries and supranational regions, extensively regulate, among other things, the research, development, testing, manufacture, quality, packaging, storage, recordkeeping, labeling, advertising, promotion, distribution, marketing, import, and export of pharmaceutical products such as those we are developing.
In addition, both PALISADE-3 and PALISADE-4 will have an open-label extension for a period of up to 12 months. We are also planning to initiate the Repeat Dose Study in the second half of 2024.
In addition, both PALISADE-3 and PALISADE-4 have an open-label extension for a period of up to 12 months. We initiated the Repeat Dose Study in early 2025.
The Federal Civil False Claims Act (FCA) prohibits, among other things, any person or entity from knowingly presenting, or causing to be presented, a false or fraudulent claim for payment to, or approval by, the federal government, knowingly making, using, or causing to be made or used a false record or statement material to a false or fraudulent claim to the federal government, or avoiding, decreasing, or concealing an obligation to pay money to the federal government.
In addition, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. 20 Table of Contents The Federal Civil False Claims Act (FCA) prohibits, among other things, any person or entity from knowingly presenting, or causing to be presented, a false or fraudulent claim for payment to, or approval by, the federal government, knowingly making, using, or causing to be made or used a false record or statement material to a false or fraudulent claim to the federal government, or avoiding, decreasing, or concealing an obligation to pay money to the federal government.
The Repeat Dose Study will also have an open-label extension for a period of up to 12 months. We believe either PALISADE-3 or PALISADE-4, if successful, together with PALISADE-2, may establish substantial evidence of the effectiveness of fasedienol in support of a potential fasedienol New Drug Application (NDA) submission to the FDA for the acute treatment of SAD.
We believe either PALISADE-3 or PALISADE-4, if successful, together with PALISADE-2, may establish substantial evidence of the effectiveness of fasedienol in support of a potential New Drug Application (NDA) submission to the FDA for the acute treatment of anxiety in adults with SAD.
The randomized, double-blind, placebo-controlled exploratory Phase 2A clinical study of PH80 was designed to explore the efficacy, safety, and tolerability of intranasal administration of PH80 for the management of menopausal hot flashes in women.
A randomized, double-blind, placebo-controlled exploratory Phase 2A clinical study of PH80 that was designed to explore the efficacy, safety, and tolerability of intranasal administration of PH80 for the management of menopausal hot flashes in women was conducted in a real-world setting in Mexico and was sponsored by Pherin prior to our acquisition of Pherin in February 2023.
As of June 10, 2024, we employed 39 full-time employees and one part-time employees. 25 full-time employees work in research and development and laboratory support services and 14 full-time employees work in management, corporate development and communications, legal, human resources, general and administrative roles.
As of May 31, 2025, we employed 56 full-time employees and one part-time employee. 40 full-time employees work in research and development and laboratory support services, and 16 full-time employees work in management, corporate development and communications, legal, human resources, general and administrative roles.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Securing regulatory approval requires the submission of extensive preclinical and clinical data and supporting information to the various regulatory authorities for each therapeutic indication to establish the product candidate’s safety and efficacy. Securing regulatory approval also requires the submission of information about the product manufacturing process to, and inspection of manufacturing facilities by, the relevant regulatory authority.
Securing regulatory approval requires the submission of extensive preclinical and clinical data and supporting information to the various regulatory authorities for each therapeutic indication to establish the product candidate’s safety and efficacy. Securing regulatory approval also requires the submission of extensive information about the product manufacturing process to, and inspection of manufacturing facilities by, the relevant regulatory authority.
Competitive products may reduce or eliminate the commercial opportunity for our product candidates, if approved. If our competitors develop technologies or product candidates more rapidly than we do, or their technologies or product candidates are more effective or safer than ours, our ability to develop and successfully commercialize our product candidates may be adversely affected.
Competitive products may reduce or eliminate the commercial opportunity for our product candidates, if approved. If our competitors develop technologies or product candidates more rapidly than we do, or their technologies or product candidates are more effective and/or safer than ours, our ability to develop and successfully commercialize our product candidates may be adversely affected.
This process is difficult and time consuming and we may face competition for access to manufacturing facilities as there are a limited number of contract manufacturers operating under cGMPs that are capable of manufacturing our product candidates. Consequently, we may not be able to reach agreement with third-party manufacturers on satisfactory terms, which could delay our commercialization.
This process is difficult and time consuming and we may face competition for access to manufacturing facilities as there are a limited number of contract manufacturers operating under cGMPs that are capable of manufacturing our product candidates. Consequently, we may not be able to reach agreement with third-party contract manufacturers on satisfactory terms, which could delay our commercialization.
In addition, if any such claim is successfully asserted against us and we are unable to obtain such a license, we may be forced to stop or delay developing, manufacturing, selling or otherwise commercializing one or more our product candidates. Patent litigation and other types of intellectual property litigation is costly and time-consuming.
In addition, if any such claim is successfully asserted against us and we are unable to obtain such a license, we may be forced to stop or delay developing, manufacturing, selling or otherwise commercializing one or more of our product candidates. Patent litigation and other types of intellectual property litigation is costly and time-consuming.
Our business could be harmed if the prevailing party does not offer us or our licensors or collaborators a license on commercially reasonable terms or at all. Even if we or our licensors or collaborators obtain a license, it may be non-exclusive, thereby giving our competitors access to the same technologies licensed to us or our licensors or collaborators.
Our business could be harmed if the prevailing party does not offer us or our licensors or collaborators a license on commercially reasonable terms or at all. Even if we or our licensors or collaborators obtain a license, it may be non-exclusive, thereby giving our competitors access to the same technologies licensed to us or our licensors or collaborators.
In addition, we could be found liable for monetary damages, including treble damages and attorneys’ fees, if we are found to have willfully infringed a patent. A finding of infringement could prevent us from commercializing our product candidates or force us to cease some of our business operations, which could materially harm our business.
In addition, we could be found liable for monetary damages, including treble damages and attorneys’ fees, if we are found to have willfully infringed a patent. A finding of infringement could prevent us from commercializing our product candidates or force us to cease some of our business operations, which could materially harm our business.
Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation. There could also be public announcements of the results of hearings, motions, or other interim proceedings or developments.
Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation. There could also be public announcements of the results of hearings, motions, or other interim proceedings or developments.
The manufacturing preference requirement can be waived if the owner of the intellectual property can show that reasonable but unsuccessful efforts have been made to grant licenses on similar terms to potential licensees that would be likely to manufacture substantially in the U.S. or that under the circumstances domestic manufacture is not commercially feasible.
The manufacturing preference requirement can be waived if the owner of the intellectual property can show that reasonable but unsuccessful efforts have been made to grant licenses on similar terms to potential licensees that would be likely to manufacture substantially in the U.S. or that under the circumstances domestic manufacture is not commercially feasible.
There may be future issuances of shares of preferred stock in the future. Our Restated Articles of Incorporation, as amended (the Articles ), permit us to issue up to 10.0 million shares of preferred stock.
There may be issuances of shares of preferred stock in the future . Our Restated Articles of Incorporation, as amended (the Articles), permit us to issue up to 10.0 million shares of preferred stock.
The price of our common stock may fluctuate due to a variety of factors, including: • changes in the industries in which we and our customers operate; • variations in our operating performance and the performance of our competitors in general; • material and adverse impact of the COVID-19 pandemic and post-COVID environment on the markets and the broader global economy; • actual or anticipated fluctuations in our quarterly or annual operating results; • publication of research reports by securities analysts about us, our competitors or our industry; • the public’s reaction to our press releases, other public announcements and filings with the SEC; • our failure or the failure of our competitors to meet analysts’ projections or guidance that we or our competitors may give to the market; • additions and departures of key personnel; • changes in laws and regulations affecting our business; • commencement of, or involvement in, litigation involving us; • changes in our capital structure, such as future issuances of securities or the incurrence of additional debt; • the volume of shares of our common stock available for public sale; and 78 Table of Contents • general economic and political conditions such as recessions, rising interest rates, inflation, fuel prices, foreign currency fluctuations, international tariffs, boycotts, curtailment of trade and other business restrictions, social, political and economic risks, natural disasters and acts of war or terrorism, such as the conflicts involving Ukraine and Russia, or Israel and its surrounding regions.
The price of our common stock may fluctuate due to a variety of factors, including: • changes in the industries in which we and our customers operate; • variations in our operating performance and the performance of our competitors in general; • material and adverse impact of the COVID-19 pandemic and post-COVID environment on the markets and the broader global economy; • actual or anticipated fluctuations in our quarterly or annual operating results; • publication of research reports by securities analysts about us, our competitors or our industry; • the public’s reaction to our press releases, other public announcements and filings with the SEC; • our failure or the failure of our competitors to meet analysts’ projections or guidance that we or our competitors may give to the market; • additions and departures of key personnel; • changes in laws and regulations affecting our business; • commencement of, or involvement in, litigation involving us; • changes in our capital structure, such as future issuances of securities or the incurrence of additional debt; 78 Table of Contents • the volume of shares of our common stock available for public sale; and • general economic and political conditions such as recessions, rising or unchanged interest rates, inflation, fuel prices, foreign currency fluctuations, international tariffs, boycotts, curtailment of trade and other business restrictions, social, political and economic risks, natural disasters and acts of war or terrorism, such as the conflicts involving Ukraine and Russia, or Israel and its surrounding regions.
If Nasdaq delists our shares of common stock from trading on its exchange for failure to meet Nasdaq’s listing standards, we and our stockholders could face significant material adverse consequences including: • a limited availability of market quotations for our securities; • reduced liquidity for our securities; • a determination that our common stock is a “penny stock” which will require brokers trading in our common stock to adhere to more stringent rules and possibly result in a reduced level of trading activity in the secondary trading market for our securities; • a limited amount of news and analyst coverage; and • a decreased ability to issue additional securities or obtain additional financing in the future.
If, in the future, Nasdaq delists our shares of common stock from trading on its exchange for failure to meet Nasdaq’s continued listing standards, we and our stockholders could face significant material adverse consequences including: • a limited availability of market quotations for our securities; • reduced liquidity for our securities; • a determination that our common stock is a “penny stock” which will require brokers trading in our common stock to adhere to more stringent rules and possibly result in a reduced level of trading activity in the secondary trading market for our securities; • a limited amount of news and analyst coverage; and • a decreased ability to issue additional securities or obtain additional financing in the future.
In addition, royalty-based financing or debt financing, if available, may result in our relinquishing rights to valuable future revenue streams or fixed payment obligations and may involve agreements that include restrictive covenants that limit our ability to take specific actions, such as incurring additional debt, making capital expenditures, creating liens, redeeming stock or declaring dividends, that could adversely impact our ability to conduct our business.
In addition, royalty-based financing or debt financing, if available, may result in our relinquishing significant rights to valuable future revenue streams or fixed payment obligations and may involve agreements that include restrictive covenants that limit our ability to take specific actions, such as incurring additional debt, making capital expenditures, creating liens, redeeming stock or declaring dividends, that could adversely impact our ability to conduct our business.
Overall, the degree of future protection for our proprietary rights is uncertain, and we cannot ensure that: • any granted patents related to our product candidates or any pending patent applications, if granted and challenged by others, will include or maintain claims having a scope sufficient to protect these product candidates or any other products or product candidates against generic or other competition, particularly considering that any patent rights to these compounds per se have expired; • any of our pending patent applications will issue as patents at all; • we will be able to successfully commercialize our product candidates, if approved, before our relevant patents expire; • we were the first to make the inventions covered by each of our patents and pending patent applications; • we were the first to file patent applications for these inventions; • others will not develop similar or alternative technologies that do not infringe our patents; • others will not use pre-existing technology to effectively compete against us; • any of our patents, if issued, will ultimately be found to be valid and enforceable, including on the basis of prior art relating to our patent applications and patents; • any of our U.S. patents, if issued, will be eligible for listing in the FDA’s “Approved Drug Products with Therapeutics Equivalents Evaluations” (commonly known as the Orange Book); • patents that are listed in the Orange Book may be challenged by the Federal Trade Commission or other as being listed inappropriately and subsequently removed, thereby depriving the Company of significant patent enforcement protections; • any patents currently held or issued to us in the future will provide a basis for an exclusive market for our commercially viable products, will provide us with any competitive advantages or will not be challenged by third parties; • we will develop additional proprietary technologies or product candidates that are separately patentable; or • our commercial activities or products will not infringe the patents or proprietary rights of others.
Overall, the degree of future protection for our proprietary rights is uncertain, and we cannot ensure that: • any granted patents related to our product candidates or any pending patent applications, if granted and challenged by others, will include or maintain claims having a scope sufficient to protect these product candidates or any other products or product candidates against generic or other competition, particularly considering that any patent rights to these compounds per se have expired; • any of our pending patent applications will issue as patents at all; • we will be able to successfully commercialize our product candidates, if approved, before our relevant patents expire; • we were the first to make the inventions covered by each of our patents and pending patent applications; • we were the first to file patent applications for these inventions; • others will not develop similar or alternative technologies that do not infringe our patents; • others will not use pre-existing technology to effectively compete against us; • any of our patents, if issued, will ultimately be found to be valid and enforceable, including on the basis of prior art relating to our patent applications and patents; • any of our U.S. patents, if issued, will be eligible for listing in the FDA’s “Approved Drug Products with Therapeutics Equivalents Evaluations” (commonly known as the Orange Book); 67 Table of Contents • patents that are listed in the Orange Book may be challenged by the Federal Trade Commission or other as being listed inappropriately and subsequently removed, thereby depriving the Company of significant patent enforcement protections; • any patents currently held or issued to us in the future will provide a basis for an exclusive market for our commercially viable products, will provide us with any competitive advantages or will not be challenged by third parties; • we will develop additional proprietary technologies or product candidates that are separately patentable; or • our commercial activities or products will not infringe the patents or proprietary rights of others.
Given the unpredictable regulatory environment in China and the U.S. and uncertainty regarding how the U.S. or foreign governments will act with respect to tariffs, international trade agreements and policies, further governmental action related to tariffs, additional taxes, regulatory changes or other retaliatory trade measures in the future could occur with a corresponding detrimental impact on our business and financial condition.
Given the unpredictable regulatory environment in the U.S. and uncertainty regarding how the U.S. or foreign governments will act with respect to tariffs, international trade agreements and policies, further governmental action related to tariffs, additional taxes, regulatory changes or other retaliatory trade measures in the future could occur with a corresponding detrimental impact on our business and financial condition.
Our failure, or the failure of our third-party manufacturers, to comply with applicable regulations could result in sanctions being imposed on us, including clinical holds, fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, seizures or voluntary recalls of product candidates, operating restrictions and criminal prosecutions, any of which could significantly affect supplies of our product candidates.
Our failure, or the failure of our third-party contract manufacturers, to comply with applicable regulations could result in sanctions being imposed on us, including clinical holds, fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, seizures or voluntary recalls of product candidates, operating restrictions and criminal prosecutions, any of which could significantly affect supplies of our product candidates.
An NDA submitted for a Fast Track product candidate may also be eligible for rolling review, where the FDA may consider for review sections of the NDA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the NDA, the FDA agrees to accept sections of the NDA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the application.
A NDA submitted for a Fast Track product candidate may also be eligible for rolling review, where the FDA may consider for review sections of the NDA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the NDA, the FDA agrees to accept sections of the NDA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the application.
In order to produce sufficient quantities to meet the demand for clinical trials and, if approved, subsequent commercialization of our product candidates, our third-party manufacturers will be required to increase their production and optimize their manufacturing processes while maintaining the quality of our product candidates. The transition to larger scale production could prove difficult.
In order to produce sufficient quantities to meet the demand for clinical trials and, if approved, subsequent commercialization of our product candidates, our third-party contract manufacturers will be required to increase their production and optimize their manufacturing processes while maintaining the quality of our product candidates. The transition to larger scale production could prove difficult.
In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development. To date, we have not submitted an NDA to the FDA or similar drug approval submissions to comparable foreign regulatory authorities for any product candidate.
In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development. To date, we have not submitted a NDA to the FDA or similar drug approval submissions to comparable foreign regulatory authorities for any product candidate.
Fast Track designation applies to the combination of the product candidate and the specific indication for which it is being studied. The sponsor of a Fast Track product candidate has opportunities for more frequent interactions with the applicable FDA review team during product development and, once an NDA is submitted, the application may be eligible for priority review.
Fast Track designation applies to the combination of the product candidate and the specific indication for which it is being studied. The sponsor of a Fast Track product candidate has opportunities for more frequent interactions with the applicable FDA review team during product development and, once a NDA is submitted, the application may be eligible for priority review.
Unless otherwise indicated, reference in this section and elsewhere in this Annual Report to our business being adversely affected, negatively impacted or harmed will include an adverse effect on, or a negative impact or harm to, the business, reputation, financial condition, results of operations, revenue and our future prospects.
Unless otherwise indicated, reference in this section and elsewhere in this Report to our business being adversely affected, negatively impacted or harmed will include an adverse effect on, or a negative impact or harm to, the business, reputation, financial condition, results of operations, revenue and our future prospects.
The delays associated with the verification of a new third-party manufacturer could negatively affect our ability to develop product candidates or commercialize our products in a timely manner or within budget. Furthermore, a third-party manufacturer may possess technology related to the manufacture of our product candidate that such third party owns independently.
The delays associated with the verification of a new third-party manufacturer could negatively affect our ability to develop product candidates or commercialize our products in a timely manner or within budget. Furthermore, a third-party contract manufacturer may possess technology related to the manufacture of our product candidate that such third party owns independently.
Third-party manufacturers may not be able to comply with cGMP requirements applicable to drug/device combination products, including applicable provisions of the FDA’s or a comparable foreign regulatory authority’s drug cGMP regulations, device cGMP requirements embodied in the Quality System Regulation ( QSR ) or similar regulatory requirements outside the U.S.
Third-party contract manufacturers may not be able to comply with cGMP requirements applicable to drug/device combination products, including applicable provisions of the FDA’s or a comparable foreign regulatory authority’s drug cGMP regulations, device cGMP requirements embodied in the Quality System Regulation (QSR) or similar regulatory requirements outside the U.S.
The material and other risks and uncertainties summarized elsewhere in this Annual Report and described below are not intended to be exhaustive and are not the only ones we face. Additional risks and uncertainties not presently known to us, or that we currently deem immaterial, may also impair our business operations.
The material and other risks and uncertainties summarized elsewhere in this Report and described below are not intended to be exhaustive and are not the only ones we face. Additional risks and uncertainties not presently known to us, or that we currently deem immaterial, may also impair our business operations.
To the extent that we raise additional capital through the sale of common stock, convertible securities or other equity securities, the ownership interest of our stockholders may be diluted, and the terms of these securities could include liquidation or other preferences and anti-dilution protections that could adversely affect the rights of our common stockholders.
To the extent that we raise additional capital through the sale of common stock, convertible securities or other equity securities, the ownership interest of our stockholders may be substantially diluted, and the terms of these securities could include liquidation or other preferences and anti-dilution protections that could adversely affect the rights of our common stockholders.
From time to time, we may publicly announce the expected timing of some of these milestones, such as the completion of an ongoing clinical trial, the initiation of other clinical programs, receipt of marketing approval or a commercial launch of a product. The achievement of many of these milestones may be outside of our control.
From time to time, we may publicly announce the expected timing of some of these milestones, such as the completion of an ongoing clinical trial of a product candidate, the initiation of other clinical programs, receipt of marketing approval or a commercial launch of a product. The achievement of many of these milestones may be outside of our control.
We, along with our collaborators, CROs, third-party logistics providers, distributors and other contractors and consultants, utilize information technology (IT) systems and networks to process, transmit and store electronic information, including confidential information such as proprietary business information and personal information of our employees and contractors, in connection with our business activities.
We, along with our collaborators, CDMOs, CROs, third-party logistics providers, distributors and other contractors and consultants, utilize information technology (IT) systems and networks to process, transmit and store electronic information, including confidential information such as proprietary business information and personal information of our employees and contractors, in connection with our business activities.
Even if such product candidates are successfully developed and approved, the markets for our products may be smaller than we expect and our revenue potential and ability to achieve profitability may be materially adversely affected. Our pipeline includes product candidates for a variety of neuroscience disorders.
Even if such product candidates are successfully developed and approved, the markets for our products may be smaller than we expect and our revenue potential and ability to achieve profitability may be materially adversely affected. Our neuroscience pipeline includes product candidates for a variety of conditions and disorders.
The ability of the FDA and comparable foreign regulatory authorities to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory, and policy changes.
The ability of the FDA and comparable foreign regulatory authorities to review and approve new products can be affected by a variety of factors, including staffing levels, government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory, and policy changes.
In addition, any further deterioration in the macroeconomic economy or financial services industry could lead to losses or defaults by our partners, vendors or suppliers, which in turn, could have a material adverse effect on our current and/or projected business operations and results of operations and financial condition.
In addition, any deterioration in the macroeconomic economy or financial services industry could lead to losses or defaults by our partners, vendors or suppliers, which in turn, could have a material adverse effect on our current and/or projected business operations and results of operations and financial condition.
In each case, there is a range of estimates in the published literature and in marketing studies, which include estimates within the range that are lower than our estimates. The actual number of patients with these disease indications may, however, be significantly lower than we believe.
In each case, there is a range of estimates in the published literature and in marketing studies, which include estimates within the range that are lower than our estimates. The actual number of patients with these and other disease indications may, however, be significantly lower than we believe.
We intend to establish a sales and marketing organization, either on our own or in collaboration with third parties, with technical expertise and supporting distribution capabilities to commercialize one or more of our product candidates that may receive regulatory approval in key territories.
We intend to establish a sales and marketing capabilities, either on our own or in collaboration with third parties, with technical expertise and supporting distribution capabilities to commercialize one or more of our product candidates that may receive regulatory approval in key territories.
We are not permitted to market our product candidates in the U.S. until we receive approval of an NDA from the FDA, or in any foreign countries until we receive the requisite approval from such countries. Obtaining FDA approval of an NDA is a complex, lengthy, expensive and uncertain process.
We are not permitted to market our product candidates in the U.S. until we receive approval of a NDA from the FDA, or in any foreign countries until we receive the requisite approval from such countries. Obtaining FDA approval of a NDA is a complex, lengthy, expensive and uncertain process.
The following examples are illustrative: • others may be able to develop and/or practice technology that is similar to our technology or aspects of our technology but that is not covered by the claims of patents, should such patents issue from our patent applications; • we might not have been the first to make the inventions covered by a pending patent application that we own; • we might not have been the first to file patent applications covering an invention; • others may independently develop similar or alternative technologies without infringing our intellectual property rights; • pending patent applications that we own or license may not lead to issued patents • patents, if issued, that we own or license may not provide us with any competitive advantages, or may be held invalid or unenforceable or be narrowed, as a result of legal challenges by our competitors; • third parties may compete with us in jurisdictions where we do not pursue and obtain patent protection; • we may not be able to obtain and/or maintain necessary or useful licenses on reasonable terms or at all; and • the patents of others may have an adverse effect on our business.
The following examples are illustrative: • others may be able to develop and/or practice technology that is similar to our technology or aspects of our technology but that is not covered by the claims of patents, should such patents issue from our patent applications; • we might not have been the first to make the inventions covered by a pending patent application that we own; • we might not have been the first to file patent applications covering an invention; • others may independently develop similar or alternative technologies without infringing our intellectual property rights; 72 Table of Contents • pending patent applications that we own or license may not lead to issued patents • patents, if issued, that we own or license may not provide us with any competitive advantages, or may be held invalid or unenforceable or be narrowed, as a result of legal challenges by our competitors; • third parties may compete with us in jurisdictions where we do not pursue and obtain patent protection; • we may not be able to obtain and/or maintain necessary or useful licenses on reasonable terms or at all; and • the patents of others may have an adverse effect on our business.
This Annual Report also contains forward-looking statements that involve risks and uncertainties. Our actual results could differ materially from those anticipated in the forward-looking statements as a result of a number of factors, including the risks described below.
This Report also contains forward-looking statements that involve risks and uncertainties. Our actual results could differ materially from those anticipated in the forward-looking statements as a result of a number of factors, including the risks described below.
In addition, if we are required to change third-party manufacturers for any reason, we will be required to verify that the new manufacturer maintains facilities and procedures that comply with quality standards and with all applicable regulations.
In addition, if we are required to change third-party manufacturers for any reason, we will be required to verify that the new third-party contract manufacturer maintains facilities and procedures that comply with quality standards and with all applicable regulations.
The degree of market acceptance of our product candidates, if approved for commercial sale, will depend on a number of factors, including: • the efficacy and safety of the product; • the potential advantages of the product compared to competitive therapies; • the prevalence and severity of any side effects; • whether the product is designated under physician treatment guidelines as a first-, second- or third-line therapy; • our ability, or the ability of any future collaborators, to offer the product for sale at competitive prices; • the product’s convenience and ease of administration compared to alternative treatments; • the willingness of the target patient population to try, and of physicians to prescribe, the product; • limitations or warnings, including distribution or use restrictions contained in the product’s approved labeling; • the strength of sales, marketing and distribution support; • changes in the standard of care for the targeted indications for the product; and • availability and adequacy of coverage and reimbursement from government payors, managed care plans and other third-party payors.
The degree of market acceptance of our product candidates, if approved for commercial sale, will depend on a number of factors, including: • the efficacy and safety of the product; • the potential advantages of the product compared to any competitive therapies; • the prevalence and severity of any side effects; • whether the product is designated under physician treatment guidelines as a first-, second- or third-line therapy; • our ability, or the ability of any future collaborators, to offer the product for sale at competitive prices; 42 Table of Contents • the product’s convenience and ease of administration compared to alternative treatments; • the willingness of the target patient population to try, and of physicians to prescribe, the product; • limitations or warnings, including distribution or use restrictions contained in the product’s approved labeling; • the strength of sales, marketing and distribution support; • changes in the standard of care for the targeted indications for the product; and • availability and adequacy of coverage and reimbursement from government payors, managed care plans and other third-party payors.
This could delay or prevent completion of clinical trials, require conducting bridging clinical trials or the repetition of one or more clinical trials, increase clinical trial costs, delay or prevent approval of our product candidates and jeopardize our ability to commence sales and generate revenue.
This could delay or prevent completion of clinical development, require conducting bridging clinical trials or the repetition of one or more clinical trials, increase clinical trial costs, delay or prevent approval of our product candidates and jeopardize our ability to commence sales and generate revenue.
Cyberattacks or other failures in our telecommunications or information technology systems, or those of our collaborators, CROs, third-party logistics providers, distributors or other contractors or consultants, could result in information theft, data corruption and significant disruption of our business operations.
Cyberattacks or other failures in our telecommunications or information technology systems, or those of our collaborators, CDMOs, CROs, third-party logistics providers, distributors or other contractors or consultants, could result in information theft, data corruption and significant disruption of our business operations.
General Risk Factors Adverse market or macroeconomic conditions or market volatility resulting from global economic developments, including those affecting the financial services industry, could adversely affect our business operations and our financial condition and results of operations.
General Risk Factors Adverse market or macroeconomic conditions or market volatility resulting from global economic and political developments, including those affecting the financial services industry, could adversely affect our business operations and our financial condition and results of operations.
These other potential product candidates will require additional, time-consuming development efforts prior to commercial sale, including preclinical studies, clinical trials and approval by the FDA and applicable foreign regulatory authorities.
These other potential product candidates will require additional, time-consuming development efforts prior to commercial sale, including manufacturing, preclinical studies, clinical trials and approval by the FDA and applicable foreign regulatory authorities.
Some of the intellectual property rights we have licensed or will license in the future may have been generated through the use of U.S. government funding and may therefore be subject to certain federal regulations.
Some of the intellectual property rights we have licensed or may license in the future may have been generated through the use of U.S. government funding and may therefore be subject to certain federal regulations.
The replacement of an existing CRO or other third party may result in the delay of the affected trials or otherwise adversely affect our efforts to obtain regulatory approvals and commercialize our product candidates.
The replacement of an existing CRO, manufacturer or other third party may result in the delay of the affected trials or otherwise adversely affect our efforts to obtain regulatory approvals and commercialize our product candidates.
As a result of any arrangement involving government funding, and if we make inventions as a result of such funding, intellectual property rights to such discoveries may be subject to the applicable provisions of the Bayh-Dole Act.
As a result of any future arrangement involving government funding, and if we make inventions as a result of such funding, intellectual property rights to such discoveries may be subject to the applicable provisions of the Bayh-Dole Act.
We expect to expand our organization, and as a result, we may encounter difficulties in managing our growth, which could disrupt our operations. We expect to experience significant growth in the number of our employees and the scope of our operations.
We expect to expand our organization, and as a result, we may encounter difficulties in managing our growth, which could disrupt our operations. We expect to continue to experience significant growth in the number of our employees and the scope of our operations.
If any third-party manufacturer of our product candidates is unable to increase the scale of its production of our product candidates or increase the product yield of its manufacturing, then our manufacturing costs may increase and commercialization may be delayed.
If any third-party contract manufacturer of our product candidates is unable to increase the scale of its production of our product candidates or increase the product yield of its manufacturing, then our manufacturing costs may increase and commercialization may be delayed.
Issuing additional shares of our common stock or other equity securities or securities convertible into equity may dilute the economic and voting rights of our existing stockholders or reduce the market price of our common stock or both.
Issuing additional shares of our common stock or other equity securities or securities convertible into equity will dilute the economic and voting rights of our existing stockholders and may reduce the market price of our common stock or both.
If we develop and commercialize our product candidates in foreign markets, we would be subject to additional risks and uncertainties, including: • our customers’ ability to obtain reimbursement for our product candidates in foreign markets; • our inability to directly control commercial activities because we are relying on third parties; • the burden of complying with complex and changing foreign regulatory, tax, accounting and legal requirements; • different medical practices and customs in foreign countries affecting acceptance in the marketplace; • import or export licensing requirements; • longer accounts receivable collection times; • longer lead times for shipping; • language barriers for technical training; • reduced protection of intellectual property rights, different standards of patentability and different availability of prior art in some foreign countries as compared with the U.S.; • the existence of additional potentially relevant third-party intellectual property rights; • foreign currency exchange rate fluctuations; and • the interpretation of contractual provisions governed by foreign laws in the event of a contract dispute.
If we develop and commercialize our product candidates in markets outside of the U.S., we would be subject to additional risks and uncertainties, including: • our customers’ ability to obtain reimbursement for our product candidates; • our inability to directly control commercial activities because we are relying on third parties; • the burden of complying with complex and changing foreign regulatory, tax, accounting and legal requirements; • different medical practices and customs in foreign countries affecting acceptance in the marketplace; • import or export licensing requirements; 48 Table of Contents • longer accounts receivable collection times; • longer lead times for shipping; • language barriers for technical training; • reduced protection of intellectual property rights, different standards of patentability and different availability of prior art in some foreign countries as compared with the U.S.; • the existence of additional potentially relevant third-party intellectual property rights; • foreign currency exchange rate fluctuations; and • the interpretation of contractual provisions governed by foreign laws in the event of a contract dispute.
As use of digital technologies has increased, our IT systems and those of our third-party service providers, strategic partners and other contractors or consultants are increasingly vulnerable to attack, damage and interruption from cyber incidents, including third parties gaining access to employee accounts using stolen or inferred credentials, computer malware (e.g., ransomware), viruses, malicious code, spamming, phishing attacks 46 Table of Contents and other social engineering schemes, employee theft or misuse, human error, fraud, denial or degradation of service attacks, sophisticated nation-state and nation-state-supported actors, natural disasters, terrorism, war, telecommunication and electrical failures or other threats.
As use of digital technologies has increased, our IT systems and those of our third-party service providers, strategic partners and other contractors or consultants are increasingly vulnerable to attack, damage and interruption from cyber incidents, including third parties gaining access to employee accounts using stolen or inferred credentials, computer malware (e.g., ransomware), viruses, malicious code, spamming, phishing attacks and other social engineering schemes, employee theft or misuse, human error, fraud, denial or degradation of service attacks, sophisticated nation-state and nation-state-supported actors, natural disasters, terrorism, war, telecommunication and electrical failures or other threats.
If a natural disaster, power outage or other event occurred that prevented us from using all or a significant portion of our headquarters, that damaged critical infrastructure, such as the manufacturing facilities of our third-party CMOs, or that otherwise disrupted operations, it may be difficult or, in certain cases, impossible for us to continue our business for a substantial period of time.
If a natural disaster, power outage or other event occurred that prevented us from using all or a significant portion of our headquarters, that damaged critical infrastructure, such as the manufacturing facilities of our third-party CDMOs, or that otherwise disrupted operations, it may be difficult or, in certain cases, impossible for us to continue our business for a substantial period of time.
We are subject to the reporting requirements of the Exchange Act which requires that we file annual, quarterly and current reports with respect to our business and financial condition, and the rules and regulations implemented by the SEC, the Sarbanes-Oxley Act of 2022, as amended (the Sarbanes-Oxley Act) , the Dodd-Frank Act, and the Public Company Accounting Oversight Board, each of which imposes additional reporting and other obligations on public companies.
We are subject to the reporting requirements of the Exchange Act which requires that we file annual, quarterly and current reports with respect to our business and financial condition, and the rules and regulations implemented by the SEC, the Sarbanes-Oxley Act of 2002, as amended (the Sarbanes-Oxley Act), the Dodd-Frank Act, and the Public Company Accounting Oversight Board, each of which imposes additional reporting and other obligations on public companies.
Inadequate funding for the FDA or other government agencies could hinder their ability to hire and retain key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business.
Reduction in staffing and/or inadequate funding for the FDA or other government agencies could hinder their ability to hire and retain key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business.
If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business and results of operations, including the imposition of civil, criminal and administrative penalties, damages, monetary fines, disgorgement, integrity oversight and reporting obligations, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, and curtailment of our operations, any of which could have a material adverse effect on our ability to operate our business and our results of operations.
If any such actions are instituted against 50 Table of Contents us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business and results of operations, including the imposition of civil, criminal and administrative penalties, damages, monetary fines, disgorgement, integrity oversight and reporting obligations, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, and curtailment of our operations, any of which could have a material adverse effect on our ability to operate our business and our results of operations.
Even if we are able to establish and maintain arrangements with third-party manufacturers, reliance on third-party manufacturers entails additional risks, including: • the failure of the third-party manufacturer to comply with applicable regulatory requirements and reliance on third parties for manufacturing process development, regulatory compliance and quality assurance; • manufacturing delays if our third-party manufacturers give greater priority to the supply of other products over our product candidates or otherwise do not satisfactorily perform according to the terms of the agreement between us; • limitations on supply availability resulting from capacity and scheduling constraints of third parties; • the possible breach of manufacturing agreements by third parties because of factors beyond our control; • the possible termination or non-renewal of the manufacturing agreements by the third party, at a time that is costly or inconvenient to us; and • the possible misappropriation of our proprietary information, including our trade secrets and know-how.
Even if we are able to establish and maintain arrangements with third-party contract manufacturers, reliance on third-party contract manufacturers entails additional risks, including: • the failure of the third-party manufacturer to comply with applicable regulatory requirements and reliance on third parties for manufacturing process development, regulatory compliance and quality assurance; • manufacturing delays if our third-party manufacturers give greater priority to the supply of other products over our product candidates or otherwise do not satisfactorily perform according to the terms of the agreement between us; • limitations on supply availability resulting from capacity and scheduling constraints of third parties; • the possible breach of manufacturing agreements by third parties because of factors beyond our control; 53 Table of Contents • the possible termination or non-renewal of the manufacturing agreements by the third party, at a time that is costly or inconvenient to us; and • the possible misappropriation of our proprietary information, including our trade secrets and know-how.
Our future need for additional funding depends on many factors, including: • the number and characteristics of future product candidates we pursue and their development requirements; • the scope, progress, results and costs of researching, developing and commercializing our product candidates and any other additional product candidates we may develop and pursue in the future; • the timing of, and the costs involved in, obtaining marketing approvals for our product candidates and any other additional product candidates we may develop and pursue in the future; • subject to receipt of regulatory approval, the costs of commercialization activities for our product candidates, to the extent such costs are not the responsibility of any future collaborators, including the costs and timing of establishing product sales, marketing, distribution and manufacturing capabilities; • subject to receipt of regulatory approval, revenue, if any, received from commercial sales of our product candidates or any other additional product candidates we may develop and pursue in the future; • the cost of manufacturing and formulating our product candidates; • the extent to which we establish and maintain strategic partnerships, licensing or other collaborative arrangements for the development of our product candidates, on favorable financial terms, if at all; • subject to regulatory approval, market acceptance of our product candidates; • the effect of competing technological and market developments; • our headcount growth and associated costs as we expand our research and development and market development and pre-commercial planning activities; • the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights, including enforcing and defending intellectual property related claims; and • the costs of operating as a public company.
Our future need for additional funding depends on many factors, including: • the number and characteristics of future product candidates we pursue and their development requirements; • the scope, progress, results and costs of researching, developing and commercializing our product candidates and any other additional product candidates we may develop and pursue in the future; 31 Table of Contents • the timing of, and the costs involved in, obtaining marketing approvals for our product candidates and any other additional product candidates we may develop and pursue in the future; • subject to receipt of regulatory approval, the costs of commercialization activities for our product candidates, to the extent such costs are not the responsibility of any future collaborators, including the costs and timing of establishing product sales, marketing, distribution and manufacturing capabilities; • subject to receipt of regulatory approval, revenue, if any, received from commercial sales of our product candidates or any other additional product candidates we may develop and pursue in the future; • the cost of formulating and manufacturing our product candidates; • the extent to which we establish and maintain strategic partnerships, licensing or other collaborative arrangements necessary for the development and commercialization of our product candidates, on favorable financial terms, if at all; • subject to regulatory approval, market acceptance of our product candidates; • the effect of competing technological and market developments; • our headcount growth and associated costs as we expand our research and development, market development, pre-commercial and commercial activities; • the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights, including enforcing and defending intellectual property related claims; and • the costs of operating as a public company.
As product candidates proceed through preclinical studies to late-stage clinical trials towards potential approval and commercialization, it is common that various aspects of the development program, such as the vendors used to manufacture drug product or manufacturing methods and formulation, are altered along the way in an effort to optimize processes and results.
As product candidates proceed through preclinical studies and clinical development trials towards potential approval and commercialization, it is common that various aspects of the development program, such as the vendors used to manufacture drug product or manufacturing methods and formulation, are altered along the way in an effort to optimize processes and results.
A weak or declining economy could also strain our suppliers, possibly resulting in supply disruption, or cause our customers to delay making payments for our services. Any of the foregoing could harm our business and we cannot anticipate all of the ways in which the current economic climate and financial market conditions could adversely impact our business.
A weak or declining domestic or global economy could also strain our suppliers, possibly resulting in supply disruption, or cause our customers to delay making payments for our services. Any of the foregoing could harm our business and we cannot anticipate all of the ways in which the current economic climate and financial market conditions could adversely impact our business.
Adequate and well-controlled clinical trials typically involve a large number of patients, have significant costs and take years to complete. The FDA or other regulatory authorities may disagree with us about whether a clinical trial is adequate and well-controlled or may request that we conduct additional clinical trials prior to granting any regulatory approval.
Adequate and well-controlled clinical trials typically involve a large number of patients, have significant costs and take years to complete. The FDA or other regulatory authorities may disagree with us about whether a clinical trial is adequate and well-controlled or may request that we conduct additional nonclinical studies or clinical trials prior to granting any regulatory approval.
Should we conduct future clinical trials in the U.K. or European Union, we cannot assure you that our efforts to comply with any obligations under European privacy laws will be sufficient. If we are investigated by a European data protection authority, we may face fines and other penalties.
Should we conduct future clinical trials in the U.K. or EU, we cannot assure you that our efforts to comply with any obligations under European privacy laws will be sufficient. If we are investigated by a European data protection authority, we may face fines and other penalties.
Other potentially significant negative consequences associated with adverse events include: • we may be required to suspend marketing of a product, or we may decide to remove such product from the marketplace; • regulatory authorities may withdraw or modify their approvals of our product; • we may be required to conduct post-marketing studies; 40 Table of Contents • we may be required to change the way our product is administered; • we could be subject to fines, injunctions, or the imposition of criminal or civil penalties, or be sued and held liable for harm caused to subjects or patients; • our product may become less competitive, and • our reputation may suffer.
Other potentially significant negative consequences associated with adverse events include: • we may be required to suspend marketing of a product, or we may decide to remove such product from the marketplace; • regulatory authorities may withdraw or modify their approvals of our product; • we may be required to conduct post-marketing studies; • we may be required to change the way our product is administered; • we could be subject to fines, injunctions, or the imposition of criminal or civil penalties, or be sued and held liable for harm caused to subjects or patients; • our product may become less competitive, and • our reputation may suffer.
We will need substantial additional financing to execute our long-term business plan, and if we are unable to raise capital when needed, we could be forced to delay, reduce or terminate our research and development programs or pre-commercialization efforts. Our operations have consumed substantial amounts of cash since inception.
We will need substantial additional financing to execute our business plan, and if we are unable to raise capital when needed, we could be forced to delay, reduce or terminate our research and development programs, pre-commercialization or commercialization efforts. Our operations have consumed substantial amounts of cash since inception.
We may also observe safety or tolerability issues with our product candidates in ongoing or future clinical trials. Many compounds that initially showed promise in clinical or earlier-stage testing are later found to cause undesirable or unexpected side effects that prevented further development of the compound.
We may also observe safety or tolerability issues with our product candidates in ongoing or future clinical trials. Many compounds that initially showed promise in clinical or earlier-stage testing are later found to cause undesirable or unexpected side effects that prevent further development of the compound.
If any of our product candidates are ultimately regulated as controlled substances, we, our CMOs, as well as future distributors, prescribers, and dispensers will be required to comply with additional regulatory requirements which could delay the marketing of our product candidates, and increase the cost and burden of manufacturing, distributing, dispensing, and prescribing our product candidates.
If any of our product candidates are ultimately regulated as controlled substances, we, our CDMOs, as well as future distributors, prescribers, and dispensers will be required to comply with additional regulatory requirements which could delay the marketing of our product candidates, and increase the cost and burden of manufacturing, distributing, dispensing, and prescribing our product candidates.
There is no precise method of establishing the actual number of patients with any of these disorders in any geography over any time period. With respect to many of the indications in which we have developed, are developing, or plan to develop our product candidates, we have estimates of the prevalence of the disease or disorder.
There is no precise method of establishing the actual number of patients with any of these conditions and disorders in any geography over any time period. With respect to many of the indications in which we have developed, are developing, or plan to develop our product candidates, we have estimates of the prevalence of the disease or disorder.
The GDPR imposes strict rules on the transfer of personal data out of the EEA/UK to countries not regarded by European Commission and the United Kingdom government as providing adequate protection, or the third countries, including the U.S. and the efficacy and longevity of current transfer mechanisms between the European Economic Area (the EEA) and the U.S. remains uncertain.
The GDPR imposes strict rules on the transfer of personal data out of the EEA/UK to countries not regarded by European Commission and the United Kingdom government as providing adequate protection, or the third countries, including the U.S. and the efficacy and longevity of current transfer mechanisms between the EEA and the U.S. remains uncertain.
In estimating the potential prevalence of indications we are pursuing, or may in the future pursue, including our estimates as to the prevalence of SAD, MDD and vasomotor symptoms (hot flashes) due to menopause, we apply assumptions to available information that may not prove to be accurate.
In estimating the potential prevalence of indications we are pursuing, or may in the future pursue, including, among others, our estimates as to the prevalence of SAD, MDD and vasomotor symptoms (hot flashes) due to menopause, we apply assumptions to available information that may not prove to be accurate.
For a product candidate that have been designated as a Breakthrough Therapy, interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens.
For a product candidate that has been designated as a Breakthrough Therapy, interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens.
Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; 58 Table of Contents • the federal Physician Payments Sunshine Act, which requires applicable manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program to report annually to the U.S.
Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • the federal Physician Payments Sunshine Act, which requires applicable manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program to report annually to the U.S.
The clinical development of our initial and potential additional product candidates is susceptible to the risk of failure inherent at any stage of development, including failure to demonstrate efficacy in a clinical trial or across a broad population of patients, the occurrence of adverse events that are severe or medically or commercially unacceptable, failure to comply with protocols or applicable regulatory requirements and determination by the FDA or any comparable foreign regulatory authority that a product candidate may not continue development or is not approvable.
The clinical development of our product candidates is susceptible to the risk of failure inherent at any stage of development, including failure to demonstrate efficacy in a clinical trial or across a broad population of patients, the occurrence of adverse events that are severe or medically or commercially unacceptable, failure to comply with protocols or applicable regulatory requirements and determination by the FDA or any comparable foreign regulatory authority that a product candidate may not continue development or is not approvable.
If our contract manufacturers cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA or others, we may not be able to secure and/or maintain regulatory approval for our product candidates manufactured at these facilities.
If our third-party contract manufacturers cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA or others, we may not be able to secure and/or maintain regulatory approval for our product candidates manufactured at these facilities.
Ongoing healthcare legislative and regulatory reform measures may have a material adverse effect on our business and results of operations.
Healthcare legislative and regulatory reform measures may have a material adverse effect on our business and results of operations.
These risks also apply to any additional product candidates that we may acquire or in-license in the future. If these activities were not compliant, accurate or correct, the clinical development, regulatory approval or commercialization of our product candidates will be adversely affected.
These risks also apply to any product candidates that we may acquire or in-license in the future, if any. If these activities were not compliant, accurate or correct, the clinical development, regulatory approval or commercialization of our pherine product candidates will be adversely affected.
The continuing efforts of the government, insurance companies, managed care organizations and other payers of healthcare services to contain or reduce costs of healthcare may adversely affect: • the demand for any of our product candidates, if approved; • the ability to set a price that we believe is fair for any of our product candidates, if approved; • our ability to generate revenues and achieve or maintain profitability; • the level of taxes that we are required to pay; and • the availability of capital.
The 61 Table of Contents continuing efforts of the government, insurance companies, managed care organizations and other payers of healthcare services to contain or reduce costs of healthcare may adversely affect: • the demand for any of our product candidates, if approved; • the ability to set a price that we believe is fair for any of our product candidates, if approved; • our ability to generate revenues and achieve or maintain profitability; • the level of taxes that we are required to pay; and • the availability of capital.
In addition, any testing we conduct in connection with Section 404 of the Sarbanes-Oxley Act of 2022, as amended (the Sarbanes-Oxley Act), or any subsequent testing by our independent registered public accounting firm, may reveal deficiencies in our internal controls over financial reporting that are deemed to be material weaknesses or that may require prospective or retroactive changes to our consolidated financial statements or identify other areas for further attention or improvement.
In addition, any testing we conduct in connection with Section 404 of the Sarbanes-Oxley Act, or any subsequent testing by our independent registered public accounting firm, may reveal deficiencies in our internal controls over financial reporting that are deemed to be material weaknesses or that may require prospective or retroactive changes to our consolidated financial statements or identify other areas for further attention or improvement.
This lengthy approval process, as well as the unpredictability of clinical trial results, may result in our failing to obtain regulatory approval to market any product candidate we develop, which would substantially harm our business, results of operations and prospects.
This lengthy approval process, as well as the unpredictability of nonclinical studies and clinical trial results, may result in our failing to obtain regulatory approval to market any product candidate we develop, which would substantially harm our business, results of operations and prospects.
Our quarterly and annual operating results may fluctuate significantly in the future due to a variety of factors, many of which are outside of our control and may be difficult to predict, including the following: • the timing and success or failure of clinical trials for our product candidates or competing product candidates, or any other change in the competitive landscape of our industry, • our ability to successfully recruit and retain subjects for clinical trials, and any delays caused by difficulties in such efforts; • the risk/benefit profile, cost and reimbursement policies with respect to our product candidates, if approved, and existing and potential future therapeutics that compete with our product candidates; • our ability to obtain marketing approval for our product candidates and the timing and scope of any such approvals we may receive; • the timing and cost of, and level of investment in, research and development activities relating to our product candidates, which may change from time to time; • the cost of manufacturing our product candidates, which may vary depending on the quantity of production and the terms of our agreements with manufacturers; • our ability to attract, hire and retain qualified personnel; 74 Table of Contents • expenditures that we will or may incur to develop additional product candidates; • the level of demand for our product candidates should they receive approval, which may vary significantly; • the changing and volatile U.S. and global economic environments, including the impact of inflation and rising interest rates, and domestic or international political instability; and • future accounting pronouncements or changes in our accounting policies.
Our quarterly and annual operating results may fluctuate significantly in the future due to a variety of factors, many of which are outside of our control and may be difficult to predict, including the following: • the timing and success or failure of clinical trials for our product candidates or competing product candidates, or any other change in the competitive landscape of our industry, • our ability to successfully recruit, enroll and retain subjects who meet our eligibility criteria for participation in our clinical trials, and any delays caused by difficulties in such efforts; 74 Table of Contents • the risk/benefit profile, cost and reimbursement policies with respect to our product candidates, if approved, and existing and potential future therapeutics that compete with our product candidates; • our ability to obtain marketing approval for our product candidates and the timing and scope of any such approvals we may receive; • the timing and cost of, and level of investment in, research and development and commercialization activities relating to our product candidates, which may change from time to time; • the cost of manufacturing our product candidates, which may vary depending on the quantity of production and the terms of our agreements with contract manufacturers; • our ability to attract, hire and retain qualified personnel; • expenditures that we will or may incur to develop additional product candidates; • the level of demand for our product candidates should they receive approval, which may vary significantly; • the changing and volatile U.S. and global economic and political environments, including the impact of inflation and rising interest rates, and domestic or international political instability; and • future accounting pronouncements or changes in our accounting policies.
Contract manufacturers may face manufacturing or quality control problems causing drug substance production and shipment delays or a situation where the contractor may not be able to maintain compliance with the applicable cGMP requirements.
Third-party contract manufacturers may face manufacturing or quality control problems causing drug substance production and shipment delays or a situation where the contractor may not be able to maintain compliance with the applicable cGMP requirements.
We cannot assure you that our clinical trials will begin as planned or be completed on schedule, if at all, or that we will not need to restructure or otherwise modify our trials after they have begun.
We cannot assure you that our nonclinical studies or clinical trials will begin as planned or be completed on schedule, if at all, or that we will not need to restructure or otherwise modify our trials after they have begun.
We will also need to verify, such as through a manufacturing comparability study, that any new manufacturing process will produce our product candidate according to the specifications previously submitted to the FDA or another regulatory authority. We may be unsuccessful in demonstrating the comparability of clinical supplies, which could require 53 Table of Contents the conduct of additional clinical trials.
We will also need to verify, such as through a manufacturing comparability study, that any new manufacturing process will produce our product candidate according to the specifications previously submitted to the FDA or another regulatory authority. We may be unsuccessful in demonstrating the comparability of clinical supplies, which could require the conduct of additional clinical trials.
If the FDA finds deficiencies or a comparable foreign regulatory authority does not approve these facilities for the manufacture of our product candidates or if it withdraws any such approval in the future, we may need to find alternative manufacturing facilities, which would significantly impact our ability to develop, obtain regulatory approval for or market our product candidates, if approved.
If the FDA finds deficiencies or a comparable foreign regulatory authority does not approve these facilities for 54 Table of Contents the manufacture of our product candidates or if it withdraws any such approval in the future, we may need to find alternative manufacturing facilities, which would significantly impact our ability to develop, obtain regulatory approval for or market our product candidates, if approved.
These programs are designed to encourage the research and development of product candidates that are intended to address serious conditions. These designations may confer benefits such as additional interaction with regulatory authorities and eligibility for expedited review procedures. However, there can be no assurance that we will successfully obtain such designations for 56 Table of Contents our product candidates.
These programs are designed to encourage the research and development of product candidates that are intended to address serious conditions. These designations may confer benefits such as additional interaction with regulatory authorities and eligibility for expedited review procedures. However, there can be no assurance that we will successfully obtain such designations for our product candidates.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Our cybersecurity management team supervises efforts to prevent, detect, mitigate, and remediate cybersecurity risks and incidents through various means, which may include briefings from internal security personnel; threat intelligence and other information obtained from governmental, public or private sources, including external consultants engaged by us; and alerts and reports produced by security tools deployed in the information technology environment.
Our cybersecurity management team supervises efforts to prevent, detect, mitigate, and remediate cybersecurity risks and incidents through various means, which may include briefings from cybersecurity experts; threat intelligence and other information obtained from governmental, public or private sources, including external consultants engaged by us; and alerts and reports produced by security tools deployed in the information technology environment.
Cybersecurity Governance Our Board of Directors (the Board) considers cybersecurity risk as part of its risk oversight function and has delegated to the Audit Committee (the Committee) oversight of cybersecurity risks. The Committee oversees our cybersecurity risk management program. 79 Table of Contents The Committee receives periodic reports from management on our cybersecurity risks.
Cybersecurity Governance Our Board of Directors (the Board) considers cybersecurity risk as part of its risk oversight function and the Audit Committee (the Committee) contributes to oversight of cybersecurity risks. 79 Table of Contents The Board receives periodic reports from management on our cybersecurity risks.
This cybersecurity management team has primary responsibility for our overall cybersecurity risk management program and supervises both our internal cybersecurity personnel and our retained external cybersecurity consultants. This team includes individuals with significant experience running or overseeing cybersecurity programs at similarly sized biotechnology organizations and navigating the associated risk landscape.
This cybersecurity management team has primary responsibility for our overall cybersecurity risk management program and oversees our retained external cybersecurity experts, which includes individuals with significant experience running or overseeing cybersecurity programs at similarly sized biotechnology organizations and navigating the associated risk landscape.
Board members may receive presentations on cybersecurity topics from our Chief Financial Officer (CFO), internal security staff or external experts as part of the Board's continuing education on topics that impact public companies. Members of our management team, including our Chief Executive Officer (CEO), CFO, and General Counsel, are responsible for assessing and managing our material risks from cybersecurity threats.
The Board may also receive briefings from management on our cyber risk management program, and may receive presentations on cybersecurity topics from our Chief Financial Officer (CFO) or external experts as part of the Board's continuing education on topics that impact public companies.
In addition, management updates the Committee, as necessary or appropriate, regarding any material cybersecurity incidents, as well as any incidents with lesser impact potential. The Committee reports to the Board regarding its activities, including those related to cybersecurity. The Board of directors may also receive briefings from management on our cyber risk management program.
In addition, management updates the Committee, as necessary or appropriate, regarding any material cybersecurity incidents, as well as any incidents with lesser impact potential, as appropriate.
Added
Members of our management team, including our CFO, Head of Information Technology, General Counsel and our Vice President of Quality Assurance, are responsible for assessing and managing our material risks from cybersecurity threats.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Securities Authorized for Issuance Under Equity Compensation Plans See Item 12 of Part III of this Annual Report for information about our equity compensation plans, which information will be incorporated by reference to the information that will be contained in our proxy statement related to the 2024 Annual Meeting of Stockholders, which we intend to file with the SEC on or before July 29, 2024.
Securities Authorized for Issuance Under Equity Compensation Plans See Item 12 of Part III of this Annual Report for information about our equity compensation plans, which information will be incorporated by reference to the information that will be contained in our proxy statement related to the 2025 Annual Meeting of Stockholders, which we intend to file with the SEC on or before July 29, 2025.
Item 5. Market for Registrant ’ s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities Market Information Our common stock trades on The Nasdaq Capital Market under the symbol “VTGN”. Holders of Common Stock As of May 31, 2024, there were approximately 365 holders of record of our common stock.
Item 5. Market for Registrant ’ s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities Market Information Our common stock trades on The Nasdaq Capital Market under the symbol “VTGN”. Holders of Common Stock As of June 10, 2025, there were approximately 357 holders of record of our common stock.
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I tem 6. [Reserved] 81 Table of Contents
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Performance Graph Not applicable. Unregistered Sales of Equity Securities None. Use of Proceeds Not Applicable Issuer Repurchases of Equity Securities and Affiliated Purchasers None. I tem 6. [Reserved] 81 Table of Contents

Item 7. Management's Discussion & Analysis

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

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In May 2021, we entered into an Open Market Sale Agreement (the Sales Agreement) with Jefferies LLC (Jefferies) as sales agent, with respect to an at-the-market offering program (the ATM) under which we were permitted, at our option, offer and sell, from time to time, shares of our common stock having an aggregate offering price of up to $75.0 million through Jefferies as our sales agent.
In May 2021, we entered into an Open Market Sale Agreement (the Sales Agreement) with Jefferies LLC (Jefferies) as sales agent, with respect to an at-the-market offering program (the ATM) under which we were permitted, at our option, to offer and sell, from time to time, shares of our common stock having an aggregate offering price of up to $75.0 million through Jefferies as our sales agent.
Investing Activities Net cash used in investing activities for the year ended March 31, 2024 was $ 0.1 million, consisting of purchases of property and equipment.
Net cash used in investing activities for the year ended March 31, 2024 was $0.1 million, consisting of purchases of property and equipment.
Recently Issued Accounting Pronouncements A description of recently issued accounting pronouncements that may potentially impact our financial condition and results of operations is disclosed in Note 2 to our audited Consolidated Financial Statements appearing elsewhere in this Annual Report.
A description of recently issued accounting pronouncements that may potentially impact our financial condition and results of operations is disclosed in Note 2 to our audited Consolidated Financial Statements appearing elsewhere in this Annual Report.
In light of these risks, uncertainties and assumptions, the future events and trends discussed in this Report may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Accordingly, you should not rely upon forward-looking statements in this Report as predictions of future events.
In light of these risks, challenges, uncertainties and assumptions, the future events and trends discussed in this Annual Report may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Accordingly, you should not rely upon the forward-looking statements in this Annual Report as predictions of future events.
To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownership interest of our stockholders could be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our common stockholders.
To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownership interest of our stockholders could, and likely will, be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our common stockholders.
Our future capital requirements will depend on many factors, including: 89 Table of Contents • the initiation, type, number, scope, results, costs and timing of, our ongoing and planned preclinical studies and clinical trials of existing product candidates or clinical trials of other potential product candidates we may choose to pursue in the future, including based on feedback received from regulatory authorities; • the costs and timing of manufacturing for current or future product candidates, including commercial scale manufacturing if any product candidate is approved; • the costs, timing and outcome of regulatory review of current or future product candidates; • the costs of obtaining, maintaining and enforcing our patents and other intellectual property rights; • our efforts to enhance operational systems and hire additional personnel to satisfy our obligations as a public company, including enhanced internal controls over financial reporting; • the costs and timing of establishing or securing sales and marketing capabilities if any current or future product candidate is approved; • our ability to achieve sufficient market acceptance, coverage and adequate reimbursement from third-party payers and adequate market share and revenue for any approved products; • costs associated with any products or technologies that we may in-license or acquire; and • delays or issues with any of the above, including that the risk of each may be exacerbated any future pandemics or epidemic diseases, potential geopolitical instability and war, inflation or rising interest rates.
Our future capital requirements will depend on many factors, including: 88 Table of Contents • the initiation, type, number, scope, results, costs and timing of, our ongoing and planned nonclinical studies and clinical trials of existing product candidates or clinical trials of other potential product candidates we may choose to pursue in the future, including based on feedback received from regulatory authorities; • the costs and timing of manufacturing for current or future product candidates, including commercial scale manufacturing if any product candidate is approved; • the costs, timing and outcome of regulatory review of current or future product candidates; • the costs of obtaining, maintaining and enforcing our patents and other intellectual property rights; • our efforts to enhance operational systems and hire additional personnel to satisfy our obligations as a public company, including enhanced internal controls over financial reporting; • the costs and timing of establishing or securing sales and marketing capabilities if any current or future product candidate is approved, and should we decide to commercialize them on our own; • our ability to achieve sufficient market acceptance, coverage and adequate reimbursement from third-party payers and adequate market share and revenue for any approved products; • costs associated with any products or technologies that we may in-license or acquire; and • delays or issues with any of the above, including that the risk of each may be exacerbated any future pandemics or epidemic diseases, potential geopolitical instability and war, inflation or rising interest rates.
Additionally, we have issued equity securities with an approximate value 87 Table of Contents at issuance of $41.3 million in non-cash acquisitions of product licenses, the Pherin Acquisition, and in settlements of certain liabilities, including liabilities for professional services rendered to us or as compensation for such services.
Additionally, we have issued equity securities with an approximate value at issuance of $41.3 million for non-cash acquisitions of product licenses, the Pherin Acquisition, and in settlements of certain liabilities, including liabilities for professional services rendered to us or as compensation for such services.
This consisted primarily of net proceeds of $ 93.5 million resulting from the October 2023 Public Offering, net proceeds of $ 35.9 million resulting from the sale of shares of our common stock under the Sales Agreement, partially offset by costs related to repayment of notes payable of $ 1.0 million .
This consisted primarily of net proceeds of $93.5 resulting from the October 2023 Public Offering, net proceeds of $35.9 million resulting from the sale of shares of our common stock under the Sales Agreement, partially offset by the repayment of notes payable of notes payable of 1.0 million.
Our actual results may differ from these estimates under different assumptions or conditions. While our significant accounting policies are described in more detail in Note 2 to our Consolidated Financial Statements included elsewhere in this Annual Report, we believe the following accounting policies and estimates to be most critical to the preparation of our financial statements.
Our actual results may differ from these estimates under different assumptions or conditions. While our significant accounting policies are described in more detail in Note 2 to our Consolidated Financial Statements included elsewhere in this Annual Report, we believe the following accounting estimate to be most critical to the preparation of our financial statements. Research and Development Expenses.
It is not possible for our management or Board to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make in this Report or otherwise.
It is not possible for our management or Board to predict all challenges and risks we will face, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make in this Annual Report or otherwise.
Our future research and development expenses may vary significantly based on a wide variety of factors, such as: • the number and scope, rate of progress, expense and results of our discovery and preclinical development activities and clinical trials; • the number of trials required for regulatory approval; • the number of sites included in each of our clinical trials; • the countries in which clinical and non-clincial trials are conducted; 84 Table of Contents • the length of time required to enroll eligible patients; • the number of patients that participate in the trials; • the ability to identify appropriate patients eligible for our clinical trials; • the number of doses that patients receive, during such clinical trials; • the drop-out or discontinuation rates of patients; • potential additional safety monitoring requested by regulatory agencies; • the duration of patient participation in the trials and follow-up; • the phase of development of the product candidate; • the efficacy and safety profile of the product candidate; • the timing, receipt, and terms of any approvals from applicable regulatory authorities including the FDA and non-U.S. regulators; • maintaining a continued acceptable safety profile of our product candidates following approval, if any; • the cost and timing of manufacturing our product candidates; • significant and changing government regulation and regulatory guidance; • the impact of any business interruptions to our operations or to those of the third parties with whom we work; • geopolitical instability, such as the war in Ukraine and, more recently, the war between Israel and Hamas; • adverse effects on the financial markets, the global economy, the supply chain and our expenses due to pandemics or other epidemic diseases, geopolitical instability, inflation, rising interest rates and other factors; and • the extent to which we establish additional strategic collaborations or other arrangements.
Our future research and development expenses may vary significantly based on a wide variety of factors, such as: • the number and scope, rate of progress, expense and results of our preclinical development activities and clinical trials; • the number of trials required for regulatory approval; • the number of sites included in each of our clinical trials; • the length of time required to enroll eligible patients; • the number of patients that participate in the trials; • the ability to identify appropriate patients eligible for our clinical trials; • the number of doses that patients receive during such clinical trials; • the drop-out or discontinuation rates of patients; • potential additional safety monitoring requested by regulatory agencies; • the duration of patient participation in the trials and follow-up; • the phase of development of the product candidate; • the efficacy and safety profile of the product candidate; • the timing, receipt, and terms of any approvals from applicable regulatory authorities including the FDA and non-U.S. regulators; • maintaining a continued acceptable safety profile of our product candidates following approval, if any; • the cost and timing of manufacturing our product candidates; • significant and changing government regulation and regulatory guidance; • the impact of any business interruptions to our operations or to those of the third parties with whom we work; • adverse effects on the financial markets, the global economy, the supply chain and our expenses due to pandemics or other epidemic diseases, geopolitical instability, inflation, rising interest rates and other factors; and • the extent to which we establish additional strategic collaborations or other arrangements.
When evaluating the adequacy of the accrued liabilities, we analyze progress of the services, including the phase or completion of events, invoices received and contracted costs. We hold discussions with applicable personnel and outside service providers as to the progress of our clinical trials, or the services completed.
When evaluating the adequacy of the accrued liabilities, we analyze progress of the services, including the phase or completion of events, invoices received and contracted costs. We hold discussions with applicable personnel and outside service providers as to the progress of our manufacturing, nonclinical studies, clinical trials, or contracted services are completed.
These obligations are further described in Note 5 to our audited consolidated financial statements. In addition, we enter into agreements in the normal course of business with certain vendors for the provision of goods and services, which includes manufacturing services with CMOs, development services with CROs, and research and development services from other industry consultants.
These obligations are further described in Note 5 to our audited consolidated financial statements. In addition, we enter into agreements in the normal course of business with certain vendors for the provision of goods and services, which includes third-party contract manufacturing services with CDMOs, development services with CROs, and research and development services from other industry consultants.
Contractual Obligations and Commitments We lease our corporate office and laboratory space in South San Francisco, California. As of March 31, 2024, total future aggregate operating lease commitments were $ 2.4 million, with approximately $ 0.7 million due during the year ending March 31, 2025, and the remaining due in periods ending March 31, 2026 through 2028.
Contractual Obligations and Commitments We lease our corporate office and laboratory space in South San Francisco, California. As of March 31, 2025, total future aggregate operating lease commitments were $1.7 million, with approximately $0.7 million due during the year ending March 31, 2026, and the remaining due in periods ending March 31, 2027 through 2028.
In the future, to further advance the clinical development of our product candidates, as well as support our operating activities, we plan to seek additional financing, including both equity-based capital and funding from non-dilutive sources, and continue to carefully manage our operating costs, including, but not limited to, our clinical, nonclinical, and pre-commercialization programs.
In the future, to further advance the clinical development of our product candidates, as well as support our operating activities, we plan to seek additional financing, including both equity-based and/or debt-based capital and potentially from non-dilutive sources other than debt-based capital, and continue to carefully manage our operating costs, including, but not limited to, our clinical, nonclinical, and pre-commercialization programs.
We have based this estimate on assumptions that may prove to be wrong, and we could deplete our capital resources sooner than we expect. Additionally, the process of conducting preclinical studies and testing product candidates in clinical trials is costly, and the timing of progress and expenses in these studies and trials is uncertain.
See "Risk Factors " above. We have based this estimate on assumptions that may prove to be wrong, and we could deplete our capital resources sooner than we expect. Additionally, the process of conducting nonclinical studies and testing product candidates in clinical trials is costly, and the timing of progress and expenses in these studies and trials is uncertain.
To date, we have financed our operations and technology acquisitions primarily through the issuance and sale of our equity and debt securities for cash proceeds of approximately $338.5 million, as well as from an aggregate of approximately $22.7 million of government research grant awards (excluding the fair market value of government-sponsored and funded clinical trials), strategic collaboration payments, intellectual property licensing payments, and other revenues.
To date, as of March 31, 2025, we have financed our operations and technology acquisitions primarily through the issuance and sale of our equity securities for cash proceeds of approximately $340.4 million, as well as from an aggregate of approximately $22.7 million of government research grant awards (excluding the fair market value of government-sponsored and funded clinical trials), strategic collaboration payments, intellectual property licensing payments, and other revenues.
The 90 Table of Contents preparation of these financial statements requires us to make estimates and judgments that affect the reported amounts of assets, liabilities, revenue and expenses and the disclosure of contingent assets and liabilities in our financial statements.
The preparation of these consolidated financial statements requires us to make estimates and judgments that affect the reported amounts of assets, liabilities, revenue and expenses and the disclosure of contingent assets and liabilities in our consolidated financial statements.
The events and circumstances reflected in the forward-looking statements in this Report may not be achieved or occur. Although we believe that the expectations reflected in the forward-looking statements in this Report are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.
The events and circumstances reflected in the forward-looking statements in this Annual Report may not be achieved or occur in part or at all. Although we believe that the expectations reflected in the forward-looking statements in this Annual Report are reasonable as of the date of this Annual Report, we cannot guarantee future results, levels of activity, performance or achievements.
Our research and development expenses primarily include: • External costs, including: ◦ expenses incurred in connection with conducting clinical trials, including investigator grants and site payments for time and pass-through expenses and expenses incurred under agreements with CROs, central laboratories and other vendors and service providers engaged to conduct our trials; ◦ expenses incurred in connection with the discovery and preclinical development of our product candidates, including under agreements with third parties, such as consultants and CROs; ◦ costs associated with consultants for CMC development, and other services; ◦ the cost of manufacturing compounds for use in our preclinical studies, including under agreements with third parties, such as consultants and third-party manufacturers; and ◦ costs related to compliance with drug development regulatory requirements. • Internal costs, including: ◦ employee-related expenses, including salaries, related benefits, travel and share-based compensation expenses for employees engaged in research and development functions; ◦ the costs of laboratory supplies and acquiring, developing and manufacturing preclinical study materials; and ◦ facilities, depreciation and other expenses, which include allocated expenses for rent and maintenance of facilities, and supplies.
Our research and development expenses primarily include: • External costs, including: ◦ expenses incurred in connection with planning, preparing for and conducting clinical trials, including investigator grants and site payments, and pass-through expenses and expenses incurred under agreements with CROs, central laboratories and other vendors and service providers engaged to conduct our trials; ◦ expenses incurred in connection with the discovery and preclinical development of our product candidates, including under agreements with third parties, such as consultants and CROs; ◦ costs associated with consultants for chemistry, manufacturing, and control (CMC) development, and other manufacturing-related services; ◦ the cost of manufacturing compounds for use in our nonclinical studies and clinical trials, including under agreements with third parties, such as consultants and third-party contract manufacturers; and ◦ costs related to compliance with development regulatory requirements. • Internal costs, including: ◦ employee-related expenses, including salaries, related benefits, travel and share-based compensation expenses for employees engaged in research and development functions; ◦ the costs of laboratory supplies and acquiring and developing preclinical study materials; and ◦ facilities, depreciation and other expenses, which include allocated expenses for rent and maintenance of facilities, and supplies. 83 Table of Contents We expense research and development expenses in the periods in which they are incurred.
These obligations and commitments are not separately presented. Critical Accounting Policies and Significant Judgements and Estimates Our management’s discussion and analysis of our financial condition and results of operations are based on our financial statements, which have been prepared in accordance with U.S. Generally Accepted Accounting Principles (GAAP).
These obligations and commitments are not separately presented. Critical Accounting Estimates Our management’s discussion and analysis of our financial condition and results of operations are based on our consolidated financial statements, which have been prepared in accordance with U.S. Generally Accepted Accounting 89 Table of Contents Principles (GAAP).
Research and Development Expenses Research and development expenses consist of external and internal costs associated with our research and development activities, including its discovery and research efforts and the preclinical and clinical development of its product candidates. Research and development costs are expensed in the period incurred.
Prepaids, and Accruals Research and development expenses consist of external and internal costs associated with our research and development activities, including its discovery and research efforts and the manufacturing, nonclinical and clinical development of our neuroscience product candidates. Research and development costs are expensed in the period incurred.
Notwithstanding the foregoing, there can be no assurance that future financings will be available to us in sufficient amounts, in a timely manner, or on terms acceptable to us, if at all, or that current or future development and commercialization collaborations will generate revenue from future potential milestone payments or otherwise. 88 Table of Contents Cash Flows The following table summarizes changes in cash and cash equivalents for the fiscal years stated (in thousands): Year Ended March 31, 2024 2023 Net cash used in operating activities $ (25,813) $ (49,716) Net cash used in investing activities (61) (740) Net cash provided by (used in) financing activities 128,402 (1,041) Net decrease in cash and cash equivalents 102,528 (51,497) Cash and cash equivalents at beginning of period 16,638 68,135 Cash and cash equivalents at end of period $ 119,166 $ 16,638 Operating Activities Net cash used in operating activities for the year ended March 31, 2024 was $ 25.8 million, consisting primarily of our net loss of $ 29.4 million, adjusted for $ 2.8 million of non-cash charges primarily related to stock-based compensation expense and amortization of our operating lease right-of-use asset, and $ 0.8 million for net changes in operating assets and liabilities.
Notwithstanding the foregoing, there can be no assurance that future financings will be available to us in sufficient amounts, in a timely manner, or on terms acceptable to us, if at all, or that current or future development and commercialization collaborations will generate revenue from future potential milestone payments or otherwise. 87 Table of Contents Cash Flows The following table summarizes changes in cash and cash equivalents for the fiscal years stated (in thousands): Year Ended March 31, 2025 2024 Net cash used in operating activities $ (42,097) $ (25,813) Net cash used in investing activities (13,148) (61) Net cash provided by (used in) financing activities 3,210 128,402 Net decrease in cash and cash equivalents (52,035) 102,528 Cash and cash equivalents at beginning of period 119,166 16,638 Cash and cash equivalents at end of period $ 67,131 $ 119,166 Operating Activities Net cash used in operating activities for the year ended March 31, 2025 was $42.1 million, consisting primarily of our net loss of $51.4 million, adjusted for $4.6 million of non-cash charges primarily related to stock-based compensation expense and amortization of our operating lease right-of-use asset, and $4.8 million for net changes in operating assets and liabilities.
We have entered into various research and development contracts with clinical research organizations, clinical manufacturing organizations, clinical sites and other vendors and consultants.
We have entered into various research and development contracts with CROs, CDMOs, clinical sites and other vendors and consultants.
Further, even if our product candidates appear promising at various stages of development, our share price may decrease such that we are unable to raise additional capital without significant dilution or other terms that may be unacceptable to our management and Board or disadvantageous to our stockholders. Moreover, we operate in a very competitive and rapidly changing environment.
Further, even if our product candidates appear promising at various stages of development, our share price may decrease such that we are unable to raise additional capital without significant dilution or other terms that may be unacceptable to our management and our Board of Directors (the Board) or disadvantageous to our stockholders.
We expense research and development expenses in the periods in which they are incurred. External expenses are recognized based on an evaluation of the progress to completion of specific tasks using information provided to us by our service providers or our estimate of the level of service that has been performed at each reporting date.
External expenses are recognized based on an evaluation of the progress to completion of specific tasks using information provided to us by our service providers or our estimate of the level of service that has been performed at each reporting date. Research and development activities are central to our business model.
Costs incurred in obtaining product or technology licenses are charged immediately to research and development expense if, at acquisition, the product or technology licensed has not achieved regulatory approval or reached technical feasibility and has no alternative future uses. We treated the Pherin Acquisition as an acquisition of assets for accounting purposes.
Costs incurred in obtaining product or technology licenses are charged immediately to research and development expense if, at acquisition, the product or technology licensed has not achieved regulatory approval or reached technical feasibility and has no alternative future uses.
The actual probability of success for our product candidates or any future candidates may be affected by a variety of factors. We may never succeed in achieving regulatory approval for any of our product candidates or any future candidates.
The actual probability of success for our product candidates or any future candidates may be affected by a variety of factors.
Research and development activities are central to our business model. There are numerous factors associated with the successful development of any of our product candidates, including future trial design and various regulatory requirements, many of which cannot be determined with accuracy at this time based on our stage of development.
There are numerous factors associated with the successful development of any of our product candidates, including future trial design and various regulatory requirements, many of which cannot be determined with accuracy at this time based on our stage of development. In addition, future regulatory factors beyond our control may impact our clinical development programs.
We are under no duty to update any of these forward-looking statements after the date of this Report or to conform these statements to actual results or revised expectations. If we do update one or more forward-looking statements, no inference should be drawn that we will make additional updates with respect to those or other forward-looking statements.
If we do update one or more of the forward-looking statements in this Annual Report, no inference should be drawn that we will make additional updates with respect to those or any other forward-looking statements.
General and Administrative Expenses General and administrative expenses consist of salaries, bonuses, related benefits and stock-based compensation expense for personnel in executive, legal, finance and administrative functions; professional fees for legal, consulting, accounting and audit services; and travel expenses, technology costs and other allocated expenses.
We may never succeed in achieving regulatory approval for any of our product candidates or any future candidates. 84 Table of Contents General and Administrative Expenses General and administrative expenses consist of salaries, bonuses, related benefits and stock-based compensation expense for personnel in executive, legal, finance and administrative functions; professional fees for legal, consulting, accounting and audit services; and travel expenses, technology costs and other allocated expenses.
In addition, during the fiscal year ended March 31, 2024, we received net proceeds of approximately $93.5 million from the October 2023 Public Offering and $1.5 million from Fuji Pharma under the Negotiation Agreement.
We pay Jefferies a commission of up to three percent (3.0%) of the aggregate gross proceeds from any sales under the Sales Agreement. In addition, during the year ended March 31, 2024, we received net proceeds of approximately $93.5 million from the October 2023 Public Offering and $1.5 million from Fuji Pharma under the Negotiation Agreement.
We expect that our general and administrative expenses will increase substantially over the next several years as we hire additional personnel to support the growth of our business and incur additional expenses associated with being a public company.
We expect that our general and administrative expenses may increase substantially over the next fiscal year as we hire additional personnel to support the continued growth of our research and development, contract manufacturing and pre-commercialization operations and incur additional expenses associated with being a public company.
Net cash used in operating activities for the year ended March 31, 2023 was $ 49.7 million, consisting primarily of our net loss of $ 59.2 million, adjusted for $ 7.5 million of non-cash charges primarily related to stock-based compensation expense, non-operating expenses related to our acquisition of Pherin Pharmaceuticals, Inc. completed in February 2023 (the Pherin Acquisition), and amortization of our operating right-of-use asset, partially offset by $ 2.0 million for net changes in operating assets and liabilities.
Net cash used in operating activities for the year ended March 31, 2024 was $25.8 million, consisting primarily of our net loss of $29.4 million, adjusted for $2.8 million of non-cash charges primarily related to stock-based compensation expense and amortization of our operating lease right-of-use asset, and $0.8 million for net changes in operating assets and liabilities.
However, our forecast of the period of time through which our financial resources will be adequate to support our operations is a forward-looking statement that involves risks and uncertainties, and actual results could vary materially. See "Risk Factors " above.
We anticipate that we will continue to seek additional funding, though the precise timing and nature of such additional funding may prove uncertain. Our forecast of the period of time through which our financial resources will be adequate to support our operations is a forward-looking statement that involves risks and uncertainties, and actual results could vary materially.
Research and Development Expenses The following table summarizes our research and development expenses by development program for the years ended March 31, 2024 and 2023 (in thousands): 86 Table of Contents Year Ended March 31, 2024 2023 Clinical and nonclinical studies and development expenses by program Fasedienol $ 7,791 $ 28,025 Itruvone 931 2,301 AV-101 232 1,163 All other 200 72 Total clinical and nonclinical studies and development expenses 9,154 31,561 Cost of Pherin Acquisition — 3,559 Salaries and benefits 7,323 6,255 Stock-based compensation 1,174 1,365 Consulting and professional services 1,374 817 Occupancy and all other costs 997 820 Total research and development expenses $ 20,022 $ 44,377 Research and development expenses were $ 20.0 million and $ 44.4 million for the years ended March 31, 2024 and 2023 , respectively.
Research and Development Expenses The following table summarizes our research and development expenses for the years ended March 31, 2025 and 2024 (in thousands): 85 Table of Contents Year Ended March 31, 2025 2024 Clinical and nonclinical studies and development expenses by program Fasedienol $ 21,892 $ 7,791 Itruvone 765 931 AV-101 135 232 All other 2,203 200 Total clinical and nonclinical studies and development expenses 24,995 9,154 Salaries and benefits 9,402 7,323 Stock-based compensation 1,938 1,174 Consulting and professional services 1,565 1,374 Occupancy and all other costs 1,475 997 Total research and development expenses $ 39,375 $ 20,022 Research and development expense was $39.4 million and $20.0 million for the years ended March 31, 2025 and 2024, respectively.
We expense general and administrative expenses in the periods in which they are incurred. 85 Table of Contents Results of Operations for the Years Ended March 31, 2024 and 2023 The following table summarizes our results of operations for the periods indicated (in thousands): Year Ended March 31, 2024 2023 Revenues: Sublicense and other revenue $ 1,064 $ (227) Total revenues 1,064 (227) Operating expenses: Research and development 20,022 44,377 General and administrative 14,063 14,664 Total operating expenses 34,085 59,041 Loss from operations (33,021) (59,268) Other income (expense) Interest Income 3,351 26 Other income 312 — Total other income, net 3,663 26 Loss before income taxes (29,358) (59,242) Income taxes (4) (6) Net loss $ (29,362) $ (59,248) Sublicense and Other Revenue Sublicense and other revenue was $ 1.1 million and $ (0.2) million for the years ended March 31, 2024 and 2023 , respectively.
Results of Operations for the Years Ended March 31, 2025 and 2024 The following table summarizes our results of operations for the periods indicated (in thousands): Year Ended March 31, 2025 2024 Revenues: Sublicense and other revenue $ 486 $ 1,064 Total revenues 486 1,064 Operating expenses: Research and development 39,375 20,022 General and administrative 17,084 14,063 Total operating expenses 56,459 34,085 Loss from operations (55,973) (33,021) Other income (expense) Interest Income 4,557 3,351 Other income 5 312 Total other income, net 4,562 3,663 Loss before income taxes (51,411) (29,358) Income taxes (7) (4) Net loss $ (51,418) $ (29,362) Sublicense and Other Revenue Sublicense and other revenue were $0.5 million and $1.1 million for the years ended March 31, 2025 and 2024, respectively.
In addition, future regulatory factors beyond our control may impact our clinical development programs. Product candidates in later stages of development generally have higher development costs than those in earlier stages of development.
Product candidates in later stages of development generally have higher development costs than those in earlier stages of development.
Future Funding Requirements Based on our current operating plan, we believe that our existing cash and cash equivalents, will be sufficient to meet our anticipated operating expenses and capital expenditures through at least the next twelve months.
Future Funding Requirements Based on our current operating plan, we believe that our existing cash, cash equivalents, and marketable securities will not be sufficient to fund our operations beyond the next twelve months from the date of this Annual Report.
Significant judgments and estimates may be made in determining the prepaid or accrued balances at the end of any reporting period. Actual results could differ from our estimates. Non-refundable advance payments for goods and services, including fees for process development, are deferred and recognized as expense in the period that the related goods are consumed, or services are performed.
Non-refundable advance payments for goods and services, including fees for process development, are deferred and recognized as expense in the period that the related goods are consumed, or services are performed.
We expect that our research and development expenses will increase substantially over the next several years as we advance our product candidates through clinical trials, continue to develop additional product candidates and expand our pipeline, maintain, expand, protect and enforce our intellectual property portfolio, and hire additional personnel.
We expect that our research and development expense may increase over the next fiscal year as we continue to advance our pherine product candidates through nonclinical studies, clinical trials, and expand third-party contract manufacturing and regulatory activities required to advance further research and development of our current pherine product candidates and additional pherine product candidates, maintain, expand, protect and enforce our intellectual property portfolio, and hire additional headcount.
Liquidity and Capital Resources Sources of Liquidity Since our inception, we have not generated any revenue from product sales and have incurred significant operating losses and negative cash flows from our operations.
The increase of $0.9 million was primarily related to an increase in interest rate return on our cash, cash equivalents, and marketable securities due to increased investment balances. 86 Table of Contents Liquidity and Capital Resources Sources of Liquidity Since our inception, we have not generated any revenue from product sales and have incurred significant operating losses and negative cash flows from our operations.
Our business is subject to significant risks including, but not limited to, our ability to obtain substantial additional financing, the results of our research and development efforts, the results of nonclinical and clinical testing, the effect of regulation by the FDA and other domestic and foreign regulatory agencies, our ability to obtain, maintain and enforce patents on our products once approved for marketing, the impact of competitive products, product development, commercialization potential and technological difficulties, the effect of our accounting policies, and other risks as detailed in the section entitled “Risk Factors” in this Report.
Food and Drug Administration (the FDA) and other domestic and foreign regulatory agencies; current and potential future healthcare reforms; our ability to obtain, maintain and enforce patents on our products if/or when we receive regulatory approval of any of our products; the impact of competitive products, product development, commercialization potential and technological difficulties; the effect of our accounting policies; and other risks as detailed in the section entitled “Risk Factors” in this Annual Report.
Net cash used in investing activities for the year ended March 31, 2023 was $ 0.7 million, consisting of $ 0.5 million related to the Pherin Acquisition and $ 0.2 million for purchases of property and equipment. Financing Activities Net cash provided by financing activities during the year ended March 31, 2024 was $ 128.4 million.
Investing Activities Net cash used in investing activities for the year ended March 31, 2025 was $13.1 million, consisting of purchases of marketable securities and property and equipment, partially offset by the sale and maturity of marketable securities.
General and Administrative Expenses General and administrative expenses were $ 14.1 million and $ 14.7 million for the years ended March 31, 2024 and 2023 , respectively.
Other Income Other income was $4.6 million and $3.7 million for the years ended March 31, 2025 and 2024, respectively.
I n early August 2023, we received and reported positive topline results from our PALISADE-2 Phase 3 clinical trial of fasedienol in adults with SAD.
Our most advanced intranasal pherine product candidate is fasedienol, which is being investigated in our U.S. registration-directed PALISADE Program for the acute treatment of social anxiety disorder (SAD). In August 2023, we received and reported positive topline results from our PALISADE-2 Phase 3 trial of fasedienol for the acute treatment of SAD.
During the first-half of the fiscal year ended March 31, 2024, we sold 4,698,495 shares of our common stock under the terms of our Sales Agreement for net cash proceeds of approximately $36.2 million. We did not sell any shares of our common stock under the Sales Agreement during the second half of the fiscal year ended March 31, 2024.
Financing Activities Net cash provided by financing activities during the year ended March 31, 2025 was $3.2 million. consisting primarily of net proceeds from the sale of shares of our common stock in ATM transactions under the Sales Agreement. Net cash provided by financing activities during the year ended March 31, 2024 was $128.4 million.
Business Overview We are a neuroscience-focused biopharmaceutical company dedicated to pursuing a pioneering approach to the development and commercialization of groundbreaking therapies for psychiatric and neurological disorders based on our deep understanding of nose-to-brain neurocircuitry. Our clinical-stage pipeline consists of intranasal product candidates from a new class of potential neuroscience therapies called pherines.
Business Overview We are a late clinical-stage biopharmaceutical company leveraging a deep understanding of nose-to-brain neurocircuitry to develop and commercialize a new class of non-systemic intranasal product candidates called pherines. Our broad and diverse neuroscience pipeline currently consists of five clinical-stage pherine product candidates, each with a novel mechanism of action (MOA) and positive clinical data in their targeted indication(s).
For the relevant periods, our condensed consolidated financial statements in this Report also include the accounts of Vistastem’s two wholly-owned inactive subsidiaries, Artemis Neuroscience, Inc., a Maryland corporation (Artemis), which was dissolved in April 2022, and VistaStem Canada, Inc., a corporation organized under the laws of Ontario, Canada (VistaStem Canada), which was dissolved in June 2022. 83 Table of Contents Components of Results of Operations Sublicense and Other Revenue Sublicense and other revenue consists of revenue recognized under the AffaMed Agreement and Negotiation Agreement with Fuji Pharma.
Subsidiaries Our wholly-owned subsidiaries consist of Pherin Pharmaceuticals, Inc, a Delaware corporation (Pherin), which we acquired in February 2023, and Vistastem, Inc., a California corporation founded in 1998 (Vistastem). Components of Results of Operations Sublicense and Other Revenue Sublicense and other revenue consist of revenue recognized under the AffaMed Agreement and Negotiation Agreement with Fuji Pharma.
The decrease was partially offset by an increase in compensation and related costs of $0.9 million and an increase in consulting professional fees of $0.6 million.
The increase of $3.0 million in general and administrative expense for the year ended March 31, 2025, as compared to the year ended March 31, 2024, was primarily due to an increase in headcount and related costs of $1.8 million, as well as an increase in consulting and professional fees of $0.6 million.
The increase in sublicense and other revenue of $ 1.3 million is due to timing of revenue recognized under the AffaMed Agreement and a one-time true up of expense during the year ended March 31, 2023 due to a change in estimate, as well as revenue recognized under the Negotiation Agreement with Fuji Pharma executed in September 2023.
The decrease in sublicense and other revenue of $0.6 million is due to timing of revenue recognized under the AffaMed Agreement.
Removed
Designed exclusively as nasal sprays, each of our pherine product candidates is centered on our innovative approach to addressing neuroscience disorders with the nose as a new portal for the administration of novel, rapid-onset neuroactive therapies that do not require systemic absorption or binding to neurons in the brain to achieve desired therapeutic effects.
Added
Our business is subject to significant risks including, but not limited to: our ability to obtain substantial additional financing; our ability to successfully complete ongoing or future clinical trials of our product candidates within estimated timelines or at all, receive regulatory approval or be commercially successful; our dependence on third-party collaborators for the development, manufacturing, regulatory approval, and/or commercialization of our product candidates and other aspects of our business, which are outside of our full control; the effect of regulation by the U.S.
Removed
In addition, our neuroscience pipeline also includes a clinical-stage investigational oral prodrug candidate, AV-101, focused on neurological disorders involving the NMDA receptor. We are advancing our pipeline with multiple clinical and nonclinical studies underway or planned, including our ongoing PALISADE-3 Phase 3 trial and open label extension for fasedienol as an acute treatment of SAD.
Added
Moreover, the biopharmaceutical industry in which we operate is very competitive and rapidly changing. New challenges and risks emerge frequently.
Removed
Our primary goal is to develop and commercialize a broad and diversified pipeline of innovative neuroactive pherine therapies for multiple highly prevalent neuroscience indications, such as SAD, MDD, and vasomotor symptoms (hot flashes) associated with menopause, with limited or inadequate current treatment options to meet the needs of millions of underserved patients in the U.S. and worldwide.
Added
We are under no duty to update any of the forward-looking statements in this Annual Report after the date of this Annual Report or to conform the forward-looking statements to actual results or revised expectations.
Removed
See “Our Neuroscience Pipeline , ” “ Our Lead Programs ” and “Our Other Programs” in Part I, Item 1 above. 82 Table of Contents The following summarizes material developments during the fiscal year ended March 31, 2024. • Results of PALISADE-2.
Added
Pherines specifically and selectively bind to peripheral receptors in human nasal chemosensory neurons, and are designed to rapidly activate nose-to-brain neurocircuits believed to regulate brain areas without requiring systemic absorption or uptake into the brain to achieve desired therapeutic benefits.
Removed
The PALISADE-2 trial met its primary efficacy endpoint, the difference in mean SUDS scores during the public speaking challenge at baseline (Visit 2) and treatment (Visit 3) for subjects treated with fasedienol versus placebo at Visit 3.
Added
The ongoing clinical trials in our PALISADE Program include our PALISADE-3 and PALISADE-4 Phase 3 trials, which are designed similarly to PALISADE-2, and a small exploratory Phase 2 repeat dose study (the Repeat Dose Study).
Removed
The trial also met its secondary endpoint, demonstrating a statistically significant difference in the proportion of clinician-assessed responders between fasedienol and placebo as measured by the CGI-I. Fasedienol was observed to be well-tolerated with no SAEs, and the adverse event profiles were comparable between fasedienol and placebo. • Exclusive Negotiation Agreement with Fuji Pharma Co., Ltd.
Added
Topline data for PALISADE-3 are expected in the fourth quarter of 2025 and topline results for PALISADE-4 and the Repeat Dose Study are expected in the first half of 2026.
Removed
On September 1, 2023, we entered into an Exclusive Negotiation Agreement (the Negotiation Agreement) with Fuji Pharma Co., Ltd. (Fuji Pharma), a Tokyo Stock Exchange-listed, Japan-based pharmaceutical company.
Added
We believe either PALISADE-3 or PALISADE-4, if successful, together with the positive results from PALISADE-2, may establish substantial evidence of the effectiveness of fasedienol in support of a potential New Drug Application (NDA) submission to the U.S. FDA for the acute treatment of SAD.
Removed
Pursuant to the terms and conditions of the Negotiation Agreement, we agreed, for a limited period of time, to negotiate exclusively with Fuji Pharma for a potential exclusive license agreement to develop and commercialize our PH80 product candidate in Japan (the Potential Definitive Agreement). As consideration for the Exclusive Negotiation Period, Fuji Pharma paid to us $1.5 million (Purchase Price).
Added
The FDA has granted 82 Table of Contents Fast Track designation for the investigation of fasedienol for the acute treatment of SAD. Fasedienol has the potential to be the first FDA-approved acute treatment of SAD and provide significant advantages relative to the current standard of care.
Removed
Should we enter into the Potential Definitive Agreement with Fuji Pharma, the Purchase Price will be creditable against any upfront fee due in connection with the execution of such agreement. • October 2023 Public Offering.
Added
We have also reported positive results from an exploratory Phase 2A clinical trial for each of our next most advanced pherine product candidates, itruvone for treatment of major depressive disorder, and PH80 for both vasomotor symptoms (hot flashes) due to menopause and premenstrual dysphoric disorder (PMDD), as well as a pilot Phase 2A study of PH15 for improvement of psychomotor impairment due to mental fatigue and an exploratory Phase 2A study of PH284 for treatment of cancer cachexia.
Removed
On October 2, 2023, we entered into an underwriting agreement (the Underwriting Agreement) with Jefferies, Stifel, Nicolaus & Company, Incorporated, and William Blair & Company, L.L.C., as the representatives of the underwriters identified therein (the Underwriters), in connection with the underwritten offering, issuance and sale by us of 15,010,810 shares of our common stock, pre-funded warrants to purchase up to 3,577,240 shares of common stock (the Pre-Funded Warrants), warrants to purchase up to 9,294,022 shares of common stock (or pre-funded warrants to purchase up to 9,294,022 shares of common stock in lieu thereof) (the T1 Warrants) and warrants to purchase 11,265,086 shares of common stock (or pre-funded warrants to purchase up to 11,265,086 shares of common stock in lieu thereof) (the T2 Warrants).
Added
We are passionate about developing transformative treatment options with potential to meet clear and growing unmet needs and bring meaningful relief to patients underserved by the current standard of care for multiple highly prevalent indications, all while delivering long term value to our shareholders.
Removed
The combined offering price for each share of common stock, accompanying T1 Warrant, and accompanying T2 Warrant was $5.38. The combined offering price per Pre-Funded Warrant, accompanying T1 Warrant, and accompanying T2 Warrant was $5.379 (the October 2023 Public Offering).
Added
We expense general and administrative expenses in the periods in which they are incurred.
Removed
We received net proceeds of approximately $93.5 million from the October 2023 Public Offering, after deducting underwriting discounts and commissions and estimated offering expense payable by us. • Launch of PALISADE-3 and Planned Launch of PALISADE-4.
Added
The increase of $19.4 million in research and development expense for the year ended March 31, 2025, as compared to the year ended March 31, 2024, was primarily due to an increase in expense of $15.8 million related to our U.S. registration-directed PALISADE Program for fasedienol for the acute treatment of SAD, including manufacturing, nonclinical studies and our PALISADE-3 and PALISADE-4 Phase 3 clinical trials and the Repeat Dose Study, as well as manufacturing and nonclinical studies to support our planned PH80 U.S.
Removed
To complement the positive topline results from PALISADE-2, we launched PALISADE-3 in March 2024, and are preparing to launch PALISADE-4 in the second half of 2024.
Added
Investigational New Drug Application (IND) to facilitate further Phase 2 development for the treatment of VMS, and increase of $2.8 million in connection with the increased headcount, an increase in consulting and professional fees of $0.2 million, and an increase in occupancy and other costs of $0.5 million.
Removed
Like PALISADE-2, both PALISADE-3 and PALISADE-4 are or are planned to be multi-center, randomized, double-blind, placebo-controlled studies designed to evaluate the efficacy, safety, and tolerability of the acute administration of fasedienol to relieve anxiety symptoms in adult patients with SAD after a single dose of fasedienol during a simulated, anxiety-provoking public speaking challenge in a clinical setting, as measured using the patient-reported SUDS as the primary efficacy endpoint.
Added
At this time, we cannot accurately estimate or know the nature, timing and costs of the efforts that will be necessary to complete the preclinical and clinical development of any pherine product candidates we may develop.
Removed
In addition, both PALISADE-3 and PALISADE-4 will have an open-label extension for a period of up to 12 months. We are also planning to initiate the Repeat Dose Study in the second half of 2024.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk The disclosures in this section are not required because we qualify as a "smaller reporting company," as such term is defined in Rule 12b-2 under the Exchange Act. 93 Table of Contents
Item 7A. Quantitative and Qualitative Disclosures About Market Risk The disclosures in this section are not required because we qualify as a "smaller reporting company," as such term is defined in Rule 12b-2 under the Exchange Act. 90 Table of Contents

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