−Removed: 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.
−Removed: 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).
−Removed: 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: Our most advanced intranasal pherine product candidate is fasedienol, which is being investigated in our U.S.
−Removed: registration-directed PALISADE Program for the acute treatment of social anxiety disorder (SAD).
−Removed: 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.
−Removed: 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: 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: We believe either PALISADE-3 or PALISADE-4, if successful, together with the positive results reported 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.
−Removed: FDA for the acute treatment of SAD.
−Removed: The FDA has granted Fast Track designation for the investigation of fasedienol for the acute treatment of SAD.
−Removed: Fasedienol has the potential to be the first FDA-approved acute treatment for SAD and provide significant advantages relative to the current standard of care.
−Removed: 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, 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: See “Our Neuroscience Product Candidates” below.
−Removed: 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: Our Neuroscience Product Candidates
+Added: We are a late clinical-stage therapeutics company focused on developing and potentially commercializing new medicines for patients with social anxiety disorder, depression, menopausal hot flashes, psychomotor impairment due to mental fatigue, and cancer cachexia.
+Added: Each of the five clinical-stage intranasal pherine product candidates in our neuroscience pipeline has a novel neurocircuitry-focused proposed mechanism of action (MOA) and at least one positive clinical study in its targeted patient population.
+Added: Leveraging our deep understanding of nose-to-brain neurocircuitry, we have designed our intranasal pherine product candidates are designed to rapidly, specifically and selectively bind to peripheral receptors in human nasal chemosensory neurons and rapidly activate neurocircuits believed to regulate brain areas, without requiring systemic absorption or uptake into the brain to achieve desired therapeutic benefits.
+Added: Our most advanced intranasal pherine product candidate, fasedienol, is being investigated in a U.S.
+Added: Phase 3 development program for the acute treatment of social anxiety disorder.
+Added: Itruvone is being developed for treatment of major depressive disorder, refisolone for the treatment of moderate to severe vasomotor symptoms (hot flashes) due to menopause, PH15 for improvement of psychomotor impairment due to mental fatigue and PH284 for the treatment of cancer cachexia.
+Added: We are passionate about developing transformative treatment options with potential to meet clear and growing unmet patient needs and delivering long-term value to our stockholders.
+Added: Our Intranasal Pherine Product Candidates
+Added: IND enabling activities are necessary to facilitate further Phase 2 development in the U.S.
Overview of Social Anxiety Disorder
−Removed: Social anxiety disorder (SAD) is a highly prevalent, serious, and life-threatening psychiatric mental health disorder affecting over 30 million adults in the U.S.
+Added: Social anxiety disorder (SAD) is a highly prevalent, serious, and sometimes life-threatening psychiatric mental health disorder affecting over 30 million adults in the U.S.
With onset typically early in life, usually during adolescence, SAD persists for many years thereafter, with a reported mean duration of about 20 years.
−Removed: While often a long-term disorder, SAD can manifest acutely when triggered by anxiety-provoking social and performance situations .
−Removed: I n those situations, individuals with SAD experience extreme anxiety, distress, fear, and impairment due to their fear of embarrassment, judgment, humiliation, negative evaluation, and scrutiny.
−Removed: The disorder can significantly disrupt family and social life, diminish self-esteem, and hinder work performance.
−Removed: People with SAD may struggle to form social or vocational relationships, which can lead to feelings of powerlessness and shame.
−Removed: The profound anxiety associated with SAD often results in avoidance of everyday interactions and opportunities in academic, social and vocational settings.
−Removed: This avoidance can lead to loneliness, a lack of personal and professional achievements and relationships, as well as economic difficulties, ultimately impacting various aspects of daily life and adding to societal burden.
−Removed: The pervasive effects of SAD often lead to depression and a sense of hopelessness, transforming what is sometimes perceived as extreme shyness into a debilitating mental illness.
−Removed: SAD has a lifetime comorbidity rate of approximately 81% with other serious psychiatric disorders, and individuals with SAD face an increased risk of serious and life-threatening co-morbid depression, substance abuse, suicidal ideation and suicide.
+Added: Individuals with SAD experience extreme anxiety, distress, fear, and impairment due to their fear of being watched, embarrassed, judged, humiliated, negatively evaluated, and scrutinized.
+Added: The profound acute anxiety associated with SAD often results in avoidance of everyday interactions and opportunities in academic, social and vocational settings, which can lead to impaired personal relationships, unsatisfactory work performance, and substance abuse, significantly impacting various aspects of daily life.
+Added: Individuals with SAD face an increased risk of serious and life-threatening co-morbid depression, substance abuse, suicidal ideation and suicide.
Fasedienol for the Acute Treatment of Social Anxiety Disorder
−Removed: Fasedienol, our lead clinical-stage product candidate, is a synthetic neuroactive intranasal pherine in an ongoing U.S.
−Removed: registration-directed Phase 3 clinical development program for the acute treatment of anxiety in adults with SAD.
−Removed: Fasedienol's MOA is fundamentally differentiated from all FDA-approved anti-anxiety medications.
−Removed: 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.
−Removed: Neurocircuitry-focused fasedienol is pharmacologically active without requiring apparent systemic absorption or direct binding on neurons in the brain to achieve its rapid-onset anxiolytic effects.
−Removed: Fasedienol does not exert effects on certain cellular receptors that are associated with known drug abuse liability potential (for example, dopamine and opiate receptors) when activated by certain other pharmaceutical compounds for neuropsychiatric and neurological disorders.
−Removed: Unlike benzodiazepines, fasedienol does not potentiate GABA-A receptors.
−Removed: 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-
−Removed: 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.
+Added: Fasedienol our most advanced neurocircuitry-focused pherine product candidate is in U.S.
+Added: Phase 3 clinical development for the acute treatment of anxiety in adults with SAD.
+Added: Fasedienol's proposed MOA is fundamentally differentiated from all FDA-approved anti-anxiety medications.
+Added: When administered intranasally in microgram-level doses, neurocircuitry-focused fasedienol is proposed to modulate the nasal-limbic amygdala fear and anxiety neurocircuits involved in the pathophysiology of SAD.
+Added: Fasedienol is pharmacologically active without requiring apparent systemic absorption or uptake into the brain to achieve its rapid-onset anxiolytic effects.
+Added: Fasedienol also has no observed binding on certain cellular receptors isolated from the brain that are associated with known drug abuse liability potential (for example, dopamine and opiate receptors) which are activated by certain other pharmaceutical compounds used for neuropsychiatric and neurological disorders.
+Added: Unlike benzodiazepines, data showed that fasedienol has no observed potentiation of GABA-A receptors.
+Added: Because of its innovative non-systemic neurocircuitry-focused proposed MOA, Vistagen believes fasedienol has the potential to achieve rapid-onset anxiolytic effects for individuals with social anxiety disorder on an acute, as-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.
Fasedienol's U.S.
Registration-directed PALISADE Program
−Removed: There is no FDA-approved pharmacological therapy for the acute treatment of SAD.
−Removed: We believe fasedienol has the potential to allow individuals affected by SAD to engage in stressful or previously avoided social or performance situations with fewer or less severe symptoms.
−Removed: Because of its rapid-onset non-systemic proposed MOA and pharmacological effect, a key and substantial difference between fasedienol and all other available therapies approved by the FDA is that fasedienol is being developed with potential to be the first FDA-approved acute treatment of SAD.
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: The Phase 3 clinical trials in our PALISADE Program are randomized, double-blind, placebo-controlled, U.S.
−Removed: 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.
−Removed: Two of the Phase 3 trials in our PALISADE Program were previously concluded;
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: Fasedienol-treated patients demonstrated a greater mean change from baseline (least-squares (LS) mean = -13.8) compared to placebo (LS mean = -8.0), for a statistically significant, and we believe clinically relevant, difference between groups of -5.8 (p=0.015).
−Removed: 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.
−Removed: 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).
−Removed: 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.
−Removed: 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).
−Removed: 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).
−Removed: 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).
−Removed: 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.
−Removed: Overall, no TEAEs, except for pyrexia in the placebo group (2.49%), was more prevalent than 2.0%.
−Removed: To complement our successful PALISADE-2 Phase 3 trial, we launched our PALISADE-3 and PALISADE-4 Phase 3 trials 2024.
−Removed: Like PALISADE-2, PALISADE-3 and PALISADE-4 are U.S.
−Removed: 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.
−Removed: In addition, both PALISADE-3 and PALISADE-4 have an open-label extension for a period of up to 12 months.
−Removed: We initiated the Repeat Dose Study in early 2025.
−Removed: This study is a small U.S.
−Removed: multi-center, randomized, double-blind, placebo-controlled, three-arm exploratory Phase 2 clinical trial designed to evaluate repeated dosing (up to
−Removed: 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.
−Removed: The Repeat Dose Study also includes an open-label extension study for a period of up to 12 months.
−Removed: 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.
−Removed: The FDA has granted Fast Track designation for the investigation of fasedienol for the acute treatment of SAD.
+Added: Fasedienol is in Phase 3 development for the acute treatment of SAD and has received fast track designation from the FDA for development for that indication.
+Added: It is designed 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.
+Added: While there are approved treatments for SAD, none is approved for the acute treatment of SAD on an as-needed basis in connection with an anxiety-provoking social or performance-based event.
+Added: We have designed fasedienol nasal spray with the goal of creating a product candidate with a rapid-onset, non-systemic proposed MOA and pharmacological effect, a key and substantial difference between fasedienol and all other available therapies approved by the FDA for the treatment of SAD.
+Added: Our PALISADE Program includes the PALISADE-1, PALISADE-2, PALISADE-3, and PALISADE-4 Phase 3 clinical trials and a small exploratory Phase 2 repeat dose study (the Repeat Dose Study).
+Added: These PALISADE Phase 3 clinical trials in the PALISADE Program are randomized, double-blind, placebo-controlled, U.S.
+Added: 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 five-minute, simulated, anxiety-provoking public speaking challenge conducted in a clinical setting, as measured by the least squares (LS) mean change from baseline on the patient-rated Subjective Units of Distress Scale (SUDS) score for fasedienol compared with placebo as the primary efficacy endpoint.
+Added: Neither PALISADE-1, completed in 2022, nor PALISADE-3, the randomized portion of which was completed in December 2025, achieved its primary endpoint in the randomized phase of each study, as measured by the LS mean change from baseline on the SUDS score for fasedienol compared with placebo.
+Added: After receipt of negative top-line results from PALISADE-1 during the COVID-19 pandemic, we terminated PALISADE-2 prior to completion (after enrolling 141 patients out of a planned 208) and analyzed the data from the 141 enrolled subjects.
+Added: In August 2023, we announced that PALISADE-2 achieved its primary efficacy endpoint as measured by the LS mean change from baseline on the SUDS score for fasedienol compared with placebo.
+Added: Safety data for fasedienol have been consistently favorable across all placebo-controlled clinical trials and open label clinical studies completed to date.
+Added: Based on the positive data from PALISADE-2, we initiated PALISADE-3 and PALISADE-4, as well as the Repeat Dose Study, using the same randomized public speaking challenge trial designs and primary efficacy endpoint utilized in PALISADE-2, and we added a real-world open-label extension (OLE) to each of the trials.
+Added: As noted above, PALISADE-3,
+Added: the randomized portion of which was completed in December 2025, did not achieve its primary endpoint.
+Added: Topline results from the randomized portion of PALISADE-4 are expected in the second quarter of calendar 2026.
+Added: We refined the statistical analysis plan (SAP) for PALISADE-4 to incorporate each participant's distress level immediately prior to dosing, as measured by the SUDS (pre-IP SUDS), into the primary efficacy analysis.
+Added: No changes were made to the PALISADE-4 clinical study protocol as a result of ongoing dataset analyses of prior studies or refinement of the PALISADE-4 SAP.
+Added: We have completed the randomized portion of the Repeat Dose Study and expect topline results from the randomized portion of the Repeat Dose Study in the third quarter of calendar 2026.
+Added: The OLE portion of PALISADE-3, PALISADE-4 and the Repeat Dose Study remains ongoing.
+Added: In May 2026, we announced preliminary data from the ongoing real-world OLE portion of PALISADE-3.
+Added: Based on an analysis of subjects who elected to participate in the OLE portion of PALISADE-3 (a safety population of 341 subjects), as of a May 8, 2026 data cutoff, administration of 3.2 µg of fasedienol, taken as needed up to six times per day in real-world, anxiety-provoking situations in daily life for up to 12 months, was observed to be well-tolerated, with no new drug-related safety findings or trends identified.
+Added: Preliminary exploratory efficacy data over the first four months of treatment in the OLE portion of PALISADE-3 showed improvement over time on both the clinician-administered Liebowitz Social Anxiety Scale (LSAS) and the Social Phobia Inventory (SPIN).
+Added: Because the OLE portion of PALISADE-3 is open-label and uncontrolled, these exploratory efficacy observations are not based on a comparison to placebo and should be interpreted with caution.
+Added: We believe the preliminary safety and exploratory efficacy results of the OLE are generally consistent with the safety and efficacy results previously reported in the fasedienol open label, real-world Long-Term Safety Study completed in conjunction with PALISADE-1 and PALISADE-2, and in a prior randomized, double-blind, placebo-controlled multiple-dose Phase 2 crossover study of fasedienol, conducted in a real-world environment involving anxiety-provoking social and performance situations in daily life.
+Added: In June 2026, we announced that we achieved the minimum fasedienol patient exposures as recommended under ICH E1, the international regulatory standard governing safety database exposure recommendations for drugs intended for long-term treatment (chronic or repeated intermittent use for longer than 6 months) of non-life-threatening conditions.
+Added: As of May 31, 2026, we estimate that the fasedienol clinical development program now exceeds ICH E1 minimum recommendations with over 1,500 subjects receiving at least a single exposure to fasedienol, over 300 subjects with at least 6-months of exposure, and over 100 subjects with at least 12 months of exposure.
+Added: The 6-month and 12-month exposure numbers represent our estimate of the number of subjects who have completed the 6-month and 12-month visits in the fasedienol open-label safety studies.
+Added: These exposure estimates are expected to continue to increase to the extent they include subjects currently participating in the ongoing OLE portions of PALISADE-3, PALISADE-4 and the Repeat Dose Study.
+Added: Although we believe the minimum ICH E1 recommendations have been met, we have not yet aligned with the FDA on the specific patient exposure requirements to support a potential fasedienol NDA submission.
+Added: We believe PALISADE-4, if successful, together with the positive results from PALISADE-2 and confirmatory evidence from our overall fasedienol development program in SAD, including the Repeat Dose Study and OLE data, as well as confirmatory evidence we plan to generate based on FDA feedback to support the clinical meaningfulness of the duration and magnitude of effect of fasedienol, may establish substantial evidence of the effectiveness of fasedienol in support of a potential New Drug Application (NDA) submission for the acute treatment of SAD, although we have not discussed this plan with the FDA subsequent to receipt of topline results from the randomized portion of PALISADE-3.
+Added: As we move closer toward potential completion of Phase 3 development of fasedienol, we plan to seek further feedback from the FDA regarding a potential NDA submission.
+Added: We believe fasedienol has the potential to be the first FDA-approved acute treatment of SAD in adults, and may provide significant advantages relative to the current suboptimal standard of care for this highly prevalent and serious mental health disorder.
+Added: Overview of Vasomotor Symptoms (Hot Flashes) due to Menopause
+Added: Vasomotor symptoms (VMS), comprised of hot flashes and night sweats are the most common symptoms of the menopausal transition, affecting 60% - 80% of menopausal women in the U.S.
+Added: according to SWAN (Study of Women Across the Nation) and other published studies.
+Added: VMS can be described as a sudden, intense feeling of warmth spreading through the upper body and face, flushed appearance with red, blotchy skin, rapid heartbeat, and perspiration on the upper body.
+Added: Each episode typically lasts between one and five minutes and may be accompanied by sweating, chills, and anxiety.
+Added: Although there is individual variability in the frequency and severity of symptoms, VMS negatively impacts physical, emotional, social, and occupational well-being, and can significantly diminish the overall quality of life, mental health and work productivity for those who experience symptoms.
+Added: While there are FDA-approved therapies for the treatment of
+Added: moderate to severe VMS due to menopause, many women are unable to use current therapies due to contraindications and safety concerns, such as cardiovascular disorders, dementia, breast cancer, and liver toxicity.
+Added: Refisolone for the Treatment of Moderate to Severe Vasomotor Symptoms (Hot Flashes) due to Menopause
+Added: Refisolone is our non-hormonal, non-systemic, as-needed pherine product candidate under development for the treatment of moderate to severe VMS (hot flashes) due to menopause, and potentially for the treatment of additional women’s health-focused indications.
+Added: Refisolone’s proposed MOA is fundamentally differentiated from all currently approved treatments for VMS (hot flashes) due to menopause.
+Added: Administration of low microgram doses of refisolone appears to rapidly activate peripheral nasal chemosensory neurons that is proposed to modulate the nasal-limbic amygdala-hypothalamic depressed mood and thermoregulatory neurocircuits.
+Added: Notably, in vitro studies showed that refisolone had no observed engagement with hormonal receptors.
+Added: An in vivo study in mice showed no observed estrogenic and/or androgenic activity and no changes in weight of the uterus or seminal vesicles after intranasal administration.
+Added: Additionally, in an in vitro study refisolone did not exert observable effects on receptor targets with known abuse potential.
+Added: Furthermore, a clinical study in human volunteers showed no detectable refisolone in blood plasma after administration of 12.8 ug/day, indicating the non-systemic nature of refisolone's potential therapeutic benefit.
+Added: In a randomized, double-blind, placebo-controlled exploratory Phase 2A clinical study of refisolone conducted in Mexico and designed to explore the efficacy, safety, and tolerability of intranasal administration of refisolone for the management of menopausal hot flashes in women, refisolone produced a significant reduction in the daily number of hot flashes compared to placebo at the end of the first week of treatment, and the improvement was maintained through each treatment week until the end of the four consecutive week treatment period.
+Added: Refisolone was well-tolerated with no treatment-related serious adverse events (SAEs) reported, and the adverse event profiles were comparable between refisolone and placebo.
+Added: No subject discontinued participation in the study as a result of adverse events.
+Added: In April 2026, we announced that we received a “Study May Proceed” letter from the FDA under our U.S.
+Added: Investigational New Drug Application (IND) application for refisolone.
+Added: Our open IND enables us to pursue further Phase 2 clinical development of refisolone in the U.S.
+Added: for the treatment of moderate to severe VMS (hot flashes) due to menopause, building on the successful exploratory Phase 2A clinical study described above.
+Added: Overview of Premenstrual Dysphoric Disorder
+Added: According to the U.S.
+Added: National Institutes of Health (NIH), 5% to 8% of menarcheal (menstruating women) 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).
+Added: Like PMS, PMDD can cause bloating, breast tenderness, fatigue, and changes in sleep and eating habits but, distinctively, it can also cause extreme mood shifts that can disrupt daily life and damage relationships.
+Added: The cause of PMDD is not clearly understood, but it is thought that neurotransmitter systems may trigger PMDD.
+Added: Treatment of PMDD is aimed at preventing or minimizing symptomology.
+Added: Refisolone for Premenstrual Dysphoric Disorder
+Added: In an exploratory, randomized, double-blind, placebo-controlled Phase 2A clinical study of refisolone conducted in Mexico for management of the symptoms of PMDD in subjects with a regular menstrual cycle and at least a one-year history of PMDD, refisolone demonstrated a statistically significant improvement versus placebo in management of the symptoms of PMDD, including negative mood and physical and behavioral symptoms, using the subject-rated Penn Daily Symptom Report (DSR).
+Added: Refisolone was well-tolerated with no SAEs.
Overview of Major Depressive Disorder
Depression is a serious medical condition and a global public health concern that can arise at any time during a person's life.
−Removed: According to the World Health Organization (WHO), depression is the leading cause of disability worldwide, affecting over 250 million people.
−Removed: Statistics reported by the U.S.
−Removed: National Institute of Mental Health (NIMH) indicate that approximately 21 million adults in the U.S., or approximately 8.4% of all adults in the U.S., experienced at least one major depressive episode in 2020.
−Removed: While many individuals will experience a depressed mood at some point during their lifetime, major depressive disorder (MDD) is different.
+Added: According to the World Health Organization (WHO), depression affects over 300 million people worldwide.
+Added: National Institute of Mental Health (NIMH) reports that approximately 21 million adults in the U.S., or approximately 8.4% of all adults in the U.S., experienced at least one major depressive episode in 2020.
+Added: While many individuals will experience a depressive episode at some point during their lifetime, major depressive disorder (MDD) is different.
MDD is the chronic, pervasive feeling of utter unhappiness and suffering, which impairs daily functioning.
−Removed: During a typical depressive episode, an individual experiences depressed mood, loss of interest and enjoyment, and reduced energy leading to diminished activity and impaired daily functioning for at least two weeks and often much longer.
−Removed: 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.
+Added: 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
+Added: thinking, concentrating or making decisions, and thoughts of death or suicide and attempts at suicide.
MDD is the psychiatric diagnosis most commonly associated with suicide.
For many people, depression cannot be controlled for any length of time without treatment.
−Removed: However, approximately two out of every three people with depression do not experience adequate therapeutic benefits from their initial treatment with a standard antidepressant.
−Removed: Furthermore, the likelihood of achieving remission of depressive symptoms decreases with each successive treatment attempt.
−Removed: Even after multiple treatment attempts with current antidepressants, about one-third of individuals with depression still do not find a sufficiently effective therapy.
+Added: However, approximately two out of every three people who are treated for depression do not experience adequate therapeutic benefits from their initial treatment with a standard antidepressant.
+Added: Even after multiple treatment attempts, about one-third of treated individuals are unable to find a sufficiently effective therapy.
Inadequate response to current treatments is among the key reasons MDD is one of the leading public health concerns in the U.S., creating a significant unmet medical need for new agents with fundamentally differentiated MOAs and differentiated safety.
Itruvone for the Treatment of Major Depressive Disorder
−Removed: Itruvone is our investigational neurocircuitry-focused non-systemic pherine product candidate with transformative potential as a stand-alone treatment of MDD.
−Removed: Itruvone’s potential for rapid-onset activity in nasal chemosensory receptors at a low microgram-level dose without requiring systemic absorption or direct binding on neurons in the brain to achieve antidepressant effects, and its favorable safety data observed in all studies completed to date, is fundamentally differentiated from all current pharmacological therapies for depression.
−Removed: Unlike other antidepressants which rely on single or double-receptor occupancy in the brain, itruvone activates neural circuits that regulate the amygdala, hypothalamus, entorhinal area and hippocampus, prefrontal cortex, locus coeruleus, and raphe nucleus, all involved in the pathophysiology of depression.
−Removed: The scope of itruvone's neural circuit activation, and potential impact on the brain, appears, in studies completed to date, to be wider, faster and safer than can be achieved with current therapies targeting binding to any specific brain receptor.
−Removed: We believe non-systemic itruvone has the potential to treat MDD without causing the side effects and safety concerns that may be associated with current systemic antidepressant therapies, including, among others, drug-drug interactions, sexual side effects, sedation, weight gain and suicidal ideation.
−Removed: 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).
−Removed: 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.
−Removed: The trial was sponsored by Pherin Pharmaceuticals, Inc.
−Removed: (Pherin), which is
−Removed: now our wholly-owned subsidiary, and was conducted in Mexico prior to our acquisition of Pherin in February 2023.
+Added: Itruvone is our intranasal pherine product candidate under development for the treatment of MDD.
+Added: The FDA has granted fast track designation for development of itruvone for MDD.
+Added: Unlike other antidepressants which rely on single or double-receptor occupancy in the brain, itruvone's proposed MOA involves modulation of the nasal-limbic amygdala anhedonia and depressed mood neurocircuits.
+Added: The scope of itruvone's neural circuit activation, and potential impact on the brain, appears, in studies completed to date, to be faster and safer than can be achieved with current therapies targeting binding to any specific brain receptor.
+Added: We believe non-systemic itruvone has the potential to treat MDD without causing the side effects and safety concerns that may be associated with currently approved systemic antidepressant therapies, including, among others, drug-drug interactions, psychological side effects, sexual side effects, sedation, weight gain and suicidal ideation.
+Added: In a randomized, double-blind, placebo-controlled parallel design exploratory Phase 2A clinical trial of itruvone as a stand-alone treatment for MDD conducted in Mexico, itruvone reduced depressive symptoms as soon as one week based on the 17-item Hamilton Depression Scale (HAM-D-17) scores compared to placebo.
+Added: Itruvone was well-tolerated and did not cause psychological side effects (such as dissociation), sexual side effects, weight gain, or other safety concerns that may be associated with other approved pharmacological therapies for MDD.
Positive data from our June 2023 U.S.
−Removed: 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.
−Removed: Overall, itruvone was well-tolerated and continued to demonstrate the favorable safety data in all clinical trials completed to date.
−Removed: As a result, building on the positive results from Phase 2A clinical development of itruvone in MDD, we are currently planning for potential U.S.
−Removed: Phase 2B clinical development of itruvone under our U.S.
−Removed: IND as a novel, non-systemic stand-alone treatment for MDD.
−Removed: FDA has granted Fast Track designation for the investigation of itruvone for the treatment of MDD.
−Removed: Overview of Vasomotor Symptoms (Hot Flashes) due to Menopause
−Removed: Vasomotor symptoms (VMS), comprising of hot flashes and night sweats, are the most common symptoms of the menopausal transition, affecting 60% to 80% of menopausal women and approximately 40% of women in perimenopause.
−Removed: On average, hot flashes last seven to nine years and, for up to one-third of women, can last more than 10 years.
−Removed: VMS can be described as a sudden, intense feeling of warmth spreading through the upper body and face, flushed appearance with red, blotchy skin, rapid heartbeat, and perspiration on the upper body.
−Removed: Each episode typically lasts between one and five minutes and may be accompanied by sweating, chills, and anxiety.
−Removed: Although there is substantial individual variability in the frequency and severity of VMS, there is universal agreement that VMS negatively impacts physical, emotional, social, and occupational well-being, and can significantly diminish the overall quality of life and work productivity for those who experience them.
−Removed: VMS can cause new-onset sleep interruptions and deprivation, with night sweats commonly interrupting sleep and causing difficulty in returning to sleep.
−Removed: Such sleep problems are associated with reduced productivity and an increased risk of job loss for these affected individuals.
−Removed: VMS are also often accompanied by various comorbidities, including new onset anxiety, depression, and cognitive dysfunction, which can further exacerbate functional impairment.
−Removed: While there are FDA-approved therapies for the treatment of moderate to severe VMS, many women cannot take or choose not to take currently available hormonal and/or other systemic products due to contraindications and safety concerns, such as cardiovascular disorders, dementia, breast cancer, and liver toxicity.
−Removed: Treatment of VMS is complicated by fear of these safety risks associated with systemic hormonal therapy and the recently approved non-hormonal, neurokinin 3 receptor (NK3R) antagonist.
−Removed: PH80 for the Treatment of Vasomotor Symptoms (Hot Flashes) due to Menopause
−Removed: PH80 is our investigational non-hormonal, non-systemic, neurocircuitry-focused pherine product candidate with a novel, rapid-onset proposed MOA that is fundamentally differentiated from all currently approved treatments for VMS (hot flashes) due to menopause.
−Removed: With more than one million U.S.
−Removed: women entering menopause every year, the number of symptomatic women with VMS who could potentially benefit from a novel, non-hormonal, non-systemic, as-needed treatment such as PH80 is substantial.
−Removed: Rapid activation of peripheral nasal chemosensory neurons via self-administration of low microgram doses of PH80 rapidly stimulates a subgroup of neuromicrocircuits (glomeruli) in the olfactory bulbs (OBs) that are connected to the limbic amygdala and hypothalamus, which are involved in the regulation of the autonomic nervous system and thermoregulatory areas of the hypothalamus.
−Removed: Notably, in vitro studies show that PH80 does not engage steroid receptors;
−Removed: an in vivo study in mice showed no estrogenic and/or androgenic activity and no changes in weight of the uterus or seminal vesicles after intranasal administration.
−Removed: Additionally, an in vitro study has demonstrated that PH80 does not exert effects on receptor targets with known abuse potential.
−Removed: We are developing PH80 as a novel, non-hormonal, non-systemic, as-needed treatment of moderate to severe VMS (hot flashes) due to menopause, and potentially additional women’s health-focused indications.
−Removed: 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.
−Removed: In the study, PH80 (0.8 µg/50 µL) was self-administered by subjects intranasally, with two sprays in each nostril (total dose = 3.2µg) up to four times daily, as needed for four consecutive weeks.
−Removed: One additional dose was allowed at night if subjects were awakened by hot flashes.
−Removed: Through the course of the study, subjects recorded the number, severity, disruption in function, and sweating related to hot flashes.
−Removed: PH80 induced a significant reduction in the daily number of hot flashes compared to placebo at the end of the first week of treatment, and the improvement was maintained through each treatment week until the end of the treatment period.
−Removed: At baseline, subjects reported a mean daily number of hot flashes of 7.7 (PH80, n=18) and 8.0 (placebo, n=18).
−Removed: After one week of treatment, the number of hot flashes dropped to 2.8 (PH80) and 6.4 (placebo) (p<.001), and after four weeks of treatment, the number of hot flashes dropped to 1.5 (PH80) and 5.1 (placebo)
−Removed: PH80 treatment also significantly reduced the severity, disruption in function, and sweating related to hot flashes during the treatment period, as compared with placebo.
−Removed: PH80 was well-tolerated with no SAEs, and the adverse event profiles were comparable between PH80 and placebo.
−Removed: All 36 subjects completed four weeks of treatment and no subject discontinued participation in the study as a result of adverse events.
−Removed: We are currently conducting customary nonclinical manufacturing-related studies necessary to support our planned submission of our U.S.
−Removed: IND to facilitate further Phase 2 clinical development of PH80 in the U.S.
−Removed: as a novel non-hormonal, non-systemic treatment of moderate to severe VMS (hot flashes) due to menopause and potentially additional women’s health indications.
−Removed: Overview of Premenstrual Dysphoric Disorder
−Removed: 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).
−Removed: PMDD symptoms usually begin in the luteal phase (approximately seven to ten days before a person’s period starts) and continue for the first few days of the period.
−Removed: Like PMS, PMDD can cause bloating, breast tenderness, fatigue, and changes in sleep and eating habits, but distinctively, it can also cause extreme mood shifts that can disrupt daily life and damage relationships.
−Removed: The cause of PMDD is not clearly understood, but it is thought that neurotransmitter systems may trigger PMDD.
−Removed: Brain areas that regulate emotion and behavior are studded with receptors for estrogen, progesterone, and other sex hormones.
−Removed: These hormones affect the functioning of neurotransmitter systems that influence mood and thinking, possibly triggering PMDD.
−Removed: Treatment of PMDD is aimed at preventing or minimizing symptomology.
−Removed: PH80 for Premenstrual Dysphoric Disorder
−Removed: An exploratory Phase 2A clinical study of PH80 for management of the symptoms of PMDD, including negative mood and physical and behavioral symptoms, in subjects with a regular menstrual cycle and at least a one-year history of PMDD, was conducted by Pherin in a real-world setting in Mexico prior to our acquisition of Pherin in February 2023.
−Removed: In this randomized, double-blind, placebo-controlled exploratory Phase 2A study, PH80 demonstrated a statistically significant improvement versus placebo in management of the symptoms of PMDD, including negative mood and physical and behavioral symptoms.
−Removed: The initial study visit occurred after the onset of symptoms.
−Removed: All subjects were administered a placebo nasal spray, and those who showed no symptom improvement were eligible to return for the second visit, which occurred after the onset of symptoms during the next menstrual cycle.
−Removed: At the second study visit, subjects were randomized to receive a single dose of 0.9 µg PH80 nasal spray or placebo in the clinic.
−Removed: PH80 demonstrated statistically and clinically significant improvement versus placebo in symptoms of PMDD using the subject-rated Penn Daily Symptom Report (DSR) as early as Day 4 and continuing to Day 6 (p=0.008).
−Removed: PH80 also demonstrated statistically and clinically significant improvement versus placebo at Day 6 on the clinician-rated Premenstrual Tension Scale (PMTS) total score (p=0.006).
−Removed: PH80 was well-tolerated with no SAEs.
−Removed: The most common TEAE was headache, reported by 17% in the placebo group and 7% in the PH80 group.
−Removed: No other TEAE occurred more than once per subject.
+Added: Phase 1 trial of itruvone demonstrated that there were no reported treatment-related serious adverse events (SAEs) or discontinuations due to adverse events in the trial, consistent with the previous clinical study of itruvone.
+Added: We have an open IND for itruvone in the U.S.
+Added: and plan to pursue Phase 2 clinical development of itruvone in the U.S.
+Added: for the treatment of MDD, in an effort to build on the positive results from the previous exploratory Phase 2A clinical trial of itruvone in MDD described above.
Overview of Cognitive and Psychomotor Impairment due to Mental Fatigue
−Removed: Numerous disorders, such as shift work disorder, sleep apnea, and narcolepsy, can lead to debilitating sleep deprivation and mental fatigue.
−Removed: The prevalence of these disorders is high.
+Added: Numerous conditions and disorders, such as shift work disorder, sleep apnea, and narcolepsy, can lead to debilitating sleep deprivation and mental fatigue.
+Added: The prevalence of these conditions and disorders is high.
For example, moderate to severe sleep apnea affects approximately 20% of adult men and 10% of postmenopausal women.
−Removed: The potential consequences of mental fatigue from sleep deprivation are troubling, with higher rates of accidents and increased risk of dementia.
Individuals affected by mental fatigue require improved treatment options with a differentiated safety profile, one without the potential for abuse liability or negative and treatment-limiting side effects and safety concerns that may lead to self-treatment and subsequent substance use disorders.
−Removed: PH15 for Improvement of Cognitive and Psychomotor Impairment due to Mental Fatigue
−Removed: 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.
−Removed: 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
−Removed: cognition, without requiring systemic absorption or direct action on neurons in the brain.
−Removed: PH15 has demonstrated excellent safety data in all clinical trials completed to date.
−Removed: 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.
−Removed: 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.
−Removed: In the Phase 2A pilot study, ten participants were randomly administered PH15 (multiple 1.6 µg doses, total dose of 9.6 µg), placebo (nasal spray and oral), or caffeine (single 400 mg oral dose administered one hour before the session) in sequential sleep deprivation study sessions spaced one week apart.
−Removed: During each sleep deprivation session, participants received blinded treatments before the start of each of four testing periods, at 6:00 p.m., 9:00 p.m., midnight, and 3:00 a.m.
−Removed: The participants’ reaction times to both isochronous (regular interval) and stochastic (random interval) “flash” light stimuli were computer-measured during each testing period as participants responded to the luminous stimuli.
−Removed: During both isochronous and stochastic reaction time tests, administration of 1.6 µg PH15 nasal spray induced a significantly faster mean reaction time compared to placebo nasal spray across all time points (p<0.001).
−Removed: PH15 also demonstrated a statistically significant improvement in reaction time compared to oral caffeine (p<0.001) for both reaction time tests during the testing periods at midnight and 3:00 a.m.
−Removed: when subjects were most fatigued.
−Removed: PH15 was well-tolerated in this study, with no SAEs reported.
−Removed: The adverse event profiles of PH15 and placebo were comparable, with brief nasal itching in one PH15-dosed participant and three placebo-dosed subjects.
−Removed: Participants on oral caffeine, however, experienced palpitations, euphoria, dry mouth, stomachache, and polyuria.
−Removed: We are currently evaluating the potential Phase 2 development path forward for PH15 and the manufacturing, nonclinical and clinical program required to support submission of a U.S.
+Added: PH15 for Improvement of Psychomotor Impairment due to Mental Fatigue
+Added: PH15 is our intranasal pherine product candidate under development for the improvement of psychomotor impairment caused by mental fatigue.
+Added: PH15 is thought to target nasal receptors that modulate the nasal-entorhinal cortex area/hippocampus cognition neurocircuits, which are known to be associated with psychomotor activity and cognition, without requiring systemic absorption or direct action on neurons in the brain.
+Added: PH15 has demonstrated favorable safety data in all clinical trials completed to date and we believe PH15’s potential MOA is differentiated from the MOA of all currently approved treatments to improve psychomotor impairment caused by mental fatigue.
+Added: In a randomized, double-blind, placebo-controlled, crossover Phase 2A pilot study conducted in Mexico 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 and the number of errors on both isochronous and stochastic stimuli reactions tests as compared to placebo and caffeine in the sleep-deprived study participants.
+Added: PH15 was well-tolerated in this study, with no treatment-related SAEs reported.
+Added: The adverse event profiles of PH15 and placebo were comparable.
+Added: We are currently evaluating the potential Phase 2 development path forward for PH15 and the manufacturing, nonclinical and Phase 1 clinical programs required to support submission of a U.S.
IND to facilitate further potential Phase 2 development of PH15 in the U.S.
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Cachexia is associated with chronic diseases like cancer, AIDS, heart failure, chronic obstructive pulmonary disease, anorexia nervosa, multiple sclerosis, tuberculosis, and anemia.
−Removed: The current definition of cancer cachexia is a loss of 5% or more of body weight over the preceding six months, accompanied by any of a handful of other symptoms, including fatigue and reduced strength.
−Removed: According to the National Cancer Institute, cachexia is estimated to occur in up to 80% of people with advanced cancer, depending on the type of cancer and how well they respond to cancer treatment.
+Added: According to the National Cancer Institute (NCI), cachexia is estimated to occur in up to 80% of people with advanced cancer, depending on the type of cancer and how well they respond to cancer treatment.
Cachexia is thought to directly cause up to 30% of cancer deaths, often because of heart or respiratory failure related to muscle loss.
Maintaining nutritional support and alleviating cachexia has the potential to improve the underlying condition of cancer.
−Removed: Currently, there are no effective medical interventions or approved drugs proven to alleviate cachexia.
+Added: Currently, there are no medical interventions or approved drugs proven to optimally alleviate cachexia.
PH284 for Cancer Cachexia
−Removed: PH284 is our investigational pherine product candidate with a novel, rapid-onset, neurocircuitry-focused proposed MOA that is fundamentally differentiated from the MOA of all current treatments for the loss of appetite associated with chronic disorders, such as cancer or heart disease.
−Removed: PH284 is thought to act by regulating olfactory to mediobasal-hypothalamus neural circuits involved in appetite control.
−Removed: In a double-blind, placebo-controlled exploratory Phase 2A study designed to evaluate the efficacy, safety, and tolerability of intranasal administration of PH284 in female patients diagnosed with cachexia (induced by chronic loss of appetite) due to terminal cancer (n=40), PH284 (0.4 µg/50 µL) was administered intranasally, one spray in each nostril (total daily dose = 3.2µg), four times daily before meals (breakfast, mid-morning snack, lunch, and dinner).
−Removed: From Day 1 through Day 4, all subjects were administered placebo 30 minutes prior to each meal.
−Removed: Beginning on Day 5 through Day 11 subjects were randomized in a 1:1 fashion to receive either PH284 or placebo.
−Removed: Patients measured Subjective Feeling of Hunger (SFH) ten minutes before each meal.
−Removed: PH284, as compared to placebo, induced a cumulative effect on mean SFH scores, with scores increasing from breakfast to lunch and lunch to dinner throughout the treatment period.
−Removed: Specifically, prior to dinner on Day 7 of treatment, PH284 subjects reported a 71% improvement in SFH versus baseline, while placebo subjects reported a less
−Removed: than 1% improvement.
+Added: PH284 is our intranasal pherine product candidate with a novel, rapid-onset, neurocircuitry-focused proposed MOA that, we believe, is differentiated from all current treatments for the loss of appetite associated with chronic disorders, such as cancer or heart disease.
+Added: PH284 is thought to act by modulating the nasal-limbic amygdala-hypothalamic depressed mood and appetite control neurocircuits.
+Added: In a double-blind, placebo-controlled exploratory Phase 2A study in Mexico designed to evaluate the efficacy, safety, and tolerability of intranasal administration of PH284 in female patients diagnosed with cachexia (induced by chronic loss of appetite) due to terminal cancer, PH284 induced a cumulative effect on mean Subjective Feeling of Hunger (SFH) scores, as compared to placebo.
No unusual changes in body weight were observed in either the PH284 or placebo groups, though on average, there was a small gain in body weight for PH284 versus a small loss in placebo.
−Removed: PH284 demonstrated no serious adverse events, and adverse events reported for the PH284 group were similar to those reported in the placebo-treated group.
+Added: PH284 demonstrated no serious treatment-related adverse events, and adverse events reported for the PH284 group were similar to those reported in the placebo-treated group.
All the adverse events reported were attributed to the underlying medical condition (cancer) and were not deemed to be related to the administration of PH284 or placebo.
−Removed: PH284 has demonstrated an excellent safety profile in all clinical trials completed to date.
−Removed: This study of PH284 was sponsored by Pherin and conducted at the National Institute of Oncology and National Institute of Nutrition in Mexico City, Mexico prior to our acquisition of Pherin in February 2023.
−Removed: Vistagen is currently evaluating the potential path forward for PH284, including an assessment of the manufacturing, nonclinical and clinical program required to support a U.S.
−Removed: IND application for potential further Phase 2 clinical development of PH284 for the treatment of cancer cachexia or other appetite-related disorders.
+Added: We are currently evaluating the potential path forward for PH284, including an assessment of the manufacturing, nonclinical and Phase 1 clinical programs required to support a U.S.
+Added: IND application for potential further Phase 2 clinical development of PH284 in the U.S.
+Added: for the treatment of cancer cachexia or other appetite-related disorders.
AV-101 for NMDAR-related Neurological Disorders
−Removed: AV-101 (4-Cl-KYN) is our novel, oral prodrug candidate that targets the NMDAR (N-methyl-D-aspartate receptor), an ionotropic glutamate receptor in the brain.
+Added: AV-101 (4-Cl-KYN) is our oral prodrug candidate that targets the NMDAR (N-methyl-D-aspartate receptor), an ionotropic glutamate receptor in the brain.
Abnormal NMDAR function is associated with numerous neurological diseases and disorders.
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Unlike ketamine and many other NMDAR antagonists, 7-Cl-KYNA is not an ion channel blocker.
−Removed: In clinical and nonclinical testing completed to date, AV-101 has demonstrated good oral bioavailability and an excellent pharmacokinetic (PK) profile.
+Added: In clinical and nonclinical testing completed to date, AV-101 has demonstrated favorable oral bioavailability and pharmacokinetic results.
No binding of AV-101 or 7-Cl-KYNA to off-site targets was identified by an extensive receptor screening study.
−Removed: Moreover, in all clinical trials completed to date, AV-101 has been safe and very well-tolerated with no psychological side effects or safety concerns and no treatment-related SAEs that are often observed with classic channel-blocking NMDAR antagonists such as ketamine and amantadine.
−Removed: Nonclinical results also indicate that chronic administration of 4-Cl-KYN induces hippocampal neurogenesis, a hallmark of drugs that have anti-depressive effects, and increases endogenous levels of KYNA, which also is a functional NMDAR glycine site antagonist.
−Removed: Based on observations and findings from preclinical studies, we believe AV-101 has the potential to become a new oral treatment alternative for multiple neuroscience disorders, including levodopa-induced dyskinesia (LID) and neuropathic pain (NP) among others.
−Removed: We are currently assessing whether there is a path forward for potential collaborative Phase 2A clinical development of AV-101 for one or more additional neurological disorders involving the NMDAR receptor.
−Removed: FDA has granted Fast Track designation for the investigation of AV-101 for the treatment of neuropathic pain and for the adjunctive treatment of MDD.
+Added: Moreover, in all clinical trials completed to date, AV-101 has been well-tolerated with no psychological side effects or safety concerns and no treatment-related SAEs that are often observed with classic channel-blocking NMDAR antagonists such as ketamine and amantadine.
+Added: Nonclinical results also indicate that chronic administration of 4-Cl-KYN induces hippocampal neurogenesis and increases endogenous levels of KYNA, which also is a functional NMDAR glycine site antagonist.
+Added: Based on observations and findings from preclinical, animal model, and human clinical studies, we believe AV-101 has the potential to become an oral treatment alternative for certain neuroscience disorders involving the NMDAR, including potentially levodopa-induced dyskinesia ( LID ) and neuropathic pain ( NP ).
+Added: We do not anticipate further development and commercialization of AV-101 on our own.
+Added: We are currently assessing whether there is a path forward for potential third-party collaborative manufacturing, late-stage clinical development and commercialization of AV-101 for one or more neurological disorders involving the NMDAR.
+Added: The FDA has granted fast track designation for the investigation of AV-101 for the treatment of NP and for the adjunctive treatment of MDD.
Intellectual Property
−Removed: We strive to protect the proprietary know-how and technology that we believe is important to our business, including seeking and maintaining patents intended to cover our product candidates and related pharmaceutical compositions, their therapeutic methods of use, including treatment and prognostic methods, as well as processes for their manufacture, and any other aspects of our discoveries and inventions that are commercially important to the development of our business.
+Added: We strive to protect the proprietary know-how and technology that we believe is important to our business, including seeking and maintaining patents to the extent available for a particular product candidate, intended to cover their therapeutic methods of use, including treatment and prognostic methods, as well as processes for their manufacture, nasal spray devices for their administration and any other aspects of our discoveries and inventions that are commercially important to the development of our business.
We may also rely on trade secrets to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection.
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To protect our rights to our proprietary technology, we require all employees, as well as our external collaborators, consultants and CROs when feasible, to enter into agreements that require disclosure and assignment to us of ideas, developments, discoveries and inventions made by these employees, consultants, and CROs in the course of their service to us.
−Removed: We plan to continue to expand our intellectual property portfolio by filing patent applications related to pharmaceutical compositions, methods of use, including treatment and patient selection, formulations, nasal administration devices, and manufacturing processes created or identified from the ongoing development of our product candidates.
+Added: We plan to continue to expand our intellectual property portfolio by filing patent applications to the extent available for a particular product candidate related to methods of use, including treatment and patient selection, formulations, nasal administration devices, and manufacturing processes created or identified from the ongoing development of our product candidates.
We own granted patents and pending patent applications in the U.S.
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The granted U.S.
−Removed: 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.
+Added: patents relate to the use of fasedienol for the acute treatment of SAD and nominally expired or will in 2025 or 2028 and foreign patents which will nominally expire in 2026, subject to patent term extensions that may be available in the U.S.
and in certain foreign countries.
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and certain foreign countries.
−Removed: PH80 for the Treatment of Vasomotor Symptoms (Hot Flashes) Due to Menopause and Other Indications
+Added: Refisolone for the Treatment of Vasomotor Symptoms (Hot Flashes) Due to Menopause and Other Indications
The granted U.S.
−Removed: 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.
+Added: and foreign patents and corresponding pending foreign patent applications relate to the use of refisolone to treat VMS (hot flashes) due to menopause.
Patents that have been or may yet be granted will expire in 2029.
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or foreign countries.
−Removed: However, w e expect regulatory and data exclusivity will be available upon product approval of PH80 in the U.S.
+Added: However, we expect regulatory and data exclusivity will be available upon product approval of refisolone in the U.S.
and certain foreign countries.
−Removed: We filed a non-provisional U.S.
−Removed: national phase patent application and a Patent Cooperation Treaty (PCT) patent application relating to the use of PH80 to treat dysmenorrhea in April 2025.
+Added: Other granted U.S.
+Added: and foreign patents and corresponding pending foreign patent applications relate to the use of refisolone to treat migraines.
Patents that may be granted on such patent applications nominally will expire in 2040, subject to patent term extensions that may be available in the U.S.
and certain foreign countries.
−Removed: We expect regulatory and data exclusivity will be available upon approval of PH80 for this indication in the U.S.
+Added: We expect regulatory and data exclusivity will be available should refisolone be approved for the treatment migraines in the U.S.
and certain foreign countries.
+Added: We also have patent applications pending in the U.S.
+Added: and certain foreign countries relating to the use of refisolone to treat dysmenorrhea.
+Added: Patents that may be granted on such patent applications nominally will expire in 2045, subject to patent
+Added: term extensions that may be available in the U.S.
+Added: and certain foreign countries.
+Added: We expect regulatory and data exclusivity will be available should refisolone be approved for the treatment of dysmenorrhea in the U.S.
+Added: and certain foreign countries.
PH15 for the Improvement of Psychomotor and Cognitive Impairment due to Mental Fatigue
−Removed: We filed a non-provisional U.S.
−Removed: national phase patent application and a PCT patent application relating to the use of PH15 to improve psychomotor and cognitive impairment due to mental fatigue in 2024.
+Added: We have patent applications filed in 2024 pending in the U.S.
+Added: and certain foreign countries relating to the use of PH15 to improve psychomotor and cognitive impairment due to mental fatigue.
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.
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Nasal Spray Device for Administration of Pherines
−Removed: We filed a non-provisional U.S.
−Removed: national phase patent application and a PCT patent application relating to nasal spray devices intended to improve the administration of pherines (including, for example, fasedienol, itruvone, PH80, and PH15 discussed above) in April 2025.
+Added: We have patent applications pending in the U.S.
+Added: and certain foreign countries relating to nasal spray devices intended to improve the administration of pherines (including, for example, fasedienol, itruvone, refisolone, and PH15 discussed above) and the combination of the nasal spray device with these pherine product candidates.
Patents that may be granted on such patent applications nominally will expire in 2045, subject to patent term extensions that may be available in the U.S.
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patent can be lengthened by patent term adjustment, in case of certain administrative delays at the U.S.
−Removed: Patent and Trademark Office (PTO).
+Added: Patent and Trademark Office (U.S.
In some cases, the term of a U.S.
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In the future, if circumstances permit, we intend to apply for extension or restoration of patent term for our applicable patents, if any, to extend patent life beyond their nominal expiration dates depending on the length of the clinical trials and other factors that affect the filing date of the relevant NDA.
−Removed: In the future, if and when our pharmaceutical products receive FDA approval, we expect to apply for available patent term extensions on patents related to those products, their methods of use, or methods of manufacture.
+Added: In the future, if and when our pharmaceutical
+Added: products receive FDA approval, we expect to apply for available patent term extensions on patents related to those products, their methods of use, or methods of manufacture.
Some foreign jurisdictions, including various countries in Europe and Japan, have similar patent term extension provisions, which allow for the extension of the term of a patent that covers a drug approved by the applicable foreign regulatory agency.
−Removed: Data Exclusivity
−Removed: Some of our products may also be entitled to certain data exclusivity (that is not patent-related) under the Federal Food, Drug and Cosmetic Act (FDCA) and its related regulations.
−Removed: The FDCA provides a five-year period of non-patent data exclusivity within the U.S.
−Removed: to the first applicant to obtain approval for an NDA for a new chemical entity (NCE).
−Removed: An NCE is a new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule responsible for the pharmacological action of the drug substance.
−Removed: During the data exclusivity period, an abbreviated NDA (ANDA), or a 505(b)(2) NDA submitted by another company may not be approved by the FDA for another drug containing the same active moiety, regardless of whether the drug is intended for the same indication as the original innovator drug or for another indication, where the applicant does not own or have a legal right of reference to all the data that served as the basis of granting the original NDA.
−Removed: However, an ANDA or a 505(b)(2) NDA application may be submitted to the FDA for evaluation after four years from the original NDA approval if the innovator NDA holder does not have a patent covering the product listed with the FDA Orange Book or if the application contains a certification of patent invalidity or non-infringement to one of the patents listed with the FDA Orange Book.
−Removed: The FDCA also provides three years of data exclusivity for a full NDA, or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example, for new indications, dosages or strengths of an existing drug.
−Removed: Three-year exclusivity prevents the FDA from approving ANDAs and 505(b)(2) applications that rely on the information that served as the basis of granting the new full or supplemental NDA.
−Removed: This three-year exclusivity covers only the modification for which the drug received approval on the basis of the new clinical investigations and does not prohibit the FDA from approving ANDAs for drugs containing the active moiety for the original indication or condition of use.
−Removed: Five-year and three-year exclusivity will not delay the submission or approval of a full NDA.
−Removed: 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
13 unchanged sentences
In particular, we retain third parties for certain accounting, legal, manufacturing, nonclinical development, clinical development, and regulatory affairs support.
−Removed: We have entered into, and plan to seek multiple additional global and regional strategic relationships focused on the development and/or commercialization of our product candidates in key pharmaceutical markets in the U.S.
+Added: We have previously entered into, and may continue to seek multiple additional global and regional strategic relationships focused on the development and/or commercialization of our product candidates in key pharmaceutical markets in the U.S.
and worldwide.
−Removed: Commercial Agreements
−Removed: We have customary clinical supply agreements with multiple contract development and manufacturing organizations (CDMOs) and customary agreements with multiple CROs to assist us with the advancement and management of our nonclinical (including manufacturing) and clinical development programs.
−Removed: Each of our commercial agreements is non‑exclusive, and we have no material contractual obligations under such agreements, except to the extent we order supplies or request services to be performed under specific work orders that we generate with such third parties from time to time.
+Added: Commercial Supply Agreements
+Added: We engage contract development and manufacturing organizations (CDMOs) to manufacture supplies for our nonclinical and clinical development programs, and contract research organizations (CROs) to assist us with the advancement and management of our nonclinical and clinical development programs.
+Added: We do not currently have long-term or exclusive supply agreements with any of our CDMOs, and we obtain manufacturing services on a purchase order or work order basis.
+Added: Similarly, our agreements with CROs are non-exclusive.
+Added: We have no material contractual purchase obligations under these arrangements, except to the extent we order supplies or request services under specific work orders that we generate with these third parties from time to time.
+Added: We plan to negotiate a commercial supply agreement with one or more of our current CDMOs, or with a new CDMO following successful process transfer, to support potential commercialization of our product candidates, if approved.
Material License Agreements
7 unchanged sentences
Under the terms of the AffaMed Agreement, we received an upfront payment of $5.0 million in August 2020.
−Removed: We may also receive up to an additional $172 million in milestone payments upon AffaMed’s achievement of certain developmental, regulatory and sales milestone events related to fasedienol.
+Added: We may also receive additional milestone payments upon AffaMed’s achievement of certain developmental, regulatory and sales milestone events related to fasedienol.
In addition, we are entitled to receive certain royalties on net sales, if any, of fasedienol in the Territory following receipt of any required regulatory approval.
2 unchanged sentences
AffaMed is responsible for all costs related to developing, obtaining regulatory approval of and commercializing fasedienol in the Territory.
−Removed: A joint development committee has been established between the Company and AffaMed to coordinate and review the development, manufacturing and commercialization plans with respect to fasedienol in the Territory.
+Added: A joint development committee was established between the Company and AffaMed to coordinate and review the development, manufacturing and commercialization plans with respect to fasedienol in the Territory.
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.
2 unchanged sentences
(Fuji Pharma), a Tokyo Stock Exchange-listed, Japan-based pharmaceutical company.
−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 a potential exclusive license agreement, to develop and commercialize our PH80 product candidate in Japan (the Potential Definitive Agreement).
−Removed: The Negotiation Agreement provides for an exclusive negotiation period beginning on the date of formal written notice being received by Fuji Pharma that we have selected a contract development and manufacturing organization to conduct certain toxicology studies for the product candidate (Payment Event), and terminating on the later to occur of (i) fourteen (14) months from the date of the Payment Event or (ii) ninety (90) days from the date that the FDA accepts an IND application for PH80 for the treatment of vasomotor symptoms (hot flashes) due to menopause (Exclusive Negotiation Period).
+Added: Pursuant to the terms and conditions of the Negotiation Agreement, we agreed, for a limited period of time, to negotiate exclusively with Fuji Pharma a potential exclusive license agreement, to develop and commercialize refisolone in Japan (the Potential Definitive Agreement).
+Added: The Negotiation Agreement provides for an exclusive negotiation period beginning on the date of formal written notice being received by Fuji Pharma that we have selected a CDMO to conduct certain toxicology studies for the product candidate (Payment Event), and terminating on the later to occur of (i) fourteen (14) months from the date of the Payment Event or (ii) ninety (90) days from the date that the FDA accepts an IND application for refisolone for the treatment of vasomotor symptoms (hot flashes) due to menopause (Exclusive Negotiation Period).
+Added: Following the receipt of the Study May Proceed letter from the FDA under our U.S.
+Added: IND for refisolone, we expect the Exclusive Negotiation Period will end on or about June 20, 2026.
As consideration for the Exclusive Negotiation Period, we received from Fuji Pharma a payment of $1.5 million (Purchase Price).
2 unchanged sentences
Manufacturing and Supply
−Removed: Manufacturing of the drug substance and drug product for our product candidates is performed by contract development and manufacturing organizations (CDMOs) who must comply with current good manufacturing practice (cGMP) regulations.
−Removed: Our product candidates are comprised of synthetic small molecules that are manufactured through a series of organic chemistry steps starting with commercially available organic chemical raw materials.
−Removed: 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.
−Removed: 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.
−Removed: We conduct periodic quality audits of each of the CDMO’s facilities to ensure that they are fully compliant with cGMPs.
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: We plan to mitigate potential commercial supply risks for any products that are approved in the future through inventory management and through exploring additional back-up manufacturers, both in the U.S.
−Removed: and outside the U.S., to provide drug substance and/or drug product.
+Added: Manufacturing of our pherine drug substances and drug product is performed by CDMOs who must comply with current good manufacturing practice (cGMP) regulations governed by the FDA.
+Added: Our pherine drug substances are synthetic small molecules that are manufactured through a series of chemical reactions using key starting materials and/or with commercially available raw materials necessary to complete the chemical reactions.
+Added: 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 for nonclinical, clinical or commercial use.
+Added: We conduct manufacturing and analytical testing activities at various different CDMOs outlined by individual project scopes of work to supply all of our nonclinical and clinical trial needs.
+Added: We conduct periodic quality audits on all of the CDMO’s facilities to ensure that their quality systems are fully compliant with cGMPs.
+Added: We believe that all of our existing CDMOs are, or will be, capable of providing sufficient quantities of both drug substances and drug products to meet our projected needs.
+Added: New CDMOs may be added to our supply chain strategy in t he future to supplement and/or replace existing CDMO to ensure that our nonclinical, clinical and, subject to NDA approval, commercial manufacturing and testing needs are satisfied.
+Added: By design, we do not currently have any supply agreements in place with any CDMOs, for either long-term supply or redundant supply of our pherine drug substances or drug products If our pherine drug products are approved for commercial distribution, we intend to execute long-term commercial supply agreement(s) with our CDMOs to manufacture future commercial supplies.
+Added: We plan to mitigate potential commercial supply risks for any of our products that are approved in the future through inventory management and through exploring additional back-up manufacturers, both in the U.S.
+Added: and outside the U.S., to diversify our drug substance and/or drug product supply chains.
Our industry is highly competitive and subject to rapid and significant technological change.
The large size and expanding scope of the neuroscience markets, especially the high unmet need in large and growing global markets for anxiety and depression disorders, make them attractive therapeutic areas for biopharmaceutical businesses.
−Removed: While we believe that our employees and consultants, scientific knowledge, technology, and development experience provide us with competitive
−Removed: 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.
+Added: 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.
Several of these entities have robust drug pipelines, readily available capital, and large and established research and development and commercial organizations.
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Currently there is no FDA-approved acute treatment of SAD, and we are aware of no company developing a potential acute treatment of SAD that is a nasal spray and involves the same neurocircuitry-focused MOA as fasedienol.
−Removed: 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.
−Removed: 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.
+Added: We are aware of companies that are or may be developing therapies targeting acute treatment in the SAD market, including, among others, Vanda Pharmaceuticals, Tonix Pharmaceuticals, Sensorium Therapeutics, Engrail Therapeutics, and others.
+Added: 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 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.
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.
−Removed: Cognitive behavioral therapy is also an important treatment approach to SAD that may be used along with or instead of pharmacological treatments, including antidepressants, benzodiazepines, beta blockers, fasedienol and other drug candidates in clinical development.
+Added: Cognitive behavioral therapy is also an important treatment approach to SAD that may be used along with or instead of pharmacological treatments, including antidepressants, benzodiazepines, beta blockers and potentially fasedienol or other drug candidates in clinical development .
Major Depressive Disorder
2 unchanged sentences
fluoxetine (Prozac), previously marketed by Eli Lilly and Company;
−Removed: sertraline (Zoloft) and venlaxafine (Effexor), both previously marketed by Pfizer, Inc.;
+Added: sertraline (Zoloft) and venlafaxine (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.
Treatments may also include currently marketed proprietary branded medications indicated for MDD such as:
−Removed: Trintellix, which is marketed by Takeda Pharmaceuticals America, Inc and H.
+Added: Trintellix, which is marketed by Takeda Pharmaceuticals America, Inc.
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.
−Removed: 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.
+Added: 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, Definium Therapeutics , Xenon Pharmaceuticals, Johnson & Johnson, Usona Institute, Neumora Therapeutics, Boehringer Ingelheim, Syndeio Biosciences, Suven Life Sciences, GH Research, Draig Therapeutics, HMNC Brain Health, and Sirtsei Pharmaceuticals.
Additionally, with respect to MDD, we expect that itruvone will have to compete with a variety of non-pharmacological alternatives for treatment of MDD, such as psychotherapy and electroconvulsive therapy.
+Added: Psychedelic and rapid-acting neuropsychiatric therapies for depression are advancing in clinical development, including programs targeting glutamatergic, neuroplasticity, and broader neuromodulatory pathways.
+Added: These development candidates are being advanced by companies such as Compass Pathways, Otsuka Pharmaceutical (through its acquisition of Transcend Therapeutics), and AbbVie (through its acquisition of Gilgamesh Pharmaceuticals), among others.
+Added: These therapies are being developed based on the potential for rapid onset of antidepressant activity, with some patients potentially experiencing meaningful improvement in depressive symptoms within hours to days.
+Added: Many of these programs require supervised dosing sessions in controlled clinical settings, differentiating them from traditional chronic outpatient antidepressant therapies.
+Added: As a result, we expect these therapies to be positioned primarily for treatment-resistant depression (TRD) and other difficult-to-treat patient populations.
+Added: We will continue to monitor the advancement of these development candidates and evaluate their potential impact on the depression treatment landscape as they advance through development and potentially enter the U.S.
+Added: and global markets.
Vasomotor Symptoms (hot flashes) due to Menopause
−Removed: 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.
+Added: 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, Lynkuet, marketed by Bayer.
+Added: Additional companies with potential products in development for VMS include Gedeon Richter, Changchun, AbCellera, Noema Pharma, Tioga Pharma, Hansoh BioMedical.
+Added: The VMS market continues to evolve following the FDA’s removal of the boxed warning from certain estrogen-based therapies in the first quarter of 2026, contributing to broader re-evaluation of hormone replacement therapy (HRT) risk perceptions among patients and prescribing physicians.
+Added: The market remains open and in strong need for differentiated non-hormonal options due to persistent concerns around systemic hormone exposure, contraindications, tolerability, and patient preference.
+Added: We continue to monitor the development and commercial activity as the VMS competitive market evolves and advances.
Other Indications
6 unchanged sentences
FDA Regulation
−Removed: In the U.S., the FDA regulates drugs under the FDCA and its implementing regulations.
+Added: In the U.S., the FDA regulates drugs under the Federal Food, Drug and Cosmetic Act (FDCA) and its implementing regulations.
The process required by the FDA before product candidates may be marketed in the U.S.
1 unchanged sentence
• completion of preclinical laboratory tests, animal studies, and formulation studies in compliance with the FDA’s Good Laboratory Practice (GLP) regulations;
−Removed: • submission to the FDA of an IND, which must become effective before human clinical trials may begin;
+Added: • submission to the FDA of an IND application, which must become effective before human clinical trials may begin;
• approval by an independent Institutional Review Board (IRB) or ethics committee for each clinical site, or through a centralized process, before each trial may be initiated;
• performance of adequate and well‑controlled human clinical trials in accordance with Good Clinical Practice regulations (GCPs) to evaluate the safety and efficacy of the product candidate for its intended use;
−Removed: • compilation of required information and submission to the FDA of a NDA after completion of pivotal clinical trials;
+Added: • compilation of required information and submission to the FDA of a New Drug Application (NDA) after completion of pivotal clinical trial(s);
• satisfactory completion of an FDA advisory committee review, if applicable;
−Removed: • satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the product candidate is produced to assess compliance with cGMPs, and to assure that the facilities, methods, and controls are adequate to preserve the drug candidate’s identity, strength, quality, and purity;
+Added: • satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the product candidate is produced to assess compliance with current cGMPs, and to assure that the facilities, methods, and controls are adequate to preserve the drug candidate’s identity, strength, quality, and purity;
• satisfactory completion of potential FDA inspection of selected clinical investigation sites to assess compliance with GCPs;
9 unchanged sentences
In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin.
−Removed: 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
−Removed: continue until the FDA notifies the IND sponsor that the hold has been lifted.
+Added: Clinical holds also may be imposed by the FDA at any time before or during trials due to safety
+Added: 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.
As a result, submission of an IND may not result in FDA authorization to commence a clinical trial.
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Phase 3 trials are intended to establish the overall risk‑benefit profile of the product, and to provide adequate information for the labeling of the product.
−Removed: Typically, two successful Phase 3 trials are required by the FDA for product approval.
The FDA may also require, or companies may conduct, additional clinical trials for the same indication after a product is approved.
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The deficiencies identified may be minor, for example, requiring labeling changes, or major, for example, requiring the sponsor to conduct additional clinical trials.
−Removed: If a CRL is issued, the applicant may either resubmit the NDA, addressing all of the deficiencies identified in the letter;
−Removed: withdraw the application;
+Added: If a CRL is issued, the applicant may either resubmit the NDA, addressing all of the deficiencies identified in the CLR;
+Added: withdraw the NDA;
or request an opportunity for a hearing.
If the sponsor resubmits the NDA, the FDA has the goal of reviewing 90% of resubmitted applications in either two or six months (from receipt) depending on the content of the resubmission.
−Removed: Even with the submission of additional information, the FDA ultimately may decide that the resubmitted application does not satisfy the regulatory criteria for approval.
+Added: Even with the submission of additional information, the FDA ultimately may decide that the resubmitted NDA does not satisfy the regulatory criteria for approval.
If and when the issues identified in a CRL have been addressed and resolved to the FDA’s satisfaction, the FDA may issue an approval letter.
25 unchanged sentences
Orphan designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.
−Removed: If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications to market the same drug for the same disease or condition for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity or inability to manufacture the product in sufficient quantities.
+Added: If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications to market the same drug for the same approved indication or use within the relevant disease or condition for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity within the relevant indication or use or inability to manufacture the product in sufficient quantities to meet the needs relating to the approved indication or use.
The designation of such drug also entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers.
−Removed: However, competitors may receive approval of different products for the disease or condition for which the orphan product has exclusivity or obtain approval for the same product but for a different disease or condition for which the orphan product has exclusivity.
+Added: However, competitors may receive approval of different products for the same indication or use for which the orphan product has exclusivity or obtain approval for the same product but for a different indication or use for which the orphan product has exclusivity.
In addition, if an orphan designated product receives marketing approval for a disease or condition broader than what is designated, it may not be entitled to orphan exclusivity.
2 unchanged sentences
These products are known as combination products.
−Removed: Under the FDCA and its implementing regulations, the FDA is charged with assigning a center with primary jurisdiction, or a lead center, for review of a combination product.
+Added: Under the Federal Food, Drug and Cosmetic Act (FDCA) and its implementing regulations, the FDA is charged with assigning a center with primary jurisdiction, or a lead center, for review of a combination product.
The designation of a lead center generally eliminates the need to receive approvals from more than one FDA component for combination products, although it does not preclude consultations by the lead center with other components of the FDA.
9 unchanged sentences
certain electronic records and signatures;
−Removed: licensure in certain states for the manufacturing and distribution of drug products;
+Added: licensure in certain states for the manufacturing and
+Added: 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.
27 unchanged sentences
An NCE is a drug that contains no active moiety that has been approved by the FDA in any other NDA.
−Removed: 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
−Removed: molecule, responsible for the therapeutic activity of the drug substance.
−Removed: During the NCE exclusivity period, the FDA may not accept for review an ANDA or an NDA submitted under Section 505(b)(2) NDA that contains the previously approved active moiety.
+Added: An active moiety
+Added: 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.
+Added: During the NCE exclusivity period, the FDA may not accept for review an Abbreviated New Drug Application (ANDA) or an NDA submitted under Section 505(b)(2) NDA that contains the previously approved active moiety.
An ANDA or 505(b)(2) application, however, may be submitted one year before NCE exclusivity expires if the application contains a certification of patent invalidity or non-infringement to one of the patents listed with the FDA by the innovator NDA holder.
3 unchanged sentences
NCE and NCI exclusivities will not delay the submission or approval of a full NDA;
−Removed: 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.
+Added: however, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all preclinical studies and adequate and well‑controlled clinical trials necessary to demonstrate safety and efficacy.
Pediatric exclusivity is a regulatory exclusivity in the United States that provides for the attachment of an additional six months of marketing protection to the term of any existing regulatory and statutory exclusivity, including the non‑patent exclusivity periods described above as well as applicable patent terms.
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Fraud and Abuse, and Transparency Laws and Regulations
−Removed: Following product approval, our business activities, including but not limited to research, sales, promotion, marketing, distribution, medical education, sponsorships, relationships with prescribers and other referral sources, and other activities will be subject to regulation by numerous federal and state regulatory and law enforcement authorities in the United States in addition to the FDA, including potentially the Department of Justice, the Department of Health and Human Services and its various divisions (including the Centers for Medicare & Medicaid Services (CMS), the Office of Inspector General (OIG), and the Health Resources and Services Administration (HRSA)), the Department of Veterans Affairs (VA), the Department of Defense (DOD), and certain state and local governmental authorities.
+Added: Following product approval, our business activities, including but not limited to research, sales, promotion, marketing, distribution, medical education, sponsorships, relationships with prescribers and other referral sources, and other activities will be subject to regulation by numerous federal and state regulatory and law enforcement authorities in the United States in addition to the FDA, including the Department of Justice, the Department of Health and Human Services and its various divisions (including the Centers for Medicare & Medicaid Services (CMS), the Office of Inspector General (OIG), and the Health Resources and Services Administration (HRSA)), the Department of Veterans Affairs (VA), the Department of Defense (DOD), and certain state and local governmental authorities.
Sales, marketing and business arrangements in the healthcare industry are also subject to extensive laws and regulations intended to prevent fraud, kickbacks, self-dealing and other abusive practices.
23 unchanged sentences
The federal Health Insurance Portability and Accountability Act of 1996 (HIPAA) also created federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud or to obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, a healthcare benefit program, regardless of whether the payer is public or private, knowingly and willfully embezzling or stealing from a health care benefit program, willfully obstructing a criminal investigation of a health care offense, and knowingly and willfully falsifying, concealing, or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items, or services relating to healthcare matters.
−Removed: In addition, similar to the Anti-Kickback Statute, a person or entity no longer needs to have actual knowledge of the statute or specific intent to violate it.
+Added: In addition, similar to the 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 civil monetary penalties statute is another potential statute under which biopharmaceutical companies may be subject to enforcement.
7 unchanged sentences
Such enforcement actions would prohibit the manufacturer from engaging those individuals, which could adversely affect operations, and could result in significant reputational harm.
−Removed: 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
−Removed: 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.
+Added: 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.
Many states have also adopted laws similar to each of the above federal laws, which may be broader in scope and apply to items or services reimbursed by any third‑party payer, including commercial insurers, and some have transparency laws that require reporting price increases and related information.
21 unchanged sentences
Therefore, coverage and reimbursement can differ significantly from payor to payor and health care provider to health care provider.
−Removed: 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
−Removed: new products to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.
+Added: As a result, the coverage determination
+Added: 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.
There may also be significant delays in obtaining coverage and reimbursement for newly approved products, and coverage may be more limited than the purposes for which the product is approved by the FDA.
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Since its enactment, there have been executive, judicial and Congressional challenges to certain aspects of the ACA.
−Removed: On June 17, 2021, the U.S.
−Removed: Supreme Court dismissed the most recent judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA.
−Removed: Thus, the ACA will remain in place in its current form.
In addition, other legislative and regulatory changes have been proposed and adopted in the U.S.
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In addition, the American Taxpayer Relief Act of 2012, which further reduced Medicare payments to several providers, including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.
−Removed: On March 11, 2021, the American Rescue Plan Act of 2021 was signed into law, which eliminated the statutory Medicaid drug rebate cap, beginning January 1, 2024.
−Removed: The rebate was previously capped at 100% of a drug’s AMP.
−Removed: Most recently, on August 16, 2022, President Biden signed the Inflation Reduction Act of 2022 (the IRA) into law.
+Added: On March 11, 2021, the American Rescue Plan Act of 2021 was signed into law, which eliminated the statutory cap on manufacturers’ Medicaid drug rebate liability, beginning January 1, 2024.
+Added: The rebate was previously capped at 100% of a drug’s average manufacturer's price.
+Added: On August 16, 2022, President Biden signed the Inflation Reduction Act of 2022 (the IRA) into law.
Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare, with prices that can be negotiated subject to a cap (with resulting prices for the initial ten drugs first effective in 2026);
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and replaces the Medicare Part D coverage gap discount program with a new discounting program (beginning in 2025).
+Added: CMS has published the negotiated prices for the initial ten drugs, which went into effect in January 2026, and the subsequent 15 drugs, which will first be effective in 2027.
+Added: CMS has also published the next set of 15 drugs that will be subject to negotiation.
The IRA permits the Secretary of the Department of Health and Human Services (HHS) to implement many of these provisions through guidance, as opposed to regulation, for the initial years.
−Removed: HHS has issued guidance, and is expected to continue to issue guidance, even while multiple lawsuits challenging the IRA negotiation requirement remain pending.
+Added: HHS has issued guidance, and is expected to continue to issue guidance, even while multiple lawsuits challenging the IRA drug price negotiation requirement remain pending.
The impact of the IRA on the pharmaceutical industry and our business cannot yet be fully determined but is likely to be significant.
However, because our anticipated patient demographic for our product candidates, if approved, is unlikely to include a significant number of Medicare beneficiaries, we do not expect that the IRA will directly impact our ability to commercialize our drug candidates.
+Added: The One Big Beautiful Bill Act, which was enacted in July 2025, imposes significant reductions in the funding of the Medicaid program.
+Added: Such reductions are expected to decrease the number of persons enrolled in Medicaid and reduce the services covered by Medicaid, which could adversely affect our sales of any product candidate that we commercialize.
+Added: The current administration is also pursuing a two-fold strategy to reduce drug costs in the U.S.
+Added: On the one hand, the current U.S.
+Added: President threatened to impose significant tariffs on pharmaceutical manufacturers that do not adopt pricing policies such as most favored nation pricing, which would tie the price for drugs in the U.S.
+Added: to the lowest price in a group of other countries.
+Added: In response, multiple manufacturers entered into confidential pricing agreements with the federal government.
+Added: Subsequently, in April 2026, the current administration issued a proclamation imposing tariffs under Section 232 of the Trade Expansion Act on imports of brand pharmaceuticals, biologics and associated pharmaceutical ingredients, beginning July 31, 2026.
+Added: Exempted from these tariffs, among others, are companies that have executed or are negotiating agreements with the federal government regarding most favored nation pricing and onshoring of production and research and development.
+Added: On the other hand, the current administration is also pursuing traditional regulatory pathways to impose drug pricing policies and published two proposed regulations in December 2025, referred to as GLOBE and GUARD.
+Added: If finalized, these regulations would implement mandatory payment models under which manufacturers of eligible drugs would be required to pay rebates to the federal government on a portion of the units of their drugs that are reimbursed by Medicare, with the rebate amount based on most favored nation pricing.
+Added: While the impact of the GLOBE and GUARD proposed regulations, if finalized, cannot yet be determined, it is likely to be significant.
+Added: Even regulatory proposals or executive actions that are ultimately deemed unlawful could impact the U.S.
+Added: pharmaceutical sector and potentially our business.
+Added: Moreover, pharmaceutical pricing and marketing has long been the subject of considerable discussion in Congress and among policymakers, and it is possible that Congress could enact additional laws that further affect the pharmaceutical industry.
At the state level, individual states in the U.S.
have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
−Removed: Some third-party payors also require pre-
−Removed: approval of coverage for new or innovative devices or therapies before they will reimburse healthcare providers that use such therapies.
+Added: 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.
We expect that these initiatives, as well as other healthcare reform measures that may be adopted in the future, as well as the trend toward managed healthcare and increasing influence of managed care organizations, may result in more rigorous coverage criteria and lower reimbursement, and in additional downward pressure on the price that we receive for any approved product.
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For example, in the European Union (EU) we must obtain authorization of a clinical trial application in each member state in which we intend to conduct a clinical trial.
−Removed: In addition, certain foreign laws govern the privacy and security of personal data, including health-related data and clinical trial data.
+Added: In addition, certain foreign laws govern the
+Added: privacy and security of personal data, including health-related data and clinical trial data.
Whether or not we obtain U.S.
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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.
−Removed: As of May 31, 2025, we employed 56 full-time employees and one part-time employee.
−Removed: 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.
+Added: As of March 31, 2026, we employed 41 full-time employees;
+Added: 30 full-time employees work in research and development and laboratory support services, and 11 full-time employees work in management, corporate development and communications, legal, human resources, and other general and administrative roles.
Staffing for other functional areas is achieved through our broad and diverse network of strategic relationships with multiple CROs, CDMOs, and other third-party service providers and consultants.
These service providers and consultants provide us with support services on a flexible, real-time, as-needed basis, including services related to, among others, payroll, information technology, legal, investor and public relations, manufacturing, product development, regulatory affairs and FDA program management to complement our internal resources in these areas.
+Added: On March 5, 2026, our Board of Directors approved a reduction of approximately 20% in our workforce.
+Added: The reduction was implemented to provide disciplined cash management while prioritizing efficient execution of the ongoing clinical studies in our PALISADE Program for fasedienol for the acute treatment of SAD.
+Added: In connection with the workforce reduction, affected employees were offered cash severance and temporary healthcare coverage subject to their eligibility for and election of such coverage and their execution of an effective separation agreement, including a general release of claims against the Company.
+Added: Costs incurred in connection with the workforce reduction were not material to our consolidated financial statements for the fiscal year ended March 31, 2026.
+Added: We continue to rely on our network of third-party service providers and consultants to supplement our internal capabilities following the workforce reduction.
+Added: Following the workforce reduction, in April 2026 our Compensation Committee approved retention stock option awards to all of our remaining employees, including our executive officer, under our Amended and Restated 2019 Omnibus Equity Incentive Plan.
+Added: The awards are subject to time-based vesting over a two-year period.
+Added: The retention awards are intended to support employee retention and align employee incentives with the achievement of our clinical and strategic objectives.
We have never had a work stoppage, and none of our employees is represented by a labor organization or under any collective bargaining agreement.
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We file reports and other information with the U.S.
−Removed: Securities and Exchange Commission (SEC), as required by the Securities Exchange Act of 1934, as amended (the Exchange Act).
+Added: Securities and Exchange Commission (SEC), as required by the Securities Exchange Act of 1934, as amended (Exchange Act).
We make available free of charge through our website ( http://www.vistagen.com ) our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and any amendments to those reports filed or furnished pursuant to Sections 13(a) and 15(d) of the Exchange Act.
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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.