Vistagen Therapeutics, Inc.

Previous wording

•the format, objectives, strategy, likelihood of success, and cost of our preclinical studies and clinical trials and other product development activities, including the design of our preclinical studies and clinical trials;

Current wording

•the format, objectives, strategy, likelihood of success, and cost of our preclinical studies and clinical trials and other product development activities, including the design of our preclinical studies and clinical trials and/or our ability to replicate past clinical trial results;

Previous wording

This Quarterly Report contains summaries of certain provisions contained in some of the documents described herein, but reference is made to the actual documents for complete information. All of the summaries are qualified in their entirety by the actual documents. Copies of some of the documents referred to herein have been filed as exhibits to this Quarterly Report. Unless the context otherwise requires, reference in this Quarterly Report to the terms “Vistagen,” “the Company,” “we,” “us,” “our,” and similar designations refer to Vistagen Therapeutics, Inc., a Nevada corporation, and where appropriate, our consolidated subsidiaries.

Current wording

This Quarterly Report contains summaries of certain provisions contained in some of the documents described herein, but reference is made to the actual documents for complete information. All summaries are qualified in their entirety by the actual documents. Copies of some of the documents referred to in this Quarterly Report have been filed as exhibits to this Quarterly Report. Unless the context otherwise requires, reference in this Quarterly Report to the terms “Vistagen,” “the Company,” “we,” “us,” “our,” and similar designations refer to Vistagen Therapeutics, Inc., a Nevada corporation, and where appropriate, our consolidated subsidiaries.

Previous wording

Refisolone for the Treatment of Vasomotor Symptoms (Hot Flashes) due to Menopause

Current wording

We are a late clinical-stage biopharmaceutical company focused on leveraging a deep understanding of nose-to-brain neurocircuitry to develop and commercialize a new class of rapid-onset neurocircuitry-focused intranasal product candidates called pherines. Our pherine product candidates are designed to achieve therapeutic benefits without requiring absorption into the blood or uptake into the brain, giving them the potential to be a safer alternative to other pharmacological options, if successfully developed and approved. Our most advanced intranasal pherine product candidates are fasedienol for the acute treatment of social anxiety disorder, itruvone for treatment of major depressive disorder, and refisolone for treatment of vasomotor symptoms (hot flashes) due to menopause.

Previous wording

Our PALISADE Program includes the PALISADE-1, PALISADE-2, PALISADE-3, and PALISADE-4 Phase 3 studies. These clinical trials are randomized, double-blind, placebo-controlled, U.S. multi-center Phase 3 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. 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. 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. 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. Safety data for fasedienol have been consistently favorable across all clinical trials completed to date.

Current wording

Fasedienol PALISADE-4 Phase 3 Clinical Trial

Previous wording

SAD is a highly prevalent, serious, and life-threatening psychiatric mental health disorder affecting over 30 million adults in the U.S. With onset typically early in life, usually during adolescence, SADpersists for many years thereafter, with areported mean duration of about 20 years. Individuals with SAD experience extreme anxiety, distress, fear, and impairment due to their fear of being watched, embarrassed, judged, humiliated, negatively evaluated, and scrutinized. 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. Individuals with SAD face an increased risk of serious and life-threatening co-morbid depression, substance abuse, suicidal ideation and suicide.

Current wording

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, SADpersists for many years thereafter, with areported mean duration of about 20 years. Individuals with SAD experience extreme anxiety, distress, fear, and impairment due to their fear of being watched, embarrassed, judged, humiliated, negatively evaluated, and scrutinized. 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. Individuals with SAD face an increased risk of serious and life-threatening co-morbid depression, substance abuse, suicidal ideation and suicide.

Previous wording

Our most advanced intranasal pherine product candidate is fasedienol, which is being investigated in our U.S. registration-directed PALISADE Program for the acute treatment of social anxiety disorder (SAD). There are four Phase 3 trials of fasedienol for the acute treatment of SAD in our PALISADE Program – PALISADE-1, PALISADE-2, PALISADE-3 and PALISADE-4. We have concluded PALISADE-1, PALISADE-2 and the randomized portion of PALISADE-3. PALISADE-2 achieved its primary endpoint; neither PALISADE-1 nor PALISADE-3 achieved its primary endpoint. PALISADE-4, and a small exploratory Phase 2B trial designed to assess efficacy, safety and tolerability of a repeat dose of fasedienol in adults with SAD in a public speaking challenge in a clinical setting (the Repeat Dose Study), are ongoing. Topline data for PALISADE-4 and the Repeat Dose Study are expected in the first half of calendar year 2026.

Current wording

Fasedienol for the Acute Treatment of Social Anxiety Disorder

Previous wording

Fasedienol, our lead clinical-stage product candidate, is a synthetic neurocircuitry-focused intranasal pherine in an ongoing U.S. registration-directed Phase 3 clinical development program for the acute treatment of anxiety in adults with SAD. Fasedienol's proposed MOA is fundamentally differentiated from all FDA-approved anti-anxiety medications. When administered intranasally in microgram-level doses, neurocircuitry-focused fasedienol modulates the nasal-limbic amygdala fear and anxiety neurocircuits involved in the pathophysiology of SAD. Fasedienol is pharmacologically active without requiring apparent systemic absorption or direct binding on neurons in the brain to achieve its rapid-onset anxiolytic effects. Fasedienol has no observed binding on certain cellular receptors in the brain 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. Unlike benzodiazepines, fasedienol has no observed potentiation of GABA-A. Because of its innovative non-systemic neurocircuitry-focused proposed MOA, we believe fasedienol has the potential to achieve rapid-onset anxiolytic effects for individuals with SAD 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.

Current wording

Fasedienol, our most advanced neurocircuitry-focused pherine product candidate, is in U.S. Phase 3 clinical development for the acute treatment of anxiety in adults with SAD. Fasedienol's proposed MOA is fundamentally differentiated from all FDA-approved anti-anxiety medications. 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. Fasedienol is pharmacologically active without requiring apparent systemic absorption or uptake into the brain to achieve its rapid-onset anxiolytic effects. 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. Unlike benzodiazepines, data showed that fasedienol has no observed potentiation of GABA-A receptors. 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.

Previous wording

Fasedienol is under development, and has received fast track designation, for the acute treatment of SAD, and 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. While there are approved treatments for SAD, none are approved for the acute treatment of SAD on an as-needed basis in connection with an anxiety-producing social or performance-based event. 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.

Current wording

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. 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. 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. We have designed fasedienol nasal spray with the goal of creating a product candidate with a rapid-onset, non-systemic proposed mechanism of action (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.

Previous wording

We believe fasedienol has the potential to be the first FDA-approved acute treatment of SAD and may provide significant advantages relative to the suboptimal standard of care for the highly prevalent disorder.

Current wording

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.

Previous wording

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., according to SWAN (Study of Women Across the Nation) and other published studies. 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. Each episode typically lasts between one and five minutes and may be accompanied by sweating, chills, and anxiety. 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 and work productivity for those who experience symptoms. While there are FDA-approved therapies for the treatment of 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.

Current wording

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. according to SWAN (Study of Women Across the Nation) and other published studies. 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. Each episode typically lasts between one and five minutes and may be accompanied by sweating, chills, and anxiety. 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. While there are FDA-approved therapies for the treatment of 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.

Previous wording

Refisolone (formerly PH80) is our investigational pherine product candidate under development 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. Refisolone’s proposed MOA is fundamentally differentiated from all currently approved treatments for VMS (hot flashes) due to menopause. Administration of low microgram doses of refisolone appears to rapidly activate peripheral nasal chemosensory neurons that modulate the nasal-limbic amygdala-hypothalamic depressed mood and thermoregulatory neurocircuits. Notably, in vitro studies showed that refisolone had no observed engagement with steroid receptors. 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. Additionally, in an in vitro study refisolone did not exert observable effects on receptor targets with known abuse potential, and a clinical study in human volunteers showed no detectable refisolone in blood plasma, indicating the non-systemic nature of refisolone's potential therapeutic benefit.

Current wording

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. Refisolone’s proposed MOA is fundamentally differentiated from all currently approved treatments for VMS (hot flashes) due to menopause. Administration of low microgram doses of refisolone appears to rapidly activate peripheral nasal chemosensory neurons that modulate the nasal-limbic amygdala-hypothalamic depressed mood and thermoregulatory neurocircuits. Notably, in vitro studies showed that refisolone had no observed engagement with hormonal receptors. 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. Additionally, in an in vitro study refisolone did not exert observable effects on receptor targets with known abuse potential. 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.

Previous wording

In a randomized, double-blind, placebo-controlled exploratory Phase 2A clinical study of refisolone that was 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. Refisolone was well-tolerated with no treatment-related SAEs reported, and the adverse event profiles were comparable between refisolone and placebo. No subject discontinued participation in the study as a result of adverse events.

Current wording

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 statistically significant reduction in the daily number of hot flashes compared to placebo at the end of the first week of treatment (p=<0.001), and the improvement was maintained through each treatment week until the end of the four consecutive week treatment period. Refisolone was well-tolerated with no treatment-related serious adverse events (SAEs) reported, and the adverse event profiles were comparable between refisolone and placebo. No subject discontinued participation in the study as a result of adverse events.

Previous wording

In an exploratory, randomized, double-blind, placebo-controlled Phase 2A clinical study of refisolone 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). Refisolone was well-tolerated with no SAEs.

Current wording

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). Refisolone was well-tolerated with no SAEs.

Previous wording

Itruvone is our investigational pherine product candidate under development as a stand-alone treatment of MDD. The FDA has granted fast track designation for development of itruvone for MDD. 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. 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. 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.

Current wording

Itruvone is our intranasal pherine product candidate under development for the treatment of MDD. The FDA has granted fast track designation for development of itruvone for MDD. 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. 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. 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.

Previous wording

In a randomized, double-blind, placebo-controlled parallel design exploratory Phase 2A clinical trial of itruvone as a stand-alone treatment for MDD, itruvone reduced depressive symptoms in as soon as one week based on the 17-item Hamilton Depression Scale (HAM-D-17) scores compared to placebo. 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 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 previous clinical studies of itruvone. As a result, building on the positive results from the previous Phase 2A clinical development of itruvone in MDD, we are currently planning for potential U.S. Phase 2B clinical development of itruvone as a stand-alone treatment for MDD.

Current wording

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. 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. 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. We have an open IND for itruvone in the U.S. and plan to pursue Phase 2 clinical development of itruvone in the U.S. 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.

Previous wording

PH15 is our investigational pherine product candidate under development as a treatment to improve psychomotor impairment caused by mental fatigue. 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. 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.

Current wording

PH15 is our intranasal pherine product candidate under development for the improvement of psychomotor impairment caused by mental fatigue. 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. 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.

Previous wording

In a randomized, double-blind, placebo-controlled, crossover Phase 2A pilot study (n=10) 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 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. PH15 was well-tolerated in this study, with no treatment-related SAEs reported. The adverse event profiles of PH15 and placebo were comparable.

Current wording

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. PH15 was well-tolerated in this study, with no treatment-related SAEs reported. The adverse event profiles of PH15 and placebo were comparable.

Previous wording

PH284 is our investigational 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. PH284 is thought to act by modulating the nasal-limbic amygdala-hypothalamic depressed mood and appetite control neurocircuits.

Current wording

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. PH284 is thought to act by modulating the nasal-limbic amygdala-hypothalamic depressed mood and appetite control neurocircuits.

Previous wording

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, 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. 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.

Current wording

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. 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.

Previous wording

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. IND application for potential further Phase 2 clinical development of PH284 for the treatment of cancer cachexia or other appetite-related disorders.

Current wording

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. IND application for potential further Phase 2 clinical development of PH284 in the U.S. for the treatment of cancer cachexia or other appetite-related disorders.

Previous wording

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. Abnormal NMDAR function is associated with numerous neurological diseases and disorders. The active metabolite of AV-101, 7-chloro-kynurenic acid (7-Cl-KYNA), is a potent and selective full antagonist of the glycine binding site of the NMDAR that inhibits the function of the NMDAR. Unlike ketamine and many other NMDAR antagonists, 7-Cl-KYNA is not an ion channel blocker. 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. Moreover, in all clinical trials completed to date, AV-101 has been safe and 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. 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.

Current wording

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. The active metabolite of AV-101, 7-chloro-kynurenic acid (7-Cl-KYNA), is a potent and selective full antagonist of the glycine binding site of the NMDAR that inhibits the function of the NMDAR. Unlike ketamine and many other NMDAR antagonists, 7-Cl-KYNA is not an ion channel blocker. 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. 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. 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.

Previous wording

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 multiple neuroscience disorders, including levodopa-induced dyskinesia (LID) and neuropathic pain (NP) potentially among others. We are currently assessing whether there is a path forward for potential collaborative manufacturing, clinical development and commercialization of AV-101 for one or more neurological disorders involving the NMDAR.

Current wording

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). We do not anticipate further development and commercialization of AV-101 on our own. We are currently assessing whether there is a path forward for potential third-party collaborative manufacturing, development and commercialization of AV-101 for one or more neurological disorders involving the NMDAR.

Previous wording

Since inception, we have devoted substantial resources to advancing initiatives related to research, development, and contract manufacturing of our neuroscience pipeline, including initiatives related to manufacturing processes, analytical methods and production programs for drug substance and finished drug product, as well as for preclinical studies and clinical trials focused on development and potential commercialization of our product candidates, with substantial emphasis on our lead pherine product candidates, fasedienol, itruvone, and refisolone, for the acute treatment of SAD, and treatment of MDD and VMS due to menopause, respectively. At the end of our fiscal year ended March 31, 2024, we launched our PALISADE-3 Phase 3 clinical trial as part of our U.S. registration-directed PALISADE Phase 3 program evaluating fasedienol for the acute treatment of anxiety in adults with SAD, and in September 2024, we initiated our PALISADE-4 Phase 3 clinical trial for the same indication, and incurred costs to plan and prepare for the initiation of the Repeat Dose Study, which we initiated in January 2025. Both the PALISADE-4 Phase 3 trial and the Repeat Dose Study are also parts of our PALISADE Phase 3 program for fasedienol in SAD. In addition, we are continuing to conduct various nonclinical studies and contract manufacturing activities involving other clinical-stage pherine product candidates in our neuroscience pipeline. We also have ongoing initiatives for creating, protecting and patenting intellectual property (IP) related to our neuroscience product candidates and nasal spray delivery device technologies.

Current wording

Since inception, we have devoted substantial resources to advancing initiatives related to research, development, and contract manufacturing of our neuroscience pipeline, including initiatives related to manufacturing processes, analytical methods and production programs for drug substance and finished drug product, as well as for preclinical studies and clinical trials focused on development and potential commercialization of our product candidates, with substantial emphasis on our lead pherine product candidates, fasedienol, itruvone, and refisolone, for the acute treatment of SAD, and treatment of MDD and VMS due to menopause, respectively. We also have ongoing initiatives for creating, protecting and patenting intellectual property (IP) related to our neuroscience product candidates and nasal spray delivery device technologies.

Previous wording

At December 31, 2025, we had an accumulated deficit of approximately $461.0 million. Our net loss for the year ended March 31, 2025 (Fiscal 2025) and the year ended March 31, 2024 (Fiscal 2024) was approximately $51.4 million and $29.4 million, respectively. We incurred a net loss of approximately $18.9 million and $53.4 million for the three and nine months ended December 31, 2025, respectively. We expect losses to continue for the foreseeable future as we engage in further research, clinical and nonclinical development, contract manufacturing and regulatory activities related to fasedienol, itruvone, refisolone and our other pherine product candidates. We have not yet achieved revenue-generating status from any of our product candidates or technologies in amounts sufficient to sustain our operations and fund our strategic business plans.

Current wording

At June 30, 2026, we had an accumulated deficit of approximately $490.3 million. Our net loss for the year ended March 31, 2026 (Fiscal 2026) and the year ended March 31, 2025 (Fiscal 2025) was approximately $69.7 million and $51.4 million, respectively. We incurred a net loss of approximately $13.0 million and $15.1 million for the three months ended June 30, 2026 and 2025, respectively. We expect losses to continue for the foreseeable future as we engage in further research, clinical and nonclinical development, contract manufacturing and regulatory activities related to fasedienol, itruvone, refisolone and our other pherine product candidates. We have not yet achieved revenue-generating status from any of our product candidates or technologies in amounts sufficient to sustain our operations and fund our strategic business plans.

Previous wording

•the cost and timing of manufacturing our product candidates and our reliance on third-party CDMOs;

Current wording

•the cost and timing of manufacturing our product candidates;

Previous wording

•the impact of any business interruptions to our operations or to those of the third parties with whom we work, including consolidation of third-party CROs, CDMOs or preclinical and clinical research sites involved in our product development programs;

Current wording

•the impact of any business interruptions to our operations or to those of the third parties with whom we work;

Previous wording

•adverse effects on the financial markets, the global economy, the supply chain and our expenses due to pandemics or other epidemic diseases, geopolitical instability, government shutdowns and RIFs, inflation, rising interest rates, government tariffs and other factors; and

Current wording

•adverse effects on the financial markets, the global economy, the supply chain and our expenses due to pandemics or other epidemic diseases, geopolitical instability, government shutdowns and reductions in force, inflation, rising interest rates, government tariffs and other factors; and

Previous wording

Results of Operations for the Three and Nine Months Ended December 31, 2025

Current wording

Results of Operations for the Three Months Ended June 30, 2026

Previous wording

The following table summarizes the results of our operations for the three and nine months ended December 31, 2025 and 2024 (in thousands):

Current wording

The following table summarizes the results of our operations for the three months ended June 30, 2026 and 2025 (in thousands):

Previous wording

Absent the achievement of milestones under the AffaMed Agreement, or the execution of similar agreements in the future, if any, we expect sublicense and other revenue to stay materially consistent in future periods as we continue to recognize revenue under the AffaMed Agreement.

Current wording

Accordingly, absent the achievement of milestones under the AffaMed Agreement, or the execution of similar agreements in the future, if any, we expect sublicense and other revenue in future periods to be substantially lower than the amount recognized in the current period.

Previous wording

The following table summarizes our research and development expense for the three and nine months ended December 31, 2025 and 2024 (in thousands):

Current wording

The following table summarizes our research and development expense for the three months ended June 30, 2026 and 2025 (in thousands):

Previous wording

The increase of $2.9 million in research and development expense for the three months ended December 31, 2025 as compared to the same period in Fiscal 2025 was primarily due to an increase in clinical development expense of $4.0 million related to our U.S. registration-directed PALISADE program for fasedienol for the acute treatment of SAD, and an increase of $0.3 million in connection with the increased headcount, partially offset by a decrease in expense related to our other product candidates.

Current wording

The decrease of $0.8 million in research and development expense for the three months ended June 30, 2026 as compared to the same period in 2025 was primarily due to a decrease in clinical development expense of $1.0 million related to our U.S. registration-directed PALISADE program for fasedienol for the acute treatment of SAD, and an increase of $0.2 million in connection with increased headcount and retention bonuses.

Previous wording

During the quarter ended December 31, 2025, we began realizing a decrease in research and development expenses as a result of cash preservation measures implemented following the announcement of top-line results from our PALISADE-3 clinical trial. We expect research and development expenses to continue to decrease in future periods as a result of these cash preservation measures. However, should PALISADE-4 be successful, we expect that our research and development expense will increase over the next fiscal year as we continue to advance research and development of our pherine product candidates and maintain, expand, protect and enforce our intellectual property portfolio, and hire additional headcount. At this time, we cannot accurately estimate or know the nature, timing and costs of the efforts that will be necessary to complete the nonclinical and clinical development of any pherine product candidates we are developing or may develop. A change in the outcome of any number of variables could significantly alter the costs and timing associated with the development of any of our pherine product candidates.

Current wording

During the quarter ended December 31, 2025, we began realizing a decrease in research and development expenses as a result of cash preservation measures implemented following the announcement of top-line results from our PALISADE-3 clinical trial. We expect research and development expenses to continue to decrease in future periods as a result of these cash preservation measures and the conclusion of our current Phase 3 PALISADE-4 trial and Repeat Dose Study. Future research and development expenses will be dependent on feedback from FDA regarding a potential registrational pathway for fasedienol for the acute treatment of SAD supported by a single, future multi-dose Phase 3 trial with the LSAS as the primary endpoint, as well as confirmatory evidence from the PALISADE program and aggregate safety data collected to date. At this time, we cannot accurately estimate or know the nature, timing and costs of the efforts that will be necessary to complete the nonclinical and clinical development of any pherine product candidates we are developing or may develop. A change in the outcome of any number of variables could significantly alter the costs and timing associated with the development of any of our pherine product candidates.

Previous wording

Interest income, net, decreased for the three and nine months ended December 31, 2025 as compared to the same period in Fiscal 2025 primarily due to a decrease in amounts invested in interest bearing securities.

Current wording

Interest income, net, decreased for the three months ended June 30, 2026 as compared to the same period in 2025 primarily due to a decrease in amounts invested in interest bearing securities.

Previous wording

Since our inception, we have not generated any revenue from product sales and have incurred significant operating losses and negative cash flows from our operations. To date, as of December 31, 2025, we have financed our operations and technology acquisitions primarily through the issuance and sale of our equity securities for cash proceeds of approximately $372.5 million, as well as from an aggregate of approximately $22.7 million of government research grant awards (excluding the fair market value of government-sponsored and funded clinical trials), strategic collaboration payments, intellectual property licensing payments, and other revenues. Additionally, we have issued equity securities with an approximate value at issuance of $41.3 million for non-cash acquisitions of product licenses, consideration for our acquisition of Pherin Pharmaceuticals, Inc. in February 2023 (the Pherin Acquisition), and in settlements of certain liabilities, including liabilities for professional services rendered to us or as compensation for such services.

Current wording

Since our inception, we have not generated any revenue from product sales and have incurred significant operating losses and negative cash flows from our operations. To date we have financed our operations and technology acquisitions primarily through the issuance and sale of our equity securities for cash proceeds of approximately $372.2 million, as well as from an aggregate of approximately $22.7 million of government research grant awards (excluding the fair market value of government-sponsored and funded clinical trials), strategic collaboration payments, intellectual property licensing payments, and other revenues. Additionally, we have issued equity securities with an approximate value at issuance of $41.3 million for non-cash acquisitions of product licenses, consideration for our acquisition of Pherin Pharmaceuticals, Inc. in February 2023 (the Pherin Acquisition), and in settlements of certain liabilities, including liabilities for professional services rendered to us or as compensation for such services.

Previous wording

In May 2021, we entered into an Open Market Sale Agreement (the Sales Agreement) with Jefferies LLC (Jefferies) as sales agent, with respect to an at-the-market offering program, under which we were permitted, at our option, to offer and sell, from time to time, shares of our common stock having an aggregate offering price of up to $75.0 million. In February 2024, the aggregate offering price available under the Sales Agreement was increased to up to $100 million, and in June 2025, the aggregate offering price available under the Sales Agreement was increased to up to $175 million. During the three and nine months ended December 31, 2025, we sold an aggregate of 604,405 and 10,403,244 shares under the Sales Agreement, for net proceeds of $2.3 million and $30.6 million, respectively. During the three and nine months ended December 31, 2024, we sold an aggregate of 428,322 shares under the Sales Agreement, for net proceeds of $1.1 million.

Current wording

In May 2021, we entered into an Open Market Sale Agreement, as amended, (the Sales Agreement) with Jefferies LLC (Jefferies) as sales agent, with respect to an at-the-market offering program, under which we were permitted, at our option, to offer and sell, from time to time, shares of our common stock having an aggregate offering price of up to $175 million. During the three months ended June 30, 2026, we sold an aggregate of 1,580,176 shares under the Sales Agreement, for net proceeds of $0.9 million. During the three months ended June 30, 2025, we sold an aggregate of 190,067 shares under the Sales Agreement, for net proceeds of $0.4 million.

Previous wording

As of December 31, 2025, we had cash, cash equivalents, and marketable securities of approximately $61.8 million. As of February 12, 2026, the issuance date of the condensed consolidated financial statements in this Quarterly Report as of and for the three and nine months ended December 31, 2025, there is uncertainty about whether our combined cash, cash equivalents, and marketable securities will be sufficient to fund operations beyond twelve months from the issuance date of the condensed consolidated financial statements in this Report and therefore we concluded that substantial doubt existed about our ability to continue as a going concern.

Current wording

As of June 30, 2026, we had cash, cash equivalents, and marketable securities of approximately $31.7 million. As of August 14, 2026, the issuance date of the condensed consolidated financial statements in this Quarterly Report as of and for the three months ended June 30, 2026, there is uncertainty about whether our combined cash, cash equivalents, and marketable securities will be sufficient to fund operations beyond twelve months from the issuance date of the condensed consolidated financial statements in this Report and therefore we concluded that substantial doubt exists about our ability to continue as a going concern.

Previous wording

There can be no assurance that future financings will be available to us in sufficient amounts, in a timely manner, or on terms acceptable to us, if at all, or that any current or future development and commercialization collaborations will generate revenue from future potential milestone payments or otherwise. Further, on February 3, 2026, we received a letter from the Listing Qualifications Staff of The Nasdaq Stock Market, LLC (Nasdaq) indicating that, based upon the closing bid price of our common stock for the previous 30 consecutive business days, we are not currently in compliance with the requirement to maintain a minimum bid price of $1.00 per share for continued listing on the Nasdaq Capital Market. While the letter has no immediate effect on the listing of our common stock on the Nasdaq Capital Market, failure to meet applicable Nasdaq continued listing standards by August 3, 2026, the expiration of the 180-day period in which to regain compliance, unless extended, could potentially result in a delisting of our common stock. If we are unable to regain timely compliance with the Nasdaq continued listing standards and/or obtain additional financing on a timely basis when needed, our business, financial condition, and results of operations may be harmed, the price of our common stock may decline, we may be required to reduce, defer, or discontinue certain of our research and development activities, and we may not be able to continue as a going concern.

Current wording

There can be no assurance that future financings will be available to us in sufficient amounts, in a timely manner, or on terms acceptable to us, if at all, or that any current or future development and commercialization collaborations will generate revenue from future potential milestone payments or otherwise. Further, on August 4, 2026, the Company received a notification (the Extension Notice) from the Listing Qualifications Staff of The Nasdaq Stock Market LLC (Nasdaq) granting the Company an additional 180 calendar day compliance period, until February 1, 2027 (the Extension Period), to regain compliance with the requirement that the Company's common stock maintain a minimum closing bid price of $1.00 per share for continued listing on the Nasdaq Capital Market pursuant to Nasdaq Listing Rule 5550(a)(2) (the Minimum Bid Price Requirement).

Previous wording

Net cash used in operating activities for the nine months ended December 31, 2025 was $50.2 million, consisting primarily of our net loss of $53.4 million, adjusted for $3.2 million of non-cash charges primarily related to stock-based compensation expense and amortization of our operating lease right-of-use asset, and $0.1 million in net changes in operating assets and liabilities.

Current wording

Net cash used in operating activities for the three months ended June 30, 2026 was $14.7 million, consisting primarily of our net loss of $13.0 million, adjusted for $1.1 million of non-cash charges primarily related to stock-based compensation expense and amortization of our operating lease right-of-use asset, and $2.7 million in net changes in operating assets and liabilities.

Previous wording

Net cash used in operating activities for the nine months ended December 31, 2024 was $32.0 million, consisting primarily of our net loss of $37.8 million, adjusted for $3.6 million of non-cash charges primarily related to stock-based compensation expense and amortization of our operating lease right-of-use asset, and $2.2 million in net changes in operating assets and liabilities.

Current wording

Net cash used in operating activities for the three months ended June 30, 2025 was $18.8 million, consisting primarily of our net loss of $15.1 million, adjusted for $1.0 million of non-cash charges primarily related to stock-based compensation expense and amortization of our operating lease right-of-use asset, and $4.7 million in net changes in operating assets and liabilities.