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Item 1. Business

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We are a neuroscience-focused biopharmaceutical company dedicated to pursuing a pioneering approach to the development and commercialization of groundbreaking therapies for psychiatric and neurological disorders based on our deep understanding of nose-to-brain neurocircuitry.

Our clinical-stage pipeline consists of intranasal product candidates from a new class of potential neuroscience therapies called pherines.

Designed exclusively as nasal sprays, each of our pherine product candidates is centered on our innovative approach to addressing neuroscience disorders with the nose as a new portal for the administration of novel, rapid-onset neuroactive therapies that do not require systemic absorption or binding to neurons in the brain to achieve desired therapeutic effects.

Microgram-level doses of our pherine nasal sprays rapidly activate chemosensory neurons in the nasal cavity to impact fundamental neurocircuitry in the olfactory system and the brain with a differentiated safety profile observed in all clinical studies completed to date.

Our goal is to develop and commercialize a broad and diversified pipeline of innovative neuroactive pherine therapies for multiple highly prevalent neuroscience indications, such as social anxiety disorder, major depressive disorder, and vasomotor symptoms (hot flashes) associated with menopause, with limited or inadequate current treatment options to meet the needs of millions of underserved patients in the U.S.

and worldwide.

See “Our Neuroscience Pipeline” below.

As we pursue our goal to efficiently develop and commercialize novel, differentiated neuroactive pherine therapies for psychiatric and neurological disorders, our primary strategy is as follows:

Target High-Growth Neuroscience Markets :

Pursue commercially attractive, high-prevalence, high-growth neuroscience markets with limited differentiated FDA-approved treatment options, as to both efficacy and safety, and an inadequate or non-existent standard of care.

Develop Differentiated Neuroscience Products :

Apply our unique understanding of olfactory and brain neurocircuitry to develop a broad and diversified neuroscience pherine pipeline with novel mechanisms of action (MOAs), clearly differentiated efficacy and safety profiles, and groundbreaking potential to transform lives across multiple therapeutic areas.

Rights and Partner Ex-U.S.

We plan to retain all U.S.

commercial rights to the pherine product candidates in our neuroscience pipeline, and develop and commercialize our pherine portfolio in the U.S.

when advantageous to us, selectively partner development and commercialization of our pherine product candidates outside the U.S.;

and selectively partner rights to develop and commercialize AV-101 in the U.S.

Our Clinical-Stage Neuroscience Pipeline

Our pherines are a novel class of synthetic neurocircuitry-focused drug candidates for psychiatric and neurological disorders.

They are odorless and tasteless neuroactive steroids, delivered only intranasally, each with a differentiated MOA and safety profile from all currently approved drugs.

Our neuroactive pherines rapidly activate olfactory system neurocircuitry to achieve therapeutic effects via nose-to-brain neural connections.

Through these connections, pherines activate neural circuitry to specific brain regions that impact the neuroscience disorders we are targeting, without requiring apparent systemic absorption or central nervous system (CNS) uptake.

As a result of their novel non-systemic MOAs, we believe our pherine drug candidates have favorable and differentiated safety profiles, and have been observed to be well-tolerated in all clinical trials completed to date.

Our Lead Clinical-Stage Programs

Social Anxiety Disorder (SAD)

Based on the 2023 National Health and Wellness Survey, an estimated 31 million adults, or approximately 12% of the adult population in the U.S., are affected by SAD.

SAD can be viewed as a chronic series of acute, socially stressful events in which patients exhibit excessive anxiety and fear of embarrassment, humiliation, scrutiny, evaluation, or rejection by others (Liebowitz, Gorman, Fyer, & Klein, 1985).

The avoidance, fear, or anxious anticipation of these situations interferes significantly with the person’s daily routine, having a marked impact on occupational functioning and/or social life.

In the absence of anxiety-provoking social or performance events, generally, patients with SAD are asymptomatic.

SAD typically does not resolve naturally, and may lead to alcohol use disorder, major depressive disorder (MDD), suicidal ideation and suicide as sequalae.

A key psychotherapy mechanism by which individuals with SAD overcome this disorder, or lessen their symptoms, is believed to be by gradually exposing themselves to feared or avoided situations.

This is a key component of cognitive-behavioral treatment (CBT) for SAD.

However, it is difficult for most individuals with SAD to even consider engaging in stressful, anxiety-provoking social or performance situations, preventing initiation and continuation of CBT as a psychotherapeutic approach.

The three antidepressants currently approved by the U.S.

Food and Drug Administration (FDA) for the treatment of SAD were approved over 20 years ago.

If successful, they exert their therapeutic effect over time with the objective of gradually reducing the anxiety and physical symptoms that SAD patients experience when they find themselves in feared or avoided situations.

If these oral antidepressants begin to produce a clinical therapeutic benefit, usually many weeks following the start of daily systemic dosing, they require long-term daily maintenance dosing, regardless of whether the SAD patient actually experiences social anxiety on a given day.

Chronic treatment is typically associated with a range of bothersome side effects, such as gastrointestinal symptoms, agitation, sleep disturbances, weight changes, and sexual dysfunction.

None of the antidepressants approved for the treatment of SAD is approved for the acute treatment of SAD.

Fasedienol for the Acute Treatment of SAD

Fasedienol is a synthetic investigational neuroactive pherine nasal spray from the androstane family currently in Phase 3 clinical development for the acute treatment of SAD.

The proposed MOA of fasedienol is fundamentally differentiated from all currently approved anti-anxiety medications, including the three antidepressants approved by the FDA for the treatment of SAD, as well as all benzodiazepines and beta blockers, which, although not FDA-approved for the treatment of SAD, are sometimes prescribed for treatment of SAD on an off-label basis.

When administered intranasally in microgram-level doses, odorless and tasteless fasedienol activates receptors of peripheral nasal chemosensory neurons connected to subsets of neurons in the olfactory bulbs that, in turn, connect to neurons in the limbic amygdala involved in the pathophysiology of SAD, and potentially other acute anxiety and mood disorders.

Fasedienol is pharmacologically active without requiring apparent systemic absorption or direct binding on neurons in the brain to achieve its rapid-onset and short-duration anxiolytic effects.

Fasedienol does not exert effects on certain cellular receptors that are associated with known drug abuse liability potential (for example, dopamine, nicotinic, and opiate receptors) when activated by certain other pharmaceutical compounds for neuropsychiatric and neurological disorders.

Fasedienol also does not produce agonistic or antagonistic effects on GABA A α1/β2/γ2 ion channels.

Because of its innovative non-systemic neurocircuitry-focused MOA, we believe fasedienol has the potential to achieve these rapid-onset anxiolytic effects on an as-needed basis rather than chronic daily dosing, and with a significantly reduced risk of unwanted side effects and safety concerns, such as potential drug-drug interactions, abuse, misuse, and addiction, associated with current oral and certain other systemically absorbed neuropsychiatric pharmaceuticals that act directly on neurons in the brain and are sometimes prescribed for anxiety disorders.

Fasedienol PALISADE Phase 3 Program for the Acute Treatment of SAD

We believe fasedienol allows individuals affected by SAD to engage in stressful or previously avoided social or performance situations with fewer or less severe symptoms.

A key and substantial difference between fasedienol and each of the three oral antidepressants approved by the FDA for the treatment of SAD is that fasedienol is being developed for use on a patient-tailored as-needed basis, before or during a stressful social or performance situation because of its rapid-onset MOA and pharmacological effect.

Hence, acute treatment with fasedienol has the potential to reduce the wave of anxiety usually experienced by SAD patients before engaging in or during a feared social or performance situation.

Through more frequent exposure to socially stressful events, we believe treatment with fasedienol may help individuals with SAD to begin to cognitively separate the negative physiological symptoms of anxiety from specific anxiety-provoking events.

Currently, there is no FDA-approved drug therapy for the acute treatment of SAD.

Given how fasedienol’s rapid-onset MOA is differentiated from all current FDA-approved anxiety drugs, our initial and primary target indication for fasedienol is the acute treatment of SAD.

For that acute indication, we have aligned with the FDA that a clinic-based public speaking challenge and the Subjective Units of Distress Scale (SUDS) are the appropriate study design and primary efficacy endpoint, respectively, to measure anxiety immediately related to the specific stressor, and is the most appropriate and efficient path for our registration-directed PALISADE Phase 3 Program, which is focused on fasedienol’s potential to become the first FDA-approved acute treatment of SAD.

Accordingly, our Phase 3 clinical trials in our PALISADE Phase 3 Program are randomized, double-blind, placebo-controlled, clinical trials designed to evaluate the efficacy, safety, and tolerability of a single dose of fasedienol to relieve anxiety symptoms in adult patients with SAD during a simulated, anxiety-provoking public speaking challenge conducted in a clinical setting, as measured using the patient-reported SUDS as the primary efficacy endpoint.

Two of the Phase 3 trials in our PALISADE Phase 3 Program were previously concluded, PALISADE-1, concluded in 2022 and did not meet its primary endpoint, and PALISADE-2, concluded in 2023 and successfully met its primary endpoint, and as further described below, two Phase 3 trials, PALISADE-3 and PALISADE-4 are ongoing or will be initiated in 2024.

Our PALISADE Phase 3 Program also includes open-label extension safety studies, a small Phase 2 repeat dose study (Repeat Dose Study), certain standard preclinical studies, and a small human factor study.

In early August 2023, we received and reported positive topline results from our PALISADE-2 Phase 3 trial of fasedienol for the acute treatment of SAD.

Our PALISADE-2 Phase 3 trial met its primary efficacy endpoint, which was the difference in mean SUDS scores during the public speaking challenge at baseline (Visit 2) and treatment (Visit 3) for subjects treated with fasedienol versus placebo at Visit 3.

We are a late clinical-stage biopharmaceutical company leveraging a deep understanding of nose-to-brain neurocircuitry to develop and commercialize a new class of non-systemic intranasal product candidates called pherines.

Our broad and diverse neuroscience pipeline currently consists of five clinical-stage pherine product candidates, each with a novel mechanism of action (MOA) and positive clinical data in their targeted indication(s).

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.

Our most advanced intranasal pherine product candidate is fasedienol, which is being investigated in our U.S.

registration-directed PALISADE Program for the acute treatment of social anxiety disorder (SAD).

In August 2023, we received and reported positive topline results from our PALISADE-2 Phase 3 trial of fasedienol for the acute treatment of SAD.

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).

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.

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.

FDA for the acute treatment of SAD.

The FDA has granted Fast Track designation for the investigation of fasedienol for the acute treatment of SAD.

Fasedienol has the potential to be the first FDA-approved acute treatment for SAD and provide significant advantages relative to the current standard of care.

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.

See “Our Neuroscience Product Candidates” below.

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.

Our Neuroscience Product Candidates

Overview of Social Anxiety Disorder

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.

With onset typically early in life, usually during adolescence, SAD persists for many years thereafter, with a reported mean duration of about 20 years.

While often a long-term disorder, SAD can manifest acutely when triggered by anxiety-provoking social and performance situations .

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.

The disorder can significantly disrupt family and social life, diminish self-esteem, and hinder work performance.

People with SAD may struggle to form social or vocational relationships, which can lead to feelings of powerlessness and shame.

The profound anxiety associated with SAD often results in avoidance of everyday interactions and opportunities in academic, social and vocational settings.

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.

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.

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.

Fasedienol for the Acute Treatment of Social Anxiety Disorder

Fasedienol, our lead clinical-stage product candidate, is a synthetic neuroactive 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 MOA is fundamentally differentiated from all FDA-approved anti-anxiety medications.

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.

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.

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.

Unlike benzodiazepines, fasedienol does not potentiate GABA-A receptors.

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-

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

There is no FDA-approved pharmacological therapy for the acute treatment of SAD.

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.

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.

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.

We have aligned with the FDA that a clinic-based public speaking challenge and the Subjective Units of Distress Scale (SUDS) are the appropriate study design and primary efficacy endpoint, respectively, to measure anxiety immediately related to the specific stressor, and is the most appropriate and efficient path for our U.S.

registration-directed PALISADE Program, which is focused on fasedienol’s potential to become the first FDA-approved acute treatment of anxiety for adults with SAD.

The Phase 3 clinical trials in our PALISADE Program are randomized, double-blind, placebo-controlled, U.S.

multi-center clinical trials designed to evaluate the efficacy, safety, and tolerability of a single dose of fasedienol to relieve anxiety symptoms in adult patients with SAD during a simulated, anxiety-provoking public speaking challenge conducted in a clinical setting, as measured using the patient-rated SUDS as the primary efficacy endpoint.

Two of the Phase 3 trials in our PALISADE Program were previously concluded;

PALISADE-1, reported in 2022, did not meet its primary endpoint, and PALISADE-2, reported in 2023, successfully met its primary efficacy endpoint, and as further described below, two Phase 3 trials, PALISADE-3 and PALISADE-4, are ongoing.

Our PALISADE Program also includes open-label extension safety studies, the ongoing small Phase 2 Repeat Dose Study, certain standard preclinical studies, and a small human factor study.

In August 2023, we received and reported positive topline results from our PALISADE-2 Phase 3 trial of fasedienol for the acute treatment of anxiety in adults with SAD.

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.

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).

The trial also met its secondary endpoint, demonstrating a statistically significant difference in the proportion of clinician-assessed responders between fasedienol and placebo as measured by the Clinical Global Impressions – Improvement (CGI-I) scale.

PALISADE-2 also met its secondary endpoint, demonstrating a statistically significant difference in the proportion of clinician-assessed responders between fasedienol and placebo as measured by the Clinical Global Impressions – Improvement (CGI-I) scale.

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).

The trial also met an important exploratory patient-reported endpoint focused on the difference in the proportion of patient-assessed responders between fasedienol and placebo as measured by the Patient’s Global Impression of Change (PGI-C) scale.

Responders were identified as those who self-rated ‘very much less anxious’ or ‘much less anxious’ and 40.6% of fasedienol-treated patients were rated as responders, as compared to 18.6% of those treated with placebo (p=0.003).

Our PALISADE-2 trial also met an additional exploratory endpoint, the difference in the proportion of patients in each treatment group with a 20-point or greater improvement in patient-assessed SUDS score from baseline (Visit 2) to treatment (Visit 3).

Of the fasedienol-treated patients, 35.7% demonstrated this statistically significant and clinically meaningful improvement in SUDS score, as compared to 18.6% in the placebo-treated group (p=0.020).

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.

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).

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).

Of the fasedienol-treated patients, 35.7% demonstrated this statistically significant improvement in SUDS score, as compared to 18.6% in the placebo-treated group (p=0.020).

Fasedienol was observed to be well-tolerated with no serious adverse events (SAEs), and the treatment-emergent adverse event (TEAE) profiles were comparable between fasedienol and placebo.

Overall, no TEAEs, except for pyrexia in the placebo group (2.49%), was more prevalent than 2.0%.

To complement our successful PALISADE-2 Phase 3 trial, we launched our PALISADE-3 Phase 3 trial in March 2024 and we are preparing to launch our PALISADE-4 Phase 3 trial in the second half of 2024.

Like PALISADE-2, PALISADE-3 is, and PALISADE-4 will be, multi-center, randomized, double-blind, placebo-controlled studies designed to evaluate the efficacy, safety, and tolerability of the acute administration of fasedienol to relieve anxiety symptoms in adult patients with SAD after a single dose of fasedienol during a simulated, anxiety-provoking public speaking challenge conducted in a clinical setting, as measured using the patient-reported SUDS as the primary efficacy endpoint.

In addition, both PALISADE-3 and PALISADE-4 will have an open-label extension for a period of up to 12 months.

We are also planning to initiate the Repeat Dose Study in the second half of 2024.

This study will be a small multi-center, randomized, double-blind, placebo-controlled, three-arm Phase 2 clinical trial designed to evaluate repeated dosing (up to two doses within ten minutes) of fasedienol in adult patients with SAD during a single, simulated, anxiety-provoking public speaking challenge in a clinical setting.

The Repeat Dose Study will also have an open-label extension for a period of up to 12 months.

We believe either PALISADE-3 or PALISADE-4, if successful, together with PALISADE-2, may establish substantial evidence of the effectiveness of fasedienol in support of a potential fasedienol New Drug Application (NDA) submission to the FDA for the acute treatment of SAD.

The FDA has designated fasedienol as a Fast Track product candidate.

Major Depressive Disorder (MDD)

Depression is a serious medical illness and a global public health concern that can occur at any time during a person's life.

To complement our successful PALISADE-2 Phase 3 trial, we launched our PALISADE-3 and PALISADE-4 Phase 3 trials 2024.

Like PALISADE-2, PALISADE-3 and PALISADE-4 are U.S.

multi-center, randomized, double-blind, placebo-controlled Phase 3 studies designed to evaluate the efficacy, safety, and tolerability of the acute administration of fasedienol to relieve anxiety symptoms in adults with SAD after a single dose of fasedienol during a simulated, anxiety-provoking public speaking challenge conducted in a clinical setting, as measured using the patient-reported SUDS as the primary efficacy endpoint.

In addition, both PALISADE-3 and PALISADE-4 have an open-label extension for a period of up to 12 months.

We initiated the Repeat Dose Study in early 2025.

This study is a small U.S.

multi-center, randomized, double-blind, placebo-controlled, three-arm exploratory Phase 2 clinical trial designed to evaluate repeated dosing (up to

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.

The Repeat Dose Study also includes an open-label extension study for a period of up to 12 months.

We believe either PALISADE-3 or PALISADE-4, if successful, together with PALISADE-2, may establish substantial evidence of the effectiveness of fasedienol in support of a potential New Drug Application (NDA) submission to the FDA for the acute treatment of anxiety in adults with SAD.

The FDA has granted Fast Track designation for the investigation of fasedienol for the acute treatment of SAD.

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.

According to the World Health Organization (WHO), depression is the leading cause of disability worldwide, affecting over 250 million people.

Statistics reported by the U.S.

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., had at least one major depressive episode in 2020.

While most people will experience a depressed mood at some point during their lifetime, MDD is different.

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.

While many individuals will experience a depressed mood 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.

In typical depressive episodes, 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.

Symptoms of MDD also may include diminished pleasure in activities, changes in appetite that result in weight changes, insomnia or oversleeping, psychomotor agitation, loss of energy or increased fatigue, feelings of worthlessness or inappropriate guilt, difficulty thinking, concentrating or making decisions, and thoughts of death or suicide and attempts at suicide.

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.

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.

MDD is the psychiatric diagnosis most commonly associated with suicide.

For many people, depression cannot be controlled for any length of time without treatment.

Current oral antidepressants have modest efficacy, substantial lag of onset of action, and considerable side effects.

Approximately two out of every three depression sufferers do not receive adequate therapeutic benefits from their initial treatment with a standard antidepressant, and the likelihood of achieving remission of depressive symptoms declines with each successive treatment attempt.

Even after multiple treatment attempts with current antidepressants, approximately one-third of depression sufferers still fail to find an adequately effective therapy.

In addition, this trial and error process and the systemic effects of the various antidepressants involved may increase the risk of patient tolerability issues and serious side effects, including suicidal thoughts and behaviors in certain groups.

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 safety profiles.

Itruvone for the Treatment of MDD

Itruvone is an odorless, tasteless synthetic investigational neuroactive pherine from the pregnane family with a novel, rapid-onset proposed neurocircuitry-focused MOA that is fundamentally differentiated from the MOA of all currently approved treatments for depression disorders.

Itruvone is administered intranasally at low microgram-level doses and is designed to engage and activate chemosensory neurons in the nasal cavity, which are connected to neural circuits in the brain that produce antidepressant effects.

Specifically, in a manner similar to fasedienol, itruvone’s proposed MOA involves the regulation of the olfactory-to-amygdala neural circuitry, but, unlike fasdienol, itruvone is believed to increase the activity of the limbic-hypothalamic sympathetic nervous system and increase the release of catecholamines.

Unlike all currently approved antidepressant therapies, we believe itruvone does not require systemic absorption or binding to neurons in the brain to produce antidepressant effects and achieve those antidepressant effects without the side effects and safety concerns that may be associated with current antidepressant therapies, including, among others, sexual side effects, sedation, weight gain and suicidal ideation.

With its potential for rapid-onset activity at a microgram-level dose that we believe does not require systemic absorption and distribution to achieve sustained antidepressant effects, as well as a safety profile in studies completed to date that is fundamentally differentiated from current depression therapeutics, we believe itruvone has transformative potential an innovative stand-alone treatment for MDD and presents potential opportunities for development in multiple additional depression disorders, including postpartum depression, treatment-resistant depression, and suicidal ideation.

In a randomized, double-blind, placebo-controlled parallel design exploratory Phase 2A clinical trial of itruvone in MDD, the results of which were published in the peer-reviewed British Journal of Pharmaceutical and Medical Research , at a 6.4 μg dose administered intranasally twice daily for eight weeks, itruvone significantly reduced depressive symptoms as early as one week based on the 17-item Hamilton Depression Scale (HAM-D-17) scores compared to placebo (p=0.022).

However, approximately two out of every three people with depression do not experience adequate therapeutic benefits from their initial treatment with a standard antidepressant.

Furthermore, the likelihood of achieving remission of depressive symptoms decreases with each successive treatment attempt.

Even after multiple treatment attempts with current antidepressants, about one-third of individuals with depression still do not find a sufficiently effective therapy.

Itruvone for the Treatment of Major Depressive Disorder

Itruvone is our investigational neurocircuitry-focused non-systemic pherine product candidate with transformative potential as a stand-alone treatment of MDD.

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.

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.

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.

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.

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).

Itruvone was well-tolerated and did not cause psychological side effects (such as dissociation or hallucinations), sexual side effects, weight gain, or other safety concerns that may be associated with other approved pharmacological therapies for MDD.

The trial was sponsored by Pherin Pharmaceuticals, Inc (Pherin), now our wholly-owned subsidiary, and was conducted in Mexico prior to our acquisition of Pherin in February 2023.

Positive data from our recent U.S.

The trial was sponsored by Pherin Pharmaceuticals, Inc.

(Pherin), which is

now our wholly-owned subsidiary, and was conducted in Mexico prior to our acquisition of Pherin in February 2023.

Positive data from our June 2023 U.S.

Investigational New Drug (IND) enabling Phase 1 trial of itruvone demonstrated that there were no reported treatment-related SAEs or discontinuations due to adverse events in the trial.

Overall, itruvone was well-tolerated and continued to demonstrate the favorable safety profile seen in all clinical trials to date.

As a result, we are currently preparing and planning for U.S.

Overall, itruvone was well-tolerated and continued to demonstrate the favorable safety data in all clinical trials completed to date.

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.

Phase 2B clinical development of itruvone under our U.S.

IND as a novel, non-systemic stand-alone treatment for MDD.

The FDA has granted Fast Track designation for our development of itruvone as a potential treatment for MDD.

Women ’ s Health Indications - Vasomotor Symptoms (Hot Flashes) due to Menopause

Vasomotor symptoms are sudden feelings of warmth in the face, neck, and chest, or sudden intense feelings of heat and sweating (hot flashes) commonly experienced by women in menopause.

Presentation of hot flashes is directly linked to changes in hormone levels due to menopause, or menopause induced by other medical treatments or co-existing conditions, and the causal mechanism is unclear.

Hot flashes are the most common symptom of the menopausal transition, affecting about 75% of menopausal women and about 40% of women in perimenopause.

Prevalence of hot flashes is estimated to be about 20 million women in the U.S.

with nine million women estimated to be suffering from severe hot flashes.

Current pharmacotherapies to treat hot flashes include hormonal therapy (estrogen with or without progesterone, or a synthetic progestin), gabapentins, certain antidepressants, clonidine, and fezolinetant, a neurokinin 3 (NK3) receptor antagonist, all of which are associated with certain potentially serious side effects and safety concerns.

FDA has granted Fast Track designation for the investigation of itruvone for the treatment of MDD.

Overview of Vasomotor Symptoms (Hot Flashes) due to Menopause

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.

On average, hot flashes last seven to nine years and, for up to one-third of women, can last more than 10 years.

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 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.

VMS can cause new-onset sleep interruptions and deprivation, with night sweats commonly interrupting sleep and causing difficulty in returning to sleep.

Such sleep problems are associated with reduced productivity and an increased risk of job loss for these affected individuals.

VMS are also often accompanied by various comorbidities, including new onset anxiety, depression, and cognitive dysfunction, which can further exacerbate functional impairment.

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.

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.

PH80 for the Treatment of Vasomotor Symptoms (Hot Flashes) due to Menopause

PH80 is a hormone-free, odorless, tasteless synthetic investigational neuroactive pherine nasal spray with a novel, rapid-onset potential MOA that is fundamentally differentiated from all currently approved treatments for vasomotor symptoms (hot flashes) due to menopause and other women’s health indications.

Microgram-level doses of PH80, administered as a nasal spray, engage and activate chemosensory neurons in the nasal cavity connected to neural circuits in the basal forebrain associated with the control of body temperature.

In June 2023, we reported positive results from a previously unpublished exploratory Phase 2A study of PH80 for the treatment of vasomotor symptoms (hot flashes) due to menopause.

The randomized, double-blind, placebo-controlled exploratory Phase 2A clinical study of PH80 was designed to explore the efficacy, safety, and tolerability of intranasal administration of PH80 for the management of menopausal hot flashes in women.

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.

With more than one million U.S.

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.

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.

Notably, in vitro studies show that PH80 does not engage steroid receptors;

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.

Additionally, an in vitro study has demonstrated that PH80 does not exert effects on receptor targets with known abuse potential.

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.

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.

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.

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At baseline, subjects reported a mean daily number of hot flashes of 7.7 (PH80, n=18) and 8.0 (placebo, n=18).

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) (p<.001).

PH80 treatment also significantly reduced the severity, disruption in function, and sweating related to hot flashes during the treatment period, as compared with placebo.

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All 36 subjects completed four weeks of treatment and no subject discontinued participation in the study as a result of adverse events.

This exploratory Phase 2A study of PH80 was conducted in a real-world setting in Mexico and was sponsored by Pherin prior to our acquisition of Pherin.

Ellen Freeman, Ph.D.

of the University of Pennsylvania served as the Principal Investigator of the study.

We are currently conducting customary nonclinical studies necessary to support our planned submission of our U.S.

We are currently conducting customary nonclinical manufacturing-related studies necessary to support our planned submission of our U.S.

IND to facilitate further Phase 2 clinical development of PH80 in the U.S.

novel non-systemic, non-hormonal treatment of vasomotor symptoms (hot flashes) due to menopause.

Our Other Clinical-Stage Programs

Premenstrual Dysphoric Disorder (PMDD)

According to the National Institutes of Health (NIH), 5% to 8% of menarcheal individuals have moderate-to-severe symptoms that can cause significant distress and functional impairment, suggestive of PMDD, a severe, sometimes disabling extension of premenstrual syndrome (PMS).

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.

Overview of Premenstrual Dysphoric Disorder

According to the National Institutes of Health (NIH), 5% to 8% of menarcheal individuals have moderate-to-severe symptoms that can cause significant distress and functional impairment, suggestive of premenstrual dysphoric disorder (PMDD), a severe, sometimes disabling extension of premenstrual syndrome (PMS).

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.

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Treatment of PMDD is aimed at preventing or minimizing symptomology.

PH80 for PMDD

In September 2023, we reported positive results from a previously unpublished 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.

PH80 for Premenstrual Dysphoric Disorder

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.

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.

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No other TEAE occurred more than once per subject.

This Phase 2A study was sponsored by Pherin, prior to our acquisition of Pherin in February 2023 .

Cognitive and Psychomotor Improvement due to Mental Fatigue

Overview of Cognitive and Psychomotor Impairment due to Mental Fatigue

Numerous disorders, such as shift work disorder, sleep apnea, and narcolepsy, can lead to debilitating sleep deprivation and mental fatigue.

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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.

PH15 for Cognitive and Psychomotor Improvement due to Mental Fatigue

PH15 is an odorless, tasteless synthetic investigational neuroactive pherine with a novel, rapid-onset proposed MOA that is fundamentally differentiated from the MOA of all currently approved treatments to improve psychomotor or cognitive impairment caused by mental fatigue.

PH15’s proposed MOA targets nasal receptors that activate olfactory-amygdala and olfactory hippocampus neural circuits in the limbic system that are known to be associated with psychomotor activity and cognition, without requiring systemic absorption or direct action on neurons in the brain.

PH15 has demonstrated an excellent safety profile in all clinical trials completed to date.

In April 2024, we reported positive results from a Phase 2A pilot study of PH15 for the improvement of psychomotor impairment caused by mental fatigue.

In the previously unreported randomized, double-blind, placebo-controlled, crossover Phase 2A pilot study designed to explore the efficacy, safety, and tolerability of intranasal administration of PH15 on psychomotor performance as measured by reaction time in sleep-deprived participants, PH15 demonstrated a statistically significant improvement in reaction time compared to placebo and caffeine in the sleep-deprived study participants.

PH15 for Improvement of Cognitive and Psychomotor Impairment due to Mental Fatigue

PH15 is our investigational pherine product candidate with a novel, rapid-onset neurocircuitry-focused proposed MOA that is differentiated from the MOA of all currently approved treatments to improve psychomotor or cognitive impairment caused by mental fatigue.

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

cognition, without requiring systemic absorption or direct action on neurons in the brain.

PH15 has demonstrated excellent safety data in all clinical trials completed to date.

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.

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.

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.

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Participants on oral caffeine, however, experienced palpitations, euphoria, dry mouth, stomachache, and polyuria.

This previously unreported Phase 2A pilot study of PH15 was sponsored by Pherin and conducted at the National Institute of Psychiatry, Sleep Disorders Clinic in Mexico City, Mexico prior to our acquisition of Pherin in February 2023.

The late Jose Maria Calvo, MD, formerly Associate Professor, National Institute of Psychiatry in Mexico City, served as the Principal Investigator of the study.

We are currently evaluating the potential Phase 2 development path forward for PH15 and a nonclinical program required to support our submission of a U.S.

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.

IND to facilitate further potential Phase 2 development of PH15 in the U.S.

Cachexia (Wasting Syndrome)

Cachexia (also known as wasting syndrome) is a serious but under-recognized and complex syndrome associated with asymmetric energy supply from food and metabolism.

It is characterized by significant fatigue, lack of hunger, and loss of appetite, weight, and muscle mass, most often affecting individuals with a severe chronic condition, such as cancer and or heart disease.

It is estimated that cachexia from any disease affects more than five million people in the U.S.

The prevalence of cachexia is growing and is estimated at 1% of the U.S.

Currently, there is no specific treatment for cachexia.

Current appetite stimulant medications such as stimulants and cannabinoids are used to treat cachexia to increase food intake, and steroids are sometimes used to stop muscle wasting, but all current options may have detrimental side effects.

PH284 for Cachexia and Appetite-related Disorders

PH284 is an odorless, tasteless synthetic investigational neuroactive pherine nasal spray with a novel, rapid-onset potential 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.

Cachexia is a serious but under-recognized consequence of many chronic diseases with body mass loss of >10% and a prevalence of 5 to 15 %.

We believe PH284 may have therapeutic potential for improving subjective feelings of hunger in patients with cachexia.

We are currently evaluating the potential path forward for PH284, including an assessment of completed studies and studies we believe are necessary to support a U.S.

IND for potential further Phase 2 clinical development of PH284 for the treatment of cachexia, including the appropriate patient populations for demonstrating an increase in appetite and weight gain.

Additional Neurological Disorders

Overview of Cancer Cachexia

Cachexia, also known as wasting syndrome, is a complex metabolic syndrome that causes a gradual loss of muscle and body weight.

Cachexia is associated with chronic diseases like cancer, AIDS, heart failure, chronic obstructive pulmonary disease, anorexia nervosa, multiple sclerosis, tuberculosis, and anemia.

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.

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.

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.

Currently, there are no effective medical interventions or approved drugs proven to alleviate cachexia.

PH284 for Cancer Cachexia

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.

PH284 is thought to act by regulating olfactory to mediobasal-hypothalamus neural circuits involved in appetite control.

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).

From Day 1 through Day 4, all subjects were administered placebo 30 minutes prior to each meal.

Beginning on Day 5 through Day 11 subjects were randomized in a 1:1 fashion to receive either PH284 or placebo.

Patients measured Subjective Feeling of Hunger (SFH) ten minutes before each meal.

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.

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

than 1% improvement.

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 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.

PH284 has demonstrated an excellent safety profile in all clinical trials completed to date.

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.

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.

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

AV-101 for NMDAR-related Neurological Disorders

AV-101 (4-Cl-KYN) is a novel, oral prodrug that targets the NMDAR (N-methyl-D-aspartate receptor), an ionotropic glutamate receptor in the brain.

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.

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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.

We are currently assessing whether there is a path forward for potential Phase 2A clinical development of AV-101 with one or more collaborators, as a treatment for LID associated with Parkinson’s disease therapy and possibly one or more additional neurological disorders involving the NMDAR receptor.

The 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.

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.

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.

Intellectual Property

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and in certain foreign countries.

We expect regulatory and data exclusivity (discussed below) will be available upon product approval of fasedienol in the U.S.

and certain foreign countries.

Itruvone for the Treatment of MDD

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and certain foreign countries.

We expect regulatory and data exclusivity will be available upon product approval of itruvone in the U.S.

and certain foreign countries.

PH80 for the Treatment of Vasomotor Symptoms (Hot Flashes) Due to Menopause and Other Indications

The granted U.S.

a nd foreign patents and corresponding pending foreign patents relate to the use of PH80 to treat vasomotor symptoms (hot flashes) due to menopause.

a nd foreign patents and corresponding pending foreign patent applications relate to the use of PH80 to treat vasomotor symptoms (hot flashes) due to menopause.

Patents that have been or may yet be granted will expire in 2029.

Because of the development timeline for this drug product candidate, it is unlikely that patent term extensions will be available in the U.S.

Because of the development timeline for this indication, it is unlikely that patent term extensions will be available in the U.S.

or foreign countries.

However, regulatory and data exclusivity (discussed below) should be available upon product approval in the U.S.

However, w e expect regulatory and data exclusivity will be available upon product approval of PH80 in the U.S.

and certain foreign countries.

A provisional patent application filed by us on April 8, 2024 relates to the use of PH80 to treat dysmenorrhea.

We plan to file a Patent Cooperation Treaty (PCT) patent application and non-provisional national phase patent applications in due course.

We filed a non-provisional U.S.

national phase patent application and a Patent Cooperation Treaty (PCT) patent application relating to the use of PH80 to treat dysmenorrhea in April 2025.

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.

and certain foreign countries.

PH15 for the Improvement of Psychomotor and Cognitive Performance

A provisional patent application filed by us on June 4, 2023 relates to the use of PH15 to improve psychomotor impairment caused by mental fatigue.

We plan to file a PCT patent application and non-provisional national phase patent applications in due course.

We expect regulatory and data exclusivity will be available upon approval of PH80 for this indication in the U.S.

and certain foreign countries.

PH15 for the Improvement of Psychomotor and Cognitive Impairment due to Mental Fatigue

We filed a non-provisional U.S.

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.

Patents that may be granted on such patent applications nominally will expire in 2044, subject to patent term extensions that may be available in the U.S.

and certain foreign countries.

Regulatory and data exclusivity may be available upon product approval of PH15 for this indication in the U.S.

and certain foreign countries.

Nasal Spray Device for Administration of Pherines

We filed a non-provisional U.S.

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.

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.

and certain foreign countries.

AV-101 for the Potential Treatment of LID, NP, and Other Disorders

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and certain foreign countries.

Regulatory and data exclusivity may be available upon product approval of AV-101 in the U.S.

and certain foreign countries.

Patent Term Adjustments and Extensions

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Strategic Transactions and Relationships

Given the depth of clinical development across our neuroscience pipeline and potential additional preclinical candidates from our pherine platform, we have the potential to pursue multiple strategic development and commercialization partnerships across our pipeline to efficiently unlock the full value of our product candidate portfolio.

We believe p artnerships designed to amplify our ongoing or past internal research and development activities may efficiently advance key development and regulatory milestones for our product candidates, especially outside the U.S.

In addition, we believe that our highly selective outsourcing of certain research, development, legal, manufacturing and regulatory advisory activities gives us flexible access to a broad range of capabilities and expertise at a lower overall cost than developing and maintaining certain of such capabilities and expertise internally on a full-time basis.

Any such partnership considerations will be designed to amplify our ongoing or past internal research and development activities, which may efficiently advance key development and regulatory milestones for our product candidates.

In addition, we believe that our highly selective outsourcing of certain research, development, legal, manufacturing and regulatory advisory activities gives us flexible access to a broad range of capabilities and expertise at a lower overall cost than developing and maintaining such capabilities and expertise internally on a full-time basis.

In particular, we retain third parties for certain accounting, legal, manufacturing, nonclinical development, clinical development, and regulatory affairs support.

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The Purchase Price is non-refundable, except upon a material breach of the Negotiation Agreement by us, however, should we and Fuji Pharma enter into the Potential Definitive Agreement, the Purchase Price will be credited against any upfront fee due in connection with the execution of such agreement.

Neither we nor Fuji Pharma is obligated to enter into the Potential Definitive Agreement, and if we and Fuji Pharma have not entered into the Potential Definitive Agreement on or before the end of the Exclusive Negotiation Period, either party may terminate any further negotiations.

Neither we nor Fuji Pharma are obligated to enter into the Potential Definitive Agreement, and if we and Fuji Pharma have not entered into the Potential Definitive Agreement on or before the end of the Exclusive Negotiation Period, either party may terminate any further negotiations.

Manufacturing and Supply

Manufacturing of the drug substance and drug product for our product candidates is performed by CMOs who must comply with current good manufacturing practice (cGMP) regulations.

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.

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.

We do not currently own or operate, nor do we plan to own or operate, manufacturing facilities for the production of our drug substances and drug product candidates for nonclinical, clinical or commercial use.

We conduct manufacturing and analytical testing activities under individual project work orders with independent CMOs to supply all of our nonclinical and clinical trial needs.

We conduct periodic quality audits of each of the CMO’s facilities to ensure that they are fully compliant with cGMPs.

We believe that all of our existing CMOs are, or will be, capable of providing sufficient quantities of both drug substance and drug product to meet our nonclinical and clinical development needs.

New CMOs may be added to our supply chain strategy in the future to ensure that our nonclinical, clinical and, subject to NDA approval, commercial manufacturing and testing needs are met.

By design, we do not currently have any fixed contractual arrangements in place with any CMOs, for either long-term supply or redundant supply, of drug substances or drug product for our drug product candidates.

If our product candidates are approved for commercial distribution, we intend to execute long-term commercial supply agreement(s) with our CMOs to produce our future commercial supplies on our behalf.

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.

We conduct periodic quality audits of each of the CDMO’s facilities to ensure that they are fully compliant with cGMPs.

We believe that all of our existing CDMOs are, or will be, capable of providing sufficient quantities of both drug substance and drug product to meet our nonclinical and clinical development needs, as well as our commercial needs.

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.

By design, we do not currently have any fixed contractual arrangements in place with any CDMOs, for either long-term supply or redundant supply of drug substances or drug product for our pherine product candidates.

If 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.

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.

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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.

While we believe that our employees and consultants, scientific knowledge, technology, and development experience provide us with competitive advantages, we face potential competition from many different sources, including major pharmaceutical, specialty pharmaceutical, and biotechnology companies, academic institutions and governmental agencies, and public and private research institutions.

While we believe that our employees and consultants, scientific knowledge, technology, and development experience provide us with competitive

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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Small or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

The key competitive factors affecting the success of all of our product

candidates, if approved, are likely to be their efficacy, safety, tolerability, convenience, price, the level of branded and generic competition, and the availability of reimbursement from government and other third‑party payers.

The key competitive factors affecting the success of all of our product candidates, if approved, are likely to be their efficacy, safety, tolerability, convenience, price, the level of branded and generic competition, and the availability of reimbursement from government and other third‑party payers.

Social Anxiety Disorder

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.

We are aware of companies that are or may be developing therapies targeting acute treatment in the SAD market, including, among others, Bionomics, Vanda Pharmaceuticals, and Receptor Life Sciences, Ananda Scientific, EmpowerPharm and PureTech.

In addition, we may face competition to fasedienol for treatment of anxiety in adult and adolescent patients with SAD from generic antidepressants as well as off-label use of generic benzodiazepines and generic beta blockers even though no drug in either of such generic drug classes has been systematically developed for treatment of SAD, acute or otherwise, and thus no drug in either of such generic drug classes has been FDA-approved for the acute treatment of SAD.

Although there are three generic oral antidepressants approved by the FDA for the treatment of SAD, such drugs do not achieve rapid-onset therapeutic effects and are associated with undesirable side effects.

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.

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.

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.

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.

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sertraline (Zoloft) and venlaxafine (Effexor), both previously marketed by Pfizer, Inc.;

and paroxetine (Paxil) and bupropion (Wellbutrin), both previously marketed by GlaxoSmithKline (now GSK).

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:

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Lundbeck A/S;

Viibryd and Vraylar, which are marketed by Abbvie;

and Rexulti which is marketed by Otsuka America.

Although currently there are no FDA-approved therapies for MDD with the neurocircuitry-focused MOA of itruvone, we are aware of numerous companies that are developing and commercializing or have commercialized therapies targeting the MDD market, including, among others, Axsome Therapeutics, Sage Therapeutics, Relmada Therapeutics, Xenon, Intra-Cellular Therapies, Johnson & Johnson, Usona Institute, Boehringer Ingelheim, and Sirtsei Pharmaceuticals.

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.

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.

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.

Vasomotor Symptoms (hot flashes) due to Menopause

We are aware of various current pharmacotherapies for vasomotor symptoms (hot flashes) due to menopause, including hormonal therapy (estrogen with or without progesterone, or a synthetic progestin), gabapentins, certain antidepressants, clonidine, as well as fezolinetant, a newly-approved non-hormonal neurokinin 3 (NK3) receptor antagonist developed and commercialized by Astellas, and a similar product candidate, elinzanetant, a non-hormonal, NK3 receptor antagonist, in late-stage development by Bayer.

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.

Other Indications

We are still assessing our potential competition for PH15 to improve cognitive and/or psychomotor impairment and PH284 for cachexia (wasting syndrome).

We are still assessing our potential competition for PH15 to improve cognitive and/or psychomotor impairment and PH284 for cancer cachexia.

Government Regulation and Product Approval

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This includes, for example, requirements that manufacturers of pharmaceutical products participating in Medicaid and Medicare comply with mandatory price reporting, discount, rebate requirements, and other cost control measures, as well as anti-kickback laws and laws prohibiting false claims.

Some states also have enacted fraud,

waste, and abuse laws that parallel (and in some cases apply more broadly than) federal laws, and in some cases price transparency requirements.

Some states also have enacted fraud, waste, and abuse laws that parallel (and in some cases apply more broadly than) federal laws, and in some cases price transparency requirements.

FDA Regulation

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In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin.

Clinical holds also may be imposed by the FDA at any time before or during trials due to safety concerns or noncompliance with applicable requirements, and in either case, the proposed trial or trials may not begin or continue until the FDA notifies the IND sponsor that the hold has been lifted.

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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Investigators must also provide certain information to the clinical trial sponsors to allow the sponsors to make certain financial disclosures to the FDA.

Clinical trials are conducted under protocols detailing, among other things, the objectives of the trial, dosing procedures, subject selection and exclusion criteria and the

safety and effectiveness criteria to be evaluated.

Clinical trials are conducted under protocols detailing, among other things, the objectives of the trial, dosing procedures, subject selection and exclusion criteria and the safety and effectiveness criteria to be evaluated.

A protocol for each clinical trial, and any subsequent protocol amendments, must be submitted to the FDA as part of the IND.

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The FDA may also require, or companies may conduct, additional clinical trials for the same indication after a product is approved.

These so-called Phase 4 studies are often conducted to gain additional experience from the treatment of patients in the intended therapeutic indication and may be required by the FDA as a condition of approval of the NDA.

These clinical trials, sometimes referred to as, Phase 4 studies are often conducted to gain additional experience from the treatment of patients in the intended therapeutic indication and may be required by the FDA as a condition of approval of the NDA.

Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the product candidate as well as finalize a process for manufacturing the product in commercial quantities in accordance with cGMPs.

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NDA Submission, Review by the FDA, and Marketing Approval

Assuming successful completion of the required clinical and preclinical testing, the results of product development, including chemistry, manufacturing, and control (CMC) information, results from non-clinical studies and clinical trial results, including negative or ambiguous results as well as positive findings, are all submitted to the FDA, along with the

proposed labeling, as part of an NDA requesting approval to market the product for one or more indications.

In most cases, the submission of an NDA is subject to a substantial application user fee, authorized every five years by Congress under the Prescription Drug User Fee Act (PDUFA).

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Before approving an NDA, the FDA typically will inspect the facility or facilities where the product and/or its drug substance is manufactured.

The FDA will not approve an application unless it determines that the manufacturing processes and facilities, including contract manufacturers and subcontractors, are in compliance with cGMP requirements and adequate to assure consistent production of the product within the required specifications.

adequate to ensure consistent production of the product within the required specifications.

Additionally, before approving an NDA, the FDA may inspect one or more clinical trial sites to assure compliance with GCPs.

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If a CRL is issued, the applicant may either resubmit the NDA, addressing all of the deficiencies identified in the letter;

withdraw the application;

or request an opportunity for a hearing.

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Specifically, drugs intended to treat serious or life-threatening diseases or conditions may be eligible for accelerated approval upon a determination that the product candidate has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

As a condition of approval, the FDA generally requires that a sponsor of a drug receiving accelerated approval perform adequate and well-controlled confirmatory clinical trials, and may require that such confirmatory trials be underway prior to granting accelerated approval.

As a condition of approval, the FDA generally requires that

a sponsor of a drug receiving accelerated approval perform adequate and well-controlled confirmatory clinical trials, and may require that such confirmatory trials be underway prior to granting accelerated approval.

Drugs receiving accelerated approval may be subject to expedited withdrawal procedures if the sponsor fails to conduct the required confirmatory trials in a timely manner or if such trials fail to verify the predicted clinical benefit.

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FDA Regulation of Combination Products

Certain product candidates may be comprised of components, such as drug components and device components, that would normally be regulated under different types of regulatory authorities, and frequently by different centers at the FDA.

Certain product candidates may be comprised of components, such as drug components and device components, which would normally be regulated under different types of regulatory authorities, and frequently by different centers at the FDA.

These products are known as combination products.

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Changes to the manufacturing process are strictly regulated and often require prior FDA approval or notification before being implemented.

FDA regulations also require investigation and correction of any deviations from cGMP and product specifications and impose reporting and documentation requirements upon the sponsor and any third‑party manufacturers

that the sponsor may decide to use.

Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain cGMP compliance.

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An NCE is a drug that contains no active moiety that has been approved by the FDA in any other NDA.

An active moiety is the molecule or ion excluding those appended portions of the molecule that cause the drug to be an ester, salt, including a salt with hydrogen or coordination bonds, or other noncovalent derivatives, such as a complex, chelate, or clathrate, of the molecule, responsible for the therapeutic activity of the drug substance.

molecule, responsible for the therapeutic activity of the drug substance.

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.

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During the NCI exclusivity period, FDA may not approve an ANDA or 505(b)(2) NDA by another company for the condition of approval of the drug to which the exclusivity applies.

exclusivities will not delay the submission or approval of a full NDA;

NCE and NCI exclusivities will not delay the submission or approval of a full NDA;

however, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well‑controlled clinical trials necessary to demonstrate safety and efficacy.

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Civil FCA actions may be brought by the government or may be brought by private individuals on behalf of the government, called “qui tam” actions.

If the government decides to intervene in a qui tam action and prevails in the lawsuit, the individual will share in the proceeds from any fines or

settlement funds.

If the government decides to intervene in a qui tam action and prevails in the lawsuit, the individual will share in the proceeds from any fines or settlement funds.

If the government declines to intervene, the individual may pursue the case alone, subject to governmental review and certain approvals.

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Such enforcement actions would prohibit the manufacturer from engaging those individuals, which could adversely affect operations, and could result in significant reputational harm.

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.

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.

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impose restrictions on marketing practices;

or require drug manufacturers to track and report information related to payments, gifts, and other

items of value to physicians and other healthcare providers.

or require drug manufacturers to track and report information related to payments, gifts, and other items of value to physicians and other healthcare providers.

These laws may affect our future sales, marketing, and other promotional activities by imposing administrative and compliance burdens.

Because of the breadth of these laws and the narrowness of the statutory exceptions and regulatory safe harbors available under such laws, it is possible that certain business activities could be subject to challenge under one or more of such laws.

The scope and enforcement of each of these laws is uncertain and subject to rapid change in the current environment of healthcare reform, especially in light of the lack of applicable precedent and regulations.

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Therefore, coverage and reimbursement can differ significantly from payor to payor and health care provider to health care provider.

As a result, the coverage determination process is often time-consuming and costly and may require the provision of scientific and clinical support for the use of new products to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.

As a result, the coverage determination process is often time-consuming and costly and may require the provision of scientific and clinical support for the use of

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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Coverage and reimbursement may impact the demand for, or the price of, any drug candidate for which we obtain marketing approval.

If coverage and reimbursement are not

available or reimbursement is available only to limited levels, we may not successfully commercialize any drug candidate for which we obtain marketing approval.

If coverage and reimbursement are not available or reimbursement is available only to limited levels, we may not successfully commercialize any drug candidate for which we obtain marketing approval.

Healthcare Reform

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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.

Some third-party payors also require pre-approval of coverage for new or innovative devices or therapies before they will reimburse healthcare providers that use such therapies.

Some third-party payors also require pre-

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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As in the U.S., post‑approval regulatory requirements, such as those regarding product manufacture, marketing, or distribution, would apply to any product that is approved outside the U.S.

Subsidiaries and Inter-Corporate Relationships

As of March 31, 2024, we had two wholly-owned subsidiaries, Pherin Pharmaceuticals, Inc., a Delaware corporation, and Vistastem Inc., a California corporation.

The operations of these subsidiaries are managed by our senior management team based in South San Francisco, California.

Corporate History

Vistastem, Inc., a California corporation (formerly VistaGen Therapeutics, Inc.) was incorporated on May 26, 1998, and is our wholly-owned subsidiary.

Excaliber Enterprises, Ltd.

(Excaliber), a publicly-held company (formerly OTCBB:

EXCA) was incorporated under the laws of the State of Nevada on October 6, 2005.

Pursuant to a strategic merger transaction on May 11, 2011, Excaliber acquired all outstanding shares of Vistastem in exchange for 341,823 shares of our common stock and assumed all of Vistastem’s outstanding obligations at that time (the Merger).

Shortly after the Merger, Excaliber’s name was changed to “Vistagen Therapeutics, Inc.” (a Nevada corporation).

Vistastem, as the accounting acquirer in the Merger, recorded the Merger as the issuance of common stock for the net monetary assets of Excaliber, accompanied by a recapitalization.

The accounting treatment for the Merger was identical to that resulting from a reverse acquisition, except that we recorded no goodwill or other intangible assets.

A total of 78,450 shares of our common stock, representing the shares held by stockholders of Excaliber immediately prior to the Merger are reflected as outstanding for all periods presented in the Consolidated Financial Statements of the Company included in

Item 8 of this Annual Report.

Additionally, the Consolidated Balance Sheets reflect the $0.001 par value of Excaliber’s common stock.

On December 20, 2022, we entered into an Agreement and Plan of Merger (the Merger Agreement) along with VTGN Merger Sub, Inc., our wholly-owned subsidiary (Merger Sub), Pherin Pharmaceuticals, Inc.

(Pherin), and Kevin McCarthy in his capacity of Stockholder Representative, in order to acquire Pherin (the Pherin Acquisition).

On February 2, 2023 (the Closing Date), we completed the Pherin Acquisition and Pherin became a wholly-owned subsidiary of the Company.

As a result of the Pherin Acquisition, we obtained full ownership of intellectual property rights to all five of our pherine drug candidates.

The Consolidated Financial Statements included in Item 8 of this Annual Report represent the activity of Vistastem from May 26, 1998, the consolidated activity of Vistastem and Excaliber (now Vistagen Therapeutics, Inc., a Nevada corporation), from May 11, 2011 (the date of the Merger) through March 31, 2024, and the activity of Pherin Pharmaceuticals, Inc.

from February 2, 2023 (the date of the Pherin Acquisition) through March 31, 2024.

For the relevant periods, the Consolidated Financial Statements included in Item 8 of this Annual Report also include the accounts of Vistastem’s two wholly owned inactive subsidiaries, Artemis Neuroscience, Inc., a Maryland corporation which was dissolved in April 2022, and VistaStem Canada, Inc., a corporation organized under the laws of Ontario, Canada which was dissolved in June 2022.

Research and Development

Conducting research and development is central to our business model.

We have invested and expect to continue to invest significant time and capital in our research and development operations.

Our research and development expenses were approximately $20.0 million and $44.4 million for the years ended March 31, 2024 and 2023, respectively.

We expect that our research and development expenses will remain a significant portion of our total operating costs for the foreseeable future as we seek to complete the development of fasedienol, itruvone, PH80 and our other product candidates.

Environmental, Social, Governance, and Human Capital

We believe corporate responsibility is fundamental to our mission and we are committed to holding ourselves to high ethical standards.

Beyond our quest to develop innovative therapeutic solutions that combat neurological disorders affecting so many lives and to improve healthcare outcomes, we strive to have a positive impact on our employees, our local communities, our shareholders, patients and the healthcare ecosystem, and society as a whole.

Governance and Leadership

As a clinical-stage biopharmaceutical company that is passionate about pioneering neuroscience to transform lives affected by anxiety, depression and other neurological disorders, we believe creating an environment that allows our team to collectively thrive and achieve its full potential begins with our Board of Directors, which consists of directors with diverse and dynamic backgrounds in pharmaceutical research and development, commercialization, finance, law, and corporate governance.

Applying the Nasdaq Stock Market’s continued listing standards for director independence, five of our seven directors are currently independent.

At the management level, we have built a team of highly experienced professionals that we believe provide us with a diverse and inclusive culture, while also providing the know-how necessary to allow us to achieve our short- and long-term goals.

Among these goals is to develop a formal environmental, social and governance ( ESG ) strategic roadmap and framework that will guide our operations, to ensure that we are operating in a manner that is consistent with our mission of developing and commercializing groundbreaking therapies for neuroscience disorders.

Core Values and Ethics

We are committed to driving improvement and innovation in the care of patients suffering from neuropsychiatric and neurological disorders.

In this pursuit, our core values of integrity, compassion, teamwork, and excellence guide our internal processes and define our mission to radically improve mental and physical health and well-being worldwide.

In addition, all of our directors, officers and employees are responsible for upholding these values as set forth in our Code of Business Conduct, which forms the foundation of our policies and practices.

Our Code of Business Conduct is available on our website at www.vistagen.com .

Environmental Commitment

We are committed to protecting the environment and attempt to mitigate any negative impact of our operations.

We strive to address the environmental impacts of the building in which we operate and minimize waste by reducing our use of paper by operating primarily in a digital environment.

We have safety protocols in place for handling biohazardous waste in our labs, and we use third-party vendors for biohazardous waste and chemical disposal.

Human Capital and Employees

We believe that our people are one of our greatest assets.

With colleagues who can contribute unique viewpoints and diverse perspectives to all aspects of the business, we believe that our culture can be more collaborative, more accepting of difference and more prepared for overall success as we seek to o develop groundbreaking therapies for psychiatric and neurological disorders.

As of June 10, 2024, we employed 39 full-time employees and one part-time employees.

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.

As of May 31, 2025, we employed 56 full-time employees and one part-time employee.

40 full-time employees work in research and development and laboratory support services, and 16 full-time employees work in management, corporate development and communications, legal, human resources, general and administrative roles.

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We consider our employee relations to be good.

We lease our office and laboratory space, which is approximately 10,900 square feet and located in South San Francisco, California, under a lease expiring on July 31, 2027, which provides a five-year option to renew.

Legal Proceedings

Available Information

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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.

What changed 10-K

Item 1. Business