PH10 nasal spray / VistaGen - LARVOL DELTA

Brain and Peripheral Tissue Distribution of Intranasal Radiolabeled Itruvone (PH10) in Laboratory Rats (ASCP 2024) - ": One male and one female rat were used for autoradiographic analysis at each time point. A single intranasal administration of 14C-itruvone was largely confined to the nasal passages and digestive system, with low or undetectable 14C-itruvone uptake in either peripheral (e.g., blood and blood plasma, kidney, pancreas testes/uterus) or central nervous system (CNS: olfactory lobes, cerebrum, cerebellum, and spinal cord) tissue at all time points- from 15 minutes to 168 hours after intranasal administration. Blood and plasma concentrations (ng Equivalents 14C-itruvone/g, where the lower limit of detection was <9.4 ng-eq/g), as measured by LSC, were also low, peaking at 15 minutes in males (12.3 and 21.3 ng-eq/g, respectively) and at 1 hour in female rats (88.4 and 145 ng-eq/g, respectively)."

Late-breaking abstract • Preclinical • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • DERL1

Contact Inhibition of Proliferation Is Accompanied by Expression of the PHF10D Subunit of the Chromatin Remodeling Complex PBAF in Mouse and Human Cell Lines. (PubMed, Dokl Biochem Biophys) - "In this work, we have established that, upon contact inhibition of mouse and human cell proliferation caused by the establishment of a tight junction and adherence junction between cells, the expression of the PHF10A isoform stops and instead the PHF10D isoform is expressed, which does not contain DPF-domain and N-terminal sequence. The function of the PHF10D isoform may be associated with the establishment of intercellular contacts."

Journal • Preclinical

A novel chromatin-remodeling complex variant, dcPBAF, is involved in maintaining transcription in differentiated neurons. (PubMed, Front Cell Dev Biol) - "dcPBAF binds promoters of the actively transcribed neuron-specific and housekeeping genes in terminally differentiated neurons of adult mice. Furthermore, in differentiated human neuronal cells, PHF10D-containing dcPBAF maintains a high transcriptional level at several neuron-specific genes."

Journal • SMARCA4

Impaired Health-Related Quality of Life in Patients with Idiopathic Inflammatory Myopathies: A Cross-Sectional Analysis from the COVAD Dataset (ACR Convergence 2023) - "Both physical and mental health are significantly impaired in patients with IIMs particularly the elderly, IBM and those with specific comorbidities, calling for greater attention and optimized multidisciplinary care to enhance patient-reported experience and global well-being in this population. Figure 1 (A) A flow diagram of participant selection (B) Demographics and clinical characteristics of the participants included the COVAD-2 e-survey (C) Multivariable regression analysis to identify factors affecting PROMIS GMH score in patients with IIMs Figure 2: HRQoL in IIM patients, in comparison with non-IIM AIRDs, NRAIDs and Controls (A): PROMIS GPH scores (B): PROMIS GMH scores (C): PROMIS PH-10a score (D): Pain VAS score (E): PROMIS Fatigue-4a score Figure 3: HRQoL in patients with IIMs subtypes (A): PROMIS GPH scores (B): PROMIS GMH scores (C): PROMIS PH-10a score (D): Pain VAS score (E): PROMIS Fatigue-4a score"

Clinical • HEOR • Cardiovascular • CNS Disorders • Diabetes • Fatigue • Hypertension • Immunology • Infectious Disease • Inflammation • Interstitial Lung Disease • Mental Retardation • Metabolic Disorders • Myositis • Novel Coronavirus Disease • Pain • Psychiatry • Pulmonary Disease • Respiratory Diseases • Rheumatology

VISTAGEN THERAPEUTIC (VSTA) Q1 2022 Earnings Call Transcript (The Motley Fool) - "Our research and development expenses increased from 1.7 million to 5.6 million for the quarters ended June 30, 2020, and 2021 respectively. This increase is primarily due to expenses related to the commencement of our PH94B PALISADE phase 3 program, notably, the initiation of the PALISADE-1 phase 3 clinical trial, but also including expenses for the preparation for and execution of other clinical and nonclinical development, outsourced manufacturing, and regulatory activities for both PH94B and PH10, which, in aggregate, accounted for increase expenses of approximately 2.7 million during the fiscal 2022 first quarter....What we expect to be about 150 subjects phase 2B study with PH10, bladed as a potential stand-alone treatment for major depressive disorder."

Clinical protocol • Commercial • CNS Disorders • Depression • Major Depressive Disorder

VistaGen Therapeutics Reports Fiscal Year 2022 First Quarter Financial Results and Provides Corporate Update (GlobeNewswire) - "PH10 Nasal Spray: Exploratory Phase 2A clinical development of PH10 as a potential rapid-onset treatment of major depressive disorder (MDD) has been completed. VistaGen is preparing to initiate a U.S. Phase 2B multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety and tolerability of PH10 as a potential rapid-onset, stand-alone treatment for MDD in mid-2022....AV-101: VistaGen is currently preparing to initiate a Phase 1B clinical study to evaluate AV-101 in combination with probenecid during the second half of calendar 2021."

New P1 trial • New P2b trial • Trial completion • CNS Disorders • Depression • Major Depressive Disorder

VistaGen’s PH10 Nasal Spray Demonstrates Different Mechanism of Action from Benzodiazepines in Preclinical Study (GlobeNewswire) - "...preclinical data demonstrating that the potential mechanism of action of PH10...does not involve direct activation of GABA-A receptors, in distinct contrast to the mechanism of action of benzodiazepines...Instead, PH10 is designed to engage receptors in nasal chemosensory neurons which in turn regulate neurons in the limbic amygdala that release excitatory neurotransmitters producing rapid-onset antidepressant effects....PH10 may have the potential to displace existing SSRIs and SNRIs as a stand-alone alternative in the drug treatment paradigm for depression disorders."

Preclinical • CNS Disorders • Depression • Major Depressive Disorder

VistaGen Therapeutics Reports Fiscal 2021 Third Quarter Financial Results and Provides Update on Expected Clinical Studies in Calendar 2021 (VistaGen Press Release) - " 'This year, we will also complete preparations to launch Phase 2B clinical development of PH10 as a potential rapid-onset stand-alone treatment for major depressive disorder in early 2022. Finally, later this year, based on successful preclinical studies involving AV-101 alone and in combination with probenecid, we will launch Phase 1B'...PH10 development expenses increased by approximately $1.5 million in the quarter ended December 31, 2020...AV-101-related expenses decreased primarily due to the completion of the Company’s multi-center Phase 2 study of AV-101 for the adjunctive treatment of major depressive disorder in the quarter ended December 31, 2019....At December 31, 2020, the Company had cash and cash equivalents of approximately $104.3 million....Sufficient to advance an important stream of potential clinical and regulatory catalysts, including...Phase 2B clinical development of PH10..."

Commercial • New P1 trial • New P2b trial • CNS Disorders • Depression • Major Depressive Disorder

VistaGen Announces Publication in CNS Spectrums Detailing Proposed Mechanism of Action of Its Investigational Neuroactive Nasal Sprays for Anxiety and Depression Disorders (GlobeNewswire) - "VistaGen Therapeutics, Inc....announced today that Dr. Louis Monti, VistaGen Vice President, Translational Medicine, and Dr. Michael Liebowitz...authored an article...on the proposed mechanism of action of the Company’s investigational neuroactive nasal sprays, PH94B and PH10...The publication details the proposed neural circuits mediating the mechanism of action of pherines, including PH94B and PH10, which are synthetic neuroactive steroids designed to engage nasal chemosensory receptors and produce rapid-onset anxiolytic and antidepressant effects, respectively."

Review • CNS Disorders • Depression • General Anxiety Disorder

VistaGen Therapeutics Announces Pricing of Underwritten Public Offering (GlobeNewswire) - "VistaGen Therapeutics, Inc....today announced the pricing of its underwritten public offering consisting of 63,000,000 shares of its common stock at an offering price of $0.92 per share...All of the securities in the offering are being sold by VistaGen....VistaGen intends to use the net proceeds from the offering for research, development and manufacturing and regulatory expenses associated with continuing development of PH94B, PH10, AV-101, and potential drug candidates to expand its CNS pipeline and for other working capital and general corporate purposes."

Financing • CNS Disorders • Depression • General Anxiety Disorder • Parkinson's Disease

VistaGen Announces Korean Intellectual Property Office Decision to Grant PH10 Patent for Treatment of Depression (PRNewswire) - "VistaGen Therapeutics...today announced that the Korean Intellectual Property Office (KIPO) in the Republic of Korea has issued a Decision to Grant Patent Application No. 10-2015-7020176 related to methods of treating depressive disorder with VistaGen's PH10...The patent is not set to expire earlier than 2034."

Patent • CNS Disorders • Depression

Form 424B5 VistaGen Therapeutics (Streetinsider.com) - "We are currently preparing PH10 for Phase 2B development as a potential stand-alone treatment for MDD. In several clinical studies, we have established that AV-101 is orally available and has an excellent safety profile....We are currently assessing potential Phase 1B and subsequent Phase 2A development of AV-101, in combination with probenecid, for treatment of depression....We believe that PH10 also has potential as a novel treatment for postpartum depression (PPD), treatment-resistant depression (TRD) and suicidal ideation (SI)."

New P2a trial • New P2b trial • Trial status • CNS Disorders • Depression

VistaGen Therapeutics Reports Fiscal Year 2020 Results and Provides CNS Pipeline Update (PRNewswire) - "Social Anxiety Disorder (SAD): The Company is currently in final-stage discussions with the FDA regarding key details of its plan for Phase 3 clinical development of PH94B....VistaGen submitted a protocol and development plan for an exploratory open-label Phase 2A study of PH94B for treatment of adjustment disorder with anxiety (AjDA) related to the COVID-19 pandemic. PH10 Neuroactive Nasal Spray: Company is preparing for planned Phase 2B clinical development of PH10 in the U.S. for MDD....U.S. Patent and Trademark Office (USPTO) granted U.S. Patent No. 10,322,138 related to methods of treating MDD with PH10. Newly granted patent will not expire until at least 2034. Counterpart foreign patents have already been issued in China, Europe, Japan and several other countries."

FDA event • New P2a trial • Patent • CNS Disorders • Depression • Social Anxiety Disorder

VistaGen up 15% premarket on positive PH10 data (SeekingAlpha) - "Nano cap VistaGen Therapeutics...jumps 15% premarket on increased volume in response to positive results from a single-site, 30-subject Phase 2a clinical trial evaluating PH10...in patients with major depressive disorder (MDD)."

P2a data • Stock price

VistaGen announces positive results of newly published exploratory phase 2a study of PH10 for rapid-onset treatment of major depressive disorder (PRNewswire) - P2a, N=30; "VistaGen Therapeutics...announced positive results from a newly published exploratory Phase 2a clinical study of PH10...for treatment of major depressive disorder (MDD). Results...have been published in the peer-reviewed British Journal of Pharmaceutical and Medical Research...Notably, both the PH10 3.2 µg and 6.4 µg treatment groups showed strong effect sizes after one week of treatment (0.72 for the 3.2 µg dose and 1.01 for the 6.4 µg dose) and at the Week 8 study endpoint (0.74 for the 3.2 µg dose and 0.95 for the 6.4 µg dose)."

P2a data

VistaGen Therapeutics reports fiscal 2020 third quarter financial results and provides CNS pipeline overview (PRNewswire) - "Research and development expense decreased to $3.0 million for the fiscal quarter ended December 31, 2019, compared with $5.3 million for the fiscal quarter ended December 31, 2018, primarily due to the 2018 noncash expense associated with the acquisition of the PH10 license. Expenses related to the Elevate study of AV-101 in MDD and other AV-101 related nonclinical activities decreased in the quarter ended December 31, 2019 compared to 2018..."

Commercial

VistaGen Therapeutics reports fiscal 2020 first quarter financial results (VistaGen Press Release) - "Research and development expense totaled $4.3 million for the fiscal quarter ended June 30, 2019, compared with $2.7 million for the fiscal quarter ended June 30, 2018. The increase in research and development expense is primarily related to the continued progress of ELEVATE, the Company’s Phase 2 clinical study...for adults with major depressive disorder (MDD), several preclinical studies, including studies supporting AV-101’s potential for treating neuropathic pain (NP) and levodopa-induced dyskinesia (LID) in patients with Parkinson’s disease, and manufacturing activities involving AV-101 and the Company’s two novel, clinical-stage neuroactive nasal spray candidates, PH94B for social anxiety disorder (SAD) and PH10 for MDD."

Commercial

VistaGen Therapeutics announces USPTO grant of patent for treatment of depression with fast-acting PH10 neuroactive nasal spray (VistaGen Press Release) - P2a, N=30; "VistaGen Therapeutics...today announced that the U.S. Patent and Trademark Office (USPTO) has granted U.S. Patent No. 10,322,138 related to methods of treating major depressive disorder (MDD) with VistaGen’s PH10 neuroactive nasal spray...The newly granted patent will not expire until at least 2034....In an exploratory 30-patient Phase 2a clinical study, PH10 was well-tolerated and, at microgram doses, demonstrated rapid-onset antidepressant effects, as measured by the Hamilton Depression Rating Scale (HAM-D), without psychological side effects or safety concerns. VistaGen is planning Phase 2b clinical development of PH10 in 2020..."

New P2b trial • P2a data • Patent

VistaGen Therapeutics reports fiscal year 2019 results and provides CNS pipeline overview (VistaGen Press Release) - "PH10 for MDD, Phase 2a Study: In an exploratory 30-patient Phase 2a clinical study, PH10 was well-tolerated and, at microgram doses, demonstrated rapid-onset antidepressant effects, as measured by the Hamilton Depression Rating Scale (HAM-D), without psychological side effects or safety concerns. VistaGen is planning Phase 2b clinical development of PH10 as a first-line treatment for MDD."

New P2b trial • P2a data

VistaGen Therapeutics reports fiscal 2019 third quarter financial results (VistaGen Press Release) - "Research and development expense totaled approximately $5.3 million for the quarter ended December 31, 2018, compared with approximately $1.6 million for the quarter ended December 31, 2017. The period over period increase is primarily attributable to expenses of the ELEVATE study, manufacturing additional supplies of AV-101 for future clinical and preclinical studies...commercialize PH10."

Commercial

VistaGen Therapeutics Receives Notice of Allowance for U.S. Patent for Treatment of Depression with PH10 (GlobeNewswire, VistaGen Therapeutics, Inc.) - "VistaGen Therapeutics...today announced that the U.S. Patent and Trademark Office (USPTO) has provided a Notice of Allowance for a patent related to methods of treating depression with PH10...'Once issued, this patent will be a key component of our commercial protection strategy for PH10 in the U.S., in a manner similar to our issued U.S. patent for therapeutic uses to treat depression with AV-101, which will not expire until at least 2034.'."

Patent