Salubrin

大部分人对“社恐”这个词并不陌生，且经常性意指“压力下的内向与不适”，常用于自我调侃，认为其仅仅只是社交能力的缺陷。但最近一项最新研究却令人大跌眼镜，原来“社恐”真的是一种病！据悉，“社恐”是指“社交恐惧症”，也叫社会焦虑症，是一种不可忽视的精神障碍，高发年龄在17-30岁之间，青少年为最主要人群。如不及时、尽早治疗，极可能发展成为长期慢性疾病，严重影响了青少年健康成长。原则上讲，社交恐惧单纯依靠自我调整可能无法根本解决，需要包括药物治疗和心理治疗等科学规范的系统治疗。且目前还没有单独针对“社恐”的药物问世，最常用的治疗药物是传统的抗抑郁药物和抗焦虑药物。但最近，关于“社恐”的新药研究终于迎来了关键性的喜讯。0115年，社恐新药三期首告捷8月7日，美国生物制药公司Vistagen官网宣布，其旗下的治疗社交焦虑症的新药Fasedienol(PH94B）的三期临床PALISADE-2取得积极数据，研究达到SUDS(Subjective units of distress，SUDS）主要终点和CGI-I次要终点。图源：Vistagen官网公开资料显示，Fasediemol是全球首创的一种基于pherine设计的作用机制新颖、快速起效的信息素鼻喷剂，其可以与鼻腔内化学感觉细胞上的受体结合，起到调节作用为控制恐惧和焦虑的嗅觉杏仁体神经回路，减弱交感自主神经系统的张力。根据Vistagen公布的PALISADE-2的多中心、随机双盲、安慰剂对照3期研究的结果显示，该试验达到主要疗效终点。即与基线相比，接受PH94B鼻喷剂治疗的患者表现出的平均SUDS评分（最小二乘均值[LS]）与安慰剂相比，展现出统计学上显著更大的下降（-13.8 vs -8.0），组间差异为-5.8。该试验同时还达到其次要终点，两组间临床医生评估的应答者比例（通过临床总体印象改善[CGI-I]量表测量）具显著差异。另外，2019年12月，Fasedienol就被FDA授予快速通道资格，用于按需治疗社交焦虑症，足可见FDA对该领域的重视。同时，2020年6月Vistagen公告宣布与EverInsight Therapeutics（后并入蔼睦医疗）达成许可和合作协议，后者以1.77亿美元（(500万美元首付款+1.72亿美元里程碑付款）的价格获得在大中华区、韩国和东南亚地区开发和商业化fasedienol（PH94B）的权益。更重要的是，据蔼睦医疗宣布，Fasedienol已于2022年1月获得中国国家药监局药品审评中心（CDE）临床试验默示许可，拟开发用于成人社交焦虑障碍的焦虑症状，并于当年4月启动了中国区临床试验。PALISADE全球研究设计基于VistaGen公司正在美国进行的名为PALISADE-1和PALISADE-2的3期研究，主要目的是为PH94B 在中国和美国以外其它市场的潜在商业化提供支持。从作用机理看，Fasedienol和现在用于治疗焦虑症的药物完全不同，同时试验中PH94B鼻喷剂耐受性良好，未发现重度或严重不良事件（AE），这是美国15年来首个社交焦虑障碍在研疗法在Ⅲ期试验中获得积极结果。02Fasedienol VS 传统治疗药物目前，社交恐惧症的治疗药物主要是抗抑郁药和抗焦虑药，多采取单药治疗和联合治疗，也可对症治疗。单药治疗时，一线的抗抑郁药主要有以下几类：一是补充5-羟色胺（选择性5-羟色胺再摄取抑制剂）类药物，代表药物为帕罗西汀、舍曲林和艾司西酞普兰等；二是补充5-羟色胺、去甲肾上腺素（5-羟色胺和去甲肾上腺素再摄取抑制剂）类药物，代表药物为文拉法辛、度洛西汀、阿米替林等；三是补充5-羟色胺和多巴胺（5-羟色胺和多巴胺再摄取抑制剂）类药物，代表药物为氟哌噻吨美利曲辛等。其次，2006年在欧洲获批用于治疗焦虑的普瑞巴林，对社交恐惧症有轻度疗效。另外，当单药疗效较低时，还可联合氯硝西泮等苯二氮卓类药物，缓解恐惧带来的躯体焦虑反应，或者使用普萘洛尔等β受体拮抗剂，解决焦虑引起的生理症状，比如震颤或心动过速。但是传统的社交恐惧症的治疗药物在疗效满足的前提下，也伴随着较多不良反应，如帕罗西汀、舍曲林可等药会让人产生难以忍受的肠胃不适、头痛失眠等；氯硝西泮等药长期服用易产生药物依赖，甚至还有部分药物可能会出现严重的5-羟色胺综合征。这些不良反应往往让患者望而却步或停药放弃，使疾病得不到有效的治疗甚至复发。另外，这些传统的治疗社交恐惧症的药物，需要4-6周起效，12-16周达到完全效果，一些患者可能需要持续治疗以维持疗效，因此，不良反应和药物起效慢都在实际治疗中限制了该类药物的大规模应用。而Fasediemol与现有的抗抑郁药的最大区别在于，其不直接激活GABA-A受体，也不直接作用于大脑的中枢神经系统，整体副作用较少。另外，Fasediemol以低微克剂量水平的鼻腔喷雾剂给药，快速起效（约10—15分钟），患者可自行给药，大大提高患者用药依从性，超越传统社恐治疗药物，成为了领域内首款新机制药物。03Vistagen能借此一举成功？在FasediemolⅢ期达到终点的公告发布当天，Vistagen的股价以一分钟暴涨1400%的惊人速度疯狂“圈粉”，盘初暴涨近1371%，盘前更是飙升近2400%，最终以677%的涨幅收盘，这一市场反应体现出了Fasedienol全新机制的用药优势备受青睐。Vistagen是一家处于临床后期的生物制药公司，旨在改变焦虑症、抑郁症和其他中枢神经系统疾病患者的治疗现状。当前，Vistagen暂无产品获批上市，Fasedienol是Vistagen的重磅在研产品，也是其管线中研发进展最快的产品。除Fasedienol，Vistagen还有五款处于临床阶段的候选产品，其中Itruvone (PH10)、PH15、PH80 和PH284，均属于 “Pherines”的1类新药，而 AV-101，是一种 N-methyl-D-aspartate受体的口服原药拮抗剂，管线中多数均已进展到了临床2期。Vistagen的在研管线，图源：Vistagen官网可以说，作为重磅潜力产品，当前Vistagen的发展与Fasedienol研发进展深度绑定。2022年7月，Vistagen曾宣布fasedienol治疗社交焦虑症的III期PALISADE-1研究未达到主要终点。考虑到PALISADE-1研究结果不佳，Vistagen在一个月后宣布暂停PALISADE-2研究的患者入组，并决定对现有数据进行中期分析，2022年9月，Vistagen宣布PALISADE-2研究的中期分析数据积极并决定按计划继续开展该研究。虽然Fasediemol的研发一波三折，好在Vistagen没有放弃，因为，Vistagen急需一款重磅产品撑起营收。根据Vistagen最新年报显示，公司2022全年亏损5924.77万美元，上年同期亏损4776.24万美元；总营收仅有22.73万美元，同比减少120.5%，由于营收不佳，投资巨头贝莱德（BlackRock）悄然离场，据悉2022年底贝莱德曾经持有Vistagen超过5%的股份，但截至今年6月底，贝莱德已经不再是持股超过5%的股东。如今三期临床获得成功对于Vistagen意义重大，无异于给资本市场重新注入一针强心剂。不过，虽然Fasediemol相比传统的社恐药物确实有潜在的巨大优势，市场前景广阔，但根据Vistagen表示其最快也将在2025年向FDA递交上市申请，而Vistagen最终能否凭借Fasediemol一举成功或许还存在未知。参考资料1. Vistagen官网2. 《股价飙升十倍，社恐的福音来了吗？莫急，让子弹飞一会儿》一个生物狗的科普小园，2023年8月8日3. 《BioNews | Vistagen：+676%, 3期Fasedienol (PH94B) 治疗社交焦虑取得积极结果》蹊之美股生物医药，2023年8月8日来源 | 博药（药智网获取授权转载）撰稿 | 米朵责任编辑 | 八角声明：本文系药智网转载内容，图片、文字版权归原作者所有，转载目的在于传递更多信息，并不代表本平台观点。如涉及作品内容、版权和其它问题，请在本平台留言，我们将在第一时间删除。商务合作 | 王存星 19922864877（同微信） 阅读原文，是昨天最受欢迎的文章哦

Positive top-line results from Phase 3 PALISADE-2 trial of rapid-onset fasedienol (PH94B) nasal spray in social anxiety disorder (SAD) Itruvone (PH10) nasal spray now staged for Phase 2B clinical development as a stand-alone, non-systemic treatment for major depressive disorder (MDD) Positive exploratory Phase 2A trial of PH80 nasal spray provides new optimism for the acute treatment of moderate to severe vasomotor symptoms (hot flashes) in women due to menopause SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Vistagen (Nasdaq: VTGN), a late clinical-stage biopharmaceutical company aiming to transform the treatment landscape for individuals living with anxiety, depression, and other central nervous system (CNS) disorders, today provided a corporate update and reported financial results for its fiscal year 2024 first quarter ended June 30, 2023. This press release features multimedia. View the full release here: "The positive outcome of our PALISADE-2 study demonstrated that fasedienol significantly reduced the mean Subjective Units of Distress Scale score, reducing anxiety during a stressful public speaking challenge. The study outcome is a pivotal achievement for fasedienol and our diverse pherine platform. These results mark the first positive U.S. Phase 3 study of an investigational therapy for social anxiety disorder in over 15 years,” said Shawn Singh, Chief Executive Officer of Vistagen. “We believe these results reinforce the promise of our pherine pipeline to address growing unmet treatment needs. We now move forward confidently advancing the Phase 3 program for fasedienol in SAD with planning for initiation of additional Phase 3 studies in 2024.” "Our strong understanding of each pherine product candidate's scientific and therapeutic potential gives us confidence in our ability to continue to innovate for patients and deliver long-term value for shareholders. With a collective body of positive safety and efficacy studies supporting our clinical-stage pipeline, we believe there are many strategic paths to accelerate our progress in achieving key clinical and regulatory milestones for each program over the next 12 months," said Mr. Singh. Corporate Update Positive Phase 3 PALISADE-2 study of fasedienol yields statistically significant top-line results for the acute treatment of anxiety in adults with SAD. The Company’s Phase 3 PALISADE-2 trial (n=141) met its primary efficacy endpoint, the difference in mean Subjective Units of Distress Scale (SUDS) score during the public speaking challenge at baseline (Visit 2) and treatment (Visit 3) for patients who received fasedienol (n=70) versus placebo (n=71) at Visit 3. Fasedienol-treated patients demonstrated a statistically significant greater change in mean SUDS score (least-squares (LS) mean = -13.8) compared to placebo (LS mean = -8.0), for a 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. Responders were identified as those who were rated ‘very much less anxious’ or ‘much less anxious’ with 37.7% (n=70) of fasedienol-treated patients rated as responders, as compared to 21.4% (n=71) of those treated with placebo (p=0.033). Additionally, the trial met the important exploratory endpoint of 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’ with 40.6% (n=70) of fasedienol-treated patients rated as responders, as compared to 18.6% (n=71) of those treated with placebo (p=0.003). Finally, the trial also met the exploratory endpoint of the difference in the proportion of patients in each treatment group with a 20-point improvement in patient-assessed SUDS score from baseline (Visit 2) to treatment (Visit 3). Of the fasedienol-treated patients, 35.7% (n=70) demonstrated this statistically significant and clinically meaningful improvement in SUDS score, as compared to 18.6% (n=71) in the placebo-treated group (p=0.020). Fasedienol was observed to be well-tolerated with no severe or serious adverse events (AEs) reported. All treatment-emergent AEs reported for the overall study were mild or moderate. There were no AEs reported in the fasedienol treatment arm above 2% occurrence. Fasedienol is a rapid-onset investigational neuroactive nasal spray with a proposed rapid-onset, non-systemic mechanism of action that sets it apart from all currently approved anti-anxiety medications. Phase 3 PALISADE-3 study of fasedienol for the acute treatment of anxiety in adults with SAD. Based on the positive top-line results of the Phase 3 PALISADE-2 study, we are currently preparing for our Phase 3 PALISADE-3 trial, with potential to initiate the trial during the first half of calendar 2024. Like PALISADE-2, PALISADE-3 will be designed as a U.S. multi-center, randomized, double-blind, placebo-controlled, Phase 3 clinical study to evaluate the efficacy, safety, and tolerability of the acute administration of fasedienol to relieve anxiety symptoms in adult patients with SAD during a simulated anxiety-provoking public speaking challenge, as measured using the patient-reported SUDS as the primary efficacy endpoint. Preparations for Phase 3 FEARLESS Program in SAD underway after positive U.S. Food and Drug Administration (FDA) feedback on use of Liebowitz Social Anxiety Scale (LSAS) as a primary efficacy endpoint in a Phase 3 real-world study. To complement our PALISADE Phase 3 Program for fasedienol in SAD, the Company is currently preparing for its Phase 3 FEARLESS trial, with potential to initiate the trial in the second half of calendar 2024 with a study design similar to the registration trials for the three drugs currently approved for the treatment of SAD using the LSAS as the primary efficacy endpoint. Accordingly, FEARLESS will be designed as a randomized, double-blind, placebo-controlled Phase 3 trial of fasedienol in adults with SAD to evaluate the efficacy, safety and tolerability of multiple administrations of fasedienol, on a patient-tailored as-needed basis, up to six times per day in their daily lives, in a real-world setting over a multiple week period. To complement the positive results of PALISADE-2, we believe the Phase 3 FEARLESS study design also will align with the way SAD patients will use fasedienol in their daily lives, should it be approved, because our planned fasedienol treatment model includes both repeated experiences of acute reduction of anxiety during performance and social events, evidenced by decreased SUDS scores as in PALISADE-2, as well as longer-term overall reduction in severity of SAD evidenced by reductions in LSAS scores, as will be assessed in FEARLESS. The Company believes that each of PALISADE-3 and FEARLESS has the potential to complement PALISADE-2 as a potential New Drug Application (NDA)-enabling adequate and well-controlled Phase 3 clinical trial of fasedienol for treatment of SAD. Successful U.S. Phase 1 study of itruvone stages Phase 2B development in MDD. Results from the successful U.S. Phase 1 trial of itruvone nasal spray build on successful Phase 1 studies and a positive randomized, double-blind, placebo-controlled Phase 2A study of itruvone in MDD previously conducted in Mexico and enable Phase 2B development of itruvone in the U.S. as an innovative stand-alone rapid-onset pherine product candidate for treatment of MDD. The U.S. Phase 1 trial was a randomized, double-blind, placebo-controlled clinical study investigating the safety and tolerability of a single dose and of multiple doses of itruvone nasal spray in healthy adult subjects. There were no reported serious AEs or discontinuations due to AEs in the study. Overall, itruvone nasal spray was well-tolerated and demonstrated a favorable safety profile, consistent with all prior clinical studies of itruvone. Newly reported preclinical data for itruvone nasal spray support potential antidepressant activity via peripheral nasal neurons without entry into the brain. Recently reported preclinical data of radiolabeled intranasal itruvone in laboratory rats further validate its potential to treat MDD without systemic absorption. These new data additionally support the proposed mechanism of action of itruvone nasal spray as binding to receptors of peripheral chemosensory neurons in the nasal cavity but not to neuronal receptors in the brain, thereby limiting the transport of molecules to the circulatory system and minimizing potential systemic exposure. The preclinical data further the substantial body of evidence supporting itruvone’s favorable safety profile. Positive exploratory Phase 2A trial of PH80 nasal spray provides new optimism for the acute treatment of moderate to severe vasomotor symptoms (hot flashes) in women due to menopause. In a previously unreported randomized, double-blind, placebo-controlled exploratory Phase 2A clinical study of PH80 designed to explore the efficacy, safety, and tolerability of PH80 for the acute management of menopausal hot flashes in women, PH80 induced significant reduction in the daily number of hot flashes compared to placebo at the end of the first week of treatment, and the improvement was maintained through each treatment week until the end of the treatment period. 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. PH80 was well-tolerated with no serious AEs, and the AE profiles were comparable between PH80 and placebo. All 36 subjects completed four weeks of treatment and no subject discontinued participation in the study as a result of AEs. Fiscal Year 2024 First Quarter Financial Results Research and development (R&D) expense: Research and development expense decreased by approximately $11.1 million, from $15.3 million to $4.2 million for the quarter ended June 30, 2022 and 2023, respectively. The decrease in R&D expense is primarily due to completing our initial Phase 3 PALISADE Program studies in SAD and the exploratory Phase 2A study in adjustment disorder, as well as reduced nonclinical development and outsourced manufacturing and regulatory activities for fasedienol and itruvone. General and administrative (G&A) expense: General and administrative expense decreased by approximately $1.8 million from $4.8 million for the quarter ended June 20, 2022, to $3.0 million for the quarter ended June 30, 2023, primarily due to the termination of pre-commercialization activities in August 2022. Net loss: Net loss attributable to common stockholders for the first quarter ended June 30, 2023, was approximately $6.9 million compared to a Net Loss of $19.8 million for June 30, 2022. Cash position: At June 30, 2023, the Company had cash and cash equivalents of approximately $9.6 million. Since June 30, 2023 and through August 10, 2023, the Company sold and settled an aggregate of 1,487,293 shares of common stock under its Sales Agreement with Jefferies and received gross cash proceeds of $16,893,700. Additional sales of 1,965,940 shares under the Sales Agreement are expected to settle on or before August 14, 2023, subject to customary settlement procedures, for expected gross cash proceeds of $15,172,023. As of August 10, 2023, the Company had 9,362,444 shares of common stock outstanding. Conference Call Vistagen will host a conference call and live audio webcast this afternoon at 4:30 p.m. Eastern Time to provide a corporate update. U.S. Dial-in (Toll-Free): 1-800-954-1051 International Dial-in Number (Toll): 1-212-231-2924 Conference ID: 22027732 Webcast Link: A live audio conference call webcast will also be available via the above link. Participants should access this webcast site 10 minutes before the start of the call. In addition, a telephone playback of the call will be available after approximately 8:00 p.m. Eastern Time on Thursday, August 10, 2023. To listen to the replay, call toll-free 1-844-512-2921 within the United States or 1-412-317-6671 when calling internationally (toll). Please use the replay access ID number: 22027732. About Vistagen Vistagen (Nasdaq: VTGN) is a late clinical-stage biopharmaceutical company aiming to transform the treatment landscape for individuals living with anxiety, depression and other CNS disorders. Vistagen is advancing therapeutics with the potential to be faster-acting, and with fewer side effects and safety concerns, than those currently available for the treatment of anxiety, depression and multiple CNS disorders. Vistagen's pipeline includes six clinical-stage product candidates, including fasedienol (PH94B), itruvone (PH10), PH15, PH80, and PH284, each an investigational agent belonging to a new class of drugs known as pherines, as well as AV-101, which is an oral prodrug antagonist of the N-methyl-D-aspartate receptor (NMDAR). Pherines are neuroactive nasal sprays designed with an innovative proposed mechanism of action that activates chemosensory neurons in the nasal cavity and can beneficially impact key neural circuits in the brain without systemic absorption or direct activity on neurons in the brain. Vistagen is passionate about transforming mental health care and redefining what is possible in the treatment of anxiety, depression and several other CNS disorders. Connect at . Forward Looking Statements This press release contains certain forward-looking statements within the meaning of the federal securities laws. These forward-looking statements involve known and unknown risks that are difficult to predict and include all matters that are not historical facts. In some cases, you can identify forward-looking statements by the use of words such as "may," "could," “expect,” “project,” “outlook,” “strategy,” “intend,” “plan,” “seek,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “strive,” “goal,” “continue,” “likely,” “will,” “would” and variations of these terms and similar expressions, or the negative of these terms or similar expressions. Such forward-looking statements are necessarily based upon estimates and assumptions that, while considered reasonable by Vistagen and its management, are inherently uncertain. As with all pharmaceutical products, there are substantial risks and uncertainties in the process of development and commercialization and actual results or developments may differ materially from those projected or implied in these forward-looking statements. Among other things, there can be no guarantee that any of the Company’s drug candidates will successfully complete ongoing or, if initiated, future clinical trials, receive regulatory approval or be commercially successful, or that the Company will be able to successfully replicate the result of past studies of its product candidates, including fasedienol, itruvone, AV-101 and/or PH80. Other factors that may cause such a difference include, without limitation, risks and uncertainties relating to the Company’s ability to secure adequate financing for its operations, including financing or collaborative support for continued clinical development of the Company’s product candidates; risks and uncertainties related to the Company’s ability to secure successful strategic global and/or regional development and commercialization partnerships; other risks and uncertainties related to delays in launching, conducting and/or completing ongoing and planned clinical trials; the scope and enforceability of the Company’s patents, including patents related to the Company’s pherine drug candidates and AV-101; fluctuating costs of materials and other resources and services required to conduct the Company’s ongoing and/or planned clinical and non-clinical trials; market conditions; the impact of general economic, industry or political conditions in the United States or internationally; and other technical and unexpected hurdles in the development, manufacture and commercialization of the Company’s product candidates. These risks are more fully discussed in the section entitled "Risk Factors" in the Company’s most recent Annual Report on Form 10-K for the fiscal year ended March 31, 2023, and in the Company’s Quarterly Report on Form 10-Q for the period ended June 30, 2023, as well as discussions of potential risks, uncertainties, and other important factors in our other filings with the U.S. Securities and Exchange Commission (SEC). The Company’s SEC filings are available on the SEC’s website at . You should not place undue reliance on these forward-looking statements, which apply only as of the date of this press release and should not be relied upon as representing the Company’s views as of any subsequent date. The Company explicitly disclaims any obligation to update any forward-looking statements other than as may be required by law. If the Company does update one or more forward-looking statements, no inference should be made that the Company will make additional updates with respect to those or other forward-looking statements. VISTAGEN THERAPEUTICS, INC. CONSOLIDATED BALANCE SHEETS (Amounts in dollars, except share amounts) June 30, March 31, 2023 2023 (Unaudited) ASSETS Current assets: Cash and cash equivalents $ 9,622,300 $ 16,637,600 Prepaid expenses and other current assets 1,889,400 802,700 Deferred contract acquisition costs - current portion 67,100 67,100 Total current assets 11,578,800 17,507,400 Property and equipment, net 475,800 507,300 Right-of-use asset - operating lease 2,153,800 2,260,300 Deferred offering costs 522,100 495,700 Deferred contract acquisition costs - non-current portion 200,900 217,600 Security deposits 100,900 100,900 Total assets $ 15,032,300 $ 21,089,200 LIABILITIES AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable $ 1,623,200 $ 2,473,100 Accrued expenses 424,700 787,400 Note payable 784,200 105,300 Deferred revenue - current portion 714,300 714,300 Operating lease obligation - current portion 501,100 485,600 Financing lease obligation - current portion 1,700 1,700 Total current liabilities 4,049,200 4,567,400 Non-current liabilities: Deferred revenue - non-current portion 2,137,000 2,314,600 Operating lease obligation - non-current portion 1,990,100 2,119,800 Financing lease obligation - non-current portion 7,000 7,400 Total non-current liabilities 4,134,100 4,441,800 Total liabilities 8,183,300 9,009,200 Commitments and contingencies Stockholders’ equity: Preferred stock, $0.001 par value; 10,000,000 shares authorized at June 30, 2023 and March 31, 2023: no shares outstanding at June 30, 2023 and March 31, 2023 - - Common stock, $0.001 par value; 325,000,000 shares authorized at June 30, 2023 and March 31, 2023; 7,879,673 and 7,315,583 shares issued at June 30, 2023 and March 31, 2023, respectively 7,900 7,300 Additional paid-in capital 344,564,000 342,892,500 Treasury stock, at cost, 4,522 shares of common stock held at June 30, 2023 and March 31, 2023 (3,968,100 ) (3,968,100 ) Accumulated deficit (333,754,800 ) (326,851,700 ) Total stockholders’ equity 6,849,000 12,080,000 Total liabilities and stockholders’ equity $ 15,032,300 $ 21,089,200 References to common shares and per share amounts have been retroactively restated to reflect the Company’s 1-for-30 reverse stock split of its common stock effective on June 6, 2023. VISTAGEN THERAPEUTICS CONDENSED CONSOLIDATED STATEMENT OF OPERATIONS (Unaudited) (Amounts in Dollars, except share amounts) Three Months Ended June 30, 2023 2022 Revenues: Sublicense revenue $ 177,600 $ 310,100 Total revenues 177,600 310,100 Operating expenses: Research and development 4,197,200 15,291,400 General and administrative 2,978,200 4,791,800 Total operating expenses 7,175,400 20,083,200 Loss from operations (6,997,800 ) (19,773,100 ) Other income, net: Interest income, net 97,200 2,300 Loss before income taxes (6,900,600 ) (19,770,800 ) Income taxes (2,500 ) (5,500 ) Net loss and comprehensive loss $ (6,903,100 ) $ (19,776,300 ) Basic and diluted net loss $ (0.94 ) $ (2.87 ) Weighted average shares used in computing basic and diluted net loss 7,377,005 6,886,736 References to common shares and per share amounts have been retroactively restated to reflect the Company’s 1-for-30 reverse stock split of its common stock effective on June 6, 2023.