VistaGen Therapeutics (NASDAQ:VTGN) used its fiscal 2026 third-quarter corporate update call to outline steps it is taking after the completion of the randomized portion of PALISADE-3, a Phase 3 trial of fasedienol in social anxiety disorder (SAD), while emphasizing execution improvements for the ongoing PALISADE-4 study. Management also provided updates on its women’s health candidate PH80, which has been designated rafisolone, and reviewed cash resources and cost-containment efforts.
PALISADE-3 review and changes implemented for PALISADE-4
Chief Executive Officer Shawn Singh said the company completed the randomized portion of PALISADE-3 “as guided” and is now focused on learning from the results while “driv[ing] high quality and efficient execution” of PALISADE-4. Singh said VistaGen has reviewed available PALISADE-3 data and implemented “moderate refinements” to PALISADE-4, including retraining, site rationalization, and other operational enhancements.
Asked what led to the refinements in PALISADE-4, Prince said VistaGen observed that PALISADE-3 differed from PALISADE-2 in part due to a “higher placebo response.” He described mitigation efforts focused on protocol and script adherence at clinical sites, including limiting informal interactions that could inadvertently increase participant comfort and inflate placebo response. Prince added that audio recordings provide a mechanism for monitoring site conduct and enabling targeted interventions when deviations occur.
Singh also pointed to a focus on “centralized recruitment” and keeping recruitment processes “tight and rationalized” as additional measures that can affect in-study execution, particularly around placebo mitigation.
Data analytics, AI/ML efforts, and potential statistical model changes
Singh said VistaGen is working with third-party collaborators to apply “innovative approaches” to analyze available datasets across the PALISADE program, including randomized and open-label studies. The goal, he said, is to better understand the drivers of both fasedienol and placebo response and to potentially inform “optimized statistical models” that consistently incorporate covariates and explanatory variables across the PALISADE studies. Singh suggested these efforts could “anchor future weight of evidence discussions with the FDA.”
Management said the analyses involve collaborators’ proprietary artificial intelligence and machine learning technologies aimed at identifying nonspecific responses and predicting susceptibility to placebo response and likelihood of response to active drug within the public speaking challenge design.
In response to analyst questions, Singh said the company does not yet know whether the work will identify covariates with a potential fixed effect that could be incorporated into an ANCOVA model, but that this is among the types of findings the company is evaluating. Prince added that the company is looking across multiple studies, including PALISADE 1, 2, and 3, noting that having a third completed study increases the size of the dataset and provides more power for exploration.
Management also addressed the procedural implications of any statistical analysis plan (SAP) changes for PALISADE-4. Prince said the SAP has already been submitted and, as he characterized it, there was “no feedback from FDA,” meaning it is set. Any future changes would require resubmission and alignment with the FDA before database lock and before reporting top-line results. Prince also said a change to the SAP would not change the planned enrollment for PALISADE-4.
PALISADE-4 status and regulatory framing
On trial timing and disclosure, Singh indicated the company expects to follow a similar communications pattern to PALISADE-3, referencing a public update after “the last patient’s last visit” and then moving toward top-line results. He said the company remains “on track with guidance” previously given for PALISADE-4 top-line results for the randomized portion, but did not provide specific enrollment numbers on the call. Prince said enrollment has not been impacted by the company’s December 17 announcement, adding that enrollment is continuing “as planned and projected.”
Regarding regulatory strategy, Singh emphasized that outcomes depend on FDA regulations and guidance, the “totality of data,” weight of evidence, risk-benefit, and the unmet-need context. He said the company is not in a position to speculate on approval scenarios, but reiterated that if PALISADE-4 is successful, the company’s strategy is for PALISADE-4 to complement PALISADE-2 along with the broader program evidence for a potential NDA for acute treatment of SAD in adults. If PALISADE-4 does not separate from placebo, Singh said the company would still focus on totality and weight of evidence across all available data. Management also declined to comment on blinded PALISADE-4 data.
Open-label extensions and real-world use measures
Singh said the open-label extension (OLE) portions of PALISADE-3 and PALISADE-4 remain ongoing, designed to evaluate safety and tolerability of repeated, as-needed intranasal fasedienol use in real-world, daily-life situations. The OLE includes exploratory longitudinal measures using the clinician-administered Liebowitz Social Anxiety Scale (LSAS) and the patient-reported Social Phobia Inventory (SPIN). Singh noted that open-label data are uncontrolled and exploratory, but said the PALISADE-3 OLE could provide useful context around patient experience and usage patterns over time.
Women’s health update: PH80 named rafisolone; IND planned
VistaGen said it received an official USAN adoption statement designating PH80 as rafisolone. Singh described rafisolone as a hormone-free, nonsystemic, intranasal product candidate for moderate to severe vasomotor symptoms (hot flashes) due to menopause, with potential applicability in other women’s health indications.
Singh said the company is preparing a U.S. investigational new drug (IND) application for rafisolone with a planned submission in the first half of 2026. He said the IND is intended to support potential Phase 2 development in the U.S. for vasomotor symptoms. He also referenced a previously completed placebo-controlled exploratory Phase 2A trial conducted in Mexico by Pherin Pharmaceuticals (now a wholly owned subsidiary), which he said demonstrated clinical benefit in the vasomotor symptoms indication.
Financial position and cost measures
Singh said the company ended the quarter with $61.2 million in cash, cash equivalents, and marketable securities, but later clarified he misspoke and that the figure reflected in the quarterly filing was $61.8 million as of December 31, 2025. He also said VistaGen implemented company-wide cash preservation measures during the quarter to enhance efficiency, extend runway, and maintain flexibility. Management said it believes it is well positioned to complete PALISADE-4 and continue pipeline planning.
In a separate Q&A item, Chief Financial Officer Nick Tressler addressed a question about the difference between period-end shares outstanding (39.7 million) and weighted average shares for the quarter (42 million). Tressler said the weighted average includes pre-funded warrants.
About VistaGen Therapeutics (NASDAQ:VTGN)
VistaGen Therapeutics, Inc (NASDAQ:VTGN) is a clinical-stage biopharmaceutical company dedicated to the discovery and development of next-generation medicines for central nervous system disorders. Incorporated in Delaware in 1998 and headquartered in South San Francisco, California, VistaGen applies advanced human pluripotent stem cell technologies to accelerate drug candidate validation and optimization. The company’s core focus is on addressing unmet medical needs in major depressive disorder, neuropathic pain and dermatological conditions.
The company’s lead candidate, AV-101, is an oral prodrug designed to modulate glutamatergic neurotransmission via the N-methyl-D-aspartate (NMDA) receptor pathway, with clinical programs targeting major depressive disorder and neuropathic pain.
