Saniona submits IND application for SAN2465 for major depressive disorder

“The IND submission for SAN2465 represents an important milestone for Saniona and demonstrates our continued focus on execution as we advance our prioritized internal programs into clinical development,” said Pierandrea Muglia, Chief Medical Officer of Saniona. “Our ambition for this compound is to deliver rapid antidepressant efficacy comparable to ketamine and esketamine, without any of the major issues associated with their use, including the acute dissociative and sedative effects that require supervised administration, making treatment impractical and expensive. We look forward to receiving FDA clearance and initiating the Phase 1 study before year-end.”

The planned Phase 1 study will evaluate the safety, tolerability and pharmacokinetics of SAN2465 in healthy volunteers. The study will also include validated cognitive tests and established pharmacodynamic measures, such as quantitative EEG, to capture the expected signature of the selective GABA-A α5 negative allosteric modulator at various dose levels, facilitating the definition of the dose range for future clinical studies in patients.

More about Major Depressive Disorder

Depression affects hundreds of millions of people worldwide [1]. Conventional antidepressants have a delayed onset of several weeks and relatively low remission rates with more than 30% of patients not responding adequately to treatment, leading to treatment-resistant depression [2]. Esketamine (Spravato®), the first approved rapid-acting antidepressant, reached worldwide sales of USD 1.7 billion in 2025 [3], highlighting the significant demand for fast-acting treatment options. However, due to the acute dissociative effect and the risks of sedation, respiratory depression, and abuse liability, esketamine is only available through a restricted Risk Evaluation and Mitigation Strategy (REMS) program requiring administration and monitoring in a certified healthcare setting [4].

More about SAN2465

SAN2465 is a GABA-A α5 negative allosteric modulator designed to deliver rapid antidepressant effects without the limitations associated with ketamine and esketamine. In the chronic mild stress model, a well-established animal model of depression [5], a single oral dose of SAN2465 produced a rapid and sustained reversal of chronic stress-induced depressive-like symptoms, including anhedonia, anxiety and cognitive impairment. The onset and magnitude of these effects were comparable to ketamine. SAN2465 has also been shown to significantly enhance hippocampal synaptic plasticity, as measured by long-term potentiation (LTP).

GABA-A α5 receptors are highly expressed in the hippocampus and related limbic regions involved in emotional regulation, mood and cognition [6,7]. Through selective modulation of these receptors, SAN2465 has the potential to deliver rapid antidepressant efficacy without the dissociative and other adverse effects associated with NMDA receptor antagonists, potentially enabling convenient oral treatment without the need for in-clinic administration and monitoring.

[1] World Health Organization. Depression fact sheet, September 2026.
https://www.who.int/news-room/fact-sheets/detail/depression

[2] Zhdanava M et al. J Clin Psychiatry 2021;82(2):20m13699

[3] Johnson & Johnson. Q4 and full-year 2025 results, January 2026

[4] SPRAVATO® (esketamine) US Prescribing Information, revised March 2026

[5] Willner P. Neurobiol Stress 2017;6:78–93

[6] Sur C et al. Brain Res 1999;822:265–270

[7] Atack JR. Pharmacol Ther 2010;125(1):11–26