Race for approval: biotechs accelerate bipolar disorder therapies

Race for approval: biotechs accelerate bipolar disorder therapies By Roohi Mariam Peter Add Labiotech as your Google Preferred Source 8 minutesmins July 15, 2026 8 minutesmins Share WhatsApp Twitter Linkedin Email Photo: Studio KVR (Unsplash) Add Labiotech as your Google Preferred Source Newsletter Signup - Under Article / In Page"*" indicates required fieldsEmailThis field is for validation purposes and should be left unchanged.Subscribe to our newsletter to get the latest biotech news!By clicking this I agree to receive Labiotech's newsletter and understand that my personal data will be processed according to the Privacy Policy.*Company name*Job title*Business email* Bipolar disorder disrupts daily life, causing severe shifts in mood and energy, flipping between extreme highs and deep lows. Most patients who are prescribed currently available drugs for the condition like mood stabilizers don’t benefit much from them, and instead, have to grapple with side effects from these medicines. The demand for new therapies that are both effective and not associated with significant side effects is pressing. New therapies in the clinic hope to meet this demand. Table of contentsCurrent standards of care: patient needs unmet Bipolar disorder affects more than 40 million people in the world, and the depressive phase is the predominant and most disabling state for the majority of patients. It causes physical changes in the brain’s emotion control centers and the chemical messengers, which then disrupt how the emotional and thinking centers communicate. The condition is marked by persistent low mood, loss of interest, fatigue, and impaired functioning. Patients lose an average of more than one month of work each year and face elevated risks of hospitalization and suicide. The current standard of care relies largely on mood stabilizers and atypical antipsychotics, often used in combination, explained Kevin Finney, president and chief executive officer (CEO) of Autobahn Therapeutics, a California-based neurodrug developer. “More than half of the patients do not receive adequate relief from currently available therapies, which are limited by modest efficacy and significant side effects, including weight gain, sexual dysfunction, movement disorders, and metabolic complications. For many patients, those side effects compound the very symptoms they are already managing,” said Finney. He pointed out that this burden is evident in atypical depression, “a prominent and highly underserved subpopulation.” It is characterized by heightened appetite, hypersomnia, and low energy. “Some standard-of-care treatments actively worsen these symptoms, and there has been no fundamentally new mechanism of action approved in bipolar depression in years,” said Finney, whose company is developing a treatment for the condition. Autobahn Therapeutics’ elunetirom reaps positive clinical results Autobahn’s elunetirom is an oral, once-daily, brain-targeted thyroid hormone receptor agonist, which acts as a central nervous system (CNS)-selective thyroid hormone receptor beta agonist. “It is designed to do something different from essentially every antidepressant developed over the last 40 years,” said Finney. Rather than modulating neurotransmitters like serotonin, dopamine, or norepinephrine, Finney explained that elunetirom targets thyroid hormone receptors in the brain to boost cellular energy and drive neuroplasticity, the brain’s ability to form and strengthen connections. In other words, it is designed to help restore healthy brain function rather than simply manage symptoms. As currently approved treatments tend to not be efficacious enough or have poor tolerability in patients, these unmet needs are what elunetirom is designed to address. It is similar to the neuroplasticity mechanism that psychedelics follow, Finney explained. “It is the same pathway behind much of the excitement around psychedelics.” The difference, however, is that the drug comes with no psychoactive effects and, it being a once-daily oral tablet, there is no treatment burden as patients can take it at home without having to make frequent visits to the clinic. Synthetic thyroid hormones have been used off-label in depression for more than 50 years, which offer decades of human evidence that this pathway matters in mood. “The underlying biology is not new,” said Finney. “What has been missing is a way to access that benefit in the brain without the peripheral effects of thyroid hormone, such as effects on the heart. That is the problem elunetirom is built to solve: bringing the benefit of thyroid hormone biology to the brain while limiting activity in the rest of the body.” Topline results from a phase 2 study in 21 patients shed some light on the drug’s benefit. Patients were given elunetirom along with their usual treatment regiment, which comprises mood stabilizers and antipsychotics. The candidate was found to successfully reduce depression severity in patients with bipolar disorder. About 75% of patients responded to the treatment after six weeks and 50% of them were in remission by then. A statistically significant 16.8-point Hamilton Depression Rating Scale (HAMD)-17 improvement was observed, hitting the primary endpoint of the study. The HAMD-17 is a test used to measure the severity of depression in patients and to check how well a treatment is working. “For the millions of people living with bipolar depression who have not found adequate relief, these recently reported data offer real encouragement,” said Finney. “Just as important, we saw the onset of statistically significant improvement as early as week two, which points to a rapid antidepressant effect. And elunetirom was safe and well-tolerated, with no severe or serious treatment-related adverse events.” Suggested Articles Six psychedelic drug companies aiming to revolutionize mental health treatment New antidepressants: Tackling treatment resistant depression Psychedelics sans side effects: neuroplastogens gain ground Reformulating psychedelics for neurodegenerative diseases Patients improved across the symptoms linked to atypical depression, including energy, sleep, and appetite, which are the areas that today’s treatments often make worse, Finney pointed out. “The patient-reported measures told the same story,” he said. “The functional recovery was just as striking.” Patients reported feeling “significantly better” based on the Patient Global Impression and the Symptoms of Depression Questionnaire. Quality of life improved too. Patients who entered the study were losing an average of 2.7 days of work each week. This dropped to 0.4 days after six weeks of taking elunetirom. “For people who have lived with this illness for years, restoring that much daily functioning is profound,” said Finney. Meanwhile, Israeli company Syremis Therapeutics launched with $165 million late last year to tackle depression associated with bipolar disorder, major depressive disorder, and schizophrenia. Its candidate for bipolar depression, however, is an NMDA receptor antagonist. ST-901, which is in the investigational new drug (IND)-enabling stage, is meant to work by blocking the NMDA (N-methyl-D-aspartate) receptor. This receptor controls glutamate levels – the brain’s main excitatory neurotransmitter. By regulating glutamate, ST-901 could prevent its overactivation, thereby resetting brain chemistry in depression. Targeting glutamate: RAP-219 for mania Mania is a core symptom of bipolar disorder. It affects the brain by hyper-activating the amygdala, the emotional center of the brain, and dulls the prefrontal cortex, which is responsible for judgement and impulse control. As dopamine tends to spike during manic episodes, the amygdala goes into overdrive. Rapport Therapeutics’ RAP-219 is designed to target the TARPγ8 protein, a helper protein attached only to AMPA receptors in specific parts of the brain. These AMPA receptors respond to glutamate. Once RAP-219 binds to a specific part of the receptor, it changes the shape so as to dial down overactive brain signals. Topline results of a phase 2 trial are expected later this year, after which the company hopes to engage in talks with the U.S. Food and Drug Administration (FDA) to potentially design a phase 3 program and plan for a new drug application to treat bipolar mania. Also in phase 2 trials is ALTO-100. Developed by Alto Neuroscience in California, ALTO-100 is another oral small molecule that is designed to enhance neural plasticity in the hippocampus, a brain region important for both cognition and mood. According to the company, it builds on the understanding that depression is in part driven by a reduction in hippocampal neuroplasticity and is targeted to those patients who lack this neuroplasticity, which is the brain’s ability to rewire and build new connections. ALTO-100 is currently in phase 2b development for the treatment of bipolar depression on top of the standard of care. Topline results are expected this year. With trials ongoing, it looks like 2026 will be a year of pivotal readouts for potential bipolar disorder treatments. Elunetirom leads the charge with its encouraging phase 2 results, as well as its recent Fast Track Designation from the FDA. Finney foresees a path for elunetirom’s approval. He said: “With a strong bipolar dataset in hand and major depressive disorder data coming later this year, we believe elunetirom has the potential to become a franchise-defining treatment across multiple forms of depression.” This article is reserved for subscribers Subscribe for free to continue reading.Enter your details to log in or subscribe. Email Company name Job title Continue Readingor Continue with Microsoft Continue with LinkedIn By continuing, I agree to receive Labiotech's newsletter and understand that my personal data will be processed according to the Privacy Policy. Neurological diseases R&D trends and breakthrough innovations Find out which indications have the fullest pipelines, where white space exists, and which early-stage innovations are drawing the most pharma attention. Download the report Explore other topics: Clinical trialmental health issuesSmall molecules ADVERTISEMENT

Facts Only

* Bipolar disorder affects over 40 million people worldwide; the depressive phase is the most disabling state.
* Current standard of care involves mood stabilizers and atypical antipsychotics, often associated with side effects like weight gain and sexual dysfunction.
* Autobahn Therapeutics is developing elunetirom, a CNS-selective thyroid hormone receptor beta agonist designed to boost cellular energy and neuroplasticity.
* A phase 2 study on elunetirom in bipolar patients showed that 75% responded to treatment after six weeks, and 50% were in remission by that time.
* Patients receiving elunetirom experienced a statistically significant 16.8-point improvement on the HAMD-17 scale.
* The study observed a rapid antidepressant effect, with statistically significant improvement starting as early as week two.
* Elunetirom demonstrated safety and well-tolerability, with no severe or serious treatment-related adverse events in the trial.
* Syremis Therapeutics is investigating ST-901, an NMDA receptor antagonist targeting glutamate, for bipolar depression.
* Rapport Therapeutics’ RAP-219 targets the TARP$\gamma$8 protein to modulate AMPA receptors responding to glutamate.
* Alto Neuroscience developed ALTO-100, an oral small molecule designed to enhance neural plasticity in the hippocampus.
* The timeline suggests 2026 will feature pivotal readouts for potential bipolar disorder treatments across these modalities.

Executive Summary

Bipolar disorder impacts over 40 million people globally, with the depressive phase being the most disabling state. Current treatments primarily rely on mood stabilizers and atypical antipsychotics, which frequently cause significant side effects such as weight gain and sexual dysfunction, leading to inadequate relief for many patients. There is a strong demand for new therapies that offer efficacy without these adverse effects. Autobahn Therapeutics is developing elunetirom, a once-daily oral treatment targeting thyroid hormone receptors in the brain to promote cellular energy and neuroplasticity, aiming to restore healthy brain function rather than just managing symptoms. Phase 2 study results showed elunetirom reduced depression severity in bipolar patients, with 75% responding after six weeks and 50% achieving remission, alongside a significant improvement in depression scores and rapid onset of effect. Other research indicates that addressing related symptoms like appetite, sleep, and energy can improve quality of life for those with atypical depression. Concurrently, other avenues are being explored, including Psychedelic-related compounds targeting neuroplasticity, and other small molecules like ST-901, which targets glutamate receptors, and ALTO-100, which aims to enhance hippocampal plasticity.

Full Take

The narrative presents a pivot from symptom management using current psychopharmacology toward targeting fundamental neurobiological mechanisms, specifically cellular energy and neuroplasticity, as the missing link in treating bipolar disorder effectively. The emergence of elunetirom positions itself not merely as another mood stabilizer but as a mechanism operating outside established neurotransmitter modulation pathways, drawing parallels to psychedelics' effects on neuroplasticity. This frames the unmet need as a failure of existing treatment paradigms rather than just a calibration issue within them.
The simultaneous pursuit of therapies targeting glutamate (ST-901, RAP-219) and hippocampal plasticity (ALTO-100) suggests a collective understanding that bipolar symptoms involve complex dysregulation across excitatory signaling and structural brain change. This constellation indicates a fragmented but rapidly diversifying approach to tackling the disorder. The emphasis on real-world functional recovery—such as regaining lost work time—suggests that efficacy must be measured not just by clinical scores, but by restored daily functioning for patients burdened by chronic illness.
The implication is a systemic shift where future successful treatments will likely integrate multiple biological targets rather than relying on single-mechanism approaches. The pattern here is the triangulation of novel mechanisms (thyroid receptors, glutamate pathways, hippocampal plasticity) seeking to influence mood and cognition in ways that bypass known limitations. The potential danger lies in the hype surrounding multi-target therapies potentially obscuring the necessary rigor in isolating which specific biological mechanism drives symptom relief across the broad spectrum of bipolar presentations. What data is required to ensure these disparate mechanisms integrate safely into a cohesive treatment strategy for diverse bipolar phenotypes?