Bipolar and Related Disorders

Company to initiate Phase 2 trial of ABX-002 for bipolar depression by yearend 2024 ABX-002 also being evaluated as an adjunctive treatment for major depressive disorder in the ongoing AMPLIFY Phase 2 trial SAN DIEGO--(BUSINESS WIRE)--Autobahn Therapeutics, a biotechnology company developing restorative treatments for people affected by neuropsychiatric and neuroimmunologic disorders, today announced the clearance of an investigational new drug (IND) application by the U.S. Food and Drug Administration (FDA) to support initiation of a Phase 2 trial of ABX-002 as an adjunctive treatment for patients with bipolar depression. ABX-002 is a highly potent, oral, thyroid hormone beta receptor (TRβ) selective agonist designed to enhance the CNS benefits of thyroid hormone biology and drug concentrations directly in the brain. “We are thrilled to expand our depression treatment program with ABX-002 and evaluate its potential to safely address the debilitating symptoms of bipolar depression, a highly prevalent and potentially life-threatening disorder,” said Kevin Finney, Autobahn’s President and CEO. “In the U.S. alone, seven million patients suffer from bipolar disorder and there are limited safe and effective therapies that focus specifically on the depressive symptoms that patients face. Our planned Phase 2 trial is designed to provide proof-of-concept for ABX-002 and inform further clinical development in bipolar depression. With this regulatory clearance, we are excited to advance ABX-002 into a second clinical development program later this year alongside our recently initiated Phase 2 study in major depressive disorder.” The Phase 2 trial will evaluate ABX-002 as adjunctive therapy in adult patients with depressive episodes associated with bipolar I or bipolar II disorder. Autobahn will evaluate the biological and clinical proof-of-concept for ABX-002 across multiple endpoints in the trial, including changes in energy metabolism in the brain as determined by phosphorus magnetic resonance spectroscopy ( 31 P-MRS) and changes in patients’ depressive symptoms as measured by the Hamilton Depression Rating Scale (HAMD). ABX-002 is also being evaluated in the company’s ongoing AMPLIFY Phase 2 trial as an adjunctive treatment for patients with major depressive disorder (MDD), with topline data expected in the second half of 2025. About Autobahn Therapeutics Autobahn Therapeutics is a biotechnology company developing a portfolio of neuropsychiatric and neuroimmunologic clinical candidates leveraging its brain-targeting chemistry platform. Autobahn aims to unlock new therapeutic opportunities through precision tuning of CNS exposure, pursuing validated clinical and biologic targets, and guiding development with biomarkers. The company’s pipeline is led by ABX-002, a thyroid hormone receptor beta (TRβ) agonist being developed as a potential adjunctive treatment for people with major depressive disorder and bipolar disorder depression. Autobahn Therapeutics is based in San Diego. For more information, visit . About ABX-002 ABX-002 is an orally administered, potent and selective thyroid hormone beta receptor (TRβ) agonist designed to enhance the CNS benefits of thyroid hormone biology while also reducing the peripheral liabilities of synthetic thyroid hormone (e.g., triiodothyronine, T3), a treatment which has shown efficacy in numerous placebo-controlled human studies across MDD and bipolar depression. Thyroid hormone agonism has demonstrated activity on cellular energy metabolism pathways, which play an important role on the regulation of brain bioenergetics and may be uniquely suited to address symptoms of atypical depression, a highly prevalent and underserved sub-population of MDD. In nonclinical and clinical studies, ABX-002 has demonstrated optimized PK properties, target engagement in brain regions associated with depression, and an attractive safety and tolerability profile. Contacts Investors: Alex Straus THRUST Strategic Communications alex@thrustsc.com Media: Ryan Flinn In Like Flinn Communications ryan@inlikeflinncommunications.com

LAFAYETTE, Calif., May 31, 2024 /PRNewswire/ -- The Alexander Shulgin Research Institute (ASRI) has unveiled a groundbreaking discovery in the journal Molecular Pharmacology: the first bifunctional compound that acts as both a 5-HT2A receptor antagonist and a voltage-gated sodium channel blocker. This novel molecule, known as XOB, could revolutionize the treatment landscape for bipolar disorder. Key Findings: Continue Reading ASRI's discovery of XOB marks a significant milestone in psychiatric pharmacology. Post this 1. XOB's Dual Mechanism of Action: ASRI Co-Founder and President, Dr. Nicholas Cozzi, spearheaded the design and synthesis of XOB. His team collaborated with experts from leading institutions, including the University of Michigan-Ann Arbor, Stanford University, Medical College of Wisconsin, Usona Institute, and Promega Corporation. Lead author Dr. Nicholas Denomme, of the University of Michigan-Ann Arbor and Stanford University, guided and performed electrophysiology studies which revealed that XOB had a blocking effect on voltage-gated sodium channels in cultured cells and neurons. ASRI and Usona Institute scientists performed essential physical and chemical analyses of XOB, while researchers at the Medical College of Wisconsin and Promega Corporation assessed serotonin receptor binding and functional effects. 2. Potential Impact on Bipolar Disorder Treatment: Bipolar disorder management often involves a combination of drugs, such as a serotonin receptor antagonist (e.g., quetiapine) and a sodium channel blocker (e.g., lamotrigine). XOB's unique property lies in its ability to perform both functions simultaneously, at similar drug concentrations. Dr. Cozzi emphasized that XOB represents a proof-of-concept, opening doors to safer and more effective treatments for this challenging disease. 3. Polypharmacology: A New Paradigm: XOB exemplifies polypharmacology, wherein a single drug targets multiple disease-related pathways. This approach recognizes that many disorders have complex genetic origins, necessitating multifaceted therapeutic strategies. ASRI's discovery of XOB marks a significant milestone in psychiatric pharmacology. The potential to address bipolar disorder with a single, multifunctional compound could transform patient care and improve outcomes. Further research and clinical trials will determine XOB's efficacy and safety profile. Disclaimer: This press release is for informational purposes only and does not constitute medical advice. Consult a healthcare professional for personalized recommendations. About ASRI: Established on Bicycle Day in 2021 by Dr. Nicholas Cozzi, Dr. Paul Daley, and the late Ann Shulgin, ASRI continues the legacy of the esteemed chemist Alexander Shulgin, renowned for his pioneering work in discovering psychedelic compounds. At the forefront of the burgeoning interest in the potential therapeutic benefits of psychedelics, ASRI remains steadfast in its commitment to applied therapeutics, targeting neurological, neurodevelopmental, neuropsychiatric, pain syndrome, inflammation, and overall wellness enhancement domains. Drawing upon a wealth of knowledge in chemistry, pharmacology, and neuroscience, ASRI is committed to catalyzing positive change in global healthcare. Noteworthy is the Shulgin Vault, housing an extensive repository of over 500 compounds synthesized by Alexander "Sasha" Shulgin and ASRI scientists, offering a rich spectrum of novel variations spanning phenylalkylamines, tryptamines, lysergamides, isoquinolines, cathinones, and more. For more information on ASRI, please visit: . Forward-looking statement: This release contains forward-looking statements regarding ASRI's anticipated future events and outcomes, such as data projections and advancements in drug discovery methods. These statements are based on current expectations and assessments but are subject to various risks and uncertainties. Factors such as the ongoing impact of COVID-19, fluctuations in economic conditions, market dynamics, regulatory constraints, and other variables may cause actual results to differ from those anticipated. While ASRI's management has made reasonable assumptions, the actual outcomes may deviate significantly. It's important to note that ASRI has refrained from making medical assertions about its products, and regulatory bodies like the FDA have not yet evaluated their effectiveness. Rigorous clinical trials are necessary for validation, a process which ASRI has not yet undertaken. Without obtaining the required approvals or conducting essential research, ASRI's performance and operations may be negatively impacted. Therefore, stakeholders should be mindful of these uncertainties when considering the forward-looking statements contained in this release.‍ Media Contact: Kathy Lanser, [email protected] SOURCE Alexander Shulgin Research Institute

- GSK3 inhibitors showed successful CNS target engagement and efficacy comparable to lithium at significantly lower doses in models of bipolar disorder SKILLMAN, N.J.--(BUSINESS WIRE)-- 4M Therapeutics Inc., an early-stage biotechnology company developing treatments for neuropsychiatric and neurodegenerative conditions, today announced the presentation of a poster at the Society of Biological Psychiatry (SOBP) Annual Meeting, that occurred from May 9-11, 2024, in Austin, Texas. The poster, titled “The Effects of Novel Small Molecules in a Preclinical Model of Positive Affective State,” was presented on May 11, 2024. “Our presentation underscored the capability of our novel small molecules to selectively target GSK3β and demonstrate efficacy for the treatment of bipolar disorder and acute mania,” said Dr. Pablo Lapuerta, Chief Executive Officer and Co-Founder of 4M Therapeutics. “We continue to accelerate the development of much-needed therapeutic options that have the potential to significantly improve upon the safety and efficacy of the standard of care for patients with neuropsychiatric conditions. We remain on track to initiate a Phase 1 clinical trial for our lead investigational compound in 2025.” The poster examined the effects of 4M Therapeutics’ glycogen synthase kinase 3 beta (GSK3β) inhibitors, 4MT-A and 4MT-B, on amphetamine (AMP)-induced positive appetitive ultrasonic vocalizations (USVs), a validated model of positive affective state. Marked increases in USVs when treated with AMP were attenuated by lithium, and equal or greater reduction in USVs was observed when treated with 4MT-A and 4MT-B at 1/500th to 1/1000th the concentration of lithium. Similar patterns were observed across USV categories and treatment groups in both the first and second hour after AMP dosing. In addition, supporting data showed target engagement for 4MT-A through the reduction of pCRMP2 in vitro in excitatory cortical neurons and in vivo in rat brain. These statistically significant reductions in pCRMP2 demonstrated GSK3β inhibition affecting a key biomarker. About 4M Therapeutics Inc. 4M Therapeutics Inc. (4MTx) is advancing treatments for neuropsychiatric and neurodegenerative conditions. The Company focuses on targets for a wide array of disorders and indications. 4MTx applies unique insights from its living human brain cell platform, which was developed through a collaboration between Harvard, MIT, and the University of Washington to identify and design more effective and safer therapeutics. The Company’s pipeline includes potential breakthrough treatments for bipolar mania, agitation in Alzheimer’s disease, neurodegeneration, and other CNS disorders. For more information, visit .