Sprains and Strains

RSS Brexpiprazole in combination with sertraline demonstrated a statistically significant reduction in overall PTSD symptoms compared to sertraline plus placebo, as measured by change in CAPS-5 total score from Week 1 to Week 101 The safety profile of brexpiprazole in combination with sertraline was consistent with that of brexpiprazole in approved indications1 Otsuka and Lundbeck submitted an sNDA for brexpiprazole in combination with sertraline for the treatment of adults with PTSD in April 2024. The sNDA is currently under FDA review with a PDUFA target date of February 8, 2025 PTSD is a highly prevalent, trauma-based neuropsychiatric disorder that impacts approximately 13 million U.S. adults in a given year, and nearly 6 in 100 people will be diagnosed with PTSD in their lifetime2-6 Otsuka Pharmaceutical Co., Ltd. (Otsuka) announces that its US subsidiary Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) and Lundbeck Pharmaceuticals LLC (Lundbeck) today announced that the full results of a Phase 3 trial of brexpiprazole in combination with sertraline for the treatment of PTSD in adults have been published in JAMA Psychiatry. The results showed that in adults with PTSD, treatment with brexpiprazole in combination with sertraline resulted in statistically significant greater improvement of PTSD symptoms vs treatment with sertraline plus placebo, as measured by change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score from Week 1 to Week 10.1 "About 6% of the United States population will have PTSD at some point in their lives, but around only half will seek treatment," said Lori Davis, M.D., clinical professor of psychiatry in the Department of Psychiatry and Behavioral Neurobiology, University of Alabama School of Medicine, who served as lead author on the JAMA Psychiatry manuscript. "The Phase 3 results are an important and encouraging step forward in the hopes of providing PTSD patients with a new therapeutic option in the future." About the Phase 3 Trial The Phase 3 randomized, double-blind, active-controlled, parallel-arm trial (NCT04124614) evaluated the efficacy, safety, and tolerability of brexpiprazole in combination with sertraline for the treatment of PTSD. The trial included 416 adult outpatients who were randomized to receive either brexpiprazole (2-3 mg/day) with sertraline (150 mg/day) or sertraline (150 mg/day) with a placebo. The primary endpoint was the change in CAPS-5 total score from randomization (Week 1) to Week 10. Patients receiving brexpiprazole with sertraline showed a statistically significant greater improvement in CAPS-5 total score (-19.2) compared to those receiving sertraline with placebo (-13.6), with a least squares (LS) mean difference of -5.59 (95% CI: -8.79 to -2.38; P<.001). Additionally, both secondary endpoints, the change in the Clinical Global Impression- Severity of Illness score (CGI-S) randomization (week 1) to week 10 and the change in the Brief Inventory of Psychosocial Function (B-IPF) from baseline (Day 0) to week 12, were also met.1 "The clinical trial results demonstrate the potential of brexpiprazole in combination with sertraline as a treatment option for patients with PTSD, a condition that affects millions within the United States," said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc. "The combination of brexpiprazole and sertraline demonstrated meaningful improvements in PTSD symptoms." The safety profile of brexpiprazole in combination with sertraline was consistent with that of brexpiprazole in approved indications. The proportion of treated participants who discontinued due to adverse events was 3.9% (8/205) for brexpiprazole + sertraline and 10.2% (20/196) for sertraline + placebo.1 The adverse events occurring in >=5% for brexpiprazole in combination with sertraline (n=205) compared to sertraline and placebo (n=196) were nausea (12.2% vs 11.7%), fatigue (6.8% vs 4.1%), weight increase (5.9% vs 1.5%), and somnolence (5.4% vs. 2.6%), respectively.1 "The outcome of this trial provides us with an opportunity to help patients with PTSD," said Johan Luthman, executive vice president and head of Research & Development at Lundbeck. "With these promising results, we are committed to working closely with the FDA to help bring brexpiprazole in combination with sertraline to the healthcare professionals serving the PTSD patient community." About CAPS-5 The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a structured interview designed to assess PTSD diagnostic status and symptom severity as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The CAPS-5 consists of 30 items, with a higher score indicating a worse outcome.1 The CAPS-5 includes 20 DSM-5 PTSD-symptom items that are each scored from 0 (absent) to 4 (extreme/incapacitating). The total score is calculated by summing the 20 items, and symptom cluster scores by summing specific items: Intrusion (items 1-5); Avoidance (items 6-7); Negative cognitions and mood (items 8-14); and Arousal and reactivity (items 15-20).1 The CGI-S is a 7-point categorical scale, originally developed for mental disorders, but now applied to various illnesses, that requires a clinician to rate the severity of a patient's illness at the time of assessment, relative to the clinician's experience with patients who have the same diagnosis.7 The B-IPF is an abridged, 7-item version of the Inventory of Psychosocial Functioning (IPF) which assesses PTSD-related functional impairment in the prior 30 days across the same domains that are assessed by the 80-item version of the IPF; each item on the B-IPF corresponds to one IPF functional domain.8 About Post-Traumatic Stress Disorder PTSD is one of the most common mental health disorders in the United States, with approximately five percent of the population affected during a given year.2, 4, 9, 10 Most patients (>80%) with PTSD in the United States are in the civilian population.4, 11 It may occur in people who have experienced or witnessed a traumatic event, series of events or set of circumstances. An individual may experience an event that is emotionally or physically harmful or life-threatening which may affect mental, physical, social, and/or spiritual well-being. Examples of traumatic events include physical/sexual assault, natural disasters, serious accidents, terrorist acts, war/combat, historical trauma, intimate partner violence and bullying.12, 13 Symptoms of PTSD are generally grouped into four symptom clusters: intrusion (re-experiencing), persistent avoidance of stimuli, negative alterations in cognitions and mood, and marked alterations in arousal and reactivity. Individual symptom type and intensity can fluctuate over time and between individuals. To meet the criteria for PTSD diagnosis, symptoms must last longer than one month, and they must be severe enough to interfere with aspects of daily life, such as relationships or work. Symptoms also must not be due to medications, substance use, or another medical condition.10, 12 The average time from index trauma to symptom presentation is 2.2 years, and the average time from index trauma to PTSD diagnosis is 8.7 years.14 About Brexpiprazole Brexpiprazole was approved in the U.S. by the FDA in 2015, as an adjunctive therapy to antidepressants in adults with major depressive disorder (MDD) and as a treatment for schizophrenia in adults. Most recently, brexpiprazole was approved in the U.S. for the treatment of agitation associated with dementia due to Alzheimer's disease, in May 2023. Brexpiprazole was also approved by Health Canada for schizophrenia and adjunctive treatment of MDD in 2017 and 2019, respectively, and for agitation associated with dementia due to Alzheimer's disease in 2024. It was approved by the European Medicines Agency in 2018 for the treatment of schizophrenia and the Ministry of Health, Labour and Welfare in Japan for the treatment of schizophrenia and MDD in 2018 and 2023, respectively. Brexpiprazole was discovered by Otsuka and is being co-developed by Otsuka and Lundbeck. The mechanism of action of brexpiprazole is unknown. Brexpiprazole has high receptor binding affinity to norepinephrine, serotonin and dopamine receptors. It is an antagonist at norepinephrine α1B and α2C receptors and serotonin 5-HT2A receptors, as well as a partial agonist at serotonin 5-HT1A and dopamine D2 receptors.15, 16 References 1. Davis LL, Behl S, Lee D, et al. Brexpiprazole and Sertraline Combination Treatment in Posttraumatic Stress Disorder. JAMA Psychiatry. Published online December 18, 2024. doi:10.1001/jamapsychiatry.2024.3996 2. U.S. Department of Veterans Affairs. How Common Is PTSD in Adults? Accessed September 2024. www.ptsd.va.gov/understand/common/common_adults.asp. 3. US Census Bureau. (2022). National Population by Characteristics: 2020-2022. Retrieved from www.census.gov/data/tables/time-series/demo/popest/2020s-national-detail.html. 4. Lehavot K, Katon JG, Chen JA, Fortney JC, Simpson TL. Post-traumatic Stress Disorder by Gender and Veteran Status [published correction appears in Am J Prev Med. 2019 Oct;57(4):573]. Am J Prev Med. 2018;54(1):e1-e9. 5. Goldstein RB, Smith SM, Chou SP, et al. The epidemiology of DSM-5 posttraumatic stress disorder in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions-III. Soc Psychiatry Psychiatr Epidemiol. 2016;51(8):1137-1148. 6. Schein J, Houle C, Urganus A, et al. Prevalence of post-traumatic stress disorder in the United States: a systematic literature review. Curr Med Res Opin. 2021;37(12):2151-2161. 7. Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont). 2007;4(7):28-37. 8. U.S. Department of Veterans Affairs. Inventory of Psychosocial Functioning (IPF). Accessed December 2024. https://www.ptsd.va.gov/professional/assessment/functioning-other/ipf_psychosocial_function.asp 9. Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM, Wittchen H -U. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res. 2012;21(3):169-184. 10. Lancaster CL, Teeters JB, Gros DF, Back SE. Posttraumatic Stress Disorder: Overview of Evidence-Based Assessment and Treatment. J Clin Med. 2016;5(11):105. 11. Davis LL, Schein J, Cloutier M, et al. The Economic Burden of Posttraumatic Stress Disorder in the United States From a Societal Perspective. J Clin Psychiatry. 2022;83(3):21m14116. 12. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA, American Psychiatric Association, 2013 13. American Psychiatric Association. What is Posttraumatic Stress Disorder (PTSD)? Last updated: November 2022. Last accessed: August 28, 2024. Available at: www.psychiatry.org/patients-families/ptsd/what-is-ptsd. 14. Davis LL, Urganus A, Gagnon-Sanschagrin P, et al. Patient journey of civilian adults diagnosed with posttraumatic stress disorder-A chart review study. Curr Med Res Opin. 2024;40(3):505-516. 15. Maeda K, Sugino H, Akazawa H, et al. Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin-dopamine activity modulator. J Pharmacol Exp Ther. 2014;350(3):589-604. 16. REXULTI® (brexpiprazole). Prescribing Information. FDA. Reference ID: 4911319. May 2024.

388813 01: A photo illustration depicts a person typing May 4, 2001 in Denver, CO. National Academy of Sciences estimates that musculoskeletal disorders such as carpal-tunnel syndrome, tendinitis, and lower back pain cost the nation $45 billion to $54 billion in compensation, lost wages, and lower productivity each year. (Photo by Michael Smith/Newsmakers) On Monday, a Silicon Valley-based bioelectronic medicine company raised tens of millions of dollars to help the more than 7 million Americans who struggle with essential tremor (ET). The company, named Cala Health, closed a $50 million funding round co-led by Vertex Growth Fund and Nexus NeuroTech Ventures. All of the company’s existing investors also participated in the round, including GV, Johnson & Johnson, Lux Capital, OSF Ventures and Ascension Ventures. Cala was founded in 2014 as a Stanford University spinout. Its main goal is to give patients a better option for treating their ET — which is a neurological disorder characterized by involuntary shaking that usually affects the hands, head or voice. presented by Market Trends to Watch for Health Systems and Their Specialty Pharmacies The future looks bright for the integrated specialty pharmacy model – for health systems, providers, and most importantly, for patients. By Jake Gaffey, MBA, Chief Strategy Officer at Shields Health Solutions The condition can have a significant effect on people’s essential abilities, such as writing, eating and speaking, pointed out Cala CEO Deanna Harshbarger. “As a result, these tremors can impact mental health and discourage people from doing what they love. Clinical studies estimate 50% of ET patients suffer from social phobia, and 80% of ET patients suffer from depression that can severely impact quality of life,” she stated. The drugs used most often to treat ET include beta-blockers such as propranolol and an epilepsy drug called primidone. While these medications are effective for some patients, they can also induce a range of undesirable side effects such as fatigue, nausea and depression — and some patients might not be able to take these drugs due to contraindications with comorbidity, Harshbarger noted. There are also surgical options, like deep brain stimulation or ablation — but not all patients are keen on invasive procedures, she added. Exclusive Heard at HLTH 2024: Insights from Innovative Healthcare Executives Executives from Imagine360, Verily, BrightInsight, Lantern, and Rhapsody shared their approaches to reducing healthcare costs and facilitating digital transformation. By MedCity News Last year, Cala gave ET patients a new option through the commercial launch of its kIQ system, which the company says is the first noninvasive wearable device cleared by the FDA to temporarily relieve tremors in people with ET and Parkinson’s disease. “Our goal is to leverage bioelectronic medicine to transform the standard of care for chronic disease and allow patients to live life fully,” Harshbarger declared. The kIQ system is a wrist-worn device prescribed by physicians to manage a patient’s hand tremors. It senses each patient’s unique tremor signature and individualizes stimulation, Harshbarger said. The at-home therapy system delivers transcutaneous afferent patterned stimulation (TAPS) therapy, meaning it applies specific patterns of electrical stimulation through the skin to modulate neural activity and promote therapeutic effects. Using TAPS, the device noninvasively counteracts the patient’s tremor through the nerves on the wrist, she explained. Once a patient completes an at-home therapy session, they can view their body’s responses via Cala’s online patient portal. Nine out of 10 patients experience tremor reduction with a complete 40-minute session, Harshbarger noted. Medicare, the VA and several commercial health plans pay for the therapy, she said. She also said that Cala has no direct competitors, given there are no other companies selling FDA-cleared, noninvasive neurostimulation devices for the relief of hand tremor. There are some other companies developing devices to treat ET using noninvasive neurostimulation, including Allevion Therapeutics and Encora Therapeutics, but they haven’t cleared regulatory hurdles yet in the U.S. Cala is also currently in the process of developing TAPS therapy-based solutions for other indications, such as cardiology and psychiatry, Harshbarger said.

ADELAIDE, Australia, and CAMBRIDGE, Mass., Oct. 07, 2024 (GLOBE NEWSWIRE) -- Bionomics Limited (Nasdaq: BNOX) (Bionomics or Company), a clinical-stage biotechnology company developing novel, first-in-class, allosteric ion channel modulators to treat patients suffering from serious central nervous system (CNS) disorders with high unmet medical need, today announced that Spyridon “Spyros” Papapetropoulos M.D.., Ph.D., President and Chief Executive Officer of Bionomics, issued the following letter to Bionomics shareholders regarding recent achievements, executional efficiencies and the positive outlook for the Company’s future. Dear Fellow Bionomics Shareholders, This year continues to be a pivotal year for Bionomics, characterized by numerous wins and essential changes that have enhanced the Company and furthered our goal of creating therapies for the countless individuals suffering from anxiety and stress disorders. As we enter the last quarter of 2024, I would like to take a moment to highlight a few of our recent accomplishments and milestones: Strengthened the US-based management team and implemented necessary cost-cutting measures to ensure optimal runway for execution of our pipeline.Clinically, we advanced our lead program of BNC210 and initiated our first ever Phase 3 trial in social anxiety disorder (SAD) after successful regulatory interactions, expanded our IP portfolio through data-driven patent applications, extended BNC210’s IP beyond 2040, and successfully communicated our scientific achievements in numerous banking, investor and scientific conferences.Financially, we secured funding though a private placement securities transaction and an ATM facility that allow us to complete our Phase 3 SAD study without compromising operational quality and speed of execution. Additionally, we are in the final stages of redomiciling the Company to the U.S. and launching Neuphoria Inc, a company with new vision, strategy and CNS pipeline focus to fully leverage the strong U.S. biotechnology ecosystem, while maintaining our Australian presence and potential future tax benefits. During the ordinary course of this process, we plan to consolidate our issued shares of our trading securities and remain compliant with the NASDAQ Stock Market listing rules. Thanks to these efforts, we believe the company is and will be fundamentally in a much stronger position today and moving forward. As shareholders ourselves, we remain disappointed in Bionomics’ stock performance, particularly following our Annual Report (10-K) filling on September 30, 2024. Yet, we believe that Bionomics is significantly undervalued, given our lead asset BNC210 is essentially a novel, “pipeline in a pill”, small molecule with unique anxiolytic and antidepressant properties that can bring tremendous benefits to patients suffering from anxiety and stress disorders globally. Following the recent unfavorable industry developments with psychedelics in post-traumatic stress disorder (PTSD), unrelated to our product pipeline, Bionomics’ BNC210 is the only promising registrational stage program with a novel mechanism of action having demonstrated the best clinical study outcomes in decades, (as announced in September 2023) with a clear path for an NDA submission, and with one successful registrational quality study already competed, requiring one additional successful Phase 3 trial for potential registration. Of note, BNC210 also has two FDA fast track designations for SAD and PTSD programs, a sizable and favorable safety database supporting a differentiated non-sedating, non-addicting profile and positive datasets in four separate anxiety and stress-related indications. These clinical datasets and designations give us the ability to leverage regulatory privileges that can potentially accelerate review and approval. Moreover, we are also considering submitting a rebuttal in the future regarding the FDA decision to not grant a Breakthrough Designation in PTSD. It should also be noted that not being granted this designation does not in any way derail our progress or pathway in our clinical trials or intended operational success. As we continue executing the Phase 3 program in SAD with anticipated readout in Q3 2025, we are also working diligently on exploring ways to enhance efficiencies and foster potential partnerships that will ensure our ability to drive the Phase 3 trial of BNC210 in PTSD to a successful NDA submission with a single trial. This would be a major achievement for the Company following our successful End-of-Phase 2 meeting with the FDA in June 2024. We have begun trial initiation activities, and we are on track to commence the Phase 3trial in PTSD in the second half of 2025 or sooner, contingent upon successful financing. Our long-standing strategic partnership with MSD (known as Merck & Co., Inc., Rahway NJ, USA in the U.S. and Canada) on the development of α7 receptor PAMs targeting cognitive dysfunction associated with Alzheimer’s disease and other central nervous system conditions valued ~US $500M is quickly advancing and is anticipated to enter Phase 2 in the near future, triggering a sizable milestone payment for the Company. Along with you, we believe Bionomics has significant, unrealized value that is not yet reflected in the current stock price. We know from experience that transformations take time, and we strongly believe that we are on the right path and are excited for what lies ahead. We will continue to work industriously and prioritize prudent financial management, operational excellence and efficiency to further position Bionomics for future success and create shareholder value. I would like to take this opportunity to thank you for your continued support and confidence in our Company. If you have any questions or would like more information, please do not hesitate to contact us. Thank you for your continued partnership. Sincerely, Spyros Papapetropoulos M.D., Ph.D.President & CEOBionomics FOR FURTHER INFORMATION PLEASE CONTACT: GeneralRajeev Chandra Company SecretaryCoSec@bionomics.com.auInvestor RelationsKevin Gardnerkgardner@lifesciadvisors.comInvestor RelationsChris Calabreseccalabrese@lifesciadvisors.com About BNC210 Formulated as an oral solid tablet BNC210 is a negative allosteric modulator of the α7 nicotinic acetylcholine receptor under development for the treatment of social anxiety disorder (SAD) and post-traumatic stress disorder (PTSD). BNC210 has been given FDA Fast Track designation for acute treatment of SAD and other anxiety related disorders, and for treatment of PTSD and other trauma and stressor related disorders. About Bionomics LimitedBionomics (NASDAQ: BNOX) is a clinical-stage biotechnology company developing novel, potential first-in-class, allosteric ion channel modulators to treat patients suffering from serious central nervous system (CNS) disorders with high unmet medical need. Bionomics is advancing its lead drug candidate, BNC210, an oral, proprietary, selective negative allosteric modulator of the α7 nicotinic acetylcholine receptor, for the acute treatment of social anxiety disorder (SAD) and chronic treatment of post-traumatic stress disorder (PTSD). Beyond BNC210, Bionomics has a strategic partnership with Merck & Co., Inc. (known as MSD outside the United States and Canada) with two drugs in early-stage clinical trials for the treatment of cognitive deficits in Alzheimer’s disease and other CNS conditions. Bionomics’ pipeline also includes preclinical assets that target Kv3.1/3.2 and Nav1.7/1.8 ion channels being developed for CNS conditions of high unmet need. www.bionomics.com.au Forward-Looking StatementsBionomics cautions that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as “may,” “could,” “will,” “would,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “intend,” “predict,” “seek,” “contemplate,” “potential,” “continue” or “project” or the negative of these terms or other comparable terminology are intended to identify forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to: the closing of each tranche of the Company’s private placement financing, the achievement of certain milestones for the various tranches, the timely funding to the Company by each investor in the private placement, the timing, size and expectation of the closing of the private placement; and expectations regarding market conditions, the satisfaction of customary closing conditions related to the private placement and the anticipated use of proceeds therefrom; and the Company’s expectation that its current cash, cash equivalents, and marketable securities will fund our operations into the third quarter of 2025. The inclusion of forward-looking statements should not be regarded as a representation by Bionomics that any of its plans will be achieved. Actual results may differ materially from those set forth in this release due to the risks and uncertainties inherent in the Company’s business and other risks described in the Company’s filings with the Securities and Exchange Commission (SEC), including, but not limited to, the Company’s Annual Report on Form 20-F filed with the SEC, and its other reports. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Bionomics undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. Further information regarding these and other risks, uncertainties and other factors is included in Bionomics’ filings with the SEC, copies of which are available from the SEC’s website (www.sec.gov) and on Bionomics’ website (www.bionomics.com.au) under the heading “Investor Center.” All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995. Bionomics expressly disclaims all liability in respect to actions taken or not taken based on any or all the contents of this press release.