Brain Concussion

Pilot study reveals early evidence of efficacy of a pharmacologic treatment for concussion, as patients experienced faster symptom reduction and return to physical activity PHILADELPHIA, March 19, 2024 /PRNewswire/ -- In the first clinical trial of a targeted pharmacologic therapeutic for mild traumatic brain injury in pediatric patients, scientists from the Minds Matter Concussion Frontier Program at Children's Hospital of Philadelphia (CHOP) have found preliminary evidence that adolescents and young adults with concussion who take a specific formulation of branched chain amino acid (BCAA) supplements after injury experience faster symptom reduction and return to physical activity. The findings were published online by the Journal of Neurotrauma. More than 2 million concussions occur in the youth and adolescent population in the United States each year. The mainstay of treatment remains symptom management with temporary modification of cognitive and physical activity and over the counter medication. Although active rehabilitation strategies have shown promise for improving recovery time, including aerobic, vestibular, and vision interventions, these can be time and labor intensive. To date, no targeted pharmacologic intervention to improve clinical outcomes in concussion has been evaluated in humans. Animal model studies of mild to moderate traumatic brain injury, which have been led by the study's senior author, Akiva S. Cohen, PhD, Professor of Neuroscience in the Department of Anesthesiology and Critical Care Medicine at CHOP and a research professor of Anesthesiology and Critical Care at the Perelman School of Medicine of the University of Pennsylvania, have shown that supplementation with a specific formulation of three BCAAs – leucine, isoleucine and valine – improve neurocognitive function. However, prior to this study, no human studies involving adolescents and young adults have assessed the potential benefits of this formulation of BCAAs as a specific treatment to aid in concussion recovery. "The goal of this pilot study was to determine, among several different doses, whether our specific formulation of BCAAs could accelerate recovery – faster reduction in symptoms and return to baseline physical activity," Cohen said. "Based on our work in animal models, we expected that our specific formulation of BCAA supplementation would result in a more rapid resolution in symptom burden and improved physical activity levels which are key measures of recovery from a concussion." The scientists conducted a pilot, double-blind, randomized controlled trial of participants between the ages of 12-30 years who presented with concussion to outpatient clinics, urgent care and emergency departments across the CHOP Network between June of 2014 and December of 2020. Individual participants were divided into five groups consisting of a placebo arm and different treatment arms of 15 g, 30 g, 45 g and 54 g doses of a specific formulation of BCAAs. The participants were followed for a period of 21 days after enrollment. Participants were assessed with daily computerized neurocognitive tests, reported symptom score, physical and cognitive activity, treatment compliance and adverse events. A total of 38 participants had analyzable data after study completion. The study found that there was a significant reduction in and faster resolution of the total symptom score in a dose-dependent fashion with the specific formulation of BCAA supplementation, with a significant decrease in total symptoms across the study; for every 500 g of the treatment consumed, the total symptom score, on a scale of 0-54 (with 0 representing no symptoms), dropped 4 points. Similar significant improvements were seen in a faster return to physical activity, with an increase of 0.5 on a 0-5 scale of physical activity for each 500 g of the defined BCAA supplement consumed. The treatment was very well tolerated; no serious adverse events were reported in the study, and there were no differences in mild adverse events between the placebo and treatment groups. "Our results demonstrate that our specific formulation of BCAA supplementation is a highly promising treatment that addresses the underlying mechanism driving concussion symptoms in order to accelerate recovery and improve outcomes," said the study's first author Daniel Corwin, MD, MSCE, Assistant Professor of Pediatrics and Emergency Department Lead of the Minds Matter Concussion Frontier Program at CHOP. "While a larger study is needed to confirm the formulation's efficacy before routine use of BCAA supplementation should be recommended, we are extremely encouraged by these preliminary findings, the first trial to demonstrate that a targeted pharmacologic using a specific formulation of BCAAs may be useful as a treatment for youth and young adult concussion." This study was supported by The Dana Foundation, with additional support provided by Children's Hospital of Philadelphia Frontier Program, the National Institute of Neurological Disorders and Stroke of the National Institutes of Health award number K23NS128275-01, Veterans Affairs Clinical Science and Research Department Merit Award #I01 CX002022, Oregon Aging and Disability Resource Connection, National Institutes of Health grant P30 AG066518, and VA Rehabilitation Research and Development Career Development Award #1K2 RX002947. Corwin et al, "Head Injury Treatment with HEalthy and Advanced Dietary Supplements (HIT HEADS): A pilot randomized controlled trial of the tolerability, safety, and efficacy of branched chain amino acids (BCAAs) in the treatment of concussion in adolescents and young adults." J Neurotrama. Online March 12, 2024. DOI: 10.1089/neu.2023.0433. About Children's Hospital of Philadelphia: A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit . Contact: Ben Leach Children's Hospital of Philadelphia (609) 634-7906 [email protected] SOURCE Children's Hospital of Philadelphia

SARASOTA, Fla.--(BUSINESS WIRE)-- Oragenics, Inc. (NYSE American: OGEN), a company focused on developing unique, intranasal pharmaceuticals for the treatment of neurological disorders, today announced it has appointed Dr. James “Jim” Kelly, Neurologist, as its Chief Medical Officer, to oversee its upcoming Phase II clinical trial. Oragenics’ lead drug candidate, ONP-002 is combined with its intranasal device intended for the treatment of mild Traumatic Brain Injury (TBI), aka concussion. ONP-002 is a new chemical entity (NCE) designed to target the brain through delivery into the nasal cavity and onward to the brain. A 40-patient Phase I study was completed and showed the drug to be safe and well-tolerated. In the recent past, Dr. Kelly served as the Executive Director of the Marcus Institute for Brain Health (MIBH) and Professor of Neurology at the University of Colorado Anschutz Medical Campus in Aurora, Colorado. The MIBH specialized treatment program is funded by the Marcus Foundation to care for US military veterans with persistent symptoms of TBI. Dr. Kelly was also National Director of the Avalon Action Alliance TBI Programs for which the MIBH serves as the clinical coordinating center. “I am excited to join Oragenics as its Chief Medical Officer at such an important and pivotal time in the drug development process. I have been involved with the drug for many years now and look forward to testing the drug and showing it can improve patient outcomes in our upcoming Phase II clinical trials,” said Dr. Kelly. Prior to these recent positions, Dr. Kelly was the Director of the National Intrepid Center of Excellence (NICoE) at Walter Reed National Military Medical Center in Bethesda, MD. As its founding Director, he led the creation of an innovative interdisciplinary team of healthcare professionals who blended high-tech diagnosis and treatment with complementary and alternative medical interventions in a holistic, integrative approach to the care of US military personnel with the complex combination of TBI and psychological conditions, such as post-traumatic stress, depression, and anxiety. In this role, Dr. Kelly was frequently called upon by leaders of the Military Health System at the Pentagon, the US Congress, the Department of Veterans Affairs, and numerous military facilities in the continental US and abroad. Dr. Kelly has interacted with the FDA and clinical trials for brain injury throughout his esteemed career. He is a strong advocate for treatments in the acute phase of brain injury and understands the value of protecting the brain early on from inflammation, swelling and oxidative stress to gain better clinical outcomes. “We are fortunate to have such an esteemed neurologist as Dr. Kelly join our team in this important role at Oragenics. Dr. Kelly is recognized as a leading expert in concussion and other brain injuries and we are fortunate to have him lead our drug trials going forward. We are currently completing the drug manufacturing and formulation at GMP facilities to ensure the integrity of the drug before and during the trials, and we look forward to completing this work in the short-term and getting the Phase II trial underway,” stated Michael Redmond, President of Oragenics. In preclinical animal models, the drug has been shown to acutely improve molecular and behavioral outcomes following brain injury. In addition, intranasal delivery of the drug as a nanoparticle has been shown to enhance brain exposure and metabolism in animals. “Our Phase I human study has shown ONP-002 to be well tolerated in humans. Our mission now is to show that the ONP-002 brain protective mechanisms in animals translates to humans. Our Phase II study is designed to establish time to first dose, relationships between drug application and blood biomarkers, and the evaluation of clinical endpoints to determine improved in patient outcomes, ” said Dr. Kelly. Concussion is an unmet medical need. There is an estimated 69 million concussions annually reported worldwide. Common causes of concussion include falls, motor vehicle accidents, and contact sports. Other neurological disorders including Alzheimer’s Disease, Parkinson’s Disease and Chronic Traumatic Encephalopathy (CTE) have been linked to concussion. Post concussion syndrome is linked to long term disability and occurs in as high as 20% of concussed patients. Forward-Looking Statements This communication contains “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, including without limitation statements regarding the ability of the Company to timely and successfully undertake the Phase II clinical trial using its novel drug - device combination for the treatment of mild Traumatic Brain Injury. These forward-looking statements are based on management’s beliefs and assumptions and information currently available. The words "believe," "expect," "anticipate," "intend," "estimate," "project" and similar expressions that do not relate solely to historical matters identify forward-looking statements. Investors should be cautious in relying on forward-looking statements because they are subject to a variety of risks, uncertainties, and other factors that could cause actual results to differ materially from those expressed in any such forward-looking statements. These factors include, but are not limited to: the Company’s ability to advance the development of its product candidates, including the neurology assets, under the timelines and in accord with the milestones it projects; the Company’s ability to retain its key employees and independent contractors necessary to continue to develop its product candidates and in particular ONP-002 and the availability of those key employees and independent contractors; the Company’s ability to raise capital and obtain funding, non-dilutive or otherwise, for the development of its product candidates; the Company’s expectations as to the outcome of the Phase II clinical trial and the potential benefits, activity, effectiveness and safety of its product candidates including as to administration, transmission, manufacturing, storage and distribution; and general economic and market conditions and risks, as well as other uncertainties described in our filings with the U.S. Securities and Exchange Commission. All information set forth is as of the date hereof unless otherwise indicated. You should consider these factors in evaluating the forward-looking statements included and not place undue reliance on such statements. We do not assume any obligation to publicly provide revisions or updates to any forward-looking statements, whether as a result of new information, future developments or otherwise, should circumstances change, except as otherwise required by law. Released March 18, 2024 View source version on businesswire.com: Contacts Oragenics, Inc. Janet Huffman, Chief Financial Officer 813-286-7900 jhuffman@oragenics.com LHA Investor Relations Tirth T. Patel 212-201-6614 tpatel@lhai.com Source: Oragenics, Inc. View this news release online at:

TORONTO--( BUSINESS WIRE )--NeuPath Health Inc. (TSXV:NPTH), (“NeuPath” or the “Company”), owner and operator of a network of clinics delivering category-leading chronic pain treatment, today announced its financial and operating results for the three months and year ended December 31, 2023. All figures are in Canadian dollars, unless otherwise noted. “I am very proud of our team and our successes in 2023, which have resulted from a focus on our core clinic operations and improving our balance sheet,” said Joe Walewicz, NeuPath’s Chief Executive Officer. “We will continue to direct our energy towards adding more physicians, to serve more patients, in more locations, providing greater community access to medically necessary treatments.” Financial and Operational Highlights Total revenue was $16.8 million and $66.1 million for the three months and year ended December 31, 2023, up 4% versus the fourth quarter of 2022 and 6% for the year, delivering another record year of revenues; Adjusted EBITDA was $0.8 million and $3.2 million for the three months and year ended December 31, 2023, up 41% year-over-year; For the year ended December 31, 2023, capacity utilization improved to 68%, up from 62% in the prior year; The company finished the year with $3.2 million in cash and cash equivalents and long-term debt of $6.1 million, of which $2.4 million is interest-bearing; and On January 12, 2024, the Company closed the acquisition of the assets of SIBI Medical Inc., operating as the London Spine Centre in London, Ontario. The London Spine Centre has an interdisciplinary group of healthcare providers that use evidence-based care to help treat back, neck and other spinal conditions. (1) Non-International Financial Reporting Standard (“IFRS”) and Other Financial Measures defined by the Company below. Q4 2023 Financial Results Total Revenue Total revenue is comprised of clinic revenue and non-clinic revenue. Total revenue was $16.8 million for the three months ended December 31, 2023 compared to $16.1 million for the three months ended December 31, 2022. Total revenue was $66.1 million for the year ended December 31, 2023 compared to $62.7 million for the year ended December 31, 2022. Clinic Revenue Clinic revenue is generated through the provision of medical services to patients. Clinic revenue was $15.3 million for the three months ended December 31, 2023 compared to $15.0 million for the three months ended December 31, 2022. Clinic revenue was $61.0 million for the year ended December 31, 2023 compared to $58.7 million for the year ended December 31, 2022. The increase in clinic revenue for the year ended December 31, 2023 was primarily due to stronger revenues from fluoroscopy and existing medical clinics. Non-clinic Revenue Non-clinic revenue was $1.5 million for the three months ended December 31, 2023 compared to $1.1 million for the three months ended December 31, 2022. Non-clinic revenue was $5.1 million for the year ended December 31, 2023 compared to $4.0 million for the year ended December 31, 2022. Non-clinic revenue is earned from physician staffing allocation services where the Company provides physicians for provincial and federal correctional institutions across Canada, and from contract research services provided to pharmaceutical companies and clinical research organizations. This revenue fluctuates depending on the need for physicians in certain institutions and the timing and enrolment of clinical studies that the Company is working on. Gross margin % was 19.2% for the three months ended December 31, 2023 compared to 17.5% for the three months ended December 31, 2022. Gross margin % was 18.6% for the year ended December 31, 2023 compared to 17.3% for the year ended December 31, 2022. Gross margin for the comparative year was impacted by remuneration payment accruals due to the HealthPointe acquisition resulting in increased cost of medical services of $0.8 million. Excluding these transaction-related accruals, gross margin % would have been 18.7% and 18.5% for the three months and year ended December 31, 2022. (see Non-IFRS Financial Measures - Gross Margin, Gross Margin %, Adjusted Gross Margin and Adjusted Gross Margin % ) . Adjusted EBITDA was $0.8 million and $3.2 million for the three months and year ended December 31, 2023 compared to $0.8 million and $2.3 million for the three months and year ended December 31, 2022. Liquidity and Capital Resources As at December 31, 2023, the Company’s net debt was $2.9 million, compared to $5.3 million as at December 31, 2022. The Company’s net debt as at December 31, 2023 consisted of $3.2 million of cash and cash equivalents and long-term debt of $6.1 million compared to $1.5 million of cash and cash equivalents and long-term debt of $6.8 million as at December 31, 2022. Non-IFRS Financial and Other Measures The Company discloses non-IFRS measures (such as EBITDA, adjusted EBITDA, gross margin and adjusted gross margin) and non-IFRS ratios (such as gross margin % and adjusted gross margin %) that do not have standardized meanings prescribed by International Financial Reporting Standards (“IFRS”). The Company believes that shareholders, investment analysts and other readers find such measures helpful in understanding the Company’s financial performance. Non-IFRS financial measures and other measures do not have any standardized meaning prescribed by IFRS and may not have been calculated in the same way as similarly named financial measures presented by other reporting issuers and therefore unlikely to be comparable to similar measures presented by other companies. Furthermore, these non-IFRS measures and other measures should not be considered in isolation or as a substitute for measures of performance or cash flows as prepared in accordance with IFRS. These measures should be considered as supplemental in nature and not as a substitute for related financial information prepared in accordance with IFRS. EBITDA and Adjusted EBITDA EBITDA refers to net income (loss) determined in accordance with IFRS, before depreciation and amortization, net interest expense (income) and income tax expense (recovery). The Company defines adjusted EBITDA, as EBITDA, excluding stock-based compensation expense, restructuring costs, gain on derecognition of other obligations, fair value adjustments, transaction costs, impairment charges, gain on sale of building, government loan forgiveness and finance income. Management believes EBITDA and adjusted EBITDA are useful supplemental non-GAAP measures to determine the Company’s ability to generate cash available for operations, working capital, capital expenditures, debt repayments, interest expense and income taxes. The following table provides a reconciliation of net and comprehensive income (loss) to EBITDA and adjusted EBITDA: Three months ended December 31 Year ended December 31 2023 2022 2023 2022 (in thousands) $ $ $ $ Net and comprehensive loss (368 ) (1,860 ) (191 ) (4,275 ) Add back: Depreciation and amortization 738 669 2,603 2,665 Interest cost 267 214 928 832 Income tax expense (13 ) 29 246 194 EBITDA 624 (948 ) 3,586 (584 ) Add back: Stock-based compensation 44 53 183 98 Transaction costs (1) 134 202 226 808 Finance income (1 ) (4 ) (9 ) (22 ) Restructuring - 67 - 519 Gain on sale of building - - (758 ) - Gain on government loans (40 ) - (40 ) - Gain on derecognition of other obligations - (500 ) - (500 ) Impairment - 1,938 - 1,938 Adjusted EBITDA 761 808 3,188 2,257 Attributed to: Shareholders of NeuPath Health Inc. 740 829 3,190 2,350 Non-controlling interest 21 (21 ) (2 ) (93 ) 761 808 3,188 2,257 (1) For the year ended December 31, 2022, $750 of accrued contingent consideration that under IFRS 3, Business Combinations (“IFRS 3”) was not permitted to be included in the acquisition cost has been accounted for as remuneration rather than consideration transferred. Gross Margin, Gross Margin %, Adjusted Gross Margin and Adjusted Gross Margin % Management believes gross margin, gross margin %, adjusted gross margin and adjusted gross margin % are important supplemental non-GAAP measures for evaluating operating performance and to allow for operating performance comparability from period-to-period. Gross margin is calculated as total revenue minus COMS. Gross margin % is calculated as gross margin divided by total revenue. Adjusted gross margin is calculated as gross margin, plus remuneration payment accruals related to the HealthPointe acquisition. Adjusted gross margin % is calculated as adjusted gross margin divided by total revenue. The following table provides a reconciliation of total revenue to gross margin and adjusted gross margin: Year ended December 31, 2023 Year ended December 31, 2022 (in thousands, except for %s) $ $ Clinic revenue 60,988 58,702 Non-clinic revenue 5,114 3,951 Total revenue 66,102 62,653 Cost of medical services 53,805 51,834 Gross margin (1) 12,297 10,819 Gross margin % (1) 18.6% 17.3% Add back: HealthPointe remuneration payment accruals (2) - 750 Adjusted gross margin (1) 12,297 11,569 Adjusted gross margin % (1) 18.6% 18.5% (1) Gross margin, gross margin %, adjusted gross margin and adjusted gross margin % are non-IFRS measures. Please refer to Non-IFRS Financial Measures above. (2) Includes accrued contingent consideration that under IFRS 3 was not permitted to be included in the acquisition cost and has been accounted for as remuneration rather than consideration transferred. For further details on the results, please refer to NeuPath’s Management, Discussion and Analysis and Consolidated Financial Statements for the three months and year ended December 31, 2023, which are available on the Company’s website ( www.neupath.com ) and under the Company’s profile on SEDAR+ ( www.sedarplus.ca ). About NeuPath NeuPath operates a network of healthcare clinics and related businesses focused on improved access to care and outcomes for patients by leveraging best-in-class treatments and delivering patient-centered multidisciplinary care. We operate a network of medical clinics in Ontario and Alberta that provide comprehensive assessments and rehabilitation services to clients with chronic pain, musculoskeletal/back injuries, sports related injuries and concussions. In addition, NeuPath provides workplace health services and independent medical assessments to employers and disability insurers through a national network of healthcare providers, as well as contract research services to pharmaceutical and biotechnology companies. NeuPath is focused on enabling each individual to live their best life. For additional information, please visit www.neupath.com . Forward-Looking Statements This news release contains forward-looking statements. All statements, other than statements of historical fact, that address activities, events or developments that the Company believes, expects or anticipates will or may occur in the future including, without limitation, the Company’s expectation of continued operational improvements in 2024 and the execution of the Company’s growth opportunities are forward-looking statements. These forward-looking statements reflect the current expectations or beliefs of the Company based on information currently available to the Company. Forward-looking statements are subject to a number of risks and uncertainties that may cause the actual results of the Company to differ materially from those discussed in the forward-looking statements, and even if such actual results are realized or substantially realized, there can be no assurance that they will have the expected consequences to, or effects on, the Company. Factors that could cause actual results or events to differ materially from current expectations included in this news release include, among other things, adverse market conditions, risks associated with obtaining and maintaining the necessary governmental permits and licenses related to the business of the Company, increasing competition in the market and other risks generally inherent in the chronic pain, sports medicine, concussion and workplace health services markets. A comprehensive discussion of these and other risks and uncertainties can be found in the Company’s annual information form dated March 14, 2024 filed on SEDAR + under the Company’s profile at www.sedarplus.ca . Any forward-looking statement speaks only as of the date on which it is made and, except as may be required by applicable securities laws, the Company disclaims any intent or obligation to update any forward-looking statement, whether as a result of new information, future events or results or otherwise. Although the Company believes that the assumptions underlying the forward-looking statements are reasonable, forward-looking statements are not guarantees of future performance and accordingly undue reliance should not be put on such statements due to their inherent uncertainty. NEITHER TSX VENTURE EXCHANGE NOR ITS REGULATION SERVICES PROVIDER (AS THAT TERM IS DEFINED IN THE POLICIES OF THE TSX VENTURE EXCHANGE) ACCEPTS THE RESPONSIBILITY FOR THE ADEQUACY OR ACCURACY OF THIS RELEASE.