Plasma Cell Granuloma, Pulmonary

BrainStorm to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for NurOwn® for the treatment of ALS New clinical analyses reinforce the conclusions from NurOwn's® Phase 3 clinical trial Conference call and webcast at 8:00 a.m. Eastern Time today NEW YORK, Aug. 15, 2022 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of adult stem cell therapeutics for neurodegenerative diseases, today announced financial results for the second quarter ended June 30, 2022, and provided a corporate update. The company also announced its decision to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration for NurOwn® for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm announces decision to submit a BLA to the FDA for NurOwn® for the treatment of ALS "Brainstorm Cell Therapeutics is at a pivotal moment as a company as we finalize the regulatory filing for NurOwn® in the treatment of ALS. The continued analysis and the feedback received from the many scientific presentations of NurOwn's® Phase 3 data have uncovered key insights that furthered our understanding of the product mechanism of action and therapeutic potential and strengthened the conclusions of NurOwn's® efficacy," said Chaim Lebovits, Chief Executive Officer. "After carefully considering these learnings, the totality of the evidence from NurOwn's® clinical studies, and the feedback received from key opinion leaders and the broader ALS community, we will submit a Biologics License Application to the FDA. We are deeply grateful to the ALS clinical experts, members of the ALS community and faithful investors for their contribution to the development of NurOwn® and what it may mean to those living with ALS. Their contributions and commitment made our current progress possible and continue to inspire us as we prepare for the considerable work ahead. We intend to provide additional updates upon learning whether the FDA files our BLA submission." New clinical analyses strengthen the conclusions from NurOwn's® Phase 3 clinical trial A correction was made to the Muscle and Nerve publication from December 2021 describing the results of NurOwn's® Phase 3 clinical trial in ALS following new clinical analyses which strengthen the Company's original conclusions from the trial. The correction results in a statistically significant treatment difference (p=0.050) of more than 2 points for an important secondary endpoint, average change from baseline in ALSFRS-R, in the pre-specified efficacy subgroup of participants with a baseline score of at least 35. Analyses reported in the original publication utilized an efficacy model that unintentionally deviated from the trial's pre-specified statistical analysis plan by erroneously incorporating interaction terms between the subgroup and treatment. The newly published results, which includes supporting information to the publication, employ the efficacy model as pre-specified in the trial's statistical analysis plan, correcting the analyses. The correction also relates to the other subgroup analyses published for this endpoint, demonstrating that all subgroups with ALSFRS-R baseline scores of at least 26 to 35 showed a statistically significant benefit following treatment with NurOwn® (p≤0.050) on this secondary endpoint. Other Second Quarter 2022 and Recent Highlights Presented new analyses from NurOwn's® Phase 3 ALS trial that showed a treatment effect in participants predicted by the ENCALS model to have intermediate to very long survival. These analyses confirmed the importance of avoiding potentially misclassifying treatment responses due to the ALSFRS-R floor effect and were presented in a poster presentation at the 2022 European Network for the Cure of ALS (ENCALS) Meeting. The presentation was delivered by Dr. Jonathan Katz, principal investigator on the trial and Chair of the Neurology Department and Director of the Forbes Norris ALS Clinic at the California Pacific Medical Center. Biomarker analyses from NurOwn's® Phase 3 ALS trial were the subject of an abstract presented at the 2022 American Academy of Neurology Congress by Dr. James Berry, MD, MPH, principal investigator on the trial and Director of the Massachusetts General Hospital Multidisciplinary ALS Clinic and Chief of the Division of ALS and Motor Neuron Diseases. Results of the analyses showed significant changes across multiple cerebrospinal fluid (CSF) biomarkers following NurOwn® treatment, with the strongest effects observed on biomarkers related to neuroprotection and neuroinflammation. Presented a summary of analyses from the Phase 3 trial of NurOwn® in ALS that highlighted the ability of biomarkers to predict clinical treatment response and provide a window into the complex biological pathways underlying disease progression. The presentation was delivered at the ALS Drug Development Summit by BrainStorm's President and Chief Medical Officer, Dr. Ralph Kern, MD, MHSc. Reported new results from the open-label Phase 2 study of NurOwn® in progressive multiple sclerosis (MS) that highlighted post-treatment improvements in monocular and binocular low contrast letter acuity (LCLA) outcomes (1.25% and 2.5% thresholds). In contrast, matched patients from the long-term Comprehensive Longitudinal Investigation of Multiple Sclerosis (CLIMB) study and participants from the placebo arm of the SPRINT study showed worsening in LCLA outcomes over a similar time period. The results were presented in a poster presentation delivered by Dr. Kern at the 2022 Consortium of Multiple Sclerosis Centers (CMSC) Meeting. Presented biomarker analyses from the open-label Phase 2 study of NurOwn® in progressive MS showing consistent post-treatment reductions in CSF inflammatory biomarkers that may be relevant to disease progression and treatment response. The presentation was delivered by Dr. Christopher Lock, PhD, Clinical Associate Professor, Neurology and Neurological Studies, at Stanford School of Medicine, at the CMSC 2022 Meeting. Preclinical in-vitro data that showed NurOwn® cells maintaining their neurotrophic and immunomodulatory effects in the presence of Siponimod, an S1P modulator recently approved for the treatment of secondary progressive MS, were presented in a poster presentation at the CMSC 2022 Meeting. The presentation was delivered by Dr. Sidney Spector, MD, PhD, Senior Vice President, Medical Affairs and Global Strategy at BrainStorm Cell Therapeutics. Reported preclinical data from a murine lung injury model (the bleomycin model) that demonstrated intrathecal administration of NurOwn®-derived exosomes (Exo MSC-NTF) may have potential as a clinical therapy for inflammatory pulmonary pathologies and display superior macrophage immunomodulation compared to naïve mesenchymal stem cell-derived exosomes (Exo-MSC). The data were presented at the International Society for Extracellular Vesicles (ISEV) 2022 Annual Meeting by Haggai Kaspi, PhD, Preclinical Research Manager at BrainStorm Cell Therapeutics. Preclinical in vitro data demonstrating the superior anti-inflammatory effects of Exo MSC-NTF compared to Exo-MSC were featured in a poster at the International Society of Cell & Gene Therapy (ISCT) 2022 Meeting. The poster was presented by Dr. Kim Thacker, Senior Vice President, Medical Affairs and Clinical Innovation at BrainStorm Cell Therapeutics. Strengthened executive team in preparation for anticipated growth and corporate development, with the appointment of Netta Blondheim-Shraga, PhD, as VP of Research & Development and Antal Pearl-Lendner, Adv., as Chief Legal Counsel Financial Results for the Second Quarter Ended June 30, 2022 Cash, cash equivalents, and short-term bank deposits were approximately $12.2 million as of June 30, 2022, compared to $18.4 million as of March 31, 2022. Research and development expenses for the three months ended June 30, 2022, and 2021 were approximately $5.1 million and $3.6 million, respectively. General and administrative expenses for the three months ended June 30, 2022, and 2021 were approximately $2.5 million. Net loss for the three months ended June 30, 2022, was approximately $7.0 million, as compared to a net loss of approximately $6.3 million for the three months ended June 30, 2021. Net loss per share for the three months ended June 30, 2022, and 2021 was $0.19 and $0.17, respectively. Conference Call and Webcast August 15, 2022, at 8:00 a.m. Eastern Time Participant Numbers: Toll Free: 888-506-0062 International: 973-528-0011 Participant Access Code: 955552 Webcast URL: Those that wish to listen to the replay of the conference call can do so by dialing the numbers below. The replay will be available for 14 days. Toll Free: 877-481-4010 International: 919-882-2331 Replay Passcode: 46290 About NurOwn® The NurOwn® technology platform (autologous MSC-NTF cells) represents a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors (NTFs). Autologous MSC-NTF cells are designed to effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. About BrainStorm Cell Therapeutics Inc. BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwn® technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug designation status from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm has completed a Phase 3 pivotal trial in ALS (NCT03280056); this trial investigated the safety and efficacy of repeat-administration of autologous MSC-NTF cells and was supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). BrainStorm completed under an investigational new drug application a Phase 2 open-label multicenter trial (NCT03799718) of autologous MSC-NTF cells in progressive multiple sclerosis (MS) and was supported by a grant from the National MS Society (NMSS). Safe-Harbor Statement Statements in this announcement other than historical data and information, including statements regarding future BLA submission, constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may," "should," "would," "could," "will," "expect," "likely," "believe," "plan," "estimate," "predict," "potential," and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, BrainStorm's need to raise additional capital, BrainStorm's ability to continue as a going concern, BrainStorm's plan to submit a BLA for NurOwn® to the FDA, prospects that the FDA will accept BrainStorm's BLA for NurOwn® for filing and review, prospects that the FDA does not view BrainStorm's NurOwn® product candidate to have demonstrated adequate safety or effectiveness, prospects for future regulatory approval of BrainStorm's NurOwn® treatment candidate, the success of BrainStorm's product development programs and research, regulatory and personnel issues, development of a global market for BrainStorm's products, if approved, and services, the ability to secure and maintain research institutions to conduct BrainStorm's clinical trials, the ability to generate significant revenue, the ability of BrainStorm's NurOwn® treatment candidate to achieve broad acceptance as a treatment option for ALS or other neurodegenerative diseases, BrainStorm's ability to manufacture and commercialize the NurOwn® treatment candidate, obtaining patents that provide meaningful protection, competition and market developments, BrainStorm's ability to protect our intellectual property from infringement by third parties, health reform legislation, demand for our services, currency exchange rates and product liability claims and litigation; the impacts of the COVID-19 pandemic and additional strains of COVID-19 or any other health epidemic on our clinical trials, supply chain, and operations; potential delays in any planned or anticipated review or interactions with the FDA due to disruptions at, or inadequate funding of, the FDA; the impact of global economic and political developments on our business, including rising inflation and capital market disruptions; the current conflict in Ukraine, economic sanctions and economic slowdowns or recessions that may result from such development; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available at . These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations, and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance, or achievements. CONTACTS Investor Relations: John Mullaly LifeSci Advisors, LLC Phone: +1 617-429-3548 [email protected] Media: Lisa Guiterman Phone: +1 202 330-3431 [email protected] The accompanying notes are an integral part of the consolidated financial statements. The accompanying notes are an integral part of the consolidated financial statements. SOURCE BrainStorm Cell Therapeutics Inc

Highlights: Bellberry human research ethics committee approved the phase 1 clinical trial investigating safety and pharmacokinetics of IHL-675A on July 20, 2022 The trial will be performed at CMAX Clinical Research, a dedicated and experienced clinical trial centre in Australia, and managed by Avance Clinical The trial will assess the pharmacokinetics, safety, and tolerability of combination cannabinoid drug IHL-675A Trial data will be applicable to regulatory submissions for all three IHL-675A development programs, rheumatoid arthritis, inflammatory bowel disease and lung inflammation Formulation and manufacturing of IHL-675A soft gel capsules for the clinical trial has been completed; long term stability studies are ongoing Patient recruitment is scheduled to commence in August 2022 MELBOURNE, Australia, July 21, 2022 /PRNewswire/ -- Incannex Healthcare Limited (Nasdaq: IXHL) (ASX: IHL), ('Incannex' or the 'Company') a clinical-stage pharmaceutical company developing unique medicinal cannabinoid pharmaceutical products and psychedelic medicine therapies for unmet medical needs, is pleased to announce that it has received approval from the Bellberry Human Research Ethics Committee ('HREC') for a phase 1 clinical trial investigating its proprietary multi-use, anti-inflammatory drug IHL-675A. IHL-675A is a combination cannabinoid drug comprising cannabidiol ('CBD') and hydroxychloroquine ('HCQ') in a fixed dose combination. IHL-675A was observed to outperform either CBD and HCQ in various pre-clinical models of inflammation, including in vivo models of rheumatoid arthritis, inflammatory bowel disease and lung inflammation. Synergistic anti-inflammatory activity of CBD and HCQ was observed in these distinct pre-clinical studies and was evidence to support the Company's international patent application over the drug. CEO and Managing Director, Mr Joel Latham said; "Approval to begin our Australian phase 1 trial is a significant milestone for Incannex and clinicians treating patients with disorders for which inflammation is the underlying cause. There's a growing trend whereby patients are using CBD to treat, or supplement their existing treatments, for inflammation disorders. We have observed in established models of inflammation that IHL-675A is a stronger anti-inflammatory cannabinoid-based drug than CBD administered alone, hence we are delighted and excited to take IHL-675A to the clinic for the first time". The trial will measure the safety, tolerability, and pharmacokinetic profiles of IHL-675A compared to the reference listed drugs, Epidiolex (CBD) and Plaquenil (HCQ). Three cohorts of 12 participants (n = 36) will receive either IHL-675A, CBD or HCQ and the assessments will be identical across the three arms of the trial. Chief Scientific Officer of Incannex Healthcare, Dr Mark Bleackley said; "The aims of the trial are to demonstrate that there are no, or minimal, additional side effects associated with the combination of CBD and HCQ compared to each drug alone and that the uptake and metabolism, otherwise known as pharmacokinetics, of the two drugs do not materially interfere with one another". Subject to clinical success, the results of the phase 1 clinical trial will form part of three U.S. Food and Drug Administration ('FDA') investigational new drug ('IND') applications for each of the initial three indications the Company is pursuing for IHL-675A. These indications are rheumatoid arthritis, inflammatory bowel disease and lung inflammation, representing major markets for Incannex to pursue with IHL-675A. Once the IND applications are evaluated and approved, the Company intends to conduct clinical trials partly or wholly in the United States. The trial will be conducted at CMAX Clinical Research in Adelaide, South Australia, and managed by Avance Clinical. Patient recruitment is anticipated to commence in August 2022. IHL-675A Formulation and Manufacturing of Clinical Trial Supply Completed Incannex is also pleased to announce that formulation development of IHL-675A has been completed and the first batch of product has been manufactured. The formulation development process included multiple experiments conducted to determine the ideal excipients to use in formulation of IHL-675A. Other assessments included the characterization of the dissolution of both active pharmaceutical ingredients (CBD and HCQ) from the IHL-675A gel capsule and ensuring that the dissolution profile was consistent with the reference listed drugs. Data from the characterization of the IHL-675A gel capsules, the quality assessment and early timepoints in the stability analysis were a critical component of the HREC submission package. These results, along with data from the ongoing stability studies are essential to support future regulatory submissions, including IND and new drug applications with the FDA and corresponding applications with other regulatory agencies. Stability studies to establish the shelf life of the IHL-675A gel capsule product are also underway. The manufacturing facilities at Incannex's formulation partner have been inspected and approved for good manufacturing practices (GMP) by multiple regulatory agencies including FDA, TGA, Health Canada and MHRA. Production of IHL-675A soft gel capsules can quickly ramp up to commercial quantities when required. About IHL-675A IHL-675A comprises a combination of HCQ and CBD. HCQ is a disease modifying anti-rheumatic drug that regulates the activity of the immune system, which may be overactive in some conditions. HCQ can modify the underlying disease process, rather than simply treating the symptoms. Incannex has demonstrated that IHL-675A components, CBD and HCQ, act synergistically to inhibit production of key inflammatory cytokines in an in vitro study of human cells and in four distinct successful in vivo experiments using established models of inflammation. Incannex has evaluated the results of these experiments and believe IHL-675A to be a multi-use drug candidate suitable for the prevention and treatment of inflammation, with an initial focus on inflammatory lung conditions (acute respiratory distress syndrome, COPD, asthma, and bronchitis), rheumatoid arthritis, and inflammatory bowel disease. The treatment of these indications has a combined global annual market size of exceeding US$125B per annum1. IHL has completed a pre-IND meeting with the FDA to discuss the regulatory pathway for the development of IHL-675A in the United States and plan to open INDs for each of the three indications. FDA agreed that marketing applications for IHL-675A should be 505(b)(2) applications due to the existence of certain safety and efficacy information on the active ingredients of IHL-675A originating from historical studies that we are entitled to use in a new drug application. This announcement has been approved for release to ASX by the Incannex board of directors. About Incannex Healthcare Limited Incannex is a clinical stage pharmaceutical development company that is developing unique medicinal cannabis pharmaceutical products and psychedelic medicine therapies for the treatment of anxiety disorders, obstructive sleep apnoea (OSA), traumatic brain injury (TBI)/concussion, lung inflammation (ARDS, COPD, asthma, bronchitis), rheumatoid arthritis and inflammatory bowel disease. U.S. FDA approval and registration, subject to ongoing clinical success, is being pursued for each drug and therapy under development. Each indication represents major global markets and currently have no, or limited, existing registered pharmacotherapy (drug) treatments available to the public. Incannex has a strong patent filing strategy in place as it develops its products and therapies in conjunction with its medical and scientific advisory board and partners. Incannex is listed on the Australian Stock Exchange (ASX) with stock code "IHL" and also has American Depository Shares listed on NASDAQ under code "IXHL". Website: Investors: [email protected] Forward-looking statements This press release contains "forward-looking statements" within the meaning of the "safe harbor" provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements are made as of the date they were first issued and were based on current expectations and estimates, as well as the beliefs and assumptions of management. The forward-looking statements included in this press release represent Incannex's views as of the date of this press release. Incannex anticipates that subsequent events and developments may cause its views to change. Incannex undertakes no intention or obligation to update or revise any forward-looking statements, whether as of a result of new information, future events or otherwise. These forward-looking statements should not be relied upon as representing Incannex's views as of any date after the date of this press release. Contact Information Incannex Healthcare Limited Mr Joel Latham Managing Director and Chief Executive Officer +61 409 840 786 [email protected] US IR Contact Rx Communications Group Michael Miller +1-917-633-6086 [email protected] 1 SOURCE Incannex Healthcare Limited

Aug. 17, 2021 08:00 UTC First-in-human study evaluating CIT-013, a humanized monoclonal antibody targeting Neutrophil Extracellular Traps (NETs) CIT-013 binds to citrullinated Histones H2A and H4 CIT-013 inhibits NET formation, promotes tissue NET clearance, and hence blocks the proinflammatory and toxic activities of NETs Phase 1 SAD study expected to read-out by the end of 2021 OSS, The Netherlands--(BUSINESS WIRE)-- Citryll today announced that the first healthy volunteer has been enrolled and dosed in a Phase 1 clinical trial to evaluate the safety, tolerability, and pharmacokinetics of CIT-013. CIT-013 is a first in class humanized therapeutic antibody targeting Neutrophil Extracellular Trap (NET) formation and clearance. CIT-013 is being developed for autoimmune and chronic inflammatory diseases and other indications where NETs play an important role in pathogenesis. The first-in-human study is a randomised, double blind, placebo controlled, single ascending dose (SAD) study carried out by the Centre for Human Drug Research (CHDR) in Leiden, The Netherlands, a CRO specialized in early-stage human clinical trials. “We are very pleased with the progress made with our lead asset. This significant clinical milestone, recent preclinical studies in new indications, as well as partnering with the renowned CHDR for Citryll’s first in human studies all establish a platform for future success,” said Helmuth van Es, CEO of Citryll. “CIT-013 has the potential to impact many diseases where NET biology is contributing to pathology, such as lupus, rheumatoid arthritis, vasculitis, sepsis, a range of serious lung inflammatory conditions and the list is growing. The next phase of development is already in full preparation, including expanding to other countries for patient studies.” “This is a very exciting step in the development of CIT-013” said Patrick Round, Citryll’s Chief Medical Officer. “Numerous non-clinical studies including disease models, human ex vivo and safety studies have demonstrated the potential of CIT-013 to inhibit NET formation, promote NET clearance and inhibit autoimmune and chronic inflammatory pathologies”. About Citryll: Citryll is a private pharmaceutical company based in the Pivot Park, Oss, the Netherlands. Its core business is the development and commercialization of antibody therapeutics that target innate immunity, in particular aberrant NET biology and its consequences. For more information or contacting us, please visit View source version on businesswire.com: Contacts Helmuth van Es info@citryll.com Source: Citryll View this news release online at: