Sweet Syndrome

The paper, published in Pharmaceuticals, demonstrates that pyrin inflammasome-mediated inflammation induced by traumatic brain injury (TBI) contributes to cardiovascular co-morbidities through systemic release of proinflammatory mediators that activate AIM2 inflammasomes in the heart leading to damaging inflammation.Marks the third publication in 2023 supporting the potential need to attenuate the spread of inflammation to surrounding tissues to minimize the potential for co-morbidities in certain diseases.ZyVersa is developing Inflammasome ASC Inhibitor IC 100 to inhibit multiple types of inflammasomes and their associated ASC specks that trigger damaging inflammation and its spread to surrounding tissues. WESTON, Fla., Oct. 04, 2023 (GLOBE NEWSWIRE) -- ZyVersa Therapeutics, Inc. (Nasdaq: ZVSA, or “ZyVersa”), a clinical stage specialty biopharmaceutical company developing first-in-class drugs for treatment of inflammatory and renal diseases, announces that world renowned inflammasome researchers from the University of Miami Miller School of Medicine and inventors of Inflammasome ASC Inhibitor IC 100 have published a scientific paper in the peer-reviewed journal, Pharmaceuticals, highlighting how inflammation in the brain mediated by traumatic injury can trigger inflammation in the heart. In the paper titled, “Neural–Cardiac Inflammasome Axis after Traumatic Brain Injury,” the authors conducted a study in animal models of TBI and evaluated serum from patients following TBI and from healthy controls. Data indicate that pyrin inflammasome-mediated inflammation induced by TBI contributes to cardiovascular co-morbidities through systemic release of proinflammatory mediators that activate AIM2 inflammasomes in the heart leading to damaging inflammation. The role of inflammasome activation in the development of TBI-induced cardiovascular co-morbidities was substantiated by increased ASC speck formation in the brains and hearts of TBI mouse models. “A heightened systemic inflammatory response is often induced after TBI, but the underlying pathomechanisms that contribute to co-morbidities remain poorly understood. Here, we investigated whether extracellular vesicles (EVs) containing inflammasome proteins are released after severe controlled cortical impact in C57BL/6 mice and cause activation of inflammasomes in the heart that result in tissue damage,” said Dr. Robert W. Keane, Professor, Physiology and Biophysics, Neurological Surgery and Microbiology, and Immunology, University of Miami Miller School of Medicine. “TBI resulted in the release of EVs into the serum, which contain a cargo of inflammasome-, complement- and cardiovascular-related signaling proteins, and adoptive transfer of EVs from TBI patients resulted in inflammasome activation in cardiovascular cells.” “Importantly, here, we also found an increase in ASC specks in the brain and the heart of TBI mice, suggesting that these prion-like ASC structures play a significant role in the inflammatory pathogenesis observed after TBI in the brain and systemically. Moreover, this finding emphasizes the potential benefit of therapies targeting ASC specks after CNS injury,” stated Dr. Juan Pablo de Rivero Vaccari, Associate Professor, Department of Neurological Surgery, University of Miami Miller School of Medicine. To review the paper, Click Here. “This research published in the Journal, Pharmaceuticals, along with recent research published in the Journal of Clinical Investigation and Translational Research reinforces the importance of attenuating extracellular propagation of IL-1β to minimize induction and perpetuation of inflammation in surrounding tissues and organs,” commented Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO, and President. “ZyVersa’s Inflammasome ASC inhibitor IC 100 is designed to inhibit formation of multiple types of inflammasomes to attenuate initiation of the inflammatory cascade, and to inhibit their associated ASC specks to reduce perpetuation of damaging inflammation.” To review a white paper summarizing the mechanism of action and preclinical data for IC 100, Click Here. About Inflammasome ASC Inhibitor IC 100 IC 100 is a novel humanized IgG4 monoclonal antibody that inhibits the inflammasome adaptor protein ASC. IC 100 was designed to attenuate both initiation and perpetuation of the inflammatory response. It does so by binding to a specific region of the ASC component of multiple types of inflammasomes, including NLRP1, NLRP2, NLRP3, NLRC4, AIM2, Pyrin. Intracellularly, IC 100 binds to ASC monomers, inhibiting inflammasome formation, thereby blocking activation of IL-1β early in the inflammatory cascade. IC 100 also binds to ASC in ASC Specks, both intracellularly and extracellularly, further blocking activation of IL-1β and the perpetuation of the inflammatory response that is pathogenic in inflammatory diseases. Because active cytokines amplify adaptive immunity through various mechanisms, IC 100, by attenuating cytokine activation, also attenuates the adaptive immune response. About ZyVersa Therapeutics, Inc. ZyVersa (Nasdaq: ZVSA) is a clinical stage specialty biopharmaceutical company leveraging advanced, proprietary technologies to develop first-in-class drugs for patients with renal and inflammatory diseases who have significant unmet medical needs. The Company is currently advancing a therapeutic development pipeline with multiple programs built around its two proprietary technologies – Cholesterol Efflux Mediator™ VAR 200 for treatment of kidney diseases, and Inflammasome ASC Inhibitor IC 100, targeting damaging inflammation associated with numerous CNS and other inflammatory diseases. For more information, please visit www.zyversa.com. Cautionary Statement Regarding Forward-Looking Statements Certain statements contained in this press release regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. These include statements regarding management’s intentions, plans, beliefs, expectations, or forecasts for the future, and, therefore, you are cautioned not to place undue reliance on them. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. ZyVersa Therapeutics, Inc (“ZyVersa”) uses words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “guidance,” and similar expressions to identify these forward-looking statements that are intended to be covered by the safe-harbor provisions. Such forward-looking statements are based on ZyVersa’s expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including ZyVersa’s plans to develop and commercialize its product candidates, the timing of initiation of ZyVersa’s planned preclinical and clinical trials; the timing of the availability of data from ZyVersa’s preclinical and clinical trials; the timing of any planned investigational new drug application or new drug application; ZyVersa’s plans to research, develop, and commercialize its current and future product candidates; the clinical utility, potential benefits and market acceptance of ZyVersa’s product candidates; ZyVersa’s commercialization, marketing and manufacturing capabilities and strategy; ZyVersa’s ability to protect its intellectual property position; and ZyVersa’s estimates regarding future revenue, expenses, capital requirements and need for additional financing. New factors emerge from time-to-time, and it is not possible for ZyVersa to predict all such factors, nor can ZyVersa assess the impact of each such factor on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. Forward-looking statements included in this press release are based on information available to ZyVersa as of the date of this press release. ZyVersa disclaims any obligation to update such forward-looking statements to reflect events or circumstances after the date of this press release, except as required by applicable law. This press release does not constitute an offer to sell, or the solicitation of an offer to buy, any securities. Corporate and IR Contact:Karen CashmereChief Commercial Officerkcashmere@zyversa.com786-251-9641 Media ContactsTiberend Strategic Advisors, Inc.Casey McDonaldcmcdonald@tiberend.com646-577-8520 Dave Schemeliadschemelia@tiberend.com609-468-9325

Data from Phase 3 MORPHO trial selected for press briefing and to be presented as oral session during the 2023 European Hematology Association (EHA) Hybrid Congress Exploratory results demonstrated improvement of relapse-free survival (RFS) in a subgroup of patients with measurable residual disease (MRD) TOKYO and ROCKVILLE, Md., June 9, 2023 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") and the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) today presented data from the Phase 3 MORPHO clinical trial which demonstrated favorable results in subgroups of FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutated acute myeloid leukemia (AML) patients, including a subgroup of patients with detectable measurable residual disease (MRD). The data were shared during the 2023 European Hematology Association (EHA) Hybrid Congress Press Briefing, taking place in Frankfurt, Germany, and will also be presented as an oral session on June 11. These data from the Phase 3 MORPHO trial, which evaluated gilteritinib as a maintenance therapy following allogeneic hematopoietic stem cell transplantation (HSCT) for patients with FLT3-ITD AML, did not demonstrate statistically significant improvement of relapse-free survival (RFS) in the entire cohort (Hazard Ratio [HR] for gilteritinib versus placebo 0.68; P=0.0518). However, there was clinical improvement of RFS in a subgroup of patients with detectable MRD (gilteritinib [72.4%] vs placebo [57.4%] at 2 years with HR: 0.515; 95% Confidence Interval [CI], 0.316-0.838; nominal P=0.0065) compared to patients without detectable MRD (HR: 1.213; 95% CI, 0.616-2.387; nominal P=0.575). In exploratory analysis, gilteritinib showed favorable RFS for the approximate 50% of patients with detectable MRD pre- or post-HSCT, compared to those without detectable MRD. In addition, RFS in the North American sub-population showed a HR of 0.397 (P=0.0022) for gilteritinib versus placebo. Further analysis is being conducted to understand regional results across the study population. "While we are continuing to conduct a thorough assessment of the full data set from our Phase 3 MORPHO trial, we are encouraged by these data which explore the potential of gilteritinib in a maintenance setting," said Ahsan Arozullah, M.D., M.P.H., Senior Vice President and Head of Oncology Development, Astellas. "AML patients with a FLT3-ITD mutation often face worse outcomes than those with other mutations and have restricted post-HSCT treatment options with unmet need. With these findings, we remain focused on sharing updates with the scientific community to inform continued innovation for the AML community." "As the AML treatment landscape continues to evolve, the exploration of prognostic indicators like MRD, which may be used to guide the management of AML, is vital to advance science and patient care," said Mary M. Horowitz, M.D., Principal Investigator of the BMT CTN Data and Coordinating Center. "We look forward to continuing our collaboration with Astellas to explore innovative approaches for those impacted by AML." The Phase 3 MORPHO trial is a randomized, double-blind, placebo-controlled, multi-center trial that compares gilteritinib to placebo as maintenance therapy over a period of two years following HSCT in 356 patients with FLT3-ITD mutated AML and in remission after induction therapy. The study did not meet its pre-defined primary endpoint of RFS and key secondary endpoint of overall survival or patients treated with gilteritinib compared to placebo. The most frequent treatment-emergent adverse events (TEAEs) were decrease in neutrophil count, diarrhea and nausea, which were generally consistent with previous studies of gilteritinib. In FLT3-ITD AML patients, TEAEs associated with gilteritinib compared to placebo were neutrophil decrease (42.1% versus 15.8%) and increased incidence of chronic graft-versus-host disease (GVHD) (52.2% versus 42.1%). Additional data and sub-analyses will be submitted for publication and for consideration at upcoming medical meetings. Gilteritinib is a FLT3 inhibitor with demonstrated activity against FLT3-ITD, a common driver mutation that presents with a high disease burden and poor prognosis, and FLT3-tyrosine kinase domain (TKD) mutations. Gilteritinib is available as XOSPATA® in the U.S., Japan, China and selected European countries for the treatment of adult patients who have relapsed or refractory FLT3+ AML. About Gilteritinib Gilteritinib is an FMS-like tyrosine kinase 3 (FLT3) inhibitor with demonstrated activity against FLT3-ITD, a common driver mutation that presents with a high disease burden and poor prognosis, and FLT3-TKD mutations.1 It was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global development, commercialization and manufacturing rights to gilteritinib.2 XOSPATA (gilteritinib) U.S. Indication & Important Safety Information Indication XOSPATA is indicated for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an FDA-approved test. Important Safety Information Contraindications XOSPATA is contraindicated in patients with hypersensitivity to gilteritinib or any of the excipients. Anaphylactic reactions have been observed in clinical trials. WARNING: DIFFERENTIATION SYNDROME Patients treated with XOSPATA have experienced symptoms of differentiation syndrome, which can be fatal or life-threatening if not treated. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, or renal dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution. Warnings and Precautions Differentiation Syndrome (See BOXED WARNING) 3% of 319 patients treated with XOSPATA in the clinical trials experienced differentiation syndrome. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated. Symptoms and other clinical findings of differentiation syndrome in patients treated with XOSPATA included fever, dyspnea, pleural effusion, pericardial effusion, pulmonary edema, hypotension, rapid weight gain, peripheral edema, rash, and renal dysfunction. Some cases had concomitant acute febrile neutrophilic dermatosis. Differentiation syndrome occurred as early as 1 day and up to 82 days after XOSPATA initiation and has been observed with or without concomitant leukocytosis. If differentiation syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and hemodynamic monitoring until improvement. Taper corticosteroids after resolution of symptoms and administer corticosteroids for a minimum of 3 days. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid treatment. If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, interrupt XOSPATA until signs and symptoms are no longer severe. Posterior Reversible Encephalopathy Syndrome (PRES) 1% of 319 patients treated with XOSPATA in the clinical trials experienced posterior reversible encephalopathy syndrome (PRES) with symptoms including seizure and altered mental status. Symptoms have resolved after discontinuation of XOSPATA. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). Discontinue XOSPATA in patients who develop PRES. Prolonged QT Interval XOSPATA has been associated with prolonged cardiac ventricular repolarization (QT interval). 1% of the 317 patients with a post-baseline QTc measurement on treatment with XOSPATA in the clinical trial were found to have a QTc interval greater than 500 msec and 7% of patients had an increase from baseline QTc greater than 60 msec. Perform electrocardiogram (ECG) prior to initiation of treatment with XOSPATA, on days 8 and 15 of cycle 1, and prior to the start of the next two subsequent cycles. Interrupt and reduce XOSPATA dosage in patients who have a QTcF >500 msec. Hypokalemia or hypomagnesemia may increase the QT prolongation risk. Correct hypokalemia or hypomagnesemia prior to and during XOSPATA administration. Pancreatitis 4% of 319 patients treated with XOSPATA in the clinical trials experienced pancreatitis. Evaluate patients who develop signs and symptoms of pancreatitis. Interrupt and reduce the dose of XOSPATA in patients who develop pancreatitis. Embryo-Fetal Toxicity XOSPATA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with XOSPATA and for 6 months after the last dose of XOSPATA. Advise males with female partners of reproductive potential to use effective contraception during treatment with XOSPATA and for 4 months after the last dose of XOSPATA. Pregnant women, patients becoming pregnant while receiving XOSPATA or male patients with pregnant female partners should be apprised of the potential risk to the fetus. Adverse Reactions Fatal adverse reactions occurred in 2% of patients receiving XOSPATA. These were cardiac arrest (1%) and one case each of differentiation syndrome and pancreatitis. The most frequent (≥5%) nonhematological serious adverse reactions reported in patients were fever (13%), dyspnea (9%), renal impairment (8%), transaminase increased (6%) and noninfectious diarrhea (5%). 7% discontinued XOSPATA treatment permanently due to an adverse reaction. The most common (>1%) adverse reactions leading to discontinuation were aspartate aminotransferase increased (2%) and alanine aminotransferase increased (2%). The most frequent (≥5%) grade ≥3 nonhematological adverse reactions reported in patients were transaminase increased (21%), dyspnea (12%), hypotension (7%), mucositis (7%), myalgia/arthralgia (7%), and fatigue/malaise (6%). Other clinically significant adverse reactions occurring in ≤10% of patients included: electrocardiogram QT prolonged (9%), hypersensitivity (8%), pancreatitis (5%), cardiac failure (4%), pericardial effusion (4%), acute febrile neutrophilic dermatosis (3%), differentiation syndrome (3%), pericarditis/myocarditis (2%), large intestine perforation (1%), and posterior reversible encephalopathy syndrome (1%). Lab Abnormalities Shifts to grades 3-4 nonhematologic laboratory abnormalities in XOSPATA treated patients included phosphate decreased (14%), alanine aminotransferase increased (13%), sodium decreased (12%), aspartate aminotransferase increased (10%), calcium decreased (6%), creatine kinase increased (6%), triglycerides increased (6%), creatinine increased (3%), and alkaline phosphatase increased (2%). Drug Interactions Combined P-gp and Strong CYP3A Inducers Concomitant use of XOSPATA with a combined P-gp and strong CYP3A inducer decreases XOSPATA exposure which may decrease XOSPATA efficacy. Avoid concomitant use of XOSPATA with combined P-gp and strong CYP3A inducers. Strong CYP3A inhibitors Concomitant use of XOSPATA with a strong CYP3A inhibitor increases XOSPATA exposure. Consider alternative therapies that are not strong CYP3A inhibitors. If the concomitant use of these inhibitors is considered essential for the care of the patient, monitor patient more frequently for XOSPATA adverse reactions. Interrupt and reduce XOSPATA dosage in patients with serious or life-threatening toxicity. Drugs that Target 5HT2B Receptor or Sigma Nonspecific Receptor Concomitant use of XOSPATA may reduce the effects of drugs that target the 5HT2B receptor or the sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline). Avoid concomitant use of these drugs with XOSPATA unless their use is considered essential for the care of the patient. P-gp, BCRP, and OCT1 Substrates Based on in vitro data, gilteritinib is a P-gp, breast cancer resistant protein (BCRP), and organic cation transporter 1 (OCT1) inhibitor. Coadministration of gilteritinib may increase the exposure of P-gp, BCRP, and OCT1 substrates, which may increase the incidence and severity of adverse reactions of these substrates. For P-gp, BCRP, or OCT1 substrates where small concentration changes may lead to serious adverse reactions, decrease the dose or modify the dosing frequency of such substrate and monitor for adverse reactions as recommended in the respective prescribing information. Specific Populations Lactation Advise women not to breastfeed during treatment with XOSPATA and for 2 months after the last dose. Please see Full Prescribing Information, including BOXED WARNING for additional safety information. About MORPHO Phase 3 Clinical Trial The Phase 3 MORPHO Study is a two-arm, randomized, double-blind, placebo-controlled, multi-center trial in 356 patients with a diagnosis of AML harboring a FLT3/ITD mutation. Participants must be in first complete remission prior to transplant, as defined by less than five percent blasts in the bone marrow (BM) with no morphologic characteristics of acute leukemia in the BM with no evidence of extra-medullary leukemia. After undergoing transplantation, participants will be randomized to receive gilteritinib (120 mg) or placebo beginning after the time of engraftment for a two-year period. Participants will be stratified according to: 1) conditioning regimen intensity (myeloablative vs. reduced intensity/non-myeloablative), 2) time from first day of hematopoietic cell infusion to randomization (30-60 days vs. 61-90 days) and 3) presence vs. absence of or unknown minimal residual disease from the most recent pre-registration BM aspirate. The primary endpoint of the trial is RFS. The study is being conducted in countries across North America, Europe and the Asia-Pacific region, including Japan. For more information about this trial, please visit under trial identifier NCT02997202. About Acute Myeloid Leukemia (AML) Acute myeloid leukemia (AML) is an aggressive cancer that affects the bone marrow and blood, and its incidence increases with age.3,4 Of patients newly diagnosed with AML and tested for FLT3 mutations, approximately one-third have an alteration to the FLT3 gene. FLT3-ITD mutations have been associated with worsened disease-free survival and overall survival, and a higher risk of getting the disease more than once. FLT3 mutation status can change over the course of AML treatment, even after relapse.5-8 About Astellas Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into VALUE for patients. For more information, please visit our website at . About the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) conducts rigorous multi-institutional clinical trials of high scientific merit, focused on improving survival for patients undergoing hematopoietic cell transplantation and/or receiving cellular therapies. The BMT CTN has completed accrual to 52 Phase II and III trials at more than 100 transplant centers and enrolled over 16,600 study participants. BMT CTN is funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute, both parts of the National Institutes of Health (NIH), and is a collaborative effort of 20 Core Transplant Centers/Consortia, The Center for International Blood and Marrow Transplant Research (CIBMTR), the National Marrow Donor Program (NMDP)/Be The Match and the Emmes Company, LLC, a clinical research organization. CIBMTR is a research collaboration between the NMDP/Be The Match and the Medical College of Wisconsin. Together with MCW/CIBMTR and NMDP, Emmes has been providing research support to the BMT CTN since 2001, as a key member of the data coordinating center. More information about the BMT CTN can be found at About National Marrow Donor Program® (NMDP)/Be The Match® The National Marrow Donor Program® (NMDP)/Be The Match® is the leading global partner working to save lives through cellular therapy. With 35 years of experience managing the most diverse registry of potential unrelated blood stem cell donors and cord blood units in the world, NMDP/Be The Match is a proven partner in providing cures to patients with life-threatening blood and marrow cancers and diseases. Through their global network, they connect centers and patients to their best cell therapy option—from blood stem cell transplant to a next-generation therapy—and collaborate with cell and gene therapy companies to support therapy development and delivery through Be The Match BioTherapies®. NMDP/Be The Match is a tireless advocate for the cell therapy community, working with hematologists/oncologists to remove barriers to consultation and treatment, and supporting patients through no-cost programs to eliminate non-medical obstacles to cell therapy. In addition, they are a global leader in research through the CIBMTR® (Center for International Blood and Marrow Transplant Research®)—a collaboration with Medical College of Wisconsin, investing in and managing research studies that improve patient outcomes and advance the future of care. About the Medical College of Wisconsin With a history dating back to 1893, The Medical College of Wisconsin is dedicated to leadership and excellence in education, patient care, research, and community engagement. More than 1,500 students are enrolled in MCW's medical school and graduate school programs in Milwaukee, Green Bay, and Central Wisconsin. MCW's School of Pharmacy opened in 2017. A major national research center, MCW is the largest research institution in the Milwaukee metro area and second largest in Wisconsin. In the last 10 years, faculty received more than $1.5 billion in external support for research, teaching, training, and related purposes. This total includes highly competitive research and training awards from the National Institutes of Health (NIH). Annually, MCW faculty direct or collaborate on more than 3,100 research studies, including clinical trials. Additionally, more than 1,650 physicians provide care in virtually every specialty of medicine for more than 2.8 million patients annually. About Emmes Founded more than 45 years ago, Emmes is a global, full-service Clinical Research Organization dedicated to excellence in supporting the advancement of public health and biopharmaceutical innovation. The company's clients include numerous agencies and institutes of the U.S. federal government and a wide range of biotechnology, pharmaceutical and medical device companies throughout the world. To learn more about how our research is making a positive impact on human health, go to the Emmes website at . Cautionary Notes In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties. Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice. References Daver N, Schlenk RF, Russel NH, Levis MJ. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia 2019; 33, 299-312. Data on file. Northbrook, Ill. Astellas Pharma US Inc. American Cancer Society. What Is Acute Myeloid Leukemia (AML)? Available at: . Last accessed January 23, 2023. American Cancer Society. Key Statistics for Acute Myeloid Leukemia (AML). Available at: . Last accessed January 23, 2023. Whitman SP, Maharry K, Radmacher MD, et al. FLT3 internal tandem duplication associates with adverse outcome and gene- and microRNA-expression signatures in patients 60 years of age or older with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood. 2010; 116(18), 3622-3626. Whitman SP, Archer KJ, Feng L, et al. Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a Cancer and Leukemia Group B study. Cancer Res. 2001; 61(19), 7233-7239. Visser O. et al. Incidence, survival and prevalence of myeloid malignancies in Europe. Eur J Cancer (2012) 48, 3257-3266. Warren M, et al. Clinical impact of change of FLT3 mutation status in acute myeloid leukemia patients. Mod Pathol. 2012;25(10):1405-12. View original content to download multimedia: SOURCE Astellas Pharma Inc. and BMT CTN Company Codes: Tokyo:4503, OTC-PINK:ALPMY

RAANANA, Israel, Sept. 26, 2017 /PRNewswire/ -- XTL Biopharmaceuticals Ltd.(NASDAQ: XTLB) (TASE: XTLB.TA)("XTL" or the "Company"), a clinical-stage biopharmaceutical company developing treatments for autoimmune diseases, today announced financial results for the second quarter ended June 30, 2017 and provided an update on the development program for its lead drug candidate hCDR1. "The first half of 2017 included a number of accomplishments for XTL, as we continued to lay the foundation for the advancement of hCDR1 towards a global Phase 2 trial designed to have a high likelihood of success based on prior clinical study findings in lupus (SLE)," said Josh Levine, CEO of XTL. "Lupus has a large unmet clinical need, with few satisfactory treatment options and with recent failures in late stage clinical studies with the notable exception of the recent successful Phase 2 in Lupus Nephritis of Voclosporin being developed by Aurinia Pharmaceuticals. Toward that end, we raised more than $5 million from new and existing investors. We also strengthened our Board of Directors with the addition of our largest shareholder, Mr. Alex Rabinovich, who participated in our latest fundraising. In addition, we unveiled additional preclinical data, which demonstrated the role of hCDR1 as a potential treatment for Sjögren's syndrome (SS). This new data has the potential to significantly increase the market size for hCDR1 in a second indication and further supports the findings found in previous clinical studies performed on lupus. Finally, we strengthened the intellectual property of our lead asset, hCDR1, by filing a number of new patent applications on the dosing of our drug for lupus and for the treatment of SS. Clinical and Operational Update The Company raised a total gross amount of approximately $5.3 million during the first half of 2017 through a public offering to US institutional investors and a private placement with existing investors. The transactions included the issuance of registered and unregistered ADSs and unregistered warrants to purchase ADSs. The Company recently appointed Mr. Alex Rabinovitch as a member of the Company's board of directors. Mr. Rabinovitch is a leading investor in XTL holding over 18% of its outstanding shares. XTL generated new in-vitro data from studies evaluating cells obtained from serum samples of patients with SS demonstrating that incubation with hCDR1 resulted in a significant reduction of gene expression of four pathogenic cytokines known to be involved in SS and lupus (including B-lymphocyte stimulator or BLyS), as well as upregulation of two immunosuppressive genes, one of which is a marker for activity of regulatory T cells. This data corresponds to some of the in-vitro data obtained in studies testing serum samples from patients with SLE. SS impacts more than twice the number of people as SLE does in the U.S. and represents a significant unmet therapeutic need. Three provisional patent applications have been filed with the U.S. Patent and Trademark Office for hCDR1 in the treatment of SS. Based on hCDR1's well known mechanism of action and favorable safety profile, XTL can pursue an accelerated clinical development path for the treatment of Sjogren's syndrome. We added two leading experts in rheumatology, Robert Fox, MD and Simon Bowman, MD, to the Company's clinical advisory board to help guide a planned Phase II trial to evaluate hCDR1 for the treatment of SS. On August 3, 2017, the Company had its Annual General Meeting of shareholders, pursuant to which the shareholders approved: the re-appointment of Kesselman & Kesselman, Israel CPAs, a member firm of PricewaterhouseCoopers International Limited, as the Company's independent registered public accounting firm for the year ending December 31, 2017. the election or re-election of Messrs. Alexander Rabinovitch, Dr. Jonathan Schapiro, Shlomo Shalev, Doron Turgeman and Dr. Dobroslav Melamed as directors in the Company. the increase of the Company's authorized share capital by NIS 75,000,000, such that following the increase, the Company's authorized share capital shall equal NIS 145,000,000 divided into 1,450,000,000 ordinary shares, par value NIS 0.1 each. the new employment terms of Mr. Joshua Levine, the Company's Chief Executive Officer, including issuance of 1,000,000 options to purchase 1,000,000 ordinary shares of the Company available through the Company's 2011 ESOP. Financial Overview XTL reported approximately $6,325 thousand in cash and cash equivalents as of June 30, 2017, an increase of $4,306 thousand since December 31, 2016. The Company plans to use these funds to advance the hCDR1 clinical program for the treatment of SLE and SS and to identify additional assets to add to the XTL portfolio. Currently, the Company has decided to minimize its expenses in connection with research and development of its product until additional funds will be raised in the future by issuing securities or through a collaboration arrangement with a potential partner. Research and development expenses for the six months period ended June 30, 2017 were $38 thousand compared to $355 thousand for the corresponding period in 2016. During the six months period ended June 30, 2016, development activities included the completion of the trial design for the planned Phase 2 trial of hCDR1 for the treatment of SLE and production of the drug product for that trial. Such development activities did not repeat during the six months period ended June 30, 2017. General and administrative expenses for the six months period ended June 30, 2017 were $732 thousand compared to $713 thousand for the corresponding period in 2016. The change resulted mainly from decreases in salaries and expenses relating to employees (including stock-based compensation expenses), investor relations and insurance costs, offset by amortization of certain costs that were previously capitalized as an asset. Finance expenses, net for the six months period ended June 30, 2017, were $1,595 thousand compared to finance income, net of $14 thousand for the corresponding period in 2016. The difference is driven primarily by issuance costs related to the warrants granted to investors in the aforementioned fundraising transactions and revaluation of those warrants amounting to $346 and $1,268 thousand, respectively. XTL reported an operating loss for the six months period ended June 30, 2017 of $2,365 thousand, or $0.006 per share, compared to $1,054 thousand, or $0.004 per share, for the corresponding period in 2016. The increased total net loss is driven primarily by the costs related to the issuance and revaluation of warrants offset by decreased spending on research and development, as described above.    XTL Biopharmaceuticals, Ltd. and Subsidiary(USD in thousands)Condensed Consolidated Statements of Financial Position - Selected Data As of June 30, 2017 2016Cash, cash equivalents $              6,325 $              2,605Other current assets 467 612Non-current assets 380 1,120Total assets 7,172 4,337 Current liabilities 382 258 Non-current liabilities 4,700 - Share capital 13,182 6,624Premium on shares, options and warrants 146,003 150,784Reserve from transactions with non-controlling interests 20 111Other comprehensive income 125 20Accumulated deficit (157,240) (153,460)Total shareholders' equity $              2,090 $              4,079    XTL Biopharmaceuticals, Ltd. and Subsidiary(USD in thousands, except per share amounts)Consolidated Statements of Comprehensive Loss- Selected Data For the six months endedJune 30, 2017 2016 Research and Development expenses$                 (38) $               (355)General and administrative expenses(732) (713)Operating Loss(770) (1,068) Finance income24 19Finance expenses(1,619) (5)Finance income (expenses), net(1,595) 14 Total loss (2,365) (1,054)Other comprehensive income (loss): Items that may be reclassified to profit (loss): Changes in the fair value of available-for-sale financial assets(38) 111Other comprehensive income (loss)(38) 111 Total comprehensive loss for the period$           (2,403) $              (943) Basic and diluted loss per share (in U.S. dollars)$            (0.006) $            (0.004) Weighted average number of issued ordinary shares425,193,299 273,862,042     About hCDR1 hCDR1 is a novel compound with a unique mechanism of action and clinical data on over 400 patients in three clinical studies. The drug has a favorable safety profile, is well tolerated by patients and has demonstrated efficacy in at least one clinically meaningful endpoint. For more information, please see a peer reviewed article in Lupus Science and Medicine journal (full article).  About XTL Biopharmaceuticals Ltd. (XTL) XTL Biopharmaceuticals Ltd., is a clinical-stage biotech company focused on the development of pharmaceutical products for the treatment of autoimmune diseases. The Company's lead drug candidate, hCDR1, is a world-class clinical asset for the treatment of autoimmune diseases including systemic lupus erythematosus (SLE) and Sjögren's Syndrome (SS). The few treatments currently on the market for these diseases are not effective enough for most patients and some have significant side effects. hCDR1 has robust clinical data in three clinical trials with 400 patients and over 200 preclinical studies with data published in more than 40 peer reviewed scientific journals. XTL is traded on the Nasdaq Capital Market (NASDAQ: XTLB) and the Tel Aviv Stock Exchange (TASE: XTLB.TA). XTL shares are included in the following indices: Tel-Aviv Biomed, Tel-Aviv MidCap, and Tel-Aviv Tech Index. Cautionary Statement This press release may contain forward-looking statements, about XTL's expectations, beliefs or intentions regarding, among other things, its product development efforts, business, financial condition, results of operations, strategies or prospects. In addition, from time to time, XTL or its representatives have made or may make forward-looking statements, orally or in writing. Forward-looking statements can be identified by the use of forward-looking words such as "believe," "expect," "intend," "plan," "may," "should" or "anticipate" or their negatives or other variations of these words or other comparable words or by the fact that these statements do not relate strictly to historical or current matters. These forward-looking statements may be included in, but are not limited to, various filings made by XTL with the U.S. Securities and Exchange Commission, press releases or oral statements made by or with the approval of one of XTL's authorized executive officers. Forward-looking statements relate to anticipated or expected events, activities, trends or results as of the date they are made. Because forward-looking statements relate to matters that have not yet occurred, these statements are inherently subject to risks and uncertainties that could cause XTL's actual results to differ materially from any future results expressed or implied by the forward-looking statements. Many factors could cause XTL's actual activities or results to differ materially from the activities and results anticipated in such forward-looking statements, including, but not limited to, the factors summarized in XTL's filings with the SEC and in its periodic filings with the TASE. In addition, XTL operates in an industry sector where securities values are highly volatile and may be influenced by economic and other factors beyond its control. XTL does not undertake any obligation to publicly update these forward-looking statements, whether as a result of new information, future events or otherwise. Please see the risk factors associated with an investment in our ADSs or ordinary shares which are included in our Form 20-F/A filed with the U.S. Securities and Exchange Commission on April 4, 2017.   For further information, please contact: Investor Relations, XTL Biopharmaceuticals Ltd. Tel: +972-9-955-7080 E-mail: ir@xtlbio.com View original content: SOURCE XTL Biopharmaceuticals Ltd