Neonatal-Onset Multisystem Inflammatory Disease

Nes-Ziona, Israel, Feb. 15, 2023 (GLOBE NEWSWIRE) -- Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the “Company”), a clinical-stage macrophage reprogramming immunotherapy company, today announced the issuance of an Israeli patent, numbered 284985, entitled, “Combination Immune Therapy and Cytokine Control Therapy for Cancer Treatment.” The patent provides added intellectual property protection in Israel into at least 2037, with claims covering the use of for Allocetra™ for prevention or amelioration of cytokine storms in cancer patients receiving CAR-T therapy, as well as in patients whose cytokine storms result from infectious diseases or non-infectious sources. Oren Hershkovitz, PhD, CEO of Enlivex commented, “We are pleased with the continued buildup of our comprehensive intellectual property portfolio for Allocetra™.” Infectious diseases covered by this patent include influenza, bird flu, severe acute respiratory syndrome (SARS), Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (HLH), sepsis, gram-negative sepsis, malaria, an Ebola virus, a variola virus, a systemic Gram-negative bacterial infection, or Jarisch-Herxheimer syndrome, or wherein said non-infectious stimuli, condition, or syndrome comprises is hemophagocytic lymphohistiocytosis (HLH), sporadic HLH, macrophage activation syndrome (MAS), chronic arthritis, systemic Juvenile Idiopathic Arthritis (sJIA), Still’s Disease, a Cryopyrin-associated Periodic Syndrome (CAPS), Familial Cold Auto-inflammatory Syndrome (FCAS), Familial Cold Urticaria (FCU), Muckle-Well Syndrome (MWS), Chronic Infantile Neurological Cutaneous and Articular (CINCA) Syndrome, a cryopyrinopathy comprising inherited or de novo gain of function mutations in the NLRP3 gene, a hereditary auto-inflammatory disorder, acute pancreatitis, severe burns, a trauma, an acute respiratory distress syndrome, an immunotherapy, a monoclonal antibody therapy, secondary to drug use, is secondary to inhalation of toxins, a lipopolysaccharide (LPS), a Gram-positive toxins, fungal toxins, glycosylphosphatidylinositol (GPI), or modulation of RIG-1 gene expression. CAR T-cells are T-cells that have been genetically modified to include a receptor that allows them to specifically target and destroy cancer cells. While certain CAR T-cell treatments were recently approved by the FDA in several cancer indications, such treatments have been associated in many patients with a side effect named cytokine release syndrome, which describes a collection of potentially severe or life-threatening symptoms that stem from over-activation of immune pathways. Preclinical data indicate that Allocetra™ has the potential to prevent or ameliorate cytokine release syndrome associated with CAR T-cell therapies. ABOUT ALLOCETRA™Allocetra™ is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra™ has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as "unmet medical needs", as a stand-alone therapy or in combination with leading therapeutic agents. ABOUT ENLIVEX Enlivex is a clinical stage macrophage reprogramming immunotherapy company developing Allocetra™, a universal off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Resetting non-homeostatic macrophages into their homeostatic state is critical for immune system rebalancing and resolution of life-threatening conditions. For more information, visit http://www.enlivex.com. Safe Harbor Statement: This press release contains forward-looking statements, which may be identified by words such as “expects,” “plans,” “projects,” “will,” “may,” “anticipates,” “believes,” “should,” “would”, “could,” “intends,” “estimates,” “suggests,” “has the potential to” and other words of similar meaning, including statements regarding expected cash balances, market opportunities for the results of current clinical studies and preclinical experiments, the effectiveness of, and market opportunities for, ALLOCETRATM programs. All such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that forward-looking statements involve risks and uncertainties that may affect Enlivex’s business and prospects, including the risks that Enlivex may not succeed in generating any revenues or developing any commercial products; that the products in development may fail, may not achieve the expected results or effectiveness and/or may not generate data that would support the approval or marketing of these products for the indications being studied or for other indications; that ongoing studies may not continue to show substantial or any activity; and other risks and uncertainties that may cause results to differ materially from those set forth in the forward-looking statements. The results of clinical trials in humans may produce results that differ significantly from the results of clinical and other trials in animals. The results of early-stage trials may differ significantly from the results of more developed, later-stage trials. The development of any products using the ALLOCETRATM product line could also be affected by a number of other factors, including unexpected safety, efficacy or manufacturing issues, additional time requirements for data analyses and decision making, the impact of pharmaceutical industry regulation, the impact of competitive products and pricing and the impact of patents and other proprietary rights held by competitors and other third parties. In addition to the risk factors described above, investors should consider the economic, competitive, governmental, technological and other factors discussed in Enlivex’s filings with the Securities and Exchange Commission, including in the Company’s most recent Annual Report on Form 20-F filed with the Securities and Exchange Commission. The forward-looking statements contained in this press release speak only as of the date the statements were made, and we do not undertake any obligation to update forward-looking statements, except as required under applicable law. ENLIVEX CONTACT Shachar Shlosberger, CFO Enlivex Therapeutics, Ltd. shachar@enlivexpharm.com INVESTOR RELATIONS CONTACTEric RibnerLifeSci Advisorseric@lifesciadvisors.com

Astellas Pharma sees AT845 as an “important potential new treatment for adults" with late-onset Pompe disease. The FDA has handed a boost to Astellas Pharma’s stuttering push into gene therapy by lifting the clinical hold on a phase 1/2 study in late-onset Pompe disease (LOPD). Astellas was forced to pump the brakes on the AT845 program last year after a participant developed peripheral sensory neuropathy. AT845 is one of the assets that originated at Audentes Therapeutics, the gene therapy developer Astellas bought in an ill-fated $3 billion takeover three years ago. Astellas’ woes initially centered on AT132, an investigational treatment for another neuromuscular disease that was linked to deaths, but the trouble spread to the adeno-associated virus gene replacement therapy AT845 last summer. Now, seven months after imposing a clinical hold on the FORTIS study of AT845, the FDA has removed the restriction on Astellas’ activities. The Japanese drugmaker needs to complete “clinical and regulatory activities” before it can resume dosing in the study. Astellas is yet to share a timeline for the resumption of dosing or a new schedule for the rest of the trial. ClinicalTrials.gov lists the estimated primary completion target as December 2022, but that forecast dates back to when the study got underway in 2020 and therefore predates the clinical hold. In October, the company told (PDF) investors “an updated timeline for proof-of-concept judgment is under discussion.” Ha Tran, executive medical director for Astellas, gave no indication that the serious adverse event and subsequent clinical hold have dented confidence in AT845, calling the prospect an “important potential new treatment for adults living with LOPD” in a statement to disclose the FDA’s action. AT845 is designed to deliver a functional copy of the acid alpha-glucosidase gene to the muscles and thereby enable patients to express the enzyme that is at the root of Pompe disease. Patients with the disease currently undergo enzyme replacement therapy. Sanofi has built a blockbuster franchise in Pompe, across both LOPD and infantile-onset disease, with Myozyme, Lumizyme and Nexviazyme.

STOCKHOLM, Nov. 10, 2022 /PRNewswire/ -- Sobi® today announced that the US Food and Drug Administration has granted Emergency Use Authorisation (EUA) for the use of Kineret® (anakinra) for the treatment of coronavirus disease 2019 (COVID-19) in hospitalised adults with pneumonia requiring supplemental oxygen (low- or high-flow oxygen) who are at risk of progressing to severe respiratory failure. COVID-19 can progress to severe respiratory failure and death due to an excessive inflammatory response1. Kineret is an anti-inflammatory medicine that neutralises the biological activity of both cytokines IL-1α and β, which play a role in COVID19-induced hyperinflammation2. Blocking these cytokines early in the course of the hyperinflammatory phase can have an important impact on COVID-19 disease progression3. Kineret was shown to improve outcomes, reduce progression to severe respiratory failure and mortality in patients hospitalised with COVID-19 pneumonia requiring supplemental oxygen, and the benefits were maintained long-term. "This is another important milestone for Sobi. The authorisation will provide both patients and treating physicians in the US with a treatment option against COVID-19 related pneumonia," said Anders Ullman, Head of Research & Development and Chief Medical Officer at Sobi. The authorisation was based on results from the SAVE-MORE phase 3 study which were published in Nature Medicine on 3 September 2021. About Emergency Use Authorisation status Kineret (anakinra) has not been approved but has been authorised for emergency use for the treatment of coronavirus disease 2019 (COVID-19) in hospitalised adults with positive results of direct SARS-CoV-2 viral testing with pneumonia requiring supplemental oxygen (low- or high-flow oxygen) who are at risk of progressing to severe respiratory failure and likely to have an elevated plasma soluble urokinase plasminogen activator receptor (suPAR). The emergency use of Kineret is only authorised for the duration of the declaration that circumstances exist justifying the authorisation of the emergency use of drugs and biological products during the COVID-19 pandemic under Section 564(b)(1) of the Act, 21 U.S.C. § 360bbb- 3(b)(1), unless the declaration is terminated or authorisation revoked sooner. See full fact sheet for healthcare providers for the justification for emergency use of drugs during the COVID-19 pandemic, information on available alternatives, and additional information on COVID-19. About SAVE-MORE and patient population identification SAVE-MORE (NCT04680949); suPAR-Guided Anakinra Treatment for Management of Severe Respiratory Failure by COVID-19 was a pivotal, confirmatory, phase 3 double-blind randomised controlled study. The study evaluated the efficacy and safety of early start of Kineret guided by suPAR in patients with lower respiratory tract infection by SARS-CoV-2 in improving the clinical state of COVID-19 over 28 days, as measured by the ordinal scale of the 11-point World Health Organization clinical progression scale. Kineret was administered at a dose of 100mg/day SC for up to 10 days. Of 1,060 patients screened, 606 patients were randomised across 40 sites in Greece and Italy. SAVE-MORE was an investigator-sponsored study conducted independently by Professor Evangelos J. Giamarellos-Bourboulis, with the Hellenic Institute for the Study of Sepsis being the regulatory sponsor. The study protocol and the full statistical analysis plan was developed after advice from the COVID-Emergency Task Force of the EMA. Sobi has supported the study with study drug and funding. The suPAR assay is not commercially available in the US. In order to identify a comparable population as was studied in the SAVE-MORE trial, an alternative patient identification method was developed to select patients most likely to have suPAR ≥ 6 ng/mL based on commonly measured patient characteristics. Patients meeting at least three of the following eight criteria are considered likely to have suPAR ≥ 6 ng/mL at baseline. 1. Age ≥ 75 years 2. Severe pneumonia by WHO criteria4 3. Current/previous smoking status 4. Sequential Organ Failure Assessment (SOFA)5 score ≥ 3 5. Neutrophil-to-lymphocyte ratio (NLR) ≥ 7 6. Haemoglobin ≤ 10.5 g/dL 7. Medical history of ischemic stroke 8. Blood urea ≥ 50 mg/dL and/or medical history of renal disease About Kineret® Kineret (anakinra) is an interleukin-1α and β receptor antagonist that is indicated in the US for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis (RA), in patients 18 years of age or older who have failed one or more disease modifying antirheumatic drugs (DMARDs); for the treatment of neonatal-onset multisystem inflammatory disease (NOMID), a form of cryopyrin-associated periodic syndromes (CAPS); and for the treatment of Deficiency of Interleukin-1 Receptor Antagonist (DIRA). In the EU, Kineret is indicated in adults for the treatment of the signs and symptoms of rheumatoid arthritis (RA) in combination with methotrexate, with an inadequate response to methotrexate alone. In addition, Kineret is indicated in adults, adolescents, children and infants aged 8 months and older with a body weight of 10 kg or above for the treatment of cryopyrin-associated periodic syndromes (CAPS), including neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurological, cutaneous, and articular syndrome (CINCA), Muckle-Wells syndrome (MWS) and familial cold auto inflammatory syndrome (FCAS). Kineret is indicated for the treatment of Familial Mediterranean fever (FMF). Kineret should be given in combination with colchicine, if appropriate. It is also indicated in adults, adolescents, children and infants aged 8 months and older with a body weight of 10 kg or above for the treatment of Still's disease, including Systemic Juvenile Idiopathic Arthritis (SJIA) and Adult-Onset Still's Disease (AOSD), with active systemic features of moderate to high disease activity, or in patients with continued disease activity after treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or glucocorticoids. Kineret can be given as monotherapy or in combination with other anti-inflammatory drugs and disease-modifying antirheumatic drugs (DMARDs). Kineret is indicated for the treatment of coronavirus disease 2019 (COVID-19) in adult patients with pneumonia requiring supplemental oxygen (low- or high-flow oxygen) who are at risk of progressing to severe respiratory failure determined by plasma concentration of soluble urokinase plasminogen activator receptor (suPAR) ≥ 6 ng/ml. For full US prescribing information please visit and for full EU prescribing information please visit the EMA website. References 1. Tang L, et al. Controlling Cytokine Storm Is Vital in COVID-19. Front Immunol 2020;11:570993. doi: 10.3389/fimmu.2020.570993. 2. Renieris G, et al. IL-1 Mediates Tissue-Specific Inflammation and Severe Respiratory Failure in COVID-19. J Innate Immun 2022;1-14. doi: 10.1159/000524560. 3. Kyriazopoulou E, et al. Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial. Nat Med 2021;27(10):1752-1760. doi: 10.1038/s41591-021-01499-z. 4. World Health Organization. (2020, March 13). Clinical management of severe acute respiratory infection (SARI) when covid-19 disease is suspected. Interim Guidance. . 5. HHS Technical Resources, Assistance Center and Information Exchange. (2020, December 21). SOFA score: What it is and how to use it in triage - hhs.gov. . Sobi® Sobi is a specialised international biopharmaceutical company transforming the lives of people with rare diseases. Providing sustainable access to innovative medicines in the areas of haematology, immunology and specialty care, Sobi has approximately 1,600 employees across Europe, North America, the Middle East and Asia. In 2021, revenue amounted to SEK 15.5 billion. Sobi's share (STO:SOBI) is listed on Nasdaq Stockholm. More about Sobi at sobi.com, LinkedIn and YouTube. Contacts To contact the Sobi Investor Relations Team, please click here. For Sobi Media contacts, click here. The following files are available for download: SOURCE Swedish Orphan Biovitrum AB