Erythroblastosis, Fetal

NEW YORK, March 10, 2024 (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, today announced that U.S. FDA supports an accelerated approval pathway for rexlemestrocel-L, Mesoblast’s allogeneic mesenchymal precursor cell (MPC) product, in patients with end-stage ischemic heart failure with reduced ejection fraction (HFrEF) and a left ventricular assist device (LVAD). FDA provided this feedback in formal minutes to the company following the Type B meeting held with FDA on February 21, 2024 for rexlemestrocel-L (Revascor®) under the existing Regenerative Medicine Advanced Therapy (RMAT) designation. “We are very pleased with FDA’s feedback that the presented results from our pivotal study of rexlemestrocel-L in end-stage HFrEF patients with LVADs may support an accelerated approval,” said Mesoblast CEO Dr. Silviu Itescu. “We intend to request a pre-Biologics License Application (BLA) meeting to discuss data presentation, timing and FDA expectations for an accelerated approval filing.” Every year in the United States over 100,000 patients progress to end-stage HFrEF. In these patients, more than 2,500 life prolonging LVADs are implanted in the US annually, of whom approximately 80% undergo the procedure as destination or permanent therapy.1 Most patients receiving LVADs as destination therapy have an ischemic HFrEF etiology. Compared to patients with non-ischemic HFrEF, patients with ischemic HFrEF have a 76% lower likelihood of LV functional recovery following LVAD implantation,2 and increased mortality over the initial 1-2 years.3 Resistance to functional recovery in ischemic HFrEF patients is thought to be due to excessive inflammation and microvascular insufficiency in the ischemic myocardium.4 In the placebo-controlled LVAD-MPC Study #2, 70 patients with end-stage ischemic HFrEF were randomized at the time of LVAD implantation surgery to either a single intervention with rexlemestrocel-L (150 million STRO3-immunoselected and culture-expanded allogeneic cells) or placebo injected directly into the left ventricular myocardium. Key findings were: Ischemic controls were characterized by persistently elevated levels of the inflammatory cytokine IL-6, by reduced ability to be weaned from LVAD support, and by high mortality.In contrast, in ischemic patients treated with rexlemestrocel-L, IL-6 levels returned to normal by 2 months and remained low through 12 months.63% of ischemic patients who received a single administration of rexlemestrocel-L successfully underwent temporary weaning from full LVAD support as early as month 2 as compared with 36% of controls (p = 0.008).The cumulative incidence of successful temporary weans off the LVAD device over 6 months was also increased by 1.55-fold over control in ischemic patients who received rexlemestrocel-L ([95% CI 1.01, 2.36]; p=0.02).Only 4.9% of ischemic patients treated with a single administration of rexlemestrocel-L died from month 2 through month 12, as compared with 26.9% of ischemic controls, an 82% reduction (p = 0.02). In feedback provided to Mesoblast regarding potential pathways to licensure for rexlemestrocel-L, FDA’s comments indicated that the presented results may support a reasonable likelihood of clinical benefit of MPCs against mortality in LVAD patients, consistent with the criteria for accelerated approval. Mesoblast intends to request a pre-BLA meeting with FDA to discuss data presentation, timing and FDA expectations for an accelerated approval filing in end-stage ischemic HFrEF patients with LVAD implantation. About Revascor® (rexlemestrocel-L) in Heart DiseaseREVASCOR is an allogeneic preparation of immunoselected and culture-expanded mesenchymal precursor cells (MPC) and is being developed as an immunomodulatory therapy to address the high degree of inflammation in the heart and in the circulation that is present across the spectrum of heart failure and reduced ejection fraction (HFrEF) patients, from New York Heart Association (NYHA) class II through end-stage CHF, in order to reduce the high rate of major cardiac events and complications. This investigational therapy has been trialled in two large placebo-controlled randomized studies in patients with CHF, a 565-patient trial in NYHA class II/III HFrEF patients and a 159-patient trial in end-stage HFrEF patients implanted with a left ventricular assist device (LVAD). Rexlemestrocel-L has US Food and Drug Administration (FDA) Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug designations for patients with end-stage HFrEF implanted with an LVAD. About Chronic Heart Failure Chronic heart failure (CHF) is characterized by poor heart function resulting in insufficient blood flow to the body’s vital organs and extremities. This condition affects approximately 6.5 million people in the United States and 26 million people globally with increasing prevalence and incidence. CHF patients are commonly classified according to the New York Heart Association (NYHA) categories based on the patient’s physical limitations. Class I (mild) patients have no limitations while Class IV patients (severe/end stage) experience symptoms even at rest. The mortality rate approaches 50% at 5 years as patients progress beyond NYHA early class II disease in parallel with increasing inflammation in the heart and in the circulation.5,6 Despite recent approvals of new therapies for HFrEF, NYHA class II/III HFrEF patients with inflammation remain at high risk for cardiac death, heart attacks and strokes. Over 100,000 patients annually in the US progress to end-stage heart failure (NYHA class IIIB/IV) and these patients have a one-year mortality exceeding 50%.7 Use of LVADs in end-stage heart failure patients to improve survival is gaining momentum, with approximately 2,000 LVADs implanted as destination therapy annually in the US,1 the majority of whom have an ischemic etiology. About Mesoblast Mesoblast (the Company) is a world leader in developing allogeneic (off-the-shelf) cellular medicines for the treatment of severe and life-threatening inflammatory conditions. The Company has leveraged its proprietary mesenchymal lineage cell therapy technology platform to establish a broad portfolio of late-stage product candidates which respond to severe inflammation by releasing anti-inflammatory factors that counter and modulate multiple effector arms of the immune system, resulting in significant reduction of the damaging inflammatory process. Mesoblast has a strong and extensive global intellectual property portfolio with protection extending through to at least 2041 in all major markets. The Company’s proprietary manufacturing processes yield industrial-scale, cryopreserved, off-the-shelf, cellular medicines. These cell therapies, with defined pharmaceutical release criteria, are planned to be readily available to patients worldwide. Mesoblast is developing product candidates for distinct indications based on its remestemcel-L and rexlemestrocel-L allogeneic stromal cell technology platforms. Remestemcel-L is being developed for inflammatory diseases in children and adults including steroid refractory acute graft versus host disease, biologic-resistant inflammatory bowel disease, and acute respiratory distress syndrome. Rexlemestrocel-L is in development for advanced chronic heart failure and chronic low back pain. Two products have been commercialized in Japan and Europe by Mesoblast’s licensees, and the Company has established commercial partnerships in Europe and China for certain Phase 3 assets. Mesoblast has locations in Australia, the United States and Singapore and is listed on the Australian Securities Exchange (MSB) and on the Nasdaq (MESO). For more information, please see www.mesoblast.com, LinkedIn: Mesoblast Limited and Twitter: @Mesoblast References / Footnotes Yuzefpolskaya M et al. Ann Thorac Surg 2023; 115:311-28Wever-Pinzon, Selzman CH, Stoddard G, et al. Impact of Ischemic HF etiology on Cardiac Recovery During Mechanical Unloading. J Am Coll Cardiol 2016;68:1741-1752. doi: 10.1016/j.jacc.2016.07.756.Mehra MR, Goldstein DJ, Cleveland JC, et. al. Five-year outcomes in patient with fully magnetically levitated vs axial-flow left ventricular assist devices in the MOMENTUM 3 randomized trial. JAMA 2022; doi:10.1001/jama.2022.161972.Symons JD, Deeter L, Deeter N, et al. Effect of continuous-flow left ventricular assist device support on coronary artery endothelial function in ischemic and nonischemic cardiomyopathy. Cir Heart Fail 2019; 12:e006085. DOI: 10.1161/CIRCHEARTFAILURE.119.006085.AHA’s 2017 Heart Disease and Stroke StatisticsPonikowski P., et al. Heart Failure: Preventing disease and death worldwide. European Society of Cardiology. 2014; 1: 4-25Gustafsson F, Rogers JG. Left ventricular assist device therapy in advanced heart failure: patient selection and outcomes. European Journal of Heart Failure 2017;19:595-602. Forward-Looking StatementsThis press release includes forward-looking statements that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements should not be read as a guarantee of future performance or results, and actual results may differ from the results anticipated in these forward-looking statements, and the differences may be material and adverse. Forward-looking statements include, but are not limited to, statements about: the initiation, timing, progress and results of Mesoblast’s preclinical and clinical studies, and Mesoblast’s research and development programs; Mesoblast’s ability to advance product candidates into, enroll and successfully complete, clinical studies, including multi-national clinical trials; Mesoblast’s ability to advance its manufacturing capabilities; the timing or likelihood of regulatory filings and approvals (including any future decision that the FDA may make on the BLA for remestemcel-L for pediatric patients with SR-aGVHD), manufacturing activities and product marketing activities, if any; the commercialization of Mesoblast’s product candidates, if approved; regulatory or public perceptions and market acceptance surrounding the use of stem-cell based therapies; the potential for Mesoblast’s product candidates, if any are approved, to be withdrawn from the market due to patient adverse events or deaths; the potential benefits of strategic collaboration agreements and Mesoblast’s ability to enter into and maintain established strategic collaborations; Mesoblast’s ability to establish and maintain intellectual property on its product candidates and Mesoblast’s ability to successfully defend these in cases of alleged infringement; the scope of protection Mesoblast is able to establish and maintain for intellectual property rights covering its product candidates and technology; estimates of Mesoblast’s expenses, future revenues, capital requirements and its needs for additional financing; Mesoblast’s financial performance; developments relating to Mesoblast’s competitors and industry; and the pricing and reimbursement of Mesoblast’s product candidates, if approved. You should read this press release together with our risk factors, in our most recently filed reports with the SEC or on our website. Uncertainties and risks that may cause Mesoblast’s actual results, performance or achievements to be materially different from those which may be expressed or implied by such statements, and accordingly, you should not place undue reliance on these forward-looking statements. We do not undertake any obligations to publicly update or revise any forward-looking statements, whether as a result of new information, future developments or otherwise. Release authorized by the Chief Executive. For more information, please contact: Corporate Communications / InvestorsMediaPaul HughesBlueDot MediaT: +61 3 9639 6036Steve DabkowskiE: investors@mesoblast.comT: +61 419 880 486 E: steve@bluedot.net.au

Nipocalimab is the only therapy in the clinics for haemolytic disease of the foetus and newborn. Credit: Iryna Inshyna / Shutterstock.com. The US Food and Drug Administration (FDA) has granted breakthrough therapy designation (BTD) to Johnson & Johnson ’s (J&J) nipocalimab for alloimmunised pregnant people at increased risk of increased severe haemolytic disease of the foetus and newborn (HDFN), which can cause life-threatening anaemia. This investigational therapy is the only one in the clinics for the condition, which occurs when the blood types of the pregnant individual and the foetus are incompatible. Nipocalimab is a fully human, aglycosylated, effectorless, monoclonal antibody designed to hinder the neonatal fragment crystallisable receptor (FcRn) and reduce levels of circulating immunoglobulin G antibodies. The regulator granted BTD based on findings from the proof-of-concept, open-label Phase II UNITY clinical trial of the therapy. The multicentre, international, non-blinded trial assessed nipocalimab’s efficacy, safety, pharmacodynamics and pharmacokinetics. See Also: FDA grants fast track status to GSK’s bepirovirsen for hepatitis B Takeda’s EOHILIA receives FDA approval for EoE treatment Its primary endpoint was a live birth at or later than a gestational age of 32 weeks, without requiring an intrauterine transfusion throughout the pregnancy. The study met this primary endpoint with 54% of pregnant subjects. A small number of severe adverse events were reported in the study. These were found to be in line with events linked to pregnancy, HDFN and gestational age of the infant at birth. Nipocalimab for HDFN treatment received fast track status in July 2019, orphan drug status in June 2020 from the US regulator and orphan medicinal product designation from the European Medicines Agency in October 2019. The Phase III AZALEA trial is underway and is enrolling pregnant patients with a history of the condition. J&J autoantibody and maternal foetal immunology disease area leader and vice-president Katie Abouzahr stated: “Nipocalimab represents a novel approach for the treatment of patients at risk of severe HDFN who need proven, safe, non-surgical solutions to help address the serious health consequences of this condition. “We are committed to addressing the substantial unmet need in this devastating disease.” In December 2023, the company signed a licensing agreement with LegoChem Biosciences for the development and marketing of LCB84 in a $1.7bn. deal.

Breakthrough Therapy Designation for nipocalimab based on results from the Phase 2 UNITY clinical trial for HDFN Phase 3 clinical trial enrollment underway, representing the only therapy reported to be under clinical development for this serious, life-threatening and rare condition SPRING HOUSE, Pa., Feb. 9, 2024 /PRNewswire/ -- Johnson & Johnson today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for nipocalimab for the treatment of alloimmunizeda pregnant individuals at high risk of severe hemolytic disease of the fetus and newborn (HDFN). Nipocalimab is currently the only therapy reported to be in clinical development for the treatment of alloimmunized pregnant individuals at risk of severe HDFN, a serious and rare condition that occurs when the blood types of a pregnant individual and the fetus are incompatible, potentially causing life-threatening anemia in the fetus or infant.1 "Nipocalimab represents a novel approach for the treatment of patients at risk of severe HDFN who need proven, safe, non-surgical solutions to help address the serious health consequences of this condition," said Katie Abouzahr, M.D., Vice President, Autoantibody and Maternal Fetal Immunology Disease Area Leader, Johnson & Johnson. "We are committed to addressing the substantial unmet need in this devastating disease." The data from the proof-of-concept Phase 2 open-label UNITY clinical trial provided support for the BTD.2 The trial met the primary endpoint, with the majority of pregnant patients who received nipocalimab achieving a live birth at or after the gestational age of 32 weeks, without the need for an intrauterine transfusion (IUT) throughout their entire pregnancy.3 Severe or serious adverse events were generally low and consistent with events associated with pregnancy, HDFN, and gestational age at birth.3 Nipocalimab was granted Fast Track designation in July 2019, orphan drug status in June 2020 by the FDA, and orphan medicinal product designation by the European Medicines Agency in October 2019 for the HDFN indication. The FDA grants BTD to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition and is based on preliminary clinical evidence that demonstrates the drug may have substantial improvement in at least one clinically significant endpoint over available therapies. The AZALEA Phase 3 pivotal trial is currently enrolling pregnant individuals who are at risk for severe HDFN who have a history of severe HDFN in a prior pregnancy(ies).2 Editor's Notes: a. Alloimmunized: an immune response to foreign antigens upon exposure to genetically different cells or tissues.4 About the UNITY trial UNITY (NCT03842189) is a global, multicenter, non-blinded Phase 2 clinical trial designed to evaluate the safety, efficacy, pharmacokinetics and pharmacodynamics of nipocalimab for the treatment of pregnant individuals at high risk for EOS HDFN.5 The trial enrolled RhD (D) or Kell (K) alloimmunized pregnant individuals with singleton pregnancies at high risk for EOS HDFN due to an obstetric history of severe fetal anemia, fetal hydrops, or a stillbirth at ≤24 weeks gestation.3 The primary endpoint was live birth at or after gestational age of 32 weeks, without a need for an IUT throughout the entire pregnancy.3 Safety was monitored for 24 weeks post-delivery for the 13 maternal individuals enrolled, and up to 96 weeks post-birth for infants.3 Participants received once-weekly intravenous infusions.3 The trial met the primary endpoint, with 54% of pregnant patients who received nipocalimab achieving a live birth at or after the gestational age (GA) of 32 weeks, without the need for an intrauterine transfusion throughout their entire pregnancy. About HDFN Hemolytic disease of the fetus and newborn (HDFN) is a rare disease (and in its severe form, even rarer) that arises in pregnancies with maternal-fetal incompatibility in certain red blood cell types. Alloantibodies produced by the maternal immune system against fetal red blood cells cross the placenta during pregnancy and attack fetal red blood cells causing fetal anemia or persist after birth in the neonate to cause neonatal hyperbilirubinemia and anemia.1 The symptoms of HDFN can range from mild jaundice, to neurotoxic hyperbilirubinema in the neonate, to life-threatening fetal anemia requiring invasive intervention.6 The potential for in utero onset at increasingly earlier gestational age with increasing risk of severe outcomes may occur with each incompatible pregnancy due to pregnancy-related alloimmunization.7 Currently no non-surgical interventions are approved for pregnancies at high risk of early-onset severe (EOS) HDFN in the U.S. Pregnancies affected by severe HDFN may necessitate repeated intrauterine transfusions (IUTs).8 IUTs are invasive, technically complex surgical procedures performed by specialists at specialized medical centers, and these procedures may be associated with an increased rate of fetal mortality and premature birth.9,10 The most difficult to treat cases of HDFN are those that develop before 24 weeks gestational age, defined here as EOS, due to high rates of IUT-related complications associated with mortality.11 According to the American Journal of Obstetrics and Gynecology, in the U.S., it is estimated that up to 80 of every 100,000 pregnancies are affected by HDFN each year.12 About Nipocalimab Nipocalimab is an investigational, high-affinity, fully human, aglycosylated, effectorless, monoclonal antibody that aims to selectively block FcRn to reduce levels of circulating immunoglobulin G (IgG) antibodies, including autoantibodies and alloantibodies that underlie multiple conditions.13 Nipocalimab is the only anti-FcRn being studied across three key segments in the autoantibody space: Rare Autoantibody diseases (e.g., generalized myasthenia gravis in adults and children, chronic inflammatory demyelinating polyneuropathy, warm autoimmune hemolytic anemia, and idiopathic inflammatory myopathies); Maternal Fetal diseases mediated by maternal alloantibodies (e.g., HDFN); and Prevalent Rheumatology (e.g., rheumatoid arthritis, Sjögren's disease, and systemic lupus erythematosus).5,14,15,16,17,18,19,20,21 Blockade of FcRn has the potential to reduce overall autoantibody levels while preserving immune function without causing broad immunosuppression. Blockade of IgG binding to FcRn in the placenta is also believed to prevent transplacental transfer of maternal alloantibodies to the fetus.5,22 About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at or at . Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of nipocalimab. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 1, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. © Johnson & Johnson 2024. All rights reserved. Media contact: Bridget Kimmel Mobile: (215) 688-6033 [email protected] Investor contact: Raychel Kruper [email protected] SOURCE Johnson & Johnson