Anemia, Neonatal

Marks first EMA submission for nipocalimab, an investigational treatment that binds with high affinity and specificity to block FcRn and reduce levels of autoantibodies Filing based on the Phase 3 Vivacity-MG3 programme, the first registrational study results in the class demonstrating sustained disease control over 24 weeks in antibody-positive adult patients: anti-AChR+, anti-MuSK+, anti-LRP4+ BEERSE, Belgium I September 12, 2024 I Janssen-Cilag International NV, a Johnson & Johnson company, today announced the submission of the Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) seeking first approval of nipocalimab for the treatment of people living with generalised myasthenia gravis (gMG). The application included data from the Phase 3 Vivacity-MG3 study which showed that outcomes for a broad population of antibody-positive participants who received nipocalimab plus standard of care (SOC) were superior compared to those who received placebo plus SOC. 1 The primary endpoint of the study measured improvement in the Myasthenia Gravis – Activities of Daily Living (MG-ADL) a score from baseline over 24 weeks and study participants included anti-AChR+, anti-MuSK+, and anti-LRP4+ b antibody-positive adults, which account for approximately 95 percent of the gMG patient population, making Vivacity-MG3 the first registrational study to demonstrate sustained disease control in these subtypes. 1,2 Safety and tolerability were consistent with other nipocalimab studies. 3,4,5,c “We are encouraged by the potential of nipocalimab to provide sustained disease control for people living with generalised myasthenia gravis, a chronic, life-long disease,” said Bill Martin, Ph.D., Global Therapeutic Area Head, Neuroscience, Johnson & Johnson Innovative Medicine. “The filing for approval of nipocalimab represents an important step forward as Johnson & Johnson continues to push the boundaries of research to develop innovative solutions to treat autoantibody-driven diseases, building on decades of expertise in neuroscience and immunology. We look forward to working with the EMA in their review of the data supporting the submission.” Nipocalimab is the first FcRn blocker to demonstrate sustained disease control measured by improvement in MG-ADL when added to background SOC compared with placebo plus SOC over a period of six months of consistent dosing (every other week). 1,6,d Editor’s notes: About Generalised Myasthenia Gravis (gMG) Myasthenia gravis (MG) is an autoantibody disease in which autoantibodies target proteins at the neuromuscular junction, disrupt neuromuscular signalling, and impair or prevent muscle contraction. 8,9 In MG, the immune system mistakenly attacks proteins at the neuromuscular junction, e.g., anti-acetylcholine receptor [AChR], anti-muscle-specific tyrosine kinase [MuSK] or anti-lipoprotein-related protein 4 [LRP4], that can block or disrupt normal functioning, preventing signals from transferring from nerves to muscles. 10 The disease impacts between 56,000 and 123,000 people in Europe and an estimated 700,000 people worldwide. 8,11 The disease affects both men and women and occurs across all ages, racial and ethnic groups, but most frequently impacts young women and older men. 12 Roughly 50 percent of individuals diagnosed with MG are women, and about one in five of those women are of child-bearing potential. 13,14,15 Initial disease manifestations are usually ocular but in 85 percent or more the disease generalises (gMG), which is characterised by fluctuating weakness of the skeletal muscles leading to symptoms like limb weakness, drooping eyelids, double vision and difficulties with chewing, swallowing, speech, and breathing. 9,16,17 Although gMG may be managed with current SOC therapies, research is needed to develop new treatments for those who may not respond well enough to or tolerate these options. 9 About the Phase 3 Vivacity-MG3 Study The Phase 3 Vivacity-MG3 study was specifically designed to measure sustained efficacy and safety with consistent dosing in this unpredictable chronic condition where unmet need remains high. Antibody positive or negative adult gMG patients with insufficient response (MG-ADL ≥6) to ongoing standard of care (SOC) therapy were identified and 199 patients, 153 of which were antibody positive, enrolled in the 24-week double-blind placebo-controlled trial. 18,19 Randomisation was 1:1, nipocalimab plus current SOC (30 mg/kg IV loading dose followed by 15 mg/kg every two weeks) or placebo plus current SOC. 19 Baseline demographics were balanced across arms (77 nipocalimab, 76 placebo). 19 The primary endpoint of the study was mean change in MG-ADL b score from baseline over Weeks 22, 23 and 24 in antibody-positive patients. A key secondary endpoint included change in Quantitative Myasthenia Gravis (QMG) score, which is a 13-item assessment by a clinician that quantifies MG disease severity. Long-term safety and efficacy were further assessed in an ongoing OLE phase. 18 About Nipocalimab Nipocalimab is an investigational monoclonal antibody, purposefully designed to bind with high affinity to block FcRn and reduce levels of circulating immunoglobulin G (IgG) antibodies, while preserving immune function without causing broad immunosuppression. 20 This includes autoantibodies and alloantibodies that underlie multiple conditions across three key segments in the autoantibody space including Rare Autoantibody diseases, Maternal Foetal diseases mediated by maternal alloantibodies and Prevalent Rheumatology. 18,21,22,23,24,25,26,27,28 Blockade of IgG binding to FcRn in the placenta is also believed to prevent transplacental transfer of maternal alloantibodies to the foetus. 29 The European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA) have granted several key designations to nipocalimab including: 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 www.janssen.com/emea . Follow us at www.linkedin.com/jnj-innovative-medicine-emea . References 1 Antozzi, C et al., Efficacy and Safety of Nipocalimab in patients with Generalized Myasthenia Gravis- Top Line Results from the Double-Blind, Placebo-Controlled, Randomized Phase 3 Vivacity-MG3 study. 2024 European Academy of Neurology Congress. June 2024. 2 J&J Data on file (RF-421587). Approximate incidence of seronegativity in generalised myasthenia gravis (gMG). Date of preparation: June 2024. 3 Kenneth J. Moise Jr., et al. Nipocalimab in Early-onset Severe Hemolytic Disease of the Fetus & Newborn. N Engl J Med. 2024; DOI: 10.1056/NEJMoa2314466. 4 Efficacy and safety of nipocalimab, an anti-FcRn monoclonal antibody, in primary Sjogren’s disease: results from a Phase 2, multicenter, randomized, placebo-controlled, double-blind study (DAHLIAS). Late-breaking presentation at European Alliance of Associations for Rheumatology (EULAR) Annual Meeting; June 12–15, 2924. LBA0010 5 Guptill et.al. Vivacity-MG: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Nipocalimab Administered to Adults with Generalized Myasthenia Gravis (2157). Neurology Journals. April 13, 2021. https://doi.org/10.1212/WNL.96.15_supplement.2157 6 Johnson & Johnson EMEA. Nipocalimab pivotal Phase 3 trial demonstrates sustained disease control in FcRn class for a broad population of myasthenia gravis patients. Available at: https://www.janssen.com/sites/www_janssen_com_emea/files/jj_emea_ean_nipocalimab_press_release_final.pdf . Last accessed: September 2024. 7 Wolfe GI Myasthenia gravis activities of daily living profile. Neurology. 1999;22;52(7):1487-9. doi: 10.1212/wnl.52.7.1487. 8 Chen J, Tian D-C, Zhang C, et al. Incidence, mortality, and economic burden of myasthenia gravis in China: A nationwide population-based study. The Lancet Regional Health – Western Pacific. 2020;5(100063). https://doi.org/10.1016/j.lanwpc.2020.100063. 9 Bacci ED et al. Understanding side effects of therapy for myasthenia gravis and their impact on daily life. BMC Neurol. 2019;19(1):335. 10 Wiendl, H., et al., Guideline for the management of myasthenic syndromes. Therapeutic advances in neurological disorders, 16, 17562864231213240. https://doi.org/10.1177/17562864231213240 . Last accessed: September 2024. 11 Bubuioc A, et al. The epidemiology of myasthenia gravis. Journal of Medicine & Life (2021). Jan-Mar;14(1):7-16. doi: 10.25122/jml-2020-0145 12 National Institute of Neurological Disorders and Stroke. Myasthenia Gravis. Available at: https://www.ninds.nih.gov/health-information/disorders/myasthenia-gravis . Last accessed: September 2024. 13 Ye, Yun et al. Epidemiology of myasthenia gravis in the United States. Frontiers in neurology vol. 15 1339167. 16 Feb. 2024, doi:10.3389/fneur.2024.1339167 14 Dresser, Laura et al. Myasthenia Gravis: Epidemiology, Pathophysiology and Clinical Manifestations. Journal of clinical medicine vol. 10,11 2235. 21 May. 2021, doi:10.3390/jcm10112235. 15 Johnson & Johnson Data on file. (RF-430993). MG: Proportion of Diagnosed Patients who are People of Child-bearing Potential (POCBP). Date of preparation: May 2024. 16 Bever, C.T., Jr, Aquino, A.V., Penn, A.S., Lovelace, R.E. and Rowland, L.P. (1983), Prognosis of ocular myasthenia. Ann Neurol., 14: 516-519. https://doi.org/10.1002/ana.410140504 17 Gilhus N. E, et al. Myasthenia Gravis. Nat Rev Dis Primers. (2019) 5(30): DOI: https://doi.org/10.1038/s41572-019-0079-y 18 ClinicalTrials.gov Identifier: NCT04951622. Available at: https://clinicaltrials.gov/ct2/show/NCT04951622 . Last accessed: September 2024. 19 Antozzi, C et al., Nipocalimab in Generalized Myasthenia Gravis: Results from a Double-Blind, Placebo-Controlled, Randomized Phase 3 Study. Abstract at 2024 European Academy of Neurology Congress. June 2024. 20 Ling LE., et al. M281, an anti‐fcrn antibody: Pharmacodynamics, pharmacokinetics, and safety across the full range of IGG reduction in a first‐in‐human study. Clinical Pharmacology & Therapeutics., 2018;105;4:1031–1039. https://doi.org/10.1002/cpt.1276. 21 ClinicalTrials.gov. NCT03842189. Available at: https://clinicaltrials.gov/ct2/show/NCT03842189. Last accessed: September 2024 22 ClinicalTrials.gov Identifier: NCT05327114. Available at: https://www.clinicaltrials.gov/study/NCT05327114 . Last accessed: September 2024 23 ClinicalTrials.gov Identifier: NCT04119050. Available at: https://clinicaltrials.gov/study/NCT04119050 . Last accessed: September 2024. 24 ClinicalTrials.gov Identifier: NCT05379634. Available at: https://clinicaltrials.gov/study/NCT05379634 . Last accessed: September 2024. 25 ClinicalTrials.gov Identifier: NCT05912517. Available at: https://www.clinicaltrials.gov/study/NCT05912517 . Last accessed: September 2024 26 ClinicalTrials.gov Identifier: NCT06028438. Available at: https://clinicaltrials.gov/study/NCT06028438 . Last accessed: September 2024. 27 ClinicalTrials.gov Identifier: NCT04968912. Available at: https://clinicaltrials.gov/study/NCT04968912 . Last accessed: September 2024. 28 ClinicalTrials.gov Identifier: NCT04882878. Available at: https://clinicaltrials.gov/study/NCT04882878 . Last accessed: September 2024. 29 Roy S, Nanovskaya T, Patrikeeva S, et al. M281, an anti-FcRn antibody, inhibits IgG transfer in a human ex vivo placental perfusion model. Am J Obstet Gynecol. 2019;220(5):498 e491-498 e499. SOURCE: Johnson & Johnson

NEW HAVEN, Conn.--( BUSINESS WIRE )--Rallybio Corporation (Nasdaq: RLYB), a clinical-stage biotechnology company translating scientific advances into transformative therapies for patients with devastating rare diseases, announced today that data from the Phase 1 proof-of-concept study of RLYB212, a novel monoclonal anti-HPA-1a antibody in development for the prevention of maternal alloimmunization and fetal and neonatal alloimmune thrombocytopenia (FNAIT), were published in Thrombosis and Haemostasis . Top-line results from this study were previously presented at the 31 st Congress of the International Society on Thrombosis and Haemostasis (ISTH) in 2023. “These data were instrumental in our selection of the initial dose for the upcoming Phase 2 trial of RLYB212, which is on track for initiation in the fourth quarter of 2024,” said Stephen Uden, M.D., Chief Executive Officer of Rallybio. “Our primary focus is to advance RLYB212 through development with a goal of bringing a new therapy to a completely underserved area of maternal fetal health.” Data from the Phase 1 proof-of-concept study demonstrated that subcutaneous administration of RLYB212 produced a dose-dependent, rapid, and complete elimination of transfused HPA-1a positive platelets in HPA-1a negative subjects, with both doses (0.09 mg and 0.29 mg) meeting the prespecified proof-of-concept criteria of ≥90% reduction in mean platelet elimination half-life as compared to placebo. These data along with a significant body of preclinical data generated to date were critical to the establishment of therapeutic exposure targets that Rallybio believes will safely and effectively prevent maternal alloimmunization to fetal antigen, the prerequisite event leading to FNAIT. The bolus challenge of HPA-1a positive platelets was designed as a surrogate for a large 30 mL fetal-maternal hemorrhage. Platelet elimination profiles after subcutaneous administration of RLYB212 were consistent with those of Rhesus factor D (RhD)-positive erythrocytes after intramuscular administration of anti-RhD agents, which are well-established to safely and effectively prevent RhD alloimmunization during pregnancy. Consistent with previously reported data, RLYB212 was generally well-tolerated with no reports of serious or severe adverse events. Rallybio is on track to initiate a Phase 2 dose confirmation trial in pregnant women at higher risk for HPA-1a alloimmunization and FNAIT in the fourth quarter of 2024. The Company also continues to screen pregnant women in its ongoing FNAIT natural history study, which is designed to provide a contemporary dataset for HPA-1a alloimmunization frequency in a racially and ethnically diverse population that can serve as a control arm for a planned Phase 3 trial. About FNAIT Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) is a potentially life-threatening rare disease that can cause uncontrolled bleeding in fetuses and newborns. FNAIT can arise during pregnancy due to an immune incompatibility between an expectant mother and her fetus in a specific platelet antigen called human platelet antigen 1, or HPA-1. There are two predominant forms of HPA-1, known as HPA-1a and HPA-1b, which are expressed on the surface of platelets. Individuals who are homozygous for HPA-1b, meaning that they have two copies of the HPA-1b allele and no copies of the HPA-1a allele, are also known as HPA-1a negative. Upon exposure to the HPA-1a antigen, these individuals can develop antibodies to that antigen in a process known as alloimmunization. In HPA-1a-negative expectant mothers bearing a HPA-1a-positive fetus, alloimmunization can occur upon mixing of fetal blood with maternal blood. When alloimmunization occurs in an expectant mother, the anti-HPA-1a antibodies that develop in the mother can cross the placenta and destroy platelets in the fetus. The destruction of platelets in the fetus can result in severely low platelet counts, or thrombocytopenia, and potentially lead to devastating consequences including miscarriage, stillbirth, death of the newborn, or severe lifelong neurological disability in those babies who survive. There is currently no approved therapy for the prevention or prenatal treatment of FNAIT. About Rallybio Rallybio (NASDAQ: RLYB) is a clinical-stage biotechnology company with a mission to develop and commercialize life-transforming therapies for patients with severe and rare diseases. Rallybio has built a broad pipeline of promising product candidates aimed at addressing diseases with unmet medical need in areas of maternal fetal health, complement dysregulation, hematology, and metabolic disorders. The Company has two clinical stage programs: RLYB212, an anti-HPA-1a antibody for the prevention of fetal and neonatal alloimmune thrombocytopenia (FNAIT) and RLYB116, an inhibitor of complement component 5 (C5), with the potential to treat several diseases of complement dysregulation, as well as additional programs in preclinical development. Rallybio is headquartered in New Haven, Connecticut. For more information, please visit www.rallybio.com and follow us on LinkedIn and Twitter . Forward-Looking Statements This press release contains forward-looking statements that are based on our management’s beliefs and assumptions and on currently available information. All statements, other than statements of historical facts contained in this press release are forward-looking statements. In some cases, forward-looking statements can be identified by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements concerning the timing of initiation of the Phase 2 dose confirmation study for RLYB212, our expectations regarding the usefulness of data from our clinical studies and the FNAIT natural history study, and the timing of publications relating to FNAIT and RLYB212. The forward-looking statements in this press release are only predictions and are based largely on management’s current expectations and projections about future events and financial trends that management believes may affect Rallybio’s business, financial condition and results of operations. These forward-looking statements speak only as of the date of this press release and are subject to a number of known and unknown risks, uncertainties and assumptions, including, but not limited to, our ability to successfully initiate and conduct our planned clinical trials, including the FNAIT natural history study, and the Phase 2 clinical trial for RLYB212, and complete such clinical trials and obtain results on our expected timelines, or at all, whether our cash resources will be sufficient to fund our operating expenses and capital expenditure requirements and whether we will be successful raising additional capital, our ability to enter into strategic partnerships or other arrangements, competition from other biotechnology and pharmaceutical companies, and those risks and uncertainties described in Rallybio’s filings with the U.S. Securities and Exchange Commission (SEC), including Rallybio’s Quarterly Report on Form 10-Q for the period ended June 30, 2024, and subsequent filings with the SEC. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual future results, levels of activity, performance and events and circumstances could differ materially from those projected in the forward-looking statements. Except as required by applicable law, we are not obligated to publicly update or revise any forward-looking statements contained in this press release, whether as a result of any new information, future events, changed circumstances or otherwise.

Yearly event reunites patients treated in the Richard D. Wood Jr. Center for Fetal Diagnosis and Treatment with their care team and other families PHILADELPHIA, June 3, 2024 /PRNewswire/ -- Yesterday, more than 2,700 people gathered at the Philadelphia Zoo to celebrate Children's Hospital of Philadelphia's (CHOP) 28th annual reunion for patients and families treated at the Richard D. Wood Jr. Center for Fetal Diagnosis and Treatment (CFDT). This year the event was newly named the "Lori J. Howell Fetal Family Reunion" in honor of Lori J. Howell, DNP, MS, RN, a beloved colleague, clinical innovator, and former executive director of the CFDT, who passed away earlier this year. The annual event provides an opportunity for those treated in the Center, many of whom underwent fetal surgery before they were even born, to reconnect with their care team and other families who share an indescribable bond. Continue Reading CHOP Celebrates 28th Annual Fetal Surgery Family Reunion "Each year, this day serves as both a celebration and a reflection point for how far our Center has come, but never has this event been more significant than this year," said N. Scott Adzick, MD, Surgeon-In-Chief at CHOP and Director of the CFDT. "It is truly a bittersweet occasion as we remember our beloved colleague, Lori Howell. Lori was a true champion and advocate on behalf of every patient here. We are grateful for all her contributions in making this event all it has grown to be." The reunion brings together a unique community of families who have shared similar experiences. Nearly all of the children in attendance were prenatally diagnosed with a birth defect, such as spina bifida, congenital diaphragmatic hernia, or twin-twin transfusion syndrome, that had potentially devastating outcomes. Babies diagnosed before birth either underwent fetal surgery to treat the condition in utero or received highly complex care immediately after birth. The event began in 1997 and has grown from a handful of attendees in its first year to more than 850 families today. Opened in 1995, the CFDT is the largest and most comprehensive fetal program in the world, treating more than 32,000 expectant mothers and their unborn babies from all 50 states and more than 70 countries. To date, the CFDT team has performed more than 2,400 fetal surgeries and helped make fetal surgery a widespread and life-changing option for babies and families. CHOP's CFDT is a pioneer in the field of fetal medicine largely due to Lori Howell's contributions. For the 27 years she spent at CHOP, Lori was committed to ensuring the highest standard of care for families facing birth defects. She catapulted the fetal therapy program into the largest and most comprehensive program in the world. Lori helped recruit and build the stellar multidisciplinary team that is in place today, established innovative and personalized patient care approaches, developed important patient education, and championed both innovative research approaches and the importance of long-term follow-up, all of which are now the gold standard in fetal medicine and have been modeled by colleagues around the world. Lori's legacy will forever be woven into the fabric that is the CFDT. Patients and families experience the highest level of care for complex fetal surgeries at CHOP. Our surgical teams specialize in advanced procedures to treat a variety of birth defects, ensuring the best possible outcomes for both mother and baby, providing expert care from prenatal diagnosis to delivery in our Garbose Family Special Delivery Unit, and beyond. Contact: Kaila Revello Children's Hospital of Philadelphia 610.457.5916 [email protected] SOURCE Children's Hospital of Philadelphia