T-Cell Leukemia

Mission BioCapital and 4BIO Capital led the financing with significant participation from new and existing investors, raising over $51 million to date Funds will support Phase 2 development of March Bio’s lead CD5 CAR-T therapy, MB-105, for T-cell lymphoma and pipeline candidates HOUSTON, Oct. 23, 2024 (GLOBE NEWSWIRE) -- March Biosciences (March Bio), an emerging clinical stage biotechnology company committed to combating challenging cancers and other diseases, today announced the close of a $28.4 million oversubscribed Series A financing. Mission BioCapital and 4BIO Capital led the financing, with participation from KdT Ventures, Alexandria Venture Investments, Volnay Therapeutics, Modi Ventures, and Mansueto Investments. Existing investors TMC Venture Fund, Cancer Focus Fund, and Small Ventures also participated in the round. March Bio has raised over $51 million to date inclusive of all dilutive and non-dilutive funding. Since its inception as a spinout of the Center for Cell and Gene Therapy (Baylor College of Medicine, Houston Methodist Hospital, Texas Children’s Hospital), March Bio has rapidly advanced its innovative autologous chimeric antigen receptor T-cell (CAR-T) therapy, MB-105, in development for the treatment of relapsed and refractory CD5 positive T-cell lymphoma. MB-105 is specifically engineered to overcome major hurdles related to T-cell targeting by overcoming T-cell fratricide while maintaining high potency against CD5 positive tumor cells. MB-105 has demonstrated a favorable safety profile and durable remissions in relapsed T-cell lymphoma patients in a Phase 1 clinical trial at Baylor College of Medicine, with plans to begin a Phase 2 clinical trial in early 2025. Proceeds from the financing will support the Phase 2 clinical development of MB-105 to expand on this data with optimized manufacturing processes. “This oversubscribed financing enables us to advance our first-in-class CAR-T therapy, MB-105, into a Phase 2 trial for T-cell lymphoma – an indication with an exceptionally poor prognosis and few treatment options,” said Sarah Hein, Co-Founder and Chief Executive Officer of March Biosciences. “With the support and confidence of our investors, we are not only advancing our lead program but also expanding our pipeline, underscoring our commitment to delivering best-in-class therapies to patients that can change the treatment paradigm for these challenging cancers.” The new financing coincides with an announcement that the company has partnered with Volnay Therapeutics, a cell therapy venture studio led by a team of highly experienced cell therapy development veterans. March Biosciences will work with Volnay for technical oversight to develop a robust and scalable manufacturing process for MB-105 through clinical development and potential commercialization, a critical component of a successful autologous cell therapy program. Concurrent with the partnership announcement, Volnay Co-Founder and CEO Stefan Wildt, who held key R&D leadership positions in cell and gene therapy units at Novartis and Takeda, is joining March Bio’s Board of Directors. “For far too long, T-cell cancers have been an innovation desert with patients facing a dismal prognosis. March Bio’s innovative autologous CAR-T approach brings patients new hope,” said Owen Smith, Partner at 4BIO Capital. “MB-105 is specifically engineered for relapsed and refractory CD5 positive T-cell lymphomas and I am delighted that this targeted approach combined with the incredible team led by Sarah is moving rapidly into Phase 2 to bring this exciting new treatment to patients. We are honored to be a co-lead investor in March Bio and to help support the company as it continues in its mission to bring transformative therapies to those in urgent need.” “The team at March Biosciences is leveraging powerful science and promising clinical data to tackle cancers with significant unmet need,” said Cassidy Blundell, Partner at Mission BioCapital. “We're excited to support their journey and believe their focused approach with MB-105 could lead to significant breakthroughs in the CAR-T space.” Cassidy Blundell of Mission BioCapital and Owen Smith of 4BIO Capital are also joining March Bio’s Board of Directors. The financing will also provide resources for the ongoing development of undisclosed pipeline products, as well as for general corporate proceeds. About March BiosciencesHouston-based March Biosciences, launched from the Center for Cell and Gene Therapy (Baylor College of Medicine, Houston Methodist Hospital, Texas Children’s Hospital), is dedicated to addressing challenging cancers unresponsive to current immunotherapies. Its lead asset, MB-105, is a CD5-targeted CAR-T cell therapy currently in Phase 1 trials in patients with refractory T-cell lymphoma and leukemia, with promising signals of efficacy and safety to date. A Phase 2 trial is expected to begin next early year. The company has raised over $50M to date, inclusive of this current financing and support from the Cancer Prevention & Research Institute of Texas (CPRIT) and the NIH SBIR program. Learn more at www.march.bio. About 4BIO Capital4BIO Capital (“4BIO”) is an international venture capital firm focused on investing in advanced therapies, including genomic medicines and other emerging technologies, to unlock the treatments of the future. 4BIO’s objective is to invest in, support, and grow early-stage companies developing treatments in areas of high unmet medical need, with the ultimate goal of ensuring access to these potentially curative therapies for all patients. Specifically, it looks for viable, high-quality opportunities in cell and gene therapy, RNA-based therapy, targeted therapies, and the microbiome. The 4BIO team comprises leading advanced therapy scientists and experienced life science investors who have collectively published over 250 scientific articles in prestigious academic journals including Nature, The Lancet, Cell, and the New England Journal of Medicine. 4BIO has both an unrivalled network within the advanced therapy sector and a unique understanding of the criteria that define a successful investment opportunity in this space. For more information, visit www.4biocapital.com. About Mission BioCapitalMission BioCapital is a biotech venture capital firm focused on making pivotal early-stage investments in life sciences companies. They support portfolio companies through a unique combination of shared lab space, capital investment, and access to strategic partners. With offices in the nation’s leading life sciences clusters in Cambridge, MA and San Francisco, Mission BioCapital is dedicated to helping entrepreneurial scientists build successful companies, from idea to exit. Learn more at missionbiocapital.com. About Volnay TherapeuticsVolnay Therapeutics is a biotech venture builder dedicated to accelerating the development of innovative cell and gene therapies. With decades of experience in drug development, Volnay identifies promising therapeutic assets and enabling technologies with disruptive potential and provides both capital and operational expertise to drive these ventures forward. By focusing on innovation in product manufacturing, commercial viability and capital efficiency, Volnay aims to deliver significant value to patients and investors alike. Visit www.volnaytx.com. Forward-Looking StatementThis press release contains forward-looking statements that involve risks and uncertainties, including those related to the clinical development of MB-105 and other potential therapies. Actual results may differ materially from those projected in these forward-looking statements. Factors that could cause actual results to differ materially include, but are not limited to, the progress of clinical trials, regulatory approvals, market demand for new therapies, and competitive dynamics in the biotechnology sector. Contacts: Corporate:Sarah HeinChief Executive Officer sarah@march.bio Media:Jon YuMarchBioPR@icrhealthcare.com

Phoenix, Arizona/ iStock, Sean Pavone Stephen Majors from the Alliance for Regenerative Medicine, which hosts the conference, spoke with BioSpace about what the more than 2,000 attendees can expect to learn next week in Phoenix about the pressing issues confronting the industry. The 2024 Cell & Gene Meeting on the Mesa has a new location this year—held Oct. 7–9 in Phoenix, having moved from Carlsbad, Calif. Despite the change in venue, the industry continues to face the same regulatory, manufacturing and commercialization challenges as the sector hits an inflection point. BioSpace will provide on-site coverage of the three-day event, where more than 2,000 attendees will get an update from key stakeholders on the industry’s progress and the stumbling blocks that are impeding the advancement of cell and gene therapies (CGTs). One of the biggest business challenges for the sector is the investment headwinds that have continued this year, according to the Alliance for Regenerative Medicine (ARM), the Washington, DC–based advocacy organization that represents the industry and hosts the annual Meeting on the Mesa. Stephen Majors, global head of communications at ARM, told BioSpace that capital markets “have been really tough” the past few years for CGT. “There’s a lot of companies in the space pursuing a smaller amount of money,” he observed. “Inflation projections were, of course, a driver of this because the gene therapy companies tend to be the furthest away from commercialization and therefore inflation concerns hit them hardest,” Majors said. “We’re hopeful that with the reduction of interest rates and a better inflation outlook going forward, we’ll start to see more money flow into the sector.” Manufacturing, Commercialization Hurdles Majors said that manufacturing is also a major challenge for the industry due to a lack of standardization and the fact that scale-up has often been an obstacle to regulatory approval and commercialization. “There are still some manufacturing challenges and the ability to produce these therapies at scale at the demand that they’re needed. That’s something that the sector’s still working through,” according to Majors. A Government Accountability Office report last year found that while regenerative medicine technologies—including gene therapies, cell therapies and tissue-engineered products—are highly promising, they are being held back by the lack of widely accepted standards and guidelines to govern their use, development and manufacture. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research (CBER), provided a sobering assessment in May at the 2024 American Society of Gene & Cell Therapy conference about the opportunities and challenges facing the CGT industry. He said that while it’s “an exciting time” for gene therapies in particular—including the approval of competing therapies for sickle cell disease —there are “some real challenges” including manufacturing, clinical development timelines and different global regulatory requirements . After their groundbreaking approvals in late 2023, infusions of Vertex-CRISPR Therapeutics’ and bluebird bio’s sickle cell gene therapies have recently begun, offering hope to patients and the companies, which are looking to jumpstart revenues. “Those of us who have been watching this for a while were always expecting these launches to be kind of slow with steady uptick over time, because of the length of time involved in the identification of eligible patients and in the consultation process they have with their doctors about whether this is the right therapy for them,” Majors said. A panel session at Meeting on the Mesa on commercializing cell and gene therapies in today’s “dynamic market” environment will be a “hot” session given other recent product launches, according to Majors. He expects “some lessons learned from that, maybe some wisdom and advice for launches yet to come.” For the second year at the conference, ARM CEO Tim Hunt will lead a session on the importance of ethics in cell and gene therapies. Majors said it is meant to be a broad-based look at several issues, including “the pricing and value” of CGT, global access such as “how long it will be” before therapies reach patients in developing and low- and middle-income countries, and ultra-rare diseases in which the sizes of patient populations “fall outside what usually works from a commercialization perspective.” According to market research and consulting firm Nova One Advisor, the global CGT market was valued at more than $18.1 billion in 2023 and is expected to reach approximately $97.3 billion by 2033. While CGT developers face challenges along several key stages of the product life cycle, the firm notes that “key success factors such as enabling patient access, managing supply chain and manufacturing operations, evidencing compliance with increasingly complex regulatory requirements and alternate business models impose a greater burden” for CGTs than for chemical-based pharmaceuticals. Regulatory Environment Takes Center Stage On the regulatory front at Meeting on the Mesa, the conference will hear from Nicole Verdun, director of the FDA’s Office of Therapeutic Products within CBER. According to Majors, Verdun will “give us an update on where the FDA is in terms of how they’re looking at cell and gene therapies, their staffing levels to ramp up with the submissions,” as well as accelerated approvals and “other details about the regulatory frameworks they’re looking at” for CGT. Scott Gottlieb, former FDA commissioner, will participate in a fireside chat at the conference. In 2019, as the head of the agency, Gottlieb predicted that the regulator would be approving 10 to 20 cell and gene therapy products annually by 2025. Early next year, his book The Miracle Century: Making Sense of the Cell Therapy Revolution is slated to be published. In it, he “tackles the issues that must be addressed to enable wide adoption of these treatments,” according to the publisher’s description . Majors said that Gottlieb will provide Meeting on the Mesa with an overview of “where we are in the field right now” and “what we can expect over the next few years.” “Historically, we haven’t seen much of a difference between the U.S. and Europe in approvals,” according to Majors. “There were a handful of gene therapies that got approved in Europe first before they got approved here. But what we’re seeing more recently is the U.S. starting to have more approvals.” ARM in its annual Cell & Gene State of the Industry Briefing in January predicted that the sector could see up to 17 regulatory approvals in the U.S. and European Union this year. However, Majors in an update to BioSpace said the organization has cut its forecast a bit and is now predicting up to 14 approvals, with eight in the U.S.—including the FDA’s first approval in March for an autologous gene therapy from Orchard Therapeutics to treat the rare metabolic disease metachromatic leukodystrophy in children, and the FDA nod in April for Pfizer’s hemophilia B gene therapy Beqvez. “If we looked at last year as kind of the breakthrough year of gene therapy, which it certainly was, this year we’re seeing a lot of advances in cell therapy,” Majors said. “There’s been a number of really impressive fundraises from cell therapy companies. There’s been a lot of excitement and progress in autoimmune diseases. And there’s been expansion of CAR T therapies into earlier lines of treatment.” In February, the FDA granted approval to Iovance Biotherapeutics’ li as the first one-time cell therapy for a solid tumor and the first tumor-infiltrating lymphocytes therapy. In April, the regulator greenlit two CAR T cell therapies for the earlier treatment of multiple myeloma —BMS and 2seventy Bio’s Abecma, and J&J and Legend Biotech’s Carvykti. And in August, Adaptimmune Therapeutics’ Tecelra became the first FDA-approved engineered cell therapy for solid tumors and the first new synovial sarcoma therapy in more than a decade. Majors sees Autolus Therapeutics’ FDA application for its next-generation CAR T therapy obe-cel in relapsed/refractory adult acute lymphoblastic leukemia as an important milestone, with a PDUFA target action date of Nov. 16. According to Autolus, obe-cel is a CD19 CAR T cell investigational therapy designed to overcome the limitations in clinical activity and safety compared to current CD19 CAR T cell therapies. The FDA in January pushed for a class-wide boxed warning on all commercial BCMA- and CD19-directed CAR T cell immunotherapies due to the “risk of T cell malignancies, with serious outcomes, including hospitalization and death.” “There was correlation but there wasn’t necessarily causation,” Majors said about the regulator’s findings on CAR T therapies and secondary cancers, noting that “the benefits of these therapies continue to outweigh the risks” providing an “important tool at the disposal of physicians for patients with serious, aggressive forms of cancer.”

45 percent reduction in risk of death achieved with CARVYKTI® after three-year follow-up in landmark CARTITUDE-4 study Data featured in a late-breaking oral presentation at the 2024 International Myeloma Society Annual Meeting RIO DE JANEIRO, Sept. 27, 2024 /PRNewswire/ -- Johnson & Johnson (NYSE:JNJ) announced today long-term results from the Phase 3 CARTITUDE-4 study that show a single infusion of CARVYKTI® (ciltacabtagene autoleucel) significantly extended overall survival (OS) in patients with relapsed or lenalidomide-refractory multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor (PI), reducing the risk of death by 45 percent versus standard therapies of pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd).1 With these data, CARVYKTI® is now the first and only cell therapy to improve OS versus standard therapies for patients with lenalidomide-refractory multiple myeloma as early as second line.1 Findings were featured as a late-breaking oral presentation at the 2024 International Myeloma Society (IMS) Annual Meeting (Abstract #OA-65).1 "The three-year follow-up data from the Phase 3 CARTITUDE-4 study show a statistically significant and clinically meaningful improvement in overall survival and quality-of-life measures with CARVYKTI versus standard therapies—meaningful results that have the potential to transform the multiple myeloma treatment landscape," said Binod Dhakal, M.D., M.S., Associate Professor of Medicine at the Medical College of Wisconsin, Division of Hematology, and study investigator.* "This adds to the growing body of data reinforcing the promise of a single infusion of CARVYKTI, which, in addition to demonstrating a significant overall survival benefit, also offers patients the opportunity of a period free from multiple myeloma treatment as early as second line." The Phase 3 CARTITUDE-4 study evaluated CARVYKTI® compared to standard therapies of PVd or DPd for the treatment of patients with relapsed or lenalidomide-refractory multiple myeloma after one prior line of therapy.1 Patients who received one to three prior lines of therapy, including a PI and immunomodulatory agent (IMiD), and were lenalidomide-refractory were randomized (CARVYKTI® [cilta-cel], n=208, standard therapies, n=211).1 At median follow-up of almost three years (34 months), median OS for patients treated with both CARVYKTI® or standard therapies was not reached (NR) (95 percent Confidence Interval [CI], not estimable (NE) – NE) and (95 percent CI, 37.75 months – NE) (Hazard Ratio [HR], 0.55; 95 percent CI, 0.39-0.79; P=0.0009).1 At 30-month follow-up, OS rates were 76 percent for patients on the CARVYKTI® arm and 64 percent for patients on the standard therapies arm.1 These data show CARVYKTI® significantly extended OS for patients compared to standard therapies.1 In patients randomized to the CARVYKTI® arm, CARVYKTI® reduced the risk of death by 45 percent compared to standard therapies demonstrating clinically meaningful responses for patients as early as after first relapse.1 Median progression-free survival (PFS) was NR in patients treated with CARVYKTI® (95 percent CI, 34.50 months – NE) and 11.79 months (95 percent CI, 9.66-14.00) in patients treated with standard therapies demonstrating sustained deep and durable responses.1 Patients treated with CARVYKTI® had a 77 percent complete response or better, and 85 percent overall response rate. Patients treated with CARVYKTI® demonstrated a 62 percent minimal residual disease (MRD) negativity (10^-5) and 57 percent MRD-negativity (10^-6) compared to patients treated with standard therapies (18.5 percent, 9 percent), respectively.1 Median duration of response was NR (95 percent CI, NE-NE) in patients treated with CARVYKTI® and 18.7 months (95 percent CI, 12.9-23.7) for patients treated with standard therapies.1 Median time to symptom worsening based on the Multiple Myeloma Symptom and Impact Questionnaire (MySlm-Q) was NR (95 percent CI, NE-NE) with CARVYKTI® and 34.33 months (95 percent CI, 32,20-NE) with patients treated with standard therapies (HR, 0.38; 95 percent CI, 0.24-0.61; P<0.0001).1 The safety profile of cilta-cel versus standard therapies was consistent with previous analysis. In the safety analysis [cilta-cel, n=208, standard therapies, n=208], 97 percent of patients in both arms experienced grade 3/4 treatment-emergent adverse events (TEAEs) with cytopenia being the most common.1 Treatment-emergent infections occurred in 64 percent of patients in the CARVYKTI® arm and 76 percent of patients who received standard therapies with 28 percent and 30 percent being classified as grade 3/4, respectively.1 In the CARVYKTI® arm, there were seven patients with hematologic second primary malignancies, 50 patients died and of those patients, 21 died due to progressive disease.1 One patient treated with standard therapies experienced a hematologic second primary malignancy, 82 patients died and of those patients, 51 died due to progressive disease.1 "CARVYKTI is the first and only cell therapy approved for the treatment of patients with myeloma as early as second line, and now also the first and only cell therapy to improve overall survival and demonstrate improved patient quality-of-life outcomes versus standard therapies for patients with lenalidomide-refractory multiple myeloma," said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Innovative Medicine, Johnson & Johnson. "At Johnson & Johnson, we remain committed to addressing unmet need through the development of innovative treatments for patients and healthcare providers, and we look forward to submitting these results to local health authorities worldwide." The U.S. FDA and European Commission approved CARVYKTI® for the treatment of adult patients with relapsed or refractory multiple myeloma who have received a least one prior line of therapy including a PI, IMiD, and are refractory to lenalidomide earlier this year. Globally, we have now launched CARVYKTI® in 5 countries and treated more than 3,500 patients. About CARTITUDE-4 CARTITUDE-4 (NCT04181827) is the first randomized Phase 3 study evaluating the efficacy and safety of CARVYKTI®. The study compares CARVYKTI® with standard of care treatments PVd or DPd in adult patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy. The primary endpoint of the study is progression-free survival (PFS); safety, OS, minimal residual disease negative rate and overall response rate are secondary endpoints. About CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) CARVYKTI® (cilta-cel) received U.S. Food and Drug Administration approval in February 2022 for the treatment of adults with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. In April 2024, CARVYKTI® was approved in the U.S. for treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor, an immunomodulatory agent, and who are refractory to lenalidomide, following a unanimous (11 to 0) FDA Oncologic Drugs Advisory Committee (ODAC) recommendation in support of this new indication. In April 2024, the European Medicines Agency (EMA) approved a Type II variation for CARVYKTI® for the treatment of adults with relapsed and refractory multiple myeloma who have received at least one prior therapy, including an immunomodulatory agent and a proteasome inhibitor, have demonstrated disease progression on the last therapy, and are refractory to lenalidomide. In September 2022, Japan's Ministry of Health, Labour and Welfare (MHLW) approved CARVYKTI® for the treatment of adults with relapsed or refractory multiple myeloma in patients that have no history of CAR-positive T cell infusion therapy targeting BCMA and who have received three or more lines of therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 monoclonal antibody, and in whom multiple myeloma has not responded to or has relapsed following the most recent therapy. CARVYKTI® is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient's own T-cells with a transgene encoding chimeric antigen receptor (CAR) that directs the CAR-positive T cells to eliminate cells that express BCMA. BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells. The CARVYKTI® CAR protein features two BCMA-targeting single domains designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells. In December 2017, Janssen Biotech, Inc., a Johnson & Johnson company, entered into an exclusive worldwide license and collaboration agreement with Legend Biotech USA, Inc. to develop and commercialize CARVYKTI®. For more information, visit . About Multiple Myeloma Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.2 In multiple myeloma, these plasma cells proliferate and spread rapidly and replace normal cells in the bone marrow with tumors.3 Multiple myeloma is the third most common blood cancer worldwide and remains an incurable disease.4 In 2024, it was estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 people would die from the disease.5 People living with multiple myeloma have a 5-year survival rate of 59.8 percent.6 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels and kidney problems or infections.7,8 CARVYKTI® IMPORTANT SAFETY INFORMATION INDICATIONS AND USAGE CARVYKTI® (ciltacabtagene autoleucel) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Increased early mortality - In CARTITUDE-4, a (1:1) randomized controlled trial, there was a numerically higher percentage of early deaths in patients randomized to the CARVYKTI® treatment arm compared to the control arm. Among patients with deaths occurring within the first 10 months from randomization, a greater proportion (29/208; 14%) occurred in the CARVYKTI® arm compared to (25/211; 12%) in the control arm. Of the 29 deaths that occurred in the CARVYKTI® arm within the first 10 months of randomization, 10 deaths occurred prior to CARVYKTI® infusion, and 19 deaths occurred after CARVYKTI® infusion. Of the 10 deaths that occurred prior to CARVYKTI® infusion, all occurred due to disease progression, and none occurred due to adverse events. Of the 19 deaths that occurred after CARVYKTI® infusion, 3 occurred due to disease progression, and 16 occurred due to adverse events. The most common adverse events were due to infection (n=12). Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® for RRMM in the CARTITUDE-1 & 4 studies (N=285), CRS occurred in 84% (238/285), including ≥Grade 3 CRS (ASCT 2019) in 4% (11/285) of patients. Median time to onset of CRS, any grade, was 7 days (range: 1 to 23 days). CRS resolved in 82% with a median duration of 4 days (range: 1 to 97 days). The most common manifestations of CRS in all patients combined (≥10%) included fever (84%), hypotension (29%) and aspartate aminotransferase increased (11%). Serious events that may be associated with CRS include pyrexia, hemophagocytic lymphohistiocytosis, respiratory failure, disseminated intravascular coagulation, capillary leak syndrome, and supraventricular and ventricular tachycardia. CRS occurred in 78% of patients in CARTITUDE-4 (3% Grade 3 to 4) and in 95% of patients in CARTITUDE-1 (4% Grade 3 to 4). Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS. Ensure that a minimum of two doses of tocilizumab are available prior to infusion of CARVYKTI®. Of the 285 patients who received CARVYKTI® in clinical trials, 53% (150/285) patients received tocilizumab; 35% (100/285) received a single dose, while 18% (50/285) received more than 1 dose of tocilizumab. Overall, 14% (39/285) of patients received at least one dose of corticosteroids for treatment of CRS. Monitor patients at least daily for 10 days following CARVYKTI® infusion at a REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion. At the first sign of CRS, immediately institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. Neurologic toxicities, which may be severe, life-threatening, or fatal, occurred following treatment with CARVYKTI®. Neurologic toxicities included ICANS, neurologic toxicity with signs and symptoms of parkinsonism, GBS, immune mediated myelitis, peripheral neuropathies, and cranial nerve palsies. Counsel patients on the signs and symptoms of these neurologic toxicities, and on the delayed nature of onset of some of these toxicities. Instruct patients to seek immediate medical attention for further assessment and management if signs or symptoms of any of these neurologic toxicities occur at any time. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies for RRMM, one or more neurologic toxicities occurred in 24% (69/285), including ≥Grade 3 cases in 7% (19/285) of patients. Median time to onset was 10 days (range: 1 to 101) with 63/69 (91%) of cases developing by 30 days. Neurologic toxicities resolved in 72% (50/69) of patients with a median duration to resolution of 23 days (range: 1 to 544). Of patients developing neurotoxicity, 96% (66/69) also developed CRS. Subtypes of neurologic toxicities included ICANS in 13%, peripheral neuropathy in 7%, cranial nerve palsy in 7%, parkinsonism in 3%, and immune mediated myelitis in 0.4% of the patients. Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS): Patients receiving CARVYKTI® may experience fatal or life-threatening ICANS following treatment with CARVYKTI®, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, ICANS occurred in 13% (36/285), including Grade ≥3 in 2% (6/285) of the patients. Median time to onset of ICANS was 8 days (range: 1 to 28 days). ICANS resolved in 30 of 36 (83%) of patients with a median time to resolution of 3 days (range: 1 to 143 days). Median duration of ICANS was 6 days (range: 1 to 1229 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. Of patients with ICANS 97% (35/36) had CRS. The onset of ICANS occurred during CRS in 69% of patients, before and after the onset of CRS in 14% of patients respectively. Immune Effector Cell-associated Neurotoxicity Syndrome occurred in 7% of patients in CARTITUDE-4 (0.5% Grade 3) and in 23% of patients in CARTITUDE-1 (3% Grade 3). The most frequent ≥2% manifestations of ICANS included encephalopathy (12%), aphasia (4%), headache (3%), motor dysfunction (3%), ataxia (2%) and sleep disorder (2%). Monitor patients at least daily for 10 days following CARVYKTI® infusion at the REMS-certified healthcare facility for signs and symptoms of ICANS. Rule out other causes of ICANS symptoms. Monitor patients for signs or symptoms of ICANS for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed. Parkinsonism: Neurologic toxicity with parkinsonism has been reported in clinical trials of CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, parkinsonism occurred in 3% (8/285), including Grade ≥ 3 in 2% (5/285) of the patients. Median time to onset of parkinsonism was 56 days (range: 14 to 914 days). Parkinsonism resolved in 1 of 8 (13%) of patients with a median time to resolution of 523 days. Median duration of parkinsonism was 243.5 days (range: 62 to 720 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. The onset of parkinsonism occurred after CRS for all patients and after ICANS for 6 patients. Parkinsonism occurred in 1% of patients in CARTITUDE-4 (no Grade 3 to 4) and in 6% of patients in CARTITUDE-1 (4% Grade 3 to 4). Manifestations of parkinsonism included movement disorders, cognitive impairment, and personality changes. Monitor patients for signs and symptoms of parkinsonism that may be delayed in onset and managed with supportive care measures. There is limited efficacy information with medications used for the treatment of Parkinson's disease for the improvement or resolution of parkinsonism symptoms following CARVYKTI® treatment. Guillain-Barré syndrome: A fatal outcome following GBS occurred following treatment with CARVYKTI® despite treatment with intravenous immunoglobulins. Symptoms reported include those consistent with Miller-Fisher variant of GBS, encephalopathy, motor weakness, speech disturbances, and polyradiculoneuritis. Monitor for GBS. Evaluate patients presenting with peripheral neuropathy for GBS. Consider treatment of GBS with supportive care measures and in conjunction with immunoglobulins and plasma exchange, depending on severity of GBS. Immune mediated myelitis: Grade 3 myelitis occurred 25 days following treatment with CARVYKTI® in CARTITUDE-4 in a patient who received CARVYKTI® as subsequent therapy. Symptoms reported included hypoesthesia of the lower extremities and the lower abdomen with impaired sphincter control. Symptoms improved with the use of corticosteroids and intravenous immune globulin. Myelitis was ongoing at the time of death from other cause. Peripheral neuropathy occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, peripheral neuropathy occurred in 7% (21/285), including Grade ≥3 in 1% (3/285) of the patients. Median time to onset of peripheral neuropathy was 57 days (range: 1 to 914 days). Peripheral neuropathy resolved in 11 of 21 (52%) of patients with a median time to resolution of 58 days (range: 1 to 215 days). Median duration of peripheral neuropathy was 149.5 days (range: 1 to 692 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. Peripheral neuropathies occurred in 7% of patients in CARTITUDE-4 (0.5% Grade 3 to 4) and in 7% of patients in CARTITUDE-1 (2% Grade 3 to 4). Monitor patients for signs and symptoms of peripheral neuropathies. Patients who experience peripheral neuropathy may also experience cranial nerve palsies or GBS. Cranial nerve palsies occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, cranial nerve palsies occurred in 7% (19/285), including Grade ≥3 in 1% (1/285) of the patients. Median time to onset of cranial nerve palsies was 21 days (range: 17 to 101 days). Cranial nerve palsies resolved in 17 of 19 (89%) of patients with a median time to resolution of 66 days (range: 1 to 209 days). Median duration of cranial nerve palsies was 70 days (range: 1 to 262 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. Cranial nerve palsies occurred in 9% of patients in CARTITUDE-4 (1% Grade 3 to 4) and in 3% of patients in CARTITUDE-1 (1% Grade 3 to 4). The most frequent cranial nerve affected was the 7th cranial nerve. Additionally, cranial nerves III, V, and VI have been reported to be affected. Monitor patients for signs and symptoms of cranial nerve palsies. Consider management with systemic corticosteroids, depending on the severity and progression of signs and symptoms. Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS): Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, HLH/MAS occurred in 1% (3/285) of patients. All events of HLH/MAS had onset within 99 days of receiving CARVYKTI®, with a median onset of 10 days (range: 8 to 99 days) and all occurred in the setting of ongoing or worsening CRS. The manifestations of HLH/MAS included hyperferritinemia, hypotension, hypoxia with diffuse alveolar damage, coagulopathy and hemorrhage, cytopenia and multi-organ dysfunction, including renal dysfunction and respiratory failure. Patients who develop HLH/MAS have an increased risk of severe bleeding. Monitor hematologic parameters in patients with HLH/MAS and transfuse per institutional guidelines. Fatal cases of HLH/MAS occurred following treatment with CARVYKTI®. HLH is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of HLH/MAS should be administered per institutional standards. CARVYKTI® REMS: Because of the risk of CRS and neurologic toxicities, CARVYKTI® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI® REMS. Further information is available at or 1-844-672-0067. Prolonged and Recurrent Cytopenias: Patients may exhibit prolonged and recurrent cytopenias following lymphodepleting chemotherapy and CARVYKTI® infusion. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, Grade 3 or higher cytopenias not resolved by day 30 following CARVYKTI® infusion occurred in 62% (176/285) of the patients and included thrombocytopenia 33% (94/285), neutropenia 27% (76/285), lymphopenia 24% (67/285) and anemia 2% (6/285). After Day 60 following CARVYKTI® infusion 22%, 20%, 5%, and 6% of patients had a recurrence of Grade 3 or 4 lymphopenia, neutropenia, thrombocytopenia, and anemia respectively, after initial recovery of their Grade 3 or 4 cytopenia. Seventy-seven percent (219/285) of patients had one, two or three or more recurrences of Grade 3 or 4 cytopenias after initial recovery of Grade 3 or 4 cytopenia. Sixteen and 25 patients had Grade 3 or 4 neutropenia and thrombocytopenia, respectively, at the time of death. Monitor blood counts prior to and after CARVYKTI® infusion. Manage cytopenias with growth factors and blood product transfusion support according to local institutional guidelines. Infections: CARVYKTI® should not be administered to patients with active infection or inflammatory disorders. Severe, life-threatening, or fatal infections, occurred in patients after CARVYKTI® infusion. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, infections occurred in 57% (163/285), including ≥Grade 3 in 24% (69/285) of patients. Grade 3 or 4 infections with an unspecified pathogen occurred in 12%, viral infections in 6%, bacterial infections in 5%, and fungal infections in 1% of patients. Overall, 5% (13/285) of patients had Grade 5 infections, 2.5% of which were due to COVID-19. Patients treated with CARVYKTI® had an increased rate of fatal COVID-19 infections compared to the standard therapy arm. Monitor patients for signs and symptoms of infection before and after CARVYKTI® infusion and treat patients appropriately. Administer prophylactic, pre-emptive and/or therapeutic antimicrobials according to the standard institutional guidelines. Febrile neutropenia was observed in 5% of patients after CARVYKTI® infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids and other supportive care, as medically indicated. Counsel patients on the importance of prevention measures. Follow institutional guidelines for the vaccination and management of immunocompromised patients with COVID-19. Viral Reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients with hypogammaglobulinemia. Perform screening for Cytomegalovirus (CMV), HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) or any other infectious agents if clinically indicated in accordance with clinical guidelines before collection of cells for manufacturing. Consider antiviral therapy to prevent viral reactivation per local institutional guidelines/clinical practice. Hypogammaglobulinemia: can occur in patients receiving treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, hypogammaglobulinemia adverse event was reported in 36% (102/285) of patients; laboratory IgG levels fell below 500mg/dl after infusion in 93% (265/285) of patients. Hypogammaglobulinemia either as an adverse reaction or laboratory IgG level below 500mg/dl, after infusion occurred in 94% (267/285) of patients treated. Fifty six percent (161/285) of patients received intravenous immunoglobulin (IVIG) post CARVYKTI® for either an adverse reaction or prophylaxis. Monitor immunoglobulin levels after treatment with CARVYKTI® and administer IVIG for IgG <400 mg/dL. Manage per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis. Use of Live Vaccines: The safety of immunization with live viral vaccines during or following CARVYKTI® treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during CARVYKTI® treatment, and until immune recovery following treatment with CARVYKTI®. Hypersensitivity Reactions occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, hypersensitivity reactions occurred in 5% (13/285), all of which were ≤Grade 2. Manifestations of hypersensitivity reactions included flushing, chest discomfort, tachycardia, wheezing, tremor, burning sensation, non-cardiac chest pain, and pyrexia. Serious hypersensitivity reactions, including anaphylaxis, may be due to the dimethyl sulfoxide (DMSO) in CARVYKTI®. Patients should be carefully monitored for 2 hours after infusion for signs and symptoms of severe reaction. Treat promptly and manage patients appropriately according to the severity of the hypersensitivity reaction. Secondary Malignancies: Patients treated with CARVYKTI® may develop secondary malignancies. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, myeloid neoplasms occurred in 5% (13/285) of patients (9 cases of myelodysplastic syndrome, 3 cases of acute myeloid leukemia, and 1 case of myelodysplastic syndrome followed by acute myeloid leukemia). The median time to onset of myeloid neoplasms was 447 days (range: 56 to 870 days) after treatment with CARVYKTI®. Ten of these 13 patients died following the development of myeloid neoplasms; 2 of the 13 cases of myeloid neoplasm occurred after initiation of subsequent antimyeloma therapy. Cases of myelodysplastic syndrome and acute myeloid leukemia have also been reported in the post marketing setting. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including CARVYKTI®. Mature T-cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusions, and may include fatal outcomes. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Janssen Biotech, Inc. at 1-800-526-7736 for reporting and to obtain instructions on collection of patient samples. Effects on Ability to Drive and Use Machines: Due to the potential for neurologic events, including altered mental status, seizures, neurocognitive decline or neuropathy, patients receiving CARVYKTI® are at risk for altered or decreased consciousness or coordination in the 8 weeks following CARVYKTI® infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery during this initial period, and in the event of new onset of any neurologic toxicities. ADVERSE REACTIONS The most common nonlaboratory adverse reactions (incidence greater than 20%) are pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections-pathogen unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting. The most common Grade 3 or 4 laboratory adverse reactions (incidence greater than or equal to 50%) include lymphopenia, neutropenia, white blood cell decreased, thrombocytopenia, and anemia. Please read full Prescribing Information, including Boxed Warning, for CARVYKTI®. 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., and Janssen Global Services, LLC are 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 CARVYKTI® (ciltacabtagene autoleucel; cilta-cel). 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, Janssen Biotech, Inc. Janssen Global Services, LLC 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 December 31, 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 Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen Global Services, LLC, nor Johnson & Johnson undertake to update any forward-looking statement as a result of new information or future events or developments. * Dr. Binod Dhakal, Associate Professor of Medicine at the Medical College of Wisconsin, Division of Hematology, has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work. 1 Mateos, et al. Overall Survival (OS) With Ciltacabtagene Autoleucel (Cilta-cel) Versus Standard of Care (SoC) in Lenalidomide (Len)-Refractory Multiple Myeloma (MM): Phase 3 CARTITUDE-4 Study Update. International Myeloma Society 2024 Annual Meeting. September 2024. 2 Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol. 2020;95(5):548-5672020;95(5):548-567. 3 National Cancer Institute. Plasma Cell Neoplasms. . Accessed June 2024. 4 City of Hope. Multiple Myeloma: Causes, Symptoms & Treatments. . Accessed June 2024. 5 American Cancer Society. Key Statistics About Multiple Myeloma. . Accessed June 2024. 6 SEER Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. . Accessed June 2024. 7 American Cancer Society. What is Multiple Myeloma? . Accessed June 2024. 8 American Cancer Society. Multiple Myeloma Early Detection, Diagnosis, and Staging. . Accessed June 2024. SOURCE Johnson & Johnson WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED