Bleximenib

SPRING HOUSE, Pa., (May 12, 2026) – Johnson & Johnson (NYSE: JNJ) announced today more than 30 hematology abstracts featuring data in multiple myeloma and leukemia, as well as in warm autoimmune hemolytic anemia (wAIHA), will be shared at the European Hematology Association (EHA) 2026 Congress from June 11-14 in Stockholm, Sweden. Among the results to be presented in a plenary session is the Phase 3 MonumenTAL-3 study investigating TALVEY® (talquetamab-tgvs), a GPRC5D bispecific antibody, in combination with DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) with or without pomalidomide in relapsed/refractory multiple myeloma. New pivotal data from the Phase 2/3 ENERGY study evaluating IMAAVY® (nipocalimab-aahu)a in wAIHA, a rare autoantibody-driven disease in which autoantibodies attach to and destroy red blood cells, will also be presented in an oral session.1 The U.S. Food and Drug Administration (FDA) recently granted Priority Review to IMAAVY ® in wAIHA. Perspectives on key data readouts at EHA“The data we are sharing at EHA 2026 reflect the depth and breadth of our clinical innovations in blood cancer, led by the Phase 3 MonumenTAL-3 results, which are an exciting next step in exploring how we can continue to expand our portfolio of differentiated and combinable therapies in multiple myeloma,” said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson. “Together with additional data in leukemia, these findings underscore our leadership in hematology and our continued commitment to advancing meaningful innovation for patients living with complex blood cancers.” “wAIHA is marked by debilitating fatigue and serious complications of severe anemia. There is an unmet need for an approved treatment for wAIHA that may provide rapid control and sustained relief from symptoms while preserving critical immune functions,” said David Lee, M.D., Ph.D., Global Immunology Therapeutic Area Head, Johnson & Johnson. “The first presentation of Phase 2/3 results from the ENERGY study highlights the potential of an immunoselective treatment approach for wAIHA, which is a rare disease with no U.S. FDA-approved treatments.” Updated data in multiple myelomaData at EHA will highlight advances in multiple myeloma treatment, including combination regimens and emerging therapies for patients with newly diagnosed and relapsed/refractory multiple myeloma. New results from the Phase 3 MonumenTAL-3 study evaluating TALVEY® in combination with DARZALEX FASPRO® with or without pomalidomide versus DARZALEX FASPRO®, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma (Presented as “One of the six best abstracts” during the Plenary Abstracts Session #S100) Subgroup analysis based on cytogenetic and functional risk from the MajesTEC-3 study evaluating TECVAYLI® (teclistamab-cqyv) in combination with DARZALEX FASPRO® in relapsed/refractory multiple myeloma (Oral Abstract #S198) Cytogenetic subgroup analysis from the Phase 3 CARTITUDE-4 study evaluating CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) in patients with lenalidomide-refractory multiple myeloma responding to bridging therapy (Poster Abstract #PF767) [Encore of ASCO 2026] Subgroup analysis from the Phase 3 PERSEUS study evaluating the benefit of DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) in transplant-eligible patients with high- and standard-risk multiple myeloma (Poster Abstract #PS1869) [Encore of ASCO 2026] Final subgroup analysis from the Phase 3 CEPHEUS study evaluating DARZALEX FASPRO® in combination with bortezomib, lenalidomide, and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma (Oral Abstract #S196) [Encore of ASCO 2026] Results from the Phase 3 MajesTEC-9 study of TECVAYLI® versus standard of care therapies as early as second line in patients with multiple myeloma (Oral Abstract #S195) [Encore of ASCO 2026] New research in warm autoimmune hemolytic anemia (wAIHA)Pivotal study assessed hemoglobin response and fatigue improvement compared to placebo in patients with warm autoimmune hemolytic anemia. Results from the pivotal ENERGY Phase 2/3 study evaluating the efficacy and safety of IMAAVY®in patients with wAIHA compared with placebo (Oral Abstract #S300) Assessment of the effects of IMAAVY®on fatigue in patients with wAIHA, measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale (Oral Abstract #S325) Confirmatory evidence on the pharmacodynamic effect of IMAAVY®and the correlation with clinical improvement in patients with wAIHA (Poster Abstract #PF1297) Key data presentations in leukemiaNew and updated data highlight clinical advances in leukemia, including acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL), across targeted therapies and fixed-duration treatment approaches. Safety analyses from the cAMelot-1 and ALE1002 clinical trials of bleximenib (JNJ-75276617), an investigational oral menin inhibitor, evaluating the presence of QTc interval prolongation when given as monotherapy or in combination with AML-directed therapies for KMT2A or NPM1 Altered AML (Poster Abstract #PF555) Primary analysis from the Phase 2 TAILOR study evaluating the safety and efficacy of dose-modified fixed-duration IMBRUVICA®(ibrutinib) plus venetoclax in previously untreated CLL (Poster Abstract #PF606) Real-world analysis from the prospective REALITY-WW study evaluating first-line fixed-duration IMBRUVICA® in combination with venetoclax in patients with CLL (Poster Abstract #PF613) Information on Johnson & Johnson sponsored abstracts is available on JNJ.com. Editor’s Notesa. IMAAVY® is not approved by the U.S. FDA for the treatment of wAIHAABOUT MULTIPLE MYELOMA Multiple myeloma is a complex 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.4 More than 180,000 new cases of multiple myeloma are diagnosed globally each year.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 In recent years, overall survival has improved from years to decades, with effective treatment options now available across every stage and line of therapy.9 ABOUT WARM AUTOIMMUNE HEMOLYTIC ANEMIAWarm autoimmune hemolytic anemia (wAIHA) is a rare, life-threatening condition where autoantibodies attach to and destroy red blood cells (RBCs), resulting in anemia. Approximately 1-3 new people per 100,000 are affected by wAIHA per year, and about 1 in 8,000 individuals are living with the condition.10,11 This condition affects both women and men, and can affect people at any age with incidence increasing over the age of 50.12,13 Additionally, people with wAIHA are at increased risk of other serious complications such as venous thrombotic events, acute renal failure, and infection.14 There are no U.S. FDA-approved drugs indicated for wAIHA, and treatment typically consists of unapproved corticosteroids, broad immunosuppressants, and B-cell directed therapies.11 With an unmet need for treatment in wAIHA, novel therapies like nipocalimab are being developed to potentially address this need.13 ABOUT ACUTE MYELOID LEUKEMIA Acute myeloid leukemia (AML) is an aggressive, fast-growing blood cancer that originates in the bone marrow and is marked by the uncontrolled proliferation of immature white blood cells known as myeloblasts.15,16 These malignant cells crowd out healthy blood-forming cells, leading to complications such as anemia, infections and bleeding.17 Acute myeloid leukemia progresses rapidly, often requiring immediate treatment after diagnosis.16 It is the most common type of acute leukemia in adults, with a median age of diagnosis around 70 years.15 Despite treatment advances, acute myeloid leukemia remains associated with poor patient outcomes, particularly in older adults or those with high-risk genetic profiles.18 The five-year survival rate remains the lowest among leukemias, with outcomes especially poor in patients with KMT2Ar or NPM1m where relapse/refractory disease survival can be as short as 2 to 3 months after a second relapse – highlighting a significant unmet medical need.18 ABOUT TALVEY® TALVEY® (talquetamab-tgvs) received approval from the U.S. FDA in August 2023 as a first-in-class GPRC5D-targeting bispecific antibody for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.19 Since U.S. FDA approval, 7,700 patients were treated with TALVEY®. The European Commission (EC) granted conditional marketing authorization (CMA) of TALVEY®(talquetamab-tgvs) in August 2023 as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.20 TALVEY® is a bispecific T-cell engaging antibody that binds to the CD3 receptor expressed on the surface of T-cells and G protein-coupled receptor class C group 5 member D (GPRC5D), a novel multiple myeloma target which is highly expressed on the surface of multiple myeloma cells and non-malignant plasma cells, as well as some healthy tissues such as epithelial cells of the skin and tongue. ABOUT DARZALEX FASPRO® AND DARZALEX® DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for 11 indications in multiple myeloma, four of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.21 It is the only subcutaneous CD38-directed antibody approved to treat patients with multiple myeloma. DARZALEX FASPRO® is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology. DARZALEX® (daratumumab) received U.S. FDA approval in November 2015 and is approved in eight indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant-eligible and ineligible.22 In 2025, DARZALEX FASPRO® was approved by the U.S. FDA and EMA as the first and only treatment for patients with high-risk smoldering multiple myeloma. DARZALEX® is the first CD38-directed antibody approved to treat multiple myeloma.22 DARZALEX®-based regimens have been used in the treatment of more than 748,000 patients worldwide and more than 68,000 patients in the U.S. alone. In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab. For more information, visit www.DARZALEX.com. ABOUT IMAAVY®IMAAVY® (nipocalimab-aahu) is an immunoselective treatment designed to target, bind with high affinity, and block FcRn, reducing circulating immunoglobulin G (IgG) antibodies that drive disease while also preserving key immune functions. IMAAVY® is currently approved for the treatment of generalized Myasthenia Gravis (gMG) in adults and pediatric patients 12 years of age and older who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive.23 Nipocalimab is being investigated across three key segments in the autoantibody space including Rheumatologic diseases, Rare Autoantibody diseases, and Maternal Fetal diseases mediated by maternal alloantibodies, in which blockade of IgG binding to FcRn in the placenta is believed to limit transplacental transfer of maternal alloantibodies to the fetus.24,25,26,27,28,29,30,31,32,33 The U.S. FDA and European Medicines Agency (EMA) have granted several key designations to nipocalimab including: EU EMA Orphan medicinal product designation for HDFN in October 2019 and fetal and neonatal alloimmune thrombocytopenia (FNAIT in April 2025 U.S. FDA Fast Track designation in hemolytic disease of the fetus and newborn (HDFN) and warm autoimmune hemolytic anemia (wAIHA) in July 2019, gMG in December 2021, fetal and neonatal alloimmune thrombocytopenia (FNAIT) in March 2024, Sjögren’s disease (SjD) in March 2025, and systemic lupus erythematosus (SLE) in January 2026 U.S. FDA Orphan drug status for wAIHA in December 2019, HDFN in June 2020, gMG in February 2021, chronic inflammatory demyelinating polyneuropathy (CIDP) in October 2021 and FNAIT in December 2023 U.S. FDA Breakthrough Therapy designation for HDFN in February 2024 and for SjD in November 2024 U.S. FDA granted Priority Review in gMG in Q4 2024 and wAIHA in Q2 2026 The legal manufacturer for IMAAVY ® is Janssen Biotech, Inc. ABOUT TECVAYLI®TECVAYLI® (teclistamab-cqyv) is a first-in-class, bispecific T-cell engager antibody therapy that uses innovative science to activate the immune system by binding to the CD3 receptor expressed on the surface of T-cells and to the B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells.34 TECVAYLI® received accelerated approval from the U.S. FDA in October 2022 as an off-the-shelf (or ready-to-use) antibody that is administered as a subcutaneous treatment for adult patients with relapsed or refractory multiple myeloma (RRMM) who received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody. In February 2024, the U.S. FDA approved the supplemental Biologics License Application (sBLA) for TECVAYLI® for a reduced dosing frequency of 1.5 mg/kg every two weeks in patients with RRMM who achieved and maintained a complete response (CR) or better for a minimum of six months. In March 2026, the U.S. FDA approved TECVAYLI® in combination with DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent. The supplemental Biologics License Application was proactively selected for the Commissioner’s National Priority Voucher Pilot Program and also granted the application Breakthrough Therapy Designation and Real-Time Oncology Review. This approval expanded the use of TECVAYLI® into earlier lines of therapy and is the first bispecific antibody-based combination regimen in this setting, offering a potential new standard of care as early as second line. To date, more than 26,000 patients have been treated worldwide with TECVAYLI®. The European Commission (EC) granted TECVAYLI® conditional marketing authorization in August 2022 as monotherapy for the treatment of adult patients with RRMM who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody, and have demonstrated disease progression since the last therapy. In August 2023, the EC approved a Type II variation application for TECVAYLI®, providing the option for a reduced dosing frequency of 1.5 mg/kg every two weeks (Q2W) in patients who have achieved a complete response or better for a minimum of six months. For more information, visit www.TECVAYLI.com. ABOUT CARVYKTI® 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.35 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) U.S. 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, 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. CARVYKTI® is available in 17 markets worldwide and has been used to treat more than 11,000 patients globally. 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 www.CARVYKTI.com. ABOUT IMBRUVICA®IMBRUVICA® (ibrutinib) is a once-daily oral medication that is jointly developed and commercialized by Janssen Biotech, Inc., and Pharmacyclics LLC, an AbbVie company. IMBRUVICA® blocks the BTK protein, which is needed by normal and abnormal B cells, including specific cancer cells, to multiply and spread. By blocking BTK, IMBRUVICA® may help move abnormal B cells out of their nourishing environments and inhibit their proliferation.36,37,38 IMBRUVICA® has been used to treat more than 325,000 patients worldwide over the last decade. There are more 70 company-sponsored clinical trials, including 18 Phase 3 studies, spanning more than 13 years evaluating the efficacy and safety of IMBRUVICA®. IMBRUVICA® was first approved by the U.S. FDA in November 2013, and today is indicated for adult patients in four disease areas. To date, IMBRUVICA® has been approved in more than 100 countries/territories for one or more of the following indications: the treatment of adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with or without 17p deletion (del17p); adults with Waldenström’s macroglobulinemia (WM); adults with mantle cell lymphoma (MCL); adults with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy; and adult and pediatric patients aged one year and older with previously treated chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy.39 TALVEY® IMPORTANT SAFETY INFORMATION INDICATION AND USAGE TALVEY® (talquetamab-tgvs) is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). IMPORTANT SAFETY INFORMATION WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY, including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TALVEY®. Initiate TALVEY® treatment with step-up dosing to reduce the risk of CRS. Withhold TALVEY® until CRS resolves or permanently discontinue based on severity. Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), and serious and life-threatening or fatal reactions, can occur with TALVEY®. Monitor patients for signs and symptoms of neurologic toxicity including ICANS during treatment and treat promptly. Withhold or permanently discontinue TALVEY® based on severity. Because of the risk of CRS and neurologic toxicity, including ICANS, TALVEY® is available only through a restricted program called the TECVAYLI® and TALVEY® Risk Evaluation and Mitigation Strategy (REMS). CONTRAINDICATIONS: None. WARNINGS AND PRECAUTIONS Cytokine Release Syndrome (CRS): TALVEY® can cause cytokine release syndrome, including life-threatening or fatal reactions. In the clinical trial, CRS occurred in 76% of patients who received TALVEY® at the recommended dosages, with Grade 1 CRS occurring in 57% of patients, Grade 2 in 17%, and Grade 3 in 1.5%. Recurrent CRS occurred in 30% of patients. Most events occurred following step-up dose 1 (29%) or step-up dose 2(44%) at the recommended dosages. CRS occurred in 33% of patients with step-up dose 3 in the biweekly dosing schedule (N=153). CRS occurred in 30% of patients with the first 0.4 mg/kg treatment dose and in 12% of patients treated with the first 0.8 mg/kg treatment dose. The CRS rate for both dosing schedules combined was less than 3% for each of the remaining doses in Cycle 1 and less than 3% cumulatively from Cycle 2 onward. The median time to onset of CRS was 27 (range: 0.1 to 167) hours from the last dose, and the median duration was 17 (range: 0 to 622) hours. Clinical signs and symptoms of CRS include but are not limited to pyrexia, hypotension, chills, hypoxia, headache, and tachycardia. Potentially life-threatening complications of CRS may include cardiac dysfunction, acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC). Initiate therapy with step-up dosing and administer pre-treatment medications (corticosteroids, antihistamine, and antipyretics) prior to each dose of TALVEY® in the step-up dosing schedule to reduce the risk of CRS. Monitor patients following administration accordingly. In patients who experience CRS, pre-treatment medications should be administered prior to the next TALVEY® dose. Counsel patients to seek medical attention should signs or symptoms of CRS occur. At the first sign of CRS, immediately evaluate patient for hospitalization and institute treatment with supportive care based on severity, and consider further management per current practice guidelines. Withhold TALVEY® until CRS resolves or permanently discontinue based on severity. Neurologic Toxicity including ICANS: TALVEY® can cause serious, or life-threatening neurologic toxicity or fatal neurologic toxicity including immune effector cell-associated neurotoxicity syndrome (ICANS), including fatal reactions. In the clinical trial, neurologic toxicity, including ICANS, occurred in 55% of patients who received the recommended dosages, with Grade 3 or 4 neurologic toxicity occurring in 6% of patients. The most frequent neurologic toxicities were headache (20%), encephalopathy (15%), sensory neuropathy (14%), and motor dysfunction (10%). ICANS was reported in 9% of 265 patients where ICANS was collected and who received the recommended dosages. Recurrent ICANS occurred in 3% of patients. Most patients experienced ICANS following step-up dose 1 (3%), step-up dose 2 (3%), step-up dose 3 of the biweekly dosing schedule (1.8%), or the initial treatment dose of the weekly dosing schedule (2.6%) (N=156) or the biweekly dosing schedule (3.7%) (N=109). The median time to onset of ICANS was 2.5 (range: 1 to 16) days after the most recent dose with a median duration of 2 (range: 1 to 22) days. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical signs and symptoms of ICANS may include but are not limited to confusional state, depressed level of consciousness, disorientation, somnolence, lethargy, and bradyphrenia. Monitor patients for signs and symptoms of neurologic toxicity during treatment and treat promptly. At the first sign of neurologic toxicity, including ICANS, immediately evaluate the patient and provide supportive care based on severity. Withhold or permanently discontinue TALVEY® based on severity and consider further management per current practice guidelines [see Dosage and Administration (2.5)]. Due to the potential for neurologic toxicity, patients receiving TALVEY® are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during the step-up dosing schedule and for 48 hours after completion of the step-up dosing schedule, and in the event of new onset of any neurological symptoms, until symptoms resolve. TECVAYLI® and TALVEY® REMS: TALVEY® is available only through a restricted program under a REMS, called the TECVAYLI® and TALVEY® REMS because of the risks of CRS and neurologic toxicity, including ICANS. Further information about the TECVAYLI® and TALVEY® REMS program is available at www.TEC-TALREMS.com or by telephone at 1-855-810-8064. Oral Toxicity and Weight Loss: TALVEY® can cause oral toxicities, including dysgeusia, dry mouth, dysphagia, and stomatitis. In the clinical trial, 80% of patients had oral toxicity, with Grade 3 occurring in 2.1% of patients who received the recommended dosages. The most frequent oral toxicities were dysgeusia (49%), dry mouth (34%), dysphagia (23%), and ageusia (18%). The median time to onset of oral toxicity was 15 (range: 1 to 634) days, and the median time to resolution to baseline was 43 (1 to 530) days. Oral toxicity did not resolve to baseline in 65% of patients. TALVEY® can cause weight loss. In the clinical trial, 62% of patients experienced weight loss, regardless of having an oral toxicity, including 29% of patients with Grade 2 (10% or greater) weight loss and 2.7% of patients with Grade 3 (20% or greater) weight loss. The median time to onset of Grade 2 or higher weight loss was 67 (range: 6 to 407) days, and the median time to resolution was 50 (range: 1 to 403) days. Weight loss did not resolve in 57% of patients who reported weight loss. Monitor patients for signs and symptoms of oral toxicity. Counsel patients to seek medical attention should signs or symptoms of oral toxicity occur and provide supportive care as per current clinical practice, including consultation with a nutritionist. Monitor weight regularly during therapy. Evaluate clinically significant weight loss further. Withhold TALVEY® or permanently discontinue based on severity. Infections: TALVEY® can cause infections, including life-threatening or fatal infections. Serious infections occurred in 16% of patients, with fatal infections in 1.5% of patients. Grade 3 or 4 infections occurred in 17% of patients. The most common serious infections reported were bacterial infection (8%), which included sepsis and COVID-19 (2.7%). Monitor patients for signs and symptoms of infection prior to and during treatment with TALVEY® and treat appropriately. Administer prophylactic antimicrobials according to local guidelines. Withhold or consider permanent discontinuation of TALVEY® as recommended, based on severity. Cytopenias: TALVEY® can cause cytopenias, including neutropenia and thrombocytopenia. In the clinical trial, Grade 3 or 4 decreased neutrophils occurred in 35% of patients, and Grade 3 or 4 decreased platelets occurred in 22% of patients who received TALVEY®. The median time to onset for Grade 3 or 4 neutropenia was 22 (range: 1 to 312) days, and the median time to resolution to Grade 2 or lower was 8 (range: 1 to 79) days. The median time to onset for Grade 3 or 4 thrombocytopenia was 12 (range: 2 to 183) days, and the median time to resolution to Grade 2 or lower was 10 (range: 1 to 64) days. Monitor complete blood counts during treatment and withhold TALVEY® as recommended, based on severity. Skin Toxicity: TALVEY® can cause serious skin reactions, including rash, maculo-papular rash, erythema, and erythematous rash. In the clinical trial, skin reactions occurred in 62% of patients, with Grade 3 skin reactions in 0.3%. The median time to onset was 25 (range: 1 to 630) days. The median time to improvement to Grade 1 or less was 33 days. Monitor for skin toxicity, including rash progression. Consider early intervention and treatment to manage skin toxicity. Withhold TALVEY® as recommended based on severity. Hepatotoxicity: TALVEY® can cause hepatotoxicity. Elevated ALT occurred in 33% of patients, with Grade 3 or 4 ALT elevation occurring in 2.7%; elevated AST occurred in 31% of patients, with Grade 3 or 4 AST elevation occurring in 3.3%. Grade 3 or 4 elevations of total bilirubin occurred in 0.3% of patients. Liver enzyme elevation can occur with or without concurrent CRS. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TALVEY® or consider permanent discontinuation of TALVEY®, based on severity [see Dosage and Administration (2.5)]. Embryo-Fetal Toxicity: Based on its mechanism of action, TALVEY® may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TALVEY® and for 3 months after the last dose. Adverse Reactions: The most common adverse reactions (≥20%) are pyrexia, CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight decreased, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache. The most common Grade 3 or 4 laboratory abnormalities (≥30%) are lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hemoglobin decreased. Please read full Prescribing Information, including Boxed WARNING, for TALVEY®. DARZALEX FASPRO® INDICATIONS AND IMPORTANT SAFETY INFORMATION INDICATIONS DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma: · In combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed patients who are eligible for autologous stem cell transplant · In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant · In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy · In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant · In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor (PI) · In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy · In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy · As monotherapy in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent DARZALEX FASPRO® as monotherapy is indicated for the treatment of adult patients with high-risk smoldering multiple myeloma. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS DARZALEX FASPRO® is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation. WARNINGS AND PRECAUTIONS Hypersensitivity and Other Administration Reactions Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO®. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO®. Systemic Reactions In a pooled safety population of 1446 patients with multiple myeloma (N=1235) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO® as monotherapy or in combination, 7% of patients experienced a systemic administration-related reaction (Grade 2: 3%, Grade 3: 0.8%, Grade 4: 0.1%). In patients with high-risk smoldering multiple myeloma (N=193), systemic administration-related reactions occurred in 17% of patients in AQUILA (Grade 2: 7%, Grade 3: 1%). In all patients (N=1639), systemic administration-related reactions occurred in 7% of patients with the first injection, 0.5% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 3.2 hours (range: 4 minutes to 3.5 days). Of the 283 systemic administration-related reactions that occurred in 135 patients, 240 (85%) occurred on the day of DARZALEX FASPRO® administration. Delayed systemic administration-related reactions have occurred in 1% of the patients. Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision. Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO®. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO® depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions. Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO® and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO®. Local Reactions In this pooled safety population of 1446 patients with multiple myeloma (N=1253) or light chain amyloidosis (N=193), injection-site reactions occurred in 8% of patients, including Grade 2 reactions in 1.1%. The most frequent (>1%) injection-site reaction were injection site erythema and injection site rash. In patients with high-risk smoldering multiple myeloma (N=193), injection-site reactions occurred in 28% of patients, including Grade 2 reactions in 3%. These local reactions occurred a median of 6 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO®. Monitor for local reactions and consider symptomatic management. Infections DARZALEX FASPRO® can cause serious, life-threatening, or fatal infections. In patients who received DARZALEX FASPRO® in a pooled safety population including patients with smoldering multiple myeloma and light chain (AL) amyloidosis (N=1639), serious infections, including opportunistic infections, occurred in 24% of patients, Grade 3 or 4 infections occurred in 22%, and fatal infections occurred in 2.5%. The most common type of serious infection reported was pneumonia (8.5%). Monitor patients for signs and symptoms of infection prior to and during treatment with DARZALEX FASPRO® and treat appropriately. Administer prophylactic antimicrobials according to guidelines. Neutropenia Daratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO® until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO®, higher rates of Grade 3-4 neutropenia were observed. Thrombocytopenia Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Consider withholding DARZALEX FASPRO® until recovery of platelets. Embryo-Fetal Toxicity Based on the mechanism of action, DARZALEX FASPRO® can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO® and for 3 months after the last dose. The combination of DARZALEX FASPRO® with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy. Interference With Serological Testing Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO®. Type and screen patients prior to starting DARZALEX FASPRO®. Interference With Determination of Complete Response Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO®-treated patients with IgG kappa myeloma protein. ADVERSE REACTIONS In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO® monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, rash, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, musculoskeletal pain, upper respiratory tract infection, , peripheral neuropathy, peripheral sensory neuropathy, constipation, pneumonia, edema, peripheral edema, and anemia. The most common adverse reactions (≥20%) in patients with high-risk smoldering multiple myeloma who received DARZALEX FASPRO® monotherapy are upper respiratory tract infection, musculoskeletal pain, fatigue, diarrhea, rash, sleep disorder, sensory neuropathy, and injection site reactions. The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO® are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin. Please click here to read the full Prescribing Information for DARZALEX FASPRO®. DARZALEX® INDICATIONS AND IMPORTANT SAFETY INFORMATION INDICATIONS DARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma: · In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant · In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy · In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant · In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor · In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy · In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy · As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent CONTRAINDICATIONS DARZALEX® is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation. WARNINGS AND PRECAUTIONS Infusion-Related Reactions DARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX®. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension and blurred vision. When DARZALEX® dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX®, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX® following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days, ie, 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions. Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion. To reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX® infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease. Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®. Interference With Serological Testing Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX®. Type and screen patients prior to starting DARZALEX®. Neutropenia and Thrombocytopenia DARZALEX® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX® until recovery of neutrophils or for recovery of platelets. Interference With Determination of Complete Response Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein. Embryo-Fetal Toxicity Based on the mechanism of action, DARZALEX® can cause fetal harm when administered to a pregnant woman. DARZALEX® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX® and for 3 months after the last dose The combination of DARZALEX® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy. ADVERSE REACTIONS The most frequently reported adverse reactions (incidence ≥20%) were: upper respiratory infection, neutropenia, infusion related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40%) with DARZALEX® are: neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia. Please click here to read the full Prescribing Information for DARZALEX®. WHAT IS IMAAVY® (nipocalimab-aahu)? IMAAVY® is a prescription medicine used to treat adults and children 12 years of age and older with a disease called generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive. It is not known if IMAAVY® is safe and effective in children under 12 years of age. IMPORTANT SAFETY INFORMATION What is the most important information I should know about IMAAVY®? IMAAVY® is a prescription medicine that may cause serious side effects, including:· Infections are a common side effect of IMAAVY® that can be serious. Receiving IMAAVY® may increase your risk of infection. Tell your healthcare provider right away if you have any of the following infection symptoms: · Allergic (hypersensitivity) reactions may happen during or up to a few weeks after your IMAAVY® infusion. Get emergency medical help right away if you get any of these symptoms during or after your IMAAVY® infusion: · Infusion-related reactions are possible. Tell your healthcare provider right away if you get any of these symptoms during or a few days after your IMAAVY® infusion: Do not receive IMAAVY® if you have a severe allergic reaction to nipocalimab-aahu or any of the ingredients in IMAAVY®. Reactions have included angioedema and anaphylaxis. Before using IMAAVY®, tell your healthcare provider about all of your medical conditions, including if you: · ever had an allergic reaction to IMAAVY®.· have or had any recent infections or symptoms of infection.· have recently received or are scheduled to receive an immunization (vaccine). People who take IMAAVY® should not receive live vaccines.· are pregnant, plan to become pregnant, or are breastfeeding. It is not known whether IMAAVY® will harm your baby.Pregnancy Safety Study. There is a pregnancy safety study for IMAAVY® if IMAAVY® is given during pregnancy or you become pregnant while receiving IMAAVY®. Your healthcare provider should report IMAAVY exposure by contacting Janssen at 1-800-526-7736 or www.IMAAVY®.com. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. What are the possible side effects of IMAAVY ®?IMAAVY® may cause serious side effects. See “What is the most important information I should know about IMAAVY®?” The most common side effects of IMAAVY® include: respiratory tract infection, peripheral edema (swelling in your hands, ankles, or feet), and muscle spasms. These are not all the possible side effects of IMAAVY®. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. Please see the full Prescribing Information and Medication Guide for IMAAVY® and discuss any questions you have with your doctor. Dosage Form and Strengths: IMAAVY® is supplied as a 300 mg/1.62 mL and a 1,200 mg/6.5 mL (185 mg/mL) single-dose vial per carton for intravenous injection. TECVAYLI® IMPORTANT SAFETY INFORMATION INDICATION AND USAGE TECVAYLI® (teclistamab-cqyv) is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma: · in combination with daratumumab and hyaluronidase-fihj in patients who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent.· as monotherapy, in patients who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. IMPORTANT SAFETY INFORMATION WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TECVAYLI. Initiate treatment with TECVAYLI step-up dosing schedule to reduce risk of CRS. Withhold TECVAYLI until CRS resolves or permanently discontinue based on severity. Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and serious, life-threatening, or fatal reactions, can occur in patients receiving TECVAYLI. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold TECVAYLI until neurologic toxicity resolves or permanently discontinue based on severity. TECVAYLI is available only through a restricted program called the TECVAYLI and TALVEY® Risk Evaluation and Mitigation Strategy (REMS). WARNINGS AND PRECAUTIONS Cytokine Release Syndrome - TECVAYLIcan cause cytokine release syndrome (CRS), including life-threatening or fatal reactions. In the clinical trials (monotherapy and combination therapy; N=448), CRS occurred in 64% of patients who received TECVAYLI at the recommended dose, with Grade 1 CRS occurring in 46% of patients, Grade 2 in 18%, and Grade 3 in 0.2%. Recurrent CRS occurred in 27% of patients. Most patients experienced CRS during the initial step-up dosing schedule (step-up dose 1 [37%], step-up dose 2 [32%], or the initial treatment dose [20%]). CRS first occurred following subsequent doses of TECVAYLI in 2.5% of patients. The median time to onset of CRS was 2 (range: 1 to 9) days after the most recent dose and the median duration of CRS was 2 (range: 1 to 22) days. Clinical signs and symptoms of CRS included, but were not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation). Initiate therapy according to TECVAYLI step-up dosing schedule to reduce risk of CRS. Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI accordingly. At the first sign of CRS, immediately evaluate patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold until CRS resolves or permanently discontinue TECVAYLI based on severity. TECVAYLI is available only through a restricted program under a REMS. Neurologic Toxicity including Immune Effector Cell-Associated Neurotoxicity Syndrome - TECVAYLI can cause serious, life-threatening, or fatal neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS). In the clinical trials (monotherapy and combination therapy trials; N=448), neurologic toxicity occurred in 60% of patients who received TECVAYLI at the recommended dosage, with Grade 3 or 4 neurologic toxicity in 6%. Neurologic toxicities reported in ≥5% of patients included headache (27%), sensory neuropathy (16%), motor dysfunction (15%), insomnia (12%), encephalopathy (11%), and dizziness (8%). Fatal neurologic toxicity occurred in 0.4% of patients, including Guillain-Barré syndrome and status epilepticus (one patient each). In MajesTEC-1, ICANS was reported in 6% of patients who received TECVAYLI as monotherapy at the recommended dosage. Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the initial treatment dose (1.8%). Less than 3% of patients developed first occurrence of ICANS following subsequent TECVAYLI doses. The median time to onset of ICANS was 4 (range: 2 to 8) days after the most recent dose with a median duration of 3 (range: 1 to 20) days. The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia. In MajesTEC-3, ICANS was reported in 1.1% of patients who received the recommended TECVAYLI dosage in combination with daratumumab and hyaluronidase-fihj, including Grade 4 ICANS in 1 patient. All events of ICANS occurred during the step-up dosing schedule. The median time to onset of ICANS was 2 (range: 1 to 3) days after the most recent dose and the median duration of ICANS was 2 (range: 1 to 2) days. The clinical manifestations of ICANS reported were amnesia, encephalopathy and delirium. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS during TECVAYLI treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold until neurologic toxicity resolves or permanently discontinue TECVAYLI based on severity per recommendations and consider further management per current practice guidelines. Due to the potential for neurologic toxicity, patients receiving TECVAYLI are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves. TECVAYLI is available only through a restricted program under a REMS. TECVAYLI and TALVEY REMS - TECVAYLI is available only through a restricted program under a REMS called the TECVAYLI and TALVEY REMS because of the risks of CRS and neurologic toxicity, including ICANS. Hepatotoxicity - TECVAYLI can cause hepatotoxicity, including fatalities. There was one fatal case of hepatic failure in MajesTEC-1. In patients who received TECVAYLI at the recommended dose in the clinical trials (monotherapy and combination therapy trials; N=448) elevated aspartate aminotransferase (AST) occurred in 47% of patients, with Grade 3 or 4 elevations in 2.9%. Elevated alanine aminotransferase (ALT) occurred in 48% of patients, with Grade 3 or 4 elevations in 3.8%. Elevated total bilirubin occurred in 10% of patients with Grade 3 or 4 elevations in 0.7%. Liver enzyme elevation can occur with or without concurrent CRS. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity. Infections - TECVAYLI can cause severe, life-threatening, or fatal infections. In MajesTEC-1 (N=165), in patients who received the recommended TECVAYLI dosage, serious infections, including opportunistic infections, occurred in 30% of patients, Grade 3 or 4 infections in 35% of patients, and fatal infections in 4.2% of patients. In MajesTEC-3 (N=283), in patients who received TECVAYLI in combination with daratumumab and hyaluronidase-fihj at the recommended dosage, serious infections, including opportunistic infections, occurred in 54% of patients, Grade 3 or Grade 4 infections in 54% of patients, and fatal infections in 4.6% of patients. Monitor patients for signs and symptoms of infection prior to and during treatment with TECVAYLI and treat appropriately. Administer prophylactic antimicrobials according to current practice guidelines. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity. Monitor immunoglobulin levels prior to and during treatment with TECVAYLI and administer subcutaneous or intravenous immunoglobulin (IVIG) to maintain the serum levels >400 mg/dL. Neutropenia - TECVAYLI can cause neutropenia and febrile neutropenia. In patients who received TECVAYLI at the recommended dose in the clinical trials (monotherapy and combination therapy trials; N=448), decreased neutrophils occurred in 88% of patients, with Grade 3 or 4 decreased neutrophils in 70%. Febrile neutropenia occurred in 6% of patients. Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local institutional guidelines. Monitor patients with neutropenia for signs of infection. Withhold TECVAYLI based on severity. Hypersensitivity and Other Administration Reactions - TECVAYLI can cause both systemic administration-related and local injection-site reactions. Systemic Reactions - In patients who received the recommended TECVAYLI dosage in the clinical trials (monotherapy and combination therapy trials; N=448), 2.5% of patients experienced systemic-administration reactions, which included recurrent pyrexia and rash. Local Reactions - In patients who received TECVAYLI at the recommended dosage in the clinical trials (monotherapy and combination therapy trials; N=448), injection-site reactions occurred in 37% of patients, with Grade 1 injection-site reactions in 29% and Grade 2 in 9%. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity. Embryo-Fetal Toxicity - Based on its mechanism of action, TECVAYLI may cause fetal harm when administered to a pregnant patient. Advise pregnant patients of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TECVAYLI and for 5 months after the last dose. ADVERSE REACTIONSThe most common adverse reactions (≥20%) in patients who received TECVAYLI monotherapy were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common adverse reactions (≥20%) in patients who received TECVAYLI in combination with daratumumab and hyaluronidase-fihj were hypogammaglobulinemia, upper respiratory tract infection, CRS, cough, diarrhea, musculoskeletal pain, COVID-19, pneumonia, injection site reaction, fatigue, pyrexia, headache, nausea, gastroenteritis, and weight decreased. The most common Grade 3 to 4 laboratory abnormalities (≥20%) with TECVAYLI (as monotherapy or in combination with daratumumab and hyaluronidase-fihj) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets. Please read full Prescribing Information, including Boxed WARNING, for TECVAYLI. CARVYKTI® IMPORTANT SAFETY INFORMATION WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, PROLONGED and RECURRENT CYTOPENIA, and SECONDARY HEMATOLOGICAL MALIGNANCIES Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with CARVYKTI®. Do not administer CARVYKTI® to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids. Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS), which may be fatal or life-threatening, occurred following treatment with CARVYKTI®, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with CARVYKTI®. Provide supportive care and/or corticosteroids as needed. Parkinsonism and Guillain-Barré syndrome (GBS) and their associated complications resulting in fatal or life-threatening reactions have occurred following treatment with CARVYKTI®. Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), including fatal and life-threatening reactions, occurred in patients following treatment with CARVYKTI®. HLH/MAS can occur with CRS or neurologic toxicities. Prolonged and/or recurrent cytopenias with bleeding and infection and requirement for stem cell transplantation for hematopoietic recovery occurred following treatment with CARVYKTI®. Immune Effector Cell-associated Enterocolitis (IEC-EC), including fatal or life-threatening reactions, occurred following treatment with CARVYKTI®. Secondary hematological malignancies, including myelodysplastic syndrome and acute myeloid leukemia, have occurred in patients following treatment with CARVYKTI®. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including CARVYKTI®. 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 (ASTCT 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. Confirm that a minimum of 2 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 1 dose of corticosteroids for treatment of CRS. Monitor patients at least daily for 7 days following CARVYKTI® infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 2 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 cutoff. 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 7 days following CARVYKTI® infusion for signs and symptoms of ICANS. Rule out other causes of ICANS symptoms. Monitor patients for signs or symptoms of ICANS for at least 2 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed. Advise patients to avoid driving for at least 2 weeks following infusion. 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 cutoff. 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 cutoff. 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 cutoff. 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. 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. Reactivation of John Cunningham (JC) virus, leading to progressive multifocal leukoencephalopathy (PML), including cases with fatal outcomes, have been reported following treatment. Perform appropriate diagnostic evaluations in patients with neurological adverse events. 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 500 mg/dL after infusion in 93% (265/285) of patients. Hypogammaglobulinemia either as an adverse reaction or laboratory IgG level below 500 mg/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 ≤2 Grade. 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. IMMUNE EFFECTOR CELL-ASSOCIATED ENTERCOLITIS (IEC-EC) has occurred in patients treated with CARVYKTI®. Manifestations include severe or prolonged diarrhea, abdominal pain, and weight loss requiring parenteral nutrition. IEC-EC has been associated with fatal outcome from perforation or sepsis. Manage according to institutional guidelines, including referral to gastroenterology and infectious disease specialists. In cases of refractory IEC-EC, consider additional workup to exclude alternative etiologies, including T-cell lymphoma of the GI tract, which has been reported in the post marketing setting. 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 lifelong 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. 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®. IMBRUVICA® IMPORTANT SAFETY INFORMATION INDICATIONS IMBRUVICA® is a kinase inhibitor indicated for the treatment of: Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL). Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion. Adult patients with Waldenström’s macroglobulinemia (WM). Adult and pediatric patients age 1 year and older with chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy. For more information, visit www.IMBRUVICA.com. WARNINGS AND PRECAUTIONS Hemorrhage: Fatal bleeding events have occurred in patients who received IMBRUVICA®. Major hemorrhage (≥ Grade 3, serious, or any central nervous system events; e.g., intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post procedural hemorrhage) occurred in 4.2% of patients, with fatalities occurring in 0.4% of 2,838 patients who received IMBRUVICA® in 27 clinical trials. Bleeding events of any grade including bruising and petechiae occurred in 39%, and excluding bruising and petechiae occurred in 23% of patients who received IMBRUVICA®, respectively. The mechanism for the bleeding events is not well understood. Use of either anticoagulant or antiplatelet agents concomitantly with IMBRUVICA® increases the risk of major hemorrhage. Across clinical trials, 3.1% of 2,838 patients who received IMBRUVICA® without antiplatelet or anticoagulant therapy experienced major hemorrhage. The addition of antiplatelet therapy with or without anticoagulant therapy increased this percentage to 4.4%, and the addition of anticoagulant therapy with or without antiplatelet therapy increased this percentage to 6.1%. Consider the risks and benefits of anticoagulant or antiplatelet therapy when co-administered with IMBRUVICA®. Monitor for signs and symptoms of bleeding. Consider the benefit-risk of withholding IMBRUVICA® for at least 3 to 7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding. Infections: Fatal and non-fatal infections (including bacterial, viral, or fungal) have occurred with IMBRUVICA® therapy. Grade 3 or greater infections occurred in 21% of 1,476 patients with B-cell malignancies who received IMBRUVICA® in clinical trials. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA®. Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections. Monitor and evaluate patients for fever and infections and treat appropriately. Cardiac Arrhythmias, Cardiac Failure, and Sudden Death: Fatal and serious cardiac arrhythmias and cardiac failure have occurred with IMBRUVICA®. Deaths due to cardiac causes or sudden deaths occurred in 1% of 4,896 patients who received IMBRUVICA® in clinical trials, including in patients who received IMBRUVICA® in unapproved monotherapy or combination regimens. These adverse reactions occurred in patients with and without preexisting hypertension or cardiac comorbidities. Patients with cardiac comorbidities may be at greater risk of these events. Grade 3 or greater ventricular tachyarrhythmias were reported in 0.2%, Grade 3 or greater atrial fibrillation and atrial flutter were reported in 3.7%, and Grade 3 or greater cardiac failure was reported in 1.3% of 4,896 patients who received IMBRUVICA® in clinical trials, including in patients who received IMBRUVICA® in unapproved monotherapy or combination regimens. These events have occurred particularly in patients with cardiac risk factors including hypertension and diabetes mellitus, a previous history of cardiac arrhythmias, and in patients with acute infections. Evaluate cardiac history and function at baseline, and monitor patients for cardiac arrhythmias and cardiac function. Obtain further evaluation (e.g., ECG, echocardiogram) as indicated for patients who develop symptoms of arrhythmia (e.g., palpitations, lightheadedness, syncope, chest pain), new onset dyspnea, or other cardiovascular concerns. Manage cardiac arrhythmias and cardiac failure appropriately, follow dose modification guidelines, and consider the risks and benefits of continued IMBRUVICA® treatment. Hypertension: Hypertension occurred in 19% of 1,476 patients with B-cell malignancies who received IMBRUVICA® in clinical trials. Grade 3 or greater hypertension occurred in 8% of patients. Based on data from a subset of these patients, (N=1,124), the median time to onset was 5.9 months (range, 0 to 24 months). In a long-term safety analysis over 5 years of 1,284 patients with B-cell malignancies treated for a median of 36 months (range, 0 to 98 months), the cumulative rate of hypertension increased over time. The prevalence for Grade 3 or greater hypertension was 4% (year 0-1), 7% (year 1-2), 9% (year 2-3), 9% (year 3-4), and 9% (year 4-5); the overall incidence for the 5-year period was 11%. Monitor blood pressure in patients treated with IMBRUVICA®, initiate or adjust anti-hypertensive medication throughout treatment with IMBRUVICA® as appropriate, and follow dosage modification guidelines for Grade 3 or higher hypertension. Cytopenias: In 645 patients with B-cell malignancies who received IMBRUVICA® as a single agent, grade 3 or 4 neutropenia occurred in 23% of patients, grade 3 or 4 thrombocytopenia in 8% and grade 3 or 4 anemia in 2.8%, based on laboratory measurements. Monitor complete blood counts monthly. Second Primary Malignancies: Other malignancies (10%), including non-skin carcinomas (3.9%), occurred among the 1,476 patients with B-cell malignancies who received IMBRUVICA® in clinical trials. The most frequent second primary malignancy was non-melanoma skin cancer (6%). Tumor Lysis Syndrome: Tumor lysis syndrome has been infrequently reported with IMBRUVICA®. Assess the baseline risk (e.g., high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate. Embryo-Fetal Toxicity: Based on findings in animals, IMBRUVICA® can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMBRUVICA® and for 1 month after the last dose. Advise males with female partners of reproductive potential to use effective contraception during the same time period. ADVERSE REACTIONS B-cell malignancies: The most common adverse reactions (≥30%) in adult patients with B-cell malignancies were thrombocytopenia (55%)*, diarrhea (44%), fatigue (39%), musculoskeletal pain (39%), neutropenia (39%)*, rash (36%), anemia (35%)*, bruising (32%), and nausea (30%). The most common Grade ≥ 3 adverse reactions (≥5%) in adult patients with B-cell malignancies were neutropenia (21%)*, thrombocytopenia (14%)*, pneumonia (8%), and hypertension (8%). Approximately 9% (CLL/SLL), and 14% (WM) of adult patients had a dose reduction due to adverse reactions.Approximately 4-10% (CLL/SLL) and 5% (WM) of adult patients discontinued due to adverse reactions.cGVHD: The most common adverse reactions (≥20%) in adult or pediatric patients with cGVHD were fatigue (57%), anemia (49%)*, bruising (40%), diarrhea (36%), thrombocytopenia (33%)*, musculoskeletal pain (30%), pyrexia (30%), muscle spasms (29%), stomatitis (29%), hemorrhage (26%), nausea (26%), abdominal pain (23%), pneumonia (23%), and headache (21%). The most common Grade 3 or higher adverse reactions (≥5%) reported in adult or pediatric patients with cGVHD were pneumonia (14%), anemia (13%)*, fatigue (12%), pyrexia (11%), diarrhea (10%), neutropenia (10%)*, sepsis (10%), osteonecrosis (9%), stomatitis (9%), hypokalemia (7%), headache (5%), and musculoskeletal pain (5%). Discontinuation of IMBRUVICA® treatment due to an adverse reaction occurred in 24% of adult patients and 23% of pediatric patients. Adverse reactions leading to dose reduction occurred in 26% of adult patients and 19% of pediatric patients. *Treatment-emergent decreases (all grades) were based on laboratory measurements. DRUG INTERACTIONS CYP3A Inhibitors: Co-administration of IMBRUVICA® with strong or moderate CYP3A inhibitors may increase ibrutinib plasma concentrations. Increased ibrutinib concentrations may increase the risk of drug-related toxicity. Dose modifications of IMBRUVICA® are recommended when used concomitantly with posaconazole, voriconazole, and moderate CYP3A inhibitors. Avoid concomitant use of other strong CYP3A inhibitors. Interrupt IMBRUVICA® if strong inhibitors are used short-term (e.g., for ≤ 7 days). Avoid grapefruit and Seville oranges during IMBRUVICA® treatment, as these contain strong or moderate inhibitors of CYP3A. See dose modification guidelines in USPI sections 2.3 and 7.1. CYP3A Inducers: Avoid coadministration with strong CYP3A inducers. SPECIFIC POPULATIONS Pediatric Use: The safety and effectiveness of IMBRUVICA® have not been established for the treatment of cGVHD after failure of one or more lines of therapy in pediatric patients less than 1 year of age. The safety and effectiveness of IMBRUVICA® in pediatric patients have not been established in CLL/SLL, CLL/SLL with 17p deletion, WM, or in patients with mature B-cell non-Hodgkin lymphoma. In the randomized population from a study that included 35 patients (26 pediatric patients age 5 to less than 17 years) with previously treated mature B-cell non-Hodgkin lymphoma, major hemorrhage and discontinuation of chemoimmunotherapy due to adverse reactions occurred more frequently in the ibrutinib plus chemoimmunotherapy arm compared to the chemoimmunotherapy alone arm. Hepatic Impairment:Adult Patients with B-cell Malignancies: Hepatic Impairment (based on Child-Pugh criteria): Avoid use of IMBRUVICA® in patients with severe hepatic impairment. In patients with mild or moderate impairment, reduce recommended IMBRUVICA® dose and monitor more frequently for adverse reactions of IMBRUVICA®. Patients with cGVHD: Avoid use of IMBRUVICA® in patients with total bilirubin level > 3x upper limit of normal (ULN) (unless of non-hepatic origin or due to Gilbert’s syndrome). Reduce recommended dose when administering IMBRUVICA® to patients with total bilirubin level > 1.5 to 3x ULN (unless of non-hepatic origin or due to Gilbert’s syndrome). Please click here to see the full Prescribing Information. ABOUT JOHNSON & JOHNSONAt 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 https://www.jnj.com/ or at www.innovativemedicine.jnj.com. Follow us at @JNJInnovMed. Janssen Biotech, Inc., is a Johnson & Johnson company. Cautions Concerning Forward-Looking StatementsThis press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 related to TALVEY ® (talquetamab), DARZALEX FASPRO® (daratumumab), IMAAVY ® (nipocalimab-aahu), TECVAYLI ® (teclistamab), CARVYKTI ® (ciltacabtagene autoleucel; cilta-cel), bleximenib (JNJ-75276617) and IMBRUVICA® (ibrutinib). 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 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 most recent Annual Report on Form 10-K, 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 www.sec.gov, www.jnj.com, www.investor.jnj.com or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments. # # # 1 Rarediseases.org. Warm Autoimmune Hemolytic Anemia. Available at https://rarediseases.org/rare-diseases/warm-autoimmune-hemolytic-anemia/. Last accessed: May 2026. 2 Rajkumar SV. Multiple Myeloma: 2020 Update on Diagnosis, Risk-Stratification and Management. Am J Hematol. 2020;95(5):548-567. 3 National Cancer Institute. Plasma cell neoplasms. Avaliable at https://www.cancer.gov/types/myeloma/patient/myeloma-treatment-pdq. Last accessed May 2026. 4 City of Hope (2022) Multiple myeloma: Causes, symptoms & treatments. Avaliable at https://www.cancercenter.com/cancer-types/multiple-myeloma. Last accessed: May 2026. 5 International Agency for Research on Cancer (World Health Organization). (2024). Multiple myeloma fact sheet. Avaliable at https://gco.iarc.who.int/media/globocan/factsheets/cancers/35-multiple-myeloma-fact-sheet.pdf. Last accessed: May 2026. 6 SEER Explorer: An interactive website for SEER cancer statistics. Surveillance Research Program, National Cancer Institute. Avaliable at https://seer.cancer.gov/explorer/. Last accessed May 2026. 7 American Cancer Society. What is multiple myeloma? Avaliable at https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html. Last accessed: May 2026. 8 American Cancer Society. Multiple myeloma early detection, diagnosis, and staging. Avaliable at https://www.cancer.org/cancer/types/multiple-myeloma/detection-diagnosis-staging/detection.html. Last accessed May 2026. 9 Kazandjian D. Multiple myeloma epidemiology and survival: a unique malignancy. J Clin Oncol. 2018;36(15):1479–1487. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC6119139/ 10 Tranekær S, et al. Epidemiology of secondary warm autoimmune haemolytic anaemia-A systematic review and meta-analysis. J Clin Med. 2021 Mar 17;10(6):1244. 11 Sudulagunta SR, et al. Warm Autoimmune Hemolytic Anemia: Clinical Profile and Management. J Hematol. 2017 Mar; 6(1): 12–20. Published online 2017 Mar 21. doi: 10.14740/jh303w. 12 National Organization for Rare Disorders, Warm autoimmune Hemolytic Anemia. Available at: https://rarediseases.org/rare-diseases/warm-autoimmune-hemolytic-anemia/. Last accessed: May 2026. 13 Cherif H, Cai Q, Crivera C, Leon A, Rahman I, Leval A, Noel W, Kjellander C. Overall survival and treatment patterns among patients with warm autoimmune hemolytic anemia in Sweden: A nationwide population-based study. Eur J Haematol, 2025 Jan;114(1):129-138. 14 Fattizzo B, Barcellini W. New therapies for the treatment of warm autoimmune hemolytic anemia. Transfusion Medical Reviews. 2022;36(4). 15 The Leukemia & Lymphoma Society. Facts 2022–2023: Updated data on blood cancers. Avaliable athttps://www.lls.org/sites/default/files/2023-08/PS80_Facts_2022_2023.pdf. Last accessed: May 2026. 16 MD Anderson Cancer Center. Acute myeloid leukemia. Avaliable at https://www.mdanderson.org/cancer-types/acute-myeloid-leukemia.html. Last accessed: May 2026. 17 American Cancer Society. Signs and symptoms of acute myeloid leukemia (AML). Avaliable at https://www.cancer.org/cancer/types/acute-myeloid-leukemia/detection-diagnosis-staging/signs-symptoms.html. Last accessed: May 2026. 18 Shimony S, Stahl M, Stone RM. Acute myeloid leukemia: 2023 update on diagnosis, risk‑stratification, and management. Am J Hematol. 2023;98(3):502–526.https://doi.org/10.1002/ajh.26822. Accessed June 2026. 19 TALVEY® U.S. Prescribing Information. Horsham, PA: Janssen Biotech, Inc. August 2023. 20 European Medicines Agency. TALVEY Summary of Product Characteristics. August 2023. 21 DARZALEX FASPRO® U.S. Prescribing Information. 2025. Horsham, PA: Janssen Biotech, Inc. 22 DARZALEX® U.S. Prescribing Information. 2022. Horsham, PA: Janssen Biotech, Inc. 23 IMAAVY® U.S. Prescribing Information. 2025. Horsham, PA: Janssen Biotech, Inc. 24 ClinicalTrials.gov Identifier: NCT04951622. Available at: https://clinicaltrials.gov/ct2/show/NCT04951622. Last accessed: May 2026. 25 ClinicalTrials.gov Identifier: NCT03842189. Available at: https://clinicaltrials.gov/ct2/show/NCT03842189. Last accessed: May 2026. 26 ClinicalTrials.gov Identifier: NCT05327114. Available at: https://www.clinicaltrials.gov/study/NCT05327114. Last accessed: May 2026. 27 ClinicalTrials.gov Identifier: NCT04119050. Available at: https://clinicaltrials.gov/study/NCT04119050. Last accessed: May 2026. 28 ClinicalTrials.gov Identifier: NCT05379634. Available at: https://clinicaltrials.gov/study/NCT05379634. Last accessed: May 2026. 29 ClinicalTrials.gov Identifier: NCT05912517. Available at: https://www.clinicaltrials.gov/study/NCT05912517. Last accessed: May 2026. 30 ClinicalTrials.gov Identifier: NCT04968912. Available at: https://clinicaltrials.gov/study/NCT04968912. Last accessed: May 2026. 31 ClinicalTrials.gov Identifier: NCT04882878. Available at: https://clinicaltrials.gov/study/NCT04882878. Last accessed: May 2026. 32 ClinicalTrials.gov Identifier: NCT06449651. Available at: https://clinicaltrials.gov/study/NCT06449651. Last accessed: May 2026. 33 ClinicalTrials.gov Identifier: NCT06533098 Available at: https://clinicaltrials.gov/study/NCT06533098. Last accessed: May 2026. 34 U.S. FDA Approves TECVAYLI® (teclistamab-cqyv), the First Bispecific T-cell Engager Antibody for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma. Avaliable at https://www.jnj.com/u-s-fda-approves-tecvayli-teclistamab-cqyv-the-first-bispecific-t-cell-engager-antibody-for-the-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma. Last accessed: May 2025. 35 CARVYKTI® U.S. Prescribing Information. 2025. Horsham, PA: Janssen Biotech, Inc. 36 Genetics Home Reference. Isolated growth hormone deficiency. Avaliable at http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency. Last accessed: May 2026. 37 Turetsky A, et al. Single cell imaging of Bruton’s tyrosine kinase using an irreversible inhibitor. Scientific Reports. 2014;6:4782. 38 de Rooij MF, et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012;119(11):2590-2594. 39 IMBRUVICA® U.S. Prescribing Information, February 2024. Horsham, PA: Janssen Biotech, Inc. Media contact:Bridget Kimmelbkimmel@its.jnj.com Oncology Media Relationsoncology_media_relations@its.jnj.com Investor contact:Jess Margevichinvestor-relations@its.jnj.com

在生物医药投资领域，有一句古老的谚语：“资本总是流向希望，而非痛苦。”然而，当全球最大的私募股权巨头黑石（Blackstone）押注时，它寻找的往往是那些被主流忽视、深藏在临床数据背后的巨大“痛苦”，并将其转化为具有垄断潜力的商业叙事。 2026年5月，黑石生命科学（Blackstone Life Sciences）投下了其迄今为止最具象的一枚棋子：斥资2.5亿美元独家投资临床阶段生物技术公司Anagram Therapeutics。这不仅是一笔巨额支票，更是一次关于“减法”哲学的精准狙击。 然而，这笔交易的价值远不止于其金额本身。它是一扇窗口，透过它我们可以窥见：全球最大的另类资产管理公司如何重塑生物技术投资的游戏规则；私募资本如何从“晚期接盘侠”蜕变为“创新共谋者”；以及在一个充满不确定性的时代，什么样的科学逻辑能够穿越周期。Anagram Therapeutics：一家“把40颗药丸变成1颗”的公司公司概况与使命 Anagram Therapeutics是一家总部位于马萨诸塞州弗雷明汉的临床阶段生物制药公司，成立于2017年。公司的核心使命是开发创新的口服酶疗法，用于治疗由吸收不良综合征和营养代谢紊乱引起的严重疾病——这些疾病使人体无法正常处理或吸收某些脂肪、糖类、蛋白质、维生素或其他关键营养素。 公司名称“Anagram”（字面意为“变位词”）本身蕴含着深刻的战略哲学：正如字母的重新排列可以创造出全新的词汇，Anagram致力于重新排列和重新构想口服酶的设计，以创造出能够从根本上改变现有治疗范式的突破性疗法。核心产品线：ANG003 Anagram的领先候选药物ANG003是一种新型广谱口服酶替代疗法，用于治疗胰腺外分泌功能不全（EPI）。EPI是一种身体无法产生足够消化酶来分解食物和吸收营养的疾病，可导致营养不良、脂肪酸异常、严重的胃肠道症状以及预期寿命缩短。 在当前的标准治疗（Standard of Care）下，患有囊性纤维化（CF）并伴随EPI的患者，每天需要服用多达40颗药丸。这些药物主要是从猪胰腺提取的酶替代疗法（PERT）。这不仅构成沉重的生理负担——患者的每一次进食都被精确到每一餐、每一次零食的药丸计数所绑架；更存在供应链风险——猪源产品长期面临供应短缺、批次差异和质量波动问题，且在特定宗教文化群体中存在接受度限制。 ANG003的目标，正是将这一负担从每日40颗药丸压缩至每餐仅需1片。 该药物通过重组DNA技术，利用细胞工厂生产精准生物酶，具有更高的比活性、更稳定的质量和更可预测的药代动力学特征。2025年，ANG003已在美国约20个囊性纤维化护理中心启动了针对囊性纤维化相关EPI患者的Phase 1临床试验，第一批受试者已完成给药。临床前研究表明，ANG003可能以剂量依赖的方式改善有益脂肪和其他关键宏量营养素的吸收。多元化的产品管线 除ANG003外，Anagram还布局了多条针对先天性吸收不良综合征、碳水化合物代谢异常等适应症的在研管线（ANG011、ANG021、ANG031），构建了一个深度覆盖胃肠道疾病的产品矩阵。这种“核心资产+纵深布局”的结构，为未来的并购退出提供了多元化的价值锚点。黑石生命科学：从“门外汉”到“规则制定者” 在理解Anagram交易的全部意义之前，有必要将视角拉升至一个更高的维度：黑石生命科学（Blackstone Life Sciences, BXLS）究竟是如何在短短数年内，从一家以房地产和并购起家的私募巨头，蜕变为全球生物制药领域最具话语权的非传统力量的？起源：一次“恍然大悟”的董事会 这一故事的起点颇具戏剧性。2016年，黑石集团董事长兼CEO苏世民（Stephen Schwarzman）加入纽约长老会医院董事会。在他作为新董事的VIP参观日期间，两位研究人员向他介绍了医院在医学突破领域的最新进展。苏世民被这些突破的健康效益所震撼，但作为一个天生的交易家，他的第二反应更为直接：“这可以是一个非常有利可图的生意，黑石应该想办法成为主要玩家。” 这一顿悟催生了黑石历史上一次重要的战略转型。然而，黑石的执行层并未急于出手。时任黑石私募股权业务负责人的Joseph Baratta花费了整整一年时间进行战略推演：是自建生命科学团队，还是收购一家成熟公司？ 答案是后者。2018年，黑石收购了一家名为Clarus的小型投资公司——这家公司专注于为晚期临床资产（Phase 3）提供融资，拥有一支由医生和博士组成的专业团队，且已展现出可验证的业绩记录。苏世民素以成本控制著称，因此收购一个“已被验证”的团队远比从零搭建更为高效。收购完成后，Clarus创始人Nicholas Galakatos出任黑石生命科学全球负责人，一个全新的行业巨擘由此诞生。投资的“圣杯”：86%的Phase 3获批率 黑石生命科学拥有一项令同行艳羡的数据：其所支持的项目Phase 3审批通过率高达86%，而行业平均水平仅为48%-53%。这意味着当其他投资者还在晚期临床阶段“抛硬币”时，黑石已经能够以接近确定性的方式预测其资产的监管命运。 这一数据的魔力在于复利效应：如果黑石投资10个药物，接近9个能够成功上市并产生持续现金流。在金融世界里，这种确定性允许黑石动用巨大的杠杆和资金体量——单笔投资可达数亿乃至十亿美元以上——而无需承担传统风险投资所面临的高波动性。那些载入史册的交易 黑石为何能够在2025年关闭其最新生命科学基金时，募资额高达63亿美元——这是有史以来规模最大的私募生命科学基金，较其2020年的46亿美元前身基金增长近40%？因为其有限合伙人（LP）已经看到了真金白银的证据。 其一，Alnylam与Leqvio：开创性的“特许权使用费”模式。 Alnylam研发的降胆固醇药物Leqvio（每年仅需注射两次）拥有巨大潜力，但完成Phase 3试验需耗资约20亿美元。如果Alnylam自行融资，将严重稀释股东权益。黑石的解决方案是以10亿美元买断Alnylam未来从诺华获得的Leqvio销售的一半特许权使用费。在这笔交易中，黑石无需管理实验室或承担研发风险，只需等待药品上市后的销售分成。Leqvio正朝着数十亿美元的峰值年销售额迈进。 其二，Anthos Therapeutics：“所有权战略”的教科书级案例。 诺华曾拥有一款预防中风的Factor XI抑制剂（abelacimab）资产，但因战略优先级调整而准备搁置。黑石主导将其从诺华分拆出来，成立独立的Anthos Therapeutics，投入资金推进Phase 3临床试验。经过数年的培育与价值创造，诺华于2025年以31亿美元的价格将Anthos重新收购。黑石在其中扮演了“资产修复者”和“价值加速器”的角色，以“建造-出售”模式实现了数倍回报。 其三，近期大动作（2024-2026年）。 手握重金且模式成熟的黑石在近期动作频频，进一步验证了其“扫货”晚期资产的决心： 默克（Merck）：投入7亿美元换取癌症ADC药物Sacituzumab tirumotecan的未来分成。 Moderna：投入7.5亿美元助力mRNA流感疫苗的开发推进。 Teva：投入4亿美元开发自免疫新药Duvakitug。 强生（J&J）：共同投资4亿美元推进白血病药物Bleximenib。黑石的核心策略：不投“公司”，只投“药方” 与传统风险投资相比，黑石生命科学的策略在行业中可谓标新立异。其核心可以概括为：绕过公司估值的泡沫，直接投资单个药物的“最后一公里”。 维度 黑石生命科学策略 传统VC策略投资标的 特定晚期临床资产（Phase 3为主） 公司股权决策核心 分子机制、监管路径、市场规模 团队、赛道、叙事回报来源 里程碑付款 + 未来销售分成 股权增值与退出风险控制 深度科学尽调 + 运营赋能 投资组合分散洞察一：填补“资本缺口”的桥梁角色 黑石生命科学高管Paris Panayiotopoulos曾指出，大型制药企业历史上将约16%的收入投入研发，但面对越来越昂贵的Phase 3试验（动辄数十亿美元），这一比例已经捉襟见肘。行业评估数据显示，每年的研发资本供需缺口高达1700亿美元。 黑石的角色并非取代药企，而是作为“杠杆”或“桥梁”——利用外部资本补足药企的预算缺口，同时换取重磅炸弹药物的未来分成。这种模式对双方都具有高度吸引力：药企获得非稀释性资金，黑石获得可预测的现金流锚点。洞察二：可怕的“非对称”人才结构 黑石不仅仅是一群金融家。BXLS团队中包含20多位拥有医学博士或博士学位的医疗专家。苏世民曾担心要花费巨资自建团队，但收购Clarus的妙处在于，他获得了一群“前药企研发负责人”——这些人读得懂临床数据，审得通过监管文件，看得透科学假说。 当黑石评估Anagram的ANG003时，它不是在进行一场关于生物学命运的赌博，而是在经过系统性的科学尽调之后，计算“重组蛋白酶对胰酶的替代效率”的商业可行性。这种“金融资本+科学智慧”的双重结构，构成了黑石在生物技术投资领域最深的护城河。洞察三：所有权资本主义 黑石此次对Anagram的投资，并非简单的少数股权融资，而是其独特的“所有权战略”（Ownership Strategy）的体现。Nicholas Galakatos明确指出，这是该战略的典型案例。 在过去，大型机构往往满足于通过购买上市公司股票或获取销售特许权来分享收益。但黑石此次通过2.5亿美元的独家投资，深度绑定Anagram的未来——不仅提供资金，更带来庞大的商业开发资源和监管专业能力。Anagram此前已获得囊性纤维化基金会（Cystic Fibrosis Foundation）超过3000万美元的资助，证明了其科学逻辑的可行性。黑石的任务，则是充当那个将“科学证真”转化为“商业垄断”的加速器。宏观趋势：顶级PE正在重塑生物科技投资格局 Anagram交易并非孤立事件，它折射出整个私募资本向生命科学领域结构性迁移的宏大趋势。趋势一：资金向头部PE集中，“巨无霸”基金时代的到来 尽管全球生物科技风险投资在2023-2025年间持续低迷——PitchBook数据显示2024年全球生命科学VC募资同比下降约15%——但顶级PE的募资势头反而逆势上扬。黑石63亿美元基金的关闭、KKR, EQT和Carlyle等同行在该领域的持续加注，共同构成了一个清晰信号：有限合伙人正在将资本集中到拥有成熟退出记录和结构化交易能力的大型管理机构手中。 “小而美”的风险投资模式在生物科技领域的失灵，源于一个简单的经济学事实：一个Phase 3试验可能消耗相当于一个传统VC基金全部体量的资金。只有拥有足够资产负债表的机构，才有资格参与这场游戏。趋势二：从“股权思维”到“资产思维”的范式迁移 区别于传统VC分散投资初创企业股权的做法，黑石生命科学的策略正引领一种新范式——直接资助单个晚期临床资产，回报来自里程碑付款和销售收入分成，从而规避早期公司整体的估值波动风险。 Galakatos将黑石的角色定义为一座 “桥梁”：“我们寻找那些已经显示出疗效信号、距离监管批准和市场仅一步之遥的资产。黑石的资本和经验就是那座桥梁。”这一策略的底气来自其86%的Phase 3审批通过率——一种在制药行业近乎奇迹的确定性。趋势三：资产稀缺与“更早期、更精准”的竞争 麦肯锡在2026年初的分析中指出，生命科学交易市场正在发生结构性转变：晚期可规模化资产的稀缺和迫在眉睫的专利悬崖（预计到2028年将吞噬近3000亿美元的制药收入）正迫使大型制药公司和PE机构向更早期阶段布局。2024年，大型药企超过一半的交易瞄准了Phase 1或更早期的资产。 这种“资产荒”使得像Anagram这样拥有差异化科学逻辑（重组酶替代传统猪源酶）和明确的临床需求（每日40粒到1粒的体验飞跃）的公司，成为资本追逐的稀缺标的。在资产稀缺的时代，率先识别并锁定优质资产的能力，本身就是一种核心竞争力。趋势四：技术驱动的价值创造——AI与重组技术的产业落地 2025年生命科学投资论坛的共识是：增长——而非简单的成本削减——是估值和退出的首要驱动因素。这意味着PE不再是单纯的金融操盘手。 对于Anagram，黑石看重的不仅是其在改良一个成熟机制上的能力，更是其利用重组DNA技术和蛋白质工程对一个百亿美元级成熟市场进行的“工业化重构”。这是一种“降维打击”思路——用更现代的科技手段改造传统的治疗基建。 与此同时，人工智能在药物发现中的应用已经不再是可有可无的非必需品，而是正在成为价值创造的基础设施。顶级投资机构越来越要求被投公司拥有经过验证的数据能力和AI赋能证据。这并不是一种时髦的叙事，而是一个现实的门槛：没有数据能力的生物技术公司，正在被排除在顶级PE的尽职调查框架之外。 退出逻辑与未来展望一条清晰的黄金路径 对于专业投资者而言，Anagram的退出路径异常清晰。 美国PERT市场目前规模约为每年20亿美元，长期由少数几家制药企业寡头垄断。鉴于ANG003在患者体验上的显著改善——从每日40粒到每餐1粒——一旦获得监管批准，它将极快地侵蚀现有市场份额。 更重要的是，当前大型制药公司在交易定价上变得更加理性——2025年的交易溢价较2020-2024年的高位下降了近40%。这意味着黑石能够以更合理的价格构建和培育资产。待ANG003完成后期临床开发后，那些在消化科和罕见病领域拥有战略布局的大型制药巨头，将成为这张优质资产的天然买家。 黑石此前在Anthos Therapeutics等交易中已经成功验证了这一“建造-培育-出售”模式。Anagram代表了这一模式的再一次精准复制——以独家重注锁定资产，以科学和商业双重能力进行价值创造，在资产价值达到峰值时寻求战略性退出。一个更深层的信号 然而，Anagram交易的意义超越了单个退出案例本身。 它向市场传递了一个更深层的信号：在生物技术的钟摆从“疯狂追新”摆回“价值回归”的时刻，最具备商业确定性的投资，不再是那些拥有光鲜CRISPR或基因编辑概念的明星公司，而是那些踏踏实实解决“吃饭问题”、切中临床刚需的传统赛道革新者。 Anagram用一颗药丸，不仅解放了患者的口袋，也为黑石打开了一个确定性极高的退出门。而在更宏观的层面，63亿美元基金的关闭、86%的Phase 3通过率、从“投公司”到“投资产”的范式迁移，以及从金融操盘手到科学赋能者的角色进化，共同勾勒出一个新纪元的轮廓。 私募股权已不再是生物技术的旁观者或晚期接盘侠。它已经成长为与大型制药巨头并驾齐驱的创新共谋者与价值缔造者 黑石与Anagram的交易提供了一种穿越周期的方法论：寻找那些被主流忽视但真实存在的临床痛苦，用现代科技手段对成熟治疗领域进行工业化重构，以资本和科学能力的双重杠杆放大价值，最终在资产价值最大化的时刻完成退出。 这是一种源自“常识”与“人性”的洞察。而在这个充满不确定性的时代，或许这正是唯一能够穿越周期的硬通货。