TALVEY

1 INDICATIONS AND USAGE TALVEY 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 [see Clinical Studies (14) ]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). TALVEY is a bispecific GPRC5D-directed CD3 T-cell engager 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). ( 1 )

2 DOSAGE AND ADMINISTRATION For subcutaneous injection. ( 2.2 ) Patients should be hospitalized for 48 hours after all doses within the step-up dosing schedule. ( 2.1 ) Administer pretreatment medications as recommended. ( 2.3 ) See Full Prescribing Information for instructions on preparation and administration. ( 2.6 ) TALVEY Weekly Dosing Schedule ( 2.2 ) Dosing schedule Day Dose Based on actual body weight. Step-up dosing schedule Day 1 Step-up dose 1 0.01 mg/kg Day 4 Dose may be administered between 2 to 4 days after the previous dose and may be given up to 7 days after the previous dose to allow for resolution of adverse reactions. Step-up dose 2 0.06 mg/kg Day 7 First treatment dose 0.4 mg/kg Weekly dosing schedule One week after first treatment dose and weekly thereafter Maintain a minimum of 6 days between weekly doses. Subsequent treatment doses 0.4 mg/kg once weekly TALVEY Biweekly (Every 2 Weeks) Dosing Schedule ( 2.2 ) Dosing schedule Day Dose Based on actual body weight. Step-up dosing schedule Day 1 Step-up dose 1 0.01 mg/kg Day 4 Dose may be administered between 2 to 4 days after the previous dose and may be given up to 7 days after the previous dose to allow for resolution of adverse reactions. Step-up dose 2 0.06 mg/kg Day 7 Step-up dose 3 0.4 mg/kg Day 10 Dose may be administered between 2 to 7 days after step-up dose 3. First treatment dose 0.8 mg/kg Biweekly (every 2 weeks) dosing schedule Two weeks after first treatment dose and every 2 weeks thereafter Maintain a minimum of 12 days between biweekly (every 2 weeks) doses. Subsequent treatment doses 0.8 mg/kg every 2 weeks 2.1 Important Dosing Information Administer TALVEY subcutaneously according to the step-up dosing schedule in Tables 1 and 2 to reduce the incidence and severity of cytokine release syndrome (CRS) [see Dosage and Administration (2.2) ] . Administer pretreatment medications prior to each dose of TALVEY in the step-up dosing schedule as recommended [see Dosage and Administration (2.2 , 2.3) ]. TALVEY should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and neurologic toxicity including immune effector cell-associated neurotoxicity syndrome (ICANS) [see Warnings and Precautions (5.1 , 5.2) ] . Due to the risk of CRS and neurologic toxicity, including ICANS, patients should be hospitalized for 48 hours after administration of all doses within the TALVEY step-up dosing schedule [see Dosage and Administration (2.5) and Warnings and Precautions (5.1 , 5.2) ] . 2.2 Recommended Dosage For subcutaneous injection. Administer pretreatment medications prior to each dose of TALVEY in the step-up dosing schedule [see Dosage and Administration (2.3) ] . Administer TALVEY subcutaneously on a weekly or biweekly (every 2 weeks) dosing schedule according to Table 1 or Table 2. Continue treatment until disease progression or unacceptable toxicity. Table 1: TALVEY Weekly Dosing Schedule Dosing schedule Day Dose Based on actual body weight. Step-up dosing schedule Day 1 Step-up dose 1 0.01 mg/kg Day 4 Dose may be administered between 2 to 4 days after the previous dose and may be given up to 7 days after the previous dose to allow for resolution of adverse reactions. Step-up dose 2 0.06 mg/kg Day 7 First treatment dose 0.4 mg/kg Weekly dosing schedule One week after first treatment dose and weekly thereafter Maintain a minimum of 6 days between weekly doses. Subsequent treatment doses 0.4 mg/kg once weekly Table 2: TALVEY Biweekly (Every 2 Weeks) Dosing Schedule Dosing schedule Day Dose Based on actual body weight. Step-up dosing schedule Day 1 Step-up dose 1 0.01 mg/kg Day 4 Dose may be administered between 2 to 4 days after the previous dose and may be given up to 7 days after the previous dose to allow for resolution of adverse reactions. Step-up dose 2 0.06 mg/kg Day 7 Step-up dose 3 0.4 mg/kg Day 10 Dose may be administered between 2 to 7 days after step-up dose 3. First …

5 WARNINGS AND PRECAUTIONS Oral Toxicity and Weight Loss : Monitor for oral toxicity and weight loss. Withhold or permanently discontinue based on severity. ( 5.4 ) Infections : Can cause serious, life-threatening, or fatal infections. Monitor for signs and symptoms of infection; treat appropriately. Withhold or consider permanent discontinuation based on severity. ( 5.5 ) Cytopenias : Monitor complete blood counts. ( 5.6 ) Skin Toxicity : Monitor for skin toxicity, including rash progression, for early intervention and treat appropriately. Withhold as recommended based on severity. ( 5.7 ) Hepatotoxicity: Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold or consider permanent discontinuation based on severity. ( 5.8 ) Embryo-Fetal Toxicity : May cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception. ( 5.9 , 8.1 , 8.3 ) 5.1 Cytokine Release Syndrome (CRS) TALVEY can cause cytokine release syndrome, including life-threatening or fatal reactions [see Adverse Reactions (6.1) ] . 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 TALVEY 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 [see Dosage and Administration (2.2 , 2.3) ]. 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 [see Dosage and Administration (2.5) ] . TALVEY is available only through a restricted program under a REMS [see Warnings and Precautions (5.3) ] . 5.2 Neurologic Toxicity including ICANS TALVEY can cause serious, life-threatening, or fatal neurologic toxicity, including ICANS [see Adverse Reactions (6.1) ] . In the clinical trial, neurologic toxicity, including ICANS, occurred in 55% of patients who received TALVEY at 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, including ataxia/cerebellar ataxia (10%). ICANS was reported in 9% of 265 patients where ICANS was collected and who received TALVEY at the recommended dosages [see Adverse Reactions (6.1) ] . Recurrent ICANS o…

4 CONTRAINDICATIONS None. None. ( 4 )

7 DRUG INTERACTIONS For certain cytochrome P450 (CYP) substrates, minimal changes in the substrate concentration may lead to serious adverse reactions. Monitor for toxicity or drug concentrations of such CYP substrates when co-administered with TALVEY. Talquetamab-tgvs causes release of cytokines [see Clinical Pharmacology (12.2) ] that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. Increased exposure of CYP substrates is more likely to occur from initiation of the TALVEY step-up dosing schedule up to 14 days after the first treatment dose and during and after CRS [see Warnings and Precautions (5.1) ] .

8.1 Pregnancy Risk Summary Based on the mechanism of action, TALVEY may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of TALVEY in pregnant women to evaluate for a drug associated risk. No animal reproductive or developmental toxicity studies have been conducted with talquetamab-tgvs. Talquetamab-tgvs causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. Human immunoglobulin G (IgG) is known to cross the placenta; therefore, TALVEY has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

6 ADVERSE REACTIONS The following adverse reactions are also described elsewhere in the labeling: Cytokine Release Syndrome [see Warnings and Precautions (5.1) ] Neurologic Toxicity, including ICANS [see Warnings and Precautions (5.2) ] Oral Toxicity and Weight Loss [see Warnings and Precautions (5.4) ] Infections [see Warnings and Precautions (5.5) ] Cytopenias [see Warnings and Precautions (5.6) ] Skin Toxicity [see Warnings and Precautions (5.7) ] Hepatotoxicity [see Warnings and Precautions (5.8) ] 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. ( 6.1 ) The most common Grade 3 or 4 laboratory abnormalities (≥30%) are lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hemoglobin decreased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. at 1-800-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Relapsed/Refractory Multiple Myeloma MonumenTAL-1 The safety of TALVEY was evaluated in 339 adult patients with relapsed or refractory multiple myeloma. Patients treated with the weekly dosing schedule received step-up doses of 0.01 mg/kg and 0.06 mg/kg of TALVEY followed by TALVEY 0.4 mg/kg subcutaneously weekly thereafter. Patients treated with the biweekly (every 2 weeks) dosing schedule received step-up doses of 0.01 mg/kg, 0.06 mg/kg, and 0.3 mg/kg (0.75 times the recommended step-up dose 3) followed by TALVEY 0.8 mg/kg subcutaneously every 2 weeks thereafter. The duration of exposure for the 0.4 mg/kg weekly regimen was 5.9 (range: 0.0 to 25.3) months (N=186) and for the 0.8 mg/kg biweekly (every 2 weeks) regimen, it was 3.7 (range: 0.0 to 17.9) months (N=153). Serious adverse reactions occurred in 47% of patients who received TALVEY. Serious adverse reactions in ≥ 2% of patients included CRS (13%), bacterial infection (8%) including sepsis, pyrexia (4.7%), ICANS (3.8%), COVID-19 (2.7%), neutropenia (2.1%), and upper respiratory tract infection (2.1%). Fatal adverse reactions occurred in 3.2% of patients who received TALVEY, including COVID - 19 (0.6%), dyspnea (0.6%), general physical health deterioration (0.6%), bacterial infection (0.3%) including sepsis, basilar artery occlusion (0.3%), fungal infection (0.3%), infection (0.3%), and pulmonary embolism (0.3%). Permanent discontinuation of TALVEY due to an adverse reaction occurred in 9% of patients. Adverse reactions which resulted in permanent discontinuation of TALVEY in > 1% of patients included ICANS. Dosage interruptions of TALVEY due to an adverse reaction occurred in 56% of patients. Adverse reactions which required dosage interruption in > 5% of patients included pyrexia (15%), CRS (12%), upper respiratory tract infection (9%), COVID-19 (9%), bacterial infection (7%) including sepsis, neutropenia (6%), and rash (6%). The most common adverse reactions (≥ 20%) were 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%) were lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hemoglobin decreased. Table 13 summarizes the adverse reactions in MonumenTAL-1. Table 13: Adverse Reactions (≥10%) in Patients with Relapsed or Refractory Multiple Myeloma Who Received TALVEY in MonumenTAL-1 TALVEY N=339 System Organ Class Adverse Reaction Any G…