b'DO NOT RE-SIZELAB-11532/COM-US-EPK-0001102 MASTERClinically relevant adverse reactions in 10% of patients who receivedTable5 summarizes the adverse reactions in EPCORE NHL-1. Table 6: Select Laboratory Abnormalities ( 20%) That Worsened from EPKINLY included ICANS, sepsis, pleural effusion, COVID-19, pneumoniaTable 5: Adverse Reactions ( 10%) in Patients with Relapsed orBaseline in Patients with Relapsed or Refractory FL Who Received (including pneumonia and COVID-19 pneumonia), tumor flare, febrile Refractory FL Who Received EPKINLY in EPCORE NHL-1 EPKINLY in EPCORE NHL-1neutropenia, upper respiratory tract infections, and tumor lysis syndrome. EPKINLY EPKINLY1Table 4 summarizes laboratory abnormalities in EPCORE NHL-1. Laboratory Abnormality* (N=127)Table 4: Select Laboratory Abnormalities ( 20%) That Worsened fromAdverse Reaction All Grades Grade 3 or 4All Grades Grade 3 or 4 (%)Baseline in Patients with Relapsed or Refractory LBCL Who Received(%) (%)EPKINLY in EPCORE NHL-1 (N=86) HematologyLymphocytes decreased 94 82EPKINLY1 Immune system disorders Hemoglobin decreased 59 10Laboratory Abnormality* All Grades (%) Grade 3 or 4 (%) Cytokine release syndrome* 49 0 White blood cells decreased 58 19Hematology (N=127) Neutrophils decreased 55 30Lymphocyte count decreased 8777 General disorders and administration site conditions Platelets decreased 49 8Injection site reactionsa 58 0 ChemistryHemoglobin decreased 62 12 a # Sodium decreased 51 1.6White blood cells decreased 5322 Fatigue 37 5 ALT increased 47 8Neutrophils decreased 50 32 Pyrexiaa 26 2# AST increased 44 6Platelets decreased 48 12 Edemaa 17 0 Creatinine increased 36 0.8Chemistry Infections and Infestations Alkaline phosphatase increased 29 0COVID-19b 40 19 Bilirubin increased 28 1.6Sodium decreased 56 2.6 Upper respiratory tract infectionc 29 2# Potassium decreased 20 3.1Phosphate decreased2 56 N/A Pneumoniad 17 13# Magnesium decreased 20 0.8Aspartate aminotransferase increased 48 4.6 a # * Laboratory abnormalities were graded based on CTCAE Version 5.0Urinary tract infection 13 5 1 The denominator used to calculate the rate varied from 123 to 127 Alanine aminotransferase increased 45 5.3 Herpesvirus infectione 12 1.6# based on the number of patients with a baseline value and at least one Potassium decreased 34 5.3 post-treatment value.Musculoskeletal and connective tissue disorders DRUG INTERACTIONSMagnesium decreased 31 0 Musculoskeletal paina 28 0.8# For certain CYP substrates, minimal changes in the concentration may lead Creatinine increased 24 3.3 Arthralgia 14 0.8# to serious adverse reactions. Monitor for toxicity or drug concentrations of such CYP substrates when co-administered with EPKINLY.Epcoritamab-bysp Potassium increased 21 1.3 Skin and subcutaneous disorders causes release of cytokines that may suppress activity of CYP enzymes, * Laboratory abnormalities were graded based on CTCAE Version 5.0 Rasha 28 0 resulting in increased exposure of CYP substrates. Increased exposure of 1 The denominator used to calculate the rate varied from 146 to 153CYP substrates is more likely to occur after the first dose of EPKINLY and up based on the number of patients with a baseline value and at least oneGastrointestinal disorders to 14days after the first 48mg dose, and during and after CRS.post-treatment value. Diarrhea 26 1.6# USE IN SPECIFIC POPULATIONS2 CTCAE Version 5.0 does not include numeric thresholds for grading ofNausea 17 0 Pregnancy - Risk Summary:Based on the mechanism of action, EPKINLY hypophosphatemia; all grades represent patients with lab value Lowermay cause fetal harm when administered to a pregnant woman. There are Limit of Normal (LLN). Abdominal paina 17 0.8# no available data on the use of EPKINLY in pregnant women to evaluate for a Relapsed or Refractory Follicular Lymphoma (FL) Constipation 16 0 drug-associated risk. No animal reproductive or developmental toxicity stud-EPCORE NHL-1Mucositisf 12 0 ies have been conducted with epcoritamab-bysp.The safety of EPKINLY was evaluated in EPCORE NHL-1, a single-arm studyEpcoritamab-bysp causes T-cell activation and cytokine release; immune of patients with relapsed or refractory FL after two or more lines of systemicRespiratory disorders activation may compromise pregnancy maintenance. In addition, based on expression of CD20 on B-cells and the finding of B-cell depletion in therapy who received EPKINLY following a 2-step up dosage scheduleCougha 20 0 non-pregnant animals, epcoritamab-bysp can cause B-cell lymphocytopenia (N=127). A separate dose optimization cohort evaluated the recommendedDyspneaa 17 0 in infants exposed to epcoritamab-bysp in-utero. Human immunoglobulin G 3-step up dosage schedule for CRS mitigation (N=86), where EPKINLY was(IgG) is known to cross the placenta; therefore, EPKINLY has the potential to administered via subcutaneous injection until disease progression or Nervous system disorders be transmitted from the mother to the developing fetus. Advise women of unacceptable toxicities according to the following 28-day cycle schedule: Headache 20 0 the potential risk to the fetus. Cycle 1:EPKINLY 0.16 mg on Day 1, 0.8 mg on Day 8, 3 mg on Day 15,g In the U.S. general population, the estimated background risk of major birth and 48 mg on Day 22; Cycle 2-3:EPKINLY 48 mg on Days 1, 8, 15, andNeurological changes 13 0 defects and miscarriage in clinically recognized pregnancies is 2% to 4% 22; Cycles 4-9:EPKINLY 48 mg on Days 1 and 15; Cycles 10 and beyond: Peripheral neuropathy and paresthesiah 13 1.6# and 15% to 20%, respectively.EPKINLY 48 mg on Day 1. Lactation - Risk Summary:There is no information regarding the presence With the exception of CRS, the safety results presented below and inDizziness 11 0 of epcoritamab-bysp in human milk, the effect on the breastfed child, or milk tables 5 and 6 represent data from patients who received the 2-step upPsychiatric disorders production. Because maternal IgG is present in human milk, and there isdosage schedule. The data presented for CRS reflects the 86 patients whoInsomnia 13 0 potential for epcoritamab-bysp absorption leading to serious adversereceived the recommended 3-step up dosage schedule. The study excludedreactions in a breastfed child, advise women not to breastfeed duringpatients with CNS involvement of lymphoma, allogeneic HSCT or solid organRenal and urinary disorders treatment with EPKINLY and for 4 months after the last dose.transplant, ongoing active infection, any patients with known impaired T-cellRenal insufficiencyi 10 1.6# Females and Males of Reproductive Potential:EPKINLY may cause fetal immunity, creatinine clearance 45 ml/min, alanine aminotransferase 3harm when administered to a pregnant woman.times the upper limit of normal, and a cardiac ejection fraction 45%. Adverse reactions were graded based on CTCAE Version 5.0. Pregnancy Testing:Verify pregnancy status in females of reproductive Recommended 3-step up Dosage ScheduleThe frequency of CRS is based on 86 patients with FL who received thepotential prior to initiating EPKINLY.Of the 86 patients with relapsed or refractory FL who received EPKINLY recommended 3-step up dosage schedule in EPCORE NHL-1. Contraception - Females:Advise females of reproductive potential to use following the recommended 3-step up dosage schedule, the median age CRS was graded using ASTCT consensus criteria (Lee et al., 2019). effective contraception during treatment with EPKINLY and for 4months was 63.5 years (range: 33-90), 57%were male, and 100% had an ECOG* The frequency of CRS based on the 127 patients with FL who receivedafter the last dose.performance status of 0 or 1.The median duration of exposure was 5 cyclesthe 2-step up dosage schedule in EPCORE NHL-1 was the following:Pediatric Use:The safety and efficacy of EPKINLY in pediatric patients have (range: 1 to 12cycles). CRS occurred in 49% of patients, with Grade1 CRSAny grade CRS 66%; Grade 1 CRS: 50%; Grade 2 CRS: 26%; Grade 3not been established.occurring in 45% and Grade2 in 9% of patients. Serious adverse reactions# CRS: 1.6%.due to CRS occurred in 28% of patients who received EPKINLY. Dose aOnly grade 3 adverse reactions occurred. Geriatric Useinterruptions due to CRS occurred in 19% of patients who received EPKINLY.bIncludes related grouped terms. LBCL:In patients with relapsed or refractory LBCL who received EPKINLYCOVID-19 includes COVID-19, COVID-19 pneumonia, SARS-CoV-2 testin EPCORE NHL-1, 77 (49%) were 65 years of age and older, and 29 (19%) 2-step up Dosage Schedule c positive. were 75 years of age or older. No clinically meaningful differences in safety Of the 127patients with relapsed or refractory FL who received EPKINLYUpper respiratory tract infection includes preferred terms with upperor efficacy were observed between patients with relapsed or refractory LBCL following a 2-step up dosage schedule, the median age was 65 yearsrespiratory infection and sinusitis, laryngitis viral, nasopharyngitis,who were 65years of age and older compared with younger adult patients.(range: 39 to 84), 62% were male, and 95% had an ECOG performanced oropharyngitis fungal, pharyngitis, rhinitis, rhinovirus infection, tonsillitis.FL:In patients with relapsed or refractory FL who received EPKINLY in status of 0 or 1. The median duration of exposure for patients receiving Pneumonia includes preferred terms with pneumonia, bronchopulmonaryEPCORE NHL-1, 66 (52%) were 65 years of age or older, and 16 (13%) were EPKINLY was 8cycles (range: 1 to 33 cycles). aspergillosis, infectious pleural effusion, infective exacerbation of75 years of age and older.In patients with relapsed or refractory FL, there Serious adverse reactions occurred in 66% of patients who receivedbronchiectasis, Pneumocystis jirovecii pneumonia, pneumonia was a higher rate of fatal adverse reactions, primarily infections, including EPKINLY. Serious adverse reactions in 5% of patients included CRS,e respiratory syncytial viral. COVID-19, in patients older than 65 years of age compared to younger adult COVID-19, pneumonia, and second primary malignancies.Fatal adverse Herpesvirus infection includes herpes simplex, herpes simplex patients. No overall difference in efficacy was observed in patients with reactions occurred in 9% of patients who received EPKINLY, includingreactivation, herpes virus infection, herpes zoster, oral herpes, varicellarelapsed or refractory FL who were 65years of age and older compared COVID-19 (5%), pneumonitis (1.6%), cardiac failure (0.8%), pneumoniaf zoster virus infection. with younger adult patients.(0.8%), and sepsis(0.8%).Mucositis includes aphthous ulcer, mouth ulceration, mucosal inflammation,Manufactured by:g oral pain, oropharyngeal pain, stomatitis, tongue ulceration. Genmab US, Inc.Permanent discontinuation of EPKINLY due to an adverse reaction occurred Neurological changes includes amnesia, aphasia, balance disorder,Plainsboro, NJ 08536, USAin 19% of patients who received EPKINLY. Adverse reactions which resultedbrain fog, confusional state, dysphonia, encephalopathy, extrapyramidal1-855-4GENMAB (1-855-443-6622)in permanent discontinuation of EPKINLY in 2% of patients includeddisorder, hallucination, hypoacusis, memory impairment, mental statusU.S. License Number: 2293COVID-19, Hepatitis E, pneumonitis, and second primary malignancy.changes, tremor, vertigo.Dosage interruptions of EPKINLY due to an adverse reaction occurred in h Peripheral neuropathy and paresthesia includes bells palsy, Marketed by:59% of patients who received EPKINLY. Adverse reactions which requiredhypoesthesia, neuralgia, neuropathy peripheral, paraesthesia, Genmab US, Inc.dosage interruption in 5% of patients included COVID-19, CRS, peripheral sensory neuropathy, polyneuropathy. Plainsboro, NJ 08536pneumonia, upper respiratory tract infection, and fatigue. iRenal insufficiency includes acute kidney injury, blood creatinineandAbbVie Inc.The most common (20%) adverse reactions were injection site reactions,increased, renal impairment. North Chicago, IL 60064CRS, COVID-19, fatigue, upper respiratory tract infection, musculoskeletalClinically relevant adverse reactions in 10% of patients (N=127) whoEPKINLY is a trademark owned by Genmab A/Spain, rash, diarrhea, pyrexia, cough, and headache. The most commonreceived EPKINLY included vomiting, pruritis, hepatotoxicity, ICANS, lower Grade3 to 4 laboratory abnormalities (10%) were decreased lymphocyterespiratory tract infections, cardiac arrhythmias, respiratory tract infections,2024 Genmab A/Scount, decreased neutrophil count, decreased white blood cell count, andpneumonitis, second primary malignancy, vision changes, cellulitis, febrileREF:June 2024decreased hemoglobin. neutropenia, cardiac failure, cytomegalovirus infection and sepsis. CLA-US-240116REF-01422 v3Table 6 summarizes laboratory abnormalities in EPCORE NHL-1. LAB-11532/COM-US-EPK-0001102 MASTER'