DANYELZA

6 ADVERSE REACTIONS The following clinically significant adverse reactions are also described elsewhere in the labeling: Serious Infusion-Related Reactions [see Warnings and Precautions (5.1) ] Neurotoxicity [see Warnings and Precautions (5.2) ] Hypertension [see Warnings and Precautions (5.3) ] The most common adverse reactions (≥25%) are infusion-related reaction, pain, tachycardia, vomiting, cough, nausea, diarrhea, decreased appetite, hypertension, fatigue, erythema multiforme, peripheral neuropathy, urticaria, pyrexia, headache, injection site reaction, edema, anxiety, localized edema, and irritability ( 6.1 ). The most common Grade 3 or 4 laboratory abnormalities (≥5%) are decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased platelet count, decreased potassium, increased alanine aminotransferase, decreased glucose, decreased calcium, decreased albumin, decreased sodium, and decreased phosphate ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Y-mAbs Therapeutics, Inc, at 1-833-339-6227 (1-833-33YMABS), or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical TrialsExperience 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. The safety of DANYELZA in combination with GM-CSF was evaluated in patients with refractory or relapsed high-risk neuroblastoma in bone or bone marrow who had demonstrated a partial response, minor response, or stable disease following initial or subsequent therapy, and in patients who were in second complete remission, from two open-label, single arm studies, Study 201 (n=25) and Study 12-230 (n=72). Patients received DANYELZA 9 mg/kg/cycle administered as three separate intravenous infusions of 3 mg/kg (Day 1, 3 and 5) in the first week of each cycle. Patients also received GM-CSF 250 µg/m 2 /day subcutaneously on Days -4 to 0 and GM-CSF 500 µg/m 2 /day subcutaneously on Days 1 to 5 [see Clinical Studies (14) ]. The most common adverse reactions in Studies 201 and 12-230 (≥25% in either study) were infusion-related reaction, pain, tachycardia, vomiting, cough, nausea, diarrhea, decreased appetite, hypertension, fatigue, erythema multiforme, peripheral neuropathy, urticaria, pyrexia, headache, injection site reaction, edema, anxiety, localized edema and irritability. The most common Grade 3 or 4 laboratory abnormalities (≥5% in either study) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased platelet count, decreased potassium, increased alanine aminotransferase, decreased glucose, decreased calcium, decreased albumin, decreased sodium and decreased phosphate. Study 201 In Study 201, among 25 patients who received DANYELZA in combination with GM-CSF, 12% were exposed for 6 months or longer and none were exposed for greater than one year. Serious adverse reactions occurred in 32% of patients who received DANYELZA in combination with GM-CSF. Serious adverse reactions in more than one patient included anaphylactic reaction (12%) and pain (8%). Permanent discontinuation of DANYELZA due to an adverse reaction occurred in 12% of patients. Adverse reactions resulting in permanent discontinuation of DANYELZA included anaphylactic reaction (8%) and respiratory depression (4%). Dosage interruptions of DANYELZA due to an adverse reaction occurred in 84% of patients. Adverse reactions requiring dosage interruption in > 10% of patients included hypotension and bronchospasm. Table 4 summarizes adverse reactions in Study 201. Table 4. Adverse Reactions (>10%) in Patients with Refractory or Relapsed High-Risk Neuroblastoma in Bone or Bone Marrow Who Received DANYELZA with GM-CSF in Study 201 Adverse Reaction DANYELZA with GM-CSF Adverse reactions were graded using CTCAE version 4.0. (n=25) All Grades (%) Grade 3 or 4 (%) Body system General disorders and administration site conditions Pain Pain includes pain, abdominal pain, pain in extremity, bone pain, neck pain, back pain, and musculoskeletal pain. 100 72 Infusion-related reaction Infusion-related reaction includes hypotension, bronchospasm, flushing, wheezing, stridor, urticaria, dyspnea, pyrexia, infusion-related reaction, face edema, edema mouth, tongue edema, lip edema, respiratory tract edema, chills, hypoxia, pruritis and rash occurring on the day of infusion or the day following an infusion. 100 68 Edema 28 0 Fatigue Fatigue includes fatigue, asthenia. 28 0 Pyrexia Pyrexia not occurring on the day of infusion or the day following an infusion 28 0 Respiratory, thoracic and mediastinal disorders Cough 60 0 Rhinorrhea 24 0 Vascular disorders Hypertension 44 4 Gastrointestinal disorders Vomiting 60 4 Diarrhea 56 8 Nausea 56 0 Skin and subcutaneous tissue disorders Urticaria Urticaria, not occurring on the day of infusion or the day following an infusion 32 4 Cardiac disorders Tachycardia Tachycardia includes sinus tachycardia and tachycardia 84 4 Nervous system disorders Peripheral neuropathy Peripheral neuropathy includes peripheral sensory neuropathy, paresthesia, neuralgia. 32 0 Headache 28 8 Depressed level of consciousness 24 16 Eye disorders Neurological disorders of the eye Neurological disorders of the eye includes unequal pupils, blurred vision, and mydriasis. 24 0 Immune system disorders Anaphylactic reaction 12 12 Metabolism and nutrition disorders Decreased appetite 16 0 Infections and infestations Influenza 12 0 Rhinovirus infection 12 0 Upper respiratory tract infection 12 0 Investigations Weight decreased 12 0 Psychiatric disorders Anxiety 12 0 Clinically relevant adverse reactions occurring in ≤10% of patients who received DANYELZA with GM-CSF included peripheral edema (8%). Table 5 summarizes the laboratory abnormalities in Study 201. Table 5. Selected Laboratory Abnormalities (>20%) Worsening from Baseline in Patients with Refractory or Relapsed High-Risk Neuroblastoma in Bone or Bone Marrow Who Received DANYELZA with GM-CSF in Study 201 Laboratory Abnormality DANYELZA with GM-CSF The table presents laboratory parameters with available grading according to CTCAE version 4.0. Baseline evaluation was the last non-missing value prior to first DANYELZA dosing. Each test incidence is based on the number of patients who had both a baseline value and at least one on-study laboratory measurement (range: 23 to 24 patients). n=25 All Grades (%) Grade 3 or 4 (%) Chemistry Decreased potassium 63 8 Decreased albumin 50 0 Increased alanine aminotransferase 42 8 Decreased sodium 29 0 Hematology Decreased lymphocytes 74 30 Decreased platelet count 65 17 Decreased neutrophils 61 39 Decreased hemoglobin 48 4 Study 12-230 In Study 12-230, among 72 patients who received DANYELZA in combination with GM-CSF, 32% were exposed for 6 months or longer and 8% were exposed for greater than one year. Serious adverse reactions occurred in 40% of patients who received DANYELZA in combination with GM-CSF. Serious adverse reactions in > 5% of patients included hypertension (14%), hypotension (11%), and pyrexia (8%). Permanent discontinuation of DANYELZA due to an adverse reaction occurred in 8% of patients. Four (6%) patients permanently discontinued DANYELZA due to hypertension and one (1.4%) patient discontinued due to RPLS. Table 6 summarizes adverse reactions in Study 12-230. Table 6. Adverse Reactions (>10%) in Patients with Refractory or Relapsed High-Risk Neuroblastoma in Bone or Bone Marrow Who Received DANYELZA with GM-CSF in Study 12-230 Adverse Reaction DANYELZA with GM-CSF In Study 12-230, all adverse reactions occurring in Cycle 1 and 2, and adverse reactions of ≥ Grade 3 severity occurring in subsequent cycles were reported. In the dose finding phase, Grade 2 unexpected adverse reactions were also reported for Cycles 3 and later. , Adverse reactions were graded using CTCAE version 4.0. (n=72) All Grades (%) Grade 3 or 4 (%) Body system General disorders and administration site conditions Infusion-related reaction Infusion-related reaction includes hypotension, bronchospasm, flushing, wheezing, stridor, urticaria, dyspnea, pyrexia, face edema, periorbital edema, lip swelling, swollen tongue, chills, hypoxia, pruritis, rash maculopapular and rash erythematous occurring on the day of infusion or the day following an infusion. 94 32 Pain Pain includes pain, abdominal pain, pain in extremity, bone pain, neck pain, back pain, non-cardiac chest pain, flank pain, and musculoskeletal pain. 94 2.8 Fatigue Fatigue includes fatigue, asthenia. 44 0 Injection site reaction 28 0 Localized edema 25 0 Pyrexia Pyrexia not occurring on the day of infusion or the day following an infusion. 11 0 Vascular disorders Hypertension 28 7 Gastrointestinal disorders Vomiting 63 2.8 Nausea 57 1.4 Diarrhea 50 4.2 Constipation 15 0 Skin and subcutaneous tissue disorders Erythema multiforme 33 0 Hyperhidrosis 17 0 Erythema 11 0 Respiratory, thoracic and mediastinal disorders Cough 57 0 Oropharyngeal pain 15 0 Rhinorrhea 15 0 Nervous system disorders Peripheral neuropathy Peripheral neuropathy includes peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia, neuralgia. 25 0 Headache 18 0 Lethargy 14 0 Metabolism and nutrition disorders Decreased appetite 53 4.2 Cardiac disorders Sinus tachycardia 44 1.4 Psychiatric disorders Anxiety 26 0 Irritability 25 0 Investigations Breath sounds abnormal 15 0 Injury and procedural complications Contusion 15 0 Infections and infestations Rhinovirus infection 14 0 Enterovirus infection 13 0 Eye Disorders Neurological disorders of the eye Neurological disorders of the eye includes unequal pupils, blurred vision, accommodation disorder, visual impairment and photophobia. 19 0 Clinically relevant adverse reactions in ≤10% of patients who received DANYELZA with GM-CSF included apnea (4.2%), hypopnea (2.8%), generalized edema (2.8%), peripheral edema (8.3%), and device related infection (4.2%). Table 7 summarizes the laboratory abnormalities in Study 12-230. Table 7. Selected Laboratory Abnormalities (>20%) Worsening from Baseline in Patients with Refractory or Relapsed High-Risk Neuroblastoma in Bone or Bone Marrow Who Received DANYELZA with GM-CSF in Study 12-230 Laboratory Abnormality DANYELZA with GM-CSF The table presents laboratory parameters with available grading according to CTCAE version 4.0. Baseline evaluation was the last non-missing value prior to first DANYELZA dosing. Each test incidence is based on the number of patients who had both a baseline value and at least one on-study laboratory measurement (range 19 to 72 patients). n=72 All Grades (%) Grade 3 or 4 (%) Chemistry Increased glucose 74 0 Decreased albumin 68 7 Decreased calcium 64 8 Increased alanine aminotransferase 55 9 Decreased magnesium 54 0 Increased aspartate aminotransferase 49 4 Decreased phosphate 47 5 Decreased potassium 47 32 Decreased sodium 38 6 Decreased glucose 29 8 Hematology Decreased lymphocytes 79 56 Decreased hemoglobin 76 42 Decreased neutrophils 72 46 Decreased platelets 71 40 6.2 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The detection of anti-drug antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of anti-drug antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies or to other naxitamab products may be misleading. In Study 201, 2 of 24 (8%) patients tested positive for anti-drug antibodies (ADA) after treatment with DANYELZA. In Study 12-230, 27 of 117 patients (23%) tested positive for ADA after treatment with DANYELZA by an assay that was not fully validated; therefore, the incidence of ADA may not be reliable. 6.3 Postmarketing Experience/Spontaneous Reports The following adverse reactions have been identified from expanded access reports with use of DANYELZA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Neurological: Transverse myelitis

4 CONTRAINDICATIONS DANYELZA is contraindicated in patients with a history of severe hypersensitivity reaction to naxitamab-gqgk. Reactions have included anaphylaxis [see Warnings and Precautions (5.1) ]. History of severe hypersensitivity reaction to naxitamab-gqgk. ( 4 )

11 DESCRIPTION Naxitamab-gqgk is a glycolipid disialoganglioside (GD2)-binding recombinant humanized monoclonal IgG1 antibody, that contains human framework regions and murine complementarity-determining regions. Naxitamab-gqgk is produced in a Chinese hamster ovary cell line and has an approximate molecular weight of 144 kDa without glycosylation. DANYELZA (naxitamab-gqgk) injection is a sterile, preservative-free, clear to slightly opalescent and colorless to slightly yellow solution for intravenous infusion. Each single-dose vial contains 40 mg of naxitamab-gqgk in 10 mL of solution. Each mL of solution contains 4 mg of naxitamab-gqgk, and citric acid anhydrous (0.71 mg), poloxamer 188 (1.5 mg), sodium chloride (7.01 mg), sodium citrate (6.3 mg), and Water for Injection, USP. The pH is approximately 5.7.

2 DOSAGE AND ADMINISTRATION The recommended dosage of DANYELZA is 3 mg/kg/day (up to 150 mg/day), administered as an intravenous infusion after dilution on Days 1, 3, and 5 of each treatment cycle. Treatment cycles are repeated every 4 weeks until complete response or partial response, followed by 5 additional cycles every 4 weeks. Subsequent cycles may be repeated every 8 weeks. Discontinue DANYELZA and GM-CSF for disease progression or unacceptable toxicity. Administer GM-CSF subcutaneously prior to and during each treatment cycle as recommended. ( 2.1 ) 2.1 Recommended Dosage The recommended dosage of DANYELZA is 3 mg/kg/day (up to 150 mg/day) on Days 1, 3, and 5 of each treatment cycle, administered as an intravenous infusion after dilution [see Dosage and Administration (2.4 and 2.5) ] in combination with GM-CSF subcutaneously as shown in Table 1. Refer to the GM-CSF Prescribing Information for recommended dosing information. Treatment cycles are repeated every 4 weeks until complete response or partial response, followed by 5 additional cycles every 4 weeks. Subsequent cycles may be repeated every 8 weeks. Discontinue DANYELZA and GM-CSF for disease progression or unacceptable toxicity. Administer pre-infusion medications and supportive treatment, as appropriate, during infusion. [see Dosage and Administration (2.2) ] The recommended dosage regimen for each treatment cycle is described below and in Table 1: Days -4 to 0: administer GM-CSF 250 µg/m 2 /day by subcutaneous injection, beginning 5 days prior to DANYELZA infusion. Days 1 to 5: administer GM-CSF 500 µg/m 2 /day by subcutaneous injection. Administer at least 1 hour prior to DANYELZA administration on Days 1, 3, and 5. Days, 1, 3, and 5: administer DANYELZA 3 mg/kg/day (up to 150 mg/day) by intravenous infusion. Table 1 Dose and Schedule of GM-CSF and DANYELZA Within One Treatment Cycle Day -4 -3 -2 -1 0 1 2 3 4 5 Subcutaneous GM-CSF 250 µg/m 2 /day 500 µg/m 2 /day Intravenous DANYELZA 3 mg/kg/day 3 mg/kg/day 3 mg/kg/day Missed Dose If a DANYELZA dose is missed, administer the missed dose the following week by Day 10. Administer GM-CSF 500 µg /m 2 /day on the first day of the DANYELZA infusion, and on the day before and on the day of the second and third infusion, respectively (i.e. a total of 5 days with 500 µg /m 2 /day). 2.2 Premedications and Supportive Medications Pain Management Prior to and During Infusion [see Warnings and Precautions (5.2) ]: Five days prior to the first infusion of DANYELZA in each cycle, initiate a 12-day course (Day -4 through Day 7) of prophylactic medication for neuropathic pain, such as gabapentin. Administer oral opioids 45-60 minutes prior to initiation of each DANYELZA infusion and additional intravenous opioids as needed for breakthrough pain during the infusion. Consider use of ketamine for pain that is not adequately controlled by opioids. Premedication: Reduce Risk of Infusion-Related Reactions and Nausea/Vomiting [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ] . Administer intravenous corticosteroids (e.g. methylprednisolone 2 mg/kg with maximum dose of 80 mg or equivalent corticosteroid dose) 30 minutes to 2 hours prior to the first infusion of DANYELZA. Administer corticosteroid premedication for subsequent infusions if a severe infusion reaction occurred with the previous infusion or during the previous cycle. Administer an antihistamine, an H2 antagonist, acetaminophen and an antiemetic 30 minutes prior to each infusion. 2.3 Dosage Modifications for Adverse Reactions The recommended dosage modifications for DANYELZA for adverse reactions are presented in Table 2. Table 2. Recommended DANYELZA Dosage Modifications for Adverse Reactions Adverse Reaction Severity Based on Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 Dosage Modifications Infusion-related reactions [see Warnings and Precautions (5.1) ] Grade 2 Defined as: Therapy or infusion interruption indicated but responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics, IV fluids); prophylactic medications indicated for ≤24 hours Reduce DANYELZA infusion rate to 50% of previous rate and monitor closely until recovery to Grade ≤ 1 Increase infusion rate gradually to rate prior to the event as tolerated Grade 3 Defined as: Prolonged (e.g., not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae Immediately interrupt DANYELZA infusion and monitor closely until recovery to Grade ≤ 2 Resume infusion at 50% of the rate prior to the event and increase infusion rate gradually to infusion rate prior to the event as tolerated. Permanently discontinue DANYELZA in patients not responding to medical intervention. Grade 4 infusion-related reactions Defined as: Life-threatening consequences: urgent intervention indicated or Grade 3 or 4 anaphylaxis Permanently discontinue DANYELZA Pain [see Warnings and Precautions (5.2) ] Grade 3 unresponsive to maximum supportive measures Permanently discontinue DANYELZA Reversible posterior leukoencephalopathy syndrome (RPLS) [see Warnings and Precautions (5.2) ] All Grades Permanently discontinue DANYELZA Transverse myelitis [see Warnings and Precautions (5.2) ] All Grades Permanently discontinue DANYELZA Peripheral neuropathy [see Warnings and Precautions (5.2) ] Motor neuropathy: Grade 2 or greater or Sensory neuropathy: Grade 3 or 4 Permanently discontinue DANYELZA Neurological disorders of the eye [see Warnings and Precautions (5.2) ] Grade 2 to 4 resulting in decreased visual acuity or limiting activities of daily living Withhold DANYELZA until resolution If resolved resume DANYELZA at 50% of the prior dose; if tolerated without recurrence of symptoms, gradually increase DANYELZA to dose prior to onset of symptoms Permanently discontinue DANYELZA if not resolved within 2 weeks or upon recurrence Subtotal or total vision loss Permanently discontinue DANYELZA Prolonged urinary retention [see Warnings and Precautions (5.2) ] Persisting following discontinuation of opioids Permanently discontinue DANYELZA Hypertension [see Warnings and Precautions (5.3) ] Grade 3 Withhold DANYELZA or pause infusion until recovery to ≤ Grade 2 Resume infusion at 50% of prior rate; if tolerated without recurrence of symptoms, gradually increase DANYELZA to rate prior to onset of symptoms Permanently discontinue DANYELZA in patients not responding to medical intervention Grade 4 Permanently discontinue DANYELZA Other Adverse Reactions [see Adverse Reactions (6.1) ] Grade 3 Withhold DANYELZA until recovery to Grade ≤ 2 If resolved to Grade ≤ 2 resume DANYELZA at same rate Permanently discontinue DANYELZA if not resolved to Grade ≤2 within 2 weeks Grade 4 Permanently discontinue DANYELZA 2.4 Preparation Use appropriate aseptic technique. Visually inspect vial for particulate matter and discoloration prior to administration. Discard vial if solution is discolored, cloudy, or contains particulate matter. Add appropriate quantities of 5% Albumin (Human), USP and 0.9% Sodium Chloride Injection, USP to an empty, sterile intravenous infusion bag large enough to hold the volume needed for the relevant dose as indicated in Table 3. Allow for 5-10 minutes of passive mixing. Withdraw the required dose of DANYELZA and inject into the infusion bag containing the 5% Albumin (Human), USP and 0.9% Sodium Chloride Injection, USP. Discard any unused portion of DANYELZA left in the vial. Preparation instructions for DANYELZA are described in Table 3. Table 3. Preparation of DANYELZA, 4 mg/ml DANYELZA dose (mg) DANYELZA volume (mL) Volume of 5% Albumin (Human), USP (mL) Total infusion volume achieved by adding sufficient 0.9% Sodium Chloride Injection, USP (mL) Final concentration of prepared DANYELZA infusion (mg/mL) ≤ 80 ≤ 20 10 50 ≤ 1.6 81 to 120 > 20 to 30 15 75 1.1 to 1.6 121 to 160 > 30 to 40 20 100 1.2 to 1.6 161 to 200 > 40 to 50 25 125 1.3 to 1.6 201 to 240 > 50 to 60 30 150 1.3 to 1.6 241 to 280 > 60 to 70 35 175 1.4 to 1.6 If not used immediately, store the diluted DANYELZA infusion solution at room temperature (15°C to 25°C [59ºF to 77ºF]) for up to 8 hours or refrigerate (2°C to 8°C [36°F to 46°F]) for up to 24 hours. Once removed from refrigeration, initiate infusion within 8 hours. 2.5 Administration Administer DANYELZA as a diluted intravenous infusion as recommended. Do not administer DANYELZA as an intravenous push or bolus [see Dosage and Administration (2.4) ] . For the first infusion (Cycle 1, Day 1), administer DANYELZA intravenously over 60 minutes. For subsequent infusions, administer DANYELZA intravenously over 30 to 60 minutes, as tolerated. [see Dosage and Administration (2.1 , 2.3) ]. Observe patients for a minimum of 2 hours following each infusion.

1 INDICATIONS AND USAGE DANYELZA is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy. This indication is approved under accelerated approval based on overall response rate and duration 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). DANYELZA is a GD2-binding monoclonal antibody indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). ( 1 )

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Naxitamab-gqgk binds to the glycolipid GD2. GD2 is a disialoganglioside that is overexpressed on neuroblastoma cells and other cells of neuroectodermal origin, including the central nervous system and peripheral nerves. In vitro, naxitamab-gqgk was able to bind to cell surface GD2 and induce complement dependent cytotoxicity (CDC) and antibody dependent cell-mediated cytotoxicity (ADCC). 12.2 Pharmacodynamics The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of naxitamab-gqgk have not been fully characterized. 12.3 Pharmacokinetics The geometric mean (CV%) maximum plasma concentration (C max ) of naxitamab-gqgk was 57.4 µg/mL (49%) following DANYELZA 3 mg/kg intravenous infusion over 30 minutes. Elimination The mean terminal half-life of naxitamab-gqgk was 8.2 days. Metabolism Naxitamab-gqgk is expected to be metabolized into small peptides by catabolic pathways. Specific Populations Population pharmacokinetic analyses suggest that age (range: 1 to 34 years), sex and race have no clinically important effect on the clearance (CL) of naxitamab-gqgk. The naxitamab-gqgk systemic exposure (AUC) at 150 mg/day (450 mg per cycle) for patients with body weight over 50 kg is not expected to differ clinically from that of the naxitamab-gqgk exposures at 3 mg/kg/day (9 mg/kg per cycle) for patients with body weight of 30 - 50 kg.

12.1 Mechanism of Action Naxitamab-gqgk binds to the glycolipid GD2. GD2 is a disialoganglioside that is overexpressed on neuroblastoma cells and other cells of neuroectodermal origin, including the central nervous system and peripheral nerves. In vitro, naxitamab-gqgk was able to bind to cell surface GD2 and induce complement dependent cytotoxicity (CDC) and antibody dependent cell-mediated cytotoxicity (ADCC).

12.2 Pharmacodynamics The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of naxitamab-gqgk have not been fully characterized.

12.3 Pharmacokinetics The geometric mean (CV%) maximum plasma concentration (C max ) of naxitamab-gqgk was 57.4 µg/mL (49%) following DANYELZA 3 mg/kg intravenous infusion over 30 minutes. Elimination The mean terminal half-life of naxitamab-gqgk was 8.2 days. Metabolism Naxitamab-gqgk is expected to be metabolized into small peptides by catabolic pathways. Specific Populations Population pharmacokinetic analyses suggest that age (range: 1 to 34 years), sex and race have no clinically important effect on the clearance (CL) of naxitamab-gqgk. The naxitamab-gqgk systemic exposure (AUC) at 150 mg/day (450 mg per cycle) for patients with body weight over 50 kg is not expected to differ clinically from that of the naxitamab-gqgk exposures at 3 mg/kg/day (9 mg/kg per cycle) for patients with body weight of 30 - 50 kg.

20230714

5

3 DOSAGE FORMS AND STRENGTHS Injection: 40 mg/10 mL (4 mg/mL) clear to slightly opalescent and colorless to slightly yellow solution in a single-dose vial. Injection: 40 mg/10 mL (4 mg/mL) in a single-dose vial. ( 3 )

DANYELZA Naxitamab Naxitamab Naxitamab TRISODIUM CITRATE DIHYDRATE ANHYDROUS CITRIC ACID SODIUM CHLORIDE POLOXAMER 188 Water

13.2 Animal Toxicology and/or Pharmacology Non-clinical studies suggest that naxitamab-gqgk-induced neuropathic pain is mediated by binding of the antibody to the GD2 antigen located on the surface of peripheral nerve fibers and myelin and subsequent induction of immune-mediated cytotoxic activity. In a nude rat model, slight-moderate hyperplasia and erosion of the glandular mucosa of the stomach occurred, occasionally accompanied by diffuse inflammation. Complete recovery of all histopathological findings in the stomachs of male rats was observed; however, only partial recovery was observed in the stomachs of female rats during the four week off-drug period.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No animal studies have been conducted to evaluate the carcinogenic or mutagenic potential of naxitamab-gqgk. Dedicated studies evaluating the effects of naxitamab-gqgk on fertility in animals have not been conducted.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No animal studies have been conducted to evaluate the carcinogenic or mutagenic potential of naxitamab-gqgk. Dedicated studies evaluating the effects of naxitamab-gqgk on fertility in animals have not been conducted. 13.2 Animal Toxicology and/or Pharmacology Non-clinical studies suggest that naxitamab-gqgk-induced neuropathic pain is mediated by binding of the antibody to the GD2 antigen located on the surface of peripheral nerve fibers and myelin and subsequent induction of immune-mediated cytotoxic activity. In a nude rat model, slight-moderate hyperplasia and erosion of the glandular mucosa of the stomach occurred, occasionally accompanied by diffuse inflammation. Complete recovery of all histopathological findings in the stomachs of male rats was observed; however, only partial recovery was observed in the stomachs of female rats during the four week off-drug period.

BLA761171

DANYELZA

Naxitamab

73042-201

HUMAN PRESCRIPTION DRUG

INTRAVENOUS

PRINCIPAL DISPLAY PANEL - 40 mg/10 mL Vial Carton NDC 73042-201-01 DANYELZA™ (naxitamab-gqgk) Injection 40 mg/10 mL (4 mg/mL) Rx ONLY For intravenous infusion after dilution Single-dose vial Discard unused portion No preservative Y-mAbs Therapeutics, Inc.™ PRINCIPAL DISPLAY PANEL - 40 mg/10 mL Vial Carton

DANYELZA is a trademark of Y-mAbs Therapeutics, Inc. © 2020 Y-mAbs Therapeutics, Inc. – All rights reserved. Manufactured by: Y-mAbs Therapeutics, Inc 230 Park Avenue, Suite 3350 New York, NY 10169 U.S. License No. 2209

17 PATIENT COUNSELING INFORMATION Advise the patient and caregiver to read the FDA-approved patient labeling (Patient Information). Serious Infusion-Related Reactions Advise patients and caregivers that DANYELZA can cause serious infusion-related reactions and anaphylaxis and to immediately report any signs or symptoms, such as facial or lip swelling, urticaria, or difficulty breathing, that occur during or following the infusion [see Warnings and Precautions (5.1) ] . Neurotoxicity Advise patients and caregivers that DANYELZA can cause neurotoxicity, including severe pain, peripheral neuropathy, neurological disorders of the eye, prolonged urinary retention, transverse myelitis, and reverse posterior leukoencephalopathy syndrome. Advise patients to contact their healthcare provider for any new or worsening neurological symptoms. [see Warnings and Precautions (5.2) ]. Hypertension Advise patients and caregivers that DANYELZA can cause hypertension and to immediately report signs or symptoms of hypertension [see Warnings and Precautions (5.3) ]. Embryo-Fetal Toxicity [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1 , 8.3) ] . Advise females of reproductive potential, including pregnant women, of the potential risk to the fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy and to use effective contraception during treatment with and for 2 months after the final dose of DANYELZA Lactation Advise women not to breastfeed during treatment with DANYELZA and for 2 months after the final dose [see Use in Specific Populations (8.2) ].

14 CLINICAL STUDIES The efficacy of DANYELZA in combination with GM-CSF was evaluated in two open-label, single arm trials in patients with high-risk neuroblastoma with refractory or relapsed disease in the bone or bone marrow, Study 201 and Study 12-230. Study 201 The efficacy of DANYELZA in combination with GM-CSF was evaluated in Study 201 (NCT03363373), a multicenter open-label, single arm trial, in a subpopulation of patients who had refractory or relapsed high-risk neuroblastoma in the bone or bone marrow and demonstrated a partial response, minor response, or stable disease to prior therapy. Patients with progressive disease were excluded. All patients received at least one systemic therapy to treat disease outside of the bone or bone marrow prior to enrollment. Patients received DANYELZA 9 mg/kg/cycle administered as three separate intravenous infusions of 3 mg/kg on Days 1, 3 and 5 of each cycle. Patients received GM-CSF subcutaneously at 250 µg/m 2 /day on Days -4 to 0 and at 500 µg/m 2 /day on Days 1 to 5. Preplanned radiation to the primary site was allowed. The major efficacy outcome measure was overall response rate (ORR) according to the revised International Neuroblastoma Response Criteria (INRC), as determined by independent pathology and imaging review and confirmed by at least one subsequent assessment. An additional efficacy outcome measure was duration of response (DOR). Of the 22 patients included in the efficacy analysis, 64% had refractory disease and 36% had relapsed disease; the median age was 5 years (range 3 to 10 years), 59% were male; 45% were White, 50% were Asian and 5% were Black. MYCN amplification was present in 14% of patients and 86% of patients were International Neuroblastoma Staging System (INSS) stage 4 at time of diagnosis. Disease sites included 59% in the bone only, 9% in bone marrow only, and 32% in both. Prior therapies included surgery (91%), chemotherapy (95%), radiation (36%), autologous stem cell transplant (ASCT) (18%), and anti-GD2 antibody treatment (18%). Efficacy results for Study 201 are described in Table 8. Table 8. Efficacy Results from Study 201 DANYELZA with GM-CSF (n=22) CI = confidence interval NE: not estimable. Overall response rate Overall response rate is defined as a complete or partial response according to the revised INRC (2017) that was confirmed by at least one subsequent assessment. Responses were observed in the bone, bone marrow, or both bone and bone marrow. (95% CI) 45% (24%, 68%) Complete response rate 36% Partial response rate 9% Duration of response Median (95% CI), months 6.2 (4.9, NE) Responders with DOR ≥ 6 months 30% In an exploratory analysis in the subset of patients previously treated with an anti-GD2 antibody (n=4), one patient demonstrated a confirmed complete response and no patients demonstrated a partial response. Study 12-230 The efficacy of DANYELZA in combination with GM-CSF was evaluated in Study 12-230 (NCT01757626), a single center, open-label, single arm trial, in a subpopulation of patients who had relapsed or refractory high-risk neuroblastoma in bone or bone marrow and demonstrated a partial response, minor response, or stable disease to prior therapy. Patients with progressive disease were excluded. All patients received at least one systemic therapy to treat disease outside of the bone or bone marrow prior to enrollment. Patients were required to have received at least one dose of DANYELZA at a dose of 3 mg/kg or greater per infusion and have evaluable disease at baseline according to independent review per the revised INRC. Patients received DANYELZA 9 mg/kg/cycle administered as three separate intravenous infusions of 3 mg/kg (on Days 1, 3 and 5) in the first week of each cycle. Patients received GM-CSF subcutaneously at 250 µg/m 2 /day on Days -4 to 0 and at 500 µg/m 2 /day on Days 1 to 5. Radiation to non-target bony lesions and soft tissue lesions was permitted at the investigator's discretion; assessment of response excluded sites that received radiation. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR), as determined by independent pathology and imaging review according to the revised INRC and confirmed by at least one subsequent assessment. Of the 38 patients included in the efficacy analysis, 55% had relapsed neuroblastoma and 45% had refractory disease; 50% were male, the median age was 5 years (range 2 to 23 years), 74% were White, 8% Asian and 5% were Black, 5% Native American/American Indian/Alaska Native, 3% other races and 5% was not available. MYCN-amplification was present in 16% of patients and most patients were International Neuroblastoma Staging System (INSS) stage 4 (95%). Fifty percent (50%) of patients had disease involvement in the bone only, 11% only in bone marrow, and 39% in both. Prior therapies included surgery (100%), chemotherapy (100%), radiation (47%), autologous stem cell transplant (ASCT) (42%), and anti-GD2 antibody treatment (58%). Efficacy results are provided in Table 9. Table 9. Efficacy Results from Study 12-230 DANYELZA with GM-CSF (n=38) CI = confidence interval Overall response rate Overall response rate is defined as a complete or partial response according to the revised INRC (2017) that was confirmed by at least one subsequent assessment. Responses were observed in the bone, bone marrow, or both bone and bone marrow. (95% CI) 34% (20%, 51%) Complete response rate 26% Partial response rate 8% Duration of Response Responders with DOR ≥ 6 months 23% In an exploratory analysis in the subset of patients previously treated with an anti-GD2 antibody (n=22), the ORR was 18% (95% CI 5%, 40%), with no patients having a documented response of 6 months or greater.

8.5 Geriatric Use Neuroblastoma is largely a disease of pediatric and young adult patients. Clinical studies of DANYELZA in combination with GM-CSF did not include patients 65 years of age and older.

8.4 Pediatric Use The safety and effectiveness of DANYELZA, in combination with GM-CSF for the treatment of relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response or stable disease following prior therapy, have been established in pediatric patients 1 year of age and older. Safety and effectiveness have not been established in pediatric patients younger than 1 year of age.

8.1 Pregnancy Risk Summary Based on its mechanism of action, DANYELZA may cause fetal harm when administered to pregnant women [see Clinical Pharmacology (12.1) ]. There are no available data on the use of DANYELZA in pregnant women and no animal reproduction studies have been conducted with DANYELZA. IgG1 monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses, with the largest amount transferred during the third trimester. Advise pregnant women of potential risk to a 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.

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on its mechanism of action, DANYELZA may cause fetal harm when administered to pregnant women [see Clinical Pharmacology (12.1) ]. There are no available data on the use of DANYELZA in pregnant women and no animal reproduction studies have been conducted with DANYELZA. IgG1 monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses, with the largest amount transferred during the third trimester. Advise pregnant women of potential risk to a 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. 8.2 Lactation Risk Summary There are no data on the presence of naxitamab-gqgk in human milk or its effects on the breastfed child, or on milk production, however, human IgG is present in human milk. Because of the potential for serious adverse reactions in a breastfed child from DANYELZA, advise women not to breastfeed during treatment and for 2 months after the final dose of DANYELZA. 8.3 Females and Males of Reproductive Potential DANYELZA may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ]. Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating DANYELZA. Contraception Females Advise females of reproductive potential to use effective contraception during treatment and for 2 months after the final dose of DANYELZA. 8.4 Pediatric Use The safety and effectiveness of DANYELZA, in combination with GM-CSF for the treatment of relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response or stable disease following prior therapy, have been established in pediatric patients 1 year of age and older. Safety and effectiveness have not been established in pediatric patients younger than 1 year of age. 8.5 Geriatric Use Neuroblastoma is largely a disease of pediatric and young adult patients. Clinical studies of DANYELZA in combination with GM-CSF did not include patients 65 years of age and older.

16 HOW SUPPLIED / STORAGE AND HANDLING DANYELZA (naxitamab-gqgk) injection is a sterile, preservative-free, clear to slightly opalescent and colorless to slightly yellow solution for intravenous infusion supplied as a carton containing one 40mg/10 mL (4 mg/mL) single-dose vial. NDC 73042-201-01 Store DANYELZA vial refrigerated at 2°C to 8°C (36°F to 46°F) in the outer carton to protect from light until time of use.

Store DANYELZA vial refrigerated at 2°C to 8°C (36°F to 46°F) in the outer carton to protect from light until time of use.

WARNING: SERIOUS INFUSION-RELATED REACTIONS and NEUROTOXICITY WARNING: SERIOUS INFUSION-RELATED REACTIONS and NEUROTOXICITY See full prescribing information for complete boxed warning Serious Infusion-Related Reactions: DANYELZA can cause serious infusion reactions, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor. Premedicate prior to each DANYELZA infusion as recommended. Reduce the rate, interrupt infusion, or permanently discontinue DANYELZA based on severity ( 2.2 , 2.3 , 4 , 5.1 ). Neurotoxicity: DANYELZA can cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis, and reversible posterior leukoencephalopathy syndrome (RPLS). Premedicate to treat neuropathic pain as recommended. Permanently discontinue DANYELZA based on the adverse reaction and severity ( 2.2 , 2.3 , 5.2 ). Serious Infusion-Related Reactions DANYELZA can cause serious infusion reactions, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor. Infusion reactions of any Grade occurred in 94-100% of patients. Severe infusion reactions occurred in 32-68% and serious infusion reactions occurred in 4 - 18% of patients in DANYELZA clinical studies [see Warnings and Precautions (5.1) ]. Premedicate prior to each DANYELZA infusion as recommended and monitor patients for at least 2 hours following completion of each infusion. Reduce the rate, interrupt infusion, or permanently discontinue DANYELZA based on severity [see Dosage and Administration (2.2 , 2.3) , Contraindications (4) , and Warnings and Precautions (5.1) ]. Neurotoxicity DANYELZA can cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis and reversible posterior leukoencephalopathy syndrome (RPLS). Pain of any Grade occurred in 94-100% of patients in DANYELZA clinical studies [see Warnings and Precautions (5.2) ]. Premedicate to treat neuropathic pain as recommended. Permanently discontinue DANYELZA based on the adverse reaction and severity [see Dosage and Administration (2.2 , 2.3) and Warnings and Precautions (5.2) ].