Video Chapter 1: High-risk neuroblastoma with bone and/or bone marrow disease

[PRESENTER: David Dickens, MD, FAAP, Pediatric Hematologist-Oncologist. Dr. Dickens received compensation from Y-mAbs Therapeutics for his participation in this video.]

DR. DICKENS: Hello, I’m David Dickens, a pediatric oncologist for over 20 years. In this video, I will address high-risk neuroblastoma with bone and/or bone marrow disease.

Neuroblastoma is the most common pediatric extracranial solid tumor.¹ Half of neuroblastoma cases are classified as high risk, which typically involves metastatic disease.^2,3 Bone and bone marrow are the most common sites of metastatic neuroblastoma.^4,5 In children presenting with metastatic disease, 70% of metastases involve bone marrow and 55% involve cortical bone.⁴

Despite advances in care, response to high-risk neuroblastoma treatment remains poor, with approximately 2/3 of patients not obtaining a complete metastatic response to induction therapy.⁶ In other words, some patients are refractory to induction therapy, meaning they achieve a partial response, a minor response, or stable disease following treatment. Furthermore, despite intensive multimodal frontline treatment, 2 in 5 patients eventually relapse.⁷

So, what are the treatment goals for these patients? When high-risk neuroblastoma involves disease in the bone and/or bone marrow, reducing or eliminating that disease is a goal.² Monitoring this goal involves assessing disease in the bone and bone marrow, which requires both biopsy and imaging.² Some details are presented here.

[TEXT ON SCREEN: Bilateral aspirates, bilateral trephine biopsies detect and quantify NB cells in bone marrow; ¹²³I-MIBG imaging detects metastases in bone for MIBG-avid tumors; FDG-PET, PET/CT scans for MIBG-nonavid tumors.]

DR DICKENS: Note that MIBG imaging is widely used as a diagnostic and prognostic indicator for high-risk neuroblastoma.⁸ Specifically, MIBG imaging is used to quantify metastatic disease in the bone and soft tissue, generating a Curie score.^2,8-10

To determine Curie score, the body is subdivided into 10 regions: 9 skeletal regions and 1 soft tissue region.⁸ Each region is designated a score of 0-3 points, with a maximum collective score of 30 points—the higher the score, the greater the extent of disease. Most of the score—up to 27 of the 30 points—is allocated to bone disease, with the remaining 3 potential points allocated to soft tissue.⁸

[VISUAL ON SCREEN: Diagram of a child’s body subdivided into 9 skeletal regions.]

Just as higher Curie scores reflect greater extent of disease, lower scores reflect less disease, with a score of 0 representing no disease in the bone or soft tissue.

Tracking Curie score throughout treatment allows you to monitor the disease course and treatment response. Importantly, an absolute Curie score of 0-2 prior to transplant has been shown to be more clinically prognostic than relative reduction in Curie score.^8-10

Again, an incomplete response to treatment signifies residual disease, and if that disease is in the bone or soft tissue, the Curie score will be above 0.

I hope you found this video informative. To learn more about DANYELZA, you can watch the other chapters in this video series and visit danyelzahcp.com. Now, please take a moment to view the Important Safety Information for DANYELZA. Thank you.

References: 1. Smith V, Foster J. Children (Basel). 2018;5(9):114. 2. Park JR, Bagatell R, Cohn SL, et al. J Clin Oncol. 2017;35(22):2580-2587. 3. Irwin MS, Naranjo A, Zhang FF, et al. J Clin Oncol. 2021;39:3229-3241. 4. DuBois SG, Kalika Y, Lukens JN, et al. J Pediatr Hematol Oncol. 1999;21(3):181-189. 5. Sharp SE, Trout AT, Weiss BD, et al. Radiographics. 2016;36:258-278. 6. Garaventa A, Poetschger U, Valteau-Couanet D, et al. J Clin Oncol. 2021;39(23):2552-2563. 7. Pinto N, Naranjo A, Hibbitts E, et al. Eur J Cancer. 2019;112:66-79. 8. Yanik GA, Parisi MT, Naranjo A, et al. J Nucl Med. 2018;59:502-508. 9. Yanik GA, Parisi MT, Shulkin BL, et al. J Nucl Med. 2013;54(4):541-548. 10. Streby KA, Parisi MT, Shulkin BL, et al. Pediatr Blood Cancer. 2023;e30418. https://doi.org/10.1002/pbc.30418.

Video Chapter 2: DANYELZA clinical studies: design and patient population

[PRESENTER: David Dickens, MD, FAAP, Pediatric Hematologist-Oncologist. Dr. Dickens received compensation from Y-mAbs Therapeutics for his participation in this video.]

DR. DICKENS: Hello, I’m David Dickens, a pediatric oncologist for over 20 years. In this video, I’ll address the DANYELZA clinical studies.

DANYELZA is the only FDA-approved therapy for high-risk neuroblastoma in the bone and/or bone marrow when response to induction therapy or when response to relapse therapy is incomplete.¹ Note that “incomplete response” is defined as a partial response, minor response, or stable disease to prior therapy. Treatment with DANYELZA is backed by more than a decade of clinical trial experience and was approved by the FDA in 2020.²

Excluded from the studies were patients with actively progressing disease and/or evaluable neuroblastoma outside of the bone and bone marrow.¹

Study 12-230 was a phase 1/2, open-label, single-arm, single-center trial with a total of 72 participants.¹ The safety analysis included all 72 patients who started an infusion of DANYELZA. The efficacy analysis included only patients with evaluable disease in the bone and/or bone marrow at baseline, which was 38 patients.

The second study, Study 201, is an ongoing phase 2, open-label, single-arm, global, multicenter trial.¹ The initial analysis included 25 patients. All 25 patients who started an infusion were included in the safety analysis, and 22 of the 25 patients had evaluable disease in the bone and/or bone marrow at baseline and were included in the efficacy analysis.

A subsequent pre-specified interim analysis for Study 201 was conducted, for which additional patients were recruited, bringing the total number of participants up from 25 to 74.³ Trial sites are in the US, Canada, Denmark, Germany, Italy, Spain, and Hong Kong. Again, all patients who started an infusion were included in the safety analysis, and 52 of the 74 patients were included in the efficacy analysis.

The primary endpoint in both studies was overall response rate. Secondary endpoints included duration of response, complete response, and safety.¹

Now let’s take a look at some baseline patient and disease characteristics in the DANYELZA with GM-CSF trials.

[VISUAL ON SCREEN: Table showing baseline patient and disease characteristics in Study 12-230, the Study 201 initial analysis, and the Study 201 pre-specified interim analysis.]

DR. DICKENS: The table shown breaks out the information by study, delineating patients included in the efficacy analysis for Study 12-230, the initial analysis of Study 201, and the pre-specified interim analysis of Study 201.^1,3

As you can see, the table presents details on the patients’ type of disease, site of disease, and prior treatments. For instance, both refractory and relapsed patients were included in the trials, and many patients had poor prognostic factors, such as MYCN amplification and INSS stage 4 disease. Some patients had disease in bone only, some in bone marrow only, and some in both bone and bone marrow. The majority of patients had prior surgery and chemotherapy. Patients with prior radiation, stem cell transplant, and anti-GD2 antibody treatment were also included.^1,3

The trials’ efficacy results are discussed in chapters 3-6. Feel free to pause the video if you’d like to take a few moments to review this information.

I hope you found this video informative. To learn more about DANYELZA, you can watch the other chapters in this video series and visit danyelzahcp.com. Now, please take a moment to view the Important Safety Information for DANYELZA. Thank you.

References: 1. DANYELZA. [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; 2024. 2. NIH US National Library of Medicine. https://clinicaltrials.gov/ct2/show/NCT01419834?term=NCT01419834&draw=2&rank=1. Accessed June 15, 2023. 3. Data on file. Y-mAbs Therapeutics, Inc.

Video Chapter 3: DANYELZA efficacy results in registrational studies

[PRESENTER: David Dickens, MD, FAAP, Pediatric Hematologist-Oncologist. Dr. Dickens received compensation from Y-mAbs Therapeutics for his participation in this video.]

DR. DICKENS: Hello, I’m David Dickens, a pediatric oncologist for over 20 years. In this video, I’ll address efficacy data from the DANYELZA with GM-CSF registrational studies.

As a reminder, DANYELZA may be considered for high-risk neuroblastoma patients with disease in the bone and/or bone marrow who have an incomplete response to induction therapy or who have an incomplete response to relapse therapy.¹ Note that “incomplete response” is defined as a partial response, minor response, or stable disease to prior therapy.

There were 2 DANYELZA with GM-CSF registrational studies: Study 12-230 and Study 201. Details about the study designs and baseline patient and disease characteristics are described in chapter 2.¹ Study 12-230 was a phase 1/2 trial with 38 patients included in the efficacy analysis. Study 201 is an ongoing phase 2 trial that had 22 patients in its initial efficacy analysis. A pre-specified interim analysis for Study 201 was conducted, and results from that interim analysis are presented in chapters 4 through 6.

For both studies, the primary endpoint was overall response rate, or ORR. ORR was defined as a complete response or partial response according to the INRC 2017 and confirmed by at least 1 subsequent assessment. Responses were evaluated by independent review.¹

Now to the results. In Study 12-230 and the Study 201 initial analysis, more than 1/3 of patients responded and more than 1/4 of patients achieved a complete response with DANYELZA with GM-CSF.¹

[VISUAL ON SCREEN: Bar graph showing overall response rate, complete response, and partial response data from Study 12-230.]

DR. DICKENS: As you can see in this bar graph from Study 12-230, 34% of patients responded and 26% achieved a complete response.¹

[VISUAL ON SCREEN: Bar graph showing overall response rate, complete response, and partial response data from the Study 201 initial analysis.]

DR. DICKENS: This bar graph shows the results from the Study 201 initial analysis, in which 45% of patients responded and 36% achieved a complete response. The median duration of response was 6.2 months.¹

To learn more about DANYELZA efficacy, including results of the Study 201 pre-specified interim analysis, please refer to chapters 4-6.

I hope you found this video informative. To learn more about DANYELZA, you can watch the other chapters in this video series and visit danyelzahcp.com. Now, please take a moment to view the Important Safety Information for DANYELZA. Thank you.

Reference: 1. DANYELZA. [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; 2024.

Video Chapter 4: DANYELZA efficacy results in Study 201 pre-specified interim analysis, patients with an incomplete response to induction

[PRESENTER: David Dickens, MD, FAAP, Pediatric Hematologist-Oncologist. Dr. Dickens received compensation from Y-mAbs Therapeutics for his participation in this video.]

DR. DICKENS: Hello, I’m David Dickens, a pediatric oncologist for over 20 years. In this video, I’ll address responses seen in the DANYELZA with GM-CSF registrational studies and then focus on results from the Study 201 pre-specified interim analysis. Specifically, I’ll present the results in all efficacy-evaluable patients and in those with a prior incomplete response to induction therapy.

As a reminder, DANYELZA may be considered for high-risk neuroblastoma patients with disease in the bone and/or bone marrow who have an incomplete response to induction therapy or who have an incomplete response to relapse therapy.¹ Note that “incomplete response” is defined as a partial response, minor response, or stable disease to prior therapy.

There were 2 DANYELZA with GM-CSF registrational studies, which are described in detail in chapter 2.¹ Study 12-230 was a phase 1/2 trial with 38 patients included in the efficacy analysis. Study 201 is a phase 2 trial that had 22 patients in its initial efficacy analysis¹; a pre-specified interim analysis for Study 201 was conducted, for which additional patients were recruited, bringing the number of patients in the efficacy analysis to 52.²

The primary endpoint was overall response rate, or ORR. ORR was defined as a complete response or partial response according to the INRC 2017 and confirmed by at least 1 subsequent assessment.¹

In Study 12-230 and the initial analysis of Study 201—in other words, the registrational studies—more than 1/3 of patients responded and more than 1/4 achieved a complete response.¹

[VISUAL ON SCREEN: Bar graph showing overall response rate, complete response, and partial response data from the Study 201 pre-specified interim analysis.]

DR. DICKENS: Now let’s look at results from the Study 201 interim analysis. Shown here are the overall, complete, and partial responses for all 52 patients in the efficacy analysis.² With a median follow-up of 5.9 months, 40% of patients responded to DANYELZA with GM-CSF, and 29% achieved a complete response. The remaining 11% of responders achieved a partial response.

For these responding patients, the median duration of response was not estimable because responses were ongoing or patients were censored at the time of data cutoff.²

[VISUAL ON SCREEN: Bar graph showing overall response, partial response, and complete response data from the Study 201 pre-specified interim analysis in patients with incomplete response to induction.]

DR. DICKENS: Next, let’s review response rates in the pre-specified subgroup of patients with an incomplete response to induction therapy. As a reminder from chapter 2, which includes baseline characteristics, half the efficacy-evaluable patients in the Study 201 interim analysis fell into this category.²

Shown here are the overall, complete, and partial responses for these patients. As you can see, 46% responded to DANYELZA with GM-CSF, and 31% achieved a complete response. The remaining 15% of responders achieved a partial response.²

[VISUAL ON SCREEN: Swimmer plot of patients in the Study 201 pre-specified interim analysis with incomplete response to induction.]

DR. DICKENS: In the swimmer plot, you see patient-level data of patients who had an incomplete response to induction therapy.²

The plot shows responses and Curie scores at baseline and at subsequent points following initiation of treatment with DANYELZA plus GM-CSF.

The colors within the bars correspond to the response, with gray reflecting that no assessment was performed and darkening shades of blue reflecting deeper responses. The letters represent an assessment timepoint and a dark square represents progressive disease.

The numbers to the right of the bars are each patient’s Curie scores during treatment, and they are plotted in the bars at the times they were assessed. Curie score assessments were performed at baseline, at first assessment of response, and at each subsequent assessment of response.

The baseline Curie score, which is the second column of numbers, is the Curie score assessed before the first administration of DANYELZA with GM-CSF.

Feel free to pause the video if you’d like to take a few moments to review this information.

To learn more about Curie score in high-risk neuroblastoma, please refer to chapter 1.

To learn about results in the subgroup of patients in the Study 201 interim analysis with an incomplete response to relapse therapy, please refer to chapter 5.

I hope you found this video informative. To learn more about DANYELZA, you can watch the other chapters in this video series and visit danyelzahcp.com. Now, please take a moment to view the Important Safety Information for DANYELZA. Thank you.

Reference: 1. DANYELZA. [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; 2024. 2. Data on file. Y-mAbs Therapeutics, Inc.

Video Chapter 5: DANYELZA efficacy results in Study 201 pre-specified interim analysis, patients with an incomplete response to relapse therapy

[PRESENTER: David Dickens, MD, FAAP, Pediatric Hematologist-Oncologist. Dr. Dickens received compensation from Y-mAbs Therapeutics for his participation in this video.]

DR. DICKENS: Hello, I’m David Dickens, a pediatric oncologist for over 20 years. In this video, I’ll address responses seen in the DANYELZA with GM-CSF registrational studies and then focus on results from the Study 201 pre-specified interim analysis. Specifically, I’ll present the results in all efficacy-evaluable patients and in those with an incomplete response to relapse therapy.

As a reminder, DANYELZA may be considered for patients with high-risk neuroblastoma in the bone and/or bone marrow who have an incomplete response to induction therapy or who have an incomplete response to relapse therapy.¹ Note that “incomplete response” is defined as a partial response, minor response, or stable disease to prior therapy.

There were 2 DANYELZA with GM-CSF registrational studies, which are described in detail in chapter 2.¹ Study 12-230 was a phase 1/2 trial with 38 patients included in the efficacy analysis. Study 201 is a phase 2 trial that had 22 patients in its initial efficacy analysis¹; a pre-specified interim analysis for Study 201 was conducted, for which additional patients were recruited, bringing the number of patients in the efficacy analysis to 52.²

The study’s primary endpoint was overall response rate, or ORR. ORR was defined as a complete response or partial response according to the INRC 2017 and confirmed by at least 1 subsequent assessment.¹

In Study 12-230 and the initial analysis of Study 201—in other words, the registrational studies—more than one-third of patients responded and more than one-fourth achieved a complete response.¹

[VISUAL ON SCREEN: Bar graph showing overall response rate, complete response, and partial response data from the Study 201 pre-specified interim analysis.]

DR. DICKENS: Now let’s look at results from the Study 201 interim analysis. Shown here are the overall, complete, and partial responses for all patients in the efficacy analysis. With a median follow-up of 5.9 months, 40% of patients responded to DANYELZA with GM-CSF, and 29% achieved a complete response. The remaining 11% of responders achieved a partial response.²

For these responding patients, the median duration of response was not estimable because responses were ongoing or patients were censored at the time of data cutoff.

[VISUAL ON SCREEN: Bar graph showing overall response rate, complete response, and partial response data from the Study 201 pre-specified interim analysis in patients with incomplete response to relapse therapy.]

DR. DICKENS: Next, let’s review response rates in the pre-specified subgroup of patients with a prior incomplete response to relapse therapy. As a reminder from chapter 2, which includes baseline characteristics, half the patients in the Study 201 interim efficacy analysis fell into this category.²

Shown here are the overall, complete, and partial responses for these patients. As you can see, 35% responded to DANYELZA with GM-CSF, and 27% achieved a complete response. The remaining 8% of responders achieved a partial response.²

[VISUAL ON SCREEN: Swimmer plot of patients in the Study 201 pre-specified interim analysis with incomplete response to relapse therapy.]

DR. DICKENS: In the swimmer plot, you see patient-level data of patients who’d had an incomplete response to relapse therapy.²

The plot shows responses and Curie scores at baseline and at subsequent points following initiation of treatment with DANYELZA plus GM-CSF.

The colors within the bars correspond to the response, with gray reflecting that no assessment was performed and darkening shades of purple reflecting deeper responses. The letters represent an assessment timepoint and a dark square represents progressive disease.

The numbers to the right of the bars are each patient’s Curie scores during treatment, and they are plotted in the bars at the times they were assessed. Curie score assessments were performed at baseline, at first assessment of response, and at each subsequent assessment of response.

The baseline Curie score, which is the second column of numbers, is the Curie score assessed before the first administration of DANYELZA with GM-CSF.

Feel free to pause the video if you’d like to take a few moments to review this information.

For more information about Curie score in high-risk neuroblastoma, please refer to chapter 1. To learn about results in the subgroup of patients in the Study 201 interim analysis with an incomplete response to induction therapy, please refer to chapter 4. To learn about results in the subgroup of patients in the Study 201 interim analysis with prior anti-GD2 treatment, please refer to chapter 6.

I hope you found this video informative. To learn more about DANYELZA, you can watch the other chapters in this video series and visit danyelzahcp.com. Now, please take a moment to view the Important Safety Information for DANYELZA. Thank you.

Reference: 1. DANYELZA. [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; 2024. 2. Data on file. Y-mAbs Therapeutics, Inc. 3. Yanik GA, Parisi MT, Naranjo A, et al. J Nucl Med. 2018;59:502-508.

Video Chapter 6: DANYELZA efficacy results in Study 201 pre-specified interim analysis, patients with prior anti-GD2 therapy

[PRESENTER: David Dickens, MD, FAAP, Pediatric Hematologist-Oncologist. Dr. Dickens received compensation from Y-mAbs Therapeutics for his participation in this video.]

DR. DICKENS: Hello, I’m David Dickens, a pediatric oncologist for over 20 years. In this video, I’ll review responses seen in the DANYELZA with GM-CSF registrational studies and then focus on results from the Study 201 pre-specified interim analysis. Specifically, I’ll present the results in all efficacy-evaluable patients, those with and without prior anti-GD2 therapy, and those who developed anti-drug antibodies during treatment with DANYELZA plus GM-CSF.

As a reminder, DANYELZA may be considered for patients with high-risk neuroblastoma in the bone and/or bone marrow who have an incomplete response to induction therapy or who have an incomplete response to relapse therapy.¹ Note that “incomplete response” is defined as a partial response, minor response, or stable disease to prior therapy.¹

There were 2 DANYELZA with GM-CSF registrational studies, which are described in detail in chapter 2.¹ Study 12-230 was a phase 1/2 trial with 38 patients included in the efficacy analysis. Study 201 is a phase 2 trial that had 22 patients in its initial efficacy analysis¹; a pre-specified interim analysis for Study 201 was conducted, for which additional patients were recruited, bringing the number of patients in the efficacy analysis to 52.²

[VISUAL ON SCREEN: Table showing baseline patient and disease characteristics in Study 12-230, the Study 201 initial analysis, and the Study 201 pre-specified interim analysis.]

DR. DICKENS: Shown here are baseline patient and disease characteristics in the DANYELZA with GM-CSF trials.^1,2 The table breaks out the information by study and includes details about disease type, disease site, and prior treatments. One of those prior treatments is anti-GD2 antibody treatment. As I’ll be focusing on the Study 201 pre-specified interim analysis, you can draw your attention to the bottom row, last column and see that a quarter of patients had received prior anti-GD2 treatment.²

OK, let’s get to the results. The study’s primary endpoint was overall response rate, or ORR. ORR was defined as a complete response or partial response according to the INRC 2017 and confirmed by at least 1 subsequent assessment.¹

In Study 12-230 and the initial analysis of Study 201—in other words, the registrational studies—more than 1/3 of patients responded and more than 1/4 achieved a complete response.¹

[VISUAL ON SCREEN: Bar graph showing overall response rate, complete response, and partial response data from the Study 201 pre-specified interim analysis.]

DR. DICKENS: Now let’s look at results from the Study 201 pre-specified interim analysis. Shown here are the overall, complete, and partial responses for all patients in the efficacy analysis. With a median follow-up of 5.9 months, 40% of patients responded to DANYELZA with GM-CSF, and 29% achieved a complete response.² The remaining 11% of responders achieved a partial response.

For these responding patients, the median duration of response was not estimable because responses were ongoing or patients were censored at the data cutoff.

Next, let’s review response rates in the pre-specified subgroups of patients with and without prior use of anti-GD2 therapy.

[VISUAL ON SCREEN: Bar graphs showing overall response rate, complete response, and partial response data from the Study 201 pre-specified interim analysis in patients by prior use of anti-GD2 antibody therapy.]

DR. DICKENS: Shown here are the overall, complete, and partial responses. As you can see, among patients with prior anti-GD2 therapy, 31% responded to DANYELZA with GM-CSF, and 23% achieved a complete response. The remaining 8% of responders achieved a partial response.²

As for patients without prior anti-GD2 therapy, 44% responded to DANYELZA with GM-CSF, and 31% achieved a complete response. The remaining 13% achieved a partial response.²

[VISUAL ON SCREEN: Bar graphs showing overall response rate, complete response, and partial response data from the Study 201 pre-specified interim analysis in patients who had developed anti-drug antibodies.]

DR. DICKENS: A quick note about anti-drug antibodies, or ADAs, and treatment with DANYELZA plus GM-CSF. Twenty-two percent of patients with positive ADA titers responded to DANYELZA with GM-CSF and 17% achieved a complete response.²

To learn more about results in other patient subgroups in the Study 201 interim analysis, please refer to chapters 4 and 5.

To learn about DANYELZA’s mechanism of action as a structurally distinct GD2-binding monoclonal antibody, refer to chapter 7.

I hope you found this video informative. To learn more about DANYELZA, you can watch the other chapters in this video series and visit danyelzahcp.com. Now, please take a moment to view the Important Safety Information for DANYELZA. Thank you.

Reference: 1. DANYELZA. [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; 2024. 2. Data on file. Y-mAbs Therapeutics, Inc.

Video Chapter 7: DANYELZA MOA

[PRESENTER: David Dickens, MD, FAAP, Pediatric Hematologist-Oncologist. Dr. Dickens received compensation from Y-mAbs Therapeutics for his participation in this video.]

DR. DICKENS: Hello, I’m David Dickens, a pediatric oncologist for over 20 years. In this video, I’ll address the mechanism of action of DANYELZA, the only FDA-approved therapy for high-risk neuroblastoma in the bone and/or bone marrow when response to induction or relapse therapy is incomplete.¹ Note that “incomplete response” is defined as a partial response, minor response, or stable disease to prior therapy.

[VISUAL ON SCREEN: Illustration of the DANYELZA monoclonal antibody.]

DR. DICKENS: DANYELZA is a structurally distinct, humanized GD2-binding monoclonal antibody.¹ This is important because GD2 is a disialoganglioside that is overexpressed on neuroblastoma cells.¹

Structurally, DANYELZA’s framework is 92% human and 8% murine.²

In vitro studies showed that the binding affinity of DANYELZA to the GD2 receptor is approximately 10 times higher than that of approved chimeric anti-GD2 antibodies due to a slower off-rate.³ Any clinical significance and product comparisons of efficacy or safety should not be inferred.

[VISUAL ON SCREEN: Illustration of the DANYELZA mechanism of action.]

DR. DICKENS: DANYELZA prompts immune-mediated cell death via two pathways: the ADCC and CDC pathways.¹

It was shown to bind GD2 and trigger immune-mediated cell death in vitro.^1,3 As an immunotherapy, DANYELZA flags neuroblastoma cells for the immune system to target and destroy, which it does via ADCC and CDC in vitro.

I hope you found this video informative. To learn more about DANYELZA, you can watch the other chapters in this video series and visit danyelzahcp.com. Now, please take a moment to view the Important Safety Information for DANYELZA. Thank you.

Reference: 1. DANYELZA [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; 2024. 2. Cheung N-KV, Guo H, Hu J, et al. Oncoimmunology. 2012;1(4):477-486. 3. Lisby S, Liebenberg N, Bukrinski J, et al. Presented at the SIOP virtual congress. Abstract #945. October 16, 2020.

Video Chapter 8: DANYELZA safety

[PRESENTER: David Dickens, MD, FAAP, Pediatric Hematologist-Oncologist. Dr. Dickens received compensation from Y-mAbs Therapeutics for his participation in this video.]

DR. DICKENS: Hello, I’m David Dickens, a pediatric oncologist for over 20 years. In this video, I’ll address DANYELZA safety, as established in clinical trials.

As a reminder, there were 2 DANYELZA with GM-CSF registrational studies, which are described in detail in chapter 2.¹ Study 12-230 was a phase 1/2 trial with 72 patients. Study 201 is a phase 2 trial that had 25 patients in its initial analysis;¹ subsequently, a pre-specified interim analysis for Study 201 was conducted, for which additional patients were recruited, bringing the number of patients to 74.² In all three analyses, all patients who started an infusion of DANYELZA were included in the safety evaluation. I’ll be presenting information from all three analyses.

[VISUAL ON SCREEN: Table showing safety analysis of patients who received DANYELZA with GM-CSF.]

DR. DICKENS: Let’s begin by reviewing potential serious adverse reactions. Note that DANYELZA can cause serious infusion reactions, including hypotension, bronchospasm, hypoxia, and stridor, as well as severe neurotoxicity, including pain.¹

The most common adverse reactions, occurring in at least 25% of patients, are shown here. It is important to familiarize yourself with these adverse reactions, so feel free to pause the video if you’d like to take a few moments to review this information.^1,2

Now you can see the percentage of patients who were exposed to DANYELZA + GM-CSF for at least 6 months and at least 1 year across Study 12-230 and the Study 201 initial and interim analyses.^1,2

Bear in mind that the DANYELZA Prescribing Information provides the full list of adverse reactions that occurred in Study 12-230 and the Study 201 initial analysis, as well as recommendations for management of adverse reactions. Chapter 9 goes into some detail about these management strategies.

[VISUAL ON SCREEN: Bar graphs showing serious adverse reactions in the DANYELZA clinical trials and permanent discontinuations.]

DR. DICKENS: Now in the DANYELZA + GM-CSF clinical studies, some adverse reactions led to treatment discontinuation. Across the 3 analyses, 32% to 45% of patients had a serious adverse reaction, and in 8% to 12% of patients, an adverse reaction led to treatment discontinuation.¹

Overall, the DANYELZA safety profile in the Study 201 interim analysis was consistent with that in the initial analysis.^1,2

Identified in this table are specific adverse reactions and the severity of those reactions that necessitate treatment discontinuation.¹ For more details about the interventions that are recommended, please refer to the DANYELZA Prescribing Information or watch chapter 9.

[VISUAL ON SCREEN: Bar graph showing resolution of select Grade 3 or 4 adverse reactions in the Study 201 pre-specified interim analysis.]

DR. DICKENS: The last DANYELZA safety consideration that I’ll review is time to resolution of select Grade 3 or 4 adverse reactions in the Study 201 interim analysis. On your screen, you’ll see two bar charts—the one on the left shows time to resolution of Grade 3 pain, and the one on the right shows time to resolution of Grade 3 or 4 hypotension.²

As you can see, the majority of Grade 3 pain was resolved within an hour and 90% was resolved in ≤5 hours.² Similarly, the majority of Grade 3 or 4 hypotension was resolved within an hour and 89% was resolved in ≤5 hours.²

To be considered “resolved,” the adverse reaction needed to resolve completely—in other words, diminish to the degree that it would no longer be on the grading scale, so the severity of these events may have decreased before completely resolved.

To learn more about strategies to manage adverse reactions, refer to chapter 9, which speaks to those approaches as part of the DANYELZA dosing and administration presentation.

I hope you found this video informative. To learn more about DANYELZA, you can watch the other chapters in this video series and visit danyelzahcp.com. Now, please take a moment to view the Important Safety Information for DANYELZA. Thank you.

Reference: 1. DANYELZA. [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; 2024. 2. Data on file. Y-mAbs Therapeutics, Inc.

Video Chapter 9: DANYELZA dosing and administration

[PRESENTER: David Dickens, MD, FAAP, Pediatric Hematologist-Oncologist. Dr. Dickens received compensation from Y-mAbs Therapeutics for his participation in this video.]

DR. DICKENS: Hello, I’m David Dickens, a pediatric oncologist for over 20 years. In this video, I’ll address DANYELZA dosing and administration.

As a reminder, DANYELZA may be considered for patients with high-risk neuroblastoma in the bone and/or bone marrow who have an incomplete response to induction therapy or who have an incomplete response to relapse therapy.¹ Note that “incomplete response” is defined as a partial response, minor response, or stable disease to prior therapy.

DANYELZA can offer the flexibility of inpatient or outpatient administration, at the treating physician’s discretion. In the Study 201 pre-specified interim analysis, more than 90% of infusions were given in an outpatient setting.²

The recommended dosage of DANYELZA is 3 mg/kg/day (up to 150 mg/day) given on Days 1, 3, and 5 of each treatment cycle.¹ DANYELZA is administered as an intravenous infusion after dilution in combination with GM-CSF, which is given subcutaneously. This timeline shows you when GM-CSF and DANYELZA are given.¹

In each cycle, GM-CSF begins five days before the first DANYELZA infusion and is dosed at 250 μg/m²/day. On Days 1-5 of each cycle, GM-CSF is continued, but its dose is increased to 500 μg/m²/day. So, in total, GM-CSF will be administered for 10 days during each cycle.¹

For the very first infusion of DANYELZA—in other words, Cycle 1, Day 1—the infusion is given over 60 minutes. Thereafter, infusions take 30-60 minutes, as tolerated.¹

After each DANYELZA infusion, patients should be closely observed for at least 2 hours in a setting where cardiopulmonary resuscitation medication and equipment are available.

The recommended treatment course of DANYELZA + GM-CSF is to continue 28-day cycles until the patient achieves a complete response or a partial response.¹ Following that response, the 28-day cycle is repeated for five more cycles. At that point, at the physician’s discretion, treatment may switch to 8-week cycles and may be discontinued for disease progression or unacceptable toxicity.

DANYELZA with GM-CSF treatment involves premedication and supportive medication.¹ To reduce the risk of infusion-related reactions and nausea or vomiting, IV corticosteroids are administered 120 to 30 minutes before the first DANYELZA infusion. They may also be given with subsequent infusions if a severe reaction occurred with the previous infusion or during the previous cycle. In addition, an antihistamine, an H2 antagonist, acetaminophen, and an antiemetic are administered 30 minutes before each infusion.

For potential pain, a 12-day course of gabapentin, or another prophylactic medication for neuropathic pain, is initiated five days before the first DANYELZA infusion in each cycle—this is the same day that GM-CSF is initiated.¹ Sixty to 45 minutes before each infusion, oral opioids are administered, and additional IV opioids may be given during the infusion if breakthrough pain occurs. Finally, ketamine may be considered for pain that is not adequately controlled by opioids.¹

For more details about management of adverse reactions, please refer to the DANYELZA full Prescribing Information.

I hope you found this video informative. To learn more about DANYELZA, you can watch the other chapters in this video series and visit danyelzahcp.com. Now, please take a moment to view the Important Safety Information for DANYELZA. Thank you.

Reference: 1. DANYELZA. [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; 2024. 2. Data on file. Y-mAbs Therapeutics, Inc.