erzotabart (GEN3014) / Genmab - LARVOL DELTA

GEN3014 (HexaBody®-CD38) in Anti-CD38 Mab–Naive Patients with Relapsed/Refractory Multiple Myeloma: Preliminary Results from a Dose‑Expansion Cohort of a Phase 1/2 Trial (ASH 2023) - P1/2 | "Background: The treatment landscape for relapsed/refractory multiple myeloma (RRMM) has changed dramatically with the approval of CD38-targeted antibodies such as daratumumab. GEN3014 showed a manageable safety profile and clinical activity in anti-CD38 mAb–naive RRMM patients in this expansion cohort. The preliminary pharmacodynamic observations were in line with observations from the dose-escalation part of the study. The study is ongoing and open for enrollment."

Clinical • IO biomarker • P1/2 data • Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Respiratory Diseases • Thrombocytopenia

GEN3014 Trial in Relapsed or Refractory Hematologic Malignancies (clinicaltrials.gov) - P1/2 | N=130 | Terminated | Sponsor: Genmab | Completed ➔ Terminated; The sponsor has decided to discontinue further development of GEN3014 after a comprehensive review of the data, market landscape, and strategic priorities.

Trial termination • Acute Myelogenous Leukemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD20

GEN3014 Trial in Relapsed or Refractory Hematologic Malignancies (clinicaltrials.gov) - P1/2 | N=130 | Completed | Sponsor: Genmab | Active, not recruiting ➔ Completed

Trial completion • Acute Myelogenous Leukemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD20

GEN3014 Trial in Relapsed or Refractory Hematologic Malignancies (clinicaltrials.gov) - P1/2 | N=130 | Active, not recruiting | Sponsor: Genmab | N=252 ➔ 130

Enrollment change • Acute Myelogenous Leukemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD20

GEN3014 Trial in Relapsed or Refractory Hematologic Malignancies (clinicaltrials.gov) - P1/2 | N=252 | Active, not recruiting | Sponsor: Genmab | Trial completion date: Dec 2026 ➔ Jul 2025 | Trial primary completion date: Mar 2025 ➔ Jun 2025

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Genmab Announces Johnson & Johnson Decision Regarding HexaBody-CD38 (GlobeNewswire) - P1/2 | N=252 | NCT04824794 | Sponsor: Genmab | "Genmab...announced today that Johnson & Johnson (J&J) has decided that it will not exercise its option to receive a worldwide license to develop, manufacture and commercialize HexaBody-CD38 (GEN3014)...Genmab’s rigorous portfolio prioritization, Genmab will not pursue further clinical development of HexaBody-CD38...The Phase 2 expansion Part B of the study assessed the objective response rate (primary endpoint) of intravenous HexaBody-CD38 versus subcutaneous daratumumab in patients with anti-CD38 antibody- naïve relapsed or refractory multiple myeloma....Preliminary data submitted by Genmab to J&J, inclusive of 88 patients who received a study treatment and 84 patients who were response evaluable (42 in each arm), demonstrated an overall response rate (ORR) of 55% (95% CI: 39%, 70%) in the HexaBoby-CD38 IV arm vs. 52% in the daratumumab SC arm (95% CI: 36%, 68%)...and complete response (CR) or better rate was 7% vs. 2%."

Commercial • Discontinued • P2 data • Multiple Myeloma

GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies (clinicaltrials.gov) - P1/2 | N=252 | Active, not recruiting | Sponsor: Genmab | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Myelogenous Leukemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD20

GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies (clinicaltrials.gov) - P1/2 | N=252 | Recruiting | Sponsor: Genmab | Trial primary completion date: Mar 2025 ➔ Oct 2024

Trial primary completion date • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD20

GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies (clinicaltrials.gov) - P1/2 | N=252 | Recruiting | Sponsor: Genmab | Trial primary completion date: Oct 2024 ➔ Mar 2025

Trial primary completion date • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD20

GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies (clinicaltrials.gov) - P1/2 | N=252 | Recruiting | Sponsor: Genmab | Trial completion date: Feb 2029 ➔ Dec 2026

Trial completion date • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Genmab Announces Multiple Abstracts to be Presented at the 65th Annual Meeting and Exposition of the American Society of Hematology (ASH) (GlobeNewswire) - "Eighteen total abstracts accepted for presentation and publication, including results from four clinical trials evaluating epcoritamab in multiple treatment settings and patient populations; Oral presentations highlighting new findings from a clinical trial of epcoritamab in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and a real-world analysis of patients with R/R large B-cell lymphoma (LBCL) will be featured; Initial data from trial of investigational cancer immunotherapy GEN3014 (HexaBody^®-CD38) also accepted."

Clinical data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

GEN3014 (HexaBody®-CD38) Versus Daratumumab in Patients With Relapsed/Refractory Multiple Myeloma: Design of Randomized Head-to-Head Expansion Cohort of Phase 1/2 Trial (IMW 2023) - P1/2 | "N/A – trial in progress."

Clinical • Head-to-Head • IO biomarker • P1/2 data • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

Preclinical anti-tumour activity of HexaBody-CD38, a next-generation CD38 antibody with superior complement-dependent cytotoxic activity. (PubMed, EBioMedicine) - "Based on these preclinical studies, a clinical trial was initiated to assess the clinical safety of HexaBody-CD38 in patients with MM."

IO biomarker • Journal • Preclinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

PHARMACODYNAMIC ACTIVITY OF GEN3014 (HEXABODY-CD38) IN PATIENTS WITH MULTIPLE MYELOMA SUPPORTS ENHANCED COMPLEMENT DEPENDENT CYTOTOXICITY OF GEN3014 COMPARED TO DARATUMUMAB (EHA 2023) - P1/2 | "GEN3014 showed potent CDC activity in vitro, with higher maximal kill compared to daratumumab, also under suboptimal complement conditions. GEN3014 induced a stronger decline of complement levels in patients compared to historical data of daratumumab, supporting its potential to induce enhanced CDC in patients. These findings support the ongoing phase 1/2 trial in patients with RRMM (NCT04824794) evaluating the safety and efficacy of GEN3014, which includes a head-to-head comparison with daratumumab."

Clinical • IO biomarker • PK/PD data • Hematological Malignancies • Multiple Myeloma • Oncology

GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies (clinicaltrials.gov) - P1/2 | N=252 | Recruiting | Sponsor: Genmab | Trial completion date: Jan 2024 ➔ Feb 2029 | Trial primary completion date: Apr 2023 ➔ Oct 2024

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD20

New Tools Emerge to Manage Relapsed/ Refractory Multiple Myeloma (Targeted Oncology) - "In an interview with Targeted Therapies in Oncology, Paul G. Richardson, MD, said, 'CELMoDs as a particular class of new agent provide such an example of an important therapeutic option for our patients with multiple myeloma, in my view.'...'As we combine these powerful, orally bioavailable agents with backbone drugs to target multiple aspects of myeloma pathobiology, we can significantly improve patient outcomes,' Richardson said."

Interview

HEXABODY-CD38 INDUCES TROGOCYTOSIS AND EFFECTIVELY INDUCES COMPLEMENT-MEDIATED TUMOR CELL LYSIS AFTER TREATMENT WITH DARATUMUMAB OR ISATUXIMAB IN VITRO (EHA 2022) - P1/2 | "Here we confirmed the CDC potency of HexaBody-CD38 even in the presence of saturating concentrations of daratumumab and isatuximab. This suggests that HexaBody-CD38 is capable of inducing CDC of CD38 + myeloma cells in patients who have received prior anti-CD38 mAb treatment with residual daratumumab or isatuximab present in their circulation."

IO biomarker • Preclinical • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

Preliminary Dose-Escalation Results from a Phase 1/2 Study of GEN3014 (HexaBody®-CD38) in Patients (pts) with Relapsed or Refractory Multiple Myeloma (RRMM) (ASH 2022) - P1/2 | "Most pts (67%) had prior exposure to a daratumumab- or isatuximab-containing regimen, with 8 pts naive to anti-CD38 mAb. Dose-escalation results show GEN3014 had a tolerable safety profile and clinical activity in pts with RRMM, including pts with prior anti-CD38 mAb. The PK profile is characterized by target-mediated drug disposition at lower doses and signs of saturation at doses >8 mg/kg. Biomarker analyses confirm biological activity in pts with RRMM at all evaluated doses."

Clinical • IO biomarker • P1/2 data • Anemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia • CXCL8 • IFNG • IL10 • IL2 • IL6 • TNFA

GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies (clinicaltrials.gov) - P1/2 | N=272 | Recruiting | Sponsor: Genmab | N=152 ➔ 272

Enrollment change • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Genmab Announces Multiple Abstracts to be Presented at the 64th Annual Meeting and Exposition of the American Society of Hematology (ASH) (Businesswire) - "Nineteen abstracts accepted, including multiple presentations on the safety and efficacy of investigational epcoritamab (DuoBody®-CD3xCD20) in a variety of treatment settings and hematologic malignancies. Four oral presentations highlighting data evaluating epcoritamab for the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL), R/R follicular lymphoma (FL), previously untreated FL, and Richter's syndrome. New data evaluating investigational medicines in Genmab’s early portfolio of cancer immunotherapies will also be presented. Genmab to host 2022 R&D Update and ASH Data Review meeting December 12."

Clinical data • Preclinical • Real-world evidence • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Mediastinal B Cell Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma

GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies (clinicaltrials.gov) - P1/2; N=152; Recruiting; Sponsor: Genmab

New P1/2 trial • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

Genmab Announces Data to be Presented at 2020 ASH Annual Meeting (GlobeNewswire) - "Abstracts accepted for presentation include data from the ongoing Phase I/II trial of epcoritamab in B-cell non-Hodgkin lymphomas, which will be presented during an oral session of the conference. Accepted abstracts also include pre-clinical data from Genmab’s next generation CD38 antibody, HexaBody®-CD38 and updates on multiple daratumumab clinical trials. In addition, data for teclistamab and talquetamab, two of Janssen’s bispecific antibodies created with Genmab’s DuoBody technology platform, were accepted for oral presentations at the conference."

Clinical data • P1 data • P1/2 data • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

[VIRTUAL] Preclinical Anti-Tumor Activity of Hexabody-CD38 in Patient-Derived B Cell Lymphoma and Acute Myeloid Leukemia Xenograft Models (ASH 2020) - "In this study, we show that in a panel of 23 MM, AML and B-NHL cell lines HexaBody-CD38 induced CDC, with EC50 values on average 7-fold lower than those of the CD38-targeting mAb daratumumab, which is part of the standard of care for MM. This indicates that besides highly potent CDC, FcɣR-mediated effector mechanisms contribute to the preclinical activity of HexaBody-CD38 in hematological tumor models. These preclinical data support clinical investigation of HexaBody-CD38 in CD38 positive hematologic malignancies, including MM, AML, and B cell lymphomas."

IO Biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD38 • CD46 • CD59