ivicentamab (GEN-3009) / Genmab - LARVOL DELTA

Pharmacologic activity, safety, and preliminary efficacy of GEN3009, a CD37-targeting DuoHexaBody, in relapsed or refractory B-cell non-Hodgkin's lymphoma. (PubMed, J Immunother Cancer) - P1/2 | "Based on safety, efficacy, and pharmacokinetics, the RP2D of GEN3009 was determined to be 1200 mg. Preliminary data suggest that GEN3009 monotherapy demonstrated an acceptable safety profile at the RP2D of 1200 mg, with modest clinical activity. These findings provide the first clinical proof-of-concept for hexamerization-potentiated molecules that induce antitumor activity through enhanced CDC."

First-in-human • Journal • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • CD37

DuoHexaBody-CD37 induces direct cytotoxic signaling in diffuse large B-cell lymphoma. (PubMed, Elife) - "DuoHexaBody-CD37 induced significant CD37 clustering and was retained at the cell surface in contrast to rituximab, which was internalized. Finally, DuoHexaBody-CD37 treatment inhibited cytokine pro-survival signaling in DLBCL cells. These findings provide novel insights into the signaling functions of CD37 upon DuoHexaBody-CD37 treatment, and open up opportunities for developing CD37-targeted immunotherapy in combination with small molecule inhibitors to maximize tumor cell death."

IO biomarker • Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD37

Future Landscapes of Bispecific Antibodies in Chronic Lymphocytic Leukemia (CLL). Systematic Review of Ongoing Trials (ASH 2024) - "The bispecific antibodies under investigation include Epcoritamab (4 trials), Mosunetuzumab (3 trials), and Plamotumab, Glofitamab, and GEN3009 (one trial each)...The trials primarily explore bispecific antibodies as third-line therapy in 5(50%) of the trials and as second-line therapy in 4(40%) of the trials, with Venetoclax being the most common combination therapy used...The diverse geographic distribution and variety of bispecific antibodies under investigation underscore the global effort to advance CLL treatment. The focus on safety and tolerability ensures that these new therapies will be effective and manageable for patients, paving the way for improved outcomes in this challenging disease."

Review • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

First-in-Human (FIH) Trial of GEN3009 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas (clinicaltrials.gov) - P1/2 | N=46 | Terminated | Sponsor: Genmab | N=182 ➔ 46 | Trial completion date: Sep 2025 ➔ Jul 2023 | Recruiting ➔ Terminated | Trial primary completion date: Sep 2023 ➔ Nov 2022; Due to strategic evaluation of GEN3009 within context of Genmab's portfolio, decision not based on any safety or regulatory concerns.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • BCL2 • CD20

NNV024, a Humanized Anti-CD37 Antibody with Enhanced ADCC and Extended Plasma Half-Life for the Treatment of B-Cell Malignancies (ASH 2022) - "The anti-CD20 Abs rituximab and obinutuzumab as well as the anti-CD37 Ab, Duohexabody-CD37, were used for benchmarking. These encouraging preclinical results support further development of NNV024 as a potential therapeutic mAb candidate for the treatment of B-cell malignancies and B-cell driven autoimmune disorders."

Burkitt Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

B-Cell Targeting Anti-CD37 Humanized Antibodies Engineered for Potent Effector Functions and Extended Plasma Half-Life (ASH 2022) - "Of note, the anti-CD37 antibody-drug conjugates (ADC) naratuximab emtansine and the CD37-targeting radioimmunotherapy (RIT) Betalutin have shown efficacy in NHL patients during clinical testing... The humanized anti-CD37 candidates were characterized in vitro and in vivo and benchmarked against the anti-CD20 antibodies approved for NHL treatment, rituximab and obinutuzumab, and a recombinant version of the bi-paratopic anti-CD37 antibody DuoHexaBody-CD37, currently in Phase I clinical development... Taken together, the humanized and Fc-engineered anti-CD37 antibodies show potent effector functions, favorable pharmacokinetic properties and in vivo therapeutic efficacy. As such, the designed CD37 antibodies should be attractive modalities in targeted treatment of B cell malignancies, such as NHL, including lymphomas non-responding to anti-CD20 treatments, but also potentially for B-cell driven autoimmune disorders."

IO biomarker • Burkitt Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

First-in-Human (FIH) Trial of GEN3009 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas (clinicaltrials.gov) - P1/2 | N=182 | Recruiting | Sponsor: Genmab | Trial completion date: Apr 2025 ➔ Sep 2025 | Trial primary completion date: Dec 2023 ➔ Sep 2023

Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • BCL2 • CD20

First-in-Human (FIH) Trial of GEN3009 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas (clinicaltrials.gov) - P1/2; N=182; Recruiting; Sponsor: Genmab; N=120 ➔ 182; Trial completion date: May 2023 ➔ Apr 2025; Trial primary completion date: Nov 2022 ➔ Dec 2023

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • CD20

Genmab and AbbVie announce broad oncology collaboration (GlobeNewswire) - "Genmab A/S…and AbbVie Inc…announced today that Genmab and AbbVie have signed a broad collaboration agreement to jointly develop and commercialize three of Genmab’s early-stage investigational bispecific antibody product candidates and enter into a discovery research collaboration for future differentiated antibody therapeutics for cancer. The companies will partner to develop Genmab’s next-generation bispecific antibody programs, epcoritamab (DuoBody®-CD3xCD20), DuoHexaBody®-CD37 and DuoBody-CD3x5T4…Under the terms of the agreement, AbbVie will pay Genmab USD 750 million in upfront payment with the potential for Genmab to receive up to USD 3.15 billion in additional development, regulatory and sales milestone payments for all programs as well as tiered royalties between 22% and 26% on net sales for epcoritamab outside the U.S. and Japan."

Licensing / partnership • Hematological Malignancies • Oncology

AbbVie and Genmab link for oncology collaboration (PharmaTimes) - "AbbVie and Genmab have signed a pact to jointly develop and commercialise three of the latter's early-stage investigational bispecific antibody product candidates, as well as a discovery research collaboration for future differentiated antibody therapeutics for cancer....The companies will develop Genmab’s next-generation bispecific antibody programmes epcoritamab (DuoBody-CD3xCD20), DuoHexaBody-CD37 and DuoBody-CD3x5T4."

Licensing / partnership • Hematological Malignancies • Oncology

[VIRTUAL] DUOHEXABODY®-CD37 SHOWS POTENT ANTI-TUMOR ACTIVITY IN PRE-CLINICAL B-CELL LYMPHOMA MODELS IN VITRO AND IN VIVO (EHA 2020) - "Non-clinical PK properties are as expected for a monomeric human IgG1 Ab. Clinical studies to explore the safety and efficacy of DuoHexaBody-CD37 (GEN3009) in patients with advanced NHL, including CLL are being planned."

Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • FCGR2A

Genmab announces data to be presented at the EHA25 Virtual Congress (GlobeNewswire) - "Genmab A/S...announced....that eight industry sponsored abstracts regarding Genmab and partner programs were accepted for presentation at the 25^th European Hematology Association (EHA) EHA25 Virtual Congress 2020, taking place virtually on June 11-14, 2020. A list of accepted Industry-sponsored abstracts featured at the congress includes two abstracts on epcoritamab (DuoBody^®-CD3xCD20), one on HexaBody^®-CD38, one on DuoHexaBody^®-CD37 and four daratumumab abstracts."

P1 data • P1/2 data • P3 data • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology

DuoHexaBody-CD37, a novel biparatopic CD37 antibody with enhanced Fc-mediated hexamerization as a potential therapy for B-cell malignancies. (PubMed, Blood Cancer J) - "Finally, potent anti-tumor activity in vivo was observed in cell line- and patient-derived xenograft models from different B-cell malignancy subtypes. These encouraging preclinical results suggest that DuoHexaBody-CD37 (GEN3009) may serve as a potential therapeutic antibody for the treatment of human B-cell malignancies."

Journal • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

First-in-Human (FIH) Trial of GEN3009 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas (clinicaltrials.gov) - P1/2; N=120; Recruiting; Sponsor: Genmab

Clinical • New P1/2 trial • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology