JNJ-63709178 / J&J, Genmab - LARVOL DELTA

Inhibition of PRMT5 with JNJ-64619178 sensitizes B-cell non-Hodgkin lymphoma cells to both intrinsic and extrinsic apoptosis (ASH 2025) - P1 | "Various cell lines, including DLBCL (TMD8, Ri-1, OCI-Ly1,OCI-Ly1R, SUDHL4), double-hit lymphoma patient-derived xenograft (DW19), MCL (Mino, Jeko-1), and BL(Raji, BL-70) were utilized to investigate the in vitro anti-cancer properties of JNJ-9178, BH3 mimetics(venetoclax [Ven, BCL-2i], S63845 [S63, MCL-1i], A1331852 [A133, BCL-xLi]) and TRAIL analogs (rhTRAIL[recombinant human TRAIL], Conatumumab [DR5 agonist], and Mapatumumab [DR4 agonist]). We identified PRMT5 as an important regulator of both intrinsic and extrinsic apoptosis. Ourdata suggest that DBP has the potential to optimize the selection of BH3 mimetics to combine with JNJ-9178 to maximize the activity of this drug across certain B-cell NHL subtypes. Additionally, JNJ-9178sensitizes B-cell NHL cell lines to TRAIL-induced cancer cell-selective extrinsic apoptosis."

IO biomarker • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Solid Tumor • ANXA5 • BCL2 • TNFRSF10B

PRMT5 as a target in CRC interception: Synthetic lethal dependency identified in APC-LOF preclinical models of FAP disease (AACR 2025) - "JNJ-64619178 (JNJ-9178), a potent clinical PRMT5 inhibitor, demonstrated an >800-fold window in growth inhibition of engineered APCKO organoids compared to wild-type (WT). To address these dose-limiting toxicities, we have developed a GI-restricted approach and discovered new compounds that only inhibit PRMT5 activity locally in the intestinal tract. This strategy is detailed in a second abstract."

Preclinical • Synthetic lethality • Colorectal Cancer • Oncology • Solid Tumor • APC

First-in-Human Study of JNJ-63709178, a CD123/CD3 Targeting Antibody, in Relapsed/Refractory Acute Myeloid Leukemia. (PubMed, Clin Transl Sci) - "Minimal clinical activity was observed across all cohorts. IV and SC dosing of JNJ-63709178 was associated with suboptimal drug exposure, unfavorable safety profiles, limited clinical activity, and inability to identify a recommended Phase 2 dose."

Journal • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123

Dose Escalation Study of JNJ-63709178, a Humanized CD123 x CD3 DuoBody in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1; N=62; Completed; Sponsor: Janssen Research & Development, LLC; Recruiting ➔ Completed; N=120 ➔ 62; Trial completion date: Oct 2022 ➔ Mar 2021; Trial primary completion date: May 2022 ➔ Mar 2021

Clinical • Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123

Dose Escalation Study of JNJ-63709178, a Humanized CD123 x CD3 DuoBody in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1; N=120; Recruiting; Sponsor: Janssen Research & Development, LLC; Trial primary completion date: Oct 2020 ➔ May 2022

Clinical • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123

Janssen to Present Key Data from Across Its Expansive Oncology Portfolio at ESMO 2020 Virtual Congress (Businesswire) - "The Janssen Pharmaceutical Companies of Johnson & Johnson today announced multiple data presentations from its oncology portfolio and pipeline, including key data in lung cancer and bladder cancer, will be featured as part of the European Society for Medical Oncology (ESMO) Virtual Congress 2020, Science Weekend taking place 19–21 September...Janssen makes its first presentation of in-human data for early-stage investigational protein arginine methyltransferase 5 (PRMT5) inhibitor JNJ-9178 in multiple tumour models (relapsed/refractory B cell non-Hodgkin lymphoma or advanced solid tumours, including patients with lower risk myelodysplastic syndromes)."

Clinical data • Hematological Malignancies • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Dose Escalation Study of JNJ-63709178, a Humanized CD123 x CD3 DuoBody in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1; N=120; Recruiting; Sponsor: Janssen Research & Development, LLC; Trial completion date: Oct 2022 ➔ May 2022

Clinical • Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123

Genmab announces abstracts to be presented at 23rd EHA Annual Congress (GlobeNewswire) - "Genmab...announced today that one abstract on Genmab’s DuoBody-CD3xCD20 and six industry sponsored abstracts on daratumumab will be presented at the 23rd European Hematology Association (EHA) Annual Congress 2018 in Stockholm, Sweden, June 14-17. An abstract containing a pre-clinical evaluation of...DuoBody-CD3xCD20 will be presented as a poster. The daratumumab abstracts...include an oral presentation on ALCYONE (MMY3007), the Phase III trial [NCT02195479] of daratumumab...in newly diagnosed multiple myeloma...There will also be an oral presentation regarding the Phase II CENTAURUS (SMM2001) study [NCT02316106] of daratumumab in smoldering multiple myeloma."

P2 data • P3 data • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology

FDA places clinical hold on AML drug co-developed by Johnson & Johnson (JNJ) and Genmab A/S (GEN.CO) (BioSpace) - P1, N=60; NCT02715011; "Johnson & Johnson...has indicated that its acute myeloid leukemia (AML) drug, JNJ-63709178, has been put on clinical hold because of serious side effects...No information regarding how far in the study patients were, or what specific adverse effects were observed."

Trial termination • Acute Myelogenous Leukemia • Oncology

Dose Escalation Study of JNJ-63709178, a Humanized CD123 x CD3 DuoBody in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1; N=120; Recruiting; Sponsor: Janssen Research & Development, LLC; Trial completion date: May 2022 ➔ Oct 2022

Clinical • Trial completion date • CD123

Dose Escalation Study of JNJ-63709178, a Humanized CD123 x CD3 DuoBody in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1; N=120; Recruiting; Sponsor: Janssen Research & Development, LLC; N=60 ➔ 120; Trial completion date: Oct 2021 ➔ May 2022

Enrollment change • Trial completion date • CD123

DARTS, Bites and ADCs for the Treatment of AML and for Conditioning for Allogeneic Stem Cell Transplantation (SOHO 2019) - "These include JNJ-63709178; (target: CD123; trial suspended), XmAb14045; (target: CD123), Flotetuzumab/DART; (target: CD123) as well as others focused on CD33 (AMG330, AMG673, AMV564, GEM333) and CLL-1 (MCLA-117). Additional correlative studies will be presented for this and other AML bispecifics currently being tested by our and other groups in the clinic. Finally, we will present data on the use of ADCs for the treatment of AML in vitro and for conditioning for stem cell transplantation within and across MHC barriers using mouse preclinical transplant models."

IO Biomarker

Bispecific Antibodies for the Treatment of Acute Myeloid Leukemia. (PubMed, Curr Hematol Malig Rep) - "T cell redirecting bispecific antibodies in early phase clinical trials for AML include AG330, flotetuzumab, JNJ-63709178, and AMV564. Bispecific antibodies represent a promising immunotherapeutic approach for the treatment of cancer. The results of ongoing studies in AML will elucidate the potential for these agents in AML."

Journal • Review

Genmab announces data to be presented at 24th EHA Annual Congress (Genmab Press Release) - "Genmab A/S...announced today that 15 industry sponsored abstracts regarding Genmab programs were accepted for presentation at the 24th European Hematology Association (EHA) Annual Congress 2019 in Amsterdam, the Netherlands, taking place June 13-16, 2019. A list of accepted Industry-sponsored abstracts featured at the congress includes 14 daratumumab abstracts, four of which were accepted for oral presentations, including a presentation of the Phase III CASSIOPEIA data, which the Scientific Program Committee of the EHA selected for presentation during the Presidential Symposium, which showcases abstracts that represent innovative research in hematology. In addition, one abstract features Genmab’s proprietary DuoBody®-CD3xCD20 product."

Clinical data • P3 data