Initial preclinical data will be presented for HMPL-506, a novel, highly potent and differentiated menin-MLL inhibitor for the treatment of certain types of acute leukemia. Compared with five other menin inhibitors in clinical development, HMPL-506 showed the stronger inhibitory potency in MLL-rearranged and NPM1 mutant leukemia cell line models. Furthermore, HMPL-506 in combination with azacytidine, venetoclax or gilteritinib synergistically improved the anti-tumor effect against MLL-rearranged leukemias both in vitro and in vivo. The investigational drug candidate displayed favorable pharmacokinetic profiles, high selectivity and low risk of cardiac toxicity. A Phase I study of HMPL-506 is planned for the second half of 2024.
Initial preclinical data will also be presented for HMPL-A067 (HMA800067), a novel CD38-targeting antibody-drug conjugate (ADC) in which daratumumab was conjugated with cytotoxic payload Monomethyl auristatin E (MMAE) via a novel linker. It demonstrated significant superior anti-tumor activity to daratumumab, including in several B-cell malignancies models with resistance to daratumumab treatment.
Other presentations include preclinical data on the ERK 1/2 inhibitor, HMPL-295; early clinical data on the Syk inhibitor, sovleplenib, in lymphoma patients; additional clinical data from global studies of VEGFR inhibitor, fruquintinib, and MET inhibitor, savolitinib; and several investigator-initiated studies of fruquintinib and VEGFR/CSF-1R/FGFR inhibitor, surufatinib.
Details of the presentations are as follows:
Abstract titlePresenter / Lead authorPresentation detailsSPONSORED STUDIES
HMPL-506, a novel, highly potent and differentiated menin-MLL inhibitor for the treatment of MLL-rearranged and NPM1mutant acute leukemia in preclinical models
Min Cheng, HUTCHMED, Shanghai, ChinaPoster Session (PO.ET07.02 – Pharmacodynamic Biomarkers of Drug Response)
Monday, April 8, 2024
HMPL-A067 (HMA800067), a novel CD38-targeting antibody-drug conjugate (ADC), demonstrated superior anti-tumor activity to daratumumab in preclinical B-cell malignancies models
Yan Xu, HUTCHMED, Shanghai, ChinaPoster Session (PO.ET01.02 – Antibody-Drug Conjugates and Bispectific Antibodies)
Monday, April 8, 2024
Preclinical characterization of HMPL-295, a potent and selective ERK1/2 inhibitor
Jia Hu, HUTCHMED, Shanghai, ChinaPoster Session (PO.MCB03.01 – Cell Signaling Components as Therapeutic Targets)
Monday, April 8, 2024
Targeting YAP1/TEAD signaling re-sensitizes MAPK/ERK pathway inhibitors in KRAS-driven cancer cells
Xianwen Yang, HUTCHMED, Shanghai, ChinaPoster Session (PO.ET03.04 – Drug Resistance 2: Ras GTPase)
Monday, April 8, 2024
Safety and Efficacy of Sovleplenib (HMPL-523), a Syk Inhibitor, in Patients with Relapsed or Refractory Lymphoma
Paolo Strati, The University of Texas MD Anderson Cancer Center, USAPoster Session (PO.CT01.03 – Phase 0 and Phase I Clinical Trials)
Monday, April 8, 2024
Early carcinoembryonic antigen (CEA) dynamics to predict the efficacy of fruquintinib (F) + best supportive care (BSC) in patients with metastatic colorectal cancer (mCRC) enrolled in FRESCO-2
Stefano Lonardi, Veneto Institute of Oncology IOV-IRCCS Padua, ItalyPoster Session (PO.CL01.10 – Predictive Biomarkers 5)
Tuesday, April 9, 2024
Savolitinib (savo) + osimertinib (osi) vs savo + placebo (PBO) in patients (pts) with EGFR-mutated (EGFRm), MET-amplified advanced NSCLC with progression on osi
James Chih-Hsin Yang, National Taiwan University Hospital and National Taiwan University Cancer Centre, Taipei, TaiwanPoster Session (PO.CL01.10 – Predictive Biomarkers 5)
Tuesday, April 9, 2024
