DP-9024 / Ono Pharmaceutical - LARVOL DELTA

DP-9024, an investigational small molecule modulator of the integrated stress response kinase GCN2, synergizes with asparaginase therapy in leukemic tumors (AACR 2023) - "In vivo asparagine depletion by Leunase (L-asparaginase) led to upregulation of ATF4 in leukemia tumors in a PK/PD xenograft model and oral dosing of DP-9024 reversed Leunase-mediated upregulation of tumoral ATF4 down to basal levels. The ISR kinase GCN2 was identified as a resistance mechanism to ASNase in ASNS-low leukemic cells. Inhibition of the ISR pathway through the potent and selective small molecule modulator of GCN2, DP-9024, synergized with ASNase and re-sensitized leukemic cells to amino acid withdrawal in vitro as well as in leukemic xenograft models in vivo."

Hematological Malignancies • Leukemia • Oncology • Solid Tumor • ATF4

DP-9024, an investigational small molecule modulator of the Integrated Stress Response kinase PERK, causes B-cell cancer growth inhibition as single agent and in combination with standard-of-care agents (AACR 2023) - "The ISR/UPR is a targetable vulnerability in cancers with high basal levels of ER stress. DP-9024 increases UPR signaling via activating PERK dimerization. This novel mechanism leads to antitumoral effects in B-cell cancers in vitro and in vivo likely through the induction of unresolved ER stress, which may potentially provide an alternative mechanism to current UPR targeting therapies."

Combination therapy • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • ATF4 • CASP3 • CASP7

Dimerization-induced activation of the integrated stress response kinase PERK by an investigational small molecule modulator, DP-9024 (AACR 2023) - "Paradoxical stimulation of the ISR family member kinase PERK, through direct binding and dimerization by DP-9024, led to unresolved ER stress that can potentially be leveraged as a novel mechanism to induce growth arrest in UPR vulnerable cancers, including myelomas and B-cell lymphomas."

Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • ATF4 • CASP3 • CASP7

Deciphera Pharmaceuticals Announces Eight Presentations Highlighting Discovery Research Programs at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Businesswire) - "...'At the upcoming AACR meeting, we look forward to presenting preclinical data supporting our next Investigational New Drug (IND) candidate, DCC-3084, a potential best-in-class pan-RAF inhibitor that broadly inhibits Class I, II, and III BRAF mutations, BRAF fusions, and BRAF/CRAF heterodimers. In addition, we will present preclinical data on our ULK inhibitor, DCC-3116, in combination with QINLOCK in gastrointestinal stromal tumor (GIST) and in combination with encorafenib and cetuximab in colorectal cancer that strongly support two new dose escalation combination studies that we expect to initiate in the second half of this year'....'We are excited to share initial preclinical data on two new programs, GCN2 and PERK, two novel targets focused on the integrated stress response'...New pan-kit development candidate DCC-3009 for GIST demonstrates potential best-in-class profile with broad coverage of KIT mutations with high selectivity."

New trial • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor