PLD-102 / PeLeMed - LARVOL DELTA

Plm-102, a Next Generation FLT3 Inhibitor, Shows Potent Anti-Leukemic Activity on Resistance to Gilteritinib in FLT3 Mutated Acute Myeloid Leukemia (ASH 2023) - "The significantly improved effects in the combination of PLM-102 and Trametinib, a MEK inhibitor, were observed through cell viability assays and a xenograft model, further supporting their potential as a synergistic therapeutic approach. Our results have confirmed that RAS-MEK-ERK signaling pathway and cytokine signaling pathway were activated by Gilteritinib resistance. Notably, PLM-102 exhibits exceptional anti-leukemic activity in Gilteritinib-resistant cell lines through the unique mechanism of inhibiting the RAS-MEK-ERK-cytokine signaling pathway. These results highlight the potential of PLM-102 as a third-generation inhibitor with favorable efficacies in patients with resistance to current FLT3 inhibitors."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • KRAS

The third-generation FLT-3 inhibitor, PLM-102, is a promising therapeutic option for venetoclax-resistant AML (AACR 2025) - "Notably, PLM-102 demonstrated the highest tumor growth inhibitory (TGI) efficacy compared with those of other FLT3 inhibitors including tuspetinib, gilteritinib and PHI-101. In conclusion, PLM-102 completely inhibited FLT3 kinase and its downstream signaling including AKT and STAT3, inducing apoptosis in VR AML cells along with significant inhibition of the tumor growth in the VR xenograft mouse model. These findings suggest that PLM-102, a third-generation FLT-3 inhibitor, is a promising candidate for overcoming venetoclax resistance and could serve as a therapeutic option for venetoclax-resistant AML."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • CASP3 • FLT3 • MCL1 • STAT3

Pelemed, ‘FLT3 inhibitor’ AML US phase 1 “FDA IND approval” [Google translation] (Biospectator) - "'PLM-102' US phase 1 IND 'approved'...clinical trial to begin this year...Pelemed received approval for a phase 1 clinical trial IND for PLM-102 from the Ministry of Food and Drug Safety last month....Through this phase 1 clinical trial, Pelemed is evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) characteristics of PLM-102 in patients with relapsed/refractory acute myeloid leukemia (AML)."

IND • New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Discovery of PLM-102, a highly potent 3rd generation FLT3 inhibitor, in drug-resistant FLT3-ITD-TKD mutated acute myeloid leukemia (AACR 2023) - "In FLT3-ITD-positive cell lines (MV4-11, MOLM-13, MOLM-14, Ba/F3-ITD-D835Y, Ba/F3-ITD-F691L), PLM-102 shows about 18~25-fold higher anti-proliferative activities than Gilteritinib. These results are very encouraging because large tumors have a limited blood supply and high interstitial fluid pressure, leading to a poor absorption of anticancer drugs. Pharmacokinetics of PLM-102 displayed higher bone-marrow exposure indicating better target engagement and benefits in the clinical translation in AML.In conclusion, PLM-102 is a promising therapeutic candidate for the FLT3-ITD-mutated AML as well as the acquired resistance to current FLT3 inhibitors."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CASP3 • FLT3

Development of PLM-102, a novel dual inhibitor of FLT3 and RET as a new therapeutic option for acute myeloid leukemia. (ASCO 2022) - " In compared to FDA-approved Gilteritinib, PLM-102 showed stronger sub-nanomolar IC50 values in FLT3 kinases regardless of wild-type, ITD, TKD and ITD/TKD mutants in both kinase- and cell-based assays. Taken together, PLM-102 showing potent anti-cancer activity against various in vitro and in vivo AML models could be developed as a valuable agent overcoming the acquired resistance to the current FLT3 inhibitor."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CASP3 • CASP7 • FLT3