Kronos Bio announced prioritization of clinical Portfolio to focus on Lanraplenib in the treatment of patients with AML
Kronos Bio, Inc. announced the prioritization of its clinical portfolio to focus on the development of its next generation SYK inhibitor, lanraplenib, and its CDK9 inhibitor, KB-0742.
The company is discontinuing the Phase 3 trial of its SYK inhibitor, entospletinib, for the treatment of newly diagnosed patients with NPM1-mutated acute myeloid leukemia (AML) and plans to close the trial to further enrollment. Patients already enrolled in the trial may complete their course of treatment. The trial is not being discontinued due to adverse events or lack of efficacy signals. Kronos Bio decided to end the trial after its recent review of enrollment data. In this assessment, the company projected significant delays due to several factors, including the operational challenges the company faced in enrolling a genetically defined subset of patients in a front-line setting, the residual and ongoing impacts of the COVID-19 pandemic, and the inability to activate planned clinical trial sites in Russia and Ukraine.
Kronos Bio believes the most promising transformational therapy for the treatment of AML is the SYK inhibitor lanraplenib, initially in the relapsed/refractory AML setting where the need is particularly acute. The company will also continue to prioritize its investigational CDK9 inhibitor, KB-0742, which is currently in a Phase 1/2 clinical trial in patients with solid tumors, with a planned update on the trial on track for the fourth quarter.
Lanraplenib has a number of advantages over entospletinib, including once daily dosing and the ability to be taken fed or fasted. Additionally, lanraplenib may be co-administered with proton-pump inhibitors for patients who require these medications to manage their gastro-esophageal reflux or related conditions.
Lanraplenib has demonstrated favorable pharmacokinetic (PK), pharmacodynamic (PD) and safety in more than 250 trial participants, including healthy volunteers and patients with autoimmune diseases. In preclinical studies, lanraplenib was shown to have anti-leukemic activity against NPM1-mutated and FLT3-mutated patient-derived AML cells and to synergize with gilteritinib.
Kronos Bio is actively enrolling patients in the dose escalation portion of a Phase 1b/2 trial. The trial is aimed at a group of patients with low response rates to gilteritinib, the only therapy currently approved for this patient population, and generally poor prognosis. Only an estimated 10% of patients with relapsed/refractory AML survive five years from the time of relapse.
Lanraplenib has the potential for use in combination with a number of additional targeted agents in genetically defined subsets of AML. This includes both additional relapsed/refractory disease indications, as well as in patients with newly diagnosed AML.
The company anticipates sharing initial data from the lanraplenib/gilteritinib trial, along with the recommended Phase 2 dose (RP2D), in the fourth quarter of 2023 or first quarter of 2024.
As for KB-0742, Kronos Bio remains on track to report PK, PD and safety data, as well as the recommended Phase 2 dose, from the Phase 1/2 trial of KB-0742 in the fourth quarter.
KB-0742 is a highly selective, orally bioavailable inhibitor of cyclin dependent kinase 9 (CDK9). CDK9 is a global regulator of transcription and key cofactor of many oncogenic transcription factors, including the MYC family of transcription factors. MYC is a long-recognized driver of cancer and sought-after drug target. MYC is amplified in approximately 30% of solid tumors, including those affecting the lungs, ovaries and breast.
After reaching RP2D, the company plans to enroll two cohorts of patients in the next stage of the trial: patients with MYC-amplified solid tumors and patients with transcriptionally addicted tumors.
Following the Q4 2022 update from ongoing KB-0742 trial, the company anticipates sharing initial KB-0742 efficacy data in the second half of 2023.