Kronos Bio has declared that it will not be continuing clinical development for its acute myeloid leukaemia (AML) spleen tyrosine kinase (SYK) inhibitor lanraplenib, after reviewing Phase Ib data. The biotech is focusing its efforts on a new candidate, KB-9558, but is still open to continuing lanraplenib’s development with a partner, according to an 18 December 2023 press release.
The San Mateo, California-headquartered company was investigating lanraplenib in combination with Astellas Pharma’s Xospata (gilteritinib) in a Phase Ib/II (NCT05028751) relapsed/refractory FLT3-mutated AML study. Kronos chose not to pursue the Phase II portion of the study as no complete response (CR) or CR with partial haematologic recovery (CRh) was shown in Phase Ib. Furthermore, multiple participants from the 24-patient study discontinued the treatment early.
In a company press release, Kronos Bio’s chief medical officer Dr Jorge DiMartino stated: “Patients in our study were older, more heavily pretreated and frailer than the relapsed/refractory patients in earlier studies. Many patients experienced non-drug related infectious disease complications leading to discontinuation during the first two months of treatment without achieving the count recovery needed to achieve a CR or CRh.” He added that the company now faced a different treatment landscape for the condition, which made it difficult to prove the clinical benefit of adding lanraplenib to Xospata in this patient group.
In 2017, the US Food and Drug Administration approved Novartis Pharmaceuticals’ Rydapt (midostaurin) for FLT3-mutant AML, making it the first treatment approved for AML in the US since 2000. The agency followed this with the approvals of Xospata in 2018 and Daiichi Sankyo’s Vanflyta (quizartinib) in July 2023. Xospata monotherapy had demonstrated a median overall survival of 9.3 months versus 5.6 months in the chemotherapy group in its Phase III trial (NCT02421939).
KB-9558 is a treatment for multiple myeloma that works through the modulation of IRF4. Kronos is undertaking an investigational new drug-enabling study with an expected completion date in the fourth quarter of 2024. This molecule, and Kronos' solid tumour therapy KB-0742, were internally discovered through the company’s proprietary product engine. Kronos forecasts a potential data readout for KB-0742’s Phase I/II trial (NCT04718675) in mid-2024. The biotech has enough money to support its clinical development plans through to 2026.
