Kronos Bio Acquires SYK Inhibitor Portfolio from Gilead to Advance Targeted AML Therapy

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Kronos Bio is an emerging company dedicated to developing drugs targeting “undruggable” cancer targets. Its President and Chief Executive Officer, Norbert Bischofberger, previously served as Vice President of Research and Development and Chief Scientific Officer at Gilead Sciences, leaving the company two years ago. Recently, Bischofberger reached an agreement with his former employer to acquire Gilead’s portfolio of spleen tyrosine kinase (SYK) inhibitor assets.

The size of the upfront payment for this acquisition was not disclosed. Kronos Bio issued a convertible note to Gilead Sciences and committed to paying milestone payments and related royalties for the transaction.

In 2010, Gilead Sciences acquired CGI Pharmaceuticals for $120 million, obtaining the preclinical SYK inhibitor entospletinib, which was then regarded as an innovative approach for treating rheumatoid arthritis and other inflammatory diseases. In the subsequent years, Gilead advanced entospletinib and another SYK inhibitor, lanraplenib, into clinical development, with one indicated for the treatment of hematologic malignancies and the other for inflammatory diseases.

Kronos Bio is now preparing to acquire two clinical-stage assets, along with Gilead’s broader portfolio of SYK inhibitors. Regarding SYK inhibitors, Kronos Bio plans to focus on a biomarker-defined subgroup of patients with acute myeloid leukemia (AML). Evidence indicates that SYK is a key target in the small subset of cancer patients who overexpress the HOXA9 and MEIS1 transcription factors, a finding confirmed by retrospective analyses of entospletinib studies.

Among the 17 patients with expression levels more than three times the upper limit of normal, 16 achieved complete tumor remission. The analysis also linked high expression to improved overall survival, thereby validating the findings from preclinical studies.

Gilead published this analysis in 2018 but did not conduct any new clinical trials. The company developed the SYK inhibitor lanraplenib to address the pharmacological limitations that hindered the development of entospletinib for inflammatory diseases, particularly its interaction with proton pump inhibitors and the requirement for twice-daily dosing. However, lanraplenib failed to improve outcomes in conditions including rheumatoid arthritis and cutaneous lupus erythematosus.

Although setbacks prevented Gilead from advancing the project, Bischofberger stated that Kronos Bio is uniquely positioned to advance these differentiated and selective SYK inhibitors by leveraging its expertise in oncology and transcriptional regulatory networks.

Kronos Bio leverages the small-molecule microarray platform developed by its founder, Angela Koehler, an Associate Professor at the Massachusetts Institute of Technology. Previously, the company had designated a CDK9 inhibitor, expected to enter clinical development early next year, as its most advanced pipeline candidate.

Last July, Kronos Bio completed a $105 million Series A financing round, part of which will be used to pay the upfront fee for its transaction with Gilead Sciences. The acquisition of entosplatinib and lanraplenib will also accelerate Kronos Bio’s clinical development pipeline.

Reference Source: Bischofberger's Kronos Buys SYK Inhibitors from Gilead