Kronos Bio Continues to Advance Investigational SYK Inhibitors Entospletinib and Lanraplenib with New Preclinical Data at EHA2022 Congress
Kronos Bio presented promising preclinical data on its SYK inhibitors, entospletinib and lanraplenib, at the European Hematology Association (EHA) 2022 Congress. These findings bolster support for targeting spleen tyrosine kinase (SYK) in genetically defined acute myeloid leukemia (AML) subsets. The Phase 3 AGILITY trial of entospletinib is exploring its efficacy alongside chemotherapy in NPM1-mutated AML, with data expected in late 2023. The research indicates potential anti-tumor activity and improved T-cell responses, highlighting a novel therapeutic mechanism.
- Promising preclinical data supporting SYK inhibition in AML treatment.
- Phase 3 AGILITY trial set to provide key data in late 2023.
- Potential novel mechanism of action via T-cell response restoration.
- Dependence on clinical trial outcomes for future success.
- Need for continued capital may pose financial risk.
Posters include preclinical data on SYK inhibition in combination with targeted agents suggesting evidence of preclinical anti-tumor activity in acute myeloid leukemia
SAN MATEO, Calif. and CAMBRIDGE, Mass., June 10, 2022 (GLOBE NEWSWIRE) -- Kronos Bio, Inc. (Nasdaq: KRON), a company dedicated to transforming the lives of those affected by cancer and other serious diseases, will present preclinical data today from studies of the company’s two novel investigational spleen tyrosine kinase (SYK) inhibitors, entospletinib and lanraplenib. The poster presentations will take place at the European Hematology Association (EHA) 2022 Congress in Vienna.
The company is enrolling patients in clinical trials studying each compound and the preclinical data provide additional support for the biological rationale for the targeting of SYK in patients with genetically defined subsets of acute myeloid leukemia (AML).
The registrational Phase 3 AGILITY trial is assessing entospletinib in combination with standard of care cytarabine and anthracycline (7+3) chemotherapy in patients with NPM1-mutated AML, with data anticipated in the second half of 2023. The AGILITY trial is the first in AML to use measurable residual disease as a primary endpoint, a novel trial design that has the potential to accelerate the development of entospletinib.
Lanraplenib is being assessed as a potential treatment for patients with relapsed/refractory AML in combination with gilteritinib in a Phase 1b/2 study.
“At Kronos Bio, we are focused on developing novel therapies targeting the dysregulated transcription that is a hallmark of cancer,” said Jorge DiMartino, M.D., Ph.D., chief medical officer and executive vice president, Clinical Development. “Our work in AML is focused on SYK, a critical dependency in NPM1-mutated and FLT3-mutated AML. The data that we are presenting today add to the growing evidence that this approach has the potential to offer a way to target genetically defined AML.”
The first poster describes the analysis of mutational and gene expression signatures from bone marrow and peripheral blood samples of patients with NPM1-mutated AML, suggesting that the NPM1 mutation, with or without co-mutation of FLT3, is a strong predictor of entospletinib anti-leukemic activity. Additional experiments suggested that entospletinib and lanraplenib could restore T-cell proliferation in a subset of AML samples from patients with dysfunctional T-cell responses, suggesting a novel mechanism of action. The data provide additional support to suggest that inhibition of SYK is a promising therapeutic approach in NPM1- and FLT3-mutated AML.
The research was conducted as part of a collaboration with scientists at the Oregon Health & Science University.
The second poster describes the company’s findings of synergistic activity of lanraplenib in combination with other targeted agents, including gilteritinib, in an NPM1-mutated/FLT3-mutated PDX model. These findings provide additional support for ongoing and future clinical studies.
Two additional posters detail the design of the entospletinib and lanraplenib clinical studies.
Presentation information
Poster Title: Pharmacological inhibition of SYK confers anti-proliferative and novel anti-tumor immune responses in AML
Abstract Code: P392
Date and Time: Friday, June 10, 2022, 4:30 – 5:45 p.m. CET
Poster Title: SYK inhibition drives deep responses in a biomarker guided subset of AML alone and in rational combinations
Abstract Code: P428
Date and Time: Friday, June 10, 2022, 4:30 – 5:45 p.m. CET
Poster Title: Phase 1b/2 study on safety, pharmacokinetic, pharmacodynamic and preliminary efficacy of the selective SYK inhibitor lanraplenib in combination with the FLT3 inhibitor gilteritinib in FLT3-mutated relapsed/refractory AML (KB-LANRA 1001)
Abstract Code: P524
Date and Time: Friday, June 10, 2022, 4:30 – 5:45 p.m. CET
Poster Title: Phase 3, randomized, double-blind, placebo-controlled study of the efficacy and safety of entospletinib added to intensive induction and consolidation chemotherapy in newly diagnosed NPM1-mutated AML
Abstract Code: P525
Date and Time: Friday, June 10, 2022, 4:30 – 5:45 p.m. CET
About Kronos Bio, Inc.
Kronos Bio is an integrated discovery through late-stage clinical development biopharmaceutical company, focused on developing therapies targeting the dysregulated transcription that causes cancer and other serious diseases. Kronos Bio’s lead investigational compound is entospletinib, an orally administered, selective inhibitor targeting spleen tyrosine kinase (SYK) in clinical development for the frontline treatment of NPM1-mutated acute myeloid leukemia (AML) in combination with intensive chemotherapy. The company is also developing KB-0742, an orally administered inhibitor of cyclin dependent kinase 9 (CDK9), in Phase 1/2 clinical development for the treatment of MYC-amplified or overexpressing solid tumors.
Kronos Bio is based in San Mateo, Calif., and has a research facility in Cambridge, Mass. For more information, visit www.kronosbio.com or follow the company on LinkedIn.
Forward-Looking Statements
Statements in this press release that are not statements of historical fact are forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release, in some cases, uses terms such as “will,” “expect,” “potential” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding Kronos Bio’s intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: that the additional preclinical data provide support for the biological rationale for the targeting of SYK in genetically defined subsets of patients with AML, and similar statements; the anticipated timing for data from the registrational Phase 3 AGILITY trial; the potential of using measurable residual disease as a primary endpoint in the AGILITY trial to accelerate the development of entospletinib; conclusions implied from preclinical data; and other statements that are not historical fact. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, without limitation: Kronos Bio’s approach to the discovery and development of product candidates is unproven; risks associated with the COVID-19 pandemic and risks inherent in the clinical development of novel therapeutics; risks related to Kronos Bio’s lack of experience as a company in conducting clinical trials; and risks associated with the sufficiency of Kronos Bio’s cash resources and need for additional capital. These and other risks are described in greater detail in Kronos Bio’s filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in its Quarterly Report on Form 10-Q for the quarter ended March 31, 2022, which was filed with the SEC on May 4, 2022. Any forward-looking statements that are made in this press release speak only as of the date of this press release and are based on management’s assumptions and estimates as of such date. Except as required by law, Kronos Bio assumes no obligation to update the forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.
Company Contact:
Marni Kottle
Corporate Communications & Investor Relations
415-218-7111
mkottle@kronosbio.com
Investors:
Claudia Styslinger
Argot Partners
212-600-1902
kronosbio@argotpartners.com
Media:
Sheryl Seapy
Real Chemistry
949-903-4750
sseapy@realchemistry.com
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