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Kronos Bio, Inc. (Nasdaq: KRON) is a clinical-stage biopharmaceutical company committed to transforming patient outcomes through the discovery and development of novel cancer therapeutics. With a focus on modulating historically challenging cancer targets, the company leverages industry-leading high-throughput screening strategies and its proprietary small molecule microarray (SMM) platform. Kronos Bio's core business revolves around developing therapies that target the deregulated transcription processes fundamental to many cancers.
The company's most prominent projects include KB-0742, an inhibitor of CDK9, which has shown promising anti-tumor activity and a manageable safety profile in early trials involving patients with transcriptionally addicted solid tumors. The ongoing phase 1/2 trial has recently escalated dosing to 80 mg, with expansion cohort data anticipated in mid-2024.
Another key development is KB-9558, targeting the lysine acetyltransferase (KAT) domain of p300, a crucial component in the IRF4 transcription regulatory network. This molecule is currently in IND-enabling studies, expected to be completed by Q4 2024. KB-9558 aims to provide a novel treatment for multiple myeloma, a disease driven by IRF4, for which existing therapies are not curative.
Despite deciding not to advance the phase 1b/2 trial of lanraplenib in combination with gilteritinib for FLT3-mutated relapsed/refractory acute myeloid leukemia (AML) to phase 2, Kronos Bio remains open to further developing lanraplenib with a partner. The company emphasizes its strong biological rationale and engagement in target modulation in AML, even though it did not observe sufficient response in the study population.
Under the leadership of President and CEO Dr. Norbert Bischofberger, Kronos Bio continues to innovate, focusing on mapping transcription regulatory networks (TRNs) to identify and target key modulators, ultimately leading to the development of novel drug candidates. The company's latest structural and leadership changes are designed to streamline operations and ensure efficient delivery on business objectives.
Kronos Bio is based in San Mateo, Calif., with a research facility in Cambridge, Mass. For more information, visit https://www.kronosbio.com/ or follow the company on LinkedIn.
Kronos Bio (NASDAQ: KRON) announced significant leadership changes and restructuring. Deborah Knobelman, Ph.D., will succeed Norbert Bischofberger, Ph.D. as President and Interim CEO effective December 3, 2024. Dr. Bischofberger will remain on the Board of Directors and serve as an advisor. The company also disclosed a major workforce reduction of approximately 83% by year-end, aligning with previously announced cost reduction strategies. The company is exploring strategic options, including potential business combinations and divestiture of preclinical assets, to maximize stockholder value.
Kronos Bio (NASDAQ: KRON) presented preclinical data for its p300 KAT inhibitor program at ACR Convergence 2024. The research focused on KB-7898, demonstrating its ability to reduce inflammation through multiple pathways. Key findings showed that KB-7898 modulated proinflammatory signaling and reduced production of disease-related inflammation markers, including IgG, IL-23, and IL-17A. In the Keyhole Limpet Hemocyanin booster, it achieved up to 50% reduction in KLH-IgG production. The compound also significantly decreased inflammation in a collagen-induced arthritis rat model. The company is currently exploring strategic alternatives, including potential partnerships for its p300 KAT inhibitor programs.
Kronos Bio (NASDAQ: KRON) announced the discontinuation of istisociclib development due to unfavorable benefit-risk profile in platinum-resistant ovarian cancer patients. The Board approved exploring strategic alternatives to maximize stockholder value. The company reported $124.9 million in cash and investments as of September 30, 2024, with a Q3 net loss of $14.1 million. Five out of seven enrolled patients experienced neurological events, leading to three discontinuations. The company will implement cost reductions while exploring options for its preclinical assets, including two p300 KAT inhibitor programs: KB-9558 for multiple myeloma and KB-7898 for Sjögren's disease.
Kronos Bio (KRON) will present preclinical data from its p300 KAT inhibitor program for multiple myeloma at the ASH Annual Meeting in San Diego from December 7-10, 2024. The presentation focuses on KB-9558, their p300 KAT inhibitor being studied for multiple myeloma and HPV-driven tumors.
The research demonstrates a strong relationship between transcription factor IRF4 and p300, a protein affecting cancer cell genes. The findings show these components have a preferential protein-protein interaction through a statistically similar network of interactors, unique among tested transcription factors.
The poster presentation, scheduled for December 9, 2024, will be available on Kronos Bio's website under Publications.
Kronos Bio (NASDAQ: KRON) presented preclinical data from its p300 KAT inhibitor program for HPV-driven tumors at the EORTC-NCI-AACR Symposium. The research demonstrates that their p300 KAT inhibitor, KB-9558, effectively suppresses HPV oncogenes E6 and E7, which are critical for tumor growth. The inhibition leads to restoration of p53 and Rb tumor suppressor pathways, potentially offering a new therapeutic approach for HPV-driven cancers. The study showed that HPV integrates into specific genome locations where p300 regulates transcription, creating a vulnerability that can be targeted by KB-9558.
Kronos Bio (Nasdaq: KRON) will present preclinical data on its p300 KAT inhibitor program for HPV-driven tumors at the EORTC-NCI-AACR Symposium in Barcelona, Spain, from October 23-25, 2024. The company's p300 KAT inhibitor, KB-9558, shows promise in targeting HPV-driven cancers by selectively inhibiting viral oncoproteins E6 and E7.
Key findings include:
- HPV-16 virus hijacks the host transcriptional cofactor p300 to drive expression of E6 and E7 oncogenes
- Inhibition of p300 KAT activity downregulates E6 and E7, reactivating the tumor suppressor p53
- KB-9558 demonstrates high selectivity against HPV oncoproteins
The poster presentation, scheduled for October 24, 2024, will showcase these results, potentially offering new targeted therapies for the estimated 38,000 new cases of HPV-driven cancers annually in the United States.
Kronos Bio has announced the selection of KB-7898, a p300 KAT inhibitor, as its first development candidate for autoimmune diseases, specifically targeting Sjögren’s disease. This candidate stems from Kronos Bio's proprietary discovery engine, which decodes complex transcription factor regulatory networks.
Preclinical data for KB-7898 will be presented at ACR Convergence 2024. The data indicate that p300 KAT inhibition can reduce antibody production in B cells and cytokine production in T cells. Kronos Bio plans to initiate IND-enabling studies of KB-7898 in Q4 2024. The company also intends to explore the candidate's utility in other autoimmune diseases in the future.
The preclinical studies showed promising results, including selective downregulation of cytokines and significant decreases in inflammation in animal models. The presentation will be available on Kronos Bio's website on November 14, 2024, and the abstract is available on the American College of Rheumatology’s website.
Kronos Bio (Nasdaq: KRON) will present preclinical data from its p300 KAT inhibitor program for autoimmune indications at ACR Convergence 2024 in Washington, DC. The presentation, scheduled for November 18, 2024, will showcase how p300 KAT inhibition modulates multiple pro-inflammatory signaling pathways in chronic inflammatory diseases.
The company is exploring the utility of a p300 KAT inhibitor for autoimmune indications, given the role of IRF4 and p300 in immune cells. Kronos Bio remains on track to announce a development candidate for autoimmune diseases by the end of 2024.
The data supports the role of p300 in inflammation and demonstrates that p300 KAT inhibition can modulate pro-inflammatory signaling pathways at well-tolerated in vivo exposures. This approach may address a root cause of inflammation in autoimmune diseases.
Kronos Bio (NASDAQ: KRON) presented new preclinical data on istisociclib (KB-0742), a CDK9 inhibitor, at the AACR Ovarian Cancer Research Symposium. The data supports the clinical evaluation of istisociclib in advanced ovarian cancer, particularly in platinum and PARP-inhibitor resistant cases.
Key findings include:
- Istisociclib triggered cell death in preclinical ovarian cancer models resistant to platinum and PARP inhibitors
- New PK/PD results show sustained downregulation of CDK9-dependent genes in PBMCs with an 80mg dose on a 4 days on/3 days off schedule
- Preclinical evidence suggests istisociclib induces DNA damage and subsequent cell death
- Istisociclib disrupted homologous recombination DNA damage repair, creating a "BRCAness" phenotype in resistant cells
Kronos Bio is currently evaluating istisociclib in a Phase 1/2 clinical trial expansion cohort for platinum-resistant high-grade serous ovarian cancer (HGSOC).
Kronos Bio (Nasdaq: KRON), a company developing small molecule therapeutics for cancers and diseases driven by deregulated transcription, has announced its participation in three upcoming conferences in September 2024:
1. H.C. Wainwright 26th Annual Global Investment Conference (Sept 9-11, New York): CEO Norbert Bischofberger will present on Sept 9.
2. AACR 15th Biennial Ovarian Cancer Research Symposium (Sept 20-21, Seattle): A poster on KB-0742, an oral CDK9 inhibitor, will be presented.
3. International Myeloma Society 21st Annual Meeting (Sept 25-28, Brazil): A Kronos Bio collaborator will give an oral presentation on p300 catalytic inhibition in multiple myeloma.
Live audio webcast and posters will be available on the Kronos Bio website.
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