IRF4

– KB-7898, a p300 KAT inhibitor, is the Company's first development candidate for autoimmune diseases and originates from its proprietary discovery engine that decodes complex transcription factor regulatory networks – – Preclinical data for KB-7898 will be presented at ACR Convergence 2024 – Oct. 07, 2024 -- Kronos Bio, Inc. (Nasdaq: KRON), a company dedicated to developing small molecule therapeutics that address cancers and autoimmune diseases driven by deregulated transcription, today announced the nomination of a development candidate, KB-7898, a p300 lysine acetyltransferase (KAT) inhibitor for the potential treatment of Sjögren’s disease, a chronic autoimmune disease that is characterized by the production of autoantibodies, chronic inflammation and lymphocytic infiltration of the exocrine glands that lead to uncomfortable dryness symptoms, known as sicca. Systemic effects are common and impact the lungs, kidneys and nervous system in addition to extensive dryness, profound fatigue and chronic pain. There are no approved treatments that target the underlying cause of Sjögren’s disease. Kronos Bio plans to initiate Investigational New Drug (IND)-enabling studies of KB-7898 in the fourth quarter of 2024. KB-7898 is being developed as an orally available therapy for people with Sjögren’s disease. p300 is an important cofactor for interferon regulatory factor 4 (IRF4) to enact immune responses across multiple cell types, including those that produce antibodies (B cells) and cytokines (T cells). Given this, Kronos Bio also intends to explore the utility of KB-7898 in other autoimmune diseases in the future. "Our proprietary discovery engine has enabled us to decode the multifaceted role of p300 across multiple cell types that drive inflammation and to create our second p300 KAT inhibitor—one that may treat autoimmune diseases,” said Nobert Bischofberger, Ph.D., president and chief executive officer of Kronos Bio. “Sjögren’s disease symptomatology can significantly impact quality of life and even be life threatening, and patients do not currently have access to an approved therapy that addresses the underlying disease mechanism. KB-7898 has been shown preclinically to reduce antibody production in B cells and cytokine production in T cells, and we believe could impact the etiology of Sjögren’s disease.” The Company’s preclinical data that support the role of p300 in inflammatory indications, including Sjögren’s disease, will be presented at the American College of Rheumatology's annual meeting, ACR Convergence 2024, on November 18, 2024, in Washington, DC. The data are summarized as follows: Inhibition of the KAT activity of p300, a critical cofactor of proinflammatory transcription factors, resulted in selective downregulation of cytokines such as TNFα, IL-23, IL-17A as well as soluble IgG Selective gene expression changes occurred at doses corresponding to partial inhibition of p300 KAT activity p300 KAT inhibition also led to significantly decreased inflammation in the rat CIA model, as measured by joint swelling, clinical score and histopathology In addition, p300 KAT inhibition in vitro showed a reduction in IL-17 transcript and protein levels in Th17 cells and, in vivo, showed significant decreases in the secondary immune response (i.e. IgG production) in the KLH challenge model. The ACR Convergence 2024 presentation will be available under the Science & Pipeline section of the Kronos Bio website on November 14, 2024. The abstract can be found on the American College of Rheumatology’s website. Sjögren’s disease is a chronic autoimmune disease characterized by the production of autoantibodies, chronic inflammation and lymphocytic infiltration of the exocrine glands. Systemic effects are common and impact the lungs, kidneys and nervous system in addition to extensive dryness, profound fatigue and chronic pain. Complications can include pneumonia, bronchitis, kidney problems, hepatitis, cirrhosis, peripheral neuropathy and lymphomas, and lead to a 50% increase in all-cause mortality. It is estimated that there are two to four million people in the U.S. living with this disease, making it one of the most prevalent autoimmune diseases. However, given the heterogeneous symptomatology of Sjögren’s disease, it is estimated that only one million patients in the U.S. are diagnosed. The disease is significantly more common in women; most people are older than 40 when they are diagnosed. Currently there are no approved treatments that target the underlying cause of Sjögren’s disease. Kronos Bio is a clinical-stage biopharmaceutical company dedicated to developing small molecule therapeutics that address deregulated transcription, a hallmark of cancer and autoimmune disease. Our proprietary discovery engine decodes complex transcription factor regulatory networks to identify druggable cofactors. We screen for and optimize small molecules that target these cofactors in a disease-specific context. Kronos Bio has a pipeline of three drug candidates. Istisociclib (KB-0742) is currently enrolling ovarian cancer patients in a Phase 1/2 clinical trial. Preclinical candidate KB-9558 is being developed for multiple myeloma and HPV-driven tumors. KB-7898 is Kronos Bio’s first autoimmune development candidate and has a target indication of Sjögren’s disease. Kronos Bio is based in San Mateo, Calif., and has a research facility in Cambridge, Mass. For more information, visit https://www.kronosbio.com or follow the Company on LinkedIn. 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– Through selective inhibition of proinflammatory transcription, p300 KAT inhibition modulates the activity and function of multiple pro-inflammatory signaling pathways that drive chronic inflammatory diseases – – Oral presentation taking place on Monday, November 18, 2024, from 4:15 p.m. to 4:30 p.m. EST – SAN MATEO, Calif. and CAMBRIDGE, Mass., Sept. 25, 2024 (GLOBE NEWSWIRE) -- Kronos Bio, Inc. (Nasdaq: KRON), a company dedicated to developing small molecule therapeutics that address cancers and other diseases driven by deregulated transcription, today announced that it will present preclinical data from its p300 KAT inhibitor program for autoimmune indications at the American College of Rheumatology's annual meeting, ACR Convergence 2024, being held from November 14 to 19, 2024 in Washington, DC. Kronos Bio is exploring the utility of a p300 KAT inhibitor for autoimmune indications given the role of interferon regulatory factor 4 (IRF4) and p300 in B cells, T cells and other immune cells. The data being presented at the meeting support the role of p300 in inflammation, and the Company remains on track to announce a development candidate for autoimmune diseases by the end of 2024. "We are leveraging our proprietary discovery engine that decodes complex transcription factor regulatory networks to develop a p300 KAT inhibitor to potentially treat autoimmune diseases. We are highly encouraged by these initial data demonstrating that p300 KAT inhibition can modulate the activity and function of multiple pro-inflammatory signaling pathways in chronic inflammatory diseases at well tolerated in vivo exposures,” said Peter Rahl, Ph.D., vice president of Discovery Biology at Kronos Bio, and corresponding author of the abstract. “The multifaceted and multicellular nature of autoimmune diseases suggests that an orally available therapeutic that selectively inhibits pro-inflammatory transcription in multiple cell types may address a root cause of inflammation.” Details for the ACR Convergence 2024 abstract are as follows: Title: p300 KAT Inhibition Selectively Targets Multiple Cell Types Involved in Chronic Inflammation and Downregulates Key Inflammatory CytokinesPresenter: Peter Rahl, Ph.D., Vice President, Discovery BiologyAbstract Number: 2598Poster Session: Cytokines & Cell TraffickingDate and Time: Monday, November 18, 2024, from 4:15 p.m. to 4:30 p.m. EST The presentation will be available under the Science & Pipeline section of the Kronos Bio website on November 14, 2024. The abstract can be found on the American College of Rheumatology’s website. About Kronos BioKronos Bio, Inc. (Nasdaq: KRON) is a clinical-stage company dedicated to developing small molecule therapeutics that address deregulated transcription, a hallmark of cancer and other diseases. Our proprietary discovery engine decodes complex transcription factor regulatory networks to identify druggable cofactors. We screen for and optimize small molecules that target these cofactors in a tumor-specific context. These efforts have yielded a preclinical pipeline along with two internally developed drug candidates. KB-0742 targets CDK9 to address MYC deregulation in solid tumors and KB-9558 targets p300 to address IRF4 dependence in multiple myeloma. Kronos Bio is based in San Mateo, Calif., and has a research facility in Cambridge, Mass. For more information, visit https://www.kronosbio.com or follow the Company on LinkedIn. Forward-Looking StatementsStatements 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 “anticipate,” “believe,” “could,” “expect,” “plan,” “will,” “may,” 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, Kronos Bio’s ability to leverage its proprietary discovery engine to develop a development candidate to potentially treat autoimmune diseases; the timing of an announcement of a development candidate for autoimmune diseases; potential programs in Kronos Bio’s pipeline; the potential of Kronos Bio’s product candidates, pipeline and its proprietary discovery engine; 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: changes in the macroeconomic environment or competitive landscape that impact Kronos Bio’s business; whether Kronos Bio will be able to progress its preclinical pipeline on the timelines anticipated, including due to risks inherent in the development of novel therapeutics; the risk that results of preclinical studies, early clinical trials (including preliminary results) and pharmacokinetic modeling are not necessarily predictive of future results; 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 June 30, 2024, filed with the SEC on August 8, 2024. 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.

– New data show istisociclib (KB-0742) triggered cell death in preclinical ovarian cancer models of platinum and PARP-inhibitor (PARPi) resistance – – New PK/PD results demonstrate that istisociclib given at 80mg on a 4 days on/3 days off schedule resulted in sustained downregulation of CDK9-dependent genes in peripheral blood mononuclear cells (PBMCs) – SAN MATEO, Calif. and CAMBRIDGE, Mass., Sept. 23, 2024 (GLOBE NEWSWIRE) -- Kronos Bio, Inc. (Nasdaq: KRON), a company dedicated to developing small molecule therapeutics that address cancers and other diseases driven by deregulated transcription, today highlighted new preclinical data from a study of istisociclib (KB-0742). The poster presentation took place over the weekend at the American Association for Cancer Research (AACR) 15th Biennial Ovarian Cancer Research Symposium. Kronos Bio is currently evaluating istisociclib, a CDK9 inhibitor, in an expansion cohort of a Phase 1/2 clinical trial to explore single agent activity in platinum-resistant high-grade serous ovarian cancer (HGSOC). "We’ve demonstrated preclinical evidence that istisociclib induced DNA damage and subsequent cell death, which further supports our clinical program focused on platinum-resistant high-grade serous ovarian cancer," said Luis A. Carvajal, Ph.D., Director of Translational Development at Kronos Bio, the lead author on the poster. "Importantly, platinum or PARPi insensitive cell lines showed greater sensitivity to istisociclib in cell viability assays. Moreover, ovarian cancer cells with PARPi resistance were sensitized to PARP inhibition in the presence of istisociclib.” Dr. Carvajal added, “Based on new PK data from our ongoing clinical trial, we conclude that plasma levels were consistent with efficacious exposures observed in preclinical models of ovarian cancer, and we are excited to be enrolling patients into an expansion cohort of patients with platinum-resistant high-grade serous ovarian cancer.” From the presentation, “Preclinical and clinical data support clinical expansion of istisociclib (KB-0742), an oral CDK9 inhibitor, into platinum-resistant ovarian cancer,” a summary of results is outlined below. In vitro data demonstrate that istisociclib induced apoptosis/cell deathIstisociclib resulted in the accumulation of γH2AX, a sensitive molecular marker of DNA damageIstisociclib disrupted homologous recombination (HR) DNA damage repair by downregulating BRCA1 and RAD51 creating a “BRCAness” phenotype in platinum and PARP resistant HR-proficient ovarian cancer cells From the dose escalation portion of the Company's ongoing Phase 1/2 trial of istisociclib in relapsed or refractory transcriptionally addicted advanced solid tumors, new pharmacokinetic/pharmacodynamic (PK/PD) results were presented. From the dose and schedule optimization portion of the trial evaluating 60mg and 80mg of istisociclib administered once daily on a 4 days on/3 days off schedule: Clinical exposures resulted in a long half-life of approximately 24 hours, and increased and prolonged weekly exposures consistent with efficacious levels observed in preclinical modelsConcurrent with increased and prolonged istisociclib exposure, deeper and more sustained downregulation of CDK9-dependent genes was observed in peripheral blood mononuclear cells (PBMCs) The poster from the presentation is available under the Science & Pipeline section of the Kronos Bio website. About Kronos BioKronos Bio, Inc. (Nasdaq: KRON) is a clinical-stage company dedicated to developing small molecule therapeutics that address deregulated transcription, a hallmark of cancer and other diseases. Our proprietary discovery engine decodes complex transcription factor regulatory networks to identify druggable cofactors. We screen for and optimize small molecules that target these cofactors in a tumor-specific context. These efforts have yielded a preclinical pipeline along with two internally developed drug candidates. Istisociclib (KB-0742) targets CDK9 to address MYC deregulation in solid tumors and KB-9558 targets p300 to address IRF4 dependence in multiple myeloma. Kronos Bio is based in San Mateo, Calif., and has a research facility in Cambridge, Mass.For more information, visit https://www.kronosbio.com or follow the Company on LinkedIn.