EP300 x 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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— KB-0742 cleared 80mg four-days-on, three-days-off dosing schedule in dose escalation — — Company expects to provide an efficacy update on this expansion cohort in 1H 2025 — SAN MATEO, Calif. and CAMBRIDGE, Mass., July 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 announced the first patient dosed in an expansion cohort with KB-0742 at a dose of 80mg given on a four-days-on, three-days-off schedule. This expansion cohort is enrolling platinum-resistant patients with high-grade serous ovarian cancer (HGSOC), a tumor type which is particularly sensitive to CDK9 inhibition due to MYC amplification or overexpression and deficiencies in homologous recombination (HRD+). “To date, KB-0742 has a safety database of over 100 patients, with no grade 3 or 4 neutropenia observed, and has shown preliminary anti-tumor activity in transcriptionally addicted solid tumors at the 60mg dose given three-days-on, four-days-off,” said Norbert Bischofberger, Ph.D., president and chief executive officer, Kronos Bio, Inc., “Pharmacokinetic modeling of 80mg four-days-on, three-days-off schedule shows a 1.8-fold increase in AUC over seven days relative to the 60mg three-days-on, four-days-off schedule. With this dose and schedule, we believe that KB-0742 will deliver therapeutic responses in this high unmet need population. We look forward to providing an update on the efficacy of KB-0742 in the first half of 2025.” In the United States there are an estimated 22,000 new cases of ovarian cancer each year, with a five-year survival rate of less than 50%. Approximately 85% of these tumors exhibit MYC-amplification or overexpression, and 50% are HRD+. “We are excited for the focused expansion of KB-0742 in platinum-resistant HGSOC. KB-0742 has to date provided prolonged stable disease of over 300 days in one of my platinum-resistant HGSOC patients,” said Howard “Skip” A. Burris M.D., president of Sarah Cannon Research Institute (SCRI). “HGSOC patients have limited treatment options after progressing on platinum therapy and KB-0742 brings new possibilities to those battling this devastating disease.” About Kronos Bio, Inc. Kronos 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. About KB-0742: KB-0742 is a selective, oral inhibitor of CDK9, a key cofactor of oncogenic MYC transcription factor activity. KB-0742-1001 (NCT04718675) is a Phase 1/2 open-label dose escalation and cohort expansion study of KB-0742 as a treatment for MYC-amplified and other transcriptionally addicted relapsed or refractory solid tumors. KB-0742 is currently being studied in an expansion cohort focused on platinum-resistant high-grade serous ovarian cancer patients. 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 “anticipate,” “believe,” “could,” “expect,” “plan,” “will,” 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, the next expected efficacy update on the expansion cohort in the KB-0742 trial; projections from pharmacokinetic modeling; our belief that KB-0742 will deliver therapeutic responses; estimated patient populations; the potential of Kronos Bio’s product candidates 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 clinical trials on the timelines anticipated, including due to risks inherent in the clinical development of novel therapeutics; risks related to Kronos Bio’s limited experience as a company in conducting clinical trials; the risk that results of preclinical studies, early clinical trials (including preliminary results) and pharmacokinetic modeling are not necessarily predictive of future results; risks associated with enrolling 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, 2024, filed with the SEC on May 9, 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. Source: Kronos Bio, Inc. Investor & Media Contact:Margaux BennettVice President, Corporate Development and Investor Relations, Kronos Bio, Inc.650-781-5026mbennett@kronosbio.com

— KB-0742 continues to demonstrate a manageable safety and tolerability profile with no grade 3/4 neutropenia observed — — KB-0742 continues to show dose linear pharmacokinetics up to 80mg three-days-on, four-days-off dose, including increased target engagement at the 80mg vs. 60mg doses — — The escalation cohort at 80mg four-days-on, three-days-off is currently enrolling, and the expansion cohort at this dose is expected to begin enrollment in the third quarter of 2024 — SAN MATEO, Calif. and CAMBRIDGE, Mass., May 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 announced the presentation of new data from its ongoing Phase 1/2 study, KB-0742-1001, a first-in-human, open-label dose escalation and cohort expansion study of KB-0742 in patients with relapsed or refractory solid tumors or non-Hodgkin lymphoma, in a poster session at the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting being held from May 31 – June 4, 2024 in Chicago, Illinois and online. “We are pleased that KB-0742 continues to demonstrate a manageable safety and tolerability profile as it progresses through dose escalation,” said Norbert Bischofberger, Ph.D., president and chief executive officer, Kronos Bio, Inc. “These data indicate a deepening reduction of CDK9-sensitive transcripts at the 80mg dose as compared to the 60mg dose. In addition, MYC reductions were observed in paired biopsy tumor tissues. This data provides us with confidence that the 80mg four-days-on, three-days-off dose and schedule will show increased patient benefit. We are currently enrolling the dose escalation arm at the 80mg four-days-on, three-days-off schedule and look forward to opening the expansion cohort in the third quarter of this year.” The poster features: Data from 103 patients with transcription factor (TF) fusion or MYC driven tumors treated with KB-0742 at 60mg (n=82) and 80 mg (n=21) three-days-on/four-days-off in escalation and expansion cohorts.Patients enrolled in the study had received a median of three prior treatments (range: 0-9).The most frequently reported treatment-emergent adverse events (AE) were manageable mild to moderate nausea (69.9%) and vomiting (52.4%).Notably, no grade 3/4 neutropenia was observed.Patients remained on treatment for an average of >2 cycles and a maximum of 14 completed cycles.Less than 10% of patients discontinued treatment due to adverse events.Two case studies, a platinum-resistant ovarian cancer (OC) patient, and a non-small-cell-lung cancer (NSCLC) patient with five prior lines of therapy will be presented. These patients exhibited anti-tumor activity including stable disease responses of 71 days for the NSCLC patient and greater than 195 days for the OC patient, who continues on therapy.Pharmacokinetic modeling indicates that the 80mg four-days on three-days off dose schedule results in a greater than ten-fold increase in time above a preclinically determined efficacy threshold compared to the 60mg three-days-on four-days-off dose schedule. Based on the promising initial data presented at ASCO and the pharmacokinetic modeling the Company expects to see increased efficacy in the 80mg four-day-on, three-day-off expansion cohort which is expected to begin enrolling in the third quarter of 2024. Preliminary efficacy data was presented at the 2023 AACR-NCI-EORTC meeting in October 2023 showing KB-0742’s on-mechanism anti-tumor activity in transcriptionally addicted tumors including a partial response at the 60mg three-days-on, four-days-off dose schedule. Details for the ASCO 2024 abstract are as follows: Title: Study update of the oral CDK9 inhibitor KB-0742 in relapsed or refractory transcriptionally addicted advanced solid tumorsPresenter: Brian A. Van Tine, M.D., Ph.D., Washington University in St. LouisAbstract ID#: 3102Poster Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor BiologyLocation: Hall A, McCormick Place, Chicago, IllinoisPoster Board #: 247Date and Time: Saturday, June 1, 2024, from 9:00 a.m. to 12:00 p.m. CDT About Kronos Bio, Inc. Kronos 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 (TF) 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. About KB-0742: KB-0742 is a selective, oral inhibitor of CDK9, a key cofactor of oncogenic MYC transcription factor activity. KB-0742-1001 (NCT04718675) is a Phase 1/2 open-label dose escalation and cohort expansion study of KB-0742 as a treatment for MYC-amplified and other transcriptionally addicted relapsed or refractory solid tumors. 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 “anticipate,” “believe,” “could,” “expect,” “plan,” “will,” 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, the next clinical update on KB-0742; the expected timing of enrollment of the 80mg expansion cohort of the KB-0742 trial; the expectation of increased efficacy and increased patient benefit of KB-0742 in the 80mg expansion cohort; the potential of Kronos Bio’s product candidates 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 clinical trials on the timelines anticipated, including due to risks inherent in the clinical development of novel therapeutics; risks related to Kronos Bio’s limited experience as a company in conducting clinical trials; the risk that results of preclinical studies and early clinical trials (including preliminary results) are not necessarily predictive of future results; risks associated with completing necessary preclinical studies and receiving regulatory clearance for, and enrolling, 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, 2024, filed with the SEC on May 9, 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. Source: Kronos Bio, Inc. Investor & Media Contact:Margaux BennettVice President, Corporate Development and Investor Relations, Kronos Bio, Inc.650-781-5026mbennett@kronosbio.com