HPV E6 x HPV E7

– Preclinical data demonstrate that inhibiting the p300 KAT domain reactivates p53 in HPV-driven tumors resulting in anti-tumor activity –SAN MATEO, Calif., and CAMBRIDGE, Mass., Oct. 23, 2024 (GLOBE NEWSWIRE) -- 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 preclinical data from its p300 KAT inhibitor program for human papillomavirus (HPV)-driven tumors at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics. Kronos Bio is exploring the utility of its p300 KAT inhibitor, KB-9558, for HPV-driven tumors. In the presentation, the authors show that the HPV genome preferentially integrates into transcriptionally active regions in the human genome where it becomes dependent on p300 to drive expression of its E6 and E7 oncogenes. It is widely recognized that elevated transcription of HPV E6 and E7 genes promotes degradation of tumor suppressors p53 and Rb. Importantly, inhibition of p300 KAT activity was highly selective in repressing the transcription of E6 and E7, which in turn led to restoration of the p53 and Rb pathways and drove anti-tumor effects through apoptosis and inhibition of uncontrolled tumor cell growth. "Continued expression of certain viral genes, especially E6 and E7, plays a critical role in tumor growth and progression of HPV-driven tumors, including head & neck, cervical, and other anogenital cancers. Importantly, there are no approved targeted therapies that inhibit E6 and E7,” said Charles Lin, Ph.D., chief scientific officer of Kronos Bio. "While this is early-stage research, given the ability of p300 KAT inhibition to target E6 and E7 and restore tumor suppressor pathways, we believe this p300 KAT inhibitor has the potential to be a remarkable and unique approach toward ensuring that fewer people suffer from HPV-driven cancer." In the presentation titled, "Oncogenic human papillomavirus hijacks p300 to drive viral transcription, creating a therapeutic vulnerability that can be exploited with selective p300/CBP catalytic inhibitors", the authors describe the experiments that led to the following key findings: HPV integrates into the human genome at specific locations where p300 regulates transcriptionp300 inhibition demonstrated specific and potent reduction of expression of HPV oncogenes E6 and E7, both at the RNA and protein levelLoss of E6 and E7 led to restoration of p53 and Rb tumor suppressor pathways which led to the upregulation of p53 activated genes (e.g., CDKN1A) and downregulation of Rb repressed genes (e.g., CDK1)Re-expression of E6 and E7 from an exogenous lentiviral vector where viral oncogene transcription is not mediated by p300 KAT activity reversed the effects of p300 KAT inhibition on p53 restoration and anti-tumor effectsThese findings support the potential of KB-9558, a p300 KAT inhibitor, to treat HPV-driven tumors given its potential to suppress E6 and E7 expression and restore the p53 pathway The poster presentation will take place on October 24, 2024, and is currently available under the Publications section of the Kronos Bio website. About Kronos BioKronos 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. 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, KB-9558’s ability to potentially treat HPV-driven tumors; 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.

– Data show that p300 KAT inhibitor KB-9558 was highly selective against human papillomavirus (HPV) oncoproteins E6 and E7, and therefore drove anti-tumor effects – – Poster presentation taking place on Thursday, October 24, 2024 – SAN MATEO, Calif. and CAMBRIDGE, Mass., Oct. 09, 2024 (GLOBE NEWSWIRE) -- 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 that it will present preclinical data from its p300 KAT inhibitor program for human papillomavirus (HPV)-driven tumors at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, being held from October 23 to 25, 2024 in Barcelona, Spain. Kronos Bio is exploring the utility of its p300 KAT inhibitor, KB-9558, for HPV-driven tumors. In the presentation, the authors will show that the oncogenic HPV-16 virus hijacks the host transcriptional cofactor p300 in order to drive expression of the virally encoded oncogenes E6 and E7. Inhibition of p300 KAT activity achieved anti-tumor effects by downregulating E6 and E7 which in turn leads to reactivation of p53, a known tumor suppressor. “Despite the availability of HPV vaccines, HPV still causes many cancers including head and neck cancer and cervical cancer, with an estimated 38,000 new cases of HPV-driven cancers annually in the United States alone. Viral oncoproteins such as the ones encoded by HPV provide a unique therapeutic opportunity since they are only found in tumor cells,” said Charles Lin, Ph.D., chief scientific officer of Kronos Bio. “By demonstrating that we can selectively inhibit E6 and E7 with a p300 KAT inhibitor, we hope to provide patients with HPV-driven cancers innovative targeted therapies.” Abstract details are as follows: Title: Oncogenic human papillomavirus hijacks p300 to drive viral transcription, creating a therapeutic vulnerability that can be exploited with selective p300/CBP catalytic inhibitorsPresenter: Marek Kobylarz, Ph.D., Senior ScientistPoster Session: Epigenetic modulators (HDAC Bromodomain modulators, EZH2)Date and Time: Thursday, October 24, 2024, from 9:00 a.m. to 5:30 p.m. CEST The presentation will be available under the Publications section of the Kronos Bio website on October 24, 2024. The abstract can be found on the Symposium website. About Kronos BioKronos 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. 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, KB-9558’s ability to potentially treat HPV-driven tumors; the estimated U.S. patient population with HPV-driven cancers; the therapeutic opportunity provided by oncoproteins in the treatment of cancer; 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.

Award recognizes the potential for INO-3107 to be the first therapeutic option in the United Kingdom for patients suffering from Recurrent Respiratory Papillomatosis (RRP) PLYMOUTH MEETING, Pa., July 11, 2024 /PRNewswire/ -- INOVIO (NASDAQ: INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, today announced that its lead DNA medicine candidate, INO-3107, has been designated an innovative medicine as part of the U.K.'s Innovative Licensing and Access Pathway (ILAP). The designation, called an Innovation Passport, was granted by the ILAP Steering Group to INO-3107 for the treatment of patients with Recurrent Respiratory Papillomatosis (RRP), a debilitating, chronic rare disease of the respiratory tract caused by HPV-6 and/or HPV-11. "The U.K. Innovation Passport designation is yet another recognition of the promise of INO-3107 to potentially transform the treatment paradigm for RRP patients," said Dr. Jacqueline Shea, INOVIO's President and Chief Executive Officer. "We are honored to receive this designation, which offers us enhanced access to regulators and development tools that could accelerate the timeline for achieving U.K. regulatory approval of INO-3107. We look forward to continuing our discussions with the ILAP partners as we work to deliver this promising DNA medicine to patients as quickly as possible." The Innovation Passport is the entry point to the ILAP, which aims to accelerate time to market and facilitate patient access to medicines in the United Kingdom. The Innovation Passport provides a single, streamlined roadmap for regulatory approval and development milestones. Recipients of the Innovation Passport are granted access to a range of development tools to support the design, development and approvals process in the U.K., as well as opportunities for enhanced regulatory and other stakeholder input. Specific benefits of ILAP include the potential for a 150-day accelerated Marketing Authorization Application (MAA) assessment, rolling review and a continuous benefit risk assessment. The ILAP is delivered in partnership by the U.K. Medicines and Healthcare products Regulatory Agency (MHRA), the All Wales Therapeutics and Toxicology Centre, the National Institute for Health and Care Excellence and the Scottish Medicines Consortium, part of Healthcare Improvement Scotland. The MHRA launched ILAP at the start of 2021 to accelerate the development and access to promising medicines in the early stages of development. The pathway is part of the UK's plan to attract life sciences development in the post-Brexit era. For more information about the Innovation Passport and ILAP, visit: Innovative Licensing and Access Pathway - GOV.UK About INO-3107 INO-3107 is designed to elicit an antigen-specific T cell response against both HPV-6 and HPV-11 proteins. These targeted T cells are designed to seek out and kill HPV-6 and HPV-11 infected cells, with the aim of potentially preventing or slowing the growth of new papillomas. In a Phase 1/2 clinical trial conducted with INO-3107, 81.3% (26/32) of patients had a decrease in surgical interventions in the year after INO-3107 administration compared to the prior year, including 28.1% (9/32) that required no surgical intervention during or after the dosing window. Patients in the trial had a median range of 4 surgeries (2-8) in the year prior to dosing. After dosing, there was a median decrease of 3 surgical interventions (95% confidence interval -3, -2). At the outset of the study (Day 0), patients had a clinically warranted procedure to have RRP tissue surgically removed, but any surgery performed after Day 0 during the dosing window was counted against the efficacy endpoint. Treatment with INO-3107 generated a strong immune response in the trial, inducing activated CD4 T cells and activated CD8 T cells with lytic potential. T-cell responses were also observed at Week 52, indicating a persistent cellular memory response. INO-3107 was well tolerated by participants in the trial, resulting in mostly low-grade (Grade 1) treatment-emergent adverse effects such as injection site pain and fatigue. Like other DNA medicines, INO-3107 has the ability to generate antigen-specific T cells that is not affected by anti-vector immunity impacting immunogenicity, either before administration or after the first dose unlike other T-cell generating platforms such as viral vectors. This feature of DNA medicines should allow INO-3107 to maintain T cell response and overall efficacy, which would make it an important therapeutic option for a majority of RRP patients. The FDA granted INO-3107 Orphan Drug designation and Breakthrough Therapy designation, and advised INOVIO that it could submit its BLA under the accelerated approval program using data from its already completed Phase 1/2 trial. The European Commission has also granted INO-3107 Orphan Drug designation. INOVIO's delivery device, CELLECTRA®, received CE marking, a regulatory standard that certifies that a product has met European Union's safety, health, and environmental standards. About RRP RRP is a debilitating and rare disease caused primarily by HPV-6 and/or HPV-11. RRP is characterized by the development of small, wart-like growths, or papillomas, in the respiratory tract. While papillomas are generally benign, they can cause severe, life-threatening airway obstruction and respiratory complications. RRP can also significantly affect quality of life for patients by affecting the voice box, limiting the ability to speak effectively. Surgery to remove papillomas is the standard of care for RRP; however, the papillomas often grow back. INOVIO's market research to date with patients and healthcare professionals indicates that a reduction of even one surgery matters, because every surgery poses a significant risk of causing permanent damage to the vocal cords. The most widely cited U.S. epidemiology data published in 1995 estimated that there were 14,000 active cases and about 1.8 per 100,000 new cases in adults each year. About INOVIO's DNA Medicines Platform INOVIO's DNA medicines platform has two innovative components: precisely designed DNA plasmids, delivered by INOVIO's proprietary investigational medical device, CELLECTRA®. INOVIO uses proprietary technology to design its DNA plasmids, which are small circular DNA molecules that work like software the body's cells can download to produce specific proteins to target and fight disease. INOVIO's proprietary CELLECTRA® delivery devices are designed to optimally deliver its DNA medicines to the body's cells without requiring chemical adjuvants or lipid nanoparticles and without the risk of the anti-vector response historically seen with viral vector platforms. About INOVIO INOVIO is a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases. INOVIO's technology optimizes the design and delivery of innovative DNA medicines that teach the body to manufacture its own disease-fighting tools. For more information, visit . Forward-Looking Statements This press release contains certain forward-looking statements relating to our business, including our plans to develop and commercialize DNA medicines and expectations regarding our research and development programs, including timelines and prospects for regulatory approval, as well as benefits for patients. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials, product development programs and commercialization activities and outcomes, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA medicines, our ability to support our pipeline of DNA medicine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by us or collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that we and our collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide us with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether we can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2023, our Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, and other filings we make from time to time with the Securities and Exchange Commission. There can be no assurance that any product candidate in our pipeline will be successfully developed, manufactured, or commercialized, that the results of clinical trials will be supportive of regulatory approvals required to market products, or that any of the forward-looking information provided herein will be proven accurate. Forward-looking statements speak only as of the date of this release, and we undertake no obligation to update or revise these statements, except as may be required by law. Contacts Media: Jennie Willson, (267) 429-8567, [email protected] Investors: Thomas Hong, (267) 440-4298, [email protected] SOURCE INOVIO Pharmaceuticals, Inc.