Cancer Research Malaysia

LEXINGTON, Mass.--( BUSINESS WIRE )--Agenus Inc. (NASDAQ: AGEN), a leader in developing novel immunological agents to treat various cancers, today announced the publication of a seminal study in the prestigious Cancer Discovery , a journal of the American Association for Cancer Research, detailing the novel mechanism of action and effectiveness of botensilimab, an investigational, novel multifunctional anti-CTLA-4 antibody, in various treatment-resistant cancers. The paper, entitled “Botensilimab, an Fc-Enhanced Anti-CTLA-4 Antibody, Is Effective Against Tumors Poorly Responsive to Conventional Immunotherapy,” highlights several key findings: Demonstrated Activity Across Multiple Cancers : Botensilimab has shown increased activity in multiple treatment-resistant cancers, including those that have progressed on prior checkpoint inhibitors. Fc-Enhanced Design for Multifunctional Immune Activation : Unlike traditional anti-CTLA-4 antibodies, botensilimab’s Fc-enhanced design allows it to leverage multiple immune-activating mechanisms simultaneously. This includes enhanced T cell priming, reduction of intratumoral regulatory T cells, and activation of antigen-presenting cells, leading to a robust anti-tumor response. Activity Independent of Conventional Limitations : Botensilimab shows clinical activity regardless of factors that typically limit conventional immunotherapy efficacy, such as tumor neoantigen burden and FcγRIIIA genotype. This broadens its potential applicability across diverse patient populations. Remodeling the Tumor Microenvironment : The antibody uniquely remodels the tumor microenvironment, transforming "cold" tumors that are currently unresponsive to immune therapies into "hot" immunologically active tumors. This is achieved by reducing regulatory T cells and increasing T cell inflammation gene signatures within the tumor microenvironment. Promise in Difficult-to-Treat Cancers : Botensilimab demonstrates significant promise in treating over nine difficult-to-treat cancers, including microsatellite stable colorectal cancer and may extend clinical benefits to patient populations historically unresponsive to conventional immune checkpoint inhibitors. “We are thrilled to share these groundbreaking findings with the scientific community,” said Dhan Chand, PhD, lead author and Vice President of Research at Agenus. “The compelling preclinical and clinical evidence generated with botensilimab reveal an actionable pathway to improve treatment outcomes and extend survival to patient populations historically unresponsive to conventional immune checkpoint inhibitors.” This paper underscores the potential of botensilimab to overcome some of the most challenging hurdles in cancer treatment, offering new hope to patients with limited options. Agenus is committed to advancing this promising therapy through further clinical development and regulatory pathways to ensure rapid and broad patient access. About Cancer Discovery Cancer Discovery publishes high-impact, peer-reviewed articles describing major advances in research and clinical trials. As the premier cancer information resource, the Journal also presents Review Articles, Perspectives and Commentaries, News stories, and Research Watch summaries of important journal articles to its readers to keep them informed about the latest findings in the field. Topics span the spectrum of cancer research and medicine from the laboratory to the clinic and epidemiologic studies. About Botensilimab Botensilimab is an investigational human Fc-enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to “cold” tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses. Approximately 1,100 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316. About Agenus Agenus is a leading immuno-oncology company targeting cancer with a comprehensive pipeline of immunological agents. The company was founded in 1994 with a mission is to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants (through SaponiQx). Agenus has robust end-to-end development capabilities, across commercial and clinical cGMP manufacturing facilities, research and discovery, and a global clinical operations footprint. Agenus is headquartered in Lexington, MA. For more information, visit www.agenusbio.com or @agenus_bio. Information that may be important to investors will be routinely posted on our website and social media channels. Forward-Looking Statements This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding its botensilimab and balstilimab programs, expected regulatory timelines and filings, and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "forecasts," "estimates," "will," “establish,” “potential,” “superiority,” “best in class,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Annual Report on Form 10-K for 2023, and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement.

The detailed pharmacological and mechanistic characterization of MRTX1719 demonstrates that blocking PRMT5-MTA complex is a rational and differentiated approach to treat cancers harboring MTAP deletion Partial responses observed in patients with advanced cancer along with a well-tolerated safety profile demonstrate MRTX1719 may represent a potential new therapeutic strategy for the treatment of multiple cancer types that have strong unmet medical need SAN DIEGO, Aug. 9, 2023 /PRNewswire/ -- Mirati Therapeutics, Inc. ® (NASDAQ: MRTX), a commercial stage biotechnology company, announced today Cancer Discovery published preclinical and initial clinical data from a first-in-human Phase 1/2 clinical trial of MRTX1719, a PRMT5 / methylthioadenosine (MTA)-cooperative inhibitor evaluated in methylthioadenosine phosphorylase (MTAP) deleted cancers. These results provide preclinical and early clinical proof-of-concept for this differentiated approach and demonstrate that MRTX1719 may represent a promising targeted therapy for the ~10% of cancer patients with this biomarker. The publication can be found here. In preclinical studies, MRTX1719 was demonstrated to be a potent, selective inhibitor of the PRMT5/MTA complex. This compound exploits the elevated MTA levels present in MTAP-deleted cancers and turns this altered metabolic state into a therapeutic vulnerability to selectively kill MTAP deleted cancer cells while sparing normal cells. Preclinical results showed marked anti-tumor activity of MRTX1719, including regression, across lung, pancreatic, mesothelioma, and other solid tumor models. As of June 13, 2023, there were 18 patients with solid tumors harboring MTAP deletions in the Phase 1/2 trial of MRTX1719 that were evaluable for clinical response at dose levels of 100mg QD or greater. Initial dose level started at 50mg administered once-daily orally over 21-day cycles followed by 100% dose escalations for subsequent dose levels. Six individual case narratives were selected for inclusion in the Cancer Discovery publication: There were six confirmed objective responses observed in the Phase 1 study including one patient who achieved a response which subsequently confirmed post-data cutoff MRTX1719 achieved apparent complete PRMT5 inhibition in MTAP deleted tumor cells at a dose of 200 mg QD as evidenced by pretreatment and on-treatment tumor biopsies of the PRMT5 biochemical biomarker symmetric dimethyl arginine (SDMA) It was notable that four patients were on therapy for multiple cycles before experiencing an initial objective response, with their tumors continuing to decrease in size over the course of treatment. These findings suggest that tumor response may continue to deepen over time indicating the importance of evaluating tumor response kinetics and response rates across a broader patient population with longer follow up. MRTX1719 was well-tolerated with no dose limiting toxicities observed at dose levels up to 400mg QD. None of the patients treated with MRTX1719 experienced dose-limiting adverse events associated with first generation PRMT5 inhibitors such as thrombocytopenia, anemia or neutropenia. "Many cancers with a prevalence of MTAP deletion have few treatment options so it is encouraging to see these initial responses in the clinic. These data, including the favorable safety profile, demonstrate the development of a possible therapeutic approach for a significant population of patients with MTAP-deleted cancers in need of new treatment options," said Jordi Rodon Ahnert, MD, PhD, The University of Texas MD Anderson Cancer Center. "It will be important for next-generation sequencing tests to expand their panel of targets to include for markers of PRMT5 inhibition." "The targeting strategy of MRTX1719 is differentiated from first generation PRMT5 inhibitors and has so far shown to be well tolerated in this patient population with dire unmet need," said James Christensen, Ph.D., chief scientific officer, Mirati Therapeutics, Inc. "We are pleased that Cancer Discovery recognized the importance and potential impact of this early data from MRTX1719, and we look forward to pursuing continued development of MRTX1719 for the benefit of patients living with cancer." About MRTX1719 (MTA-cooperative PRMT5 inhibitor) MRTX1719, discovered at Mirati, is an orally bioavailable, methylthioadenosine (MTA)-cooperative PRMT5 inhibitor that exhibits synthetic lethality in MTAP-deleted cancers. MTAP deletion leads to MTA accumulation in cancer cells and MRTX1719 is designed to selectively bind the PRMT5-MTA complex ultimately inhibiting PRMT5 function in MTAP-deleted cancer cells while sparing healthy non-tumor cells.1 MTAP deletions occur in around 10% of all cancers2, including a high percentage of pancreatic cancer, non-small cell lung cancer, and mesothelioma which are associated with a poor prognosis, representing a significant unmet medical need. The PRMT5-MTA complex creates a novel drug target for the treatment of MTAP-deleted cancers. Targeting this complex involves a new and potentially improved therapeutic approach. MRTX1719 is being evaluated as monotherapy and in combination with other therapeutic options to treat patients with advanced, unresectable or metastatic solid tumor malignancy with homozygous deletion of the MTAP gene. For more information visit Mirati.com/science. About Mirati Therapeutics, Inc.® Mirati Therapeutics, Inc. is a commercial stage biotechnology company whose mission is to discover, design and deliver breakthrough therapies to transform the lives of patients with cancer and their loved ones. The company is relentlessly focused on bringing forward therapies that address areas of high unmet need, including lung cancer, and advancing a pipeline of novel therapeutics targeting the genetic and immunological drivers of cancer. Unified for patients, Mirati's vision is to unlock the science behind the promise of a life beyond cancer. For more information about Mirati, visit us at Mirati.com or follow us on Twitter, LinkedIn and Facebook. Forward Looking Statements This press release includes forward-looking statements regarding Mirati's business, financial guidance and the therapeutic and commercial potential of KRAZATI® (adagrasib), MRTX1719 (MTA-cooperative PRMT5 inhibitor), MRTX0902 (SOS1 inhibitor), and MRTX1133 (selective KRASG12D inhibitor), Mirati's technologies and Mirati's other products in development. Any statement describing Mirati's goals, expectations, intentions or beliefs, financial or other projections, is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including those related to the impact COVID-19 could have on our business, and including those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Mirati's forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Mirati's forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Mirati. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Mirati's programs are described in additional detail in Mirati's annual report on Form 10-K, and most recent Form 10-Q, which are on file with the Securities and Exchange Commission and available at the SEC's Internet site (). These forward-looking statements are made as of the date of this press release, and Mirati assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law. Mirati Contacts Investor Relations: [email protected] Media Relations: [email protected] References Smith C.R., Aranda R, Bobinski T.P., Briere D.M., Burns A.C., et al. Fragment-Based Discovery of MRTX1719, a Synthetic Lethal Inhibitor of the PRMT5•MTA Complex for the Treatment of MTAP-Deleted Cancers. J Med Chem. 2022 Jan 18. doi: 10.1021/acs.jmedchem.1c01900. Online ahead of print. Han G, Yang G, Hao D, et al. 9p21 loss confers a cold tumor immune microenvironment and primary resistance to immune checkpoint therapy. Nat Commun. 2021 Sep 23;12(1):5606. doi: 10.1038/s41467-021-25894-9. SOURCE Mirati Therapeutics, Inc.

Pre-clinical data strongly supports progression of a METTL3 inhibitor in an immuno-oncology setting STC-15 is the first molecule specifically targeting METTL3 to enter clinical development CAMBRIDGE, England, Aug. 8, 2023 /PRNewswire/ -- STORM Therapeutics Ltd. (STORM), a clinical stage biotechnology company focused on discovering and developing novel small molecule therapies targeting RNA modifying enzymes (RMEs) for oncology and other diseases, is pleased to announce that it has published a scientific manuscript in the internationally recognised scientific journal Cancer Discovery . The paper, entitled 'Inhibition of METTL3 results in a cell-intrinsic interferon response that enhances anti-tumour immunity', has been published in collaboration with Professor Mark Dawson's laboratory at the Peter MacCallum Cancer Centre in Melbourne, Australia , and reveals recent findings that demonstrate the therapeutic potential of drugs targeting METTL3 as immuno-oncology agents. Using pre-clinical cancer models, the study shows that pharmacological inhibition of METTL3 induces double-stranded RNA formation and a profound cell-intrinsic interferon response that potentiates T-cell killing of cancer cells. Whilst METTL3 inhibitors are equally efficacious to anti-PD1 therapy in pre-clinical models, the combination of the two agents has far greater activity, leading to tumour regression and durable anti-cancer immunity. A detailed investigation of the mechanism of action of the two treatments revealed that they act orthogonally and provides a strong rationale for their combination. Oliver Rausch, Chief Scientific Officer of STORM Therapeutics and joint senior author of the study, said, "We are pleased to share this new data with the scientific community. Our study identifies a novel therapeutic mechanism triggered by METTL3 inhibition that opens a significant opportunity for METTL3 inhibitors in immuno-oncology. This work follows on from our previous work published in 2021 in Nature, demonstrating the efficacy of METTL3 inhibition in acute myeloid leukemia models, and illustrates the broad potential of this new class of drugs in oncology." Dr. med. Josefin-Beate Holz, Chief Medical Officer of STORM Therapeutics, commented, "This exciting new data strengthens our hypothesis for the clinical development of STC-15 as a novel anticancer therapeutic in monotherapy and in combination with standard of care, including checkpoint inhibitors. We are looking forward to exploring these concepts following the conclusion of the current Phase 1 multiple ascending dose study with STC-15 in patients with relapsed solid tumours." Jerry McMahon, Chief Executive Officer and President of STORM Therapeutics, added, "STORM is the first company devoted to pursuing RNA-modifying enzymes as drug targets, and our new study highlights the opportunities for new therapeutics targeting RNA modifications. We are encouraged by the progress of our ongoing Phase 1 trial of STC-15 in solid tumours and look forward to exploring its utility as an immuno-oncology drug in specific tumour types." Citation: Inhibition of METTL3 results in a cell-intrinsic interferon response that enhances anti-tumour immunity. Andrew A Guirguis, Yaara Ofir-Rosenfeld et al, 2023, Cancer Discovery (advanced online publication) NOTES TO EDITORS About STORM Therapeutics STORM Therapeutics (STORM) is a clinical stage biotechnology company creating novel therapies that inhibit RNA modifying enzymes (RME) for use in oncology and other diseases. There are more than 150 RNA modifications reported and approximately 300 RNA modifying enzymes which represent novel therapeutic targets. STORM has leveraged its first-mover advantage to establish a novel drug discovery and RNA analytics platform leading to the identification of novel targets and a proprietary pipeline of first-in-class small-molecule drug candidates for potential use in oncology, inflammation, viral infection and CNS diseases. The pipeline is exemplified by STORM's METTL3 inhibitor, STC-15, which has received IND approval and commenced its Phase 1 clinical study in cancer patients in November 2022. STC-15 represents the first ever RNA modifying enzyme inhibitor to enter clinical evaluation in humans. Additional programs are planned for advancement into IND-track activities. Fierce Biotech named STORM as one of its 2022 "Fierce 15", designating it as one of the most innovative, exciting biotechnology companies in the industry, pioneering novel drug targets. STORM investors include M Ventures, Pfizer Ventures, Taiho Ventures LLC, Seroba Life Sciences, Cambridge Innovation Capital I Limited, IP Group plc, UTokyo Innovation Platform Co., Ltd. (UTokyo IPC) and the Fast Track Initiative (FTI). For more information, please visit About STC-15 STORM's lead clinical program STC-15 is a first-in-class inhibitor of RNA modification and is the first ever RNA methyltransferase inhibitor to enter clinical development. STC-15 is an oral small molecule that inhibits METTL3, an RNA methyltransferase implicated in oncology and other diseases. Certain RNA methyltransferases are important regulators of RNA sensing and innate immune activation and represent novel immune-regulatory targets. STC-15 has also been shown preclinically to inhibit tumour growth through mechanisms involving anti-cancer immune responses, such as changes in interferon signalling and synergy with T cell checkpoint blockade. STORM commenced the dosing of the first patient in a Phase 1 clinical study of STC-15 in patients living with solid tumours in November 2022 and anticipates presenting first results from its study in 2024. Details of the study can be found on clinicaltrials.gov under the identifier NCT05584111. About Peter Mac Peter MacCallum Cancer Centre is a world-leading cancer research, education and treatment centre and Australia's only public health service solely dedicated to caring for people affected by cancer. About Cancer Discovery Cancer Discovery publishes high-impact, peer-reviewed articles describing major advances in research and clinical trials. As the premier cancer information resource, the Journal also presents Review Articles, Perspectives and Commentaries, News stories, and Research Watch summaries of important journal articles to its readers to keep them informed about the latest findings in the field. Topics span the spectrum of cancer research and medicine from the laboratory to the clinic and epidemiologic studies. SOURCE STORM Therapeutics