GATA3

BROOKLINE, Mass.--(BUSINESS WIRE)-- Edgewood Oncology, a clinical-stage biotechnology company focused on delivering BTX-A51 to patients with hematologic malignancies and genetically-defined solid tumors, today announced that the first two patients with metastatic breast cancer were treated with BTX-A51, a multi-specific kinase inhibitor of casein kinase 1 alpha (CK1α) and cyclin-dependent kinases 7 and 9 (CDK7 and CDK9), that synergistically targets master regulators of cancer. BTX-A51 is being evaluated in a Phase 2a study for the treatment of estrogen receptor positive / human epidermal growth factor receptor 2 negative (ER+/HER2-) metastatic breast cancer with and without GATA binding protein 3 (GATA3) mutations. GATA3 is a protein that helps maintain healthy breast cells and mutations in this protein, which are found in approximately 15% of breast cancer cases, are associated with shorter progression free (PFS) and overall survival (OS). Moreover, these mutations are almost always accompanied by a wild type (non-mutated) p53 tumor suppressor protein. Recent studies have shown that targeting MDM2, a molecule that degrades the p53 protein, could be particularly effective in treating cancers with these GATA3 mutations. Due to its ability to reduce MDM2 expression, Edgewood Oncology is testing the hypothesis that BTX-A51 may be beneficial in this breast cancer sub-population. “This represents an important milestone for both Edgewood Oncology and for patients with ER+/HER2- breast cancer, particularly those with a GATA3 mutation, who need better treatment options targeted to their underlying mutation profile,” said Zung L. Thai, M.D., Ph.D., chief medical officer of Edgewood Oncology. “Moreover, while CDK4/6 inhibitors remain a cornerstone of current treatment regimens, resistance to these therapies poses a formidable challenge. By targeting CDK7 and CDK9, key regulators of cell cycle progression, BTX-A51 not only aims to circumvent this resistance but also to transform the treatment landscape.” The ongoing Phase 2a trial of BTX-A51 is a multicenter, open-label, nonrandomized, multiple dose study evaluating the safety, toxicity, pharmacokinetics and preliminary efficacy of BTX-A51 in patients with ER+/HER2- metastatic breast cancer with and without GATA3 mutations. Multiple sites for the clinical study are open for enrollment. For more information, visit clinicaltrials.gov (NCT04872166). About Edgewood Oncology Edgewood Oncology is a clinical-stage biotechnology company that was founded to deliver on the promise of BTX-A51 for patients with hematologic malignancies and genetically-defined solid tumors. BTX-A51 is an investigational, first-in-class, small molecule, multi-selective kinase inhibitor of CK1α, CDK7 and CDK9 that synergistically co-targets master regulators of cancer to activate programmed cell death, or apoptosis. BTX-A51 holds promise in acute myeloid leukemia and genetically-defined solid tumors, which are the focus of ongoing clinical programs. For more information, please visit , and follow us on LinkedIn.

Data demonstrated soquelitinib was active in six inflammatory/immune disease models and provides rationale for development in a range of additional Th2- and Th17-mediated diseases Soquelitinib’s unique mechanism of action inhibited the production of Th2 and Th17 cells, providing upstream attenuation of several validated cytokine targets such as IL-4, IL-5, IL-13, IL-17 BURLINGAME, Calif., Nov. 01, 2023 (GLOBE NEWSWIRE) -- Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, today announced the publication of preclinical data that demonstrated the potential of ITK inhibition as a novel approach to treat T cell-mediated inflammatory and immune diseases. Corvus’ ITK inhibitors include soquelitinib (formerly known as CPI-818), which was used in the preclinical studies and is currently in clinical trials for oncology indications, and several next-generation molecules that are being optimized for use in a variety of inflammatory and immune disease indications. “Our research on soquelitinib and selective ITK inhibition is uncovering valuable new information about immune function and the role of ITK in different diseases,” said James Rosenbaum, M.D., senior vice president of research at Corvus. “The activity of soquelitinib in various inflammatory and immune disease models highlights the essential role of ITK in multiple T cell functions. Our publication demonstrates that soquelitinib can impact disease-associated cytokines by targeting the cellular sources, specifically Th2 and Th17 cells, which produce cytokines like IL-4, IL-5, IL-13 and IL-17. We believe that blocking the source of cytokine production upstream offers advantages over existing therapies that individually target specific cytokines.” Professor Yannick Allanore, M.D., Ph.D., Professor of Rheumatology, Université Paris Cité, Institut Cochin, Paris, France, and a co-author of the publication, said, “Pulmonary fibrosis and systemic sclerosis are often fatal diseases for which current therapy is inadequate. Soquelitinib utilizes a novel mechanism and was effective in our model related to systemic sclerosis which is based on Fra2 gene overexpression, a model designed to represent human lung disease manifestations. Based on these data, we are eager to evaluate soquelitinib in a clinical trial for fibrotic diseases.” The publication, entitled “Soquelitinib, A Selective Inhibitor of Interleukin- 2- Inducible T Cell Kinase (ITK), is Active in Several Murine Models of T Cell-Mediated Inflammatory Disease,” highlights data demonstrating that soquelitinib was active in six different models of T cell-mediated inflammatory and immune disease, including acute and chronic asthma, pulmonary fibrosis, systemic sclerosis (scleroderma), psoriasis, and acute graft versus host disease. The data also describe soquelitinib’s unique mechanism of action, providing rationale for the development of ITK inhibition in a range of additional Th2 and Th17 mediated diseases, including asthma, psoriasis, atopic dermatitis, chronic obstructive pulmonary disease (COPD), systemic sclerosis, lupus and other diseases. The published research was a result of collaborations between scientists at Corvus and researchers at both Memorial Sloan Kettering Cancer Center in New York and The National Institute of Health and Medical Research (INSERM) in France. The publication is now available online as a preprint at bioRxiv.org and on the Publications and Presentations page of the Corvus website. “We are making significant progress with soquelitinib and believe that Corvus is firmly positioned as a leader in the scientific and clinical development of ITK inhibition as a platform opportunity across cancer, inflammation and immune disease,” said Richard A. Miller, M.D., co-founder, president, and CEO of Corvus. “Our primary focus is treating T cell lymphomas and cancer and we are actively preparing for a registrational Phase 3 trial of soquelitinib for peripheral T cell lymphoma. With this new publication, we further demonstrate the wide range of opportunities for ITK inhibition across specific indications with ongoing patient needs for new therapies. In addition, we have a robust pipeline of next generation ITK inhibitors and a portfolio of intellectual property that we believe provide attractive partnering opportunities for companies focused on various inflammatory and immune diseases.” Key results from the preclinical studies described in the publication demonstrated that soquelitinib had the following observed effects in models of inflammatory disease: Acute and chronic asthma models: Significant reductions in Th2 cytokines IL-4, IL-5 and IL-13 in both models, along with reductions in a validated disease activity scoreReduction in IL-6 signifying amelioration of inflammation Systemic sclerosis (Fra2 gene overexpression) model: Improvement in clinical score and preservation of body weightImprovement in lung histology, reduction of fibrosis and improvement in pulmonary vascular hypertensionReduction of GATA3-expressing T cells, indicative of effect on Th2 cellsReduction of ROR gammaT cells (RORγT), indicative of effects on Th17 cells Pulmonary fibrosis (bleomycin-induced) model: More consistent reduction of pulmonary fibrosis compared to an FDA-approved medication (nintedanib)Similar reduction in GATA3 as the systemic sclerosis model resultsReduction in MMP2 and TGF beta, two messenger RNAs associated with fibrosis Psoriasis (imiquimod (IMQ)-induced) model: Improvement in epidermal thickness, erosion and inflammationIn vitro studies demonstrated a reduction in the expression of RORγT protein, a master transcription factor that is responsible for developing Th17 cells, and a corresponding dose-dependent reduction in IL-17 cytokine production Graft versus host disease (GVHD) model: Improvement in survival rates and corresponding decrease in clinical GVHD scoreNo impact on engraftment or graft-versus-tumor effect About Corvus PharmaceuticalsCorvus Pharmaceuticals is a clinical-stage biopharmaceutical company pioneering the development of ITK inhibition as a new approach to immunotherapy for a broad range of cancer and immune diseases. The Company’s lead product candidate is soquelitinib, an investigational, oral, small molecule drug that selectively inhibits ITK. Corvus plans to initiate a Phase 3 registrational clinical trial for soquelitinib in patients with relapsed peripheral T cell lymphoma. Its other clinical-stage candidates are being developed for a variety of cancer indications. For more information, visit www.corvuspharma.com. About SoquelitinibSoquelitinib (CPI-818) is an investigational small molecule drug given orally designed to selectively inhibit ITK (interleukin-2-inducible T cell kinase), an enzyme that is expressed predominantly in T cells and plays a role in T cell and natural killer (NK) cell immune function. The immunologic effects of soquelitinib lead to what is known as Th1 skewing and is made possible by the high selectivity of soquelitinib for ITK. Research on soquelitinib’s mechanism of action suggests that it has the potential to control differentiation of normal T helper cells and enhance immune responses to tumors by augmenting the generation of cytotoxic killer T cells and the production of cytokines that inhibit cancer cell survival. Soquelitinib has also been shown to prevent T cell exhaustion, a major limitation of current immunotherapy and CAR-T therapies. Optimal doses of soquelitinib have been shown to affect T cell differentiation and induce the generation of Th1 helper cells while blocking the development of both Th2 and Th17 cells and production of their secreted cytokines. Th1 T cells are required for immunity to tumors, viral infections and other infectious diseases. Th2 and Th17 helper T cells are involved in the pathogenesis of many autoimmune and allergic diseases. The Company believes the inhibition of specific molecular targets in T cells may be of therapeutic benefit for patients with cancers, including solid tumors, and in patients with autoimmune and allergic diseases. Based on interim results from a Phase 1/1b clinical trial in patients with refractory T cell lymphomas, which demonstrated tumor responses in very advanced, refractory, difficult to treat T cell malignancies, the Company plans to initiate a registrational Phase 3 clinical trial of soquelitinib in patients with relapsed peripheral T cell lymphoma (PTCL). Forward-Looking StatementsThis press release contains forward-looking statements, including statements related to the potential safety and efficacy of the Company’s product candidates including soquelitinib, ciforadenant and mupadolimab; the potential use of soquelitinib to treat a variety of solid tumors and hematological cancers; the Company’s ability and its partners’ ability, as well as the timing thereof, to develop and advance product candidates through and successfully complete preclinical studies and clinical trials; the timing of and the Company’s ability to launch clinical trials including the potential registrational Phase 3 clinical trial for soquelitinib; and whether the Company is able to secure any partnerships or advance soquelitinib in any other indications. All statements other than statements of historical fact contained in this press release are forward-looking statements. These statements often include words such as “believe,” “expect,” “anticipate,” “intend,” “plan,” “estimate,” “seek,” “will,” “may” or similar expressions. Forward-looking statements are subject to a number of risks and uncertainties, many of which involve factors or circumstances that are beyond the Company’s control. The Company’s actual results could differ materially from those stated or implied in forward-looking statements due to a number of factors, including but not limited to, risks detailed in the Company’s Quarterly Report on Form 10-Q for the three months ended June 30, 2023, filed with the Securities and Exchange Commission on August 8, 2023, as well as other documents that may be filed by the Company from time to time with the Securities and Exchange Commission. In particular, the following factors, among others, could cause results to differ materially from those expressed or implied by such forward-looking statements: the Company’s ability to demonstrate sufficient evidence of efficacy and safety in its clinical trials of soquelitinib and its other product candidates; the accuracy of the Company’s estimates relating to its ability to initiate and/or complete preclinical studies and clinical trials and release data from such studies and clinical trials; the results of preclinical studies and interim data from clinical trials not being predictive of future results; the Company’s ability to enroll a sufficient number of patients in its clinical trials; the unpredictability of the regulatory process; regulatory developments in the United States, and other foreign countries; the costs of clinical trials may exceed expectations; and the Company’s ability to raise additional capital. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the events and circumstances reflected in the forward-looking statements will be achieved or occur, and the timing of events and circumstances and actual results could differ materially from those projected in the forward-looking statements. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and the Company undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise. INVESTOR CONTACT:Leiv LeaChief Financial OfficerCorvus Pharmaceuticals, Inc.+1-650-900-4522llea@corvuspharma.com MEDIA CONTACT:Sheryl SeapyReal Chemistry+1-949-903-4750sseapy@realchemistry.com

WALTHAM, Mass.--(BUSINESS WIRE)-- BostonGene today announced that four abstracts have been accepted for poster presentations and two abstracts have been accepted for online publication for the 2023 ASCO Annual Meeting (ASCO), which will be held June 2 – 6, 2023, at McCormick Place Convention Center in Chicago, IL. BostonGene will also exhibit at booth 28155. “We look forward to sharing results from our research analyzing genomic and transcriptomic classifications and our analysis demonstrating the added benefit of comprehensive genomic profiling in a thousand diverse cancer patients at the 2023 ASCO Annual Meeting. These presentations reflect our scientific expertise and commitment to bringing innovative solutions into clinical practice,” said Nathan Fowler, MD, Chief Medical Officer at BostonGene. Details about the abstracts selected for presentation can be found below: Abstract Number: 3076 Title: Aggregated analysis of 1,000 patients with cancer to assess the benefits of integrated whole exome and whole transcriptome sequencing Date and Time: Saturday, June 3 | 8:00 AM – 11:00 AM CT Location: McCormick Place Convention Center Poster Number: 274 Speaker: Anna Ogloblina, PhD, BostonGene The deep interrogation of BostonGene’s comprehensive approach to molecular profiling demonstrates the advantages of integrated RNA sequencing (RNA-seq) and whole exome sequencing (WES) analysis, including an increase in clinically significant biomarkers and matched clinical trials, which can ultimately lead to more effective personalized treatments for cancer patients. Abstract Number: 11547 Title: Novel genomic alterations and transcriptomic-based tumor microenvironment classification of sarcoma and their impact on treatment decision-making Date and Time: Saturday, June 3 | 1:15 PM – 4:15 PM CT Location: McCormick Place Convention Center Poster Number: 481 Speaker: Krystle Nomie, PhD, BostonGene This presentation demonstrates the ability of the BostonGene’s Tumor PortraitTM test to identify genomic alterations and classify tumor microenvironment (TME) subtypes of sarcomas that ultimately provide insights on potential immunotherapy and specific gene-related treatment strategies. Research conducted in collaboration with The University of Texas MD Anderson Cancer Center Abstract Number: 579 Title: Differential genomic and transcriptomic analysis of invasive lobular and ductal carcinomas Date and Time: Sunday, June 4 | 8:00 AM – 11:00 AM Location: McCormick Place Convention Center Poster Number: 409 Speaker: Jason Mouabbi, MD, MD Anderson In this study, the use of BostonGene’s integrated analysis platform provided an in-depth understanding of the molecular differences between two breast cancer subtypes, invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC), revealing mechanistic insights for both subtypes that can be used to tailor ILC-specific interventional clinical trials. Abstract Number: 1039 Title: Genomic characterization of the GATA3 mutational landscape in breast cancer Date and Time: Sunday, June 4 | 8:00 AM – 11:00 AM Location: McCormick Place Convention Center Poster Number: 260 Speaker: Jason Mouabbi, MD, MD Anderson This presentation highlights the use of integrated genomic and transcriptomic analysis to understand further the mutational landscape of GATA3, a broadly used biomarker in breast cancer, to guide future prospective clinical studies. Online publication abstracts: Abstract Number: e15058 Title: RNA sequencing as a confirmatory assay and its impact on patient care in multiple cancer types This presentation describes the advantage of RNA sequencing (RNA-seq) to confirm the pathological detection of biomarkers, demonstrating the utility of RNA-seq analysis to drive treatment decisions in 4 cancer types. Research conducted in collaboration with Weill Cornell Medicine, Englander Institute of Precision Medicine, MD Anderson, Oncology Consultants, and Cancer Centers of South Florida Abstract Number: e14691 Title: Tumor immunity portrait: An AI-driven molecular predictor combining tumor microenvironment and tumor mutational burden for immune checkpoint inhibitor response prediction This study highlights the ability of BostonGene’s Tumor Immunity PortraitTM, an integrated approach combining the tumor’s characteristics and TME, to provide an accurate prediction of ICI non-response in 3 cancer types for personalized treatment decision-making. For more information, please visit the 2023 ASCO Annual Meeting website. The abstracts will be published online in the Journal of Clinical Oncology supplement for the ASCO Annual Meeting Proceedings. About BostonGene Corporation BostonGene’s mission is to power healthcare’s transition to personalized medicine using AI-based molecular and immune profiling to improve the standard of care, accelerate research, and reduce overall cost of cancer care. BostonGene’s tests reveal key drivers of each tumor, including immune microenvironment properties, actionable mutations, biomarkers of response to diverse therapies, and recommended therapies. Through these comprehensive analyses, BostonGene’s tests generate a personalized roadmap for therapeutic decision-making for each cancer patient. For more information, visit BostonGene at .