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Findings presented at the ENDO 2024 conference SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Veracyte, Inc. (Nasdaq: VCYT), a leading cancer diagnostics company, today announced new research findings suggesting the potential of novel molecular signatures to identify patients with thyroid nodules or cancer who have aggressive disease. The findings, which could potentially help clinicians further individualize care based on each patient’s tumor biology, are derived from research using Veracyte’s Afirma GRID (Genomic Resource for Intelligent Discovery) tool. The results were presented today at ENDO 2024, the annual meeting of The Endocrine Society in Boston. “Clinicians generally want to avoid overtreatment of patients with non-aggressive thyroid tumors while targeting more-intensive treatment to those patients with aggressive disease. The challenge is distinguishing between them, especially given the heterogeneity of thyroid tumors,” said Joshua Klopper, M.D., Veracyte’s medical director for Endocrinology. “The studies presented at ENDO 2024 today show how our Research-Use-Only Afirma GRID tool, which leverages our whole-transcriptome-derived testing approach, is helping scientists better understand important nuances in the molecular underpinnings of thyroid tumors. These insights may ultimately enable more-personalized care for patients.” Following are highlights of the three Afirma GRID-focused studies presented at the ENDO 2024 conference: Poster presentation (MON-640): Retrospective Analysis of mRNA Expression Based Signatures of Thyroid Tumor Invasion and Metastases. Presented by Sara Ahmadi, M.D., Brigham and Women’s Hospital. Summary: Researchers analyzed novel whole-transcriptome-based signatures, previously presented at the ENDO 2023 meeting, that were designed to help rule out significant thyroid tumor invasion or regional lymph node metastases in patients with indeterminate thyroid nodules. This was a retrospective study of 203 thyroid nodule patients with indeterminate cytology who had Afirma GSC-suspicious results and pathology results from subsequent thyroid surgery. The molecular signatures ruled out the clinically significant features in more than 50% of patients, with a greater than 95% negative predictive value. “Today, most patients with thyroid nodules that are suspicious for cancer are directed to surgery,” said Sara Ahmadi, M.D., of Brigham and Women’s Hospital who presented the findings. “Our results suggest that molecular testing may potentially help to further stratify risk so that clinicians could confidently perform a less-invasive surgical procedure that would reduce complications and potentially mitigate the need for lifelong thyroid hormone replacement therapy. While more study is needed, these findings are an exciting step towards the future of personalized medicine in thyroid nodules and cancer.” Oral presentation (OR28-04): Cancer-associated Fibroblasts Correlate with Aggressive Thyroid Cancer Behavior: Insights from Four Large Patient Cohorts. Presented by Matthew A. Loberg, B.A., Vanderbilt University Medical Center. Summary: Researchers identified cancer-associated fibroblasts (CAFs) in the thyroid tumor microenvironment that correlate with aggression in thyroid cancers largely by leveraging the Afirma GRID database, which includes whole-transcriptome data derived from the Afirma assay. In this multicenter study involving nearly 50,000 patients, they identified CAFs for the first time in pre-operative fine needle aspiration (FNA) samples. Notably, they found that the SFRP2+ CAF was associated with shorter progression-free survival, tumor invasion and lymph node metastasis. It was also enriched in thyroid nodules that were deemed suspicious by the Afirma Genomic Sequencing Classifier (GSC) or Bethesda V/VI by cytopathology, compared to Afirma GSC-benign nodules. While more study is needed, such insights could potentially help inform more-personalized management strategies for patients with thyroid nodules or cancer. Poster Presentation (MON-649) and Rapid-Fire Oral Presentation (RF28-01): Prostate-specific Membrane Antigen (PSMA) Expression in Cytologically Indeterminate and Malignant Thyroid Nodules. Presented by Rabail Sadiq, M.B.B.S., Johns Hopkins University School of Medicine. Prostate-specific membrane antigen (PSMA) is a protein found on the surface of cancer cells and is increasingly used as a biomarker in prostate cancer detection and treatment. Higher PSMA levels have also been associated with more-aggressive thyroid cancers. Researchers leveraged the Afirma GRID database to characterize the expression of PSMA (FOLH1) in a cohort of nearly 50,000 thyroid nodules sent for Afirma GSC molecular testing. They found that PSMA gene expression was higher in indeterminate nodules that were Afirma GSC-suspicious and in nodules whose cytopathology was classified as Bethesda V/VI, compared to Afirma GSC-benign nodules. They also found variability in PSMA expression in the context of certain molecular driver mutations. The authors conclude that PSMA expression may potentially help provide further prognostic information to inform care for thyroid nodule patients. “The studies presented at ENDO 2024 reinforce our commitment to not only developing high-performing tests, but also to helping the research community advance the science around thyroid cancer and the other indications we serve,” said Phillip Febbo, M.D., chief scientific officer and chief medical officer at Veracyte. “They also demonstrate the power of our Veracyte Diagnostics Platform, through which our comprehensive, whole-transcriptome-derived testing approach helps drive continued innovation to ultimately help more patients.” About Afirma GRID The Afirma GRID database is derived from the sequencing of over 21,000 expressed genes for nearly 200,000 patients with thyroid nodules (benign and malignant) and is used by Veracyte and its partners to contribute to continued research that helps advance understanding of thyroid tumors. Afirma GRID information is available on a Research-Use-Only basis. More information about Afirma GRID can be found here. About the Afirma GSC Veracyte’s flagship Afirma Genomic Sequencing Classifier (GSC) was developed with RNA whole-transcriptome-derived sequencing and machine learning technology and helps physicians identify patients with benign thyroid nodules among those whose fine needle aspiration (FNA) biopsy results are indeterminate by cytopathology so that they can potentially avoid unnecessary thyroid surgery. The Afirma GSC also includes Xpression Atlas, the largest thyroid gene and fusion variant panel available, to help inform treatment decisions for patients whose genomic test or cytopathology results are suspicious for cancer. Veracyte also enables physicians to order DNA testing of the TERT promoter gene, which is performed on the same FNA sample, to help further guide treatment decision-making. More information about the Afirma GSC can be found here. About Veracyte Veracyte (Nasdaq: VCYT) is a global diagnostics company whose vision is to transform cancer care for patients all over the world. We empower clinicians with the high-value insights they need to guide and assure patients at pivotal moments in the race to diagnose and treat cancer. Our Veracyte Diagnostics Platform delivers high-performing cancer tests that are fueled by broad genomic and clinical data, deep bioinformatic and AI capabilities, and a powerful evidence-generation engine, which ultimately drives durable reimbursement and guideline inclusion for our tests, along with new insights to support continued innovation and pipeline development. For more information, please visit and follow the company on X (formerly Twitter) at @veracyte. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements, including, but not limited to our statements related to the potential for the Afirma GRID research-use-only tool to help scientists better understand important nuances in the molecular underpinnings of thyroid tumors, such insights which may ultimately enable more-personalized care for patients. Forward-looking statements can be identified by words such as: “appears,” “anticipate,” “intend,” “plan,” “expect,” “believe,” “should,” “may,” “will,” “enable,” “positioned,” “offers,” “designed,” "ultimately," and similar references to future periods. Actual results may differ materially from those projected or suggested in any forward-looking statements. These statements involve risks and uncertainties, which could cause actual results to differ materially from our predictions, and include, but are not limited to the potential impact Afirma GRID can have on scientific advancements in thyroid cancer and, in turn, patients. Additional factors that may impact these forward-looking statements can be found under the caption “Risk Factors” in our Annual Report on Form 10-K filed on February 29, 2024, and our 10-Q filed on May 8, 2024. Copies of these documents, when available, may be found in the Investors section of our website at . These forward-looking statements speak only as of the date hereof and, except as required by law, we specifically disclaim any obligation to update these forward-looking statements or reasons why actual results might differ, whether as a result of new information, future events or otherwise. These forward-looking statements speak only as of the date hereof and, except as required by law, we specifically disclaim any obligation to update these forward-looking statements or reasons why actual results might differ, whether as a result of new information, future events or otherwise. Veracyte, the Veracyte logo, and Afirma are registered trademarks of Veracyte, Inc., and its subsidiaries in the U.S. and selected countries.

Esophageal squamous cell carcinoma (ESCC) accounts for around 90% of esophageal cancers, especially in East Asia. New findings in indicate that periostin, or POSTN, promotes ESCC progression by enhancing cancer and stromal cell migration in cancer-associated fibroblasts (CAFs). Therefore, it may be a novel therapeutic target for treating ESCC. Esophageal squamous cell carcinoma (ESCC) accounts for around 90% of esophageal cancers, especially in East Asia. New findings in The American Journal of Pathology, published by Elsevier, indicate that periostin, or POSTN, promotes ESCC progression by enhancing cancer and stromal cell migration in cancer-associated fibroblasts (CAFs). Therefore, it may be a novel therapeutic target for treating ESCC. Lead investigator Yu-ichiro Koma, MD, PhD, Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, explained, "Though CAFs in the tumor microenvironment are involved in the progression of various cancers, including ESCC, the underlying mechanisms are unclear. Therefore, it is critical to further investigate the mechanisms of esophageal cancer development and progression." To better understand the mechanisms of ESCC progression by CAFs, investigators generated CAF-like cells by directly coculturing human bone marrow-derived mesenchymal stem cells (MSCs) with ESCC cells, revealing elevated periostin expression. Recombinant human periostin activated the serine/threonine protein kinase (Akt) and extracellular signal-regulated kinase (Erk) signaling pathways in ESCC cells, which enhanced the survival and migration of these cancer cells. Periostin also enhanced MSC and macrophage migration and conferred tumor-associated macrophage (TAM)-like properties to macrophages. Immunohistochemistry demonstrated the clinical significance of periostin, associating its high expression with tumor invasiveness, vessel invasion, advanced pathological stage, CAF marker expression, and TAM infiltration. After direct coculture, ESCC cells showed increased characteristics of malignancy, such as tumor survival, growth, and migration, as well as increased phosphorylation of Akt and Erk. Dr. Koma commented: "We discovered that periostin, up-regulated in CAFs upon direct contact with cancer cells, promotes ESCC progression and the migration of stromal cells like CAFs and TAMs. Periostin also enhanced mesenchymal stem cell and macrophage migration and endowed macrophages with tumor-associated macrophage-like properties. Thus, CAF-secreted periostin contributed to tumor microenvironment development." Dr. Koma concluded: "The present study established a direct coculture system between ESCC cells and MSCs, which promoted the malignant phenotype of ESCC cells. Patients with ESCC with high periostin expression exhibited poorer postoperative outcomes, indicating that periostin may be a novel therapeutic target for treating this form of esophageal cancer and may serve as a prognostic indicator." Esophageal cancer is the seventh most common cancer worldwide and the sixth leading cause of cancer-related death. The most common histological subtype is ESCC. The histologic types of esophageal cancer are broadly classified into ESCC and esophageal adenocarcinoma, with ESCC accounting for approximately 90% of esophageal cancers, especially in East Asia. In East Asia and East Africa, esophageal cancer is one of the top five causes of overall cancer mortality, and the five-year overall survival of ESCC is approximately 20%, with a poor prognosis. This prognosis is associated with a high propensity for metastasis, even if the tumor is superficial, Early esophageal cancer is often asymptomatic and diagnosis typically occurs at an advanced stage.

Domain Therapeutics announces nomination of first-in-class PAR2 NAM candidate, DT-9045, to unlock new cancer treatment possibilities DT-9045 is a unique drug candidate due to its competitive differentiating pharmacological featuresStart of Phase 1 ascending dose studies in recurrent or metastatic solid tumors with DT-9045 is expected by mid-2025DT-9045 builds upon the Company’s growing pipeline which includes the clinical-stage drug candidates, M1069 (A2a/A2b antagonist) and DT-9081 (EP4 receptor antagonist) Strasbourg, France – Montreal, Canada, 5 June, 2023 – Domain Therapeutics (“Domain” or “the Company”), a clinical-stage biopharmaceutical company developing innovative drug candidates in immuno-oncology targeting G Protein-Coupled Receptors (GPCRs), today announces the nomination of a drug candidate, a Negative Allosteric Modulator (NAM) of protease-activated receptor 2 (PAR2), DT-9045, with first-in-class potential for immuno-oncology, particularly for fibrotic tumors. Domain carefully selects its immuno-oncology assets using its proprietary cross-validation platform that includes preclinical and clinical data to identify and validate GPCR targets involved in immunosuppressive mechanisms. Through this precision research strategy, backed by two decades of deep-expertise in understanding GPCRs, the Company has developed a novel series of potent and selective PAR2 NAMs. PAR2 is a novel therapeutic target in oncology and immuno-oncology, involved in several processes such as tumor proliferation, resistance to immunotherapy and fibrosis. Domain nominated DT-9045 as a first-in-class PAR2 NAM clinical candidate based on its added-value, unique properties and greater therapeutic potential in comparison to biologics targeting PAR2 currently in the clinic by several competitors. DT-9045 has demonstrated proof-of-concept efficacy in syngeneic models potentiating the anti-tumor activity of an anti-PD1 treatment. The Company’s PAR2 NAM approach is particularly advantageous compared to competitors due to its unique pharmacological features: G-protein biased NAM activity on PAR2 (with no impact on the b-Arrestin pathway and ligand-induced receptor internalization)Unsurmountable property enabling preservation of efficacy even at high concentrations of ligand that could be found in the tumor microenvironmentActivity maintained at acidic pH, typical to inflammatory and tumoral environment Domain has established a clear biomarker strategy guiding the clinical positioning for DT-9045 and with pre-IND studies in progress, the Company’s expectations are for Phase I ascending dose studies in recurrent or metastatic solid tumors to start by mid-2025. Dr. Pascal Neuville, CEO of Domain Therapeutics, commented: “The nomination of our first-in-class PAR2 NAM drug candidate, DT-9045, is an exciting step forward for Domain Therapeutics and for cancer treatment in general. With its unique features of modulating the immune system response and playing a role in immunosuppression triggered by the tumor, this asset shows unmatched potential to expand the responsiveness of immunotherapy and increase the success rate of non-responding patients. Applying our precision research, we are making steady progress in building our portfolio of assets with best-in-class and first-in-class potential. We look forward to bringing DT-9045 to the clinic by mid-2025 as we work to unlock new cancer treatment possibilities.” Dr. John Stagg, Principal investigator at the Centre Hospitalier de l’Université de Montréal (CHUM), Canada and Member of Domain Therapeutic’s Scientific Advisory Board, commented: “Working closely with Domain, we were able to identify the PAR2 therapeutic target that can potentially pave the way to new GPCR-based immunotherapies and deliver more efficient therapeutic strategies for cancer patients. I look forward to advising the team through the next stages to progress the clinical development of DT-9045 through our fruitful collaboration.” Furthermore, Cancer Associated Fibroblasts (CAF) are involved in fibrosis mediated immunoresistance leading to failure of several therapies in the clinic. The role of PAR2 in CAF modulation opens a novel therapeutic avenue for the treatment of solid tumors, including those involving fibrosis such as pancreatic or lung cancers. – ENDS – For more information, please contact: Consilium Strategic CommunicationsAmber Fennell, Namrata Taak, Andrew SternEmail: DomainTherapeutics@consilium-comms.com Tel: +44 (0)20 3709 5813 NewCap (for French media)Annie-Florence LoyerEmail: afloyer@newcap.fr Tel: +33 (0)1.44.71.02.12 About Domain Therapeutics Domain Therapeutics, a clinical-stage biopharmaceutical company operating in France and Canada, focuses on developing innovative immunotherapies targeting G Protein-Coupled Receptors (GPCRs), one of the most important drug target classes, to unlock new possibilities in cancer. As a leader in GPCRs in immuno-oncology, Domain sees cancer differently, using a precise biomarker strategy to address the specific needs of patients based on unique signatures of individual cancers. Backed by decades of research and validated by multiple pharma partnerships, the Company ensures rigorous GPCR target identification and selection as well as thorough analysis of tumor complexity and mechanisms to deliver the next generation of immunotherapies. Domain’s clinical-stage programs include M1069, an A2aR/A2b receptor antagonist identified during a research collaboration with Merck KGaA, DT-9081, its fully owned EP4 receptor antagonist and DT-9045 its PAR2 NAM antagonist, alongside a rich, optimized pipeline of first-in-class GPCR targets selected through Domain’s drug discovery platform. The Company raised €39m ($42m) in early 2022 to develop high-value drug candidates to address GPCR-mediated immunosuppression in immuno-oncology. Domain is backed by a syndicate of leading international venture capital funds from Europe, Asia and North America. For more information, please visit: www.domaintherapeutics.com