High-Risk Pregnancy

FLEX data underscores MammaPrint® utility in accurately predicting 3-year outcome in patients with High Risk early-stage breast cancer when treated with neo/adjuvant chemotherapy IRVINE, Calif. & AMSTERDAM--(BUSINESS WIRE)-- Agendia, Inc. today announced it will present new data on the 3-year outcome of patients with hormone receptor-positive (HR+), HER2-negative early-stage breast cancer when treated with two different chemotherapy regimens at the 2024 Annual American Society of Clinical Oncology (ASCO) Meeting, taking place in Chicago, IL. on May 31st, 2024. The data will be presented in an oral discussion by Joyce O’Shaughnessy MD, Director, Breast Cancer Research, Baylor University Medical Center, Texas Oncology and the Sarah Cannon Research Institute in Dallas, TX, Primary Investigator of the FLEX Study, titled [O'Shaughnessy, J., et al.]. The FLEX study investigates the 3-year outcome of patients with HR+HER2-, genomically High Risk Luminal B-Type early breast cancer, who have undergone treatment consisting of chemotherapy with taxane and cyclophosphamide (TC) or chemotherapy with anthracycline + TC (AC-T). All patients are enrolled in the prospective, non-randomized, observational FLEX Study (NCT03053193). This study utilized both MammaPrint and BluePrint® to determine tumor subtype. Results showed that patients with MammaPrint H1 Luminal B-Type tumors demonstrated similar 3-year outcomes when treated with either TC (97.1%) or AC-T (95.3%), suggesting that patients who are classified as H1 may be able to avoid the toxicity of an anthracycline. However, patients with MammaPrint H2 Luminal B-Type tumors demonstrated a significantly higher relapse-free survival when treated with AC-T (97.7%) than with TC alone (86.4%). These findings indicate that MammaPrint H2 tumors benefit from the addition of an anthracycline to their adjuvant chemotherapy regimen. "The ability to tailor treatment regimens to a patient’s tumor biology is crucial to optimize outcomes and quality of life. MammaPrint's utility in guiding treatment planning is highlighted by these new data evaluating chemotherapy selection," said Dr. O'Shaughnessy. "The FLEX Study and sub-studies, such as this one, enable increased precision in identifying patients that are more responsive to specific systemic therapy regimens, and continue to aid selection of treatments for patients with HR+/HER2-negative early-stage breast cancer." “These new findings demonstrate the strength of the FLEX research platform in evaluating the different aspects of breast cancer during its diagnosis and treatment stages, allowing for more precise and individualized treatment recommendations,” said William Audeh, MD, Chief Medical Officer at Agendia. “This study offers a preliminary signal towards groundbreaking insight into MammaPrint High Risk tumors and how they best respond to chemotherapy regimens, underscoring the clinical utility of MammaPrint in the selection of treatment. We remain committed to advancing breast cancer research to help deliver the best standard of practice to women undergoing breast cancer care.” Additional data supporting MammaPrint utility in treatment selection will be presented by investigators from the ISPY2 trial in a poster titled Hormone Receptor Positive HER2-negative/MammaPrint High-2 Breast Cancer Closely Resembles Triple Negative Breast Cancer: Results from Gene Expression Data from the ISPY2 Trial [Rios-Hoyo, A., et al.]. By using data from the ISPY-2 trial, this poster demonstrates that MammaPrint H2 tumors have molecular and clinical similarities to triple negative breast cancer tumors, underscoring critical insight into how treatment plans can be optimized to achieve the best result for the patient. Agendia will be sharing updates throughout the conference on its Twitter, Facebook and LinkedIn pages. About Agendia Agendia is a leading provider of innovative solutions in the field of precision oncology. With a focus on early-stage breast cancer, Agendia offers reliable biological insights that inform personalized treatment decisions for patients and their care teams. Their advanced genomic assays, MammaPrint® + BluePrint®, enable clinicians to quickly identify the most effective treatment plan, minimizing the risk of both under- and over-treatment. Founded in 2003 in Amsterdam, Agendia is headquartered in Irvine, California with a state-of-the-art laboratory facility. Led by world-renowned scientists and oncologists, Agendia is committed to advancing genomic insights through ongoing research. This includes the notable FLEX Study– the world's largest whole transcriptome Real-World Evidence-based Breast Cancer database which aims to revolutionize precision in breast cancer management. With cutting-edge technology, research and innovation, Agendia strives to shape the future of precision oncology and make a significant impact in the fight against breast cancer. About MammaPrint MammaPrint® is a gene expression profiling test that reveals the distinct underlying biology of an early-stage tumor to determine its risk of spreading. As the only FDA-cleared gene expression profiling test to assess a woman’s risk of distant metastasis, MammaPrint® provides critical answers that help inform the future of her treatment plan at the point of diagnosis, including the timing and benefit to chemotherapy and endocrine therapy. MammaPrint® listens to the signals from 70 key genes in a woman’s tumor to stratify her risk within four distinct categories – ranging from UltraLow, Low, High 1, and High 2– to fuel a right-sized care plan tailored to her biology and her life’s plans. About BluePrint BluePrint® is a gene expression profiling test that reveals the driving forces behind a tumor’s growth at the earliest stage possible in a woman’s breast cancer care journey to help optimize and personalize treatment planning. As the only molecular subtyping test available in the U.S., BluePrint® goes where pathology cannot, offers critical insights that providers may otherwise have not known to act on, and gives women the best chance to return to a life not defined by cancer. BluePrint® measures the activity of 80 key genes that are involved in a tumor's growth to classify a tumor as Luminal-type, HER2-type, or Basal-type, each of which warrant distinct treatment pathways. By revealing the distinct underlying biology of a woman's tumor, BluePrint® can catch often misclassified, yet highly aggressive, Basal tumors, so women can be prescribed the most appropriate treatment from the start.

FRIENDSWOOD, Texas--( BUSINESS WIRE )--Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, today announced the publication of an expert consensus article in the Journal of Clinical and Aesthetic Dermatology (JCAD) related to the utility of its DecisionDx-SCC test in clinical decision-making regarding the use of ART. 2 The consensus guidelines outline a recommended risk-based workflow that integrates DecisionDx-SCC and AJCC8 staging into current National Comprehensive Cancer Network® (NCCN) guidelines to improve precision in ART recommendations based on which patients are at the highest risk for metastasis and most likely to benefit from treatment. “ART is recommended by evidence-based guidelines to reduce the risk of recurrence in patients with high-risk SCC,” said Ramesh Gopal, M.D., Ph.D., lead author, radiation oncologist and associate professor of radiation oncology at the New Mexico Comprehensive Cancer Center in Albuquerque, New Mexico. “While the presence of perineural invasion (PNI) will typically trigger a conversation about whether to consider ART, the guidelines vary in their interpretation of which SCC patients should be considered for the treatment, which can carry a risk of side-effects for the patient and costs for our healthcare system.” The expert panel convened in June 2023 to review validation and real-world data for the DecisionDx-SCC test and to discuss their experiences, rationales and scenarios in which they have used the test to improve risk stratification and more accurately identify SCC patients at high risk of metastasis who may benefit from ART. The panel identified gaps in current clinical practice where the DecisionDx-SCC test has utility in guiding treatment decisions, including its use regarding: Escalation of care for lower-stage patients with high-risk tumors, De-escalation of care for patients for whom the risks of ART may outweigh the benefits, and Decision-making regarding elective radiation to the nodal basin. Based on these gaps, the panel developed risk-based clinical recommendations and a workflow for ART referral in patients with SCC, which can be viewed in the JCAD article. The workflow integrates DecisionDx-SCC testing, which analyzes a patient’s tumor biology to independently predict risk of nodal or distant metastasis, and AJCC8 staging, which is based on a patient’s clinicopathologic risk factors, into current NCCN guidelines with a goal of improving precision in ART recommendations in the SCC patient population. “As a panel, we agreed that the process used today to route SCC patients for ART can be improved, and DecisionDx-SCC can be a determining factor in the next step for management of high-risk SCC,” added Gaurav Singh, M.D., MPH, consensus panel member, and board-certified dermatologist, Mohs surgeon and assistant professor of dermatology in Wisconsin. “The test provides independent risk-stratification that can augment existing risk prediction systems, including AJCC8 and Brigham and Women’s Hospital (BWH) staging, to inform these important decisions with greater accuracy and ensure ART is brought to patients with the highest risk of disease progression who are most likely to benefit from treatment. DecisionDx-SCC can also help validate the decision to avoid radiation in seemingly high-risk tumors that are in fact low risk based on genetic profile.” Specific consensus recommendations and statements outlined in the article include the following: A DecisionDx-SCC Class 2A or 2B result, indicating a higher or highest risk of metastasis, in each AJCC8 tumor stage serves as a high- or very high-risk feature for consideration in recommending ART. The increased metastatic risk conferred by a Class 2A or 2B result in multivariate analysis (hazard ratio=2.3, p=0.013; and hazard ratio=6.9, p<0.001, respectively) is similar or higher than that conferred by other high-risk clinicopathologic features, including PNI and poor differentiation. Patients at the highest risk of metastasis, as indicated by a DecisionDx-SCC Class 2B test result, should be referred to radiation oncology with a recommendation for a multidisciplinary tumor board discussion. In nuanced discussions where the risks associated with ART may outweigh the benefits, the additional information provided by the DecisionDx-SCC test can assist in personalized decision-making. The DecisionDx-SCC test can help radiation oncologists determine a more precise risk-benefit ratio for elective nodal radiation. The panel recommended stronger consideration of elective nodal radiation for a DecisionDx-SCC Class 2B tumor, given the dramatically increased risk of nodal metastasis. Overall, the panel agreed the DecisionDx-SCC test provides independent risk stratification that, when combined with traditional staging and management guidelines, enhances the clinical picture, allowing clinicians to more accurately identify SCC patients who are most likely to benefit from ART, as well as lower-risk patients who would benefit less from treatment. In a validation study of the DecisionDx-SCC test by Wysong et al., metastatic risk prediction of AJCC8 and BWH staging systems was significantly improved when DecisionDx-SCC test results were included. 3 As supported by the consensus article, the objective, independent risk stratification provided by the test can improve precision in multidisciplinary treatment recommendations, such as the use of ART, which could save the U.S. healthcare system hundreds of millions of dollars through more appropriate use of the treatment. 4 About DecisionDx®-SCC DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous squamous cell carcinoma metastasis for patients with one or more risk factors. The test result, in which patients are stratified into a Class 1 (low), Class 2A (higher) or Class 2B (highest) risk category, predicts individual metastatic risk to inform risk-appropriate management. Peer-reviewed publications have demonstrated that DecisionDx-SCC is an independent predictor of metastatic risk and that integrating DecisionDx-SCC with current prognostic methods can add positive predictive value to clinician decisions regarding staging and management. About Castle Biosciences Castle Biosciences (Nasdaq: CSTL) is a leading diagnostics company improving health through innovative tests that guide patient care. The Company aims to transform disease management by keeping people first: patients, clinicians, employees and investors. Castle’s current portfolio consists of tests for skin cancers, Barrett’s esophagus, mental health conditions and uveal melanoma. Additionally, the Company has active research and development programs for tests in other diseases with high clinical need, including its test in development to help guide systemic therapy selection for patients with moderate-to-severe atopic dermatitis, psoriasis and related conditions. To learn more, please visit www.CastleBiosciences.com and connect with us on LinkedIn , Facebook , X and Instagram . DecisionDx-Melanoma, DecisionDx-CM Seq , DecisionDx-SCC, MyPath Melanoma, DiffDx-Melanoma, TissueCypher, IDgenetix, DecisionDx-UM, DecisionDx-PRAME and DecisionDx-UM Seq are trademarks of Castle Biosciences, Inc. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the “safe harbor” created by those sections. These forward-looking statements include, but are not limited to, statements concerning: the ability of the DecisionDx-SCC test to (i) improve risk stratification and more accurately identify SCC patients at high risk of metastasis who may benefit from ART, (ii) provide independent risk stratification that, when combined with traditional staging and management guidelines, allows clinicians to more accurately identify SCC patients who are most likely to benefit from ART, as well as lower-risk patients who would benefit less from treatment and (iii) save our healthcare system hundreds of millions of dollars through more appropriate use of ART. The words “can,” “potential” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. These forward-looking statements involve risks and uncertainties that could cause our actual results to differ materially from those in the forward-looking statements, including, without limitation: subsequent study or trial results and findings may contradict earlier study or trial results and findings or may not support the recommendations and guidelines presented in this report, including with respect to the discussion of DecisionDx-Melanoma in this press release; actual application of our tests may not provide the aforementioned benefits to patients; and the risks set forth under the heading “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2023, and in our other filings with the SEC. The forward-looking statements are applicable only as of the date on which they are made, and we do not assume any obligation to update any forward-looking statements, except as may be required by law. The authors of the consensus report and members of the multidisciplinary panel include the following physicians: Ramesh Gopal, M.D., Ph.D., a radiation oncologist and Associate Professor of Radiation Oncology at the New Mexico Comprehensive Cancer Center, in Albuquerque, New Mexico; Michael Marquardt, M.D., MPH, a radiation oncologist at Hall-Perrine Cancer Center, in Cedar Rapids, Iowa; Gaurav Singh, M.D., MPH, a board-certified dermatologist and Mohs surgeon in Wisconsin; Stanislav N. Tolkachjov, M.D., a board-certified dermatologist and Mohs micrographic and reconstructive surgeon at Epiphany Dermatology in Lewisville, Texas, Clinical Assistant Professor at the Department of Dermatology at University of Texas at Southwestern in Dallas, Texas, Clinical Associate Professor at the Texas A&M School of Medicine in Dallas, Texas, and a core faculty for the dermatology residency at Baylor University Medical Center in Dallas, Texas; Sarah T. Arron, M.D., Ph.D., a board-certified dermatologist and Mohs micrographic and reconstructive surgeon at Peninsula Dermatology Medical Group in Burlingame, California. Gopal R, Marquardt M, Singh G, et al. Integrating 40-GEP Testing to Improve Clinical Recommendations for Adjuvant Radiation for Cutaneous Squamous Cell Carcinoma: Multidisciplinary Consensus Guidelines. J Clin Aesthet Dermatol. 2024;17(3 Suppl 2):S3–S8. Wysong A, Newman JG, Covington KR, et al. Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma. J Am Acad Dermatol. 2021;84(2):361–369. Somani SK, Ibrahim SF, Tassavor M, et al. Use of the 40-gene expression profile (40-gep) test in Medicare-eligible patients diagnosed with cutaneous squamous cell carcinoma (cSCC) to guide adjuvant radiation therapy (ART) decisions leads to a significant reduction in healthcare costs. J Clin Aesthet Dermatol . 2024;17(1):41–44.

At the 2023 ASCO® Annual Meeting, Agendia will present data that demonstrates women within MammaPrint’s highest risk category have the strongest sensitivity to chemotherapy and more aggressive tumor types, guiding escalated care plans for improved outcomes MammaPrint is the only gene expression profiling test with refined subcategories for risk of distant metastasis to inform more personalized treatment IRVINE, Calif. & AMSTERDAM--(BUSINESS WIRE)-- At the 2023 ASCO Annual Meeting, Agendia, Inc., a gene expression profiling company advancing personalized early-stage breast cancer care, will present data that proves MammaPrint can predict chemotherapy sensitivity in women with early-stage, HR+HER- breast cancer. The research examined the clinical utility of MammaPrint’s two High Risk subcategories, High 1 (H1) and High 2 (H2), as an indicator of a woman’s predicted response to chemotherapy and five-year outcomes, in combination with BluePrint’s® molecular subtyping, to guide treatment decisions. The study found that women with H2 risk tumors are more likely to respond to chemotherapy and have aggressive, Basal-type tumors compared to women with H1 risk tumors. This data highlights the critical role MammaPrint and BluePrint play in identifying women with the highest risk tumors as early as possible to optimize and personalize treatment planning and improve their chance of survival. While other gene expression profiling tests may lump women into broad-strokes risk groupings, MammaPrint is the only test that further subcategorizes both low risk (Low and Ultra Low), and high risk (H1 and H2) [1,2]. Tumors in each subcategory vary in their response to chemotherapy and deserve of a distinct treatment regimen [3,4,5]. These distinguished risk groups empower clinicians to further refine their treatment recommendations and confidently de-escalate or escalate therapy. “Hearing that you have a high-risk tumor is scary news for any woman with early-stage breast cancer. Our ability to inform treatment decisions for high-risk tumors means we can avoid under or overtreating patients, and instead put them on the right path toward recovery at the right time,” said William Audeh, MD, Chief Medical Officer of Agendia. “There’s a sense of empowerment that comes with this additional insight and through our tests, patients and their care teams get the most refined, personalized answers to the multitude of questions surrounding an early-stage breast cancer diagnosis.” Agendia’s poster presentation, “MammaPrint Index as a predictive biomarker for neoadjuvant chemotherapy response and outcomes in patients with HR+HER2- breast cancer in NBRST” will highlight the following results: H2 is a distinct, higher-risk category than H1, with a significantly higher percentage of ER+Basal subtype tumors. Of 327 women with MammaPrint High Risk tumors, 61% had H1 tumors, and 39% had H2 tumors. Within H2 tumors, 63% were Basal-type, compared to only 2% of H1 tumors. H2 tumors are almost four times more sensitive to chemotherapy than H1 tumors. 23% of H2 tumors responded to chemotherapy, compared to only 6% of H1 tumors. A woman’s menopausal status did not impact her response to chemotherapy. Despite what other studies have suggested, there was no significant difference in chemotherapy sensitivity among premenopausal and postmenopausal women across both high-risk groups. Women with H1 or H2 tumors who achieved a complete response to chemotherapy had similar outcomes. H2 tumors with residual cancer had the worst five-year outcomes. Women with H1 and H2 tumors who responded to chemotherapy both had a 5-year distant metastasis free survival (DMFS) of around 81%. For those with residual disease, H1 tumors had a 5-year DMFS of 77%, and H2 tumors had a 5-year DMFS of 65%. "Refining prognosis and prediction of response to chemotherapy will help push more patients toward appropriate treatment. In light of the high proportion of H2 cancers being Basal subtype and carrying a worse prognosis if they do not get a complete response, it is not hard to envision that perhaps all H2 cancers should be treated more aggressively with the addition of immunotherapy to their chemotherapy,” said Peter Beitsch, MD, Surgical Oncologist, Dallas Surgical Group. Agendia’s comprehensive gene expression profiling platform is the only one that can inform a woman’s full treatment regimen. Beyond determining her predicted response to chemotherapy, Agendia’s MammaPrint and BluePrint deliver consistent insights into the optimal timing and duration of a variety of therapies, so providers, together with their patients, can confidently map out a personalized treatment plan that maximizes their survival rate while minimizing damage to their quality of life. Agendia will also present two additional posters that demonstrate its commitment to advancing research in underserved populations, and an oral presentation on the ability of genomic biomarkers to predict a woman’s response to immunotherapy. Agendia will be sharing updates throughout the conference on its Twitter, Facebook and LinkedIn pages. About Agendia Agendia is a mission-driven, commercial stage company focused on enabling optimized decision-making by providing physicians with next-generation diagnostic and information solutions that can be used to help improve outcomes for breast cancer patients worldwide. The company currently offers two commercially-available genomic profiling tests that help surgeons, oncologists and pathologists to personalize treatment for women at critical intervention points throughout their patient journey. MammaPrint is a 70-gene prognostic test that, along with other clinicopathologic factors, determines a specific patient’s breast cancer recurrence risk. BluePrint is an 80-gene molecular subtyping test that identifies the underlying biology of an individual breast cancer to provide information about its behavior. Together, MammaPrint and BluePrint provide a holistic view of the biology underlying an individual patient’s breast cancer, enabling physicians to objectively select the best treatment plan. For more information on Agendia’s assays and ongoing trials, please visit . [1] Cardoso, F., et al. (2016). 70-gene signatures as an aid to treatment decisions in early-stage breast cancer. NEJM, 375, 717-729. [2] Piccart, M., et al. (2021). 70-gene signature as an aid for treatment decisions in early breast cancer: updated results of the phase 3 randomised MINDACT trial with an exploratory analysis by age. Lancet Oncology, 22(4), 476-488. (21)00007-3/fulltext [3] Van’t Veer, L., et al. (2018). MammaPrint High1/High2 risk class as a pre-specified biomarker of response to nine different targeted agents plus standard neoadjuvant therapy for ~ 1000 breast cancer patients in the I-SPY 2 TRIAL. Presented at 2018 EORTC-NCI-AACR Symposium on Molecular Targets and cancer Therapeutics. [4] Huppert, L., et al. (2022). Pathologic complete response (pCR) rates for HR+/HER2- breast cancer by molecular subtype in the I-SPY2 trial. Journal of Clinical Oncology, 40 (16, Suppl.), 504. [5] Pusztai, L., et al. (2021). Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial. Cancer Cell, 39(7), 989-998. (21)00275-0