Poster presentations to highlight DecisionDx®-Melanoma, DecisionDx®-SCC and Castle’s Comprehensive Diagnostic Offering

Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, today announced that data on its portfolio of skin cancer gene expression profile (GEP) tests will be shared via poster presentations during the 18^th European Association of Dermato Oncology (EADO) Congress, being held virtually and in Seville, Spain, April 21-23, 2022.

The following e-Posters will be available for viewing on-site during the Congress in the ePoster area (ATRIO III) and also via the Congress platform, April 21-July 23, 2022.

Title: Incorporating the 31-gene expression profile test stratifies survival outcomes and leads to improved survival compared to clinicopathologic factors alone: A Surveillance, Epidemiology, and End Results (SEER) Program collaboration

Presenter: Sarah J. Kurley, Ph.D., Castle Biosciences, Inc.

Title: Independent multi-center cohort study confirms the performance of the prognostic 40-gene expression profile (40-GEP) test to classify risk of metastasis for high-risk cutaneous squamous cell carcinoma (cSCC) patients​

Presenter: Javier Cañueto, M.D., Ph.D., dermatologist at the University Hospital of Salamanca, Spain, associate professor at the University of Salamanca, associate researcher at the Institute for Biomedical Research of Salamanca (IBSAL) and postdoctoral researcher at the Cancer Research Institute of Salamanca (CSIC-USAL) University

Title: The current 23- and 35-gene expression profile (GEP) ancillary diagnostic testing workflow for difficult-to-diagnose melanocytic lesions increases the rate of actionable results to 99%

Presenter: Kelli L. Ahmed, Ph.D., Castle Biosciences, Inc.

About DecisionDx^®-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as the risk of sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 6,000 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. To predict risk of recurrence and likelihood of sentinel lymph node positivity, the Company utilizes its proprietary algorithms, i31-ROR and i31-SLNB, to produce an Integrated Test Result. Through Dec. 31, 2021, DecisionDx-Melanoma has been ordered 90,154 times for use with patients with cutaneous melanoma.

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), 2A (moderate) or 2B (high) 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’ Comprehensive Diagnostic Offering for Difficult-to-Diagnose Melanocytic Lesions

Castle Biosciences’ comprehensive diagnostic offering leverages the strengths of myPath® Melanoma and DecisionDx® DiffDx™-Melanoma. These gene expression profile tests are designed to provide a highly accurate, objective result to aid dermatopathologists and dermatologists in characterizing difficult-to-diagnose melanocytic lesions. Of the approximately 2 million suspicious pigmented lesions biopsied annually in the United States, Castle estimates that approximately 300,000 of those cannot be confidently classified as either benign or malignant through traditional histopathology methods. For these cases, the treatment plan can also be uncertain. Obtaining highly accurate, objective ancillary testing can mean the difference between a path of overtreatment or the risk of undertreatment. Interpreted in the context of other clinical, laboratory and histopathologic information, myPath Melanoma and DecisionDx DiffDx-Melanoma are designed to reduce uncertainty and provide confidence for dermatopathologists and help dermatologists deliver more informed patient management plans.

More information about the Castle tests can be found at www.CastleTestInfo.com.

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, uveal melanoma and Barrett’s esophagus. Additionally, the Company has active research and development programs for tests in other diseases with high clinical need, including its test in development to predict systemic therapy response in patients with moderate-to-severe psoriasis, atopic dermatitis and related conditions. To learn more, please visit www.CastleBiosciences.com and connect with us on LinkedIn, Facebook, Twitter and Instagram.

DecisionDx-Melanoma, DecisionDx-CMSeq, DecisionDx-SCC, myPath Melanoma, DecisionDx DiffDx-Melanoma, DecisionDx-UM, DecisionDx-PRAME, DecisionDx-UMSeq and TissueCypher 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 positive study results and findings contributing to confidence in disease management plans that incorporate DecisionDx-Melanoma test results and demonstrating DecisionDx-SCC’s ability to add positive predictive value to clinician decisions regarding staging and management; the ability of Castle Biosciences’ comprehensive diagnostic offering to assist clinicians in determining an appropriate course of treatment by providing highly accurate, objective ancillary testing; and the ability of the myPath Melanoma and DecisionDx DiffDx-Melanoma gene expression profile tests to provide confidence to clinicians and help them deliver more informed patient management plans. The words “anticipates,” “believes,” “estimates,” “expects,” “intends,” “may,” “plans,” “projects,” “will,” “would” 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, the effects of the COVID-19 pandemic on our business and our efforts to address its impact on our business, subsequent study results and findings may contradict earlier study results and findings, including with respect to the gene expression profile tests discussed 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 fiscal year ended December 31, 2021, 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.

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