Presentations at EADO Highlight Potential Impact of Castle Biosciences' DecisionDx®-Melanoma and DecisionDx®-SCC Tests on the Management of Patients with Skin Cancer

Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, will share new data at the 20th European Association of Dermato-Oncology (EADO) Congress, being held April 4-6, 2024, in Paris, France, that demonstrate the ability of its DecisionDx-Melanoma and DecisionDx-SCC tests to improve clinical-decision making through precise risk-stratification of patients with cutaneous melanoma (CM) and squamous cell carcinoma (SCC).

"Our DecisionDx-Melanoma test informs two questions: which patients can consider foregoing an SLNB, and what is the risk of recurrence so the most appropriate follow-up treatment plan can be implemented," said Robert Cook, Ph.D., senior vice president of research and development at Castle Biosciences. "It is of high importance that when a test identifies patients with a low likelihood of a positive SLNB, and thus they could forgo this surgical procedure, the patients also have a low risk of metastatic outcomes. The data from our prospective, multicenter study show just that ? SLNB-eligible patients who had a DecisionDx-Melanoma Class 1A (lowest risk) test result and made the decision with their physician to forego an SLNB had excellent outcomes during the follow-up period. We believe it is this kind of evidence that should be required in order for clinicians to safely adopt a molecular test that rules out an SLNB surgical procedure.

"Our second DecisionDx-Melanoma poster shows that the clinical use of our test is also associated with a 30% cost savings improvement ... a win-win situation."

Castle will present the following posters at EADO:

DecisionDx-Melanoma

• Title: Patients who forego sentinel lymph node biopsy after 31-GEP testing are not harmed: A prospective, multicenter analysis
• Abstract: A-262
• Summary: This study shares data from Castle's prospective, multicenter study of patients with T1-T2 CM tumors who were being considered for an SLNB. Within a median follow-up time of two years, none of the patients with low-risk DecisionDx-Melanoma test results (Class 1A) who decided to forego SNLB based on their results had a tumor recurrence. These study data support use of the DecisionDx-Melanoma test to inform SLNB decisions and show that it can identify patients at low risk of sentinel lymph node (SLN) positivity who may safely forego the SLNB procedure, reducing healthcare costs and procedure complications.

• Title: The health economic impact of the 31-gene expression profile test for treatment and surveillance management plans in patients with cutaneous melanoma
• Abstract: A-223
• Summary: The DecisionDx-Melanoma test has been validated to predict individual risk of SLNB positivity and five-year risk of recurrence and metastasis for patients with CM. This study explored the cost-savings impact of using the DecisionDx-Melanoma test to guide risk-aligned clinical decision-making versus using the current melanoma staging standard, a patient's AJCC stage. Costs of National Comprehensive Cancer Network (NCCN) guideline-recommended practices for patients with melanoma that were evaluated in the study included: SLNB, clinical visit schedules, imaging surveillance and adjuvant treatment for eligible patients. The study determined that using DecisionDx-Melanoma test results to guide decision-making could save commercial payers more than $3 million (30% cost savings per one million plan members over five years) compared to care guided by AJCC stage, with 95% of such potential cost savings occurring during the first year post-diagnosis (year one projected savings of approximately $2.5 million).

DecisionDx-SCC

• Title: Evaluating the performance of a clinicopathological prognostic nomogram and utility of the 40-gene expression profile (40-GEP) test in refining risk of metastasis in high-risk cutaneous squamous cell carcinoma (HR-cSCC) patients
• Abstract: A-128
• Summary: The DecisionDx-SCC test uses a patient's tumor biology to independently predict risk of regional or distant metastasis in patients with high-risk SCC. The test has also been shown to improve the accuracy of risk predictions when used with other risk assessment approaches, including NCCN guidelines. This study evaluated the performance of a risk-stratification nomogram developed in Europe (Rentroia-Pacheco, et al, 2023) in a U.S. cohort of high-risk SCC patients (n=760) and the additional prognostic value provided by the DecisionDx-SCC test. In the study, the nomogram misclassified nine out of 10 tumors that metastasized as low risk. When the same tumors were tested using DecisionDx-SCC, 42% of those that the nomogram classified as low risk of metastasis were classified as high risk by the test, as well as 70% of all tumors that metastasized. These data demonstrate that DecisionDx-SCC improves the accuracy of risk assessment based solely on clinicopathological risk factors, leading to more appropriate risk-aligned management plans for patients with high-risk SCC.

Castle's abstracts can be found in the digital Book of Abstracts available for download on the EADO website.

About DecisionDx®-Melanoma

DecisionDx-Melanoma is a gene expression profile risk stratification test. It is designed to inform two clinical questions in the management of cutaneous melanoma: a patient's individual risk of SLN positivity and a patient's personal risk of melanoma recurrence and/or metastasis. By integrating tumor biology with clinical and pathologic factors using a validated proprietary algorithm, DecisionDx-Melanoma is designed to provide a comprehensive and clinically actionable result to guide risk-aligned patient care. DecisionDx-Melanoma has been shown to be associated with improved patient survival and has been studied in more than 10,000 patient samples. DecisionDx-Melanoma's clinical value is supported by 50 peer-reviewed and published studies, providing confidence in disease management plans that incorporate the test's results. Through Dec. 31, 2023, DecisionDx-Melanoma has been ordered more than 150,000 times for patients diagnosed 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), 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-CMSeq, DecisionDx-SCC, MyPath Melanoma, DiffDx-Melanoma, TissueCypher, IDgenetix, DecisionDx-UM, DecisionDx-PRAME and DecisionDx-UMSeq 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 DecisionDx-Melanoma test results to (i) result in 30% cost savings compared to care guided by AJCC stage, (ii) inform SLNB decisions and identify patients at low risk of SLN positivity who may safely forego the SLNB procedure and (iii) reduce healthcare costs and procedure complications; the ability of DecisionDx-SCC to (i) predict metastases, (ii) improve the accuracy of risk predictions when used with other risk assessment approaches, including NCCN guidelines and (iii) improve the accuracy of risk assessment based solely on clinicopathological risk factors. The words "believe," "can," "could," "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 results obtained in these studies, including with respect to the discussion of our tests 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.