Empowering people, informing care decisions November 2025 ©2025 Castle Biosciences 1 Disclaimers Forward-Looking Statements This presentation 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: our positioning for continued grow ...

Market Potential - The estimated total addressable market (TAM) for DecisionDx-Melanoma is approximately $540 million, with around 130,000 patients diagnosed annually in the U.S.[129] - The estimated TAM for DecisionDx-SCC is approximately $820 million, with 20% of SCC patients classified as high risk, totaling about 200,000 patients annually in the U.S.[130] - The TAM for MyPath Melanoma is estimated at $600 million, with approximately 300,000 patients presenting with diagnostically ambiguous lesions each year[131] - The TAM for AdvanceAD-Tx is approximately $33 billion, targeting around 13.2 million individuals aged 12 and older with moderate-to-severe atopic dermatitis in the U.S.[132] - TissueCypher has an estimated TAM of approximately $1 billion, aimed at predicting the progression of high-grade dysplasia and/or esophageal cancer[133] - DecisionDx-UM has an estimated TAM of approximately $10 million, being the standard of care in most ocular oncology practices in the U.S.[134] Reimbursement Rates - The reimbursement rate for DecisionDx-Melanoma is set at $7,193 per test for 2024 and 2025[140] - The reimbursement rate for DecisionDx-SCC is set at $8,500 per test from April 1, 2024, through December 31, 2025[142] - The reimbursement rate for TissueCypher is set at $4,950 per test for 2025, based on median private payor rates[146] Test Volume and Growth - Test report volume increased by 3.2% and 8.1% for the three and nine months ended September 30, 2025, respectively, compared to the same periods in 2024[157] - Dermatologic test report volume rose by 9.0% and 7.6% for the three and nine months ended September 30, 2025, driven by growth in DecisionDx-Melanoma and DecisionDx-SCC tests[157] - TissueCypher test reports surged by 74.7% and 90.5% for the three and nine months ended September 30, 2025, compared to the prior year[157] - Approximately 74% of clinicians ordering DecisionDx-SCC also ordered DecisionDx-Melanoma during the nine months ended September 30, 2025[158] Financial Performance - Net revenues for the three months ended September 30, 2025 decreased by $2.7 million, or 3.2%, to $83.0 million compared to the same period in 2024[184] - Revenue from dermatologic tests decreased by $16.5 million, primarily due to lower average selling price driven by the loss of Medicare LCD coverage[185] - Revenue from non-dermatologic tests increased by $13.8 million, reflecting growth in test report volumes for the TissueCypher Barrett's Esophagus test[186] - For the nine months ended September 30, 2025, net revenues increased by $11.5 million, or 4.7%, to $257.2 million compared to the same period in 2024[196] - The gross margin percentage for the nine months ended September 30, 2025, was 66.8%, down from 79.3% in 2024, primarily due to lower average selling prices (ASP) for the DecisionDx-SCC test and increased amortization expenses[205] Expenses and Costs - Total operating expenses increased by $9.1 million, or 11.3%, to $89.8 million for the three months ended September 30, 2025[180] - Research and development expenses increased by $0.6 million, or 5.2%, primarily due to higher personnel costs[190] - Selling, general and administrative expenses increased by $5.4 million, or 10.7%, driven by higher personnel and travel expenses[191] - Selling, general and administrative (SG&A) expenses increased by $22.5 million, or 15.0%, for the nine months ended September 30, 2025, with sales and marketing expenses rising by 12.5% and general and administrative expenses increasing by 19.0%[207][208] - Cost of sales (exclusive of amortization of acquired intangible assets) increased by $8.7 million, or 19.7%, for the nine months ended September 30, 2025, primarily due to higher personnel and lab service costs[203] Cash and Investments - As of September 30, 2025, the company had cash and cash equivalents of $85.6 million and marketable investment securities of $202.0 million, compared to $119.7 million and $173.4 million, respectively, at the end of 2024[212] - The company anticipates that its existing cash, cash equivalents, and marketable investment securities will be sufficient to fund operations for at least the next 12 months[214] - Net cash provided by operating activities for the nine months ended September 30, 2025, was $37.4 million, a decrease of $3.1 million compared to $40.5 million for the same period in 2024[233][234] - Net cash used in investing activities increased to $69.2 million for the nine months ended September 30, 2025, primarily due to the acquisition of Capsulomics for $18.7 million[236][238] Corporate Developments - Castle Biosciences, Inc. plans to launch a sixth proprietary multi-analyte assay with algorithmic analysis (MAAA) test in November 2025[126] - The company is developing a new corporate headquarters in Friendswood, Texas, with a total expected cost of approximately $44.2 million, and has incurred $20.8 million in capital expenditures related to this project as of September 30, 2025[216] - The company expects significant increases in R&D expenses as it continues to invest in developing new products[170] - The company expects lease obligations to increase in the future to support anticipated growth in commercial products and pipeline tests[231] Debt and Obligations - As of September 30, 2025, total long-term debt was $10.0 million, with a net total of $10.0 million after accounting for unamortized discounts[219] - The 2024 Loan and Security Agreement includes a term loan of $10.0 million and a line of credit of $25.0 million, with the latter expiring on September 30, 2025[221][228] - The weighted-average effective interest rate for the outstanding debt under the 2024 Term Loan was 7.99% as of September 30, 2025[227] - Total undiscounted future minimum payment obligations under operating and finance leases were approximately $40.7 million as of September 30, 2025[230] - The company is subject to covenants under the 2024 LSA that restrict its ability to incur additional debt and make acquisitions[224]

Revenue Performance - Q3 2025 revenue was $83 million, a decrease from $85.8 million in Q3 2024[5] - Castle Biosciences reported net revenues of $83.043 million for the three months ended September 30, 2025, a decrease of 3.2% compared to $85.782 million in the same period of 2024[31] - Adjusted revenues for the three months ended September 30, 2025, were $80.545 million, down from $86.334 million in 2024, representing a decrease of about 6.5%[40] - Full-year 2025 revenue guidance raised to $327-335 million from $310-320 million[9] - Castle Biosciences expects total revenue guidance for 2025 to be between $327 million and $335 million[27] Profitability and Loss - Net loss for Q3 2025 was $0.5 million, compared to net income of $2.3 million in Q3 2024[7] - The company reported a net loss of $501,000 for the three months ended September 30, 2025, compared to a net income of $2.269 million in the same period of 2024[33] - Net loss for the nine months ended September 30, 2025, was $21.826 million, a significant decline from a net income of $8.655 million in the same period of 2024[37] - The company incurred an operating loss of $6.804 million for the three months ended September 30, 2025, compared to an operating income of $5.079 million in the same period of 2024[31] - The company’s comprehensive loss for the three months ended September 30, 2025, was $300,000, compared to comprehensive income of $2.914 million in the same period of 2024[33] Operating Expenses - Total operating expenses for the three months ended September 30, 2025, were $89.847 million, an increase of 11.4% from $80.703 million in the same period of 2024[31] - Stock-based compensation expense for the three months ended September 30, 2025, was $12.1 million, down from $13.027 million in the same period of 2024[32] Test Reports and Product Launches - Total test reports for core revenue drivers increased by 36% over Q3 2024, with DecisionDx-Melanoma and TissueCypher each surpassing 10,000 test reports for the first time in a single quarter[4] - The company launched AdvanceAD-Tx™, a test for guiding treatment decisions in patients with moderate-to-severe atopic dermatitis[1] - Total test reports delivered in the nine months ended September 30, 2025, were 77,817, compared to 72,000 in the same period of 2024[7] Cash and Assets - Cash, cash equivalents, and marketable investment securities totaled $287.5 million as of September 30, 2025[8] - Total assets increased to $562.786 million as of September 30, 2025, compared to $531.235 million on December 31, 2024, reflecting a growth of approximately 5.0%[35] - Cash and cash equivalents decreased to $85.556 million at the end of the period from $119.709 million at the beginning, a decline of approximately 28.3%[37] Liabilities - Total current liabilities increased to $55.308 million as of September 30, 2025, compared to $49.392 million on December 31, 2024, reflecting an increase of about 12.3%[35] - The company’s total liabilities rose to $95.740 million as of September 30, 2025, compared to $75.400 million at the end of 2024, marking an increase of approximately 27.0%[35] EBITDA - Adjusted EBITDA for Q3 2025 was $9.2 million, down from $21.6 million in Q3 2024[7] - Adjusted EBITDA for the nine months ended September 30, 2025, was not explicitly stated but is calculated by excluding certain expenses from net income, which was a loss of $21.826 million[31][32] - Adjusted EBITDA for the nine months ended September 30, 2025, was $32.546 million, down from $53.730 million in 2024, a decrease of approximately 39.4%[44] Gross Margin - Gross margin for Q3 2025 was 75%, down from 79% in Q3 2024[7] - The company reported a gross margin (GAAP) of 74.7% for the three months ended September 30, 2025, down from 79.2% in 2024[40] - Adjusted gross margin percentage for the three months ended September 30, 2025, was 76.8%, compared to 81.9% in 2024, indicating a decline of 5.1 percentage points[40]

Financial Performance - Company reported Q3 2025 revenue of $83 million, a decrease from $85.8 million in Q3 2024 [5][9] - Non-dermatologic revenue increased by 67% compared to Q3 2024 [1] - Total test reports for core revenue drivers (DecisionDx-Melanoma, TissueCypher) increased by 36% over Q3 2024 [1] - Company raised full-year 2025 revenue guidance to $327-335 million from $310-320 million [1][8] Operational Highlights - Total test reports delivered in Q3 2025 were 26,841, compared to 26,010 in Q3 2024 [5] - DecisionDx-Melanoma test reports delivered were 10,459, up from 9,367 in Q3 2024 [5] - TissueCypher Barrett's Esophagus test reports delivered were 10,609, compared to 6,073 in Q3 2024 [5] - DecisionDx-SCC test reports delivered were 4,186, slightly down from 4,195 in Q3 2024 [5] New Product Launch - Company announced the launch of AdvanceAD-Tx™, a test designed to guide systemic treatment decision-making in patients with moderate-to-severe atopic dermatitis [1][12] Gross Margin and Adjusted Metrics - Gross margin for Q3 2025 was 75%, down from 79% in Q3 2024 [5] - Adjusted gross margin was 77%, compared to 82% in the same period of 2024 [5] - Adjusted EBITDA for Q3 2025 was $9.2 million, down from $21.6 million in Q3 2024 [9] Cash and Investments - As of September 30, 2025, the company's cash, cash equivalents, and marketable investment securities totaled $287.5 million [7]

Core Insights - Castle Biosciences has launched AdvanceAD-Tx™, a gene expression profile test aimed at guiding treatment decisions for patients aged 12 and older with moderate-to-severe atopic dermatitis (AD) [1][10] - The test identifies patients with a Janus kinase inhibitor (JAKi) responder profile, indicating a higher likelihood of achieving significant improvement in their condition when treated with JAK inhibitors compared to Th2-targeted therapies [2][11] Company Overview - Castle Biosciences is focused on developing innovative diagnostic tests that enhance patient care, particularly in dermatologic and gastroenterological diseases [7] - The company aims to leverage its existing technology to address unmet needs in the field of atopic dermatitis, with a total addressable market estimated at $33 billion [3][4] Product Details - AdvanceAD-Tx is a non-invasive test that evaluates 487 genes to classify patients into JAKi responder or Th2 molecular profiles, providing insights to personalize treatment [10][11] - In clinical validation, 30.4% of tested samples showed a JAKi responder profile, with those patients achieving a 90% improvement in disease severity (EASI-90) at a significantly higher rate compared to those on Th2-targeted therapy (45.5% vs 8.3%) [4][11] Clinical Integration and Launch Strategy - The test is designed for easy integration into existing laboratory workflows, facilitating adoption by dermatologists familiar with Castle's other tests [5] - AdvanceAD-Tx will be launched in a phased manner starting November 2025, with broader availability expected throughout 2026 [5] Market Potential - The U.S. market for atopic dermatitis treatments is substantial, with approximately 13.2 million patients aged 12 and older suffering from moderate-to-severe AD [4] - The introduction of AdvanceAD-Tx is anticipated to act as a growth catalyst for Castle Biosciences alongside its established tests in dermatology and gastrointestinal areas [3]

Core Insights - Castle Biosciences is expected to report Q3 2025 results on November 3, 2025, with anticipated earnings of ($0.35) per share and revenue of $71.062 million [1][2] - The company previously reported Q2 2025 earnings of $0.15 per share, exceeding estimates by $0.66, with revenue of $86.18 million, surpassing expectations of $71.53 million [3] - Analysts project a $0 EPS for the current fiscal year and a $-2 EPS for the next fiscal year [3] Financial Performance - Castle Biosciences has a market capitalization of $739.76 million, with a price-to-earnings ratio of -72.86 and a beta of 1.13 [4] - The stock has fluctuated between a fifty-two week low of $14.59 and a high of $35.84, with a current stock price of $25.50 [4] - The company maintains a debt-to-equity ratio of 0.02, a quick ratio of 6.69, and a current ratio of 6.85 [4] Insider Activity - Insider Derek J. Maetzold sold 1,339 shares at an average price of $22.44, totaling $30,047.16, resulting in a 2.08% decrease in his position [5] - Following the sale, Maetzold holds 62,988 shares valued at approximately $1.41 million [5] Institutional Holdings - Institutional investors own 92.60% of Castle Biosciences, with notable increases in holdings from several firms, including a 10,592% increase from Jones Financial Companies [6] - Other significant increases include a 256.9% boost from Tower Research Capital and a 15,811.5% increase from Amundi [6] Analyst Ratings - Weiss Ratings issued a "sell (d-)" rating, while Wall Street Zen upgraded the stock from "sell" to "hold" [7] - Canaccord Genuity maintains a "buy" rating with a price target of $37.00, and Zacks Research upgraded the stock to "strong-buy" [7][8] - The consensus rating is "Moderate Buy" with an average target price of $36.57 [8] Company Overview - Castle Biosciences specializes in molecular diagnostics, providing testing solutions for dermatologic cancers, Barrett's esophagus, uveal melanoma, and mental health conditions [9] - Key products include DecisionDx-Melanoma, DecisionDx-SCC, MyPath Melanoma, and TissueCypher, which assist in risk stratification and diagnosis [9]

Core Viewpoint - Castle Biosciences, Inc. (CSTL) is expected to report a year-over-year decline in earnings and revenues for the quarter ended September 2025, with a consensus outlook indicating a quarterly loss of $0.34 per share and revenues of $71.3 million, down 16.9% from the previous year [1][3]. Earnings Expectations - The upcoming earnings report is anticipated to be released on November 3, and the stock may experience price movement based on whether the actual results exceed or fall short of expectations [2]. - The consensus EPS estimate has remained unchanged over the last 30 days, indicating stability in analyst expectations [4]. Earnings Surprise Prediction - The Most Accurate Estimate for Castle Biosciences aligns with the Zacks Consensus Estimate, resulting in an Earnings ESP of 0%, suggesting no recent differing analyst views [12]. - Despite the Earnings ESP of 0%, the stock holds a Zacks Rank of 1 (Strong Buy), which typically indicates a higher likelihood of an earnings beat [12]. Historical Performance - In the last reported quarter, Castle Biosciences was expected to post a loss of $0.51 per share but instead reported earnings of $0.15, resulting in a surprise of +129.41% [14]. - Over the past four quarters, the company has beaten consensus EPS estimates three times [15]. Industry Context - In the broader Zacks Medical - Biomedical and Genetics industry, Biogen Inc. (BIIB) is expected to report earnings of $3.89 per share for the same quarter, reflecting a year-over-year change of -4.7% and revenues of $2.34 billion, down 5.1% from the previous year [19][20].

Core Insights - Castle Biosciences announced new data showing that its TissueCypher® Barrett's Esophagus test provides risk insights beyond pathology, aiding in clinical management and supporting earlier interventions for patients at higher risk of progression to esophageal cancer [1][2] Group 1: Research Findings - The TissueCypher test identifies patients at higher risk of progression to esophageal cancer, which may be missed when relying solely on pathology [2] - New data from case studies indicate that TissueCypher returned high-risk results with five-year probabilities of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) of 34% and 62%, respectively, which are higher than the published rates of progression from HGD to EAC (33% over five years) [6] - In a study involving patients with non-dysplastic Barrett's esophagus (NDBE), TissueCypher identified high-risk patients with five-year probabilities of progression to HGD/EAC of 43% and 45%, leading to earlier interventions [6][13] Group 2: Clinical Impact - The TissueCypher test influenced clinical management in 93% of cases in a rural Texas study, allowing for timely interventions for higher-risk patients while reducing unnecessary procedures for lower-risk patients [13] - The test's ability to provide individualized risk stratification supports more personalized decisions around surveillance and intervention, potentially reducing the risk of progression to esophageal cancer [2][6] Group 3: Recognition and Presentation - The research findings will be presented at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting, with one abstract selected for a Presidential Poster Award, highlighting the quality and significance of the research [2][4] - A total of more than 6,400 scientific abstracts will be presented at the ACG 2025, with only a small percentage receiving the Presidential Poster Award [2] Group 4: About TissueCypher - The TissueCypher Barrett's Esophagus test is designed to predict future development of HGD and/or EAC in patients with Barrett's esophagus, and has been supported by 14 peer-reviewed publications [8] - The test received Advanced Diagnostic Laboratory Test (ADLT) status from the Centers for Medicare & Medicaid Services (CMS) in March 2022, indicating its clinical significance [8] Group 5: Company Overview - Castle Biosciences is a leading diagnostics company focused on improving health through innovative tests that guide patient care, with a portfolio that includes tests for skin cancers, Barrett's esophagus, and uveal melanoma [9][10] - The company is actively engaged in research and development for tests addressing high clinical needs, including a test for moderate-to-severe atopic dermatitis [10]

Core Insights - Castle Biosciences is presenting data on its DecisionDx®-Melanoma test and pipeline atopic dermatitis gene expression profile test at the 25th Annual Fall Clinical Dermatology Conference [1] - The DecisionDx-Melanoma test has shown clinically significant risk stratification across various histological subtypes of melanoma, confirming its clinical value [2][4] - The pipeline atopic dermatitis test aims to improve treatment decision-making by classifying patients based on their underlying disease biology [5] DecisionDx-Melanoma Insights - The DecisionDx-Melanoma test utilizes a 31-gene expression profile to stratify melanoma-specific survival across different tumor subtypes, demonstrating significant differences in five-year survival rates [4][6] - In a cohort of 13,560 patients, five-year melanoma-specific survival was 98.5% for Class 1A (lowest risk) and 82.3% for Class 2B (highest risk) patients with nodular melanoma [4] - The test can identify early-stage melanoma patients at higher risk of distant metastasis, with Class 2B patients showing significantly higher rates of metastasis compared to Class 1A patients [4] Atopic Dermatitis Pipeline Insights - The pipeline atopic dermatitis test classifies patients into Th2 Molecular Profile or JAKi Responder Profile, aiming to guide systemic therapy selection [5] - Data indicates that patients with a JAKi responder profile experience rapid and deep responses to JAK inhibitors, potentially improving treatment outcomes [5] - The test seeks to shift atopic dermatitis care from trial-and-error prescribing to more personalized treatment approaches, enhancing patient satisfaction and reducing healthcare costs [5] Company Overview - Castle Biosciences is a diagnostics company focused on innovative tests that guide patient care, with a portfolio that includes tests for skin cancers and other diseases [7][8] - The company has conducted over 210,000 orders for the DecisionDx-Melanoma test, indicating strong market adoption and clinical relevance [6]

Core Viewpoint - Castle Biosciences, Inc. (CSTL) shows potential for significant upside, with a mean price target of $35.63 indicating a 50.1% increase from the current price of $23.74 [1] Price Targets - The average price target consists of eight estimates ranging from $30.00 to $41.00, with a standard deviation of $3.54, suggesting a consensus among analysts [2] - The lowest estimate indicates a 26.4% increase, while the highest suggests a 72.7% upside [2] - A low standard deviation indicates a high degree of agreement among analysts regarding price movement [9] Analyst Sentiment - Analysts have shown increasing optimism about CSTL's earnings prospects, with a strong agreement in revising EPS estimates higher, which correlates with potential stock price increases [11] - Over the last 30 days, one estimate has increased, leading to a 1.5% rise in the Zacks Consensus Estimate [12] Zacks Rank - CSTL holds a Zacks Rank 1 (Strong Buy), placing it in the top 5% of over 4,000 ranked stocks based on earnings estimate factors, indicating strong potential for near-term upside [13] Conclusion on Price Movement - While the consensus price target may not reliably indicate the extent of potential gains, it does provide a useful guide for the direction of price movement [14]