Here are a few brief analogies for Castle Biosciences (CSTL):

• A Foundation Medicine for predicting the spread of skin and eye cancers.
• Like an Invitae or Natera, but specializing in gene expression tests to forecast metastasis risk in skin and eye cancers.

• DecisionDx-Melanoma: A multi-gene expression profile (GEP) test designed to identify the risk of metastasis for patients with invasive cutaneous melanoma.
• DecisionDx-UM: A proprietary GEP test used to predict the risk of metastasis for patients diagnosed with uveal melanoma.
• DecisionDx-SCC: A proprietary 40-gene expression profile test that predicts the individual risk of squamous cell carcinoma metastasis for patients with specific risk factors.
• DecisionDx DiffDx-Melanoma and myPath Melanoma: Proprietary GEP tests utilized for the diagnosis of suspicious pigmented lesions.

• Dermatologists and Dermatology Practices: These are key customers as the company's lead products, DecisionDx-Melanoma, DecisionDx-SCC, DecisionDx DiffDx-Melanoma, and myPath Melanoma, focus on diagnosing and predicting the risk of metastasis for dermatological cancers like cutaneous melanoma and squamous cell carcinoma. Dermatologists are typically the first point of contact for patients with suspicious lesions and make decisions regarding further testing.
• Ophthalmologists and Ocular Oncology Practices: For its DecisionDx-UM test, which predicts the risk of metastasis for patients with uveal melanoma (a rare eye cancer), ophthalmologists, particularly those specializing in ocular oncology, are crucial customers who order these specialized tests.
• Oncologists and Hospitals/Integrated Healthcare Systems: Oncologists, particularly those specializing in melanoma or skin cancers, may utilize Castle Biosciences' tests for risk stratification and management of high-risk patients. Additionally, hospitals and larger integrated healthcare systems encompassing dermatology, ophthalmology, and oncology departments are significant customers, as they provide comprehensive care and often have established pathways for ordering specialized diagnostic tests.

Derek J. Maetzold founded Castle Biosciences in September 2007, initiating operations in late 2008 with co-founders Toby Juvenal and Kristen Oelschlager. Before founding Castle Biosciences, he accumulated 24 years of experience in pharmaceutical development and commercialization, focusing on new product development through business licensing and commercial oversight of pre-approved therapies. Immediately prior to starting Castle, he prepared a public biotechnology company for its first commercial product launch, and this company was subsequently sold. His pharmaceutical career involved leadership roles at companies such as Encysive Pharmaceuticals, Schering-Plough Corporation (now Merck), Integrated Communications, Amylin Pharmaceuticals, and Sandoz Pharmaceuticals (now a division of Novartis). Mr. Maetzold has contributed to the discovery, development, and commercialization of five diagnostic and prognostic tests in cancers and is a co-inventor of multiple technologies at Castle Biosciences and Encysive Pharmaceuticals.

Frank Stokes has served as Castle Biosciences' Chief Financial Officer since December 2017. Prior to joining Castle Biosciences, he was the Chief Financial Officer of Hammock Pharmaceuticals, a specialty pharmaceutical company, where he was involved in the company's initial capitalization and the acquisition of its foundational drug delivery technology. Mr. Stokes also had a distinguished career as a senior investment banker at firms including Leerink Partners (now SVB Leerink), Robert W. Baird, and Wachovia Securities (now Wells Fargo Securities). In these roles, he led life sciences, tools, and diagnostics sector investment banking efforts, and managed various financings, and mergers and acquisitions transactions. He successfully stewarded Castle through its IPO in 2019, a move he had actively anticipated and pursued a relationship with Castle for during his banking career.

Kristen M. Oelschlager joined Castle Biosciences in October 2008 as one of the company's three initial employees, serving as the Executive Director of Operations. She has held the position of Chief Operating Officer since April 2021, and her previous roles at Castle Biosciences include Chief Operations Officer (August 2020 to April 2021), Senior Vice President, Clinical Operations (January 2018 to August 2020), and Vice President, Clinical Operations (2013 to 2018). Ms. Oelschlager brings over 15 years of experience in clinical nursing, clinical operations services, and clinical research to her role.

Tobin W. Juvenal was one of the three initial employees at Castle Biosciences, joining in October 2008 as the Executive Director, Sales and Marketing. He has served as Chief Commercial Officer since September 2020. His prior roles at the company include Senior Vice President, Sales (January 2018 to August 2020), and Vice President of Sales (2013 to 2018).

Here are the key risks to Castle Biosciences (CSTL):

1. Reimbursement Uncertainty and Challenges: Castle Biosciences faces significant risk from ongoing uncertainties and potential changes in reimbursement policies for its diagnostic tests. Management has acknowledged uncertainty, particularly for AdvanceAD-Tx and DecisionDx-SCC. Notably, a Medicare contractor, Novitas, finalized a decision for non-coverage of the DecisionDx-SCC test, which became effective in February 2025. This non-coverage is considered a "material risk to one of CSTL's highest-growth assets," potentially eliminating Medicare reimbursement for a key product. The company's financial outlook and ability to translate test volumes into sustainable earnings are highly dependent on favorable reimbursement decisions and payer coverage.
2. Concentration Risk on Key Products: While Castle Biosciences is expanding its portfolio, a substantial portion of its revenue is expected to continue coming from its core DecisionDx-Melanoma franchise and related dermatologic tests for the foreseeable future. This reliance on a limited number of products exposes the company to significant risk if new competitors emerge, reimbursement rates are cut for these specific tests, or new clinical guidelines reduce their utility or adoption.
3. Persistent Net Losses and Challenges to Profitability: Despite experiencing strong top-line revenue growth and increasing test volumes, Castle Biosciences has consistently reported net losses. The company recorded a net loss of $24.2 million for the full year 2025. High operating expenses, which are growing faster than revenue, contribute to operational inefficiencies and a challenging path to sustained profitability. While the company maintains a strong gross margin, its negative earnings per share and net margin highlight ongoing difficulties in translating revenue into positive net income.

The emergence of artificial intelligence (AI) and machine learning (ML) powered digital pathology solutions that can analyze routine histology slides to predict metastatic risk for dermatological cancers. Such solutions could provide prognostic information directly from existing tissue biopsies (e.g., H&E stained slides), potentially offering a faster, more cost-effective, and integrated alternative to specialized multi-gene expression profile (GEP) tests like those offered by Castle Biosciences, thereby reducing the demand for their proprietary testing services.

Castle Biosciences addresses significant markets with its diagnostic and prognostic tests for dermatological cancers:

• DecisionDx-Melanoma: The estimated addressable market for DecisionDx-Melanoma in the U.S. is approximately 130,000 eligible patients diagnosed with invasive cutaneous melanoma annually. The broader U.S. melanoma diagnostics and therapeutics market was valued at an estimated USD 3.45 billion in 2025 and is projected to reach USD 5.21 billion by 2030. Globally, the melanoma cancer diagnostics market was valued at USD 4.95 billion in 2024 and is expected to grow to USD 8.64 billion by 2032.
• DecisionDx-UM: The global uveal melanoma market was valued at USD 1.5 billion in 2024 and is projected to grow to USD 2.5 billion by 2034. Another report estimates the global uveal melanoma market at USD 402.5 million in 2024, expected to reach USD 609.7 million by 2030. North America, particularly the U.S., dominates this market, with about 2,500 individuals diagnosed annually in the U.S. The uveal melanoma treatment market in North America held the largest revenue share of 44.2% in 2024.
• DecisionDx-SCC: The estimated total addressable market for DecisionDx-SCC in the U.S. is approximately 200,000 patients diagnosed annually with high-risk squamous cell carcinoma. The squamous cell carcinoma market across the top 7 major markets (U.S., EU4, U.K., and Japan) was valued at USD 739.1 million in 2024 and is projected to reach USD 1,469.0 million by 2035. The global cutaneous squamous cell carcinoma treatment market size is estimated at USD 13.69 billion in 2024 and is projected to reach approximately USD 27.54 billion by 2034. The United States accounts for the largest market size in Cutaneous Squamous Cell Carcinoma.
• DecisionDx DiffDx-Melanoma and myPath Melanoma: These tests, combined as Castle's Diagnostic GEP offering for difficult-to-diagnose melanocytic lesions, represent an estimated U.S. total addressable market of $600 million. The clinical offering of DiffDx-Melanoma was suspended in February 2023, with myPath Melanoma continuing.

Castle Biosciences (CSTL) is expected to drive future revenue growth over the next 2-3 years through several key initiatives:

1. Increased Adoption and Penetration of Core Dermatology Tests: Continued growth is anticipated from the company's flagship dermatological tests, particularly DecisionDx-Melanoma. In 2025, DecisionDx-Melanoma delivered 39,083 test reports, showing a 9% year-over-year increase, and achieved approximately 31% patient penetration with nearly 17,000 ordering clinicians. The company is also working on a de novo 510(k) submission to support commercial reimbursement.

2. Expansion of TissueCypher Barrett's Esophagus Test: The TissueCypher test, which identifies the risk of progression for patients with Barrett's esophagus, is a significant growth driver. Its test volume grew 86% to 39,014 reports in 2025, with management noting only about 11% patient penetration, indicating substantial room for future expansion. The test's inclusion in the AGA Barrett's esophagus guideline further supports its adoption.

3. Commercialization of AdvanceAD-Tx for Atopic Dermatitis: Castle Biosciences launched AdvanceAD-Tx, a gene expression profile test for moderate-to-severe atopic dermatitis, on a limited-access basis in November 2025. Early results showed strong interest, with over half of the initial 150 dermatological accounts ordering the test within the first five weeks. This new product is expected to materially expand the company's total addressable market, with significant revenue contributions anticipated in 2027 or 2028 as reimbursement pathways are established and availability expands.

4. Strategic Commercial Team Expansion and Market Penetration: The company plans to enhance its commercial efforts, including potential expansion of its sales force, to drive broader adoption by both clinicians and payers for its existing and newly launched products. This strategic focus aims to capitalize on unmet clinical needs and significant market opportunities through robust clinical evidence and targeted penetration.

Share Issuance

• Castle Biosciences' common shares issued and outstanding have steadily increased over the last few years, reflecting ongoing share issuances.
• As of December 31, 2020, there were 24,812,487 shares issued and outstanding, increasing to 25,054,513 shares by March 31, 2021.
• The number of shares issued and outstanding further grew to 26,553,681 by December 31, 2022, and approximately 30 million shares by the fourth quarter of 2025.

Capital Expenditures

• Capital expenditures totaled $31.0 million in 2025 and $9.3 million in 2024.
• The capital expenditures in 2024 and 2025 were primarily related to a development project for a new building.
• The company anticipates that capital expenditures will decline in 2026.