What changed in this filing

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Item 1. Business

2026-02-26 compared with 2025-02-27 · 215 added, 223 removed, 453 unchanged (49% of the section changed)

As used in this Annual Report on Form 10-K, unless the context indicates or otherwise requires, “Castle Biosciences,” the “Company,” “we,” “us” and “our” refer to Castle Biosciences, Inc., a Delaware Corporation.

Castle Biosciences is a molecular diagnostics company offering innovative test solutions to aid clinicians in the diagnosis and treatment of dermatologic cancers, Barrett’s esophagus, uveal melanoma, and in the treatment of mental health conditions.

Castle Biosciences is a molecular diagnostics company offering innovative test solutions to aid clinicians in the diagnosis and treatment of dermatologic cancers, Barrett’s esophagus (“BE”), atopic dermatitis (“AD”), uveal melanoma (“UM”).

Since our inception in 2008, it has been our vision to transform disease management by keeping people first:

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Our Testing Solutions

Our tests are designed to deliver personalized information to help better inform care decisions.

For our tissue based tests, we use multi-analyte assays with algorithmic analysis (“MAAA”) to characterize an individual patient’s biology to inform specific risk of progression.

Our tests are designed to deliver personalized information to help better inform clinical care decisions.

For our core tissue-based tests, we use multi-analyte assays with algorithmic analysis (“MAAA”) to characterize an individual patient’s biology and generate clinically actionable information.

Depending on the specific test, this information may be used to provide information to help guide treatment and patient management decisions including potential responsiveness to therapy and to assist in the diagnosis of a disease.

Test Portfolio and Market Overview

Our portfolio consists of test offerings to aid clinicians in the diagnosis and treatment of cancers or precancerous diagnoses in the fields of dermatology, gastroenterology and ophthalmology and a pharmacogenomic (“PGx”) test to guide optimal drug treatment for patients diagnosed with depression, anxiety and other mental health conditions.

Maintaining commercial success for our existing test portfolio requires generating ongoing evidence, such as clinical performance, clinical use documentation, to support appropriate clinician adoption, reimbursement success and guideline inclusion.

Our portfolio consists of test offerings to aid clinicians in the diagnosis and treatment of cancers or precancerous diagnoses in the fields of dermatology, gastroenterology and ophthalmology, and most recently includes a test to guide systemic treatment decisions in patients with moderate-to-severe AD.

Maintaining commercial success for our existing test portfolio requires generating ongoing evidence, such as clinical performance and clinical use documentation, to support appropriate clinician adoption, reimbursement success and guideline inclusion.

The clinical validity and utility of our test portfolio is supported by peer-reviewed publications and ongoing clinical studies.

Collectively, approximately 158 peer-reviewed articles have been published demonstrating the analytical validity, clinical validity and clinical utility of the tests in our portfolio.

The following table summarizes our commercially available tests:

Dermatology Gastroenterology Ophthalmology

DecisionDx-Melanoma TissueCypher DecisionDx-UM

AdvanceAD-Tx (1)

DecisionDx-SCC

MyPath Melanoma

(1) We commenced a limited launch of our AdvanceAD-Tx TM test in November 2025.

DecisionDx-Melanoma

DecisionDx-Melanoma is our proprietary risk stratification gene expression profile (“GEP”) test that predicts (i) the likelihood of positive sentinel lymph node and (ii) the risk of metastasis, or recurrence, for patients diagnosed with invasive cutaneous melanoma (“CM”), a deadly skin cancer.

In a typical year, we estimate approximately 130,000 patients are diagnosed with invasive CM in the United States, representing an estimated U.S.

DecisionDx-Melanoma is our proprietary risk stratification gene expression profile (“GEP”) test designed to predict the likelihood of a positive sentinel lymph node and the risk of metastasis or recurrence for patients diagnosed with invasive cutaneous melanoma (“CM”), a deadly skin cancer.

In a typical year, we estimate approximately 130,000 patients are diagnosed with invasive CM in the U.S., representing an estimated U.S.

TAM of approximately $540 million.

This estimated annual incidence number is based upon a calculation using data from the U.S.

Surveillance, Epidemiology, and End Results registries and subsequently adjusted for the documented underreporting of melanoma diagnoses which range from 30%-72%.

Based on currently available data, we estimate the targetable clinician base treating melanoma is between 11,000 and 15,000.

Surveillance, Epidemiology, and End Results registries and subsequently adjusted for the documented underreporting of melanoma diagnoses, which ranges from 30%-72%.

Based on the substantial clinical evidence that we have developed, we have received Medicare coverage for DecisionDx-Melanoma.

We estimate that approximately 50% of patients diagnosed with CM are 65 years of age or older.

As of December 31, 2024, 53 peer-reviewed articles, one of which was published in 2024, support the clinical validity, clinical utility and impact on outcomes of our DecisionDx-Melanoma test.

Based on our published data, we have shown that DecisionDx-Melanoma can be an accurate, independent predictor of the risk of metastasis or recurrence, including recurrence to the sentinel lymph node.

As of December 31, 2025, 58 peer-reviewed articles, five of which were published in 2025, support the clinical validity, clinical utility and impact on outcomes of our DecisionDx-Melanoma test.

TissueCypher is our proprietary risk stratification spatialomics test designed to predict future development of high-grade dysplasia (“HGD”) and/or esophageal cancer in patients with non-dysplastic (“ND”), indefinite dysplasia (“IND”) or low-grade dysplasia (“LGD”) BE.

There are approximately 4 million patients in the U.S.

currently diagnosed with BE and approximately 415,000 patients annually undergo an endoscopic biopsy with a subsequent diagnosis of ND, IND or LGD BE, representing an estimated U.S.

TAM of approximately $1 billion.

In 2025, we expanded our capabilities in BE through the acquisition of Capsulomics, Inc., d/b/a Previse (“Previse”), which provides complementary methylation-based intellectual property and a non-endoscopic cell-collection technology.

We expect these assets to enhance the future development of TissueCypher by enabling the potential incorporation of additional molecular modalities, such as methylation markers and other genomic markers, to further strengthen the test’s performance.

In addition, sponge-based, swallowable cell-collection device may offer a non-endoscopic method for obtaining esophageal samples in certain patient populations, which could broaden access to molecular risk assessment and extend the reach of our BE and GI testing portfolio over time.

As of December 31, 2025, our TissueCypher test is supported by 17 peer-reviewed clinical validation and utility studies, three of which were published in 2025.

AdvanceAD-Tx is a non-invasive GEP test designed to guide systemic treatment selection for patients aged 12 years and older with moderate-to-severe AD.

The test evaluates the expression of 487 genes across 12 known immune, inflammatory and skin-related pathways to identify the underlying biology driving an individual patient’s disease.

Results classify AD into one of two molecular profiles:

Janus Kinase (“JAK”) Inhibitor Responder Profile or T helper 2 (“Th2”) Molecular Profile.

Using multiple data sources focused on one-year prevalence, we estimate there are approximately 10 million individuals ages 12 and older in the U.S.

with moderate-to-severe AD, representing an estimated U.S.

TAM of approximately $33 billion.

We commenced a limited access launch of the AdvanceAD-Tx test in November 2025 and plan phased expansion of availability throughout 2026.

DecisionDx-SCC

DecisionDx‑SCC is our proprietary GEP test for use in patients with cutaneous squamous cell carcinoma (“SCC”), the second most common form of skin cancer, with one or more risk factors (also referred to as “high-risk” SCC).

We estimate 20% of SCC patients, or approximately 200,000 annually in the United States, are classified as high risk, representing an estimated U.S.

DecisionDx‑SCC is our proprietary GEP test designed for use in patients with cutaneous squamous cell carcinoma (“SCC”), the second most common form of skin cancer, with one or more risk factors (also referred to as “high-risk” SCC).

We estimate 20% of SCC patients, or approximately 200,000 annually in the U.S., are classified as high risk, representing an estimated U.S.

TAM of approximately $820 million.

DecisionDx-SCC is clinically validated to (i) predict responsiveness to adjuvant radiation therapy (“ART”) and (ii) predict metastatic risk in patients with high-risk SCC.

The validity of DecisionDx-SCC for metastasis risk prediction has been shown in a cohort of 897 in a study which was representative of a high-risk SCC population.

DecisionDx-SCC is clinically validated to predict responsiveness to adjuvant radiation therapy (“ART”) and to predict metastatic risk in patients with high-risk SCC.

The validity of DecisionDx-SCC for metastasis risk prediction has been shown in a cohort of 897 patients in a study which was representative of a high-risk SCC population.

Multivariate analysis shows DecisionDx-SCC provides strong prognostic information in patients with high-risk SCC.

More recently, in 2024 two published studies confirmed the ability of DecisionDx-SCC to predict response to ART.

In 2024 two published studies confirmed the ability of DecisionDx-SCC to predict response to ART.

These two propensity matched studies were the largest and second largest studies published to date that focused on the effectiveness of ART in patients diagnosed with high-risk SCC.

As of December 31, 2024, DecisionDx-SCC was supported by 22 peer-reviewed publications, four of which were published in 2024.

TissueCypher is our proprietary risk stratification spatial-omics test designed to predict future development of high-grade dysplasia (“HGD”) and/or esophageal cancer in patients with non-dysplastic (“ND”), indefinite dysplasia (“IND”) or low-grade dysplasia (“LGD”) Barrett’s esophagus (“BE”).

There are approximately four million patients in the U.S.

currently diagnosed with BE and approximately 415,000 patients annually undergo an endoscopic biopsy with a subsequent diagnosis of ND, IND or LGD BE, representing an estimated U.S.

TAM of approximately $1 billion.

As of December 31, 2024, our TissueCypher test is supported by 16 peer-reviewed clinical validation and utility studies.

MyPath Melanoma

MyPath® Melanoma is our proprietary, diagnostic GEP test offering for use in patients with difficult-to-diagnose melanocytic lesions.

Of the two million suspicious pigmented lesions biopsied annually in the United States, we estimate approximately 300,000 of those present a difficult-to-diagnose melanocytic lesion, representing an estimated U.S.

MyPath® Melanoma is our proprietary, diagnostic GEP test for use in patients with difficult-to-diagnose melanocytic lesions.

Of the two million suspicious pigmented lesions biopsied annually in the U.S., we estimate approximately 300,000 of those present a difficult-to-diagnose melanocytic lesion, representing an estimated U.S.

TAM of approximately $600 million.

As of December 31, 2024, our MyPath Melanoma test is supported by 20 peer-reviewed publications, one of which was published in 2024.

As of December 31, 2025, our MyPath Melanoma test is supported by 20 peer-reviewed publications.

DecisionDx-UM

DecisionDx®-UM is our proprietary, risk stratification GEP test that predicts the risk of metastasis for patients with uveal melanoma (“UM”), also referred to as ocular melanoma.

We estimate approximately 2,000 patients in the United States are diagnosed annually with UM, representing an estimated U.S.

DecisionDx®-UM is our proprietary, risk stratification GEP test that predicts the risk of metastasis for patients with UM, also referred to as ocular melanoma.

We estimate approximately 2,000 patients in the U.S.

are diagnosed annually with UM, representing an estimated U.S.

TAM of approximately $10 million.

DecisionDx-UM has been clinically validated by an independent prospective, multi-center study, by multiple retrospective and prospective single-center studies.

DecisionDx-UM has been clinically validated by an independent prospective, multi-center study, and by multiple retrospective and prospective single-center studies.

As of December 31, 2025, our DecisionDx-UM test is supported by 39 peer-reviewed publications.

IDgenetix® is our proprietary PGx test that helps guide optimal drug treatment for patients diagnosed with major depressive disorder, schizophrenia, bipolar disorder, anxiety disorders, social phobia, obsessive-compulsive personality disorder, post-traumatic stress disorder, and attention deficit hyperactivity disorder.

IDgenetix is designed to provide important genetic information to clinicians to help guide personalized treatment plans for their patients, with the potential to help patients achieve a faster therapeutic response and improve their chances of remission by identifying appropriate medications more efficiently than the standard of care trial-and-error approach.

We began offering the IDgenetix test following our acquisition of AltheaDx, Inc.

(“AltheaDx”) in April 2022.

IDgenetix is supported by a published, peer-reviewed randomized controlled trial that demonstrated clinical utility over the standard of care when physicians used IDgenetix prior to prescribing a medication.

The trial was conducted across 20 independent clinical sites within the United States specializing in psychiatry, internal medicine, obstetrics & gynecology, and family medicine.

As of December 31, 2024, our IDgenetix test is supported by 19 peer-reviewed publications.

Following our acquisition of AltheaDx, Inc.

(“AltheaDx”) in April 2022, we began offering the IDgenetix® test, a proprietary pharmacogenomic (“PGx”) test that helped guide optimal drug treatment for patients diagnosed with certain mental health conditions.

IDgenetix was designed to provide important genetic information to clinicians to help guide personalized treatment plans for their patients, with the potential to help patients achieve a faster therapeutic response and improve their chances of remission by identifying appropriate medications more efficiently than the standard of care trial-and-error approach.

The IDgenetix test was discontinued in May 2025.

Pipeline Initiatives

We have significant expertise in developing proprietary algorithms, conducting clinical studies and using the necessary instrumentation required for efficiently developing our pipeline products.

Due to the biological complexity of diseases, developing accurate products takes scientific diligence, stringent clinical protocols, machine learning expertise, proprietary algorithms and significant investments of time and capital.

We have significant expertise in developing proprietary tests, conducting clinical studies and using the necessary instrumentation required for efficiently developing and validating our pipeline products.

Discovering, developing and validating clinically actionable products takes scientific diligence, stringent clinical protocols, machine learning expertise, proprietary algorithms and significant investments of time and capital.

In addition, the underlying tissue samples and associated clinical outcomes data required to develop and validate these products are difficult to obtain.

In 2021, we announced the launch of our innovative pipeline initiative to develop a genomic test, or series of tests, aimed at predicting response to systemic therapy in patients with moderate to severe atopic dermatitis (“AD”), psoriasis and related inflammatory skin conditions.

In the same year, we initiated a large, prospective, multi-center clinical study to develop and validate this pipeline test, formed a steering committee comprised of leading experts in the field and received Institutional Revenue Board (“IRB”) approval.

On December 23, 2024, we announced that preliminary data from our ongoing prospective development and validation study for our pipeline test has shown potential to identify a subset of patients with AD who have increased likelihood to achieve a super response to targeted therapies, indicated by a 90% or greater reduction in Eczema Area and Severity Index score at three months.

AD is among the most common inflammatory skin condition, and patient quality of life is severely impacted by this chronic disease.

In the United States alone, there are approximately six million patients diagnosed annually with moderate-to-severe AD and approximately 760,000 of these patients seek systemic treatment.

As of December 31, 2024, there were more than 39 active clinical study sites and over 1,100 patients enrolled in our inflammatory skin development and validation study.

Assuming successful validation, we expect to launch this pipeline test by the end of 2025.

In May 2025, we expanded our capabilities in BE through the acquisition of Previse, which provides complementary methylation-based intellectual property and a non-endoscopic cell-collection technology and includes the Esopredict methylation-based risk-stratification test.

We expect these assets to enhance the future development of TissueCypher by enabling the potential incorporation of additional molecular modalities, such as methylation and other genomic markers, to further strengthen the test’s performance.

Beginning in the first quarter of 2026, we also plan to offer the Esopredict test as a supplemental option for cases in which TissueCypher does not produce an actionable result, providing clinicians with an additional molecular tool for risk stratification when primary testing is inconclusive.

In addition, Previse’s sponge-based, swallowable cell-collection device is currently under development and is expected to be introduced in the future, subject to applicable regulatory clearances, and may offer a non-endoscopic method for obtaining esophageal samples in certain patient populations, which could broaden our GI testing portfolio.

In June 2025, we entered into a collaboration and license agreement with SciBase Holding AB (“SciBase”) to develop and commercialize diagnostic tests for dermatologic diseases, beginning with atopic dermatitis.

The collaboration combines our expertise in developing machine learning based algorithms in dermatology with SciBase’s Electrical Impedance Spectroscopy technology.

Under the agreement, we obtained exclusive rights to develop and commercialize tests incorporating SciBase’s technology in North America, while SciBase retains rights in Europe, Switzerland, Japan, and South Korea.

The initial focus of the collaboration is to develop a non-invasive diagnostic test designed to help predict disease flares in patients with atopic dermatitis.

This initiative aligns with our strategic goal of expanding our pipeline beyond dermatologic cancers into inflammatory skin conditions.

TAM is based on estimated patient population assuming average reimbursement rate among all payors.

We expect to continue pursuing pipeline initiatives for tests that will complement and expand our test offerings.

From time to time, we may consider engaging in transactions such as acquisitions of businesses, assets, products or technologies, as well as technology licenses or investments in complementary businesses where we believe strategic opportunities exist.

In April 2022, we acquired AltheaDx, a commercial-stage molecular diagnostics company specializing in the field of PGx testing services, for total consideration of $47.6 million, consisting of $30.5 million in cash and $17.1 million in shares of our common stock, adding the IDgenetix test to our portfolio.

In December 2021, we acquired Cernostics, Inc.

(“Cernostics”) and the TissueCypher platform for $30.7 million in cash consideration.

In May 2021, we acquired Myriad myPath, LLC and MyPath Melanoma test from Myriad Genetics, Inc.

for $32.5 million in cash consideration.

Test Report Volume and Revenue

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60,665 56,265 48,734 37,331 26,500

DecisionDx-UM

1,699 1,674 1,711 1,618 1,395

TissueCypher (3)

39,014 20,956 9,100 2,128 27

DecisionDx-UM

1,769 1,699 1,674 1,711 1,618

IDgenetix (4)

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Net Revenues (in thousands) $ 344,229 $ 332,069 $ 219,788 $ 137,039 $ 94,085

(1) On August 31, 2020, we commercially launched our cutaneous SCC proprietary GEP test for use in patients with one or more risk factors.

(2) Includes MyPath Melanoma and DiffDx®-Melanoma.

On November 2, 2020, we commercially launched our DiffDx-Melanoma test.

(1) We began offering MyPath Melanoma following our acquisition of the Myriad MyPath Laboratory on May 28, 2021.

We offered both MyPath Melanoma and DiffDx-Melanoma under our Diagnostic GEP offering until February 2023 when we suspended the clinical offering of DiffDx-Melanoma.

(2) We began offering AdvanceAD-Tx following our limited access launch in November 2025.

Test reports delivered for the year ended December 31, 2025, was de minimis.

We expect to expand availability throughout 2026.

(3) We began offering the TissueCypher test on December 3, 2021, following our acquisition of Cernostics, Inc.

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We temporarily paused accepting additional orders in July 2023 and resumed accepting new orders in a phased approach in September 2023.

We completed processing of our pre-existing backlog orders in October 2023 and continue to accept new orders as of December 31, 2023.

(4) We began offering the IDgenetix test on April 26, 2022, following our acquisition of AltheaDx.

We completed processing of our pre-existing backlog orders in October 2023 and continue to accept new orders.

(4) We began offering the IDgenetix test on April 26, 2022, following our acquisition of AltheaDx, and discontinued the test in May 2025.

Our Commercial Channel

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Our sales and marketing efforts are primarily focused on the U.S.

skin cancer and gastroenterology markets.

dermatology and gastroenterology markets.

We employ our primary direct sales and marketing strategy to educate clinicians and associated personnel on the clinical and economic benefits of our products.

Our sales approach is highly technical, and our team is trained to articulate the scientific and clinical evidence behind our products and how they influence the clinical care pathway and ultimately improve patient outcomes.

We continuously assess market response in determining further commercial expansions and commercial team structure.

Our sales approach is highly technical, and our team is trained to articulate the scientific and clinical evidence behind our products and how they may influence clinical care pathway decisions and ultimately improve patient outcomes.

We continuously assess market response in determining commercial team structure.

Medical Affairs

We also deploy an experienced medical affairs group to assist education of treating clinicians and key opinion leaders, to identify and engage sites for our sponsored clinical studies and to evaluate collaborative study opportunities.

Our medical affairs strategy complements our sales, marketing and clinical research operations efforts.

We will continue to assess the market needs in determining further expansion of our medical affairs team.

We also deploy an experienced medical affairs group to assist in the education of treating clinicians and key opinion leaders, to assist in identifying and engaging sites for our sponsored clinical studies and to evaluate collaborative study opportunities.

We will continue to assess the market needs in determining medical affairs team structure.

Reimbursement

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We bill third-party payors and patients for the tests we perform.

We have received Medicare coverage for our DecisionDx-Melanoma, DecisionDx-SCC, TissueCypher, MyPath Melanoma, DecisionDx-UM and IDgenetix tests

which meet certain criteria for Medicare and Medicare Advantage beneficiaries.

A “covered life” means a subscriber, or a dependent of a subscriber, who is insured under an insurance carrier’s policy.

We have received Medicare coverage for our DecisionDx-Melanoma, TissueCypher, MyPath Melanoma, DecisionDx-UM and IDgenetix tests which meet certain criteria for Medicare and Medicare Advantage beneficiaries.

DecisionDx-SCC previously received Medicare coverage, which was subsequently impacted by LCD changes finalized in 2025.

The Medicare rates discussed below are prior to giving effect to applicable sequestration in effect from time to time as described in further detail under “—Government Regulation and Product Approval—Healthcare Reform” included in Part 1, Item 1, “Business,” in this Annual Report on Form 10-K.

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Achieving in-network contracts with third-party payors can shorten the time required to receive payments.

Implementing our strategy includes our managed care, reimbursement and medical affairs teams educating third-party payors regarding our strong clinical utility and outcomes data, which we believe validates the value of our products and will persuade more third-party payors to provide value-based reimbursement.

Implementing our strategy includes our managed care, reimbursement and medical affairs teams educating third-party payors regarding our strong clinical utility and outcomes data, which we believe validates the value of our products and will increase implementation of value-based reimbursement with more third-party payors.

We have broad positive policy coverage for our DecisionDx-UM test and have executed contracts with certain commercial payors.

For our other tests, we engage third-party payors for positive coverage and have received positive policy recommendations from many third-party technical assessment review groups.

During the year ended December 31, 2024, we received multiple positive medical policy recommendations from many commercial payors for tests across our product line.

We also received multiple positive medical policies and technology assessments from Laboratory Benefit Management (“LBM”) and Technology Evaluation Companies (“TEC”) organizations.

We anticipate receiving additional positive medical policy recommendations and technology assessments in the future as we continue to develop and expand our evidence portfolio.

During the year ended December 31, 2025, we continued to receive positive coverage and payment decisions on claims across our product lines from many commercial payors.

We anticipate this trend to continue in the future as we develop and expand our evidence portfolio.

Dependence on Third-Party Payors

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Our laboratories are located in Phoenix, Arizona, and Pittsburgh, Pennsylvania.

The MAC responsible for administering claims for laboratory services located in Arizona is Noridian Healthcare Solutions, LLC (“Noridian”).

Noridian has a joint operating agreement with Palmetto GBA MolDX (“Palmetto”) where Palmetto is responsible for reviewing genomic based tests.

The MAC responsible for administering claims for laboratory services located in Arizona is Noridian Healthcare Solutions, LLC (“Noridian”), which has a joint operating agreement with Palmetto GBA MolDX (“Palmetto”) whereby Palmetto oversees the review of genomic based tests.

The MAC responsible for administering claims for laboratory services located in Pennsylvania is Novitas Solutions (“Novitas”).

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The final LCDs did not result in any changes in coverage.

DecisionDx-UM

Palmetto issued a final test-specific LCD for DecisionDx-UM, which became effective in July 2017, and Noridian issued a similar LCD that became effective in September 2017.

We estimate that a significant majority of the DecisionDx-UM tests performed for Medicare patients will meet the coverage criteria.

MyPath Melanoma and DiffDx-Melanoma

MyPath Melanoma was covered under a test-specific LCD policy through Noridian that became effective in June 2019.

Effective August 6, 2023, Palmetto and Noridian issued LCDs that converted the test-specific MyPath Melanoma LCD to a “foundational” LCD and provided coverage for both MyPath Melanoma and DiffDx-Melanoma.

We estimate that a significant majority of the MyPath Melanoma and DiffDx-Melanoma tests performed for Medicare patients will meet the coverage criteria.

DecisionDx‑SCC

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Based upon this review, DecisionDx-SCC test began receiving coverage in April 2022.

On June 9, 2022, Novitas posted a draft oncology biomarker LCD that proposes to rely upon evidentiary reviews sourced from three databases for all oncology biomarker tests:

On June 9, 2022, Novitas posted a draft oncology biomarker LCD that proposed to rely upon evidentiary reviews sourced from three databases for all oncology biomarker tests:

ClinGen, OncoKB and National Comprehensive Cancer Network (“NCCN”).

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On July 26, 2024, Novitas posted a note that it had been granted an extension by CMS.

On January 9, 2025, Novitas finalized the oncology biomarker LCD with an initial effective date of February 23, 2025.

Several days later, Novitas changed the effective date for this LCD, extending the effective date to April 24, 2025.

Should the LCD become effective as is, then we would anticipate not receiving Medicare reimbursement for DecisionDx-SCC tests performed on or after April 24, 2025.

On January 9, 2025, Novitas finalized an oncology biomarker LCD, Genetic Testing for Oncology:

Specific Tests, which also lists DecisionDx-SCC as non-covered;

that LCD became effective on April 24, 2025.

As previously discussed, the Palmetto MolDX program oversees MAAA tests that are reported from our Phoenix laboratory and Noridian is the MAC responsible for administering claims for test reports issued by our Phoenix laboratory.

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After the comment period ended on July 22, 2023, the LCD was finalized on July 4, 2024, with an effective date of August 18, 2024.

In July 2025, we submitted reconsideration requests for both Novitas and MolDX LCDs.

Both Novitas and MolDX subsequently confirmed that our requests were valid.

These confirmations represent an important procedural step in the reconsideration process, but it does not indicate coverage or a favorable review outcome.

MyPath Melanoma and DiffDx-Melanoma

MyPath Melanoma was covered under a test-specific LCD policy through Noridian that became effective in June 2019.

We estimate that a significant majority of the MyPath Melanoma and DiffDx-Melanoma tests performed for Medicare patients will meet the coverage criteria.

DecisionDx-UM

Palmetto issued a final test-specific LCD for DecisionDx-UM, which became effective in July 2017, and Noridian issued a similar LCD that became effective in September 2017.

We estimate that a significant majority of the DecisionDx-UM tests performed for Medicare patients will meet the coverage criteria.

Advanced Diagnostic Laboratory Tests

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Laboratories requesting ADLT status under this criterion are required to submit documentation of premarket approval (“PMA”) or premarket notification from the FDA.

All five of our commercially available proprietary MAAA tests have been reviewed by the CMS and have been granted ADLT status.

All of our commercially available proprietary MAAA tests , other than our recently launched AdvanceAD-Tx test, h ave been reviewed by the CMS and have been granted ADLT status.

ADLT status is not an indication of future coverage.

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For example, the rate for 2025 was set using median private payor rate data from January 1, 2023 to June 30, 2023.

Our rate for 2022, 2023 and 2024 was $7,193 per test.

Our 2025 rate is $7,193 per test.

DecisionDx-UM

On May 17, 2019, CMS determined that DecisionDx-UM meets the criteria for “existing advanced diagnostic laboratory test” status, also referred to as “existing ADLT” status.

Our rate is set annually based upon the median private payor rate for the first half of the second preceding calendar year.

For example, the rate for 2024 was set using median private payor rate data from January 1, 2022 to June 30, 2022.

Our rate for 2022, 2023 and 2024 was $7,776 per test.

Our 2025 rate is $7,776 per test.

MyPath Melanoma

On September 6, 2019, MyPath Melanoma was approved as a “new ADLT”.

Our rate is set annually based upon the median private payor rate for the first half of the second preceding calendar year.

For example, the rate for 2024 was set using median private payor rate data from January 1, 2022 to June 30, 2022.

Our rates for 2022, 2023, and 2024 were $1,950 per test, $1,755 per test, and $1,950 per test, respectively.

Our 2025 rate is $1,950 per test.

DiffDx-Melanoma

In the second quarter of 2022, we obtained a Proprietary Laboratory Analyses (“PLA”) code for DiffDx-Melanoma.

In 2023, DiffDx-Melanoma went through the CMS gapfill process which concluded in September 2023 with CMS posting a final MAC-specific gapfill rate of $1,950 per test.

Our rate for 2024 was $1,950 per test and will continue to be $1,950 per test in 2025.

Diagnostic GEP Offering

Our Diagnostic GEP offering included MyPath Melanoma and DiffDx-Melanoma.

We began offering MyPath Melanoma following our acquisition of the Myriad MyPath Laboratory on May 28, 2021.

In February 2023, we suspended the clinical offering of DiffDx-Melanoma following an internal assessment of the clinical value of DiffDx-Melanoma and MyPath Melanoma, which determined that the technical performance of both tests is comparable.

We continue to offer our MyPath Melanoma test.

Our rate for 2023 through 2025 was $7,193 per test and remains $7,193 per test for 2026.

On March 24, 2022, CMS determined TissueCypher met the criteria for “new ADLT” status.

Since TissueCypher is a protein based spatialomics test, ADLT status exempts TissueCypher from what is called the “14-day rule,” which impacts the billing process for protein based test.

From April 1, 2022 through December 31, 2022, CMS set the initial period rate equal to the original list price of $2,350 per test.

Effective January 1, 2023, the published CLFS rate for TissueCypher was set at $4,950 per test and remained effective through December 31, 2024.

This rate is based on the median private payor rates received between April 1, 2022 and August 31, 2022.

Beginning with 2025, the rate for TissueCypher has been set annually based on the median private payor rate for the first half of the second preceding calendar year.

Our 2025 rate was $4,950 per test based on the median private payor rate data from January 1, 2023 to June 30, 2023 and remains $4,950 per test for 2026.

DecisionDx-SCC

In the second quarter of 2022, following the completion of a requested medical review and pricing of our DecisionDx-SCC test by Novitas, we obtained a PLA code and began receiving reimbursement from Novitas for DecisionDx-SCC at a rate of $3,873 per test.

On June 30, 2023, CMS determined DecisionDx-SCC meets the criteria for “new ADLT” status.

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Effective July 1, 2023 and through March 31, 2024, CMS set the initial period rate equal to the list price of $8,500 per test.

Effective April 1, 2024, we continued receiving reimbursement at a rate of $8,500 per test, set by CMS using median private payor rate data for the period July 1, 2023 and November 30, 2023, and this rate will remain effective through December 31, 2025.

TissueCypher is processed in our Pittsburgh, Pennsylvania laboratory under the Medicare jurisdiction managed by Novitas.

From January 1, 2022 through March 31, 2022, we received payments for claims according to the published Clinical Laboratory Fee Schedule (“CLFS”) rate at $2,513 per test.

On March 24, 2022, CMS determined TissueCypher meets the criteria for “new ADLT” status.

ADLT status exempts TissueCypher from what is called the “14-day rule,” which simplifies the billing process for Medicare patients.

From April 1, 2022 through December 31, 2022, CMS set the initial period rate equal to the original list price of $2,350 per test.

Effective January 1, 2023, the published CLFS rate for TissueCypher was set at $4,950 per test and remained effective through December 31, 2024.

This rate is based on the median private payor rates received between April 1, 2022 and August 31, 2022.

Our 2025 rate will continue to be $4,950 per test based on the median private payor rate data from January 1, 2023 to June 30, 2023.

MyPath Melanoma

On September 6, 2019, MyPath Melanoma was approved as a “new ADLT”.

Our rate is set annually based upon the median private payor rate for the first half of the second preceding calendar year.

For example, the rate for 2025 was set using median private payor rate data from January 1, 2023 to June 30, 2023.

Our rates for 2023, 2024 and 2025 were $1,755, $1,950 and $1,950 per test, respectively.

Our 2026 rate remains $1,950 per test.

DecisionDx-UM

On May 17, 2019, CMS determined that DecisionDx-UM meets the criteria for “existing ADLT” status.

Our rate is set annually based upon the median private payor rate for the first half of the second preceding calendar year.

For example, the rate for 2025 was set using median private payor rate data from January 1, 2023 to June 30, 2023.

Our rate for 2023 through 2025 was $7,776 per test and remains $7,776 per test for 2026.

IDgenetix is currently covered under a Noridian LCD policy and accompanying billing and coding article developed by MolDX.

The Medicare coverage includes depression and the following seven additional mental health conditions beyond major depressive disorder:

schizophrenia, bipolar disorder, anxiety disorders, social phobia, obsessive-compulsive personality disorder, post-traumatic stress disorder and attention deficit hyperactivity disorder.

IDgenetix has historically been billed to Medicare using an unspecified Current Procedural Terminology (“CPT”) code along with the IDgenetix test-specific MolDX Z-code (the “IDgenetix Z-Code”).

We acquired AltheaDx and the IDgenetix test in April 2022 and received Medicare reimbursement at a rate of approximately $1,500 per test.

In February 2023, MolDX notified us that as part of its annual CPT code updates, IDgenetix should shift billing to a different multi-test generic gene sequencing CPT code (the “New CPT Code”) and continue using the IDgenetix Z-Code beginning in March 2023.

The New CPT Code was set at $917 per test while the test went through CMS’s Gapfill pricing process.

We believed the new CPT Code, in conjunction with the IDgenetix Z-Code, did not describe all of the components of the IDgenetix test and thus, was not appropriate for IDgenetix.

We subsequently obtained a test-specific PLA CPT code which became effective October 1, 2023.

In November 2023, CMS posted its final CLFS determination which crosswalks our PLA CPT code to an existing PLA code at a rate of $1,336 per test effective January 1, 2024.

In 2024, we were reimbursed at a rate of $1,336 per test and we will continue to be reimbursed at this rate in 2025.

During 2023, we obtained a test-specific Proprietary Laboratory Analyses (“PLA”) and Current Procedural Terminology (“CPT”) code for IDgenetix which became effective October 1, 2023.

The CLFS rate of $1,336 per test was effective January 1, 2024.

Our reimbursement rate for 2024 was $1,336 per test and remained at $1,336 per test in the first quarter of 2025.

Our IDgenetix test was discontinued in May 2025.

We are focused on improving health through innovative tests that guide patient care.

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This involves the ability to design and efficiently conduct the right clinical studies at the right time;

• Research and development investments to document the quality, quantity, consistency and strength of the clinical validity data, the impact our products have on clinical use, and demonstration of net health outcome improvement that reduce health system costs;

• R&D investments to document the quality, quantity, consistency and strength of the clinical validity data, the impact our products have on clinical use, and demonstration of net health outcome improvement that reduce health system costs;

• Maintaining a strong reputation with the treating clinician by providing consistent, transparent and clinically relevant information that will improve the appropriate management of their patients;

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Today, our principal competition for DecisionDx-Melanoma is existing traditional clinical and pathology staging criteria.

While some clinical and pathology criteria have changed over time, this approach has been the standard of

care in the United States for many years, and clinicians may be unwilling to accept the validity of the published data and adopt our test until it has become incorporated into national guidelines.

In addition, we currently face, or may face, competition from a limited number of companies who are working in this disease space, such as SkylineDx/Tempus/Quest, AMLo/Avero and Neracare.

In the future, we may face additional competitors.

We are unaware of late-stage work being performed to develop and validate a product that would compete with DecisionDx-SCC.

We believe that the current primary competitor for DecisionDx-SCC is existing traditional clinical and pathology staging criteria.

While some clinical and pathology criteria have changed over time, this approach has been the standard of care in the U.S.

for many years, and clinicians may be unwilling to accept the validity of the published data and adopt our test until it has become incorporated into national guidelines.

In addition, we currently face, or may face, competition from a limited number of companies who are working in this disease space, such as SkylineDx.

In the future, we may face additional competitors.

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In the future, this assessment may include the use of immunohistochemical evaluation of individual protein biomarkers as an aid to pathology.

While some clinical and pathology criteria have changed over time, this approach has been the standard of care in the United States for many years, and physicians may be unwilling to accept the validity of the published data and adopt our test until this has become incorporated into clinical guideline recommendations from gastrointestinal clinical societies, or other national guidelines.

In addition, we currently face, or may face, competition from companies such as Previse, Interpace Diagnostics, Lucid Diagnostics and other companies.

Other companies actively engaged in GERD screening to diagnose BE may also look to develop prognostic tests for patients diagnosed with BE, and these could compete with TissueCypher in the future.

While some clinical and pathology criteria have evolved over time, this approach has been the standard of care in the U.S.

for many years, and physicians may be unwilling to accept the validity of the published data and adopt our test until this has become incorporated into clinical guideline recommendations from gastrointestinal clinical societies, or other national guidelines.

In addition, we may face competition from companies such as Interpace Diagnostics and other companies.

Other companies actively engaged in GERD screening to diagnose BE, such as Lucid Diagnostics and other companies, may also look to develop prognostic tests for patients diagnosed with BE, and these could compete with TissueCypher in the future.

In 2025, we acquired Previse, whose technology complements our TissueCypher test, expanding our offerings within the gastrointestinal vertical and market position.

We may face additional competitors in the future.

We are unaware of late-stage work being performed to develop and validate a product that would compete with DecisionDx-SCC.

We believe that the current primary competitor for DecisionDx-SCC is existing traditional clinical and pathology staging criteria.

In the future, we may face additional competitors.

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In the future, we may face additional competitors.

With respect to IDgenetix, our competition arises from other parties using the same or similar methods as well as alternative methods of PGx testing.

IDgenetix competes with Myriad Genetics’s GeneSight test, Genomind’s PGx test, and tests from numerous other commercial and academic laboratories.

Laboratory Operations

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All of our facilities are Clinical Laboratory Improvement Amendments of 1988 (“CLIA”) certified, College of American Pathologists (“CAP”) accredited labs.

Additionally, all of our laboratories passed inspection by New York State Department of Health Clinical Laboratory Evaluation Program (“NYS CLEP”) with each of our proprietary tests approved by the New York State Department of Health (“NYSDOH”).

Additionally, one lab in the Phoenix and the Pittsburgh laboratories are approved labs by New York State Department of Health Clinical Laboratory Evaluation Program (“NYS CLEP”) with each of our proprietary tests, except AdvanceAD-Tx, approved by the New York State Department of Health (“NYSDOH”).

We manage these laboratories to produce the volume of testing required to cover our portfolio of products while maintaining efficiencies, redundant capabilities, and business continuity.

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Intellectual Property

Our core technology for our products is related to methods and devices for analysis of genetic expression.

Our core technology for our products is related to methods and devices for analysis of genetic and proteinomic expression.

Using this technology, we are able to provide a more accurate prediction of a patient’s metastatic risk as compared to other methods.

We have secured and continue to pursue intellectual property rights globally, including through patent protection covering analysis of metastasis in CM, the treatment of SCC, BE and gastroenterology, and PGx for mental illness.

We have secured and continue to pursue intellectual property rights in our core U.S.

market and select global countries, including through patent protection covering all of our proprietary tests.

We also rely on trademarks, trade secrets, know-how, continuing technological innovation and potential in-licensing opportunities to develop and maintain our proprietary position.

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Methods of diagnosing and treating patients with SCC 6 21 27

Determining prognosis and treatment based on clinical-pathologic factors and continuous multigene-expression profile scores 1 — 1

Diagnosing and treating AD and/or psoriasis 3 1 4

Method and kit for isolating and sequencing nucleic acid from skin samples — 1 1

Diagnosing and treating UM 1 — 1

Genes and gene signatures for diagnosis and treatment of melanoma 6 29 35

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Individual patents extend for varying periods depending on the date of filing of the patent application or the date of patent issuance and the legal term of patents in the countries in which they are obtained.

Generally, patents issued for regularly filed applications in the United States are granted a term of 20 years from the earliest effective non-provisional filing date.

In addition, in certain instances, a patent term can be extended to recapture a period due to delay by the United States Patent and Trademark Office (the “USPTO”) in issuing the patent as well as a portion of the term effectively lost as a result of the FDA regulatory review period.

Generally, patents issued for regularly filed applications in the U.S.

are granted a term of 20 years from the earliest effective non-provisional filing date.

In addition, in certain instances, a patent term can be extended to recapture a period due to delay by the U.S.

Patent and Trademark Office (the “USPTO”) in issuing the patent as well as a portion of the term effectively lost as a result of the FDA regulatory review period.

However, as to the FDA component, the restoration period cannot be longer than five years and the total patent term including the restoration period must not exceed 14 years following FDA approval.

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To renew our CLIA certificate, we are subject to survey and inspection every two years to assess compliance with program standards.

Because our Phoenix, Arizona laboratory is a CAP-accredited laboratory, CMS may defer the survey and inspection to those conducted by CAP.

Because all of our laboratories are CAP-accredited, CMS may defer the survey and inspection to those conducted by CAP.

We may also be subject to additional unannounced inspections.

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We currently provide laboratory services in all 50 states.

Additionally, we maintain licenses in New York, California, Maryland,

Pennsylvania and Rhode Island which require specific licensure for out-of-state laboratories that accept specimens from those states.

Additionally, we maintain licenses in New York, California, Maryland, Pennsylvania and Rhode Island which require specific licensure for out-of-state laboratories that accept specimens from those states.

Because we may receive specimens from residents of the state of New York, we sought and have received approval from NYSDOH.

All of our laboratories are required to be certified by NYSDOH, have a lab director with a specific certificate of qualification and are subject to biennial New York inspections to ensure the lab is compliant with New York licensing standards.

In addition to the NYSDOH lab approval both the Phoenix and Pittsburgh laboratories are both required to have a lab director with a specific certificate of qualification and are subject to biennial New York inspections to ensure the lab is compliant with New York licensing standards.

We also maintain processes and controls to ensure that specimens originating from New York are tested only in these NYSDOH-certified laboratories and not in our other laboratory locations.

New York regulations also mandate proficiency testing for laboratories licensed under New York law, regardless of whether such laboratories are located in New York.

If a laboratory is out of compliance with New York statutory or regulatory standards, NYSDOH may suspend, limit, revoke or annul the laboratory’s New York license, censure the holder of the license, or assess civil money penalties.

All of our laboratories are inspected and our proprietary tests are approved via NYSDOH.

Our Phoenix and Pittsburgh laboratories that are both licensed by NYSDOH, and our commercialized proprietary tests, excluding our recently launched AdvanceAD-Tx test, have been approved by NYSDOH.

Federal Oversight of Laboratory Developed Tests

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In addition, the Federal Food, Drug and Cosmetic Act (the “FD&C Act”) defines a medical device to include any instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory, intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, and which does not achieve its primary intended purposes via chemical action or metabolism.

Our in vitro testing products are considered by the FDA to be subject to regulation as medical devices.

Among other things, pursuant to the FD&C Act and its implementing regulations, the FDA regulates the research, testing, manufacturing, safety, labeling, storage, recordkeeping, pre-market review and marketing authorization, product, marketing and promotion, and sales and distribution of medical devices in the United States to ensure that medical devices distributed domestically are reasonably safe and effective for their intended uses.

Some of our in vitro testing products are intended for clinical or diagnostic uses, such as the DecisionDx-Melanoma test, which is considered by the FDA to be subject to regulation as a medical device and has been granted Breakthrough Device designation by the FDA.

to ensure that medical devices distributed domestically are reasonably safe and effective for their intended uses.

Although the FDA believes it has statutory authority to assure that laboratory developed tests are reasonably safe and effective for their intended uses, the FDA has generally exercised its enforcement discretion and not enforced applicable regulations with respect to in vitro diagnostics (“IVDs”) that are intended for clinical use and are designed, manufactured, and used within a single laboratory that is certified under CLIA and meets the regulatory requirements under CLIA to perform high-complexity testing.

These tests are referred to as LDTs.

On May 6, 2024, the FDA published a final rule on the regulation of LDTs which amends the FDA's regulations to make it explicit that LDTs are IVDs and regulated as devices under the FD&C Act.

Under this final rule, the FDA issued a policy to phaseout, over the course of four years, its general enforcement discretion approach to LDTs and also issued targeted enforcement discretion policies for certain categories of LDTs, including LDTs marketed as of the date of publication of the final rule on May 6, 2024, as well as LDTs that have received approval from the New York State Department of Health.

Specifically, the FDA intends to exercise enforcement discretion and not enforce certain medical device requirements (including the requirements for premarket review and marketing authorization and compliance with certain elements of the Quality System Regulation (“QSR”) with respect to LDTs that were marketed as of the date of the final rule’s publication, although such products must still comply with certain other FDA requirements, including registration and listing, portions of the QSR, medical device reporting, labeling, and corrections and removals reporting.

However, where these tests are modified in certain ways from the version of the test marketed as of the final rule’s publication date, this enforcement discretion policy will no longer apply, and the FDA intends to enforce all applicable FDA requirements (including premarket review and marketing authorization requirements) consistent with the phaseout policy.

In addition, for LDTs that receive approval from NYSDOH, FDA intends to not enforce premarket review and marketing authorization requirements when these requirements are phased in more generally at either three and a half years (for high-risk LDTs) or four years (for low-moderate risk LDTs) following the date of publication of the final rule.

Our proprietary tests, outlined above, are all NYSDOH approved.

We believe this final ruling will have no material impact on our existing test offerings given all of our tests were marketed before May 6, 2024.

On May 6, 2024, the FDA published a final rule on the regulation of Laboratory Developed Tests (“LDTs”) which amended the FDA’s regulations to make explicit that LDT’s are devices under the FD&C Act.

However, on March 31, 2025, the United States District Court for the Eastern District of Texas vacated the FDA’s LDT final rule.

government did not appeal the decision, and the FDA rescinded the rule on September 19, 2025.

Accordingly, the FDA’s phased enforcement approach and related requirements are no longer in effect.

Our proprietary tests, which were first marketed prior to May 6, 2024, remain approved by and under the oversight of the NYSDOH, and we continue to believe that changes in FDA’s regulatory approach to LDTs will have no material impact on our existing test offerings.

Separately, Congress has considered a number of proposals in the last several years, which, if enacted, would subject LDTs to certain regulatory requirements.

For example, in recent years, Congress has worked on legislation to create a novel regulatory framework governing a new category of FDA-regulated products, referred to as in vitro clinical tests (“IVCTs”), which would govern LDTs and would be separate and distinct from existing medical device regulatory framework.

For example, in March 2023, the Verifying Accurate Leading-edge IVCT Development Act of 2023 (the “VALID Act”) was introduced.

The bill would establish a risk-based approach to imposing requirements related to premarket review, quality systems, and labeling requirements on all IVCTs, including LDTs, but would

grandfather certain LDTs marketed before the effective date of the bill and exempt them from certain requirements.

Depending on the approach adopted under any potential legislation, certain LDTs (likely those of higher risk) may be required to undergo some form of premarket review of LDTs as IVCTs, potentially with a transition period for compliance and a grandfathering provision.

In July 2025, the FDA granted Breakthrough Device designation to our DecisionDx-Melanoma test.

We believe this designation highlights the test’s potential to improve melanoma care through individualized prognostic insights.

The Breakthrough Device designation is intended to expedite the development and review of certain medical devices that may offer more effective diagnosis or treatment of life-threatening conditions.

Medical Device Regulatory Framework

Although we currently market our proprietary testing products as LDTs, which are currently subject to enforcement discretion, we could be subject to FDA compliance obligations in the future.

Unless an exemption applies under the FDA's targeted enforcement discretion policies for certain categories of LDTs, each new or significantly modified medical device we seek to commercially distribute in the United States will require either a premarket notification to the FDA requesting authorization for commercial distribution under Section 510(k) of the FD&C Act, also referred to as a 510(k) clearance, de novo classification under Section 513(f)(2) of the FD&C Act, or approval of a PMA application under Section 515(c).

Unless an exemption applies under the FDA’s targeted enforcement discretion policies for certain categories of LDTs, each new or significantly modified medical device we seek to commercially distribute in the U.S.

will require either a premarket notification to the FDA requesting authorization for commercial distribution under Section 510(k) of the FD&C Act, also referred to as a 510(k) clearance, de novo classification under Section 513(f)(2) of the FD&C Act, or approval of a PMA application under Section 515(c).

These premarket review processes can be resource intensive, expensive, and lengthy, and require payment of significant user fees.

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The Investigational Device Process

In the United States, all clinical investigations of devices to determine safety and effectiveness must be conducted in accordance with the FDA’s investigational device exemption (“IDE”) regulations.

In the U.S., all clinical investigations of devices to determine safety and effectiveness must be conducted in accordance with the FDA’s investigational device exemption (“IDE”) regulations.

If the device presents a “significant risk” to human health, as defined by the FDA, the sponsor must submit an IDE application to the FDA and obtain IDE approval prior to commencing the human clinical trials.

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Generally, clinical trials for a significant risk device may begin once the IDE application is approved by the FDA and the study protocol and informed consent are approved by appropriate IRBs at the clinical trial sites.

Submission of an IDE will not necessarily result in the ability to commence clinical trials, and although the FDA’s approval of an IDE allows clinical testing to go forward for a specified number

of subjects, it does not bind the FDA to accept the results of the trial as sufficient to prove the product’s safety and efficacy, even if the trial meets its intended success criteria.

Submission of an IDE will not necessarily result in the ability to commence clinical trials, and although the FDA’s approval of an IDE allows clinical testing to go forward for a specified number of subjects, it does not bind the FDA to accept the results of the trial as sufficient to prove the product’s safety and efficacy, even if the trial meets its intended success criteria.

The IDE regulations that govern investigational device labeling, prohibit promotion and specify an array of recordkeeping, reporting and monitoring responsibilities of study sponsors and study investigators.

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A manufacturer can submit a request for de novo classification if the manufacturer is unable to identify a predicate device and the new device or new use of the device presents a moderate or low risk.

Under the de novo classification pathway, FDA may reclassify the device from Class III to class II or Class I, as appropriate.

Under the de novo classification pathway, the FDA may reclassify the device from Class III to Class II or Class I, as appropriate.

If the manufacturer seeks reclassification to Class II, the reclassification request must include proposed special controls that provide reasonable assurance of safety and effectiveness of the device.

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If it is not, the agency will refuse to file the PMA.

it is, the FDA will accept the application for filing and begin the review.

If it is, the FDA will accept the application for filing and begin the review.

The FDA has 180 days to review a filed PMA application, however, in practice the application review process often exceeds this deadline.

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The law includes a limited number of exceptions, some of which closely align with corresponding AKS exceptions and safe harbors, and others that materially differ.

Currently, there is no regulation interpreting or implementing EKRA, nor any guidance released by a federal agency regarding the scope of EKRA.

The full scope and interpretation of EKRA remain unclear.

Other Federal and State Healthcare Laws

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Therefore, most of these tests have neither undergone premarket review nor received FDA clearance, authorization or approval for marketing.

We will continue to monitor the FDA’s position as changes in this respect could materially affect our business, prospects, results of operations or financial condition.

We will continue to monitor the FDA’s position.

State equivalents of each of the above federal laws, such as anti-kickback and false claims laws, may impose similar or more prohibitive restrictions, and may apply to items or services reimbursed by non-governmental third-party payors, including private insurers.

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Other countries, including the United Kingdom (“UK”) and other OECD Anti-Bribery Convention members, have similar anti-corruption regulations, such as the United Kingdom Anti-Bribery Act.

When marketing our testing products outside of the United States, we may be subject to foreign regulatory requirements governing human clinical testing, prohibitions on the import of tissue necessary for us to perform our testing products or restrictions on the export of tissue imposed by countries outside of the United States or the import of tissue into the United States, and marketing approval.

These requirements vary by jurisdiction, differ from those in the United States and may in some cases require us to perform additional pre-clinical or clinical testing.

In many countries outside of the United States, coverage, pricing and reimbursement approvals are also required.

When marketing our testing products outside of the U.S., we may be subject to foreign regulatory requirements governing human clinical testing, prohibitions on the import of tissue necessary for us to perform our testing products or restrictions on the export of tissue imposed by countries outside of the U.S.

or the import of tissue into the U.S., and marketing approval.

These requirements vary by jurisdiction, differ from those in the U.S.

and may in some cases require us to perform additional pre-clinical or clinical testing.

In many countries outside of the U.S., coverage, pricing and reimbursement approvals are also required.

Privacy and Security Laws

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The HIPAA privacy regulations cover the use and disclosure of PHI by covered entities and business associates, which are defined to include subcontractors that create, receive, maintain, or transmit PHI on behalf of a covered entity, as well as their covered subcontractors.

They also set forth certain rights that an individual has with respect to

his or her PHI maintained by a covered entity, including the right to access or amend certain records containing PHI, or to request restrictions on the use or disclosure of PHI.

They also set forth certain rights that an individual has with respect to his or her PHI maintained by a covered entity, including the right to access or amend certain records containing PHI, or to request restrictions on the use or disclosure of PHI.

The HIPAA security regulations establish requirements for safeguarding the confidentiality, integrity, and availability of PHI that is electronically transmitted or electronically stored.

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HIPAA and HITECH impose civil and criminal penalties against covered entities and business associates for noncompliance with privacy and security requirements.

Further, various states, such as California and Massachusetts, have implemented similar privacy laws and regulations that impose restrictive requirements regulating the use and disclosure of health information and other personally identifiable information (“PII”).

Numerous other federal, state and foreign laws, including consumer protection laws and regulations, govern the collection, dissemination, use, access to, confidentiality and security of personal information.

Federal, State and Foreign Privacy and Security Laws

Federal, state, local and foreign governments have enacted numerous data privacy and security laws, including data breach notification laws, data protection laws (e.g.

European Union’s General Data Protection Regulation 2016/679), personal data privacy laws, health information privacy laws (e.g., Washington’s My Health My Data Act), consumer protection laws (e.g., Section 5 of the Federal Trade Commission Act), and other similar laws (e.g., wiretapping laws).

Numerous privacy laws impose certain obligations on covered businesses, including providing specific disclosures in privacy notices and affording residents with certain rights concerning their personal data.

As applicable, such rights may include the right to access, correct, or delete certain personal data, and to opt-out of certain data processing activities, such as targeted advertising, profiling, and automated decision-making.

The exercise of these rights may impact our business and ability to provide our products and services.

Certain laws also impose stricter requirements for processing certain personal data, including sensitive information, such as conducting data privacy impact assessments.

Certain of these laws allow for statutory fines for noncompliance.

These laws further complicate compliance efforts and increase legal risk and compliance costs for us and the third parties with whom we work.

Reimbursement for Clinical Laboratory Services

We generate revenue on our products from several sources, including third-party payors, laboratory services intermediaries, and self-paying individuals.

Depending on the billing arrangement and applicable law, we must bill various third-party payors, such as insurance companies, Medicare, Medicaid, and patients, all of which have different billing requirements.

Depending on the billing arrangement and applicable law, we must bill various third-party payors, such as insurance companies, Medicare and Medicaid, all of which have different billing requirements.

Compliance with applicable laws and regulations as well as internal compliance policies and procedures adds further complexity to the billing process.

CMS establishes new procedures and continuously evaluates and implements changes to the reimbursement process for billing the Medicare program.

To receive reimbursement from third-party payors, we bill our tests using a variety of CPT codes, as defined by the AMA CPT Editorial Panel.

For those genetic tests we conduct that do not have a dedicated CPT code, tests may be billed under a miscellaneous code for an unlisted molecular pathology procedure.

Because these miscellaneous codes do not describe a specific service, the third-party payor claim may need to be examined to determine the service that was provided, whether the service was appropriate and medically necessary and whether payment should be rendered.

This process can require a letter of medical necessity and other types of medical documentation from the ordering physician and it can result in a delay in processing the claim, a lower reimbursement amount, or denial of the claim.

With the evolution of genetic testing, we have seen individual third-party payors’ medical coverage policies around the CPT codes we bill and their associated payment rates change over time, resulting in changes to our reimbursement.

To receive reimbursement from third-party payors, we bill our tests using a variety of CPT codes and PLA codes, as defined by the American Medical Association (“AMA”).

For those genetic tests we conduct that do not have a dedicated CPT or PLA code, tests may be billed under a non-specific miscellaneous CPT code.

Because these miscellaneous codes do not describe a specific service, the claim may need to be examined by a third-party payor to determine what service was provided, whether the service was appropriate and medically necessary and whether payment should be rendered.

This process may require additional medical record documentation from the ordering physician and could result in a delay in processing the claim, a lower reimbursement amount, or denial of the claim.

With the evolution of genetic testing, we have seen individual third-party payors’ medical coverage policies around the CPT and PLA codes we bill and their associated payment rates change over time, resulting in changes to our reimbursement.

We believe all of our products provide significant clinical value and reduction in downstream healthcare spend, as evidenced in research studies and clinical publications, which we believe will continue to support and drive third-party payor reimbursement.

Under Medicare, payment for products like ours is generally made under the CLFS with payment amounts assigned to specific procedure billing codes.

In April 2014, Congress passed the Protecting Access to Medicare Act (“PAMA”), which included substantial changes to the way in which clinical laboratory services will be paid under Medicare.

Under PAMA, certain laboratories were required to report to CMS private payor payment rates and volumes for their

CMS uses this data to calculate a weighted median payment rate for each test, which will be used to establish revised Medicare CLFS reimbursement rates for the test.

In April 2014, Congress passed the Protecting Access to Medicare Act (“PAMA”), which included substantial changes to the way in which clinical diagnostic laboratory tests (“CDLTs”) are paid under Medicare.

Under PAMA, certain laboratories are required to report to CMS private payor payment rates and volumes for their tests.

CMS uses this data to calculate a weighted median payment rate for each test, which is used to establish revised Medicare CLFS reimbursement rates for the test.

Laboratories that fail to report the required payment information may be subject to substantial civil penalties.

PAMA also established a category for ADLTs and specific payment methodologies for qualifying tests.

Similar to CDLTs, laboratories offering ADLTs are required to report to CMS private payor payment rates and volumes for their tests and CMS uses this data to calculate a weighted median payment rate for each test.

The difference is that laboratories are required to report ADLT private payer data annually to CMS and the CLFS reimbursement rates are updated annually for the test.

On February 3, 2026, the Consolidated Appropriations Act of 2026 was enacted which, among other things, delayed the impositions of Medicare CLFS cuts until 2027 and updated PAMA reporting timelines and data requirements for CDLTs that aren’t ADLTs.

We bill Medicare for our products, and therefore we are subject to reporting requirements under PAMA.

See “Reimbursement—Government Payors” above for additional information.

PAMA also authorizes the adoption of new, temporary billing codes and/or unique test identifiers for FDA-cleared or approved tests as well as ADLTs.

The AMA’s CPT Editorial Panel now issues PLA codes in support of this section of PAMA.

These PLA codes may be requested by a clinical laboratory or manufacturer to specifically identify their test.

If approved, the codes are issued by the AMA on a quarterly basis.

Our DecisionDx-UM test was granted a Category I MAAA CPT code and was effective January 1, 2020.

Our DecisionDx-Melanoma test was granted a Category I MAAA CPT code and was effective January 1, 2021.

Our MyPath Melanoma test was granted a PLA CPT code prior to our May 2021 acquisition of the Myriad MyPath Laboratory.

Our TissueCypher test was granted a PLA CPT code prior to our December 2021 acquisition of Cernostics .

Our DecisionDx-SCC and DiffDx-Melanoma tests were granted PLA CPT codes effective April 1, 2022.

Our IDgenetix test was granted a new PLA CPT code and was effective October 1, 2023.

Five of our tests have been granted ADLT status by CMS:

DecisionDx-Melanoma, TissueCypher, DecisionDx-SCC, MyPath Melanoma and DecisionDx-UM.

The CLFS rate for these tests is determined by the ADLT rules under PAMA.

The CLFS rates for our tests AdvanceAD-Tx and Esopredict are determined by the CDLT rules under PAMA.

Healthcare Reform

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Further, there have been a number of health reform measures by the previous administration that have impacted the ACA.

For example, on August 16, 2022, the Inflation Reduction Act of 2022 (“IRA”) was signed into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.

It is possible that the ACA will be subject to judicial or Congressional challenges in the future.

It is unclear how any forthcoming healthcare reform measures of the Trump administration will impact the ACA and our business.

For example, on July 4, 2025, the One Big Beautiful Bill Act (the “OBBBA”), was signed into law, which narrowed access to ACA marketplace exchange enrollment and declined to extend the ACA enhanced advanced premium tax credits that expired at the end of 2025, which, among other provisions in the law, are anticipated to reduce the number of Americans with health insurance.

The OBBBA also is expected to reduce Medicaid spending and enrollment by implementing work requirements for some beneficiaries, capping state-directed payments, reducing federal funding, and limiting provider taxes used to fund the program.

Congress is considering proposed legislation intended to further reduce healthcare costs with alternatives to replace the expired ACA subsidies.

It is unclear how these and other healthcare reform measures of the Trump administration will impact the ACA and our business.

On August 2, 2011, the Budget Control Act of 2011 was signed into law, which, among other things, reduced Medicare payments to providers by 2% per fiscal year, effective on April 1, 2013 and, due to subsequent legislative amendments to the statute including the Infrastructure Investment and Jobs Act, will remain in effect through 2032, unless additional Congressional action is taken.

We anticipate there will continue to be proposals by legislators at both the federal and state levels, regulators and commercial third-party payors to reduce costs while expanding individual healthcare benefits.

The current administration is pursuing policies to reduce regulations and expenditures across government agencies including at HHS, the FDA, CMS and related agencies.

These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose policy changes that create additional uncertainty for our business.

Recent actions, for example, include directing agencies to reduce agency workforce and cut programs.

Additionally, the current administration recently called on Congress to enact “The Great Healthcare Plan,” to lower government subsidies to private insurance companies and increase healthcare price transparency, among other things.

Additionally, in June 2024, in Loper Bright Enterprises v.

Raimondo, the U.S.

Supreme Court greatly reduced judicial deference to regulatory agencies, which could increase successful legal challenges to federal regulations affecting our operations.

We expect that additional state, federal, and foreign healthcare reform measures will be adopted in the future.

We further anticipate there will continue to be proposals by legislators at both the federal and state levels, regulators and commercial third-party payors to reduce costs while expanding individual healthcare benefits.

Certain of these changes or delays in implementation of certain measures due to changes in administrations could impose additional limitations on the prices we will be able to charge for our products, the coverage of or the amounts of reimbursement available for our products from third-party payors, including government and commercial payors.

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We face competition for experienced, qualified personnel in our industry, particularly for highly skilled scientists, laboratory technicians and salespeople versed in diagnostic testing services.

The tables below provide information on the distribution of our employees by functional area and by location as of December 31, 2024:

Number of Employees

Laboratory Testing Operations 247

Research & Development 109

Sales & Marketing 218

Administrative & General 187

Total as of December 31, 2024

Number of Employees

Friendswood, Texas 102

Phoenix, Arizona 202

Pittsburgh, Pennsylvania 120

Home-based 337

Total as of December 31, 2024

Our employees are not represented by labor unions or covered by collective bargaining agreements.

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We value the unique perspective our employees bring to the organization and encourage open channels of communication.

In June 2024, we conducted our fourth annual employee engagement survey to understand what was working well at Castle and what opportunities we had for improvement.

We received feedback from over 95% of our employees and achieved an engagement score of 85%, meaning that 85% of our employees are engaged or enthusiastically engaged in the culture at Castle.

Our engagement score was higher than the healthcare benchmark average of 70% for other healthcare companies who conducted the same employee engagement survey in 2024.

In June 2025, we conducted our annual employee engagement survey to understand what was working well at Castle Biosciences and what opportunities we had for improvement.

We received feedback from over 94% of our employees and achieved an engagement score of 83%, meaning that 83% of our employees are engaged or enthusiastically engaged in the culture at Castle Biosciences.

Our engagement score was 11% higher than the healthcare benchmark average for other healthcare companies who conducted the same employee engagement survey in 2025.

Compensation, Benefits and Professional Development

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• an annual bonus opportunity;

• equity compensation, including stock options and/or restricted stock units (“RSUs”) and an employee stock purchase plan;

• equity compensation, including stock options and/or restricted stock units and an employee stock purchase plan;

• medical, dental and vision plans;

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We were incorporated in Delaware in September 2007.

Our principal executive offices are located at 505 S.

Friendswood Drive, Suite 401, Friendswood, Texas 77456 and our telephone number is (866) 788-9007.

corporate website address is www.CastleBiosciences.com.

Our principal executive offices are currently located at 1500 W.

Parkwood Ave, Suite 400, Friendswood, Texas 77546 and our telephone number is (866) 788-9007.

Our corporate website address is www.CastleBiosciences.com.

Information contained on, or accessible through, our website is not considered part of this Annual Report on Form 10-K or our other filings with the SEC.

Our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and any amendments to such reports filed or furnished pursuant to Section 13(a) and 15(d) of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) are available free of charge on our website as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC.

We may use our website as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation Fair Disclosure promulgated by the U.S.

Securities and Exchange Commission.

We may use our website as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation Fair Disclosure promulgated by the SEC.

These disclosures will be included on our website under the “Company—Investors” section.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business