New Data at DDW 2026 Show TissueCypher® Testing Improves Risk Stratification and Drives Risk-Aligned Management in Barrett's Esophagus

Rhea-AI Summary

Castle Biosciences (NASDAQ:CSTL) announced Mayo Clinic data presented at DDW 2026 showing the TissueCypher test refines risk stratification and informs risk-aligned surveillance for Barrett's esophagus.

In multicenter cohorts, physicians changed surveillance intervals in 55% of patients and aligned recommendations with TissueCypher risk in 79%; TissueCypher classified 84% as low risk versus 38% by a clinical model (κ=0.04).

Positive

• Physicians modified surveillance intervals for 55% of tested patients
• Physician recommendations aligned with TissueCypher risk in 79% of cases
• TissueCypher identified 92% of non-dysplastic patients as intermediate/high risk for shortened surveillance
• TissueCypher classified 84% of patients as low risk versus 38% by PIB

Negative

• Minimal concordance with PIB clinical model (κ=0.04) raises discordance concerns
• Findings are from poster presentations and observational cohorts, not randomized trials

Key Figures

Surveillance modified: 55% of patients Risk-aligned intervals: 79% of cases Shorter intervals high-risk: 93% of intermediate/high risk +5 more

8 metrics

Surveillance modified 55% of patients Patients whose surveillance intervals changed after TissueCypher testing

Risk-aligned intervals 79% of cases Physician surveillance intervals aligned with TissueCypher risk classification

Shorter intervals high-risk 93% of intermediate/high risk Intermediate/high-risk patients recommended shorter surveillance intervals

Shorter intervals NDBE 92% of intermediate/high risk Non-dysplastic BE patients reclassified intermediate/high risk given shorter intervals

Low-risk by TissueCypher 84% vs 38% Patients classified low risk by TissueCypher vs PIB clinical model

Concordance with PIB κ=0.04 Minimal concordance between TissueCypher and PIB risk classifications

Conference dates May 2–5, 2026 Digestive Disease Week 2026 meeting where data are presented

Risk horizon Five-year risk TissueCypher predicts five-year progression risk to HGD or EAC

Market Reality Check

Price: $24.85 Vol: Volume 128,565 is below 2...

low vol

$24.85 Last Close

Volume Volume 128,565 is below 20-day average 287,994 (relative volume 0.45). low

Technical Price 24.85 is trading below 200-day MA at 28.42, and 43.88% below 52-week high.

Peers on Argus

CSTL gained 1.31% with key peers also positive: FLGT 0.64%, CDNA 2.53%, MYGN 2.1...

CSTL gained 1.31% with key peers also positive: FLGT 0.64%, CDNA 2.53%, MYGN 2.13%, PSNL 4.33%, NEO 0.64%, indicating broader strength in Diagnostics & Research.

Common Catalyst Some peer momentum is tied to product and partnership updates within diagnostics.

Historical Context

5 past events · Latest: Apr 21 (Positive)

Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Apr 21	Clinical data update	Positive	-2.3%	New DecisionDx-Melanoma data on recurrence risk and poor outcomes.
Apr 15	Earnings timing	Neutral	+1.0%	Announcement of Q1 2026 results release and webcast schedule.
Apr 10	Corporate recognition	Positive	-1.3%	Fifth consecutive USA TODAY Top Workplaces award recognition.
Mar 27	Clinical data update	Positive	-4.7%	AAD 2026 data showing DecisionDx-Melanoma improves five-year risk prediction.
Mar 13	Clinical study results	Positive	+0.9%	Future Oncology study showing i31-SLNB outperforms staging criteria.

Pattern Detected

Recent positive clinical and product data have often seen mixed-to-negative immediate price reactions, while routine items like earnings dates showed modest gains.

Recent Company History

Over the past few months, Castle Biosciences has repeatedly highlighted data demonstrating improved risk prediction and personalized management, particularly for melanoma using DecisionDx-Melanoma, with SEER-linked and prospective multicenter results reported on Mar 13 and Mar 27, 2026. Additional data-focused news on Apr 21 and a workplace award on Apr 10 reinforced clinical and corporate strengths. Despite generally positive scientific narratives, price reactions were often negative or modest, underscoring a pattern where strong data alone did not consistently translate into immediate upside.

Market Pulse Summary

This announcement underscores new DDW 2026 data showing TissueCypher-driven risk stratification chan...

Analysis

This announcement underscores new DDW 2026 data showing TissueCypher-driven risk stratification changed surveillance in 55% of Barrett’s esophagus patients and aligned recommendations with risk classification in 79%, with high-risk groups frequently shifted to shorter follow-up. Recent history shows multiple positive data releases across Castle’s portfolio, yet price reactions were often muted or negative. Investors may focus on how effectively such evidence translates into broader clinical adoption and revenue alongside ongoing insider selling and the share price trading below its 200-day MA.

Key Terms

barrett's esophagus, high-grade dysplasia, esophageal adenocarcinoma, molecular risk stratification, +2 more

6 terms

barrett's esophagus medical

"management decisions for patients with Barrett's esophagus (BE). TissueCypher is"

A condition where the cells lining the lower esophagus change after repeated acid injury from stomach reflux, creating tissue that looks and behaves differently than normal. It matters to investors because this change raises the long-term risk of esophageal cancer and therefore drives demand for diagnostic tests, monitoring programs, medical procedures and drug development; like spotting damaged wallpaper that signals the need for repairs, its detection can affect healthcare costs and market opportunities.

high-grade dysplasia medical

"five-year risk of progression to high-grade dysplasia (HGD) or esophageal"

High-grade dysplasia is a severe abnormal change in cells of a tissue that looks much closer to cancer than normal cells and carries a high risk of becoming invasive cancer if not treated. For investors, it matters because diagnosis, treatment, or clinical trial results involving high-grade dysplasia can directly affect regulatory decisions, projected medical costs, market demand for therapies, and the commercial outlook for companies developing diagnostics or treatments—much like spotting deep cracks in a building that require urgent repair.

esophageal adenocarcinoma medical

"risk of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma"

Esophageal adenocarcinoma is a form of cancer that begins in the gland-like cells lining the lower part of the esophagus, the tube that carries food to the stomach. It matters to investors because it is often aggressive and has limited treatment options, so advances, trial results, regulatory approvals, or changes in insurance coverage for new tests and therapies can materially affect the prospects and valuations of companies working on diagnostics, drugs, or procedures—like a bridge repair changing traffic for nearby businesses.

molecular risk stratification medical

"demonstrate how molecular risk stratification with the TissueCypher test can refine"

Molecular risk stratification is the process of classifying patients by specific molecules or genetic features in their disease to predict how aggressive it will be and which treatments are likely to work. For investors, it matters because these classifications can change which drugs or tests are needed, shrink or expand target markets, affect clinical trial design and approval chances, and drive demand for precision therapies and companion diagnostics.

progression in barrett's esophagus (pib) model medical

"compared a clinical risk model, the Progression in Barrett's Esophagus (PIB) model,"

A Progression in Barrett's Esophagus (PIB) model is a clinical prediction tool that estimates the likelihood that abnormal cells in the esophagus will advance toward cancer. Think of it like a weather forecast for a patient’s disease course: it combines clinical tests and patterns to predict who is at higher risk, helping doctors decide on monitoring or treatment. For investors, reliable PIB models can shape demand for diagnostic tests, influence clinical trial design and regulatory pathways, and affect the commercial value of related therapies or medical devices.

low-grade dysplasia medical

"risk associated with low-grade dysplasia, for which guidelines recommend"

Low-grade dysplasia describes a cluster of cells that look abnormal under a microscope but are not cancer; think of them as slightly cracked tiles that signal wear and a chance of bigger damage over time. For investors, its presence matters because it raises the likelihood of future disease progression, influences clinical trial outcomes and regulatory decisions, and drives demand for monitoring, treatments, or diagnostic tools tied to related healthcare markets.

AI-generated analysis. Not financial advice.

Clinical studies from Mayo Clinic researchers demonstrate the TissueCypher test provides improved risk stratification and influences risk-aligned surveillance decisions in clinical practice, with one study showing changes in surveillance intervals in more than half of patients compared with recommendations guided by traditional histopathology, supporting more personalized, risk-aligned patient management.

FRIENDSWOOD, Texas, May 4, 2026 /PRNewswire/ -- Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, today announced that new data generated by researchers at Mayo Clinic will be presented at Digestive Disease Week® (DDW 2026), taking place May 2–5 in Chicago. The findings, featured in two poster presentations, demonstrate how molecular risk stratification with the TissueCypher test can refine risk assessment and directly inform real-world management decisions for patients with Barrett's esophagus (BE).

TissueCypher is a molecular test that can predict a patient's personalized five-year risk of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) based on their underlying disease biology.

"The findings presented at DDW 2026 suggest that relying on traditional clinical risk assessment alone may not fully capture a patient's true risk of progression," said Cadman L. Leggett, M.D., gastroenterologist at Mayo Clinic and senior author on both studies. "Molecular risk stratification with TissueCypher can provide more clinically actionable insights by more accurately identifying which patients are truly at higher or lower risk. And we see that translating into real-world changes in how physicians manage patients."

Poster Presentations at DDW 2026
The following posters are available on the DDW ePosters site and to conference attendees in the DDW meeting planner.

• Authors: Cadman L. Leggett, M.D., Wilfor Jhonathan Diaz-Fernandez, M.C., et al., Mayo Clinic
• Session Type: Abstract Poster
• Session Title: Barrett's Esophagus and Esophagogastric Junction Neoplasia: Biomarkers

Poster Sa1092: The Tissue Systems Pathology Test Impacts Barrett's Surveillance Intervals in Clinical Practice
In a multicenter cohort of patients with BE who underwent TissueCypher testing as part of their clinical care, researchers evaluated how molecular risk classification influenced physician-recommended surveillance intervals compared with population risk-guided recommendations. Following testing, physicians modified surveillance intervals in 55% of patients, demonstrating a direct impact on patient management. Physician-recommended surveillance intervals were aligned with TissueCypher risk classification in 79% of cases, and 93% of patients identified as intermediate/high risk were recommended shorter surveillance intervals, reflecting escalation of care based on the test's results. Among patients with non-dysplastic BE, 92% of those identified as intermediate/high risk were recommended shortened surveillance intervals compared with recommendations based on traditional clinical risk assessment, highlighting the ability of the test to identify higher-risk patients within a population traditionally considered lower risk. These findings demonstrate that TissueCypher can directly impact physician decision-making and surveillance strategies in clinical practice, enhancing guideline-based care and enabling more individualized, risk-aligned management, including escalation for higher-risk patients and de-escalation for those at lower risk of progression.

Poster Sa1093: Discordance Between Clinical and Molecular Risk Stratification in Barrett's Esophagus
In a multicenter cohort of patients with BE who underwent TissueCypher testing as part of their clinical care, researchers compared a clinical risk model, the Progression in Barrett's Esophagus (PIB) model, with TissueCypher, which is designed to predict patients' individualized risk of progression independent of clinicopathologic factors. PIB estimates risk based on four traditional clinical factors: sex, smoking history, BE segment length and presence of low-grade dysplasia. TissueCypher classified substantially more patients as low risk (84% vs. 38%) and showed minimal concordance with PIB (κ=0.04), with most discordance driven by patients identified as intermediate/high risk by clinical factors but low risk by TissueCypher. Patients who scored TissueCypher intermediate/high risk had a predicted progression risk that exceeds the risk associated with low-grade dysplasia, for which guidelines recommend endoscopic eradication therapy (EET) or short interval surveillance. By contrast, a PIB intermediate/high-risk result had a predicted progression risk similar to patients without dysplasia or indefinite for dysplasia, indicating that PIB lacks utility for identifying higher risk patients who may benefit from escalation of care to prevent HGD/EAC.

These findings demonstrate that molecular-based risk stratification with TissueCypher can inform refined surveillance strategies to support more appropriate, risk-aligned decisions than those guided by traditional clinical and histologic factors alone, including potentially longer surveillance intervals for low-risk patients and escalation of care to EET or short interval surveillance to prevent progression in higher risk patients. Such strategies can enable more effective use of healthcare resources and individualized, risk-aligned management to improve health outcomes for patients with BE.

Visit Castle at DDW 2026
For more information, visit Castle at booth 4828 or view the full schedule of events at info.castlebiosciences.com/ddw2026.

About Digestive Disease Week® (DDW)
Digestive Disease Week (DDW) is the largest international gathering of physicians, researchers, and academics in the fields of gastroenterology, hepatology, endoscopy, and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT), DDW is an in-person and online meeting.

About TissueCypher Barrett's Esophagus Test 
TissueCypher is a precision medicine test designed and extensively validated to predict a patient's personalized risk of progression from Barrett's esophagus (BE) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). Indicated for patients with non-dysplastic BE, indefinite for dysplasia or with low-grade dysplasia, TissueCypher's five-year risk assessment is designed to help physicians tailor care to each patient's risk of developing HGD or EAC.

Backed by more than 17 peer-reviewed publications and studied in biopsies from more than 8,000 patients, TissueCypher has been shown to be the strongest independent predictor of progression compared with traditional histopathological risk assessment. Using an AI-driven spatialomics approach, the test identifies molecular signatures that often precede the development of dysplasia, which can enable earlier identification, treatment, and management of patients at increased risk of cancer. TissueCypher is designed to integrate seamlessly into routine endoscopic practice by analyzing standard esophageal pinch biopsies, delivering actionable insights without requiring additional procedures. Learn more at CastleBiosciences.com/TissueCypher.

About Castle Biosciences 
Castle Biosciences (Nasdaq: CSTL) is a leading diagnostics company improving health through innovative tests that guide patient care. With a primary focus in dermatologic and gastroenterological disease, we develop personalized, clinically actionable solutions that help improve disease management and patient outcomes. 

We put people first—empowering patients and clinicians and informing care decisions through rigorous science and advanced molecular tests that support more confident treatment planning. To learn more, visit www.CastleBiosciences.com and connect with us on LinkedIn, Instagram, Facebook and X.  

DecisionDx-Melanoma, DecisionDx-CMSeq, i31-SLNB, i31-ROR, DecisionDx-SCC, MyPath Melanoma, AdvanceAD-Tx, TissueCypher, Esopredict, DecisionDx-UM, DecisionDx-PRAME and DecisionDx-UMSeq are trademarks of Castle Biosciences, Inc.

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the "safe harbor" created by those sections. These forward-looking statements include, but are not limited to, statements concerning: TissueCypher's ability to (i) play an important role in identifying BE patients at higher risk for progression to esophageal cancer and inform real-world management decisions , (ii) provide more clinically actionable insight and translate study results into real-world changes in how physicians manage patients and (iii) enable more personalized surveillance and intervention strategies for BE patients that help prevent cancer. The words "believe," "can," "may" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. These forward-looking statements involve risks and uncertainties that could cause our actual results to differ materially from those in the forward-looking statements, including, without limitation: subsequent study or trial results and findings may contradict earlier study or trial results and findings or may not support the results obtained in these studies, including with respect to the discussion of our tests in this press release; actual application of our tests may not provide the aforementioned benefits to patients; and the risks set forth under the heading "Risk Factors" in our Annual Report on Form 10-K for the year ended December 31, 2025, and our subsequent Quarterly Reports on Form 10-Q, each as filed or to be filed with the SEC, and in our other filings with the SEC. The forward-looking statements are applicable only as of the date on which they are made, and we do not assume any obligation to update any forward-looking statements, except as may be required by law.

Investor Contact:
Camilla Zuckero
czuckero@castlebiosciences.com

Media Contact:
Allison Marshall
amarshall@castlebiosciences.com

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SOURCE Castle Biosciences, Inc.

FAQ

What did Castle Biosciences announce about TissueCypher at DDW 2026 (CSTL)?

The company reported Mayo Clinic poster data showing TissueCypher refines risk stratification and informs surveillance decisions. According to the company, physicians changed surveillance intervals in 55% of patients and aligned recommendations with TissueCypher in 79% of cases.

How does TissueCypher affect surveillance intervals for Barrett's esophagus patients (CSTL)?

TissueCypher influenced surveillance interval recommendations, prompting changes in 55% of patients tested. According to the company, 93% of intermediate/high-risk patients were recommended shorter intervals, and 92% of non-dysplastic intermediate/high-risk patients received shortened surveillance.

How does TissueCypher compare with the PIB clinical risk model in the DDW 2026 data (CSTL)?

TissueCypher showed low concordance with the PIB model (κ=0.04) and classified more patients as low risk. According to the company, TissueCypher labeled 84% low risk versus 38% by PIB, driving most discordance where PIB flagged higher risk.

Does TissueCypher identify patients who may need escalation to endoscopic eradication therapy (EET)?

TissueCypher identified patients with predicted progression risk exceeding low-grade dysplasia thresholds that suggest EET consideration. According to the company, intermediate/high TissueCypher results correspond to risks where guidelines recommend EET or short-interval surveillance.

Where and how were the TissueCypher results presented at DDW 2026 for CSTL?

The results were presented as two Mayo Clinic poster presentations at DDW 2026 in Chicago on May 2–5, 2026. According to the company, the posters are available on the DDW ePosters site and to conference attendees.