Validation and Early Commercialization of the ENVISAGE Assay, a Prognostic Test for Barrett's Esophagus

ENVISAGE 检测（Barrett 食管的预后检测）的验证和早期商业化

• 批准号: 10761328
• 负责人: Sarah Laun
• 金额: $ 97.33万
• 依托单位: CAPSULOMICS, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10761328
• 关键词: Adenocarcinoma; Adoption; Age; Algorithms; Barrett Esophagus; Bioinformatics; Biological Assay; Biological Markers; Biometry; Biopsy Specimen; Case/Control Studies; Categories; Classification; Clinical; Clinical Management; Clinical Research; Collaborations; DNA; DNA Methylation; Data; Development; Diagnosis; Dysplasia; Early Diagnosis; Engineering; Epigenetic Process; Esophageal Adenocarcinoma; Esophagus; Feedback; Focus Groups; Foundations; Funding; Future; Generations; Genes; Guidelines; Health system; Hematoxylin and Eosin Staining Method; High grade dysplasia; Histologic; Image Analysis; Immunohistochemistry; Incidence; Interview; Journals; Laboratories; Licensing; Machine Learning; Malignant Neoplasms; Market Research; Marketing; Methylation; Modeling; Paraffin Tissue; Pathologic; Pathway interactions; Patient Care; Patients; Performance; Phase; Physicians; Precancerous Conditions; Primary Care Physician; Protocols documentation; Recommendation; Recording of previous events; Risk; Risk Estimate; Risk Factors; Sensitivity and Specificity; Site; Small Business Innovation Research Grant; Specificity; Survival Rate; System; Testing; Time; Tissues; Training; United States; Universities; Validation; biomarker panel; clinical decision-making; clinical research site; cohort; commercialization; cost; diagnostic assay; epigenetic marker; falls; gastrointestinal; high risk; improved; innovation; invention; molecular marker; multimodality; novel; novel marker; patient stratification; phase 1 study; predictive test; processing speed; prognostic assays; progression risk; quantitative imaging; risk mitigation; risk prediction; risk stratification; study population; success; tissue biomarkers; tool; tumor progression; usability; validation studies

Barrett’s esophagus (BE) is the strongest known risk factor for, and obligate precursor of, esophageal high- grade dysplasia (HGD) and adenocarcinoma (EAC). However, determining future neoplastic progression risk is quite challenging in BE patients: current risk estimation is based solely on highly variable, subjective, observer-dependent histopathologic diagnoses (i.e., non-dysplastic (ND), Low-Grade Dysplasia (LGD), Indeterminate for Dysplasia (IFD), or High-Grade Dysplasia (HGD). Our ENVISAGE assay is a validated (CLIA # 21D2256153) laboratory-developed test (LDT) based on a 4-gene-plus-patient age DNA methylation-based PCR assay that was developed at Capsulomics built on foundational studies performed at Johns Hopkins University (JHU). Our preliminary studies yielded a ready-to-launch 1st-generation assay that accurately predicts the risk of future neoplastic progression in BE patients based on levels of molecular biomarkers. This prognostic assay risk-stratifies patients to vastly improve clinical decision-making, with a sensitivity of 71% and a specificity of 90%, outperforming any other clinically available tests. Notwithstanding this early success, we have identified a need for further improvement as well as a robust commercialization pathway. With funding of this direct-to-phase II proposal, we will make significant improvements to generate a more sensitive, more robustly validated second-generation product, while building a foundation for strategic commercialization and market adoption of both the current and future assays. Aim 1 will address assay sensitivity challenges due to using limited-quantity, low-quality fragmented DNA from biopsy specimens by engineering a new assay based on multiplex PCR. This advancement will also improve throughput, efficiency, cost, and processing speed. Aims 2 and 3 will augment our study population while incorporating the new multiplex protocol from Aim 1, retain and refine our algorithm to produce a 2nd-generation ENVISAGE assay, and more sharply delineate which patients will fall into the “Intermediate” risk category for improved clinical management. Aim 4 will establish early commercialization of the 1st-generation assay as an LDT while developing a platform for the future launch of our 2nd-generation product. Thus, this direct-to-phase II SBIR proposal will expand, refine, and validate the ENVISAGE assay, a novel LDT for stratifying future neoplastic progression risk in BE patients, thereby improving clinical decision-making.

巴雷特食管 (BE) 是食管高压的已知最强危险因素，也是食管高压的必然前兆。 级不典型增生（HGD）和腺癌（EAC）。然而，确定未来肿瘤进展风险 对于 BE 患者来说这是相当具有挑战性的：当前的风险评估仅基于高度可变的、主观的、 依赖于观察者的组织病理学诊断（即非发育不良（ND）、低度发育不良（LGD）、 不确定不典型增生 (IFD) 或高度不典型增生 (HGD)。我们的 ENVISAGE 检测经过验证 (CLIA # 21D2256153) 基于 4 基因加患者年龄 DNA 的实验室开发测试 (LDT) 基于甲基化的 PCR 检测是 Capsulomics 在基础研究的基础上开发的 在约翰霍普金斯大学（JHU）。我们的初步研究得出了可以立即启动的第一代检测方法 根据分子水平准确预测 BE 患者未来肿瘤进展的风险 生物标志物。这种预后分析对患者进行风险分层，以极大地改善临床决策， 敏感性为 71%，特异性为 90%，优于任何其他临床可用的测试。 尽管取得了早期的成功，但我们已经确定需要进一步改进以及强大的 商业化途径。通过这项直接进入第二阶段提案的资助，我们将做出重大贡献 进行改进以生成更灵敏、经过更稳健验证的第二代产品，同时 为当前和未来的战略商业化和市场采用奠定基础 化验。目标 1 将解决由于使用有限数量、低质量的碎片而导致的检测灵敏度挑战 通过设计基于多重 PCR 的新检测方法，从活检标本中提取 DNA。这一进步将 还可以提高吞吐量、效率、成本和处理速度。目标 2 和 3 将增强我们的研究 人口，同时结合目标 1 中的新多重协议，保留并完善我们的算法 产生第二代 ENVISAGE 检测，并更清晰地描述哪些患者将属于 用于改进临床管理的“中级”风险类别。目标 4 将建立早期商业化 将第一代检测作为 LDT，同时为未来推出第二代检测开发平台 产品。因此，这项直接进入 II 期 SBIR 的提案将扩展、完善和验证 ENVISAGE 测定， 一种新型 LDT，用于对 BE 患者未来肿瘤进展风险进行分层，从而改善临床 决策。