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.

巴雷特氏食道(BE)是已知的最强的食管高压性食管炎的危险因素，也是食管高压性食管炎的专有先兆。 级别不典型增生(HGD)和腺癌(EAC)。然而，确定未来肿瘤进展的风险 对于BE患者来说是相当具有挑战性的：目前的风险估计完全基于高度可变的、主观的、 依赖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)、 不确定为异型增生(IFD)或高度异型增生(HGD)。我们的设想化验是经过验证的 (CLIA#21D2256153)实验室开发的基于4基因加患者年龄DNA的检测(LDT) 基于甲基化的聚合酶链式反应分析是在胶囊组学所进行的基础研究的基础上开发的 在约翰霍普金斯大学(JHU)。我们的初步研究产生了一种随时可以发射的第一代测试 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，具有 敏感度为71%，特异度为90%，优于任何其他临床可用的测试。 尽管取得了初步的成功，但我们已经确定了需要进一步改进的地方，以及健全的 商业化道路。有了这项直接进入第二阶段的提案的资金，我们将取得重大进展 改进以生成更敏感、更可靠的第二代产品，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、低质量的碎片而带来的检测灵敏度挑战 通过设计一种基于多重PCR的新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和目标3将加强我们的学习 在合并来自目标1的新的多路传输协议的同时，保留并改进我们的算法以 制作第二代预想测试，并更清晰地描述哪些患者将落入 “中级”风险类别，以改善临床管理。目标4将尽早实现商业化 将第一代测试作为LDT，同时为未来推出我们的第二代测试开发平台 产品。因此，这一直接到第二阶段的SBIR提案将扩展、改进和验证设想的化验， 一种新的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。