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.

巴雷特的食道（BE）是食管高 - 等级发育不良（HGD）和腺癌（EAC）。但是，确定未来的肿瘤进展风险 是患者的挑战：当前的风险估计仅基于高度可变，主观的， 观察者依赖性组织病理学诊断（即非塑性（ND），低度发育异常（LGD）， 不确定的发育不良（IFD）或高级发育不良（HGD）。我们的设想分析是经过验证的 （CLIA＃21D2256153）基于4-Gene-Plus-Patient年龄DNA的实验室开发测试（LDT） 基于甲基化的PCR分析，该测定在囊化学基础研究基础研究的基础研究上开发 在约翰·霍普金斯大学（JHU）。我们的初步研究产生了即将发布的第一代测定法 这准确地预测了基于分子水平的患者未来肿瘤进展的风险 生物标志物。这种预后测定的风险分解患者可以大大改善临床决策，并以 敏感性为71％，特异性为90％，表现优于任何其他临床可用测试。 尽管这一早期成功，我们已经确定了进一步改进的必要 商业化途径。通过这一直接统治II提案的资助，我们将大量 改进以生成更敏感，更牢固验证的第二代产品，而 建立战略商业化和市场采用的基础 测定。 AIM 1将通过使用有限的，低质量的碎片来解决评估敏感性挑战 基于多重PCR的新测定法，来自活检标本的DNA。这种进步将会 还提高吞吐量，效率，成本和处理速度。目标2和3将增加我们的研究 人口在AIM 1中纳入新的多重协议时，将我们的算法保留并完善我们的算法 产生第二代设想测定法，并更鲜明地描绘患者将属于 改善临床管理的“中级”风险类别。 AIM 4将建立早期商业化 在为未来的第二代推出平台时，第一代主张是LDT 产品。这是直接到相关的II SBIR提案将扩展，完善和验证设想测定法， 一种新的LDT，用于分层患者未来的肿瘤进展风险，从而改善临床 决策。