TEST:

PredicineWES+™

Detection and monitoring of utDNA MRD proved feasible in this initial investigation in BCG-unresponsive NMIBC patients treated with durvalumab containing regimens. Post-treatment utDNA MRD was detected in most samples. Post-treatment reduction of utDNA tumor fraction was associated with durable clinical benefit.

PredicineWES+ is a comprehensive assay for detecting cancer variants in blood and urine. It detects mutations across 600 cancer-related genes at a 20,000x sequencing depth, with cfDNA mutation profiles that align closely with public tissue datasets. PredicineWES+ is utilized for baseline profiling in the PredicineBEACON MRD assay and demonstrates a high correlation in TMB scores with PredicineATLAS.

In this study, we observed no significant difference in clinical outcomes between bladder cancer patients receiving bladder preservation or surgery-based intervention. Urine and blood-based MRD tests closely correlated with clinical outcomes. Our study emphasizes the value of serial monitoring of urine/plasma-based MRD assays in informing MRD status or treatment response for patients who undergo bladder preservation or cystectomy.

Minimal residual disease can be detected using utDNA prior to rTURBT with high accuracy, making this a promising urinary biomarker. If validated, the combined approach using CNB and tf from utDNA for the detection of MRD can be used to predict patients in need of maximal resection prior to starting intravesical therapy.

Urinary tumor DNA holds promise for detecting MRD prior to rTURBT. Tissue informed probes with ultra-deep sequencing improve detection of MRD where other biomarkers have fallen short. CNB independently performed excellently in detecting residual disease and combining tf with CNB may further optimize test performance.

The established subclonal deconvolution pipeline enhances biomarker analysis from assays utilizing WES with boosted sequencing depth for selected genes.

Analysis of the mutational profile of pBT and pNMIBC revealed differential patterns of somatic mutations. Many expected gene mutations were detected in pNMIBC, but surprisingly 18% of all mutated genes were shared between tumor and pathologically benign samples. The fact that only one somatically mutated gene was exclusive to pBT signifies excellent censoring of variants by the DeepSea algorithm.

Index and reTURBT tumor tissue have high variant concordance, demonstrating the rationale in utilizing tumor informed ucfDNA assays to identify residual disease prior to repeat transurethral resection. Novel mutations also arise in almost all patients highlighting the potential utility of personalized MRD tracking prior to reTURBT. We demonstrate that urinary TF derived from LPWGS of ucfDNA currently provides moderate sensitivity to detect disease prior to reTURBT.

"Predicine...announce its participation in the European Society for Medical Oncology (ESMO) 2023 Congress in Madrid, Spain. The company will present six compelling poster studies, unveiling the future of liquid biopsy solutions...These poster presentations will shine a spotlight on Predicine’s groundbreaking liquid biopsy innovations, including PredicineBEACON™, a revolutionary solution for personalized and actionable minimal residual disease (MRD) analysis."

"Predicine, Inc...announced a new study published in The New England Journal of Medicine (NEJM), demonstrating the clinical utility of its minimal residual disease (MRD) Liquid Biopsy Assay in support of Genentech's Phase 1 Clinical Trial of Divarasib. This milestone reaffirms Predicine's position as a leader in the field of liquid biopsy diagnostics....These findings underscore the clinical utility of liquid biopsy profiling in the assessment of phase I clinical trial of Divarasib."

Besides its convenience in sample collection, urine-based genomic profiling also has the potential to capture more heterogeneity of urinary tract malignancies as compared to tissue or blood based testing alone. Urine ctDNA monitoring is a useful complementary test to support standard tissue and plasma based assays in high risk bladder and UTUC patients.

Our results demonstrate the feasibility of using an ultra-sensitive, baseline-informed MRD assay to detect strong correlations between MRD status and prognosis outcomes in peri-surgical plasma samples collected as early as 7 days post-surgery in resectable HCC patients. This study highlights the clinical utility of MRD testing in peri-surgical settings.