Personalis (PSNL) Status Update summary

Advances in ultra-sensitive ctDNA detection for cancer monitoring

• NeXT Personal MRD test detects circulating tumor DNA (ctDNA) at levels as low as 1 part per million, offering 10–100 times greater sensitivity than other approaches.

• Whole genome sequencing identifies up to 1,800 mutations per patient, enabling highly personalized and sensitive monitoring for residual or recurrent cancer.

• In early-stage breast cancer, 39% of positive ctDNA detections were in the ultra-sensitive range, and the test identified recurrence a median of 15 months before clinical imaging.

• The test demonstrated 98% baseline detection and perfect longitudinal performance (100% sensitivity, specificity, PPV, and NPV) in the breast cancer cohort.

• Ultra-sensitive detection allows for earlier intervention and more accurate risk stratification for recurrence.

Clinical impact in immunotherapy response monitoring

• In a metastatic pan-cancer cohort, baseline ctDNA levels were prognostic for outcomes with immune checkpoint inhibitors; lower baseline ctDNA correlated with improved progression-free and overall survival.

• Early ctDNA dynamics (baseline to post-cycle 3) predicted molecular response and better clinical outcomes.

• Clearance of ctDNA to undetectable levels was associated with prolonged radiological responses and increased survival, with ctDNA progression preceding imaging-based progression by an average of 81 days.

• The assay achieved a 98% detection rate at baseline, a significant improvement over previous methods.

Differentiation and future directions

• The ultra-sensitive test outperformed digital PCR and whole exome sequencing in both detection rates and lead times.

• High specificity (≥99.9%) is considered critical for repeated monitoring and clinical decision-making.

• Retrospective studies are expected to support upcoming Medicare submissions, with strong interest in both escalation and de-escalation of therapy based on test results.

• Ongoing studies aim to further validate the test's clinical utility and expand its use across cancer types.