Natera

Natera's Signatera test demonstrated that patients with detectable circulating tumor DNA at diagnosis had three times higher risk of recurrence in early-stage, high-risk breast cancer, according to I-SPY 2 trial data to be presented at ESMO Breast Annual Congress.

• New study published in the American Journal of Transplantation demonstrates Prospera Heart with DQS significantly outperforms traditional dd-cfDNA percentage tests, with sensitivity increasing from 78.2% to 86.5%. • The innovative two-threshold algorithm combines donor fraction and donor quantity score, reducing false positives by over 37% and potentially decreasing the need for invasive endomyocardial biopsies. • Research involving 808 test samples from 187 heart transplant patients shows improved specificity (83.6% vs 76.9%) and area under the curve (0.881 vs 0.865) compared to conventional methods.

• Natera has enrolled the first patients in the HEROES phase II clinical trial, investigating the potential to safely discontinue anti-HER2 therapy in metastatic breast cancer patients with no detectable circulating tumor DNA. • The trial will use Natera's Signatera test to identify patients who may safely stop maintenance therapy, potentially freeing them from lifelong treatment regimens that can be costly and cause adverse effects. • Approximately 170 patients across 35 French sites will participate in the study, which could fundamentally change treatment approaches for the 15-20% of breast cancer patients with HER2-positive tumors.

• Natera's Signatera test demonstrates strong prognostic and predictive capabilities in colorectal cancer (CRC) patients, particularly in identifying minimal residual disease (MRD). • The BESPOKE CRC study reveals that post-surgical Signatera positivity is associated with inferior outcomes in stage II and III CRC patients, with significant differences in disease-free survival. • A novel tissue-free MRD detection test from Natera shows high sensitivity and specificity, indicating its potential as a non-invasive method for MRD assessment. • Data from the CIRCULATE and PROCEED-CRC studies highlight Signatera's effectiveness in early colorectal cancer detection, achieving high sensitivity and specificity rates.

• Natera's SAGITTARIUS trial uses Signatera to personalize colon cancer treatment strategies, marking a shift from the one-size-fits-all approach. • The trial randomizes Signatera-positive patients to genotype-guided therapy or standard chemotherapy, exploring immunotherapy and targeted agents. • Signatera-negative patients in the study will receive physician's choice of treatment, including observation or single-agent capecitabine. • The SAGITTARIUS project, funded by the EU, involves 9 partners across Europe and 26 clinical centers, aiming for cost-effective, tailored treatments.

ctDNA testing influenced adjuvant therapy decisions in 16.3% of stage II/III colorectal cancer cases, with de-escalation in 59.9% and escalation in 35.7%.

• Natera's Signatera MRD test shows promise in predicting overall survival in colorectal cancer (CRC) patients, potentially changing post-surgical management. • In CRC, Signatera-positive patients after liver metastasis resection benefited from adjuvant chemotherapy, while Signatera-negative patients did not show significant benefit. • The BELLINI trial indicates that ctDNA analysis with Signatera can identify clinical responders to immune checkpoint inhibitors in triple-negative breast cancer (TNBC). • These findings, from over 85 peer-reviewed publications, highlight Signatera's role in optimizing treatment decisions across multiple cancer types.

• Signatera, a ctDNA-based MRD test, demonstrates its ability to predict overall survival in resectable colorectal cancer patients, marking a significant advancement in personalized medicine. • The GALAXY study reveals that Signatera-positive patients receiving adjuvant chemotherapy experienced a 50% reduction in the risk of death, highlighting the test's predictive value for chemotherapy benefit. • Signatera status is identified as the most significant predictor of recurrence, outperforming standard clinicopathologic risk factors, with a notably higher hazard ratio for both DFS and OS. • Sustained clearance of ctDNA, as indicated by Signatera, correlates with superior survival outcomes, underscoring its potential as a surrogate endpoint for long-term prognosis in CRC patients.

• Natera will present new data on Signatera, its MRD test, at the ESMO Congress, including findings from the CIRCULATE-Japan GALAXY trial. • Signatera-positive patients in the GALAXY trial had a significantly shorter overall survival compared to Signatera-negative patients, with a hazard ratio of approximately 10. • Updated analysis from the GALAXY arm of CIRCULATE-Japan includes the first prospective read-out of overall survival based on MRD in over 2,100 patients. • Additional presentations at ESMO will highlight new Signatera data in breast cancer and squamous cell carcinoma of the head and neck.