SAFESEQ

Ultra-sensitive NGS liquid biopsy technology

SafeSEQ

Our new SafeSEQ NGS technology can detect clinically relevant mutations in circulating tumor DNA (ctDNA) with sensitivity equivalent to our OncoBEAM digital PCR liquid biopsy from across a broader range of genomic regions.

OncoBEAM set the gold standard for ctDNA analysis as the most sensitive digital PCR approach available.(1) It has been used to detect subclonal resistance mutations, such as those in ESR1 for breast cancer patients on adjuvant aromatase inhibitor therapy who demonstrate endocrine resistance.(2)

With robust detection as low as 0.03%* mutant allele frequency (MAF), SafeSEQ ensures reliable molecular information for real-time therapy selection as well as monitoring of tumor response.

The data in the figure below shows the robust accuracy at low allelic frequencies observed for SafeSEQ and demonstrates the advantages of using focused panels for defined clinical purposes.(3)

*For input of 20,000 genomic equivalents

Citations

1.Diehl F, Li M, Dressman D, He Y, et al. Detection and Quantification of Mutations in the Plasma of Patients with Colorectal Tumors. Proc Natl Acad Sci USA. 2005. 102(45):16368-16373. doi: 10.1073/pnas.0507904102.

2. Spoerke, J. M. et al. (2016) Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant. Nat Commun. 7, 11579.

3. Rugo HS, Mayer E, Storniolo Anna Maria, Isaac C, et al. Palbociclib in combination with fulvestrant or tamoxifen as treatment for hormone receptor positive metastatic breast cancer with prior chemotherapy for advanced disease (TBCRC 035): A Phase II study with pharmacodynamic markers. Presented at the American Association of Cancer Research annual conference, Atlanta, Georgia. 2019. doi: 10.1158/1538-7445.AM2019-CT128.

SafeSEQ sensitivity has 99.2% agreement with OncoBEAMTM

This chart measures the mutant allele frequency of SafeSEQ with OncoBEAMTM  technology for ESR1, PIK3CA, AKT1, ESR1, PIK3A, and AKT1 clinical samples and shows that SafeSEQ has a 99.2 percent positive agreement out of 100 for mutant allele frequency, also known as MAF, sensitivity.

R2 = 0.9709

Ultra-sensitive NGS Liquid Biopsy Technology

Our cost-effective and industry-leading ultra-sensitive NGS liquid biopsy solutions identify tumor mutations across cancer types for a range of intended uses:

  • Inform therapy selection
  • Dynamically monitor tumor response
  • Identify molecular mediators of resistance
  • Detect minimal residual disease (MRD) at a variant level

Ultra-sensitive SafeSEQ Panels

With SafeSEQ, 100% of the starting molecules are analyzed, which isn’t always the case with other methods or technologies. This chart shows that with SafeSEQ, the input molecules are not lost along the sequencing process like they commonly can be with other methods or technologies. The chart shows the sample input of benign molecules and mutant molecules remain intact throughout sample amplification, multiplexing, dilution, purification, and quantification. The second part of the chart shows that 40% of molecules could be lost during sample preparation prior to  ligation/hybrid-capture based next-generation sequencing (or NGS), which could lead to a false negative or inaccurate analysis.

Technology

Technology
  1. SafeSEQ is a low error rate (“safe”) technology. With SafeSEQ technology, each DNA molecule is assigned a unique identifier (UID). Next, UID families are amplified and deep sequenced. The SafeSEQ platform also discriminates real mutations from errors that could have been introduced by technologies during the amplification and sequencing process, so you can count on increased accuracy.

    SafeSEQ

    This figure explains the following:

    1. SafeSEQ is a low error rate (“safe”) technology. With SafeSEQ technology, each DNA molecule is assigned a unique identifier (UID). Next, UID families are amplified and deep sequenced. The SafeSEQ platform also discriminates real mutations from errors that could have been introduced by technologies during the amplification and sequencing process, so you can count on increased accuracy.
    2. When it comes to tumor profiling, dynamic NGS technology makes a world of difference. With clinical NGS-based testing, there’s no need to sacrifice sample-input DNA and costs that often occur with large, fixed pan-cancer NGS assays due to wasted sequencing power and time spent on unnecessary regions.

     

    1. By accurately identifying ctDNA across various tumor types, SafeSEQ best-in-class sensitivity can expedite and improve advanced therapeutic clinical development. Built-in workflow optimizations and conservation of input DNA molecules ensure efficient ctDNA detection for clinically relevant targets.
  2. When it comes to tumor profiling, dynamic NGS technology makes a world of difference in delivering useful clinical information. With traditional NGS testing, sample-input DNA often limits assay sensitivity and results in increased costs since fixed pan-cancer NGS assays expend sequencing power on unnecessary gene regions.

  3. By accurately identifying ctDNA across various tumor types, SafeSEQ best-in-class sensitivity can expedite and improve advanced therapeutic clinical development. Built-in workflow optimizations and conservation of input DNA molecules ensure efficient ctDNA detection for clinically relevant targets.

Routine Clinical Testing: SafeSEQ vs Pan-Cancer NGS

This table compares SafeSEQ with other ctDNA NGS methods and measures sensitivity, sample volume, gene coverage, customization ability, and cost. SafeSEQ has a minor allele frequency (MAF) of >0.05% compared to an MAF of >1% for other methods. Sample volume for SafeSEQ is 2 mL of plasma compared to 8 mL of plasma. Gene coverage for SafeSEQ is clinically relevant, adjustable coverage compared to indiscriminate, fixed coverage of 40+ genes. SafeSEQ is high fidelity customizable, and other methods have a low capability to customize. SafeSEQ is cost efficient and other methods are high cost.