Technology Advantage

Epic Sciences’ CTC Analysis

Precision medicine initiatives in oncology focus on delivering targeted therapeutics to specific patient populations in which they will be most effective. Screening patients for sensitivity to these drugs has traditionally required translational researchers to retrospectively interrogate archived tumor biopsy samples for the presence of both protein and genomic markers. In many indications, the biopsy procedure is invasive, and biased due to both sampling error of the biopsy or evolution of the disease from therapeutic and immune selective pressure. Starting from a non-invasive peripheral blood draw, a liquid biopsy provides an alternative method to screen patients for markers of therapeutic sensitivity.

End-to-end Epic Sciences Solution

Analytical Validation

The Epic Sciences CTC technology is a powerful rare cell detection and characterization platform aimed to ensure no cell left behind®. Since its incorporation, Epic Sciences has partnered with biopharma and academic institutions to provide a comprehensive view of cancer cell biology. Epic Sciences’ technology is currently being used in over 60 clinical trials and more than 150 collaboration projects. As of today, it has tested over 10,000 patient samples. The Epic Sciences CTC detection and characterization platform has been part of 50 peer reviewed papers, abstracts and posters which have been published and presented by leading academic, biotech and pharmaceutical collaborators.

Analytical validation in terms of assay performance, accuracy, linearity, specificity and precision of CTC enumeration was published in Werner et al, JCB 2015. An excerpt of data that highlights the performance of key parameters is shown below.

Performance Characteristics	Assessement Parameter	Spike-In CLCs	Measured Parameter
Accuracy	Recovery of nucleated cells	0 to 300 CLSs/slide (7 serial dilutions)	% Recovery of Nucleated Cells
Linearity (Reportable Range)	Assay Linearity	0 to 300 CLCs/Slide (7 seiral dilutions)	Linear Regression of CLC Count
Specificity	False Positive CLC Detection	Unspked healthy donor slides	CLC Count
Precision/Repeatability	Intra-Assay (n=3 replicate tests / run) Inter-Assay (n=5 runs / 3 operators) Intra-Operator (n=3 runs / operator) Inter-Operator (n=3 runs / 3 operators)	(i) 25 CLCs/slide (ii) 300 CLCs/slide	% CV CLC Count

These are the analytical characteristics assessed to benchmark the performance of the Epic Sciences CTC detection and characterization platform. Varying concentrations of COLO-205 cell line cells (CLCs) were spiked into healthy donor blood, red blood cells were lysed, and 3 x 106 nucleated cells were deposited onto slides, ranging from 0-300 CLCs/slide. Slides were stained with a cocktail of CK, CD45 and DAPI antibodies. Assay accuracy, linearity, specificity and precision were determined as described in the methods. For each analysis, a “run” is comprised of three tests, with each test consisting of two replicate slides.

CTCs Identified by the Epic Sciences Platform

Traditional CTCs

Traditional CTCs would be confirmed by a pathologist as cancer cells. Traditional CTCs have an intact nucleus and express cytokeratins, which demonstrate epithelial origin and are negative for CD45, a white blood cell marker. They also have morphology consistent with cancer.

Cytokeratin Negative (CK-) CTCs

Cytokeratin Negative (CK-) CTCs express neither cytokeratins nor CD45 but have an intact and irregular nucleus. They may be cancer stem cells or cells undergoing epithelial to mesenchymal transition (EMT). Epic Sciences has shown that this cell type has genomic aberrations and is prognostic for worse patient outcomes.

Apoptotic CTCs

Apoptotic CTCs are cells that are undergoing apoptosis (cell death). Epic Sciences’ platform can identify nuclear fragmentation associated with this process. Measuring the ratio of traditional CTCs to apoptotic CTCs from baseline to therapy may provide clues to a treatment’s efficacy in targeting and killing cancer cells.

CTC Clusters

CTC Clusters consist of two or more individual circulating tumor cells bound together. The CTC cluster can be made up of traditional and/or CK- CTCs. In preclinical models, CTC clusters have demonstrated 50X more metastatic potential than single cells.

Every time Epic’s AR-V7 test is administered the healthcare system saves about $15,000 per year of life extended. In other words approximately $7,000 to $9,000 per patient tested.
Of the roughly 30 million cells in a typical blood sample, about 5 are cancer cells on their way to form tumors elsewhere in the body. Modern cancer diagnostics technology can't see them.
We spend about $100 billion a year on cancer drugs. But because we’re not matching the right drug to the right patient and their disease in a personalized way, about 3/4ths of that drug spend is wasted.
The Epic approach answers a critical question for a doctor: When is a patient resistant? By answering that question accurately and precisely we increase patient life and save the system money at the same time.
Today, Epic Sciences is embedded in clinical trials with 48 leading producers of oncology drugs and 35 of the top academic cancer hospitals.
It takes only 7 minutes to acquire an entire image of 6 million stained cells on a 1 x 3 slide. Then that image, which is about 20GB of data, gets sent up to the cloud where the algorithms run and find the rare events in about 2 more minutes.