Sensitivity to PARP Inhibitors
PARP & PARP Inhibitor Prediction
Poly ADP Ribose Polymerase inhibitors (PARPi) are a class of drugs that serve as targeted therapy for cancers with Homologous Recombination DNA Repair Deficiency (HRD), reliant on non-homologous end joining (NHEJ). HRD can occur by inactivation of related genes such as BRCA through mutations or silencing. PARPi bind to the PARP enzyme, preventing its repair of single strand DNA nicks. The accumulation of DNA nicks results in double stranded DNA (dsDNA) breaks which proves lethal in cells using to repair dsDNA breaks. PARPi mediated synthetic lethality has been demonstrated durable responses in sub-population of patients with HRD. The key is identifying those patients who are likely to respond.
Epic HRD Test: Identification of HRD+ tumors through a liquid biopsy.
Epic Sciences has developed the Epic HRD Test, to identify patients with HRD from a simple peripheral blood draw through single cell imaging of individual circulating tumor cells (CTCs). Parallel high content image analysis and single cell sequencing characterized the observed morphological differences between cells sequenced with high genomic instability, a signature of HRD, vs. those with low genomic instability. Subsequently, the Epic Sciences team developed a propriety algorithm that can predict cells with high genomic instability and identifies an HRD phenotype (figure 1, as presented at ASCO 2016) based on image analysis alone.
This new test will facilitate both clinical trials and drug discovery by:
- Quickly identifying HRD positive patients (TAT < 1 week from blood draw)
- Identifying more HRD positive patients than a traditional genomic assay (~32% prevalence of marker in mCRPC)
- Minimally invasive, liquid biopsy allows for a time relevant analysis of HRD status and longitudinal monitoring of therapeutic efficacy
- Single cell analysis can differentiate germline vs somatic alterations and provide insight into % of active tumor burden with HRD+ vs. other driver mechanisms
Time to PSA Projection
PSA Response (% with >50% PSA Decline)
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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.