empowering effective treatment before progression of disease
The development of therapeutic resistance is a major factor in cancer-related death. And while tissue biopsies followed by DNA sequencing can detect known resistance mutations, such biopsies are invasive, expensive, and can cause serious complications. As a result, there is a high demand for non-invasive, rapid, low-cost screening technologies that can detect cancer mutations that render tumor cells resistant to specific types of treatment.
A University of Michigan team, led by Alexander Johnson-Buck, Ph.D., Muneesh Tewari, M.D., Ph.D., and Nils Walter, Ph.D., has developed Single-Molecule Recognition through Equilibrium Poisson Sampling (SIMREPS), a novel technology platform for the detection of cancer-related DNA mutations in biofluids using single-molecule kinetic fingerprinting. This groundbreaking technology has the potential to provide more accurate results, faster turnaround time, and decreased cost for mutant-target screening compared to current mutation tests on the market.
The development of resistance to cancer therapies is a common event for many types of cancer. Early detection of such resistance in cancer permits switching to potentially more effective treatments and prevents the waste of time and resources on ineffective treatments.
Significant Need
With the number of targeted cancer drugs on the market expected to increase, and with ongoing identification of specific mutations resulting in resistance against these drugs, there is a strong need for a non-invasive, rapid, low-cost screening technology that detects mutations that are resistant to or, conversely, sensitive to particular courses of treatment.
Compelling Science
Dubbed SIMREPS, this new diagnostic technology monitors the repeated binding of short, fluorescently labeled DNC probes to a complementary sequence on a target nucleic acid (DNA or RNA). By evaluating the frequency and duration of these probe binding events to a specific target sequence, it can identify and count each single molecule of target DNA or RNA with the ability to discern single-nucleotide sequence variations, directly in blood serum or urine, without needing conventional PCR amplification.
Competitive Advantage
Compared to blood-based liquid biopsies, urine-based assays offer the possibility of more frequent and easy collection, as well as potentially higher sensitivity due to larger sample volumes than blood. Not needing laborious and potentially biased enzymatic amplification or sequencing reduced time-to-result, makes the assay more reliable and accurate, and is potentially cheaper than conventional technologies.
Commercialization Path
- Commercialization Strategy – Establish company to license technology for further development- Alight Sciences LLC was founded in March 2017
- Intellectual Property – Multiple patent applications have been filed for the core technology of SIMREPS
- Regulatory Pathway – Diagnostic use in Laboratory Developed Tests (LDTs) is covered under the clinical laboratory improvement amendments (CLIA) by the Centers for Medicare and Medicaid Services (CMS)
- Product Launch Strategy – Instrument and consumables suitable for use in clinical research and diagnostics
Milestones
- Implement and evaluate two main strategies for increased detection of clinically actionable EGFR T790M mutation against a wild-type background
- Demonstrate specificity sufficient to detect T790M at < 0.01% abundance relative to wild-type EGFR
- Show separate detection of the five most common EGFR mutations related to TKI sensitivity at abundances of <0.01% relative to wild-type
- Implement and evaluate strategies for multiplexing
- Implement microfluidics; demonstrate multiplexed detection of five most common EGFR mutations related to drug sensitivity
