Applications

We’re Leading the Rapid Discovery and Commercialization of an Entirely New Class of Immune-System-Derived Epigenetic Biomarkers and Liquid Biopsies.

By decoding the immune system’s DNA methylation response to disease stress, we’re able to identify blood-based phenotypic EpiMarkers — yielding broad, clinically actionable immuno-cellular information that goes well-beyond what ctDNA, CTC’s or proteomic markers can provide.

Powered by the GenPro Platform, a proprietary machine-learning-enabled cloud-based bioinformatics platform, our unique approach targets the many unmet clinical needs across the disease spectrum that mutation-based biomarkers cannot easily address.

And unlike most other identification approaches, our EpiMarker approach delivers consistently high success rates within as little as 10 weeks, across multiple diseases, sample types, and applications.

Responder Vs Non-Responder Stratification In Clinical Trials

One of the greatest challenges in modern drug development and clinical trial conduct is determining which patients are likely to benefit from therapy.

The success of “Personalized Medicine” to date has been limited to a relatively small fraction of cancer patients whose tumors have specific genetic alterations. Most other cancer patients, and almost all other patients with conditions other than cancer, have not yet benefited.

GenPro’s technology offers the possibility of extending the promise of personalized medicine to these underserved patients. For drug developers, we offer a path to identifying response prediction biomarkers during the course of clinical development, with the potential to increase overall trial success vs an “all comers” approach.

Examples:

We applied the GenPro approach to predicting the response of lymphoma patients to a novel immunotherapy being tested in clinical trials. Using an EpiMarker discovered using pre-treatment blood samples from a sub-set of patients we predicted response to the therapy with 80% accuracy in an independent validation sample set.

In another study we performed a similar analysis to predict response to immunotherapy in NSCLC patients. Here patients that benefited were identified with a sensitivity of 76% and overall accuracy of 68%. This performance is similar to that of PD-L1 IHC testing currently used to stratify patients in the clinic but uses a liquid biopsy as starting point rather than a biopsied portion of the lung tumor. GenPro is continuing work on this assay to further improve its performance.

Companion Diagnostics, CDx

Drugs entering development are increasingly specific for their targets and have exciting new mechanisms of action, but disease biology is so complex only a fraction of patients will respond.

A Companion Diagnostic helps to identify those patients most likely to benefit and is used by the physician to make treatment decisions. Almost all approved companion diagnostics are for cancers with specific mutations, again leaving most cancer patients and virtually all other types of diseases without good options for choosing therapies.

GenPro technology can help here also, by identifying novel response prediction EpiMarkers, during clinical development and validating them during the course of trials and commercialization. Assays for these EpiMarkers can be readily converted into a low cost, high throughput technical format for widespread use in clinical testing laboratories.

Companion Diagnostics for Marketed Drugs

Many efficacious drugs on the market, while critically important and beneficial for a subset of patients, are very expensive and may have severe side effects.

Broad and flexible biomarker discovery methods like that employed by GenPro were not available when these drugs were approved. GenPro is pursuing identification of EpiMarkers for these types of drugs where success could dramatically reduce medical costs, sparing non-responding patients dangerous side effects, improve the bottom line for the drug maker, and increase payor approval likelihood.

 

Drug Efficacy Monitoring

Just as disease presence or stress leaves a specific trail in the methylation pattern of immune cells’ DNA, exposure of the body to drugs also causes changes in these cells that can be detected with GenPro technology.

These effects can be monitored during clinical drug development to detect “pharmaco-dynamic” changes that aid in understanding drug dosing and mechanism. The same approach can be used to follow the response of the disease to the drug.

Example: Drugs that affect DNA methylation are used to treat disease like AML. GenPro, in collaboration with an academic partner, was able to detect a complex pattern of DNA methylation changes in a mouse model of AML, identifying the precise locations on the chromosomes where the drug affected methylation and therefore also the affected genes. The precision of the GenPro platform allows the monitoring of disease with greater sensitivity, specificity and accuracy than any other approach today.

Early Disease Detection

Despite exciting advances in targeted and immune based therapies for cancer, the majority of patients with metastatic disease will ultimately die from their cancer.

There is an increasing recognition that changing the game for cancer survival will require reliable tests that detect cancer before it has spread, when surgery can still cure it. Many companies are now focused on creating such assays.

An inherent problem is that when tumors are early and small they don’t shed very much material that can be detected in a blood test, leading to insensitive tests for early disease. GenPro’s approach of identifying changes in immune cells, that sensitively detect and react to the presence of a tumor, may help to solve this problem. These immune cells act as biological amplifiers of these weak tumor signals, storing a record of their interaction with the tumor in their DNA methylation pattern.

Example: GenPro was able to identify distinct signatures in peripheral immune cells from women with no tumor vs those with invasive breast cancer vs those with DCIS. DCIS is an early or pre-cancer that by definition has not yet invaded local tissue. Despite this low disease burden an Epimarker was found with >85% sensitivity for detecting these early lesions.

An additional advantage is that the methylome of immune cells is a completely distinct source of biologic information from that used in most other approaches, typically rare circulating bits of DNA released from the tumor itself. This unique source of novel information may act to complement assas results from other methods to reach the level of accuracy needed for a transformative early cancer detection assay.

Disease Diagnostic

Reliable biochemical tests for disease diagnosis are rare except for some mutation-based cancer tests.

For example, in neurological diseases like Alzheimer’s or Parkinson’s diagnosis is still largely based on complex clinical assessments or imaging tests and their accuracy is still sub-optimal. GenPro’s approach is applicable to almost any disease, markers can be discovered rapidly with the same timing and work flow regardless of the underlying disease biology. Our methods have identified immune cell DNA methylation differences in Cerebral Palsy and Parkinson’s Disease patients, for example.

This unprecedented speed, flexibility, and precision enables scientists and medical professionals to diagnose and monitor disease with far greater sensitivity, specificity, accuracy, and cost-effectiveness than any other approach available today.