Q&A: Berg works to ‘put Dallas back in North Texas’

As Dr. Niven R. Narain, co-founder, president and chief technology officer of vertically integrated healthcare solutions company Berg in Framingham, Mass., notes, if disease models of a patient’s molecular makeup—genes, proteins and so on—are off the mark, they may indicate (metaphorically) that Dallas is in Oklahoma instead of North Texas, and the task becomes putting the city back where it belongs (more on that metaphor later in the Q&A)

DDNews: Dr. Narain, what was the original impetus for launching Berg, and what encouraged you to join the company?

Niven R. Narain: The need to define a patient’s disease by their biology. Berg was built to boldly “go back to biology” and make its understanding the foundation of drug development. Far too often, we depend on a chemical understanding, or its effect on the body, and drugs are either too toxic or do not address the underlying issue. This leaves the patient in a state of hopelessness and, as an industry, we must do more to provide hope. In late 2008 when the other two founders, Mitch Gray and Carl Berg, offered for me to really scale Berg in Boston in what is the world’s most innovative and robust healthcare corridor, I felt compelled to drive this vision as a full-time effort.

DDNews: How do the three operating units or divisions interact? How do they contribute separately but in harmony to the company’s overall purpose?

Narain: The working divisions of Berg operate together to enable the cross-functional capability of all components of the Berg Interrogative Biology platform with less emphasis on corporate silos. This cross-discipline environment encourages research from multiple angles to drive innovation at Berg while still allowing for the independence and creativity of the biology, omics and analytics teams to illuminate the narrative of the biology.

DDNews: Please explain your “Interrogative Biology Platform” and how it is being used in your work with the Department of Defense (DoD) and the Parkinson’s Institute.

Narain: The Berg Interrogative Biology platform integrates molecular data directly from a patient with clinical and demographic information to learn predictive patterns that are specific to the disease biology within a given patient population. We then use the output from the platform to isolate areas within the biology of given disease which are affected and use this info to create biomarkers and actionable drug candidates to normalize the phenotype.

In the work we are honored to perform with the Department of Defense, Berg uses the DoD’s extensive supply of prostate cancer data and tissue samples to analyze via the Berg Interrogative Biology platform. We are developing a prostate cancer kit with the leadership of Col. David McLeod’s group at the Center for Prostate Disease Research, whose forward thinking drove the collection that was used to validate markers that outperform PSA in diagnoses of prostate cancer but also help to define the more aggressive forms that exhibit a high Gleason score. This will allow for more accurate diagnoses and treatment of prostate cancer.

Similar to the DoD, with the Parkinson’s Institute, led by Dr. J.W. Langston’s group, a pioneer in Parkinson’s research, Berg is looking to identify potential biomarkers that could lead to breakthroughs in Parkinson’s research and treatment of the disease. Berg will utilize urine, blood and tissue samples from the Parkinson’s Institute and apply the Interrogative Biology platform to analyze the differences between healthy and diseased cells. Our goal to discover and validate the first-ever marker for Parkinson’s disease is now realistic, and we also are seeking to develop a new class of drug for the disease based on this fundamental disease understanding.

DDNews: How does the use of Big Data contribute to Berg’s understanding of, for example, prostate cancer?

Narain: The most important aspect of Big Data is the type of data you collect. At Berg we collect data on the biological activity of healthy and diseased cells. So, for example, in prostate cancer we can look at the differences in protein or peptides between the diseased and healthy states of the samples. Our analytics platform can sift through the data and help indicate key points of biological activity that could indicate the diseased state. This indication can then be developed into more reliable diagnostic tests as we are doing in our current pipeline with prostate cancer. This is the Interrogative Biology platform at work.

In addition, we feel actionable data is more important than just Big Data. Hence, as we enrich our analyses with clinical information, we are also able to help guide the physician to a more effective therapy or intervention, enabling a true precision medicine approach.

DDNews: The Warburg hypothesis is mentioned briefly on the Berg website. How does it mesh with your current research activity?

Narain: The Warburg hypothesis suggests that cancer cells operate in a less energy-efficient manner by switching the fuel cancer operates on in return for an evasion from cell death. Berg’s philosophy is that we must go well beyond genomics to really understand disease. Metabolism (lipids, metabolites) and proteomics allow for an epigenetic understanding to gain insight into the overall systems of disease. Once the cells’ metabolism returns to normal, the cell will die from apoptosis—our body’s natural way to remove old or defective cells. Our current lead cancer drug, BPM 31510, acts upon these pathways to restore the cell’s metabolism and allow the cancerous cells to die naturally.

DDNews: Please explain Berg’s approach to precision medicine and AI and how the latter “puts Dallas back in North Texas.”

Narain: Berg’s approach to precision medicine is to go much deeper than genomics to assess the full story of the patient by looking at all of the other components of their biology (proteins, kinsases, metabolites, lipids). We then create a model on the healthy population and disease population and allow the AI to produce the differences. We focus on the differences within the populations and stratify them where appropriate by phenotype or age, race, gender, etc. to create a profile of response. Thus, the actualization of giving the right patient the right treatment at the right time. The treatment is matched to the biology.

I have used the example of the Berg Interrogative Biology providing output similar to that of an airline map such as American Airlines that is headquartered in Dallas. The cities in this example would be supplemented for a patient’s molecular makeup (genes, proteins, etc). In the context of using the AI, as described above, the disease model may show that Dallas, which is usually is North Texas, is now in Oklahoma. This obviously is an issue. The AI could then tell us what in the biology is responsible for putting Dallas back into North Texas, and hence we focus on these elements for drug development and biomarker development.

DDNews: Finally, do you think we may be using the “cure” word by 2020, and if so, in a general sense, why?

Narain: I absolutely think we will be using the “cure” word, which we all shy away from. Gilead and Vertex are showing we can do it with vaccine technology for HepC and cystic fibrosis. The real challenge will be in cancer, diabetes and CNS disease, but I am confident that the technology, investment, awareness, collaboration and critical mass now are at a level where, as a community, we will help each other create “cures” for our individual assets. If this is not our goal, we should not be in healthcare.

Dr. Niven R. Narain is co-founder, president and chief technology officer of Berg, a Boston-area biopharma company that houses pharma, diagnostics, health analytics and biosystems divisions.

His primary research interest involves cancer metabolism and merging biology and machine learning (AI) technology to gain novel insight into differences in patient populations that contribute to disease. In addition, he is keenly interested in translating improved healthcare outcomes to improve the overall health economic impact. He is inventor of the Interrogative Biology platform that has produced and guided clinical development of lead molecules in cancer and diabetes. Notably, Narain is also co-discoverer of BPM 31510, currently in Phase 1b and 2b trials for solid tumors and skin cancer respectively. His technologies and scientific expertise are the subject of key collaborations within the U.S. Department of Defense, Walter Reed National Military Medical Center and the National Institutes of Health, in addition to leading academic medical centers such as Harvard Medical School, MD Anderson Cancer Center, Weill Cornell Medical College and the University of Miami Miller School of Medicine.