How Metabolomics Can Raise the Bar in Drug Development

An Interview with Metabolon Chief Scientific Officer Ranga Sarangarajan, Ph.D.

So why has this recognized R&D leader now chosen to focus on metabolomics? We sat down with Ranga to get his take on this rapidly growing technology and the potential it holds to propel drug development.

What are some of the biggest challenges companies are facing throughout the stages of drug development?

“The challenge of high failure rates in clinical development of new drugs has remained consistent over the last few decades and still represents a critical and unmet need in modern medicine. Of a few hundred to thousand compounds screened successfully, only a fraction will achieve the ultimate success of receiving FDA approval and turning a profit for the company. This is an expensive risk proposition for companies, considering they spend millions of dollars throughout this process, from the beginning of discovery all the way through clinical development. And until companies can deliver these breakthrough treatments, people impacted by many medical conditions will continue to suffer.”

How does a multi-omics approach impact drug development?

“Over the past 12 years that I’ve been involved in the space, significant progress has been made in realizing the true value of multi-omics to support decision-making along the clinical development chain. And, the fact that companion diagnostics actually reduce the failure rates of clinical development has now been well-established and evidenced in the literature. The rapid advances in technology, the evolution of analytics, the availability and access to extensive real-world data, and the ability to stitch together the multi-omics data with clinical and human health meta data is instrumental for making informed decision to improve success in clinical development. We are getting better at doing this, but I think there is an immense opportunity to improve on using some of these core technologies to further refine and improve success rates.”

What are some of the advantages of implementing metabolomics in drug development?

“One of the reasons I came to Metabolon is the appreciation of metabolomics and its place in human biology. Though my previous focus was on the generation and use of multi-omics, I realized the power of metabolomics, and being with Metabolon gives me a platform to help build awareness and adoption of this powerful technology. A comprehensive profile of metabolites basically represents the global endpoint of biology. Meaning, metabolites are the consequence or end result of biological processes accounting for the observed biological effects. So, when we comprehensively profile metabolites inside and outside the cell it provides us with a very thorough systems-wide view of events that have transpired and contributed towards the biological phenotype/effect.

“In addition, it is a cleaner matrix compared to proteins or lipids or anything else that one can leverage for accurate biological interpretations. Furthermore, metabolites represent a molecule matrix that is amenable to fairly seamless translation from preclinical discovery (where major work is performed in non-human models) to the early stages of clinical development (in the humans).  Proteins and lipids can elicit significant variation of biological flavors that are almost impossible to interpret, making it more complicated to delineate their impact on system-wide biology and is not readily translatable compared to metabolomics.  Thus, metabolomics offers a unique advantage of biological translatability from preclinical to clinical development; an opportunity for development of actionable diagnostic and prognostic solutions to improve success in clinical trial design, development, and outcome measures.

“Proteins are often used for targeting drugs because they’re the mainstay of drug development. Protein targets with significant understanding of underlying biology has been the traditional path for drug discovery and clinical development, a long history of “do’s & do not” that makes the process de-risked and success or failure predicated on the biology.  It is therefore natural for people to gravitate towards avenues of comfort & familiarity that tends to mitigate risks in drug development and discovery.  The most recent trends within the industry include the transition into the RNA space. The utility of RNA as a modality for drug discovery and development is relatively new and has its own advantages and disadvantages. Within the drug development process, the use of precision medicine is traditionally being met by the use of DNA-based strategies, and metabolomics represents the only other matrix with the ability to offer sufficient precision in biology to support drug development.”

What are companies missing out on by not utilizing metabolomics?

“Good science requires an open mind in exploring avenues that promise the best data and insights to their respective field of study, and metabolomics in particular can really help here by uncovering key insights underlying biology in general. Metabolomics is unique in its ability to influence key functions of DNA, RNA and proteins and therefore, lack of its inclusion or characterization fails to provide a complete picture of biological regulation in health and disease. This leaves significant gap not only in knowledge, but the ability to leverage the information provided to develop robust solutions with significant impact on health outcomes. Over the past decade advances in technology have moved metabolomics into the mainstream, providing deeper emphasis on its importance in influencing biology and health. It has become imperative that companies at the very least explore the use of metabolomics as a commercially viable option for a deep dive to understand its place within discovery biology, target identification, drug discovery and development.”

What are you looking forward to in the future with metabolomics?

“Metabolites are inherently part of everything in existence, from plants, animals to humans, and we’re starting to understand the breadth of information and insights they provide in biology and health.

“As a CSO, I feel that metabolomics is underserved and underrepresented. It’s the final frontier that we’re exploring in a systematic manner. DNA is a matrix that is well-established with significant understanding of its make-up, functionality, and utility. Metabolomics on the other hand is an underappreciated ‘omic, yet to reach its full potential. In my opinion the integration of metabolomics with genetic information is optimal for precision medicine, and combining it with proteins provides the synergy for understanding underlying biology. In my view, contextual use of metabolomic overlaid on genes or proteins provides the ideal human template for better understanding human biology for designing better health solutions.

“I am extremely excited about the work we’re doing at Metabolon. I couldn’t have made this transition at a better time.”

For more information about Metabolon and how metabolomics can further your company’s research objectives, visit www.metabolon.com.