Q & A with the Founders of Empiriko-Developers of the “Chemosynthetic Liver”
Earlier this month, I had the opportunity to speak with the founders of the company Empiriko, which is noted for the development of an innovative alternative that has the potential to significantly reduce the use of animals during drug development. Chief Executive Officer Pam Randhawa, and Chief Scientific Officer Dr. Mukund Chorghade, were excited to give NAVS the inside scoop about Empiriko’s Biomimiks™ chemosynthetic liver, a chemical method enabling researchers to better understand drug metabolites (break down products of drugs after they are metabolized by the body), evaluate the toxicity of metabolites, and understand drug-to-drug interactions from a metabolism perspective–while being more predictive, faster, and less expensive than traditional models. The chemosynthetic liver can even detect metabolites missed by animal models, convincing researchers at the company that their model offers a number of advantages over the currently-available models. Here is what Empiriko’s founders had to say about their powerful chemical model—a model that has both animal welfare advocates and big pharma very excited.
-Dr. Pam Osenkowski, Director of Science Programs
Q. Can you tell us more about how the chemosynthetic liver works? How does it compare to other models that are commonly used by researchers to address drug metabolism?
A. We are unique in our ability to use chemistry-based systems to study drug metabolism. Besides animal testing, the present-day methods for profiling metabolites are labor-intensive, time-consuming, costly and chemically inconclusive. Incomplete metabolism profiles can derail drug development or present serious side effects when the drug reaches the market.
Empiriko has designed synthetic chemical catalysts (Biomimiks™) that mimic the way Mother Nature metabolizes drugs, mimicking the structure and function of liver enzymes. Our Biomimiks™ catalysts (chemosynthetic livers) are designed for speed, scalability and efficiency. These chemosynthetic livers provide many advantages over traditional biological systems.
Animal-based or biological systems have slow reaction rates (days); yields are variable and often low. Biomimiks™ provides rapid turnaround that enables scientists to process more compounds in a shorter period of time. Furthermore, animal-based systems generate small quantities of metabolites and are constrained by a limited ability for isolation and comprehensive structure elucidation. Biomimiks™ generates larger quantities of metabolites, enabling scientists to conduct more complete metabolism studies, confirm structure and generate quantitative measures of toxicity, focusing their time and resources on the most promising drug candidates.
Our reactions are very fast and we can process multiple drugs simultaneously. We can save 25-50% of time using our technology to generate metabolites (vs. the use of animal testing) at 5-40% of the cost.
Q. Is data from your model more likely to predict what happens in humans than data from animal models?
A. Yes, we are more likely to predict human drug metabolism. Our early work on marketed drugs has established this correlation. Several studies have established that there are variants in the drug-metabolizing enzymes in rats, dogs, monkeys, rabbits, sheep and other animals that result in lack of accurate correlations in humans.
Q. Can you tell me more about your company’s desire to have this assay get FDA regulatory approval? What challenges do companies face, in general, when trying to meet regulatory requirements?
A. Empiriko’s goal is to test 100 or more drug combinations, and present our results to the FDA to get their buy-in as a standard research tool as a replacement for the Ames test. In addition, our vision is to develop “Chemosynthetic-liver-on-a-chip” technology as a diagnostic tool for personalized patient treatment which will require FDA approval. In the meantime, using this as a research tool (which does not require FDA approval) we can reduce animal testing significantly.
We have conducted metabolism profiling studies for 50 marketed drugs and new chemical entities. We were able to detect the same metabolites for each of these drugs as observed in animal and human studies. In addition, we found new compounds to explain observed toxicities. This validates that our chemosynthetic livers accurately predict the range of metabolites by in vitro experiments.
In terms of regulatory challenges, companies have a burden of proof to demonstrate the clinical relevance of their technology and the in vivo observations in humans. Typically, companies use biological systems and animal testing to demonstrate this. These methods are extremely expensive and time-consuming and not 100% conclusive. Empiriko’s plan includes testing over 100 marketed drugs where metabolites and toxicity are already known in order to demonstrate the validity of Biomimiks™ as a standard research tool.
Again, all of the regulatory requirements listed above are extremely expensive and time- consuming which puts an additional financial burden on small companies that are innovating.
I would like to thank Pam Randhawa and Dr. Mukund Chorghade for their time and insight on their chemosynthetic liver technology, a promising tool that has the potential to revolutionize the drug discovery process as we know it, while significantly reducing the use of animals in this area. We look forward to learning and sharing more about this exciting technology and the progress made by Empiriko to get regulatory approval for this tool.