Clinical Trial Design

About

Seres Therapeutics, a late-clinical stage biotechnology company, is a recognized pioneering developer of microbiome therapeutics. Navigating the unchartered and exceedingly complex world of live biotherapeutic products (LBPs) has been fraught with challenges for all players, and Seres is no exception. Metabolomics is rapidly gaining adoption in drug development, largely due to its ability to discover and validate biomarkers that can help support key decisions throughout the process, from discovery through clinical trials. Seres harnessed the power of metabolomics to guide drug development decision-making and advance their programs to the next phase of development.¹

The Challenge

When Seres was unsatisfied with the results of the Phase II clinical trial for its leading SER-109 candidate, its research team turned to metabolomics to find a new path forward. SER-109 is an investigational microbiome therapeutic for the prevention of C. difficile recurrence. Following a successful Phase I, Seres scientists were faced with a challenge around SER-109 Phase II due to a non-significant clinical outcome between the drug and the placebo.

Metabolon Insight

Metabolon’s Global Discovery Panel is a proprietary metabolomics untargeted panel capable of detecting and identifying over 5,400 metabolites. Seres leveraged this panel to gain a much clearer picture of the biological activity of the microbial community and to identify potential metabolite-based biomarkers that could inform drug pharmacokinetics and pharmacodynamics.

The Solution

The process of establishing metabolically active bacteria in the gastrointestinal tract is termed “engraftment.” Metabolon’s Bile Acids Targeted Panel showed an association between increased secondary bile acid concentrations (p < 0.0001) and early engraftment of SER-109. Early engraftment was also associated with clinically relevant nonrecurrence (p < 0.05). These insights helped lead to a more efficacious dosing strategy by highlighting the importance of early engraftment in preventing Clostridium difficile spore germination and vegetative outgrowth. The data and insights from the study enabled Seres to redesign the company’s clinical trial strategy for SER-109 by selecting a higher dose for the Phase 3 trial to optimize efficacy.

The Outcome

Seres leveraged Metabolon’s Good Clinical Practice (GCP)-validated Bile Acids Targeted Panel to demonstrate the mechanism of action and dose-response during the successful Phase III trial. Christopher Ford, Ph.D., Senior Director, Computational Microbiome Sciences at Seres, explains the importance of this metabolomics data for their program: “It was a pivotal moment in troubleshooting the trial and moving the product forward. The use of global metabolomics was particularly valuable in helping us evaluate drug activity in Phase I and Phase II, and to then inform a successful Phase III.” Dr. Ford continues, “We are working in a completely novel space; there is an advantage in not just defining efficacy and safety, but also the mechanism of our drugs. Having quality data that is well-documented, reproducible, and rigorous is very valuable in a regulatory setting. We need to be able to stand behind these data because it is what will allow us to engage with experts and clinicians.”

Metabolon understands the critical nature of reliable data. Our team of dedicated scientists works to provide pharmaceutical companies with the information needed to advance their programs and support the regulatory process while offering clear analysis to help with the next steps.

Seres harnessed the power of metabolomics to overcome drug development obstacles and inform critical decision-making to advance their programs. Metabolon has long been at the forefront of metabolomics utilization, having executed more than 10,000 projects over the last 20 years. Our unique ability to provide key data and interpret them for you makes us a reliable collaborator as you navigate the complex journey of drug development.