Bile Acids Targeted Panel

Metabolon’s Bile Acids Targeted Panel measures all the major human and rodent primary and secondary bile acids as well as their glycine and taurine conjugates.

Key Applications

• Drug development for the treatment of fatty liver disease (e.g. FXR receptor agonists)
• Liver diseases
• Biopharmaceutical modulation of the host microbiome
• Basic microbiome research

Why Metabolomics?

Metabolomics reveals biological insights otherwise unseen. For a successful metabolomics study, both small molecule discovery and the ability to dig deeper into specific biomarkers of interest are needed to uncover actionable insights that propel new therapeutic developments. A specific combination of liquid chromatography-mass spectrometry (LC-MS) technology and expertise is required to identify these biomarkers of interest and develop assays that are sensitive enough to explore them fully.

Why Metabolon?

At Metabolon, we understand the crucial role targeted small molecule assays play in drug development, and we’ve established best-in-class expertise. Metabolon has developed quantitative assays for more than 900 biochemicals in over 20 different matrices, including more than 150 qualified and/or validated targeted biochemical assays for pharmaceutical and biotechnology research and development. These assays focus on specific metabolites or metabolic pathways and can be used to track biomarkers and enhance biological understanding across preclinical and clinical research.

LLOQa
Metabolite	Serum/Plasma (ng/mL)b	Feces (ng/mg)b	Feces in OMNImet™·GUT tube (µg/g dry feces)c
Cholic Acid	2.5	0.25	0.63
Chenodeoxycholic Acid	5.0	0.50	0.63
Deoxycholic Acid	5.0	0.50	0.63
Lithocholic Acid	2.5	0.25	0.63
Ursodeoxycholic Acid	5.0	0.50	0.63
Glycocholic Acid	2.5	0.25	0.13
Glycochenodeoxycholic Acid	5.0	0.50	0.13
Glycodeoxycholic Acid	2.5	0.25	0.13
Glycoursodeoxycholic Acid	5.0	0.50	0.63
Taurocholic Acid	2.5	0.25	0.63
Taurochenodeoxycholic Acid	5.0	0.50	0.130
Taurodeoxycholic Acid	5.0	0.50	0.63
Taurolithocholic Acid	2.5	0.25	0.63
Tauroursodeoxycholic Acid	2.5	0.25	0.130
Glycolithocholic Acid	2.5	0.25	0.63
Additional Bile Acids in Rodent Samples
Alpha-Muricholic Acid	2.5	0.25
Beta-Muricholic Acid	2.5	0.25
Omega-Muricholic Acid	2.5	0.25
Gamma-Muricholic Acid	2.5	0.25
Tauro Alpha-Muricholic Acid	10	1.0
Tauro Beta-Muricholic Acid	10	1.0

^aLower Limit of Quantitation (LLOQ) varies for each sample type.

^bAssays with this sample type are for non-GxP testing and are not for diagnostic use.

^cGood Clinical Practice (GCP) Assays. Lower Limit of Quantitation (LLOQ) stated is based on normalization using an average dry weight of feces. The actual measurement of the assay is the concentration of analyte in the OMNImet™·GUT tube containing human feces. Analyte concentrations in the OMNImet™·GUT tubes will be normalized by measured dry weight of feces unless otherwise requested.

Analysis Method and Instrumentation

LC-MS/MS (Agilent 1290 UHPLC/Sciex QTrap 5500 (GCP) or 6500 or 6500+ (non-GxP testing)

Sample Type and Required Amounts
Sample Type	Sample Requirement
Feces (wet weight)	200 to 500 mg
Plasma/Serum	100 to 150 µL
Tissue (liver)	200 to 500 mg
Bile	50 to 100 µL
Feces in OMNImet™·GUT tube	Approx. 500 mg in OMNImet™·GUT tube, filled according to manufacturer specifications

Disclaimer: Non-GxP assays are for Research Use Only and are not to be used for diagnostic purposes.

“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.”

Christopher Ford, Ph.D.
Senior Director, Computational Microbiome Sciences at Seres Therapeutics

About Seres Therapeutics

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: Unsatisfactory Phase II Results

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.

The Solution: Bile Acid Targeted Panel

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

The Outcome: Leveraging the Bile Acids Targeted Panel

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.

Dr. Sassone-Corsi’s insightful works into the circadian rhythm have been fueled by metabolomics revealing numerous findings to support health and disease management.

References

1. McGovern BH, Ford CB, Henn MR, et al. SER-109, an Investigational Microbiome Drug to Reduce Recurrence After Clostridioides difficile Infection: Lessons Learned From a Phase 2 Trial. Clin Infect Dis. Jun 15 2021;72(12):2132-2140. doi:10.1093/cid/ciaa387