The 22nd North American ISSX meeting was held this year in Montreal where scientists joined together to discuss issues in drug development. Hot topics included transporters, pharmacogenomics, and antibody drug conjugates (ADCs). The transporter session included lectures on kidney and hepatic transporters and potential association with drug-induced liver injury (DILI).
BioIVT announced its acquisition of Optivia Biotechnology, adding transporter assay products and services to its ADME-Tox portfolio. The acquisition strengthens BioIVT’s transporter sciences capabilities and enables them to partner with customers on new drug applications and mechanistic studies related to transporters. Click here to read the press release.
BioIVT hosted a seminar featuring T. Eric Ballard, Ph.D., from Pfizer’s Biotransformation group in which Dr. Ballard spoke about his research using HEPATOPAC® cultures. He discussed the effectiveness of HEPATOPAC technology to evaluate metabolite ID in low turnover compounds and how the system can recapitulate in vivo results from humans as well as preclinical species in a single experiment. Because of their long-term viability and high metabolic capacity, HEPATOPAC cultures are uniquely capable of identifying species-specific, and low prevalence metabolites.
Dr. Jonathan Jackson, Senior Scientist at BioIVT, presented a poster entitled “An Integrated In Vitro Screen using Sandwich-Cultured Human Hepatocytes for Prediction of Cholestatic Hepatoxicity.” The poster summarized the development and qualification of the in vitro C-DILI™ Assay and its effectiveness in predicting cholestatic hepatotoxicity. The poster demonstrated that BSEP inhibition “triggers” FXR activation initiating bile acid homeostasis compensatory mechanisms (e.g., basolateral efflux of bile acids) to prevent bile acid-induced hepatotoxicity. Identification of this “triggering event” ushers in a new paradigm in cholestatic (e.g., bile acid-induced) hepatotoxicity prediction where the adaptive response must be taken into account simultaneously with inhibition of bile acid efflux to improve prediction accuracy.
Dr. Brouwer, VP Research at BioIVT participated in a lively debate session titled, “Be It Resolved that In Vitro Assays, Such As Mitochondrial Injury or BSEP Inhibition, Do Not improve Drug Candidate Safety.” This was the first debate at ISSX since a meeting in the UK in the late 80’s.
Dr. Brouwer represented the viewpoint that the majority of the current in vitro tests focus on the acute effects of a drug candidate, and what we really need are in vitro tests in whole cell models – such as models that integrate the ability of a cell to adapt to the drug candidate’s effects. He used the example of the lack of the ability of BSEP inhibition potency alone to predict hepatotoxicity (50% accuracy), however when the same compounds were evaluated in a system under physiological conditions that allowed for integration of the adaptive response of the hepatocyte (BioIVT’s C-DILI Assay), the prediction reached an accuracy of 95%. Contact Dr. Brouwer to learn more about BioIVT’s “whole cell” models that integrate acute and chronic effects of compounds, thus improving prediction of hepatotoxicity.
The Hepatocyte Researchers Association (HRA), which BioIVT sponsored, held its annual meeting on Tuesday afternoon with a program focused on hepatic induction of cytochrome P450s (CYP). Talks from Dr. David Buckley (Roivant Sciences, Inc.) and Dr. Steve Ferguson (National Institute of Environmental Health Sciences) gave some background into current issues and challenges surrounding variability and utility of current induction methodology. A panel discussion, with the speakers being joined by Jane Kenny (Genentech), Niresh Hariparsad (Vertex) and Michael Sinz (BMS), followed to answer questions and lead the dialogue into findings from the IQ Induction Working Groups recent papers. It was a well-attended session with a lively discussion on how in vitro hepatocyte assays can be optimized to be more predictive and reliable.
On Wednesday, afternoon session focused on the gut microbiome and its involvement with both drug efficacy and toxicity. Wednesday finished with another session centered around the IQ Consortium’s publication on CYP induction where extensive data sets and best practices for hepatocyte models that lead to the most reliable in vitro/in vivo correlation were presented. More publications and debates are to come in the future.
The final plenary seminar, Opportunities, and Challenges in the Discovery of Novel Agents for the Treatment of Malaria, was presented by Dr. Jeremy Burrow from the Medicines for Malaria Venture (MMV), a non-profit group focused on developing new medicines for the treatment of malaria. He highlighted the challenges and progress they have made in discovering and testing new drugs for the treatment of malaria at multiple stages of its lifecycle as it passes from hepatocytes to red blood cells and finally to a new mosquito. Much of the success his group sees comes from building collaborations between MMV, Academic Institutions, and Pharmaceutical companies. There is a lot of hope in treating this devastating disease, which affects more than 200 million people each year.
It was another successful year in the fast-paced market of drug development, always moving forward to embrace the new challenges that lie ahead.
Learn more about our new offerings and technologies that allows BioIVT to bring a more complete set of solutions for drug development scientists.