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Driving Preclinical Development Success (plus Webinar Invitation)

The pharmaceutical industry is under huge pressure to address the high attrition rates in drug development. While there are many factors that can cause efficacy- and safety-related failures, including the difficulty of detecting rare events in small clinical trial populations, a predominant reason for failure is that preclinical animal models, as well as some long-established in vitro assays, are often unable to accurately predict clinical efficacy and safety.

 For scientists working in the field, enhancing the predictability of their research efforts has, historically, proved challenging and relies on the development and selection of appropriate models to efficiently predict drug behavior in humans.

Dr. Seyoum Ayehunie, Vice President of Scientific Research and Development at MatTek Corporation, believes that novel in vitro models are needed to guide the design of molecules with lower risk and/or to develop dosing schedules that mitigate the risks in humans. His current work involves the development of an in vitro 3D primary human cell-based tissue model for drug toxicity and efficacy studies.

“Traditional in vitro cell culture approaches with immortalized human cell lines have been widely applied for assessing drug permeation properties, but these cells have unphysiological barrier properties and have not yielded validated assays for toxicity and efficacy studies,” he explains. “As a result, current preclinical tests for safety depend on in vivo testing in higher-order species to achieve translational accuracy.” However, the caveat with animal models is that they are expensive and often do not adequately recapitulate human physiology; for example, drugs showing safety and efficacy in preclinical animal models may show very different pharmacological properties when administered to humans.

Novel Model Approaches

Dr. Ayehunie says that development of predictive preclinical assays is essential to help reduce the risk of drug-induced toxicity and late-stage drug attrition. In his current work, he has developed an in vitro primary human cell-based organotypic small intestinal (SMI) microtissue for predicting intestinal drug absorption, metabolism, and drug-drug interactions that can be used to predict drug toxicity and efficacy.

“The 3D-intestinal microtissues recapitulate the structural features and physiological barrier properties of the human small intestine,” he says. “The microtissues also express drug transporters and metabolizing enzymes found on the intestinal wall.” The model is being used by major pharmaceutical drug companies involved in drug-induced gastrointestinal toxicity of cancer drugs, intestinal drug permeation, inflammation, wound healing, and microbial infection.

Another leading expert in preclinical development is Dr. Hyelim Cho, Group Lead, Immunogenicity, Global DMPK Oncology and Rare Diseases at Takeda Pharmaceuticals. She is currently leading a team developing strategies and methods for preclinical immunogenicity assessment and designing translational bioassays for the regulatory filing efforts specifically related to oncology and rare diseases.

Dr. Cho has experience using multiple pre-clinical assays, including cultured human primary immune cell-based assays and patient-derived 3D organoid assays. “Developing a predictive preclinical assay is key to success in immuno-oncology drug development,” she says. “It is critical to carefully construct biomarker studies using the most appropriate assays that better represent the complex physiology of disease for the reliable assessment of safety, efficacy, and dose predictions.”

WEBINAR INVITE: Sharing Expertise in Preclinical Studies

Dr. Ayehunie and Dr. Cho will be sharing their in-depth knowledge of preclinical studies in an upcoming webinar, which will be broadcast live on May 26. The webinar will focus on preclinical studies within a physiological context to better understand the complexity of diseases, as well as the efficacy and safety of therapeutic interventions.

Key learning objectives include:

  • How to effectively evaluate models to establish robust and reliable preclinical investigation of drug candidates prior to entering clinical trials;
  • How to gain an understanding of the advancements in preclinical model systems and assays; and
  • What to consider from the latest innovations and their impact on bioanalytical assays.

The live webinar is free to attend: Wednesday, May 26 at 8AM PDT; 11AM EDT; 4PM BST; 5PM CEST.


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