Early Analytics with PDC Modeling and Translational CROs (BIO 2024)

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Andrew Carnegie of Inaphaea BioLabs explains the role of a translational CRO and of PDC models in drug discovery.


Editor's note: this interview was originally published on PharmTech.com.

A spotlight is focused on drug discovery and early phase analytics at this year’s BIO annual meeting. Inaphaea BioLabs's Andrew Carnegie, PhD, head of Strategic Commercial Development outlines some trends in the R&D analytical space and discusses analytical advances being made to cut short timelines for discovering new drug candidates.

Carnegie explains that translational contract research organizations (CROs) aim to bring more clinically relevant humanized cell-based assays to the forefront early in the drug development pathway. Having clinically relevant data early on can help minimize the risk of failure of a compound/molecule in the preclinical and clinical stages of development, he notes.

“[A translational CRO] is really about providing design, input, and interpretation of results, in addition to just running the experiments, and sending a report based on the study,” Carnegie says. “We feel that better experimental design should lead to a more streamlined plan that is more efficient, and it provides our partners with better value for money. So, we're really looking at cutting down timelines and bringing more data points early on in the experiment so people can make decisions about their molecules early on, and hopefully be more successful in the preclinical and clinical stages.”

Carnegie also emphasizes that drug discovery is a challenging process with a low success rate of release of drugs. “Data suggests that poor prediction of efficacy remains the main cause of attrition and clinical failure. Around that, too, traditional drug discoveries relied on 2D cell cultures, often using non-human species, but animal disease models rarely reflect and represent the real causes, complexities, and phenotypes of human disease. This has really influenced a rise of 3D organoids and more clinically relevant, complex humanized cell models in paving the way for more accurate preclinical models that closely mirror human physiology and pathology,” he explains.

Thus, the humanization of the early phases of drug target validation has the potential to significantly improve how targets are validated for drug discovery, Carnegie adds. Among the tools now being used to humanize early phases of drug target validation are patient-derived cell (PDC) models. “The PDC is a primary cell culture, and it's established from the patient cancer cells, which were isolated directly from the tumor tissue or the patient body fluids. PDCs are maintained at a low-pass ID number, and result in a much higher clinical relevance than tumor cell lines. This really ties in with us wanting to bring humanized models earlier into the process to be more relevant and give more relevant clinical prediction and predictive data. The models are a great combination of accessibility and disease relevance,” he states.

Better early analytical work ultimately improves campaign success or the drug development process, Carnegie also emphasizes. “Our approach is to provide improved data by using more relevant 3D and hypoxia testing in disease-relevant systems, and bringing that [in] earlier … allows for more successful campaigns. [In addition], the kill-the-compound early approach is also very valid, allowing time and money to be better placed. So, with that early analytical R&D work, you can really get a [significant amount] of information upfront, [which] makes your decision easier on whether you'll take that molecule into preclinical and then into the clinic,” he remarks.

“PDCs are really the first step towards the true humanization of preclinical science and can be used to improve the translation of preclinical assets and enhance biological understanding,” Carnegie concludes.

Click the video above for the full interview. BIO 2024 was held in San Diego, Calif., on June 3–6.