With her extensive experience from AstraZeneca and at Quotient Sciences, Zann offers her perspectives on drug development strategies and the transformative potential of the Translational Pharmaceutics delivery platform.
Reflecting on her tenure at AstraZeneca, Zann emphasizes one critical consideration developed during her interactions with her drug development colleagues, “From an oral absorption perspective, it’s important to exercise caution when reviewing non-human data. We've all seen the Grass and Sinko and Musther et al., plots, so we know animals are frequently poor predictors of performance in humans. What really matters is the human absorption data, and the sooner we can see this, the better.”
This perspective underscores the paramount importance of human data in guiding drug development and optimization decisions, a principle she carries into her current role at Quotient Sciences.
Compelling case studies
Zann shares compelling case studies that exemplify innovative approaches in drug development. One such case study focuses on a groundbreaking program targeting amyotrophic lateral sclerosis (ALS). In response to initial preclinical indications of solubility-limited exposures, the team crafted an innovative design for the First-in-Human study (FiH) to enable head-to-head testing of three enhanced formulations within the single ascending dose study.
“The study revealed higher exposure levels in humans for the amorphous formulation than we’d seen in the rat model, thus validating the critical role of human data over animal models in these pivotal formulation decisions”. Zann elaborates, “we predicted we’d see exposures limited by the compound’s solubility characteristics. So, we designed the FiH to not only establish safety and tolerability but also to select the optimal of three different formulations using clinical PK data.”
Another intriguing case study describes the development of a gastro-retentive combination drug product for treating depression. “We knew from the compound’s properties that there was an absorption window necessitating ongoing delivery to the upper gastrointestinal tract. To achieve a patient acceptable dosage form, we had to develop a gastro-retentive formulation. To optimise the drug delivery characteristics of the dosage form, we established and clinically evaluated a flexible formulation ‘Design Space’ to allow us to iteratively vary dose and release rate from the swellable tablet technology. This innovative approach identified an optimized product to sustain drug delivery to absorptive regions of the gut and to achieve the desired reduction in dosing frequency. Ultimately this product will enhance patient compliance and treatment efficacy in individuals with depression.” Zann explains.
Abuse-resistant opioids
Furthermore, Zann discusses an ambitious project aimed at creating abuse-resistant opioid pain medication. Using prodrugs only converted to the active for in the presence of trypsin combined with trypsin inhibitors to limit this conversion, the project devised a multi-pill technology capable of delivering therapeutic levels of oxycodone while eliminating abuse potential.
By advancing approaches such as this, researchers aim to create medications that deliver pain relief while minimizing the risk of misuse and addiction. This approach represents a significant step forward in addressing the opioid crisis and improving patient safety. Looking ahead, Zann highlights the role of artificial intelligence (AI) in advancing drug development and is already working on new chemical entities emerging from drug discovery and entering clinical development. With Quotient Sciences at the forefront of AI integration, she emphasizes the further potential for AI to streamline data analysis, predict formulation outcomes, and accelerate drug development processes. As AI continues to evolve, it promises to revolutionize pharmaceutical research and development, ushering in a new era of innovation and efficiency.
In summary, Zann's insights shed light on the cutting-edge advancements and innovative strategies shaping the future of pharmaceutical research and development. From leveraging human data to develop more effective treatments, to harnessing the power of AI to accelerate drug development, the field is poised for unprecedented progress. As Quotient Sciences continues to push the boundaries, the possibilities for improving patient outcomes and addressing unmet medical needs are limitless.