Jon Moss, PhD, Scientific DirectorBut, what is new is the idea of moving M&S from a reactive role to a more active and central role, making M&S techniques a core component in supporting an efficient drug development process and facilitating better decision-making. Today, we can leverage M&S to answer questions like: Which drug candidate is likely to have the highest chance of success in a clinical setting? How to determine the ideal drug dose that will achieve the best therapeutic window? What trial design features are essential in order to maximise statistical power and achieve the required goals within a reasonable time-frame and budget? These applications of M&S, in essence, are becoming more pronounced in the drug development landscape right now.
Tapping into this immense potential of in silico M&S, BAST—a UK-based pharmaceutical CRO—offers stateof-the-art pharmacometric consultancy services, ranging from stand-alone data analyses to long-term strategic project support leading to NDA submissions. Thanks to BAST’s extensive experience in pharmacokinetic and pharmacodynamic (PK/PD) modelling and simulation, clients can rest assured that they are delivering the optimal dose of the right drug candidate to the most appropriate patient population.
BAST’s Rise to Prominence
BAST was founded in 1991 by Joachim Grevel, PhD in Pharmacology, as the first-ever company to offer consultancy services in pharmacometric M&S. After a hiatus down the line, the company was re-launched in 2010 in the UK, and has grown steadily ever since to become the experienced and respected company that it is today. The latest iteration of BAST is headed by Jon Moss, PhD in Mathematical Physics, who took over the reins from Grevel in 2019. However, Grevel still continues to actively participate as a senior scientist and plays a key role in the firm’s strategic discussions. Backed by the company’s proficiency in pharmacometric M&S and accomplished leadership team, BAST covers various aspects of M&S practices like population pharmacokinetics analysis (popPK), population pharmacodynamics analysis (popPD), exposure-response, concentration-QTc analysis, and more.
“Our core competency is in mathematics. Our highly quantitative approach allows us to drive the latest M&S techniques and account for potentially conflicting factors within even well-designed studies in order to uncover the true pharmacokinetic behaviour, pharmacokineticpharmacodynamic relationship, or exposure-response profile,” explains Moss, Scientific Director at BAST. “We are a small team of scientists with experience in both academic and commercial settings. Our company’s core values of scientific integrity, quality, empathy, and flexibility means we have built up a reputation of complete reliability. As multiple clients have said: BAST always delivers!” adds Moss, highlighting his company’s uniqueness. This highly specialised technical expertise, coupled with an earned reputation for consistency and dependability, makes BAST a preferred pharmacometric M&S service provider for many leading pharma and biotech organisations.
Through BAST’s core strengths in popPK, the company can offer a thorough description of PK behaviour within patient populations— including quantification of variability—and establish correlations between different trial variables and intrinsic/extrinsic factors while also assessing potential drugdrug interactions. Through its services in popPD analysis, on the other hand, the firm helps pharma companies create semi-mechanistic population models capable of assisting key decisionmaking by evaluating the biochemical and physiological effects of drug exposure within a population. Moreover, BAST’s robust exposureresponse analysis capabilities allow the company to analyse a wide variety of response data from efficacy and safety endpoints and their relating outcomes to exposure/ dose rate. Regression analysis, time-to-event analysis, and ANOVA are additional examples of where the company’s expertise lies.
BAST’s analytical services cover the full range of drug development, from pre-clinical to post-marketing life-cycle management
At present, BAST’s analytical services cover the full range of drug development, from preclinical to post-marketing life-cycle management. In the pre-clinical setting, M&S work by BAST can inform candidate selection and maximise the probability of success in the clinic. In Phase 1 of clinical development, BAST can help in dosage determination through real-time popPK modelling and simulation. BAST’s popPD and exposure-response modelling in Phase 2 zeroes in on the optimal dosage regimen. Whereas exposureresponse (safety) modelling of Phase 3 clinical data can defend dosage regimens during the market approval process. Finally, additional M&S work can help companies differentiate their drug against competitors in the postmarketing (Phase 4) period. “Whether it is a high-priority accelerated NDA submission or a simple low-budget exploratory analysis, we apply the same exceptional standards throughout,” underscores Moss.
What’s more? BAST also participates in collaborative statistical research with the University of Nottingham’s Department of Mathematics and Statistics. Their combined study based on the modelling of competing risks aims to benefit patients from new therapies.
How Does BAST Achieve This?
The BAST team works transparently with clients, in line with the latest regulatory guidance and internal quality assurance guidelines. To ensure the highest quality of work, BAST’s employees are given training on good clinical practice and modelling methods that include pharmacokinetics, pharmacodynamics, general concepts in non-linear mixedeffects modelling, and more. The company also conducts monthly “risk awareness” meetings where all matters relating to regulatory guidance, IT systems, and continuous improvement are discussed and documented. Owing to all these aspects, BAST recently (Q2 2021) underwent a full GCP audit by an independent contractor, which revealed no material issues in the BAST QA process.
Fostering a Culture that Breeds Success
To best explain how these capabilities help BAST’s clients, Moss shares two instances where BAST helped its clients move ahead of its competitors. On one occasion, BAST provided pharmacometrics analyses and reports to support a major German pharma company in multiple successful global NDA submissions (EMA, FDA, PMDA, and CFDA) of their oncology and cardiovascular drugs. And on another occasion, BAST leveraged its proven competencies to successfully support a medium-sized client through the MIDD (model-informed drug development) pilot program with the FDA.
Moving ahead with many similar success stories, BAST’s ambitions for the next few years is to refine and determinedly enhance its services, bolster and grow relationships with existing clients, and always stay at the forefront of the latest M&S technology whilst serving the pharma industry. “Through these well-rounded efforts, we will continue bringing cutting-edge M&S analysis techniques to the drug development world, allowing pharma and biotech companies to optimise their pipeline and better serve the needs of developers, payers, and ultimately the patients,” concludes Moss.
