Peakdale Molecular and CXR Biosciences (members of the Concept Life Sciences Group) brought together a number of eminent speakers recently as part of their Spotlight Session series. The event, which was held at the Kohn Centre at the Royal Society in London focussed on current challenges in integrating safety testing into early drug, agrochemical and consumer products R&D.
The Concept Life Sciences’ companies were joined by a number of handpicked delegates from the pharma, biotech, agrochemical and consumer products industries, in addition to CROs, academics and investment companies all keen to hear from the eminent speakers who included:
- Sir Colin Berry (former member of the Committee on Safety of Medicines and former chairman of the UK Advisory Committee on Pesticides) who discussed ‘What’s Wrong with Risk Assessment in Pharma and Agrochemicals?’;
- Prof Paul Leeson (Paul Leeson Consulting) discussing ‘Design of Compounds to Improve Success’;
- Dr Nigel Swain (Pfizer) on ‘Improving Toxicity Predictions to Design Safer Acidic Molecules’;
- Dr Phil Hewitt (Merck KGaA) who looked at ‘Recent Advances in Discovery Toxicology: Models/biomarkers for Liver and GI toxicity Assessment’;
- Dr Mark Graham (Pharma Investigative & Discovery Toxicology Consultant to CXR Biosciences) who talked about a number of Discovery Toxicology Case Studies.
Sir Colin Berry, former head of Department and Professor of Pathology at the Royal London Hospital and Dean of its Medical School, opened the Spotlight Session discussing the objectives of regulatory action, the aim of intervention and how risk may be characterised. Sir Colin gave some illustrative examples of (amongst other issues) how risk data may be misinterpreted, and the dangers of confusing correlation with causation.
The pharmaceutical industry remains under significant pressure to address the high attrition rates in drug development. Following on from Sir Colin, Professor Paul Leeson, a medicinal chemist with over 35 years’ experience, discussed ways in which to improve clinical success though compound design, focusing on the correlations between properties and toxicity. He commented that ‘despite changes made we are not seeing huge improvements of compound attrition and there are still gaps in our knowledge.’ He went on to discuss how this can be related to the limited size of data sets from individual companies and how cross collaboration in this area is crucial.
Dr Phil Hewitt, who established the Molecular Toxicology Group at the Institute of Toxicology at Merck KGaA in Germany, gave an excellent review of the state-of-the-art in novel in vitro and in vivo methods for predicting liver and GI toxicity in early R&D, and highlighted the benefits and shortfalls of these tools.
After lunch Dr Nigel Swain resumed the session and gave an overview on how to improve toxicity predictions to design safer acidic molecules. He presented case studies showing how a significant proportion (78%) of drugs associated with toxicity contained structural alerts and evidence indicating that RM formulation as a causative factor has been presented in 62% of these molecules. This design approach is not always the easiest way forward, but the results can be impressive.
Dr Mark Graham, who has almost three decades of experience in pharmaceutical toxicology including 14 years at AstraZeneca, rounded up the day with two case studies demonstrating the utility of hypothesis-driven, early safety studies in understanding and mitigating both target-related and off-target liabilities in early drug discovery.
After a Q & A session, Paul Doyle, the Chief Operating Officer at Peakdale wrapped up the day with a short summary and a thank you to guest speakers and organisers.
“We were pleased to host an event bringing together insightful thinkers on the design and analysis aspects of early toxicology. It is an extremely important area that can deliver so much in reducing attrition, establishing hypothesis-based safety testing as a key component of early discovery”