A memorable meeting on “Binding Kinetics and Mechanistic PK/PD Modelling in early Drug Discovery”

The meeting “Binding Kinetics and Mechanistic PK/PD Modelling in Early Drug Discovery” took place on 27-28 March 2023 at the Møller Institute in Cambridge, UK and it was a wonderful gathering for our scientific community.

I submitted a proposal for “Binding Kinetics” to the British Pharmacological Society (BPS)’s Meetings Committee after an inspirational ‘Mechanistic Biology and Profiling Leadership Team (MBPLT)’ meeting in January 2022. This meeting emphasised how important it would be to organise a symposium showcasing how investigators around the globe are harnessing mechanistic studies to inform decisions in early drug discovery.

The invited and sponsored speakers for this event were the most passionate advocates of implementing kinetics in early drug discovery. We had a series of oral presentations given by Early Career Researchers (ECRs) and established investigators, demonstrating the importance of kinetics in their enzyme characterisation studies. It was especially special for me since the top leadership of AstraZeneca’s Discovery Sciences arm was able to attend, leading the deliberations. As with all in-person events, this conference also provided opportunities to network and socialise across the two days.

This was the first major event that I had organised, and I learnt a lot about the process and its challenges and rewards. I also cherished the tremendous support I received from my leadership at AstraZeneca, colleagues and friends.

Organising the event

The meeting was approved in early 2022, about a year before it was set to take place. British Journal of Pharmacology (BJP) has a competitive grant to support editors in organization of meetings. As an Editor for the BJP, I was able to submit a successful proposal to draw funds to organise the meeting. I decided to seek the help of my colleague Jonathan Wingfield, a Principal Scientist at AstraZeneca, and he brought his years of experience in navigating this space as our co-organiser.


A bird’s eye view of a fraction of delegates who attended the “Binding Kinetics and Mechanistic PK/PD modelling in early drug discovery” meeting at the Møller Institute on the 27th and 28th of March 2023. Copyright: British Pharmacological Society

I put together a list of speakers, inviting investigators who had defined the evolution of this field. The criterion for selection was the academic merit and the drive to apply the concepts of kinetics within drug discovery optimization processes.  I was also mindful of the Society’s aspiration to achieve gender balance in the program and its responsibilities to promote equality of opportunity, as well as the need to reflect the views of academic and industrial investigators in equal measure. Our full list of speakers is available on the event website.
 

L-R:: Prof. Peter Tonge, Dr. Ana Corrionero, Dr. Margaret Porter-Scott, Prof. Adriaan IJzerman, Dr. Jonathan Wingfield, Dr. Maria Flocco, Dr. Amaury Fernandez, Dr. Daniel Thomas, Dr. Geoff Holdgate, Dr. Rachel Grimley, Prof. Steven Charlton, Prof. Kevin Dalby, Dr. Robert Copeland and myself. Copyright: British Pharmacological Society
 
Thanks to the exceptional list of speakers, we were inundated by abstract submissions for oral and poster presentations. The quality of the submitted science made it difficult for us to select oral presentation themes and, in this exercise, I took the help of my colleagues We anonymously shortlisted a list of oral presentation slots that included leaders in the field, alongside numerous early career researchers from across industry and academia whose research aligned with the scope of the meeting.

In September 2022, I attended the Society’s ‘Pharmacology 2022’ annual meeting, where I was able to advertise our meeting, and shortly after, we opened our meeting for registrations. The nature of the event was hybrid enabling both in-person and online participation. We were pleased that in-person registrations were popular (around 155 in-person versus 45 online), which allowed us to have a vibrant meeting.  This encouraged increased participation and networking, while still offering online participation for those registering from further afield.

As we approached the end of 2022, registrations and anticipation was growing in equal measure. With the support of the BPS Events team, I was developing sponsorship opportunities with several biotechnology firms and CROs with exclusive strength in delivering kinetic insights, including AssayQuant Technologies Inc, Enzymlogic and Applied Photophysics.

For a meeting of this kind, it is important to advertise it far and wide. I leveraged my social media networks on LinkedIn, Twitter and Facebook to advertise the event, and approached organisations directly if I knew the event would be of interest to them. I also got in touch with my extensive network of academic investigators across the globe to spread the word on this event among their respective institutions. Notably, this included advertisements in the monthly newsletters of the Southeast Enzyme conference. Additionally, the Society used its extensive network of contacts to advertise the event. I am extremely thankful for the help and support I got from the communication team at AstraZeneca led by Dr. Chiara Ceci, and the Society’s marketing lead Billy Nichols for helping me refine the communication around the event.

An event to remember

On 27 March 2023, spring had set foot in Cambridge. Daffodils, magnolias and bluebells were beginning to bloom, and the scenic city, with its vibrant community, provided a warm welcome to delegates.  There couldn’t have been a better place or time to host this event, and the Møller Institute provided the perfect setting.


We took some really long walks in Cambridge after the deliberations of the day. (Right) Evening of 27 March on Garret hostel Bridge looking towards the Trinity Bridge. From left to right: Mathias Antoine, Peter Tonge, Margaret Porter Scott and Ad IJzerman.  (left) On the evening of 28 March on the Backs looking towards the King’s College Chapel. From left to Right: Peter Tonge and Kevin Dalby.

As the venue began to fill, it was a thrilling experience to see all our role models, whose literature helped develop our whole understanding of the field, in person. Most of those who contributed to the theme of kinetics in early drug discovery were there either as speakers or as delegates.

Dr. Mike Snowden, the then senior Vice-president of Discovery Sciences at AstraZeneca and a great champion of mechanistic studies in early drug discovery, opened the proceedings, stressing the importance of why detailed mechanistic studies are critical for the success of early drug discovery initiatives. He called for more investment in training the next generation of mechanistic enzymologists as a way of filling this void, especially given the increasing importance of this discipline in understanding the mode of action of alternative modalities of intervention.

The opening plenary talk was delivered by Dr. Robert Copeland. The talk presented a wonderful exposition on why time-evolved metrics should be an integral part of the discourse in early drug discovery. It was a tour-de-force on the applicability of concepts like dissociation, association, residence time, systems pharmacology, protein turnover and so forth.

The proceedings of the second day were opened by Dr. Steve Rees OBE, the then Vice-President of Discovery Biology, at AstraZeneca. He spoke passionately about the need to have mechanistic investigations supporting modern drug discovery. The day ended with the closing plenary talk delivered by Prof Peter Tonge, stressing how a mechanistic approach to PK/PD modelling is an essential prerequisite for gaining a deeper understanding into the aspects of efficacy and dosing.

Dr Maria Flocco, the Vice-president of Mechanistic and Structural Biology division, is an ardent believer in the power of biophysical and enzyme kinetics approaches  to guide decisions in early drug discovery. She was a keen participant on both days of the meeting and presented the oral presentation and poster awards and delivered the concluding remarks, where she reiterated the importance of mechanistic enzymology and kinetics in early drug discovery decisions.

This concluded the official proceedings of the two-day meeting. It was sad to see the event end, but I felt a sense of satisfaction in the way the event enthused attendees about a topic that I am highly passionate about. The event stimulated much conversation among delegates about the potential in implementing the themes discussed during the meeting.

At the end of the event, I felt relieved that it had been a success. With the Society’s Events team, particularly project lead Bonnie Rayner, we delivered a meeting that was able to inspire our community of binding kinetics enthusiasts. It is impossible to thank everyone who supported the delivery of this event in one article, as the list is too long, but I am grateful to everyone who made it happen.

Against the backdrop of this event, I am also working ardently on getting a special themed issue on “Binding Kinetics and Mechanistic PK/PD Modelling in early Drug Discovery” published in British Journal of Pharmacology, with support from our then-Editor-in-Chief Prof. Amrita Ahluwalia, our then-Reviews and Themed Issue Senior Editor Prof. Giuseppe Cirino and the Society’s Head of Journals Publishing Charles Whalley. The effort is ongoing with the help of our current leadership at the journal helmed by our new Editor-in-Chief Prof. Péter Ferdinandy and our new senior editor for reviews and themed issues Prof. Andreas Papapetropoulos.
 
View further details on this meeting


The talks from this event can be freely accessed on the BPS YouTube Channel:

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Published: 13 Dec 2023
By Bharath Srinivasan

About the author

Bharath Srinivasan

Bharath Srinivasan studied the structure-function relationship in members of the Haloacid Dehalogenase superfamily of enzymes as part of his PhD studies. He pursued an NIH-sponsored postdoctoral fellowship at the Centre for the Study of Systems Biology, Georgia Institute of Technology, working at the interface between enzyme kinetics, computational sciences and medicinal chemistry. Subsequently, he was awarded the prestigious Marie Skłodowska-Curie Actions fellowship to study the substrate specificity of deaminases acting on double-stranded RNA at the Instituto Gulbenkian de Ciencia, Portugal. In 2019, he joined the Mechanistic Biology and Profiling unit at AstraZeneca, contributing actively to several oncology projects deducing the MoA of small-molecule leads. Bharath has published around 40 peer-reviewed publications, 1 patent and several science outreach articles. He is editor with two prominent pharmacology journals (British Journal of Pharmacology and Current opinion in Pharmacology), a faculty with H1 connect and on the editorial advisory board of FEBS J. He is an honorary Associate Professor at the Robert Gordon University, Scotland. He is passionate about enzyme kinetics with particular emphasis on studying the spatio-temporal evolution of kinetic systems, steady state kinetics, pre-steady state kinetics, single turnover kinetics and non-Michaelian kinetics. Bharath is also invested heavily in optimizing methods for in-cellulo kinetics and label-free detection methods.

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