16th European ISSX and DMDG Meeting

Programme highlights

Sunday, June 11, 2023

Short Course 1: Physiologically-based Pharmacokinetic (PBPK) Models: Basic Concepts to Advanced Applications

Chairs: Kunal Taskar, GSK and Pradeep Sharma, AstraZeneca

Short Course 2: Pharmacogenomics Basics

Chairs: Ann Daly, University of Newcastle and Ana Alfirevic, University of Liverpool

Short Course 3: The Application of Humanised Models in Drug Discovery and Development and in the Design of Clinical Trials

Chairs: Roland Wolf, University of Dundee and Lorna

Ewart, Emulate

Short Course 4: New Modalities, Beyond Rule of Five

Chairs: To be announced.

Opening Keynote Lecture: Personalised Medicine

Professor Sir Munir Pirmohamed, University of Liverpool

Tuesday, June 13, 2023

Use of PBPK in Drug Development

Aleksandra Galetin, University of Manchester

Symposium 3: Connecting AI/ML and PBPK Modeling for Lead Identification and Optimization in Early Drug Discovery

Chairs: Andres Olivares-Morales, Roche and Yanran

Wang, Genentech

Symposium 4: MicroRNAs as Biomarkers of Clinical Drug-induced Organ Injury

Chairs: To be announced.

Free Comms - Breaking Science

New Investigator/early Career Scientist Session

Monday, June 12, 2023

DMDG Fellow Presentation

Suzanne Iverson Hemberg, Toxicology Knowledge

Team Sweden AB

Symposium 1: Harnessing –omics Approaches in Drug Development

Chairs: Jim Monroe, Merck and Co. and Christopher Goldring, University of Liverpool

Symposium 2: Challenges and New Technologies in Delivering Brain Penetrant Therapies

Chairs: To be announced.

Plenary Session 1: Optimisation Challenges of Protein Degraders – Perspectives from DMPK and PK/ PD Modeling

Chairs: To be announced.

Plenary Session 2: Use of PK Enhancing Strategies / Co-therapies

Chairs: To be announced.

Wednesday, June 14, 2023

ADME Tactics in the Discovery/Development of Oral COVID-19 Protease Inhibitors

Amit S. Kalgutkar, Pfizer, Inc

Microphysiological Systems for ADME Applications

Chairs: To be announced.

War Stories: Drug Discovery from the Trenches

Chairs: To be announced.

DMDG Debate: Theme to be announced

Networking Dinner: Knebworth Barns

Hi all! My name is Claire Purdy and I am the DMDG Apprentice Committee Member for 2022-2024. I am excited to take over from Sarah Armstrong and continue her amazing work as an advocate for Early Careers Scientists in DMPK.

Following on from the success of the face-to-face 2022 Meeting hosted by Sarah, I am excited to announce the opening of registration for the 2023 Early Careers Meeting!

This is the fourth-edition the free one-day DMDG meeting designed to provide a platform for Early Career DMDG members to participate in a vibrant scientific meeting and is exclusively open to scientists who are currently in their first 5 years of working in a DMPK role. Here are some images from EC 2022...

At the meeting you can:

• Bring a poster

• Present your work to a welcoming audience

• Have your say in our forums and voting polls

• Network and learn with fellow Early Careers Scientists

The presenter voted Best Oral Presentation will be offered a free place* to the 16th European ISSX and DMDG Meeting in June 2023 to present their talk.

*travel not included

The DMDG are delighted to announce that Suzanne has been appointed as the DMDG’s 5th fellow, and to mark the occasion we asked her a few questions...

DMDG: Tell us about yourself and your work?

Suzanne: I am a scientist and a leader of scientific organisations. I have quite deliberately carved out a career where I have developed both competencies at the same time, almost every step of the way. I view organisations of people with the same fascination and eagerness to understand as biological systems. My expertise in science is in biotransformation, biomarkers of toxicity, drug metabolism and distribution as well as the bioanalytical techniques desirable to study all of these. My expertise or uniqueness in management/leadership is seeing the individual whilst keeping a sharp focus on the needs and direction of the organisation.

DMDG: What does the DMDG mean to you?

Suzanne: The DMDG means community to me. It probably does for many of us. For an expat (Canada to Sweden) as well as being impacted by an R&D site closure and moving as a result, the DMDG meant that I could maintain some sort of continuity. It didn’t hurt that I got to travel to England now and then and hear, see, and feel cultural references that I grew up with, speak English freely and buy a load of Mark’s and Spencer ginger snaps.

DMDG: Can you tell us how you’ve been involved with the DMDG over the years?

Suzanne: One of my PhD mentors was a clever bloke from Sheffield by the name of Iain Gardner! Several years later he reached out to invite the DMPK department at the Södertälje site to become members of the DMDG and he asked my managers to nominate me to become the site rep. I imagine everyone in the DMDG committee at the time thought I would be the perfect conduit to bring in the Scandinavians. The first few years after that, besides having my second child, I gave talks at two of the Open Meetings. In 2010 I joined the ”Scientific Organising Committee”, which then the DMDG committee in 2011. For the first two years on the committee I was the Training Course organiser followed by treasurer and finally Chair in 2016. I also chaired the scientific organising committees for the 2013 and 2014 Open Meetings (Robinson and Paris) and have chaired countless sessions. From 2017 onward, I have been involved in planning Joint Open Meetings between the DMDG and the Swedish Pharmaceutical Society, the latter of which I am a committee member with the PK-Metabolism section. The 2018 Joint Open Meeting was in Gothenburg, my home at the time. I was treasurer for both this and the 2022 Joint Open Meeting in Amsterdam. And then of course I have been involved in the activity that all of the other DMDG fellows have been involved in. I should have seen it coming I was in both the 2021 (on-line) and 2022 debate!

DMDG: Thanks Suzanne, and we look forward to many more years of your contribution (and debates?) in your new role.

DMDG resumes face to face training courses in 2022

The resumption in-person training in 2022 proved extremely popular and there was high demand for all of the courses run last year. This year we have a packed schedule planned, kicking-off with the inaugural Chemistry Essentials for DMPK course in March. We have scheduled an additional Fundamentals of DMPK course this year since we were unable to meet the exceptionally high demand last year. A full list of residential courses running in 2023 is given below. Please register on the website as soon as possible to avoid disappointment!

In a return to the regular cycle of training course offerings in 2022 the following residential courses are scheduled.

In recent months we have worked hard to standardise the course pricing as much as possible but ensure we still offer excellent value for money. Please register on the website as soon as possible to avoid disappointment!

Our training course blends the best of high quality lectures and tutorials led by experienced industry representatives with excellent networking and social opportunities consistent with the DMDG values. Further information on each course is available by clicking the image of the course brochure (include image and link)

As always, a big thank you to all the course leaders and tutors for volunteering their time and energy in operating the training program. We would like to give a special mention to Kevin Brady, who has stepped down from his role in leading the Large Molecules course due to other work commitments. Kevin played a key role in the inception of and leading the Large Molecules course over the past decade and we thank him for his contribution. The Large Molecules course will now be led by Rob Nelson and Rob Wilson.

Over the past year we have initiated a streamlined the process for recruitment of new tutors as required by the course leads by putting out a call to members. If you are interested in getting involved, please look out for these calls, or reach out to info@DMDG.org.

From the 3rd to 5th October last year we finally returned to face-to-face meetings with our first open meeting co-organized with GMP and SPS, held in the beautiful city of Amsterdam.

The organizing committee, which had representation from all three societies, put together a great program of sessions covering diverse topics like PK-PD of new modalities, new in vitro assays, machine learning, DDI and biotransformation.

Other sessions captured the essence of the DMDG, GMP and SPS co-organizers such as the student session, the candlelight lecture which was given by Ulf Eriksson and of course the DMDG debate.

Following a close battle between Suzanne Iverson and Jamie Henshall, speaking for the motion, and Steve Hood and Matt Segall speaking against, Steve and Matt emerged as the victors. The debate was expertly ‘refereed’ by Simon Taylor who ensured things did not get too personal

Overall the meeting was a great success, selling out well before the event. AssociAction and Hotel Mövenpick looked after us all very well, ensuring that everything ran smoothly. Many thanks to the membership for the feedback we received, which was shared with the three societies. There is a plan to run this joint meeting again in the future.

We also had workshops on Peptide and Oligonucleotide ADME and Biotransformation running just before and after the meeting, which were also very well attended. The meeting report for the Biotransformation workshop has been published and is available here

To close, I’d like to thank all those involved on the organizing committee, the session chairs, speakers , AssociAction and our many sponsors for their vital contributions to this great meeting .

Finances for 2021 continued to be impacted by the disruption resulting from the COVID-19 pandemic. As reported at the ABM, income for 2021 was £63317.94 while expenditure was £96407.66 with a net loss of approximately £33089.72. This loss was expected due to much of the income for online DMDG/SPS Joint Meeting and three training courses postponed from 2020 to 2021 being received in 2020 while costs were not incurred until 2021. The loss in 2021 is made up for by a healthy surplus in 2020 and over the two-year period (2020 and 2021) there was a modest surplus of £12,683.

Overall net assets of the DMDG stood at £127936.16 at the end of 2021. The committee agree to maintain a net worth at a level close to the cost of an Open Meeting, which represents a reasonable operating budget. The DMDG remains committed to re-investing surplus funds into education and training for example through the provision of student places ant DMDG evens and fully funding the Early Careers Meeting.

The DMDG Committee and Fellows are delighted to announce the publication of a special Issue of Xenobiotica celebrating the 50th anniversary of the Society.

The links to each article in the issue can be found in the table below. The issue comprises 16 high quality research and review articles from members highlighting the breadth and depth of ADME/DMPK science and expertise across multiple modalities supported by members of the DMDG community.

As highlighted in the Forward, the Society has made significant strides over the last decade:

• Rebranding from Drug Metabolism Discussion Group to The DMDG

• Expansion of membership with members from 30 countries and representation from pharma/ biotech, CROs and academia.

• Continuation and expansion of training course offerings.

• Incorporation of the DMDG Apprnticeship scheme and the Early Careers Meeting.

• Introduction of the DMDG Fellowship awards with 4 (soon to be 5) Fellows in place.

• Strong financial position despite the problems associated with the pandemic.

• Collaboration with AssociAction.

• Supporting the expansion of DMPK/ADME science to newer modalities, including ADCs, peptides, proteins and oligonucleotides, as shown in this issue.

• Incorporation of in silico and PBPK modelling approaches.

• Support of new technologies (such as organoids and organ on a chip).

The DMDG committee and Fellows would like to thank Professor Costas Ioannides and Informa Healthcare for facilitating the publication of the special issue. In addition, thank you to all of those Society members who submitted and contributed papers. The list of papers follows...

Continued on next page

Taylor, S, et al (2022) “The 50th Anniversary of the DMDG.” https://doi.org/10.1080/00498254.2022.2134835

Xenobiotica 52(8): 767 – 769.

Aigbogun, O. P., et al. (2022). "An HPLC-UV validated bioanalytical method for measurement of in vitro phase 1 kinetics of α-synuclein binding bifunctional compounds."

Xenobiotica 52(8): 916-927 https://doi.org/10.1080/00498254.2022.2140315 https://doi.org/10.1080/00498254.2022.2141667 https://doi.org/10.1080/00498254.2022.2119180 https://doi.org/10.1080/00498254.2022.2132426 https://doi.org/10.1080/00498254.2022.2124388 https://doi.org/10.1080/00498254.2022.2115428 https://doi.org/10.1080/00498254.2022.2124389 https://doi.org/10.1080/00498254.2022.2128468 https://doi.org/10.1080/00498254.2022.2130838 https://doi.org/10.1080/00498254.2022.2119900 https://doi.org/10.1080/00498254.2022.2130837 https://doi.org/10.1080/00498254.2022.2133649 https://doi.org/10.1080/00498254.2022.2116368 https://doi.org/10.1080/00498254.2022.2129519 https://doi.org/10.1080/00498254.2022.2136042

Beaumont, K., et al. (2022). "ADME and DMPK considerations for the discovery and development of antibody drug conjugates (ADCs)."

Xenobiotica 52(8): 770-785.

Esposito, S., et al. (2022). "Subcutaneous catabolism of peptide therapeutics: bioanalytical approaches and ADME considerations."

Xenobiotica 52(8): 828-839.

Gardner, I., et al. (2022). "Non-specific binding of compounds in in vitro metabolism assays: a comparison of microsomal and hepatocyte binding in different species and an assessment of the accuracy of prediction models."

Xenobiotica 52(8): 943-956.

Golding, M., et al. (2022). "Use of selective substrates and inhibitors to rapidly characterise batches of cryopreserved primary human hepatocytes for assessment of active uptake liability in drug discovery and development."

Xenobiotica 52(8): 868-877.

Hood, S., et al. (2022). "Meeting report: oligonucleotide ADME workshop."

Xenobiotica 52(8): 957-961.

Kendrick, J. S. and C. Webber (2022). "One small step in time, one giant leap for DMPK kind – a CRO perspective of the evolving core discipline of drug development."

Xenobiotica 52(8): 797-810.

Kerins, A., et al. (2022). "The in vitro metabolism and in vivo pharmacokinetics of the bacterial βglucuronidase inhibitor UNC10201652."

Xenobiotica 52(8): 904-915.

Martins, V., et al. (2022). "A commentary on the use of pharmacoenhancers in the pharmaceutical industry and the implication for DMPK drug discovery strategies."

Xenobiotica 52(8): 786-796.

Nwabufo, C. K. and O. P. Aigbogun (2022). "Potential application of mass spectrometry imaging in pharmacokinetic studies."

Xenobiotica 52(8): 811-827.

Poller, B., et al. (2022). "Time matters – in vitro cellular disposition kinetics help rationalizing cellular potency disconnects."

Xenobiotica 52(8): 878-889.

Rose, R. H., et al. (2022). "Application of physiologicallybased pharmacokinetic models for therapeutic proteins and other novel modalities."

Xenobiotica 52(8): 840-854.

Rynn, C., et al. (2022). "A translational strategy employing physiologically based modelling to predict the pharmacological active dose of RO7119929, an oral prodrug of a targeted cancer immunotherapy TLR7 agonist."

Xenobiotica 52(8): 855-867.

Toselli, F., et al. (2022). "Drug clearance by aldehyde oxidase: can we avoid clinical failure?"

Xenobiotica 52(8): 890-903.

Weston, D. J., et al. (2022). "A discovery biotransformation strategy: combining in silico tools with high-resolution mass spectrometry and softwareassisted data analysis for high-throughput metabolism."

Xenobiotica 52(8): 928-942.

Xenobiotica: Vol 52, No 8 (Current issue) (tandfonline.com)