This meeting is supported by:
| Monday 2nd September | |
| 09.00 - 11.00 | Delegates arrive, registration and put up posters |
| 11.00 - 11.45 | Welcome and Introduction
So what has the DMDG done for DMPK science? Retro and future perspectives for the Society Simon Taylor, Pharmaron & Kevin Beaumont, AstraZeneca |
| 11.45 - 12.30 | Keynote Lecture:
Harmonising in the Case of Diversity Scott Marshall, Vice-President Clinical Pharmacology, Modelling and Simulation Asia, GSK |
| Lunch, Posters
and Exhibition Poster organisers: Peter Kilford, Simulations Plus; Graeme Scarfe, Nxera Pharma UK Ltd; & Claire Purdy, Charles River Laboratories |
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Session 1: Supercharging Analytics to Advance Drug Discovery and
Development Chair: Scott Summerfield, Pharmaron For decades, DMPK studies in support of drug discovery and drug development projects have been underpinned by analytical tools and expertise. As DMPK science has evolved so too have the complementary analytical methodologies. The interconnectivity of PK and PD and increasing chemical diversity and complexity have required new paradigms of measurement in order to provide key data that helps increase our understanding of DMPK-related issues. This session will look at the application of novel, cutting-edge analytical technologies to address critical issues faced in the modern analytical lab such as target exposure measurements, accelerating compound selection in drug discovery, the impact of catabolism for complex molecular therapeutics, qualitative and quantitative analysis for atypical modalities and definitive safety assessments. 1-1 Taking regulated bioanalysis to the next level using automation, miniaturisation and Design of Experiments 1-2 Advanced Mass Spectrometry Imaging; a new multimodal era in metabolite analysis 1-3 High Content Bioanalysis: Connecting Pharmacokinetics and Pharmacology to Drug/Drug Metabolite Effects on Endogenous Metabolites and Proteins |
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| 15.00 - 15.30 | Tea/Coffee, Posters and Exhibition |
| 15.30 - 17.00 | Session 2: AI and
Machine Learning in DMPK - Hype or Hope? Chairs: Iain Martin, Relay Therapeutics & Andreas Reichel, Bayer Pharma Computational models to predict ADME properties have been available for many years. They have typically been used as replacements for experimental endpoints in screening funnels, thereby speeding up workflows and saving costs. In this symposium, we will attempt to explore how ML and AI approaches offer the opportunity to change our workflows, including informing on compound design, as well as predict more complex endpoints such as animal & human pharmacokinetics, and PK/PD relationships. 2-1 Using Machine Learning to Reshape DMPK Support for Small Molecule Drug Discovery 2-2 Lessons from Applying Machine Learning to Predict Permeability of
Challenging Compounds 2-3 Machine Learning Models for the Prediction of Human In Vivo Pharmokinetic Parameters 2-4 Application of Neural ODE’s to predict PK and PD profiles |
| 17.00 - 18.15 | Session 3: Early
Careers and Student Session: Poster Blitz Chairs: Claire Purdy, Charles River Laboratories & Jamie Henshall, Vertex Pharmaceuticals The Early Careers and Student Session forms part of the DMDG’s commitment to the development of Early Career DMPK/ADME scientists in industry and academia alike. Successful Student Bursary Applicants and selected Early Careers Scientists will be given the opportunity to present their posters in a Poster Blitz, to a friendly, welcoming audience. This session will also provide a chance to meet the new DMDG Apprentice Committee Member for 2024-2026. Presenters from submitted poster abstracts |
| 18.15 - 19.45 | Free time |
| 19.45 | Dinner (Roger Kirk Centre, Campus West) |
| Tuesday 3rd September | |
| 08.30 - 10.00 | Session 4: Challenges
and opportunities in in vitro alternatives with focus on FDA
Modernisation Act Chairs: Amaka Ezuruike, Certara & Beth Williamson, UCB Although animal models have been integral in our understanding of biology, safety and ADME properties, legislators and the FDA have recognized the issues inherent in animal models and took steps to address it. In December 2022, the FDA Modernization Act 2.0 was adopted as law permitting the utilization of specific alternatives to animal testing, including cell-based assays, such as organs on chips, which can be used to seek FDA exemptions for assessing drug safety and effectiveness during the preclinical phase. This session will focus on the recent advances and opportunities for some of these in vitro alternatives, as well as the challenges faced in utilising them as a surrogate for the 3R’s. 4-1 ADME perspective on the applicability of complex in vitro models in DMPK with focus on FDA Modernisation Act 2.0
4-2 The use of CIVM (complex in vitro models) to understand absorption in drug development 4-3 A primary jejunum and primary hepatocyte multi-organ MPS: a promising tool for more predictive studies of human drug ADME and oral bioavailability 4-4 Hepatic biotransformation of anti-neoplastic prodrugs towards different cancer models in a MultiOrgan-Chip test platform
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| 10.00 - 10.30 | Tea/Coffee, Posters and Exhibition |
| 10.30 - 12.00 | Session 5: Decoding
Complex DDIs using preclinical, clinical and /or modelling based
strategies Chair: Kunal Taskar, GSK Drug-drug interactions (DDIs) are mediated when the metabolic enzymes and/or transporters which are relevant for the clearance/disposition of a drug are either inhibited or induced by another perpetrator drug. Usually when a single enzyme or transporter is major determinant of drug clearance then the extrapolation and interpretation of clinical DDIs is comparatively elementary. Frequently, several published case studies have shown that several drugs involve more than one metabolizing enzyme and/or transporters in their clearance pathways. Similarly, more often, several drugs may also inhibit and/or induce more than a few enzymes and/or transporters at the same time. In such scenarios the predictions and evaluation of clinical DDIs becomes a complex task. But with several in vitro, clinical as well as model-based assessments such complex DDIs can be attempted to be decoded and assessed as well as strategies to address such complex DDIs have been or can be established. This session will discuss such complex DDIs and various strategies to address them. 5-1 How can we overcome the challenges posed when conducting complex DDI studies?
5-2 Modelling-based strategies to evaluate complex drug-drug interactions
5-3 Are Combined Oral Contraceptive DDIs Complex or Clear-cut?
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| 12.00 - 13.00 | Lunch, Posters and Exhibition |
| 12.15 - 13.00 | Lunch and Learn
Session Chair: Claire Purdy, Charles River Laboratories This session is all about networking and learning from our wide and varied DMDG community, some of whom you might not otherwise get to meet. It will involve a brief introduction, followed by introductions of mentors and mentees. We will then invite mentor/mentee groups to head to lunch! Ask questions, chat, network and learn. This session is informal and you don't need to prepare anything in advance – just register your interest in being a mentee or mentor before the 26th August, here! |
| 13.00 - 14.30 |
Session 6: Challenges
for DMPK/ADME of Anti-infective Drugs Chairs: Kevin Read, University of Dundee & Caroline Rynn, Roche The Covid pandemic showed how vulnerable society is to highly infectious disease. Future viruses, emerging bacterial resistance to antibiotics, the broader global spread of parasitic infections due to the effects of climate change, people migration and the continued need to effectively treat populations in the global south with better, safer oral therapies will lead to more extensive drug discovery and development effort in the anti-infective space. Compound property needs for pathogen entry, extensive distributional requirements to reach where pathogens reside and the demanding target candidate profiles for some diseases, such as malaria, create many challenges for ADME/DMPK. This session will focus on addressing these challenges. 6-1 The African Liver Tissue Biorepository Consortium: Capacitating Population- Appropriate Drug Metabolism, Pharmacokinetics, and Pharmacogenetics Research in Drug Discovery and Development
6-2 DMPK challenges of developing long half-life antimalarial
drugs 6-3 A hybrid minimal PBPK and machine learning approach to predict drug penetration in tuberculosis lesions
6-4 Defining a tailor-made optimization cascade for antibacterial drugs against gram-negative bacteria 6-5 Challenges in Chagas drug discovery – Assessment of drug distribution to the biophase as a predictor of PK outcome |
| 13.00 - 14.30 |
Session 7: Tissue
Targeted Drug Delivery Chairs: Jamie Henshall, Vertex Pharmaceuticals & Claire Purdy, Charles River Laboratories Drugs need to reach their site of action to exert pharmacological effect. In many cases, the site of action is a specific organ of the body determined by the disease or expression of the target. It is often desirable to maximise the free drug concentration in the target organ relative to the rest of the body to minimize any systemic toxicity or DDI liability, and reduce the required dose. This diverse session will explore developments in targeting drugs to the site of action, such as the delivery of mAbs to restricted organs, in vitro 3D models of the BBB, nanoparticle drug delivery, tumour targeting, and cell and gene therapy vector tropism. 7-1 Targeted Delivery – Getting the Elephant into the Room
7-2 Building on the success of Osimertinib. Targeting brain exposure in oncology drug discovery 7-3 The limits and constraints of tissue-targeted delivery of biologics 7-4 Human blood-brain barrier in vitro models to investigate transport of biologics to the brain |
| 14.30 - 15.00 | Tea/Coffee, Posters and Exhibition |
| 15.00 - 16.30 | Session 8: Free
communications Chairs: Graeme Scarfe, Nxera Pharma UK Ltd & Peter Kilford, Simulations Plus This is an open session for any hot topics or informative case study that you would like to share with the community but may not fit into the themes of any of the other sessions. We would particularly like to encourage Early Career Scientists to use this session to share your data and gain some experience at presenting in front of a friendly audience. Any topic submitted that is not chosen for an oral presentation, can be presented in the poster session. 8-1 Alpibectir: Early Qualitative and Quantitative Metabolic Profiling from a First-Time-in-Human Study by Combining 19F-NMR, 1H-NMR and HRMS Analyses
8-2 In Vitro Structure-Activity Relationship Stability Study of Antisense Oligonucleotide Therapeutics Using Biological Matrices and Nucleases
8-3 Disentangling the mechanism(s) underlying divergent cytochrome P450 activities between human hepatocytes and microsomes: insights from disparate reaction phenotyping
8-4 Comprehensive Evaluation of BTZ-043: From hAME Study to Metabolite Exposures: Handling the challenge of unstable hydride Meisenheimer complex metabolites
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| 16.30 - 18.00 | Session 9: Debate
Moderator: Simon Taylor, Pharmaron "This house believes that human will be the only species in DMPK evaluation by the 65th Open Meeting" |
| 18.00 - 19.00 | Free time |
| 19.00 | Drinks reception (Roger Kirk Centre, Campus West) |
| 19.45 | Conference Dinner (Roger Kirk Centre, Campus West) |
| Wednesday 4th September | |
| 09.15 - 10.45 |
Session 10: Br05 – Why will they be (im)famous – reflections on 3 decades of Macromolecule development Chairs: Simon Taylor, Pharmaron & Steve Hood, GSK (DMDG Fellow) This session will present DMPK based challenging case studies representing various aspects of ADME, PK, PKPD science associated with projects categorized in the Beyond Rule of 5 drug space. The session will be run in a dynamic TED talk style slide free format with the moderators seeking input from the audience on a list of topics across multiple modalities including targeted protein degraders, peptides, oligonucleotides, biologics….etc. If your favorite modality is not included please let us know! If you fancy contributing to a slide free, data light, deep dive down DMPK memory lane come and join the session – no need to prepare slides, just bring your recollections. |
| 09.15 - 10.45 |
Session 11: DMPK for
Gene Therapies Chairs: Alex James, Novartis & James Yates, GSK AAV gene therapy is a rapidly growing ‘new modality’ field where DMPK will still have a critical role in advancing candidates from non-clinical research to clinical development. The development strategies for these therapies are an active area of research and are still evolving. 11-1 Introduction: Considerations for Dose Selection in AAV Gene Therapies 11-2 Exploring new frontiers in therapeutics: lessons from the coalface
11-3
Title TBC |
| 10.45 - 11.15 | Tea/Coffee, Posters and Exhibition |
| 11.15 - 12.45 | Session 12: Gut
beyond absorption: from target organ to site of metabolism Chairs: Ian Wilson, Imperial College London (DMDG Fellow) & Kevin Beaumont, AstraZeneca The gastrointestinal system has been studied extensively in the context of drug and nutrient absorption. With unmet medical needs for inflammatory bowel disease, research and strategies of gut targeting therapies with limited systemic exposure for safety become important. Also, recent advancement in gut microbiome research highlights the potential of gut lumen as site of drug metabolism. In this session, we will highlight recent research in gut restricted drug discovery and development, and advancement in understanding and translating drug metabolism in gut lumen. 12-1 Have the guts: Potential strategies to design peripheral or gut-restricted molecules
12-2 Drugging the gut microflora – DMPK studies on bacterial Beta-glucuronidase inhibitors
12-3 Using cell-compatible mucus to achieve integrated in vitro modelling of digestion, mucus permeation and epithelial absorption
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| 12.45 - 13.00 | Closing Remarks |
| 13.00 | Lunch and departure |