Application of New Approach Methodologies (NAMs): Consideration for Drug development
Medicon Valley Alliance and Labcorp would like to welcome you to an exploration of New Approach Methodologies (NAMs) and their impact on diverse scientific realms.
From in vitro alternatives to non-animal methods, NAMs have evolved into an internationally accepted term with industry-agnostic applications.
Our sessions will unravel the regulatory landscape, delve into innovative seizure liability assays, and introduce a paradigm shift with virtual control groups (VCGs) in drug development.
Discover how NAMs can transform development timelines, reduce costs, and enhance safety testing without compromising scientific rigor.
Date: Thursday 7th of March 2024
Time: 9:00 – 16:00
Venue: Medicon Valley Alliance, Arne Jacobsens Allé 15, 2300 Copenhagen S, Denmark – Hub2 Auditorium
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Program
9:00 |
Networking, registration and light breakfast |
10:00 |
Welcome and introduction to Medicon Valley Alliance
David Munis Zepernick, Director, Member Engagement & Communication, Medicon Valley Alliance
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10:15 |
Opening intro – Defining NAMs (M&S, AI, in vitro, MPS)
John Kendrick, LabCorp |
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10:30 |
MORNING SYMPOSIA SESSIONS |
10:30 |
Session 1: Lessons learnt from CP&C – regulatory framework, validation and model acceptance
Darren Kidd, LabCorp |
11:00 |
Session 2: NAMs – the regulatory environment with respect to alternative approaches
Andy Gibbs, LabCorp |
11:30 |
Session 3: NAMs for the detection of seizure liability in drug discovery
Michael Morton, Apconix |
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12:00 |
Lunch and networking
Lunch is provided |
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13:00 |
AFTERNOON SYMPOSIA SESSIONS |
13:00 |
Session 4: Case study – model for Immunotoxicology
Chris Cooper, LabCorp |
13:30 |
Session 5: Support Of First-in-human Clinical Trials With Human In Vitro Toxicity Testing – Perspectives of EFPIA Safety Reflection Initiative
Harrie Boonen, Lundbeck |
13:50 |
Session 6: NAMs in the IO-space: The view from here
Case study – Insight from industry collaborators
Anna Dahlman, Genmab |
14:10 |
Session 7:
Case study – Insight from industry collaborators
Anna-Karin Sjögren, AstraZeneca
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14:30 |
Session 8: Discussion on the use of Virtual Control Groups
John Kendrick, LabCorp |
14:50 |
Expert round table discussion – Seen challenges in NAMs
Collaborators and LabCorp. Audience interaction |
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15:30 |
Networking, drinks and snacks |
16:00 |
End of Boost Seminar |
Sessions
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Session 1
Lessons from CP&C: Frameworks, validation and model acceptance
New Approach Methodologies (NAMs) have been taking the scientific landscape by storm stemming out of concepts such as in vitro alternatives and then non-animal methods leading to the overarching and now accepted term of NAMs. There are many drivers for the adoption of NAMs and over the last decade or so, a significant proportion of the more recently internationally accepted NAMs (OECD, ICH etc) are industry agnostic.
NAMs are not a new thing though and are being developed within several industry sectors. Through innovation, hard work, collaboration, using existing science and adopting mature technologies, the Chemical industry has had much success for NAM development and acceptance. That can work well when the scientific field and regulatory bodies know what is required (as some examples will show) however NAMs also span scientific disciplines where research and innovation are of greater value than regulatory approval. It’s not so much “Replacement” (3Rs) but creation of a method that is Fit-For-Purpose.
By drawing together concepts such as AOPs and harnessing both technological advancements and scientific understanding, the NAMs arena is now a large and complex space with multiple stakeholders but collaboration is driving the same goal – generating relevant data that gives confidence to the end user, be that for discovery, clinical trial entry, regulatory approval or another purpose entirely. |
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Session 2
NAMs – the regulatory environment with respect to alternative approaches
NAMs are a rapidly developing and exciting advancement in the arena of regulatory pharmaceutical development. The use of NAMs has the potential to impact not only on the 3Rs, but also overall development costs and timelines. Ensuring that the utilization of NAMs meets with acceptance by the Regulatory Authorities is an important aspect of the overall development strategy and should be based on a combination of sound science, a clear rationale for ensuring patient safety and early interaction with the authorities. |
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Session 3
NAMs for the detection of seizure liability in drug discovery
Seizure liability remains a significant cause of attrition throughout drug development. Current methods rely on in vivo or ex vivo studies. There is therefore a clear need for predictive in vitro assays. Two NAMs have been developed and validated for the detection of seizure liability: A panel of ion channel targets relevant to seizure, and a hiPSC neuronal co-culture using micro-electrode array to measure electrical activity. These assays have been deployed and case studies will be presented.
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Session 4
Human Vessel-on-a-Chip model for use in interpretation of Immunotoxicology
With the increasing number of novel drug modalities, traditional models of pre-clinical testing are becoming increasingly limited in their utility for effective prediction of immune related adverse outcomes. It is often the case with current models that we do not predict the appropriate immunotoxicology that occurs. The immunopathology within the blood vessel is often not modelled effectively in pre-clinical studies which results in our inability to predict cytokine storm responses. Since 2006 and the TGN1412 clinical trial outcome where pre-clinical studies were not predictive of human toxicology, significant efforts have been made by industry and consortia to develop approaches to better predict clinical safety outcomes for biologics and cell therapies.
To address this challenge Labcorp in collaboration with Mimetas have developed a fully autologous Human Organ-on-a-Chip (OOAC) system that models the blood vessel environment. The model used the Organoplate 2-Lane seeded Blood Outgrowth Endothelial Cells (BOECs) which are co-cultured with autologous whole blood or peripheral blood mononuclear cells (PBMCs). The talk will focus on development and validation of this novel system. Results from this work indicate how this model could become an alternative to animal models designed to predict immunotoxicology. Data will show the ability of the model to predict cytokine storm for both biologics and cell therapies.
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Session 5
Support Of First-in-human Clinical Trials With Human In Vitro Toxicity Testing – Perspectives of EFPIA Safety Reflection Initiative
Standard preclinical models used for safety assessment of novel drugs sometimes present no or insufficient pharmacological activity, in particular with more recent therapeutic modalities (e.g. bispecific antibodies, gene and cell therapies). The EMA guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials encourages the use of in vitro studies with human-derived material, either as additional support or as an alternative to in vivo testing. Under the umbrella of the safety reflection initiative of EFPIA’s preclinical development working group (PDEG), a team of toxicologists from nine pharmaceutical companies started to compile current and future options for in vitro toxicity testing that will contribute to regulatory submissions relevant for first-in-human clinical trials. By defining different drug candidate categories with their specific safety assessment options, including alternative approaches to animal testing, the team is working towards providing guidance to increase the probability and address challenges for regulatory acceptance. In addition to challenges that will be highlighted, definitions of drug candidate categories will be presented together with respective examples of how in vitro risk assessment approaches were employed to complement or even replace standard animal models. These definitions and case studies should lead to a clearer path forward on how to meet regulatory expectations using alternative approaches to animal testing as appropriate safety assessment. |
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Session 6
NAMs in the IO-space: The view from here
Case study– Insight from industry collaborators, Genmab |
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Session 7
Drug-induced kidney injury (DIKI) remains a significant reason for safety-related attrition of drug development programs and frequently presents in clinic with marketed drugs.
To successfully develop and apply predictive models for DIKI, three aspects are key: Sufficient physiological relevance of the cell model
Appropriate toxicity endpoints
Use of a fit-for-purpose approach
In this presentation, I will discuss the utility of advanced in vitro models during drug discovery to predict DIKI. The presentation will span from high-throughput multiparametric high content imaging in renal proximal tubular cells to time-course analysis of drug-induced kidney injury biomarkers in a proximal tubule-on-a-chip. Furthermore, I am also addressing the need to expand the in vitro kidney toxicity assessment beyond small molecules to meet the growing interest in pharmaceutical industry to develop new drug modalities.
AstraZeneca |
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Session 8
A NAMs initiative – Forging a path towards Virtual Control Groups in Safety Studies
The traditional paradigm of employing physical control groups in drug development balances ethical concerns and scientific value. Increasingly there is an industry movement to consider the implementation of virtual control groups (VCGs) as a promising alternative, and this is gathering momentum as a unique NAMs initiative.
Virtual control groups are not a new concept, and have been employed in certain circumstances in clinical trials already. Their inclusion is based around advanced statistical methods, real-world evidence, and historical data, which ultimately simulate a control arm without the need for a separate group of subjects. Applying VCGs in animal studies addresses some of the major concerns in preclinical development, ie the use of animals and the 3R’s, but it could also mitigate the sourcing and financial impacts of having separate groups of animals on studies impacting the speed and cost of the development of new medicines.
However, challenges such as data availability, data quality, selection bias, and variety of environmental and physical parameters defining a control group need to be carefully addressed to ensure the validity and reliability of virtual control group outcomes. Regulatory agencies, researchers, and industry stakeholders must collaboratively establish guidelines and standards for implementing and validating virtual control groups in non-clinical studies to transform this concept into a reality. While further research and validation are needed, the potential benefits of enhanced cost-effectiveness, and reduced 3R’s burden of these studies, make virtual control groups a compelling and innovative approach in shaping the future landscape of safety testing utilising animals.
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Speakers |
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Darren Kidd, LabCorp
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Andy Gibbs, LabCorp |
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Michael Morton, Apconix
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Chris Cooper, LabCorp |
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Harrie Boonen, Lundbeck
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Anna-Karin Sjögren, AstraZeneca |
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John Kendrick, LabCorp
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Organized by |
In collaboration with |
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