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Workshop Day
Tuesday, October 8

Introduction to Discovery & Design of Novel ADCs (FULL DAY)

9:00 – 4:00

This workshop will offer a one-day intense learning environment to establish core skills and understanding in the critical areas of ADC research and development. Designed for new entrants to the ADC field it will deliver critical knowledge in a number
of the key problem areas that hinder antibody drug conjugate programs.

Covering essential elements in ADC discovery and early development, this workshop will enable you to:
• Gain an overview of the development process for ADCs
• Improve payload and linker design chemistry
• Understand the impact of conjugation site selection on your ADC
• Choose/choice of optimum “antibody” format
• Select the most appropriate ADC target which is easily accessible
• Learn about cellular assays
• Review the advantages and disadvantages of different preclinical animal models
• Develop early stage assays and learn how to effectively interpret the data

Workshop Leader:

David Bramhill,

President & Founder,

Bramhill Consulting 

 

Modelling & Simulation of Antibody-Drug Conjugate Pharmacokinetics & Pharmacodynamics (PK/PD) in Drug Development (FULL DAY)

9:00 – 4:00

This will be a two-part workshop designed to accommodate both attendees new to modelling and simulation as well as researchers more seasoned in ADC development. The morning session will be geared towards modelling fundamentals while the afternoon will discuss the application and results of simulations specific to ADC preclinical and clinical development. Participants are welcome to attend either or both parts depending on their background and interests. The morning session will introduce basic tenets of antibody drug conjugate PK/PD and how to characterize these aspects using empirical and systems-based mathematical models. These models include systemic PK (plasma clearance, payload deconjugation, targetmediated drug distribution, etc.), tissue distribution (e.g. heterogeneous tumor concentrations), and cellular targeting (internalization, payload release, bystander effects, etc.). Several hands-on modelling examples will be conducted along with
strengths and limitations of these approaches.

Join us in the afternoon, where more advanced topics will be introduced towards the application of modelling for preclinical ADC development and clinical translation. This includes integrating the topics covered in the morning session into more comprehensive simulations of ADC PK/PD and what these results can tell us about efficacy and toxicity. Example topics include how the size of ADCs and related drug conjugates, tumor heterogeneity, ADC bystander effects, and antibody coadministration impact the efficacy and therapeutic index of ADCs. Finally, a strategy to translate preclinical efficacy of ADCs into the clinic using PK/PD modelling and simulation will be presented.

Workshop Leaders:

Greg Thurber,

Associate Professor,

University of Michigan

 

Dhaval Shah,

Associate Professor,

State University of New York at Buffalo

Workshop A: Advanced Design of ADCs: Principles & Applications with Next Generation Linkers & Site-Specific Technology

9:00 – 12:00

Let’s explore various ways to improve the therapeutic window of ADCs using a rational approach to improve clinical performance by building a better molecule. By incorporating improvements in solubility as well as attachment stability, great strides can be made. We will discuss various methods for obtaining a defined DAR, and the pros and cons of several key approaches. Also, attention will be given to dual and multi-warhead ADCs, and the various ways to achieve controlled multivalency on native and engineered proteins. Lastly, with the emergence of Immunooncology, dual binding bi-specific antibodies will be discussed as a platform for ADC conjugations.

Agenda Summary:

• Welcome and Introductions
• Background and Defining the Challenge
• Solubilizing the Drug-Linker
• Stabilizing the Linker
• Site-Specific Strategies for Success
• Multi-valency and Dual-Warheads
• Bi-specific constructs as ADC platforms

Workshop Leaders:

Rick Powers,

Independent Consultant

 

Ed Ha,

Founding Principal Scientist

Angiex, Inc

Workshop C: Next-generation ADC Target Discovery: The New Frontier

9:00 – 12:00

With antibody drug conjugates, much attention focuses on the physical properties of the antibody, drug and linker components. However, the characteristics of the target cell and antigen are perhaps the most critical parameters in ADC design. In the context of developing a commercial successful ADC, this workshop will share insights and discuss the considerations for you to choose the right target for your ADC candidate.

This workshop will cover:

• Summary of current ADC target landscape at both clinical and preclinical stages with a correlation of the clinical stage targets with the success or failures of their clinical trials
• Lessons learned from the clinical trials: what’s the hallmark of a successful ADC target?
• Where do we go from here: how to discover the next-generation of ADC targets?
• Key technologies to enable nextgeneration ADC target discovery

Workshop Leader:

Zhan Xiao,

Principle Scientist,

MedImmune

Workshop E: Building the Bridge from Translation to Discovery - Model-based Forward/Reverse Translational Approach to Guide the Discovery & Development of Therapeutic Monoclonal Antibody

9:00 – 12:00

Translational science with quantitative modelling and simulation approach plays an important role in moving molecules from discovery to development and eventually to patients. However, translational science is not a miracle tool that will transform junk into gold and the drug developers simply cannot develop the discovered molecules with undesirable properties into drugs for patients. Therefore, in this study, we elucidated a novel concept of reverse translational science by utilizing a model-based approach to transfer the knowledge in reverse direction from development to discovery. FcRn binding affinity profiles and charges have been shown to play an important role in the distribution and elimination of therapeutic monoclonal IgG antibody (TMAb).

Using two case studies, we will demonstrate the utility of using minimal physiologicallybased pharmacokinetic (mPBPK) modelling approach to construct detail quantitative relationships between the FcRn binding affinity/charges and the PK parameters of the TMAb. Such relationships are useful to identify the discovery “sweet spot” in designing future generation of TMAb wth desirable biodistribution and elimination properties (Reverse Translational Appraoch). Furthermore, the mPBPK model developed in the preclinical model was useful to predict the PK of the TMAb in adult human subjects (Forward Translational Approach)

Workshop Leader:

Chee Meng Ng,

Associate Professor of Pharmaceutical Science,

University of Kentucky

Workshop G: CMO Management; Challenges & Insights for Outsourcing Complex Biologics such as ADCs

9:00 – 12:00

This workshop will focus on:

• Buy vs. make: Key considerations as an enabler for an effective outsourcing strategy
• Differentiated strategies for “simple” vs “complex” biologics?
• Critical success factors for effective outsourcing
• Scale-up and site transfer of a conjugation process with impact on key product quality attributes: a case study
• Analytical transfers: considerations & lessons learned from a challenging assay transfers
• CDMO or CMO? Outsourcing of overarching development workflows vs. “just” API manufacturing?

Workshop Leader:

Jens Lohrmann,

Head of Disease Area,
Oncology & Technical Development,

Novartis

Workshop B: Exploring Novel Mechanism of Actions, Optimizing Payload & Linker Chemistry & Deepening Understanding of Payload Driven Toxicities

1:00 – 4:00

Discussion will focus on how payload-linker combinations can affect ADC clinical activity and toxicities when attached to antibodies, and how the most appropriate payload-linker combination can be chosen for a particular antibody and/or cancer type. Attend this workshop to explore the scientific biological rationale for maximizing the synergy of ADC payload- linker combinations.

Join your peers at this workshop to:

• Improve understanding of the most desirable properties of payloads and linkers
• Review current payload-linker combinations which are enhancing the therapeutic window
• We will also cover past strategies to improve and balance: payload potency, impact of homogeneous conjugations on PK/PD, protein/nucleic acid payloads & synergy with I/O
• Explore payload and linker combinations currently at the discovery or development stages
• Learn to develop linker-payloads that will not release prematurely
• Discover important considerations for designing the optimum payload-linker

Workshop Leaders:

Rick Powers,

Independent Consultant

 

Ed Ha,

Founding Principal Scientist

Angiex, Inc

Workshop D: The Chemistry of Toxins, Conjugations & Linkers for Antibody-drug Conjugates

1:00 – 4:00

The choice of linker and payload for an ADC is essential for the selection of a successful clinical candidate. This workshop will deepen the understanding of the chemistry behind conjugation technologies and be held by highly experienced leaders in the ADC field who have designed successful candidates from discovery all the way to clinical trials.

Attend this workshop to:

• Understand synthetic challenges, structural features, and stability of toxins
• Chemistry of linkers, linker choice, linker release mechanisms
• Site-specific conjugations vs non-site-specific conjugations
• Stability of ADCs
• Mitigation of aggregation

Workshop Leaders:

Thomas Nittoli,

Director of R&D Chemistry,

Regeneron Pharmaceuticals, Inc.

 

Brian Mendelsohn,

Director,

Ajinomoto Bio-Pharma Services

 

Naresh Jain,

President & CEO,

NJ Biopharmaceuticals LLC

Sean Smith,

Senior Director - Chemistry,

Silverback Therapeutics

Workshop F: From FIH to Post-commercial: ADC Reference Standard Management & Setting Specifications

1:00 – 4:00

This workshop will explore two challenges presented by ADCs during the lifecycle of a product

Identifying and managing the primary reference materials

The reference material for a FIH ADC may be derived from research or development materials, from toxicology lots or from the first GMP lot. However, this material may not be representative of the product later in its lifecycle and/or it may be limited in quantity. We will explore ways to identify and manage reference standard materials and how to bridge references as the product moves towards commercialization and beyond. The primary focus will be on the ADC reference, however the group may explore similar issues as they relate to mAb, drug or linker, impurity standards, and/or assay standards.

Setting and justifying specifications

The specifications for an ADC have been of particular interest for regulators due to the complex and toxic nature of these products. The product profile can be relatively ‘simple’ (i.e. toxic drug attached to benign targeting mAb) or much more complex – for instance if the mAb has activity, demonstrates differential binding post-conjugation, or stability is an issue. As more is learned about each particular ADC therapeutic product through pre-clinical, clinical and characterization work, identifying CQAs, managing the control strategy, and setting and justifying the specifications becomes an iterative process. As we move from FIH to a commercial product, assays may be fine-tuned or changed and activity assays may be introduced or refined, requiring bridging and specification updates. This workshop will provide an opportunity for us to discuss how we approach these challenges and meet the expectations of regulators for rigorous justifications regarding our decisions.

Workshop Leaders:

Shawn Novick,

Independent Consulant