Pre-Conference Seminar Day
Tuesday, September 6 2022
This workshop will offer a one-day intense learning environment to establish core understanding of the critical areas of ADC research and development. Designed for new entrants to the ADC field, it will deliver critical knowledge gained during the research that led to the development of the currently approved ADCs. Covering the essential elements in ADC discovery and early development, this seminar day will enable you to:
- Gain familiarity with the fundamental early learnings that inform ADC design
- Learn about the key insights that allowed early investigators to overcome the initial challenges that hindered early ADC programs
- Understand the choices and trade-offs in utilizing the Chemistry ADC toolbox
- Evaluate payload choices for ADCs
- Review linker design chemistry and what it can bring (“not just the piece in the middle”)
- Understand the impact of conjugation site selection on ADCs - Gain an understanding of the biological aspects of ADCs
- Choose an optimum antibody format
- Select the most appropriate ADC target which is easily accessible - Learn about in vitro assays
- Assess key factors in evaluation of efficacy information from in vivo preclinical models
- Gain an understanding of key considerations in toxicology assessment of ADCs
- Gain an overview of the development process for ADCs
- Learn about the challenges and opportunities for further improvement upon ADC design
John Lambert, Independent Consultant Cambridge, Massachusetts
With a growing number of nontraditional payloads being used in preclinical and clinical development over the past couple of years, ADCs with next generation payloads are becoming an increasingly appetizing proposition for ADC developers. This seminar day will showcase structures and early data from immunomodulatory, protein degrader, oligonucleotide and radioconjugate ADCs.
10.00 Designing Immune-Stimulating Antibody Conjugates
- Providing an overview of Bolt’s Immune-Stimulating Antibody Conjugates (ISAC) technology platform as the next step in ADC-based immune therapies
- Highlighting the key features and mechanism of action
- Demonstrating the use of various methods to understand and design potent ISACs
Shelley Ackerman, Associate, Director, Bolt Biotherapeutics
10.30 Tumor Targeted Immune Activation Via a Site-Specific TRL7 Agonist Antibody Conjugate
- Discussing non-natural amino acid mediated, site-specific conjugation technology enables discovery of ISACs with high homogeneity and stability
- A TLR7 agonist ISAC promotes broad immune activation in vitro and immunologic memory in syngeneic cancer pharmacology models
- Ambrx’ lead ISAC molecule exhibits favorable NGP tolerability profile and a wide therapeutic index
David Mills, Director, Preclinical Science, Ambrx
11:00 Morning Break
11.30 Exploring Antibody-Oligonucleotide Conjugates
- Discussing what are oligonucleotides
- Exploring how antibodyoligonucleotides can help solve oligo delivery challenges
- Overviewing Avidity Biosciences’ ADC technology
Ramana Doppalapudi, Vice President, Chemistry, Avidity Biosciences
12.00 Antibody-mediated Delivery of Protein Degraders
- Discussing efforts to expand ADC technology outside of pancytotoxics
- Assessing the impact of DAR and payload potency on ADC activity
- Optimizing linker-drug structure for improved pharmacokinetic
properties
Thomas Pillow, Principal Scientist, Genentech
12.30 Lunch
13.30 New Strategies for the Design of TRL7 Agonist ADCs
- Overviewing in vitro assays for optimizing immune-stimulating ADCs
- Outlining the role of Fc-gamma in the activity of immune stimulating ADCs
- Comparing linkers for immunemodulating ADCs
Nathan Tumey, Associate Professor, Binghampton University
14.00 Novel Radioconjugates, Iopofosine, Clinical Updates & Future Directions
- Discussing the targeted delivery of iodide 131
- Providing a clinical update from ongoing hematological and solid
tumor trials - Sharing what’s next, for radiotherapies and beyond
Jarrod Longcor, Chief Operating, Officer, Cellectar Biosciences
14.30 Afternoon Break
15.00 Roundtable Think Tank Discussion – Evaluating Whether to Incorporate Next-Generation Payloads into Your Pipeline
This session will provide you with a highly interactive opportunity to crowd-source opinions on why companies have decided to develop next-generation payload ADCs, with a view to understanding what scientific and logistical challenges are created by incorporating novel payloads into your pipeline. This
is a dedicated session for you to voice your thoughts and learn from your peers to advance your future development potential.
Maximizing the clinical therapeutic index of ADCs still remains the main focus for those working in this industry. Reducing toxicity is a key part of that, and challenges surrounding understanding the causes of off target toxicity, examining how well toxicities translate into humans and discussing the relationship between PK and toxicity are just a couple of questions that are front of mind. This day will bring together toxicology experts to help explain, understand and create strategies to mitigate toxicities.
10.00 Developing Smart & Fit-for-Purpose ADC Development Strategies to Improve Safety & Efficacy
- Understanding the importance of the target and the engineered
antibody - Evaluating what payloads are better suited for low vs. high target expression?
- Discussing whether on target toxicities can be minimized by intelligent engineering and combination approaches
- Sharing translational approaches to maximize the value of clinical trials
Rakesh Dixit, Chief ExecutiveOfficer, Bionavigen
10.30 Translating Preclinical Toxicity to Clinical Toxicity Using PK-PD Modelling Approaches
- Reviewing how the ability to translate data from animal toxicology studies to humans is key in optimizing the dose, regimen in early clinical development and thereby optimizing development
- Showcasing mechanistic PK/PD models can be a better approach to translate key hematologic toxicities from
cynos to humans. These models are widely used to understand
hematologic toxicity in humans and can be extended for translation across species - Sharing two examples of using a model-based approach to translate
hematologic toxicities. These examples - one for neutropenia and one for
thrombocytopenia will show how to use the model-based approach to predict hematologic toxicities in humans based on cyno data.
Rajeev Menon, Senior Director & Senior Research Fellow, AbbVie
11.00 Morning Break
11.30 Understanding Nonspecific Payload Release & Triage Linker Stability Using Non-Target Expressing Macrophage Cells
- Assessing antibody backbone optimization to reduce nonspecific payload release
- Developing a neutropenia animal model to have an early and easy tox readout
Jianzhong Wen, Principal Scientist, Merck & Co.
12.00 Characterization of Non-Specific Hepatoxicity Related to Trastuzumab Emtansine (T-DM1) in Rodent & Human Hepatocytes
- Brief overview of ADC-related toxicities
- Sharing in vitro and in vivo toxicity data
- Discussing the importance of selecting the appropriate preclinical model for ADC toxicity assessment and implication on clinical development
Ben-Quan Shen, Senior Fellow, Genentech
12.30 Lunch
13.30 NextGen CAB-ADCs: Maximizing Safety & the Therapeutic Index
- Overviewing the CAB platform to minimize antigen related toxicity by pH-selective binding in the tumor microenvironment
- Optimizing linker selection for improved serum stability and tumor-targeted payload release
- Discussing approaches to maximize the therapeutic index of ADCs
Gerhard Frey, Vice President, Technology Development, BioAtla
14.00 Examining How to Balance DAR Ratio & Toxicology
Xiangyang Tan, Chief Scientific Officer, Klus Pharma
14.30 Afternoon Break
15.00 Roundtable Think Tank Discussions – Smart Strategies to Turning Off the Off-Target Toxicities of ADCs
This session will evaluate the approaches to switching off any off-target toxicities seen through ADCs. By understanding the approaches to identifying mechanisms of off-target toxicity and what you can do to design an ADC, this dedicated deep
dive session will provide you with the toolkit to better understand causes of toxicity, and generate strategies to mitigate from them.
DCs are complex molecules; varying level of conjugation, free drug and free antibody in the drug substance are a few characteristics that can have a
distinct impact on safety and efficacy. Therefore, determining the right bioanalytical strategy is not simple. Newly repurposed for this year, the 1st CQA & Bioanalytical
Day will offer a unique learning environment to showcase technological developments to improve the characterization of your ADC post-administration and better inform clinical strategy and design.
10.00 Antibody-Drug Conjugate Bioanalytical Strategies & Applications
- Sharing a total antibody and antibody-conjugated drug 2-in-1 clinical assay development and validation
- Assessing a non-clinical case study for a pH sensitive ADC method development optimization
- Exploring a PK/PD simultaneous measurement in mouse model using microsampling to support non-clinical development
Ling Xu, Fellow, Mersana Therapeutics
10.30 Tailoring Bioanalytical Assays for ADC Biotherapeutics
- Sharing bioanalytical challengesand strategies for PK analysis
of ADCs in (pre) clinical studies, including total and conjugated
antibody assays using hybrid LCMS/ MS and LBA methods - Discussing tiered strategies for immunogenicity measurement
- Reviewing regulatory guidelines and current industry best practices, perspectives and case studies from a bioanalytical CRO
Francesoc Bonardi, Director, Bioanalysis, Ardena
11.00 Morning Break
11.30 Preclinical & Clinical ADC Bioanalysis – Bioanalytical Strategies & Assay Design
- Reviewing bioanalytical strategies and assay designs to characterize the PK of ADCs in preclinical and clinical studies
- Discussing ADA detection and characterization to interpret ADC PK in
the preclinical study - Providing a comparison of LBA and hybrid LCMS methods for measurement of ADC PK in the clinical study
Inna Vainshtein, Senior Director, Bioanalysis, Exelixis
12.00 Analyzing ADC Biotransformation Products InVivo with LC-MS Based Methods
- Examining LCMS based methods for biotransformation
- Assessing in vivo biotransformation and in vitro plasma incubation, the
similarities and the differences - Reviewing case studies of various types of ADC biotransformation and the
impact on quantification of ADC concentration
Yue Huang, Associate Director, Bioanalytical, AstraZeneca
12.30 Morning Break
13.30 Comprehensive Bioanalytical Assessment of ADCs in Early Discovery
- ADCs are complex biotherapeutics and require comprehensive bioanalytical
strategies for the assessment of their PK and biotransformation
during early discovery - Examining a combination of LBA and LC-MS/MS methodologies for the pharmacokinetic assessment of ADCs
- Discussing how hybrid LBA LC-HRMS methodologies are employed for the biotransformation assessment of ADCs
Srikanth Kotapati, Senior Principal Scientist, Bristol Myers Squibb
14.00 Development of a Hybrid Method for Quantification of ADCs by LC-MS/MS
- Sharing bioanalytical approaches to characterize ADCs in biological matrices
- Reviewing the development of a hybrid LC-MS/MS method for quantification of ADCs
Marisa Schmitt, Group Leader, Bioanalytics, Heidelberg
14.30 Afternoon Break
15.00 Panel Discussion – How to Develop Optimal Bioanalytical Strategies for ADCs Targeting Difficult to Express Targets
- Sharing current bioanalytical approaches for difficult to express targets
- Outlining current challenges with these approaches
- Benchmarking future best practices
Since the beginning of 2020 over 100 ADC combination trials have
begun, catalyzed by disease being multifactorial, drug resistance and
possible synergistic effects between drugs. With 12 ADC combination trials entering their pivotal stage and with nearly 150 being explored in the frontline setting, the spotlight has well and truly turned to ADC combinations. The 6th ADCs in Combination Day will mirror these developments by providing an insight into combination rationale, benchmark best practices on when and how to combo, and explore beyond ADC and IO combinations, to provide you with the toolkit to successfully implement your ADC into a combination trial.
10.00 ADC Combination Rationale, the Clinical Landscape & Future Opportunities
- Discussing the rationale for combinations involving ADCs
- Overviewing the clinical landscape of combinations
involving ADCs - Projecting future opportunities for combination partners for
ADCs
Jay Harper, Director, Tumor, Targeted Delivery, AstraZeneca
10.30 Antibody Drug Conjugate Combinations with PARP Inhibitors
- Discuss the strong rationale for developing ADC and PARP inhibitor combinations to target different tumor types
- Gain insight into the promising efficacy observed with the combination of ADC and PARP inhibitor
- Explore how the observation of overlapping toxicities may lead to challenges in the clinic and require alternative dose and schedule strategies
Timothy Yap, Associate Professor, University of Texas MD Anderson
Cancer Center
11.00 Morning Break
11.30 T-DM1 Combined With Cancer Immunotherapy – exCITing Prospects in HER2- Positive Breast Cancer
- Discussing scientific rationale supporting combination therapy with T-DM1 and CIT agents
- Sharing clinical evidence for combining T-DM1 with CIT
- Outlining the future of CIT and ADC combinations in HER2- positive breast cancer
Gail Lewis, Principal Scientist, Genentech
12.00 SGN-B7H4V Has Immunomodulatory Activity & Combines With Anti-PD1 Agents in Preclinical Models
- SGN-B7H4V is an investigational vedotin ADC targeting the immune checkpoint ligand B7-H4
- Understand how SGN-B7HAV elicits antitumor activity in vivo, accompanied by immune changes in the tumor microenvironment
- Assess how combination studies suggest SGN-B7H4V may pair
well with an ant-PD-1 agent
Betsy Gray, Principal Scientist,Therapeutic Discovery Research, Seagen
12.30 Lunch
13.30 Discussing Combinations with Mirvetuximab soravtansine in the Treatment of Ovarian Cancer
Michael Method, Executive Medical Director, ImmunoGen
14.00 Late Breaking Abstract
- As more clinical results from combination trials are released this session will be reserved to showcase a hot update from the world of ADCs in combination
14.30 Afternoon Break
15.00 Panel Discussion – Understanding Whether 1+1=2 –
Examining Current Combination Rationale & Future Combination Directions
- Benchmarking best approaches in selecting a combination partner
- Understanding how to move from a testing a monotherapy into a combination therapy
- Evaluating how combination therapies can be used to rescue non-responders or to increase sensitivity
Of the 1112 clinical trials ongoing within the ADC space, by the
end of 2021 46% of those were in Phase II and beyond with 7 ADCs currently being developed in pivotal trials, demonstrating an increasing demand for late stage and commercial manufacturing. The 4th CMC Day will address the unique late phase and commercial manufacturing challenges that ADC developers are facing. Benchmarking regulatory expectations, optimizing relationships with CDMOs, and understanding best practices in scale up are a few of the key themes of this day enabling you to confidently develop your CMC operations to be ready for commercialization.
10.00 Effectively Working With a CDMO for Late Phase Development & Manufacturing
- Outlining strategic planning for process characterization and
PPQ runs - Successfully executing PCPV activities at a CDMO under an
accelerated timeline - Sharing lessons learned from previous experiences
Ying Buechler, Senior Vice President, Development, Ambrx
10.30 Teamwork as a Central Feature to Optimize Your ADC
Development
- Outlining key factors for streamlined process and
analytical activities - Understanding how your CDMO becomes an extension of your
development team – a CDMOs perspective
Melanie Derde, Head, Analytical, Bioconjugation, Novasep
Bertrand Cottineau, Group Head, R&D, Novasep
11.00 Morning Break
11.30 Slot Reserved for Olon SpA
12.00 Technical Development Has Built Bridges Between R&D by Implementing an Integrated Platform-fit Assessment to Ensure Seamless Transition from Promising Research Leads to Clinical Manufacturing Processes
Chris Lieske, Senior Scientist, Seagen
12.30 Lunch
13.30 Panel Discussion –How to Effectively Tech Transfer With External Partners?
- Benchmarking best practices in tech transfer to CDMOs
- Discussing ADC commercialization challenges – what is the line of sight to
validation and post approval changes
Radhika Balasubramani, Director, ADC Global Technical Operations Lead, Merck & Co.
Ying Buechler, Senior Vice, President, Development, Ambrx
May Zhu, Director, Analytical, Development, Takeda
14.00 Outlining How to Develop a Process for a Late Stage Clinical Candidate
Hong Ren, Principal Scientist, Merck & Co.
14.30 Afternoon Break
15.00 Roundtable Think Tank Discussions – Setting the Gold
Standard for Scaling Up CMC for Late Phase Development
- Discussing improvements in process development to ready
yourself for late phase and commercial supply - Understanding the regulatory environment and key specifications for Phase II development and beyond