Pre-Conference Seminar Days
Tuesday, September 6, 2022
This seminar day 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.
Nathan Tumey, Associate Professor, Binghampton University
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
Laughing Bear Torrez Dulgeroff, Scientist, Bolt Biotherapeutics
10.30 Discovery of bispecific antibody drug conjugate (ADC) therapeutics with fully humanized RenLite common light chain transgenic mouse platform
- Introduction of Biocytogen’s antibody discovery platform with fully humanized antibody transgenic mice
- Introduction and case studies of Biocytogen’s bispecific antibody drug conjugate (ADC) discovery programs
W. Frank An, Senior Director, Antibody Therapeutics, Biocytogen
11:00 Morning Break
11.30 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
12.00 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
12.30 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 immune-modulating 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.
Chair: Rakesh Dixit, Chief Executive Officer & President, Bionavigen
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 Executive Officer & President, 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 Developing in vitro & in vivo Strategies to Triage Nonspecific ADC Uptake/Payload Release & Related Tox
- ADC processing and the importance to reduce nonspecific cellular uptake
- Develop and evaluate in vitro cellular assays to understand payload delivery and triage molecules
- Effect of FcyR interaction on payload release and tissue distribution
- Evaluate a luciferase reporter mouse model to track Ly6G+ cells to triage ADC induced neutropenia
Jianzhong Wen, Associate 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 & Senior Director, 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
- Overview of the causes of ADC toxicity
- Strategic considerations for designing a TROP2-ADC with optimal therapeutic window including preclinical validation
- Outlining the clinical safety and efficacy of SKB264
Haijun Tian, Senior Vice President, 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.
ADCs 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.
Chair: Anton Rosenbaum, Director, Integrated Bioanalysis, AstraZeneca
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 Mass Spec Strategies for Streamlined Analysis of ADCs Powered By Machine Learning
- Rapid CQA identification and quantification for CMC
Lieza M. Danan, Co-Founder & Chief Executive Officer, LiVeritas Biosciences
12.00 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
- Comparing LBA and hybrid LCMS methods for measurement of ADC PK in the clinical study
Inna Vainshtein, Senior Director, Bioanalytics, Exelixis
12.30 Morning Break
13.30 Analyzing ADC Biotransformation Products In Vivo 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, AstraZeneca
14.00 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
14.30 Afternoon Break
15.00 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 Pharma Research
15.30 Addressing Key Bioanalytical Challenges to Better Understand Our ADCs
- 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.
Chair: Jay Harper, Director, Tumor Targeted Delivery, AstraZeneca
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
*Virtual* Timothy Yap, Associate Professor & Medical Oncologist, 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
*Virtual* Betsy Gray, Principal Scientist,Therapeutic, 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 GQ1001, a HER2 Targeting ADC With Excellent Safety Profile Demonstrates a Potential for Synergistic Effect in Combination with TKI or Chemotherapeutic Agents
- GQ1001 was developed by enzyme-based site-specific conjugation leading to high linker stability and homogeneity
- GQ1001 demonstrates excellent tolerability and promising efficacy in HER2+ advanced patients
- Showcasing preclinical data that shows a good synergy in combination with HER2 TKI and chemotherapeutics, while maintaining good safety
Paul Song, Chief Scientific Officer, GeneQuantum Healthcare
14.30 Afternoon Break
15.00 Roundtable Think Tank Discussions – 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.
Chair: David Conlon, Consultant, Conlon Pharma Consulting
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 & PharmaZell Group
Bertrand Cottineau, Group Head, R&D, Novasep & PharmaZell Group
11.00 Morning Break
11.30 Manufacturing ADC: Relying on Extensive Know-How in Producing & Handling High Potent Compounds for Developing & Manufacturing Next Generation Payloads
- Presenting the long experience of Olon SpA on prodcing microbial manufacturing and modifying anthracycline such as Doxorubicine and extensive know-how in producing and handling high-potent compounds
- High potentiality in developing next-generation payloads with fun tuning of the toxicity and/or physical properties (e.g. hydrophobicity etc) taking advantage of the extensive know-how on the chemistry of anthracyclines
- New investment to support the moving in the next level of containment (OEB6) to be ready for production and handling of more active/toxic payloads
Giorgio Bertolini, Vice President, Research & Development, Olon Group
12.00 Concurrent Manufacturability Evaluation During Lead Candidate Selection Facilitates Faster CMC Timelines to Clinic for Complex Molecules
- Integration of developability assessments during candidate discovery allows for CMC considerations to be incorporated into lead candidate selection
- By analyzing candidate fit to existing platform processes, gaps in the existing process can be identified and de-risked prior to formal selection of the lead molecule
- The combination of advancing development friendly lead molecules and at-risk predevelopment activities allow for traditionally off platform novel modalities to be developed under accelerated timelines
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, Technical Product Steward & Antibody Drug Conjugates & Global Diversity Inclusion Lead, Merck & Co.
Ying Buechler, Senior Vice President, Development, Ambrx
May Zhu, Director, 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