Pre-Conference Seminar Days
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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
- Become familiar with the fundamental early learnings that informing ADC design
- 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
John Lambert
Independent Consultant
Cambridge, Massachusetts
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A huge and exciting topic in the ADC world at the moment is ’non-traditional ADCS’. A non-traditional ADC uses the exact same concept of an ADC in the sense that it is made up of three components that join together and the ‘payload’ provides the killing power. However, one aspect of the ‘ADC’ is different to a traditional ADC, usually the antibody or the payload. Join this day to gain an update on the landscape of non-traditional ADCs.
09.55 Chair's Opening Remarks
10.00 Designing Immune-Stimulating Antibody Conjugates
- Overview of Bolt’s Immune-Stimulating Antibody Conjugates (ISAC) technology platform as the next step in ADC-based immune therapy
- Highlighting the key features and the mechanism of action
- Demonstrating the use of various methods to understand and design potent ISACs
Ganapathy Sarma, Director Chemistry, Bolt Biotherapeutics
10.30 Site-specific TLR7-agonist Antibody-drug Conjugates as Next Generation ADCs
- Presenting on the site-specific TLR7a ADC developed by EuCODETM platform with an expanded genetic code
- Reviewing how protein medicinal chemistry enables fine-tuning of TLR7a ADC to balance potency and safety in preclinical studies
- Demonstrating how Ambrx’s TLR7a ADCs elicit strong anti-tumor responses as single agent as well as in combination therapies
Mingchao Kang, Project Leader, EuCode, Ambrx
11.00 Preclinical Development of GQ1007, HER2 Ab Immune Agonist Conjugate (AIAC) with the Best-in-class Potential
- HER2 is a proven target for breast cancer, gastric cancer and other solid tumors
- GQ1007 is HER2 AIAC that has been developed using GeneQuantum’s unique iLDC bioconjugation platform, leading to excellent druggability and linker stability
- GQ1007 demonstrates robust in vitro and in vivo anti-tumor activities in multiple preclinical models
- Discuss GQ1007’s potential to become an important therapeutic option for the HER2+ patients who have progressed on current standard therapies, and a combo opportunity with PD1 therapy Lunch
Paul Song, Chief Scientific Officer, GeneQuantum
11.30 Morning Break
12.30 Looking at BCL-XL Inhibitor Antibody Drug Conjugates: A Novel Approach to Increase the Therapeutic Index of ADCs
- Reviewing the narrow therapeutic index of cytotoxic-based ADCs placing limits on their clinical utility
- Describing the preclinical development and characterization of BCL-XL inhibitor ADCs and how
they expand TI - Evaluating preclinical characterization and status of the lead program mirzotamab clezutoclax
(ABBV-155)
Andrew Philips, Director of Next Generation Drug Conjugates, AbbVie
1.00 Radioligand Therapy – Leveraging ADC Experience for an Innovative Approach to Treat Cancer
- Radioligand Therapy 2021 – Renaissance of a platform
- Why should ADC experts care about RLT?
- How can we leverage R&D synergies between ADC and RLT?
Germo Gericke, Senior Vice President - Research & Development & Chief Medical Officer, Advanced Accelerator Applications
1.30 XMT-2056, a Tumor-Targeted STING-Agonist ADC
- XMT-2056 is Mersana’s first Development Candidate with the Immunosynthen platform
- Examine how XMT-2056 induces STING activity with ~100-fold increased potency over free payload, induces tumor regressions in mice after a single low dose, and is well tolerated in repeat-dose studies in non human primates
- Discover Immunosynthen-based ADCs that deliver a “one-two punch” by activating the STING pathway in both tumor cells and tumor-resident immune cells
Marc Damelin, Vice President, Biology, Mersana Therapeutics
2.00 SBT8230, an ASGR1-Directed TLR8 ImmunoTAC Therapeutic, is a Potent Myeloid Cell Agonist with Liver-Localized Activity for the Treatment of Chronic HBV
- Understand the selection and optimization of TLR7/8 payloads
- Review the design of in vitro screening funnel for immune-activating ADCs
- Analyze results of direct and indirect lymphocyte activation studies
- Discuss how unexpected activity of noncleavable ADCs informs future strategy
Sean Smith, Executive Director of Chemistry, Silverback Therapeutics
2.30 Design & Optimization of TLR-activating ADCs for Use in Cancer & Infectious Diseases
- Understand the selection and optimization of TLR7/8 payloads
- Review the design of in vitro screening funnel for immune-activating ADCs
- Analyze results of direct and indirect lymphocyte activation studies
- Discuss how unexpected activity of noncleavable ADCs informs future strategy
Nathan Tumey, Assistant Professor, Pharmaceutical Sciences, Binghamton University
3.00 Chair's Closing Remarks
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09.55 Chair’s Opening Remarks
Rakesh Dixit, President & CSO, Regio Biosciences (USA) ; CEO, Bionavigen, LLC
10.00 Datopotamab Deruxtecan (Dato-DXd), a TROP2-directed ADC with a DNA Topoisomerase I Inhibitor DXd
- DXd-ADC: Widely applicable ADC linker-payload technology platform
- Preclinical results on the mechanism of action of Dato-DXd
- Updates on clinical development of Dato-DXd
Daisuke Okajima, Scientist, Preclinical Pharmacology, Oncology, Daiichi Sankyo
10.30 The Effects of a Novel Prodrug Approach on the Antigen-independent Toxicity Profile of a PBD Antibody Drug Conjugate
- Evaluating antigen-independent toxicity and toxicokinetics of a Prodrug PBD ADC compared to Parent PBD ADC in a single dose rat toxicology study
- Demonstrating how a Prodrug PBD ADC had a 2x improvement in MTD compared to the parent in rats, but was associated with more tissue PBD accumulation and severe toxicity at higher doses
- Exploring opportunities to improve the toxicity profile with faster clearing prodrug antibody approaches
Nicola Stagg, Senior Scientist - Toxicologist & Toxicology Oncology Therapeutic Area Lead, Genentech
11.00 Preclinical to Clinical Translational Safety of ADCs : Lessons Learned
- Overview of the major toxicities of ADCs
- Review preclinical to clinical translation of ADC safety
- Explore smart designs of next generation ADCs to minimize both on and off-target toxicities
Rakesh Dixit, President & CSO, Regio Biosciences (USA) ; CEO, Bionavigen, LLC
11.30 Morning Break.
12.30 Preclinical Profile of SYD1875, a Novel Site- Specifically Conjugated Anti- 5T4 Antibody Drug Conjugate
- SYD1875 comprises a humanized, HC41-cysteine-engineered IgG1 monoclonal antibody that targets 5T4
- SYD1875 is site-specifically conjugated to a proprietary cleavable synthetic duocarmycin-based linker-drug (vc-seco-
DUBA), which yields a homogeneous and stable ADC with favorable physicochemical properties and manufacturability - SYD1875 is a potent ADC with anti-tumor activity in multiple solid tumor types with high, moderate and low 5T4 expression levels. Its preclinical profile supports the expectation that SYD1875 will be of benefit for a broad group of cancer patients. A first-in-human dose-finding trial is initiated to evaluate safety and explore efficacy (NCT04202705).
Patrick Groothuis, Principal Scientist - In Vivo Pharmacology, Toxicology, Drug Metabolism & Pharmacokinetics, Byondis
1.00 Session Reserved – CytomX
1.30 Panel Discussion: Off Target Tox VS on Target Toxicity & the Reason Behind Certain Tox & Then How do We Mitigate It?
- Looking at toxicity and is it best to mitigate via a clinical intervention
- Overcoming the limiting non-human primates model
- Administering more drug but less stable so it is cleared more rapidly, hence less toxicity
2.00 Chair’s Closing Remarks
Rakesh Dixit, President & CSO, Regio Biosciences (USA) ; CEO, Bionavigen, LLC
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09.55 Chair’s Opening Remarks
Yuyi Shen, Associate Director, Process Development & Manufacturing, Bolt Biotherapeutics
10.00 Towards ADC Purification on Membrane Technology: An Easy & Fast Process
- Understand the context to replace classical bind elute chromatography by membrane technology
- Share strategy for membrane technology evaluation
- Discuss results and possible acceptance criteria for implementation in the ADC process
Audrey Bendelac, ADC Scientific Manager, Process Development, Sanofi
10.30 Manufacturability & Transferability of ADC Unit Operation
- Integrated ADC process into downstream processing
- Separation of Biological Safety, OEB Classification and Aseptic Filling
- Flexibility of unit operations for IDS, ADCDS and ADC-DP at one or different sites
- Global market supply with decentralized manufacturing strategy
Rolf Werner, Chief Operation Officer, GeneQuantum Healthcare Co Ltd
11.00 HPAPIs & ADCs – A Journey Through High Potency
- CASE STUDY: the development, rapid scaling and commercial production of HPAPI drug substance
- Review integrated containment requirements for particle engineering and drug products
- Discuss advantages of seamless integration of HPAPI and ADC operations
- Assess impact of supporting integrated service-offerings on expansion strategies
David Lyon, Senior Fellow, Research Lonza Pharma & Biotech, Lonza
12.30 Panel Discussion: Scaling Up in a World of Accelerated Approvals
Yuyi Shen, Associate Director, Process Development & Manufacturing, Bolt Biotherapeutics
1.00 Process Development & Comparison of Analytical Approaches for a Novel Chemical Site-Specific
- Overview of the site-selective conjugation of antibodies through the use of a novel class of IgG Fc-affinity peptide reagents to install payload-compatible linkers to welldefined amino acid residues
- Discuss process development for scaleup ADC preparation suitable for GLP toxicological studies
- Compare six different analytical techniques to measure DAR
- Proof of site-selectivity using peptide mapping
Yutaka Matsuda, ADC Researcher, Ajinomoto Bio-Pharma Services
1.30 MRG004A, a Tissue Factor Targeted ADC Using GlycoConnectTM Technology: Process Optimization & Impurity Controls
- GlycoConnect is a site-specific conjugation technology which offers improved linkage stability and homogeneity of payload distribution;
- Examine how Miracogen has adopted the GlycoConnect technology and optimized it for the production of MRG004A ADC with high purity and yield, leading to a successful IND approval in the US.
Minmin Qin, Senior Vice President of CMC, Miracogen
2.00 Characterization of ADC Conjugation Sites using Stable Isotope Labeling Peptide Mapping LC-MS/MS Analysis
- Stable isotope labeling (SIL) can be used to modify the ADC payload molecule mcMMAF
- Unoccupied cysteine sites can be conjugated with SIL mcMMAF to eliminate peptide ionization differences
- Peptide mapping can then be used to determine site-specific conjugation levels for “bottom up” DAR characterization of ADCs
Ty Davis, Investigator, GSK
2.30 Chair’s Closing Remarks
Yuyi Shen, Director, Process development and Manufacturing, Bolt Biotherapeutics
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09.55 Chair’s Opening Remarks
Jay Harper, Associate Director - Research Oncology, AstraZeneca
10.00 The Clinical Landscape of ADC Combinations
- Overview of combination partners for ADCs including rationale
- Summary of clinical trials with ADC combinations
- Showcasing data from ADC combination trials in the clinic
Jay Harper, Associate Director - Research Onocology, AstraZeneca
10.30 Mirvetuximab Soravtansine Combination Development
- A FRα-targeting ADC in phase III clinical trials
- Final results of mirvetuximab plus bevacizumab in women with recurrent ovarian cancer
- Mirvetuximab demonstrates combinability with multiple standard-of-care agents used to treat women with ovarian cancer
Michael Method, Executive Medical Director, ImmunoGen
11.00 A Phase II Study to Determine the Response Kinetics, Safety & Efficacy of Brentuximab Vedotin & Nivolumab Alone & Combined with Rituximab, Cyclophosphamide, Doxorubicin & Prednisone for Patients with Untreated Primary Mediastinal Large B-Cell Lymphoma (PMLBCL)
- The Checkmate-436 trial showed that PMLBCL patients with disease resistance to at least two different lines of treatment showed an impressive response to the combination of immune therapies BV and nivolumab
- BV and Nivolumab alone (A-O) (in the immune lead-in and then combined with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) may show an overall response rate in untreated PMBL at least as high as the ORR in the relapsed/refractory setting
Raphael Steiner, Assistant Professor in the Department of Lymphoma & Myeloma, University of Texas MD Anderson Cancer Center
11.30 Morning Break.
12.30 Combining Immune Checkpoint Inhibitors with ADCS: The Case for Independent Action or Immune Combination Effect
- What is Independent Action and why is it important?
- Calculating combination results for ADCs combined with Immune Checkpoint inhibitors
- Understanding the importance of ADCs in the PD-1 experienced patient population
Emmett Schmitt, Vice President, Clinical Research Lead, External Collaborations Oncology Early Development, Merck
1.00 A First-in-human Study of Mirzotamab Clezutoclax as Monotherapy & in Combination with Taxane Therapy in Relapsed/Refractory Solid Tumors
- Mirzotamab clezutoclax is a first-in-class antibody-drug conjugate targeting the intrinsic apoptosis pathway
- Reviewing how Mirzotamab clezutoclax as monotherapy and with paclitaxel demonstrates a tolerable safety profile; monotherapy MTD not reached
- Presenting on the anti-tumor activity seen with objective responses (by RECIST 1.1) in combination with taxane
Sudhir Penugonda, Medical Director, Oncology Early Development, AbbVie
1.30 Exploring Combinability of Vedotin ADCs with Checkpoint Inhibitors
- Delving into key insights and data from combination trials in Seagen’s late stage ADC portfolio
- Exploring future initiatives to address unmet medical needs through combinations with checkpoint inhibitors
Leo Nicacio, Global Development Lead, Seagen
2.00 Chair’s Closing Remarks
Jay Harper, Associate Director - Research Oncology, AstraZeneca
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09.55 Chair’s Opening Remarks
10.00 Hybrid Immunocapture LC-MS Methods to Support ADC Pipeline
- Explore hybrid ligand binding LC-MS/MS methods to quantify conjugated toxin for different linker-payload systems
- Examine the use of immunocapture LC-MS/MS methods for total antibody determinations
- Review the Affinity Capture LC-MS (AFC LC-MS) approach for the analysis of the intact ADC molecules to better understand the drivers behind the in vitro and in vivo stability of ADC
Federico Riccardi Sirtori, Director, Head of NBEDMPK Innovative Bioanalytics, Merck KGaA
10.30 Tailoring Bioanalytical Assays for ADC Biotherapeutics
- Bioanalytical challenges and strategies for PK analysis of ADCs in (pre)clinical studies; total and conjugated antibody assays using hybrid LC-MS/MS and LBA methods.
- Tiered strategies for immunogenicity measurement.
- Regulatory guidelines and current industry best practices. Perspectives and case studies from a bioanalytical CRO.
Francesco Bonardi, Director Bioanalysis, Ardena
11.00 Mass Spectrometry Provides Insights into ADC Drug Development: PK, ADME & Biotransformations
- Conjugation site influences antibodyconjugated drug PK assays for disulfidelinked, self-immolating ADCs
- Preclinical characterization of catabolism of ADCs in Sprague Dawley rats supports clinical development
- Biotransformation analyses can provide insights into efficacy of ADCs with increasingly complex modalities
Violet Lee, Scientist, Genentech
11.30 Morning Break.
12.30 Unlocking the Potential of Analytical Ultracentrifugation: Measuring Polymer Content in an Antibody-Polymer-Drug Conjugate
- Addressing challenges in the characterization of protein-polymers
- Reviewing a novel approach to utilizing AUC for the characterization of ADCs
- Obtaining a deeper understanding of conjugation impurities
Susan Clardy, Senior Scientist - Analytical Chemistry, Manufacturing & Controls, Mersana
1.00 Preclinical Characterization of the Distribution, Catabolism & Elimination of Polatuzumab Vedotin-piiq (POLIVY®) Antibody-Drug Conjugate in Sprague Dawley Rats to Support Drug Development
- Providing a systematic approach to characterizing the distribution, catabolism and elimination of polatuzumab vedotin, an ADC to treat DLBCL
- Utilizing various radiometric tracer to track the fate of the molecules
- Profiling and identifying the catabolic products of polatuzumab vedotin to evaluate the need for DDI and special population study in clinic
Victor Yip, Principal Scientific Researcher, Genentech
1.30 Bioanalytical Challenges & Strategies for ADCs Transition from Discovery Through Development
- ADCs can undergo complex biotransformation in-vivo resulting into multiple heterogenous species, posing some unique bioanalytical challenges.
- Selection of stage appropriate fit for purpose bioanalytical platform and strategy that would enable faster decision making is crucial for ADC discovery and development.
- Understanding of the stability and biotransformation liabilities of these ADCs at early discovery stage provides an opportunity of Selecting the right assay platform; Identifying any critical reagents, and; Designing the right bioanalytical strategy for further smooth transition into development stage.
Hetal Sarvaiya, Associate Director- DMPK BA, AbbVie
2.00 Advanced Bioanalysis & Biotransformation of ADC: Strategies & Case StudiesSession Reserved for Ardena
- Overview of structural complexity and Biotransformations of ADCs
- Outlining bioanalytical approaches employed to interrogate ADC biotransformations with case studies
- Discussing future perspectives on bioanalytical approaches to better understand ADC biotransformations and their role in drug development
Anton Rosenbaum, Head of Regulated Bioanalysis & OMICS by LC-MS within Integrated Bioanalysis, AstraZeneca
2.30 Bioanalytical Learnings: Overcoming Challenges Associated with the Bioanalysis of Cysteine Conjugated Metabolites in the Presence of Antibody-drug Conjugates
- Laboratory investigations highlighted the overestimation of a cysteine conjugated linker payload when measured in the presence of antibody-drug conjugate when utilizing a solid phase extraction method. A new bioanalytical method was developed, utilizing an acidic protein precipitation, to stabilize and remove the ADC from the sample, allowing for precise and accurate determination of the cysteine conjugated linker payload in samples.
- While there was a systematic difference in study samples analyzed by both methods, the correlation between the concentrations measured by both methods was highly linear. This linear relationship allowed for the correction of historical data generated utilizing the solid phase extraction method.
- The technical and operational challenges, as well as the key learnings, will be shared which can be applied to other programs.
Andrew Mayer, Scientific Leader, GlaxoSmithKline
3.00 Chair’s Closing Remarks