Cambridge Healthtech Institute’s Antibody-Drug Conjugates conference reveals the engineering that has brought about today’s ADC revolution, and examines how to design safe and effective therapeutics. Exploring options for selecting new targets
and ensuring potency will be discussed, along with strategies for advancing ADCs to the clinic. A special focus on fighting cancer will be highlighted including tumor penetration. Analyzing ADCs to explore conjugation, stability, and payloads will
also be addressed in this leading ADC event.
TUESDAY, JANUARY 9
1:00 pm Registration
1:30 Refreshment Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Opening Remarks
Ian Schwartz, MS, CMC Expert, Antibody Drug Conjugate and Upstream/Downstream Process Development, Tech Transfer, and Manufacturing Ops, Sartorius Stedim Biotech
2:05 Case Study: Translational Safety of Antibody Drug Conjugates -- Opportunities to Mitigate Clinical Toxicities and Improve Therapeutic Index (TI)
Rakesh Dixit, Ph.D., DABT, Vice President, R&D, MedImmune/AstraZeneca
I discuss preclinical toxicity models of safety assessment, translational safety and therapeutic index, and clinical development of ADCs using precision medicine approaches.
2:45 TALK REPLACEMENT:
Blocking Salt Release with Precision
James R. Prudent, Ph.D., President & CEO, Centrose LLC
Extracellular drug conjugates (EDCs) act at the cell surface, do not internalize and do not release free drug. This talk will describe anti-cancer EDCs that induce irreversible cell swelling. Swelling is a highly evolved system that induces stress,
disrupts gradients, and activates the immune system. This talk will discuss how triggered irreversible swelling can be induced in a cancer specific manner and why this is important.
Exploration of Mechanistic Determinants of ADC Pharmacokinetics Using QSP Modeling Strategies
John Burke, Ph.D., Co-Founder, President,
CEO, Applied BioMath, LLC
The pharmacokinetics of ADC therapeutics typically show a discrepancy between PK of total antibody and of conjugated antibody, carrying one or more payload molecules. This discrepancy is often attributed to deconjugation, however recent evidence suggests
that underlying mechanisms may be more complex. This presentation will demonstrate a computational approach to understand the impact of DAR and resulting changes in molecular properties on overall PK and relative payload disposition as observed
in preclinical and clinical studies.
3:45 Refreshment Break in the Exhibit Hall with Poster Viewing
4:30 From Cells to ADCs: A Magnetic Bead-Based Workflow for Antibody Capture and Conjugation
Gianella, Ph.D., Postdoctoral Research Fellow, Amgen, Inc.
Magnetic beads are a useful research tool for manipulation and isolation of cells or proteins of interest due to their ability to be fuctionalized with a variety of affinity reagents and ease of handling. Here, we developed a process that demonstrates
the speed and ease of use of magnetic beads for highly efficient purification and conjugation of cysteine-engineered antibodies from cell culture to final antibody conjugate products in a single workflow.
5:00 Exploring Higher Order Structure of ADCs with Biophysical Characterization Techniques
David Chiu, Ph.D., Scientist, Analytical Sciences, Seattle Genetics
Conformational changes to a biotherapeutic can impact product stability, safety, and efficacy, making higher order structure (HOS) characterization fundamentally important. Multiple biophysical techniques, each with their own capabilities and limitations,
are required to elucidate HOS. ADCs can present unique biophysical analytical challenges, and as a case study, the biophysical characterization of a cysteine-conjugated ADC with a drug-to-antibody ratio of 8 will be presented.
5:30 Close of Day
5:30 - 5:45 Short Course Registration
5:45 - 8:45 Dinner Short Courses*
* Separate registration required
WEDNESDAY, JANUARY 10
8:00 am Registration and Morning Coffee
8:30 Chairperson’s Remarks
Floris Van Delft, Ph.D., Founder & CSO, SynAffix BV
8:35 Targeted Protein Therapeutic Drug Design in Oncology
Jeannick Cizeau, Ph.D., Director, Research, Eleven Biotherapeutics Inc.
Targeted protein therapeutics, or TPTs, are recombinant proteins composed of targeting moieties genetically fused via a short peptidic linker to cytotoxic protein payloads. A fit-for-purpose design approach is utilized to overcome specific
challenges inherent to antibody drug conjugates currently in use for the treatment of solid cancers. An overview of drug design for both local and systemically deliverable TPTs will be presented.
9:05 Targeting Solid Tumors with Antibody-Drug Conjugates: An Update
Dimiter S. Dimitrov, Ph.D., Senior Investigator, Center for
Cancer Research, NCI/NIH
Therapy of solid tumors continues to be a major challenge. We have been developing several antibody-drug conjugates (ADCs) to solid tumors including lung, colon and breast cancer, and neuroblastoma. The ADCs were generated by site-specific
conjugation through glycans and conjugated to PBD dimers. They were tested in vitro and in mouse models and showed promise for further evaluation in humans. Potential problems related to toxicity and efficacy
will be discussed.
9:35 Accelerate Development of Bioconjugates
Tyler Gable, Ph.D., Technology and Application Consultant, Bio and Reaction Engineering, METTLER TOLEDO AUTOCHEM
Rapid, reproducible, and data-rich process understanding Design of Experiment (DoE) can achieve accelerated process development of antibody and protein-conjugates. Gain confidence in the precise control of drug substance process with repeatable
reactions under reproducible conditions. Examine two recent industry case studies utilizing automated bioconjugate workstations to eliminate process induced aggregates, improve product distribution and monomeric drug substance composition,
optimize raw material consumption, efficiency and reduce overall process time.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
10:50 Understanding Stability of ADCs Utilizing Deconjugation of Small Molecule Drugs
Colin Medley, Ph.D., Senior Scientist, Small Molecule Pharmaceutical Sciences, Genentech, Inc.
This presentation will highlight our recent efforts to use deconjugation of the payload of ADCs to better understand the stability and degradation pathways for the linker drug portion of ADCs. We have developed methods of enzymatic and chemical
deconjugation that have proved effective for analyzing ADCs comprised of different linker drugs and different antibodies.
11:20 Balancing Selectivity and Efficacy of Bispecific EGFR x c-MET Antibodies and Antibody-Drug Conjugates
Carolin Sellmann, Ph.D., Scientist, Protein Engineering and Antibody
Technologies, Merck KGaA
Therapies targeting EGFR often suffer from toxicities due to basal EGFR expression in normal tissue and may face limited efficacy through c-MET activation. Hence, we aim to construct bispecific EGFR x c-MET antibodies employing affinity-optimized
binding moieties to balance both high selectivity and anti-tumor efficacy and to evaluate their potential for an innovative antibody-drug conjugate approach.
11:50 Development and Optimization of Antibody-Drug Conjugates Armed with DNA Damaging Payloads
Julia Gavrilyuk, Ph.D., Principal Research Scientist, Chemistry Lead,
Discovery Chemistry, Abbvie StemcentRx, Inc.
Highly potent DNA damaging payloads present unique challenges in prediction of corresponding ADCs in vivo efficacy and toxicological profile based on limited in vitro evaluation. Unexpected experimental findings in the course
of development and optimization of calicheamicin and pyrrolobenzodiazepine based ADCs will be presented.
12:20 pm Enjoy Lunch on Your Own
2:00 Chairperson’s Remarks
Julia Gavrilyuk, Ph.D., Principal Research Scientist, Chemistry Lead, Discovery Chemistry, Abbvie StemcentRx, Inc.
2:05 Optimized Site-Specific Antibody-Glucocorticoid Conjugation for Targeted Delivery of Novel Glucocorticoids to Ag+ Cells
Amy Han, Ph.D., Director, Chemistry, Regeneron Pharmaceuticals
We optimized transglutaminase-mediated site-specific conjugations, and our site-specific antibody glucocorticoid (GC) conjugates selectively delivered GCs to Ag+ cells with > 500-fold selectivity over non-target cells in vitro,
and demonstrated excellent stability in vivo. Specifically delivering GCs to disease-affected cells via an ADC could potentially reduce the systemic side effects of non-targeted GC therapy.
2:35 HydraSpace Technology: A Versatile Ionic Spacer to Further Empower Glycan-Conjugated (GlycoConnect) Antibody-Drug Conjugates
Floris Van Delft, Ph.D., Founder & CSO, SynAffix BV
Conjugation and spacer technology constitute key components of antibody-drug conjugates (ADCs). We here demonstrate that manufacturability and stability of our “GlycoConnect” technology, based on site-specific conjugation of payload
through the native glycan, is further enhanced by a novel spacer technology (“HydraSpace”). Moreover, head-to-head in vivo assessment versus all main-stream conjugation technologies, including
based on cysteine engineering, indicate a major improvement in pharmacokinetics, efficacy and safety, hence significantly enhanced therapeutic index.
3:05 Refreshment Break in the Exhibit Hall with Poster Viewing
4:00 Early and Late-Stage Development and Manufacturing Challenges for ADCs
Robert Herbst, Ph.D., Director, Process Development and Engineering, ImmunoGen,
4:30 Strategy to Advance ARX788 ADC from Development to Clinical Manufacturing
Yun Bai, Ph.D., Director, Ambrx, Inc.
ADC technology transfer and manufacturing can be very challenging, especially for CMOs in a different country with different cGMP and clinical filing regulations. This presentation will focus on various strategies used in ARX788 ADC technology
transfer project for multi-country clinical filing.
5:00 Extended Q&A with Speakers
5:30 - 6:45 Networking Reception in the Exhibit Hall with Poster Viewing
6:45 Close of Antibody-Drug Conjugates Conference