Cambridge Healthtech Institute’s Fifth Annual

Antibody-Drug Conjugates

Engineering for Clinical Success

January 9-10, 2018

 

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.

Final Agenda

TUESDAY, JANUARY 9

1:00 pm Registration

1:30 Refreshment Break in the Exhibit Hall with Poster Viewing

Improving Therapeutic Index

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

KEYNOTE PRESENTATION

2:05 Case Study: Translational Safety of Antibody Drug Conjugates -- Opportunities to Mitigate Clinical Toxicities and Improve Therapeutic Index (TI)

Rakesh_DixitRakesh 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_PrudentJames 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.

Applied Biomath3:15 Computational Exploration of Mechanistic Determinants of ADC Pharmacokinetics Using QSP Modeling Strategies 

Burke JohnJohn 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

NEXT-GEN ADC STRATEGIES

4:30 From Cells to ADCs: A Magnetic Bead-Based Workflow for Antibody Capture and Conjugation
Paul_GianellaPaul 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_ChiuDavid 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

FIGHTING CANCER WITH ADCs

8:30 Chairperson’s Remarks

Floris Van Delft, Ph.D., Founder & CSO, SynAffix BV

FEATURED PRESENTATION

8:35 Targeted Protein Therapeutic Drug Design in Oncology

Jeannick_CizeauJeannick 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_DimitrovDimiter 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

INNOVATING LINKER & PAYLOAD TECHNOLOGIES

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_SellmannCarolin 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_GavrilyukJulia 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

SITE-SPECIFIC CONJUGATION

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_DelftFloris 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

OVERCOMING PRODUCTION CHALLENGES

4:00 Early and Late-Stage Development and Manufacturing Challenges for ADCs

Robert_HerbstRobert Herbst, Ph.D., Director, Process Development and Engineering, ImmunoGen, Inc.


4:30 Strategy to Advance ARX788 ADC from Development to Clinical Manufacturing

Yun_BaiYun 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


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