Cambridge Healthtech Institute's Fifth Annual

Antibody-Drug Conjugates

( 抗体药物复合物 )

Engineering for Clinical Success

2018年1月9日 - 10日

 

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 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 Improved Therapeutic Window with Antibody Linked Pyrrolobenzodiazepine Dimers That Is Enhanced by PARP Inhibitor in BCA Mutant Tumors

Haihong (Helen) Zhong, Ph.D., Senior Scientist, Oncology Research, MedImmune, Inc.

One of the major challenges to ADCs is how to improve therapeutic index. PBDs are DNA-damaging agents that have potent cytotoxicity against a broad spectrum of tumors. In preclinical efficacy and safety studies including a "mouse PDX trial", PBD-based ADC as a single agent or in combination with PARPi demonstrated enhanced anti-tumor acitivity in BRCA mutant tumors. Furthermore, the combination was better tolerated than monotherapy, indicating an improved therapeutic index.

3:15 Sponsored Presentation (Opportunity Available)

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing

NEXT-GEN ADC STRATEGIES

4:30 Preclinical Development of a Novel FLT3 Targeting Antibody-Drug Conjugate Employing Site-Specific Conjugate for the Treatment of Acute Myeloid Leukemia

Kendall Morrison, Ph.D., Director, Protein Technologies, Agensys, Inc. (an affiliate of Astellas Pharma)

The presentation will cover multiple aspects of next-generation ADC preclinical development, such as target choice and validation, next-generation goals, antibody selection, Ambrx platform selection, payload and linker selection, preclinical modelling, and toxicology.

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

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 Cizeau, Ph.D., Director, Research, Viventia Bio, 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 Sponsored Presentation (Opportunity Available)

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 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.

12:20 pm Sponsored Presentation (Opportunity Available)

12:50 Session Break

1:00 Luncheon Presentation (Sponsorship Opportunity Available) or 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 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 Herbst, Ph.D., Director, Process Development and Engineering, ImmunoGen, Inc.

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 Blocking Salt Release with Precision

James R. Prudent, Ph.D., President & CEO, Centrose LLC

ADCs that act on the surface of the cell and require antibody drug release are termed extracellular drug conjugates or EDCs. This talk will describe EDCs that kill cancer cells and recruit immune effector cells via blocking salt transport across the outer membrane. Salt levels inside cells rise when nutrients enter and waste products exit actively growing cells. This new type of precision therapy platform that inhibits one of the most important and oldest processes known will be reviewed.

5:30 - 6:45 Networking Reception in the Exhibit Hall with Poster Viewing

6:45 Close of Antibody-Drug Conjugates Conference

* 活动内容有可能不事先告知作更动及调整。