Cambridge Healthtech Institute’s Fourth Annual
Antibody-Drug Conjugates
Engineering for Clinical Success
January 10-11, 2017 | Hilton San Diego Bayfront | San Diego, CA
With more than 30 ADCs in clinical trials, and more on the way, antibody-drug conjugates have reached an exciting point in development, particularly with the current next-generation strategies. Cambridge Healthtech Institute’s Antibody-Drug Conjugates
conference reveals the engineering that has brought about today’s revolution, and examines how to design safe and effective ADCs. In addition, strategies for advancing ADCs to the clinic will be discussed along with considerations for clinical
trial design. Analyzing ADCs to explore conjugation, stability, payloads and tumor penetration will also be addressed in this leading ADC event.
TUESDAY, JANUARY 10
1:00 pm Conference Registration
1:30 Refreshment Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Opening Remarks
Vaughn Smider, M.D., Ph.D., Assistant Professor, Molecular Biology, Scripps Research Institute; CSO, Sevion Therapeutics
Keynote Presentation
2:05 Antibody-Drug Conjugate Therapeutics and Their Evolving Role in Oncology
Arvind Rajpal, Ph.D., Vice President, Protein Therapeutics, Bristol-Myers Squibb Co.
ADCs are a maturing therapeutic class with more than 50 candidates in clinical development and two approved molecules on the market. The emergent role of immunotherapy in oncology presents several challenges and opportunities for ADCs. Successful positioning
of current and future ADC candidates, in light of these changes, will require strategic imperatives that enhance the complementary role of ADCs to immunotherapy.
2:45 Challenges to Improvement in the Therapeutic Index of ADCs in Solid Cancers
Rakesh Dixit, Ph.D., DABT, Vice President, Research & Development, and Global Head, Biologics Safety Assessment,
MedImmune (A member of AstraZeneca Group)
3:15 Nanoparticle-Based Antibody Drug Conjugates for Tumor Therapy
Raghuraman
Kannan, Ph.D., Associate Professor, Radiology and BioEngineering, University of Missouri School of Medicine
This presentation will focus on the design and development of ADCs using nanoparticles as the platform. The synthesis and characterization
of two different NANO-ADC platforms based on peptide and antibody as targeting agents conjugated with doxorubicin as a chemotherapeutic agent will be presented. New, unpublished data
3:45 Refreshment Break in the Exhibit Hall with Poster Viewing
4:30 Leveraging Ultra-Potent Toxins in Novel ADCs for Highly Effective Anti-Tumor Therapy
Ulf Grawunder, Ph.D., CEO & Founder, NBE-Therapeutics, Ltd.
The development of antibody-drug conjugates (ADCs) is associated with the challenge of selective delivery of highly potent toxins to tumors. ADC stability, homogeneity, binding specificity and the engagement of immune-mediated cell death (ICD) mechanisms
are critical factors to achieve an optimal therapeutic index of ADCs, especially if ultra-potent toxic payloads are engaged. Data on the anti-tumor activity of novel, next-generation ADCs with ultra-potent toxins will be presented.
5:00 Antigen-Targeted Amanitin-Conjugates (ATACs) – Expanding the ADC Landscape with a New Payload Targeting RNA Polymerase II
Torsten Hechler, Ph.D., Head, Biochemistry and ADC Research, Heidelberg Pharma GmbH
Antigen-Targeted Amanitin-Conjugates (ATACs) represent a new class of ADCs using the payload Amanitin. This payload introduces a novel mode of action into oncology therapy, the inhibition of RNA polymerase II. The technology platform around ATACs includes
Amanitin supply, site-specific conjugation, a demonstrated safety profile and a biomarker. A BCMA-ATAC has been selected based on favorable preclinical data to start the clinical development of the first ATAC.
5:30 Close of Day
WEDNESDAY, JANUARY 11
8:00 am Conference Registration and Morning Coffee
8:30 Chairperson’s Remarks
Dorin Toader, Ph.D., Senior Scientist, Antibody Discovery and Protein Engineering, MedImmune LLC
8:35 Clinical Pharmacology of vc-MMAE Antibody-Drug Conjugates: Platform Approach to Characterize Pharmacokinetics and Peripheral Neuropathy
Chunze Li, Ph.D., Senior Scientist, Therapeutic Area Lead for ADCs, Clinical Pharmacology, Genentech
This presentation will provide clinical pharmacology learnings and challenges for vc-MMAE antibody-drug conjugates (ADCs), and describe the innovative platform approach to integrate clinical pharmacology data across vc-MMAE ADCs to inform clinical strategy.
I will also discuss the clinical pharmacokinetic characteristics across several vc-MMAE ADCs, and the exposure response relationship and risk factors for peripheral neuropathy associated with the use of vc-MMAE ADCs in clinical testing.
9:05 Translatability of Peripheral Neuropathy with Microtubule Inhibitor Containing Antibody-Drug Conjugates from Nonclinical Toxicology Studies to the Clinical Setting
Nicola Stagg, Ph.D., Scientist/Toxicologist, Safety Assessment, Genentech
The valine citriline monomethyl auristatin E (vcMMAE) ADC platform has shown promising clinical activity in a variety of cancers, but peripheral neuropathy (PN) has been observed in the clinic that was not observed in nonclinical toxicology studies. We
evaluated four possible hypotheses for the lack of translatability of PN. The ultimate goal is to be able to have a model to screen the next generation MTI ADCs for reduced incidence and severity of peripheral neuropathy.
9:35 Immunogenetics and Structural Biology of Cow Ultralong CDR3 Antibodies
Vaughn
Smider, M.D., Ph.D., Assistant Professor, Molecular Biology, Scripps Research Institute; CSO, Sevion Therapeutics
The bovine antibody repertoire is unusual in having ultralong CDR3s which can be up to 70 amino acids in length. The structures of these antibodies contain a b-strand “stalk” and disulfide-bonded “knob” region. We have determined the genetic underpinnings for this antibody class, and studies have also revealed unique conserved structural features of the ultralong CDR3.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
10:50 How in vivo & in vitro ADC Stability Data Is Used to Advance Projects at Pfizer
Anokha Ratnayake, Ph.D., Principal Scientist, Medicine Design - ADC Oncology, Pfizer
The design and development of a successful ADC require identification and implementation of reliable analytical techniques and assays (such as LBA and DAR-based PK, plasma stability) at an early stage, to help drive decisions about project advancements.
A fundamental understanding of ADC metabolism enables problem solving that may “rescue” payloads that were previously deprioritized. Site of conjugation can play a major role in ADC metabolism, hydrophobicity and PK.
11:20 An Integrated Multiplatform Bioanalytical Strategy for Antibody–Drug Conjugates: A Novel Case Study
Vangipuram S. Rangan, Ph.D., Senior Director, Protein Chemistry, Bristol-Myers Squibb Co.
This talk describes the utilization of reagents specifically tailored to an ADC with a microtubule polymerization inhibitor payload and cathepsin B cleavable linker. The PK strategy includes the evaluation of physiological levels of total antibody,
active ADC, total ADC, antibody-conjugated payload and unconjugated payload. These data are evaluated in the context of target and antidrug antibody levels to elucidate bioactive ADC.
11:50 Neutropenia Translation of ADC: Perspective from Mechanistic Modeling
Shangchiung Chen, Ph.D., Scientist, Clinical Pharmacology, Genentech
A quantitative preclinical/clinical translational model for neutropenia was developed using PK and PD data from multiple vc-MMAE ADCs. The translational PK/PD model can be used to predict potential risk of neutropenia based on preclinical observation
in monkeys and facilitate dose/regimen selection.
12:20 pm Sponsored Presentation (Opportunity Available)
12:50 Session Break
1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
2:00 Chairperson’s Remarks
Torsten Hechler, Ph.D., Head, Biochemistry and ADC Research, Heidelberg Pharma GmbH
FEATURED PRESENTATION
2:05 Challenges and Opportunities in Design and Development of Antibody-Drug Conjugates
John M. Lambert, Ph.D., Executive Vice President & Distinguished Research Fellow, ImmunoGen, Inc.
ADCs with potent tubulin-acting and DNA-acting agents can be effective anti-cancer agents with good TI. However, not all cell-surface targets have proven susceptible to the development of effective ADCs utilizing first generation ADC chemistries.
Lessons from the past 15 years of ADC preclinical and clinical experience have created new opportunities in design and development of ADCs to meet the challenges in creating successful ADCs, as illustrated with the progress of ImmunoGen’s
advancing ADC.
2:35 MMETA – A Tubulysin Analog for Antibody-Drug Conjugates
Dorin Toader, Ph.D., Senior Scientist, Antibody Discovery and Protein Engineering, MedImmune LLC
Tubulysins are a class of naturally occurring highly cytotoxic peptides of fungal origin. The observed picomolar activity of tubulysins against a range of cancer cell lines makes them excellent candidates for targeted delivery as conjugates with monoclonal
antibodies. This presentation describes the discovery and development of a fully synthetic tubulysin analog MMETA and its application to antibody-drug conjugates for oncology.
3:05 Multiparatopic and Multispecific Nanobody-Based Drug Conjugates
Carlo Boutton, Ph.D., Director, Technology & Information Management, Ablynx nv
The modularity of the Nanobody platform allows an easy generation of multivalent, multiparatopic and multispecific constructs. By combining several Nanobodies with similar or different functionalities, the properties of the proposed drug can be tuned.
This is an extremely powerful platform to direct Nanobody-based drug conjugates to diseased cells.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing
4:30 Selecting the Optimal Cysteine Site for THIOMAB-Drug Conjugates
Hans Erickson, Ph.D., Associate Director, Protein Chemistry, Genentech
Antibodies with cysteine mutations for conjugation are widely used for the preparation of homogeneous ADCs with defined molar ratios of the payload to the antibody (site-specific). The factors that drive stability are not well understood. I propose
to describe how we have optimized our cysteine engineering (THIOMAB™) technology to build better ADCs and also share some of the research conducted to understand the factors that drive stability of protein conjugates using maleimide and
disulfide-based attachment chemistries.
5:00 Pcl and PPTase – Two Innovative Methods for the Preparation of Homogenous ADCs
Bernhard H. Geierstanger, Ph.D., Director, Protein Engineering, Genomics Institute of
the Novartis Research Foundation
Pyrroline-carboxy-lysine (Pcl) is readily incorporated by the unmodified pyrrolysyl-tRNA/tRNA synthetase pair into proteins at TAG codons and reacts specifically with 2-amino-benzaldehyde reagents. Similarly, post-translational modification catalyzed
by phosphopantetheinyl transferases (PPTases) can be used to site-specifically label proteins with structurally diverse molecules. Both methods can be used to efficiently prepare homogenous, site-specifically conjugated ADCs with excellent biophysical
and PK characteristics, and high in vitro and in vivo potency.
6:20-7:20 Reception in the Exhibit Hall with Poster Viewing
7:20 Close of Conference