THURSDAY, October 11
7:30 – 8:15am Breakfast Presentation (Sponsorship Opportunity Available)
8:30 Chairperson’s Remarks
Paul W.H.I. Parren, Ph.D., Senior Vice President & Scientific Director, Genmab
8:35 Targeted Potentiation of Endosomal Release of Macromolecular Payloads
K. Dane Wittrup, Ph.D., J.R. Mares Professor, Chemical Engineering & Bioengineering, Massachusetts Institute of Technology
Release of endocytosed payloads from endolysosomal compartments is a typical rate limiting step for gene therapy, siRNA delivery, immunotoxins, nanoparticulate drugs, and antibody drug conjugates, striking a difficult balance to avoid general plasma membrane destabilization (toxicity), while maintaining efficient permeabilization within the endosomes of targeted cells (efficacy). Natural selection has crafted solutions to this problem used by pathogens such as viruses and intracellular bacteria. We describe here targeted cytolysins that greatly potentiate siRNA and immunotoxins
9:05 Efficacy, Safety and PK/PD of Sym004 - From Bench to Bedside
Niels Jørgen Ø. Skartved, Ph.D., Principal Scientist, Symphogen A/S
Sym004 is a novel therapeutic antibody combination product consisting of two monoclonal antibodies targeting non-overlapping epitopes on the Epidermal Growth Factor Receptor (EGFR). In pre-clinical in vitro and in vivo tumor models, the antibody mixture displayed a potent and efficient anti-tumor activity, with a mode of action different from that of monoclonal antibody therapeutics. The unique mode of action translated into a distinct preclinical and clinical PK/PD relationship and an acceptable safety profile.
9:35 Pharmacokinetics of Dual Variable Domain Immunoglobulin (DVD-IgTM) Molecules
Edit Tarcsa, Associate Director, DMPK-BA Abbott Bioresearch Center
Bispecific biologics are a novel class of therapeutics that are very promising but at the same time present new challenges to identifying the best candidates with good PK and drug-like properties. DVD-IgTM molecules are versatile bispecifics that preserve many of the properties of their parental antibodies. Pre-clinical screening methods, including extensive physicochemical and PK characterization, were performed to select molecules. Discovery and development strategies for mAbs vs. DVD-Ig molecules will be compared and contrasted that lead to the identification of DVD-Ig clinical candidates.
10:05 PK/PD Evaluation of Bispecific Antibodies in Pre-Clinical Species
Steven Yu, Ph.D., Senior Scientist, PKDM Department, Amgen
New therapeutic modalities such as bispecific Abs are invented to generate additive or synergistic effect. They could differ in every possible ways from parent compounds. In this presentation, we will provide case studies to address the PK, PD and immunogenicity changes from parent compounds. Through the discussion we would like to provide some basic guidelines in support of bi-specific programs.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing (Sponsorship Opportunity Available)
11:10 In vitro and in vivo Stability of Bispecific κλ-bodies
Krzysztof Masternak, Ph.D., Head of Biology, NovImmune SA
κλ-bodies are bispecific IgG consisting of a common heavy chain paired with two different light chains, one kappa and one lambda. The physicochemical and PK characterization of these molecules will be discussed.
11:40 Generation of Bispecific Antibodies with the Duobody Platform
Paul W.H.I. Parren, Ph.D., Senior Vice President & Scientific Director, Genmab
With the DuoBody™ platform, which is based on the principle of controlled Fab-arm exchange, we have developed a novel, highly efficient, method to generate bispecific antibodies. Bispecific antibodies developed with this platform retain the biochemical structure of regular human IgGs, have Fc-mediated effector functions and regular IgG1 pharmacokinetics. Furthermore, the platform is compatible with standard unit operations for large scale IgG1 manufacturing. The technology, its scientific background and various proof-of-concept studies will be discussed.
12:10 pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
1:30 Chairperson’s Remarks
James R. Prudent, Ph.D., President and CEO, Centrose
1:35 Application of PKPD Principles in Optimizing Antibody Drug Conjugates
Kedan Lin, Ph.D., Group Leader, Department of Pharmacokinetic and Pharmacodynamic Sciences, Genentech
Despite recent success of antibody drug conjugates in various stage of clinical development, there are significant challenges in optimizing and developing these complex molecules. This talk will discuss the emerging effort in integrating ADME, PK, efficacy and safety to establish meaningful PK/PD relationships and to support ADC optimization.
2:05 Extracellular Drug Conjugates – Targeting Small Molecule Drugs Right Where You Want Them
James R. Prudent, Ph.D., President and CEO, Centrose
Integral membrane protein activity is often dictated by accompanying peripheral proteins. These interactions as well as the composition, stoichiometry and environment of the complexes that form, characteristically regulate a wide range of cellular activities. In diseased cells, these multi-variant factors change and can lead to drastic changes in protein function. This talk will highlight a novel type of drug targeting system which uses proximity effects and cooperative specificity to direct small molecule drugs not only to a specified diseased cell, but specifically to the drugs active site.
2:35 Sponsored Presentation (Opportunity Available)
3:05 Refreshment Break in the Exhibit Hall with Poster Viewing (Sponsorship Opportunity Available)
3:30 Pre-Clinical Development of IMGN853, an Antibody-Maytansinoid Conjugate Targeting FOLR1 for the Treatment of Solid Tumors
Jan Pinkas, Ph.D., Director, Pharmacology, ImmunoGen, Inc.
4:00 Panel Discussion with Speakers
4:30 Breakout Sessions
PK/PD in Optimizing ADCs
Moderator: Kedan Lin, Ph.D., Group Leader, Department of Pharmacokinetic and Pharmacodynamic Sciences, Genentech
PK/PD of Antibody Fragments
Moderator: Lu Xu, Ph.D., M.S., Director, Pharmacokinetics and Pharmacometrics, OncoMed Pharmaceuticals, Inc.
• What are the characteristics distinguish antibody fragments over full length molecules?
• Which research areas can truly benefit from antibody fragments?
• Which diagnostic or therapeutic areas can truly benefit from antibody fragments?
• What lessons have we learnt in developing antibody fragments?
PK of Bispecific Molecules
Moderstor: Edit Tarcsa, Associate Director, DMPK-BA Abbott Bioresearch Center
• PK assay for bispecifics:
• What to measure for bispecifics: 'total' or 'free' what is 'free' with 4 binding sites (free of A or B or both)?
• How to reconcile results from different assay formats?
• If running multiple assay what to use for PK calculations?
• Does the PK of bispecifics differ from mAbs (e.g. are distribution or clearance altered?)?
• PD for Bispecifics:
• Should we measure target (ligand) for bispecifics?
• Should we measure both total of free? For each target?
• ADA for Biscpecifics:
• Neutralizing ADA assay: do we need two of them?
• How should we handle immunogenicity risk analysis for bispecifics?
• Is there greater risk for immunogenicity with bispecifics?
5:30 End of Day Two