Fourth Annual Novel Antibody Constructs and Alternative Scaffolds
Part Two: Enhanced Product Properties and Therapeutic Application
Day 1 | Day 2
Part One | Download Brochure
Wednesday, 7 November
12:30 – 14:00 Conference Registration for Part Two
14:00 Chairperson's Opening Remarks
John McCafferty, Ph.D., Research Director, Biochemistry, University of Cambridge
14:05 PK Modulation of Adnectins: Experiences from Bench to Clinic
Ray Camphausen, Associate Vice President, Protein Design, Adnexus, a Bristol-Myers Squibb R & D Company - Biography
Adnectins, derived from the highly stable fibronectin 10th Fn3 domain, are among the most advanced alternative scaffolds, with multiple therapeutics in the clinic. The highly engineerable Adnectin scaffold is amenable to a wide variety of approaches to fine tune functional, biophysical, developability, and pharmacokinetic properties in a therapeutic-dependent manner. Multiple approaches to modulate the pharmacokinetics of Adnectins have been explored focused on either increasing hydrodynamic volume and/or leveraging the FcRn recycling pathway. Data reflecting our observations will be presented.
14:35 Ang-2-VEGF Crossmab, a Novel Bi-Specific Human IgG1 Antibody Blocking VEGF-A and Ang-2 Function with Favorable Stability, Half-Life, and Efficacy
Markus Thomas, Ph.D., Senior Research Scientist, Pharma Research and Early Development (pRED), Discovery Oncology, Roche Diagnostics GmbH - Biography
VEGF-A blockade has been validated clinically as a treatment for human cancers. Angiopoietin-2 (Ang-2) expression has been shown to function as a key regulator of tumor angiogenesis. We have generated a bi-specific human IgG1 antibody (CrossMab) blocking VEGF-A and Ang-2 function simultaneously. Our data show that the CrossMab has very good stability, an IgG like half-life in cynomolgus monkey and a favorable safety profile. Additionally it shows favorable efficacy in pre-clinical tumor cancer models, thereby representing a promising therapeutic agent for the therapy of cancer patients.
15:05 Novel in Silico Prediction Algorithms for the Design of Stable Biologics
Anne Goupil-Lamy, Principal Scientist, Accelrys - Biography
Understanding the effects of mutation on protein stability and protein binding affinity is an important component of successful protein design, especially in the area of protein therapeutics. In silico approaches to predict the effects of amino acid mutations can be used to guide experimental design and help reduce the cost of bringing therapeutics to market. We have implemented and validated several novel methods for fast computational mutagenesis of proteins to calculate the energy effect of mutation on protein stability, and on protein-protein binding affinity with an optional pH dependency calculation. We will present those methods and applications to antibody design.
15:35 Refreshment Break in the Exhibit Hall with Poster Viewing
16:15 Strategies to Extend the Half-Life of Small Recombinant Protein Therapeutics
Roland Kontermann, Ph.D., Professor, Biomedical Engineering, Institute of Cell Biology and Immunology, University of Stuttgart - Biography
Half-live extension strategies are becoming increasingly important to improve pharmacokinetic and pharmacodynamic properties. An overview of the various strategies to extend the half-life of recombinant antibodies as well as results from a comparative study including novel strategies utilizing binding to serum albumin and serum immunoglobulins are presented and discussed.
16:45 Optimization of Bi-Specific DART Proteins for Oncology
Syd Johnson, Ph.D., Vice President, Antibody Engineering, MacroGenics, Inc. - Biography
The major challenges to development and effective clinical use of fragment-based bi-specific formats have been manufacturability, stability and pharmacokinetics. We have developed and optimized several formats of our stable dual-affinity retargeting (DART) format that address these issues with an emphasis on oncologic applications. Multiple examples will be presented of half-life extended DART proteins that redirect T-cells to tumor-associated antigens, including CMC strategies and in vitro and in vivo potency. Challenges of non-clinical toxicology for these highly potent molecules in relevant species will also be discussed.
17:15 Problem Solving Roundtable Discussions
Table 1: Engineering of Bispecific Antibodies
Moderator: Florian Rueker, Ph.D., Professor, Biotechnology, University of Natural Resources and Life Sciences, Vienna; Co‑Founder, f-star
Table 2: Challenges of Targeting the Immune Response
Moderator: Rebecca Ashfield, Ph.D., Portfolio and Collaborations Manager, Immunocore Ltd.
Table 3: Targeting Tumor Antigens
Moderator: Gregory Adams, Ph.D., Co-Leader, Developmental Therapeutics Program, Fox Chase Cancer Center
Table 4: Measures to Increase Half-Life and Stability of the Product
Moderator: Roland Kontermann, Ph.D., Professor, Biomedical Engineering, Institute of Cell Biology and Immunology, University of Stuttgart
Table 5: Building Manufacturability into Novel Antibody Formats
Moderator: Hans de Haard, Ph.D., CSO, arGEN-X BV
Table 6: Bi/Multispecific Compound Specific Issues When Moving from Pre-Clinical to Clinical and Beyond
Guy Hermans, Ph.D., Principal Scientist, Ablynx NV
18:15 – 19:15 Reception in the Exhibit Hall with Poster Viewing
Day 1 | Day 2
Part One | Download Brochure