Day 1 | Day 2
CHI presents Engineering of Novel Antibody Constructs & Alternative Scaffolds and Therapeutic Developments with Novel Antibody Products. Investigators from industry and academia are continuing to seek improved biotherapeutics by focusing on refined targeting, enhanced effector function, increased half-life, and improved delivery, binding and stability. With this goal, novel products such as multi-specific constructs, antibody-drug conjugates and small antibody fragments and peptides are being engineered and developed. The first part of this event focuses on new engineering approaches while the second part examines the therapeutic development of these exciting new biologics.
TUESDAY, 11 OCTOBER
9:00 Conference Registration and Morning Coffee
9:30 Chairperson’s Opening Remarks
Ho Sung Cho, Ph.D., CTO, Ambrx
9:35 T Cell-Engaging Bi-Specific Antibody Constructs for Cancer Therapy
Patrick A. Baeuerle, Ph.D., CSO & Senior Vice President, Research & Development, Micromet, Inc. - Biography
Engagement of T cells for cancer therapy requires special antibody constructs. One example is the CD3/CD19-bi-specific BiTE antibody blinatumomab. First clinical results from studies in ALL and NHL patients showed very high response rates and durable remissions after monotherapy with the BiTE antibody blinatumomab. Several other BiTE antibodies are in clinical and pre-clinical development for treatment of solid tumors.
10:05 Kλ-body: A Next Generation Fully Human Bi-Specific Antibody Format with Favorable Biochemical and Manufacturability Properties
Nicolas Fischer, Ph.D. Head, Research, NovImmune SA - Biography
Bi-specific antibody formats often include linkers or mutations that can lead to poor biochemical properties and manufacturing issues. The Kλ-body represents a unique bi-specific format, undistinguishable from a standard IgG. The controlled co-expression of a kappa and a lambda light chain with a common heavy chain, combined with a multi step affinity purification process allows for efficient manufacturing.
10:35 Coffee Break - Networking with Sponsors
KEYNOTE PRESENTATION
11:15 Tri-Specific IgG/Fn3-Based Antibodies that Strongly Downregulate and Inhibit EGFR
 K. Dane Wittrup, Ph.D., Dubbs Professor & Associate Director, Koch Institute, Biological Engineering and Chemical Engineering, MIT - Biography
We describe tri-epitopic antibodies against a single receptor that produce unusually effective receptor downregulation and antagonism. Anti-EGFR Fn3 binding domains were expressed as fusions to cetuximab IgG to create a novel tri-epitopic anti-EGFR antibody that arrests tumor growth in a mouse xenograft model of cetuximab-resistant tumors possessing kinase mutations shown to clinically correlate with cetuximab resistance. The triepitopic constructs overcome cetuximab resistance through improved ADCC and improved inhibition of signaling.
|
11:45 New Protein Engineering Approaches with Repeat Proteins
Lutz Kummer, Biochemistry, University of Zürich - Biography
Specific binding proteins which constitute versatile modules and are robust and can open the door to new applications. Specific, self-indicating sensors and devices that can detect a target at the single molecule level will be presented. An additional challenge is to extend such studies to the whole proteome. Novel engineering based on the repeat protein technology developed in our lab (DARPins, Armadillo repeat proteins) may help to address these challenges.
12:15 Engineering Super Albumin for Improving Serum Half-life
Chaity Chaudhury, Ph.D., Scientist, Antibody Discovery & Protein Engineering, MedImmune LLC
12:45 Lunch for Purchase in Exhibit Hall 9
13:45 Dedicated Poster Viewing in Exhibit Hall 9
14:30 Chairperson’s Remarks
Puja Sapra, Ph.D., Director, Bioconjugates, Oncology Research, Pfizer, Inc.
14:35 Novel Linker and Drug Chemistries Yielding Highly Stable and Highly Efficacious Antibody Drug Conjugates
Vincent F.M.H. de Groot, Ph.D., CLP, CEO, Syntarga BV - Biography
Antibody-drug conjugate technology based on chemically unique releasable linkers and novel DNA alkylating duocarmycins has been validated in animal models against multiple antigens. Highly potent, proprietary DNA damaging duocarmycin derivatives are linked to antibodies via unique linker chemistry that is maximally complementary with duocarmycin chemistry, resulting in highly stable duocarmycin-based ACDs. Latest results of pre-clinical development progress will be presented along with molecular structural details of this technology.
15:05 Protein Medicinal Chemistry™ Applied to Antibody Drug Conjugates
Ho Sung Cho, Ph.D., CTO, Ambrx - Biography
Ambrx is using its proprietary Protein Medicinal Chemistry™ platform to optimize the therapeutic potential of Antibody Drug Conjugates. By creating homogeneous, novel ADCs with defined drug antibody ratios (DAR), and sites of conjugation rationally selected to preserve antibody structure and function, we are able to perform quantitative experiments to identify the best mAb, DAR, linker design, MOA and site(s) of conjugation for several cancer targets.
15:35 Refreshment Break - Networking with Sponsors
Sponsored by
16:15 An Engineered MCP-1-based Decoy with Strong Activity in Inflammatory Disease
Andreas J. Kungl, CSO, ProtAffin Biotechnologie AG
We have used our CellJammer® technology platform to develop a potent anti-inflammatory biopharmaceutical based on the chemokine MCP-1 which showed strong activity in murine models of myocardial infarction and restenosis as well as in the EAE model for MS.
16:30 Poster Announcement from the Conference Producer
16:45 Fab-Fv: an Antibody Fragment Format with Extended Serum Half-life
Sam Heywood, Ph.D., Senior Principal Scientist, Antibody Biology, UCB New Medicines - Biography
Antibody fragments have found clinical utility in both imaging and therapeutic applications; however a longer serum half-life than that of the native fragment is often desired. Extending the serum half-life is usually achieved through polymer attachment, e.g. PEGylation; or through various protein or peptide fusions. We have developed an antibody fragment format, Fab-Fv, where the Fv is a high affinity serum albumin binder and this confers a long serum half-life.
17:15 New Ways to Extend the in vivo Half-Life of Antibodies
John Desjarlais, Ph.D., Vice President, Research, Xencor, Inc. - Biography
We have previously developed Xtend® technologies for optimizing the in vivo half-life of therapeutic antibodies via Fc domain engineering to improve FcRn affinity. Antibodies targeting several classes of antigens show longer in vivo half-life in mouse and cynomolgus monkey studies. More recently we have developed novel constant domain modifications that mediate improved half-life in an FcRn-independent manner. The two technologies are complementary and combine additively to promote long in vivo half-life.
17:45 Modulating the Pharmacokinetic Properties of Bi-Specific DART Molecules Designed for Targeting Human B Lymphocytes
Paul Moore, Ph.D., Vice President, Cell Biology and Immunology, MacroGenics, Inc. - Biography
Dual-Affinity Re-Targeting (DART) molecules have been generated that efficiently target human B-lymphocytes either through co-ligation of activating and inhibitory receptors or via co-targeting with cytolytic immune cells. Approaches to modify the pharmacokinetic properties of these bi-specific antibodies either through pegylation, incorporation of albumin binding domains or by fusion to Fc regions will be discussed together with data evaluating their biological properties as potential next generation therapies for autoimmunity.
18:15 Interactive Breakout Discussion Groups
Table 1: Antibodies versus Alternative Scaffolds: Pros and Cons
Table 2: Building Manufacturability into Novel Antibody Formats
Table 3: Advancing Personalized Medicine with Antibody Drug Conjugates
Table 4: Decision Points when Moving from Pre-clinical to Clinical and Beyond
Table 5: Measures to Increase Half-life of the Product
Table 6: Issues to do with Formulation and Delivery
19:15 BIOTECHNICA EVENT NIGHT - Keynote Presentations followed by Networking Reception, Live Music and Dancing
Breakout Discussion