Development of Novel Biotherapeutics
Developability, Enhanced Product Properties and Therapeutic Application
7-8 November 2013
Day 1 | Day 2 | Download Brochure | Biographies
11:05 Medical Treatment of HER2 Positive Breast Cancer: Two Decades of a Fascinating History and More to Come
Martine Piccart, M.D., Ph.D., Head, Medical Oncology, Jules Bordet Institute; Chair, ESMO (European Society for Medical Oncology)
The talk will cover multiple aspects of anti-HER2 treatment in breast cancer. It will present a summary of the clinical results obtained with trastuzumab and several other anti-HER2 drugs in breast cancer (lapatinib, TDM1, pertuzumab). Issues like the treatment duration, biomarkers of resistance to treatment will be debated. Finally it will discuss future promising research strategies: neoadjuvant trials, comparison between anti-HER2 agents, combinations of these drugs and functional imaging.
11:50 Antibody-Drug Conjugates: From Bench to Bedside and Back
Robert Lutz, Ph.D., Vice President, Translational Research & Development, ImmunoGen, Inc.
Antibody-drug conjugates are emerging as an exciting approach to the development of antibody-based therapeutics. The growing preclinical and clinical experience with maytansinoid conjugates such as Kadcyla (T-DM1) is leading to an enhanced understanding regarding critical attributes for target antigens, antibodies, payloads and linkers. The translational knowledge is being incorporated into research and development efforts for the next generation of ADC candidates.
* For Attendees of Cancer Biotherapeutics and Development of Novel Biotherapeutics
12:35 Enjoy Lunch on Your Own
13:30 Chairperson’s Opening Remarks
Syd Johnson, Ph.D., Vice President, Antibody Engineering, MacroGenics, Inc.
13:35 In silico Prediction of Degradation Hotspots in Antibody Variable Regions
Hubert Kettenberger, Ph.D., Principal Scientist, Large Molecule Research, Roche Pharma Research and Early Development (pRED)
Besides function, chemical stability is an important selection criterion in the discovery of therapeutic proteins. Importantly, degradation “hotspots”, i.e., amino acids which degrade quickly during manufacturing, storage or in vivo, should be avoided whenever possible. By combining mass spectrometry, structural biology and machine learning, we developed a reliable, high-throughput in silico approach to predict Aspartate and Asparagine degradation hotspots in the variable regions of monoclonal antibodies.
14:05 Unique in silico Tools for Prediction of Propensity to Aggregate and for Viscosity for Monoclonal Antibodies and Therapeutic Proteins
Bernhard Helk, Ph.D., Head, New Technologies, Biologics, Novartis Pharma AG
Four in silico tools and their practical application to the prediction and characterization of protein-protein interaction are demonstrated: SAP (Spatial Aggregation Propensity) identifies hydrophobic patches and is applied to engineer mAbs and ADCs with increased stability. DI (Developability Index) predicts aggregation propensities based on SAP and net charge. SCM (Spatial Charge Map) ranks mAbs according to viscosity. SIM (Spatial Interaction Map) predicts hot spot residues for specific protein-protein interaction sites.
14:35 Engineering Aggregation Resistance in IgGs based on Lessons Learned from Comparative Expression
Jonas V. Schaefer, Ph.D., High-Throughput Laboratory, Biochemistry, University of Zurich
Aggregation is an important concern for therapeutic antibodies as it increases the risk of immunogenicity. Our comprehensive studies have systematically investigated the impact of certain sequences on these properties of IgGs using various biophysical methods and showed that their aggregation susceptibilities can be readily engineered. Our data offer an improved insight into the molecular processes causing aggregation and an understanding of the influence of certain intramolecular interactions on this process.
15:05 Refreshment Break in the Exhibit Hall with Poster Viewing
15:50 Rapid Design of Optimized Site-Specific ADCs and Manufacture by Cell-Free Protein Synthesis
Trevor J. Hallam, Ph.D., CSO, Research & Development, Sutro Biopharma, Inc.
Sutro has developed a scalable cell–free protein synthesis platform for production of full IgGs, bispecific antibodies and ADCs in hours from DNA. Expression of many non-natural amino acid positional variants enables data-driven selection of site-specific candidate ADCs that are optimal for antigen binding, suppression efficiency, folding, thermal stability, conjugation efficiency, internalization and cell killing. The same synthetic platform can be used for production of chosen variants for larger scale or cGMP manufacture within days.
16:20 CTLA4 – Fc Fusion: Engineering for Increased Affinity to CD80 and CD86 for the Treatment of Inflammatory Diseases
Katherine Vousden, Ph.D., Senior Scientist, Antibody Discovery & Protein Engineering, MedImmune LLC
CTLA4 is a selective co-stimulatory modulator capable of inhibiting the stimulation of T-cells via engagement with its binding partners CD80 and CD86. A recombinant construct of the CTLA4 extracellular domains fused to immunoglobulin IgG Fc is approved for the treatment of inflammatory diseases. In this work we have used combinatorial evolution and ribosome display to greatly enhance the affinity of CTLA4 for its binding partners. The resultant constructs exhibit greatly enhanced potency in cellular assays. They therefore represent a potential next-generation of molecules for the treatment of inflammatory diseases.
16:50 Understanding the Efficacy & Safety Issues in Developing Dual- and Multi-Specific Biologics
Tariq Ghayur, Ph.D., Senior Research Fellow, DVD – Ig & Novel Biologics, Abbvie, Inc.
17:20 End of Day One
17:20 Short Course Registration*
17:35 – 20:30 Dinner Short Course: Troubleshooting and Engineering of Antibody Constructs
*Separate registration required
Day 1 | Day 2 | Download Brochure | Biographies