Day 1  |  Day 2

TUESDAY, April 29

8:30 Dosing Strategies with Monoclonal Antibodies: Transition from Discovery to the Clinic
Mohammad Tabrizi, Ph.D. 
Therapeutic monoclonal antibodies provide a unique and novel opportunity for treatment of many human diseases. With the advancement of new technologies and the diversity in the novel therapeutic targets, many new opportunities for the clinical development of antibody-based therapeutics should arise. Successful translation of preclinical information during the course of antibody development requires particular understanding of the antibody and antigen properties as well as the pharmacology in various species. This presentation will evaluate the successful transition of preclinical data into the clinic and highlights many important considerations for effective translation of information gained from preclinical research and safety studies into the clinical development for various market antibodies.

9:00 Science-Based Regulatory Strategies in Transitioning Monoclonal Antibodies into Clinical Trials
Joy Cavagnaro, Ph.D., President, Access BIO

9:30 Preclinical and Clinical Safety of Monoclonal Antibodies
Richard Knight, Ph.D., Therapeutic Area Toxicologist for Oncology, AstraZeneca
The specific nature of monoclonal antibodies has allowed a targeted approach to the treatment of many human diseases. Therapeutic antibodies against a diverse range of target antigens have entered clinical development with an increasing number reaching the market. Although in the past monoclonal antibodies have often been considered relatively safe in comparison to other less selective approaches, recent experience has highlighted the critical importance of the effective translation of preclinical data into the clinical development arena.

10:00 Coffee Break in the Exhibit Hall

10:45 How PK/PD Impacts Translational Research and Clinical Study Design for Oncology Protein Therapeutics
Matt Hsu, Ph.D., Senior Scientist, Pharmacokinetic and Pharmacometric Group, Department of Pharmacokinetics and Drug Metabolism, Amgen, Inc.
Pharmacokinetics/Pharmacodynamics (PK/PD) is the essence of the “Learn-and-Confirm” paradigm for drug development. Advanced PK/PD principles for the “Model-Based” development approach have been applied in translational research and clinical study designs for Oncology Protein Therapeutics. Examples will be presented to illustrate how the exposure-response relationships (preclinical anti-tumor activities, safety, and tumor response) and clinical PK/PD simulations facilitated dose selection for the clinical trials. It is concluded that the future for PK/PD in Model-Based Drug Development for Oncology Protein Therapeutics is to characterize, forecast, and confirm the relationships between drug exposure and clinical outcomes, and thus provide new treatment options to cancer patients in the future.

11:15 Solution Showcase (Sponsorship Available)

11:45 Anti-CD44 Variant-Disease-Specific Monoclonal Antibody
David Naor, Ph.D., Professor of Immunology, Hebrew University Medical School
Synovial fluid inflammatory cells (SCFs) of rheumatoid (RA) or psoriatic (PSA) arthritis patients express CD44 variant (CD44vRA), which is neither expressed on blood leukocytes of the same patients nor on inflammatory cells of osteoarthritis patients (our article in JCI, 111: 12II,2003). We generated anti-CD44vRA mAbs that exclusively kill by apoptosis SFCs of RA and PSA patients and induced arthritis resistance in mice.

12:15 Luncheon Workshop (Sponsorship Available) or Lunch on Your Own

1:15 Break

CLINICAL DEVELOPMENT 

2:00 Chairperson’s Remarks

2:05 Affibody Molecules for Molecular Imaging of HER2-Expressing Malignant Tumors - Clinical and Preclinical Applications
Joachim Feldwisch, Ph.D., Project Manager, Research, Affibody AB
Molecular imaging using HER2-specific Affibody molecules not only localizes metastatic lesions in vivo, but also adds new qualitative information not available today by conventional imaging techniques. Molecular imaging may allow assessing the HER2-status of all metastatic lesions in patients opening for individualized targeted cancer therapy and treatment monitoring. For the first time a phage display selected scaffold protein was used to determine the HER2-status of lesions in patients with recurrent breast cancer. Clinical data agree with predictions from data in tumor-bearing mice, showing high specific tumor targeting, rapid biodistribution kinetics, and blood clearance. SPECT and PET/CT images allowed the detection of small metastatic lesions in humans already 2-3 hours post injection.

2:35 Anti-Inflammatory Activity of Human IgG4 Antibodies by Dynamic Fab Arm Exchange
Janine Schuurman, Ph.D., Associate Director, Research, Genmab
Antibodies play a central role in immunity by forming an interface with the innate immune system and, typically, mediate proinflammatory activity. We describe a novel posttranslational modification that leads to anti-inflammatory activity of antibodies of immunoglobulin G, isotype 4 (IgG4). IgG4 antibodies are dynamic molecules that exchange Fab arms by swapping a heavy chain and attached light chain (half-molecule) with a heavy-light chain pair from another molecule, which results in bispecific antibodies. Mutagenesis studies revealed that the third constant domain is critical for this activity. The impact of IgG4 Fab arm exchange was confirmed in vivo in a rhesus monkey model with experimental autoimmune myasthenia gravis. IgG4 Fab arm exchange is suggested to be an important biological mechanism that provides the basis for anti-inflammatory activity attributed to IgG4 antibodies

3:05  Development of Avastin in the Treatment of Metastatic Cancer
Frank A. Scappaticci, M.D., Ph.D., Associate Medical Director, Genentech

3:35 Refreshment Break in the Exhibit Hall

4:15 Novel Antibody Therapeutic Approaches for B cell Neoplasias and Inflammation
Jørgen Petersen, M.D., D.M.Sc., Vice President, Genmab A/S
Antibodies play a crucial role in host immune defense and are increasingly recognized as effective therapeutics. Genmab has a number of clinical development programs in cancer including antibodies against the targets CD4, CD20 and EGFr. This presentation will focus on ofatumumab, a fully human antibody targeting the CD20 molecule, arguably the best validated antibody therapeutic target for cancer. Derived from human Ig-transgenic mice. Ofatumumab is an IgG1,κ anti-body that mediates potent ADCC, and initiates complement dependent cytotoxicity far more effectively than earlier CD20 antibodies. Ofatumumab was shown to kill tumor cells that are resistant to rituximab. In Cynomolgus monkey models, ofatumumab effectively depleted B cells in both peripheral blood and lymph nodes. Notably, B cell depletion lasted four times longer than that induced by rituximab. Ofatumumab also efficiently stopped growth of engrafted B cell tumors in SCID mouse models. This talk will high-light the latest data in the phase I-II clinical studies of ofatumumab in relapsed or refractory follicular non-Hodgkin lymphoma and chronic lymphocytic leukemia and in rheumatoid arthritis.

4:45 Immunoprophylaxis of RSV Infection: Advancing from RSV-IGIV to Palivizumab and Motavizumab 
Herren Wu, Ph.D., Vice President and Head, Antibody Discovery and Protein Engineering and Global Head, Technology, MedImmune
For preventing respiratory syncytial virus (RSV) infection, we have successfully developed two prophylactic antibody products, RespiGam® (RSV-IGIV) and Syna-gis® (palivizumab). Palivizumab, a humanized monoclonal antibody (mAb) that binds to the RSV F protein is a potent anti-RSV mAb that is about 50-fold more potent than RSV-IGIV. To further improve protection against RSV, we have applied a directed evolution approach to enhance the binding of palivizumab to F pro-tein by engineering both the on and off rates. These efforts have generated a more potent second generation mAb, motavizumab, which is currently investigated in phase III clinical trials. Most recently, a third generation mAb, Numax-YTE, has been generated with the intent to extend the serum half-life of the mAb in humans. If successfully developed, this drug may offer the opportunity for less frequent dosing, obviating the need for the monthly treatments that are required with palivi-zumab. The development of these anti-RSV approaches exemplify the accelerated pace of drug development made possible with cutting-edge antibody engineering technologies.

5:15 End of the Clinical Development of Therapeutic Antibodies conference