Friday, February 5

ADVANCES IN ANTIBODY-DRUG CONJUGATES

8:30 AM Chairperson's Opening Remarks

Hans-Peter Gerber, Ph.D., Senior Director, Tumor Therapies, Wyeth Oncology Discovery

8:35 A Novel Minor Groove Binding Alkylating Agent for Antibody Targeted Chemotherapy of CD70 Expressing Cancers

Nils Lonberg, Ph.D., Senior Vice President and Scientific Director, Medarex, Inc.

An antibody drug conjugate comprising a CD70 targeting monoclonal antibody and a novel alkylating agent is now in Phase I clinical development for kidney cancer and lymphoma. The mechanism of action of this novel therapeutic, activated through a multistep mechanism including esterase mediated removal of a blocking group and protease mediated release of the cytotoxic drug, will be discussed. 

9:05 Pre-clinical and Clinical Development of Calicheamicin Derivatives Conjugated to Monoclonal Antibodies

Hans-Peter Gerber, Ph.D., Senior Director, Tumor Therapies, Wyeth Oncology Discovery

Gemtuzumab ozogamicin (Mylotarg), a semi-synthetic derivative of calicheamicin linked to a humanized anti-CD33 monoclonal antibody, is approved for the treatment of AML. CMC-544 (inotuzumab ozogamicin), an anti-CD22 immuno-conjugate of calicheamicin, is currently being evaluated in B-cell non-Hodgkin's lymphoma (B-NHL) patients. I will describe the mechanism of action and the pharmacology of calicheamicin conjugates and provide an overview of clinical trials.

9:35 Antibody-Maytansinoid Conjugates: Demonstrating Benefit in the Treatment of Solid and Liquid Tumors

John M. Lambert, Ph.D., Executive Vice President and CSO, ImmunoGen, Inc.

Several new highly potent cell-killing agents such as derivatives of the anti-mitotic microtubule agent, maytansine, are currently being utilized in ADCs to achieve effective, well tolerated anticancer drugs. Several AMCs show encouraging efficacy in clinical trials, including T-DM1, currently being developed by Genentech using ImmunoGen's maytansinoid technology. New payloads for ADCs are realizing the promise of antibody-mediated delivery in cancer.

10:05 Sponsored Presentation (Opportunity Available)

10:20 Coffee Break

EMERGING NEW TECHNOLOGIES

11:00 Bi-specific, High Affinity T Cell Receptor Fusions as Anti-Cancer Therapeutics

Rebecca Ashfield, D.Phil., Senior Research Project Manager, Immunocore Ltd

Bi-specific TCRs, consisting of high affinity T cell receptors fused to an anti-CD3 scFv, are being developed for the treatment of several tumor types. The presentation will cover engineering of these reagents, demonstration of efficacy including animal models, and a discussion of the planned first-in-man clinical trial including toxicity testing, a challenge since the molecules are entirely human specific.

11:30 Chemosensitization of Cancer Cells by siRNA Using Targeted Nanogel Delivery

John F. McDonald, Professor and Director, Integrated Cancer Research Center, School of Biology, Georgia Institute of Technology

Targeted cancer therapy by RNA interference (RNAi) is a promising approach to silence genes in vivo. Delivery is a major hurdle for the development of RNAi therapeutics. We report on the successful use of hydrogel nanoparticles (nanogels) functionalized with peptides that specially target the EphA2 receptor to deliver small interfering RNAs (siRNAs) targeting EGFR to increase sensitivity to Taxane therapy.

12:00 PM Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

EFFECTOR-ENHANCED BIOTHERAPEUTICS

1:00 Chairperson's Remarks

John F. McDonald, Professor and Director, Integrated Cancer Research Center, School of Biology, Georgia Institute of Technology

1:05 Human RNase Fusion Proteins for Tumor Therapy

Stefan Dbel, Ph.D., Director, Biotechnology, Technische Universitt Braunschweig, Germany

RNases are non-toxic while in circulation but highly effective in cell killing after targeted internalization. An entirely human immunoenzyme against CD30+ lymphomas was constructed from a human scFv-Fc antibody fragment and a human RNase. It did not affect the human embryonlal kidney used for its production but strongly inhibited proliferation of CD30+ lymphoma cells.

1:35 Glycoengineering for the Enhancement of Antibody Activity

Dennis Benjamin, Ph.D., Senior Director, Antibody Technologies, Seattle Genetics, Inc.

2:05 Antibody Fc Engineering to Enhance Cytotoxicity, Pharmacokinetics, and Pharmacodynamics

John R. Desjarlais, Ph.D., VP, Research, Xencor, Inc.

We have engineered the antibody Fc domain to enhance its affinity for Fc receptors, leading to a set of variants that confer high ADCC activity onto antibodies targeting a wide range of tumor targets. These variants also enhance anti-tumor activity in mouse models and cynomolgus monkeys. A phase I trial is underway to determine their effects in humans.

2:35 ArzerraTM (ofatumumab), a Novel Human Therapeutic CD20-Antibody: Mechanisms of Action and Efficacy in B-CLL