Archived Content

Cancer Biotherapeutics

ADCs, Multi-Specifics, Combined Therapies and Immunotherapy

6-7 November 2013

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Thursday, 7 November

07:45 Registration and Morning Coffee

08:30 Chairperson’s Remarks

Robert Lutz, Ph.D., Vice President, Translational Research & Development, ImmunoGen, Inc.

08:35 A Universal Chemically Driven Approach for Constructing Homogeneous ADCs

David Jackson, Ph.D., Principle Scientist, ADC Discovery, Igenica, Inc.

Current ADCs in clinical development are heterogeneous mixtures that differ in both DAR (drugs/antibody) and their conjugation sites. Igenica has invented novel site-specific linkers to enable the synthesis of homogeneous ADCs. The linkers are compatible with a variety of drug payloads and can be applied to any antibody. Homogeneous ADCs were synthesized using the novel linkers and compared to heterogeneous ADCs made with conventional linkers. Analytical data and activity of the ADCs in tumor models will be presented.

09:05 Location Matters: Site of Conjugation Modulates Stability and Pharmacokinetics of Antibody-Drug Conjugates

Pavel Strop, Ph.D., Associate Research Fellow, Protein Engineering, Rinat- Pfizer, Inc.

To understand the role of conjugation site, we developed an enzymatic method for site-specific antibody-drug conjugation. This allowed us to attach diverse compounds at multiple positions and investigate how the site influences stability, toxicity, and efficacy. We show that the conjugation site has significant impact on ADC stability and pharmacokinetics in a species-dependent manner. With this method, it is possible to produce homogeneous ADCs and tune their properties to maximize the therapeutic window.

09:35 Development of Second Generation Duocarmycin ADCs with Superior Therapeutic Window

Marion Blomenröhr, Ph.D., Program Manager Biopharmaceuticals, Synthon Biopharmaceuticals

The first generation ADCs have successfully exploited the mAb-driven tumor cell targeting for optimization of efficacy, but have failed to reduce off-target toxicities. This presentation will highlight Synthon’s second generation Linker-Drug technology and its complementarity with novel proprietary duocarmycin payloads yielding highly stable and potent ADCs, with an improved in vivo therapeutic window.

Polytherics logo10:05 Producing Better Antibody-Drug Conjugates (ADCs) Using ThioBridge™ Conjugation

Antony Godwin, Ph.D., Director, Science & Technology, PolyTherics Ltd

Next-generation antibody-drug conjugates will be required to be less heterogeneous and have better stability. PolyTherics has developed ThioBridge™ for improved conjugation of a cytotoxic payload at the disulfides bonds of antibodies, antibody fragments and other targeting proteins. With ThioBridge™, the resulting ADC has the benefit of reduced heterogeneity, as the drug to antibody ratio is limited to a maximum of 4 with little DAR 0 species. Stability is also enhanced, as unlike single thiol conjugation approaches at disulfides, ThioBridge™ is not prone to drug deconjugation reactions in serum. In vitro and in vivo data for mAb and Fab conjugates with an established payload confirms specific binding and activity.

10:35 Coffee Break in the Exhibit Hall with Poster Viewing


PLENARY SESSION* 

11:05 Medical Treatment of HER2 Positive Breast Cancer: Two Decades of a Fascinating History and More to Come

Martine PiccartMartine 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 LutzRobert 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 and Development of Novel Biotherapeutics 

12:35 End of Cancer Biotherapeutics

 

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