Cambridge Healthtech Institute’s 2nd Annual
Engineering Targeted Therapeutics
January 21-22, 2015
The therapeutic potential of antibodies is enhanced by conjugating them to small molecule drugs. This combination merges the benefits of highly potent drugs with selective binders of specific tumor antigens. Antibody-drug conjugates offer the promise of delivering more powerful tumor-killing activity while resulting in diminished side effects for cancer patients. This important Antibody-Drug Conjugates conference brings together leaders in the world of ADCs who share their R&D case studies, along with their preclinical and clinical data, to illustrate how this form of empowered antibody is transforming next-generation antibody therapeutics.
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TUESDAY, JANUARY 20
1:30 pm Conference Registration
2:00 BuzZ Session A
3:00 Refreshment Break in the Exhibit Hall with Poster Awards
3:45 BuzZ Session B
4:30-5:00 Short Course Registration
5:00-8:00 Dinner Short Courses More Details >>
WEDNESDAY, JANUARY 21
7:30 am Conference Registration and Morning Coffee
8:15 Chairperson’s Opening Remarks
Trevor Hallam, Ph.D., CSO, Sutro Biopharma, Inc.
8:20 Examination of ADC Safety Challenges in the Clinical Setting
Flavia Brunstein, M.D., Ph.D., Safety Science Leader, Safety Risk Management, Genentech, Inc. – A Member of the Roche Group
The concept of an ADC is to improve the therapeutic window of cancer chemotherapy, through targeted delivery of highly potent cytotoxic molecules directly to tumor cells expressing unique antigens that are specific to the monoclonal antibody. Preliminary clinical data are encouraging, but toxicity still occurs.
9:00 In vitro-in vivo Molecular Integrity of Antibody-Drug Conjugates: Applying Learning to Clinical Measurements for ADCs
Dan Rock, Ph.D., Scientific Director, Pharmacokinetics and Drug Metabolism, Amgen, Inc.
Characterizing the mechanisms of ADC instability and release of free cytotoxin are germane in the design of the next generation of ADCs. The methods and analytical tools useful in characterizing the ADME and stability of ADCs will be reviewed.
9:30 Engineering Antibodies and ADCs for Successful Development
Lars Linden, Ph.D., Group Leader and Head, Protein Biochemistry, Bayer HealthCare
Developability analysis of antibodies and ADCs determines, together with cell line productivity and cost-of-goods analysis, the manufacturing feasibility of a drug candidate. A thorough biochemical & biophysical characterization is performed to analyze the intrinsic stability and technical robustness of clinical candidates. Standardization is ensured by a check of antibody platform compatibility (DSP and analytics). Early buffer screening is performed for accelerated formulation development.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:50 Mechanistic Models for Designing Efficacious ADCs
Arijit Chakravarty, Ph.D., Senior Scientist II, Modeling and Simulation, DMPK, Takeda Pharmaceuticals
11:20 Translational Modeling and Simulation Approach for Optimizing Discovery and Development of Antibody-Drug Conjugates for the Treatment of Cancer
Nahor Haddish-Berhane, Ph.D., Senior Principal Scientist, Pfizer, Inc.
Antibody-Drug Conjugates (ADCs) are considered a promising approach to targeted chemotherapy. In this presentation, we showcase a mechanistic modeling and simulation approach that integrates preclinical PK and PD data along with key in vitro biomeasures to predict clinical outcome of ADCs. Additional applications of the model in antibody optimization and feasibility, precision medicine, resistance development to ADCs and cancer indication selection will be discussed.
11:50 Novel Bifunctional Linkers for the Synthesis of Homogeneous ADCs
David Jackson, Ph.D., Principal Scientist, Igenica, Inc.
Igenica has developed novel bifunctional linkers that enable the synthesis of homogeneous ADCs with an optimal DAR of 4 drugs per antibody. The linkers are compatible with a variety of payloads and no antibody engineering is required. Examples of homogeneous ADCs made with different antibodies and novel payloads will be presented and compared to their heterogeneous ADC counterparts made with conventional linkers. Supporting data will also be discussed.
12:20 pm Sponsored Presentation (Opportunity Available)
12:50 Session Break
1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
2:00 Chairperson’s Remarks
Adeela Kamal, Ph.D., Associate Director, Oncology Research, MedImmune
2:05 An EGFR Targeting Antibody-Drug Conjugate Engineered for Increased Tumor Specificity
Christopher D. Thanos, Ph.D., Director, New Molecular Entities, Halozyme Therapeutics, Inc.
Cancers with activating KRAS/BRAF mutations and EGFR+ tumor genotypes are resistant to inactivation by EGFR targeting agents and correspond to a significant unmet medical need. We hypothesized that the cytotoxic mechanism of action of anti-EGFR ADC could be active against these tumor types. We engineered an anti-EGFR monoclonal antibody with significant binding to EGFR+ tumors and attenuated binding to human skin in a mouse xenograft to target these intractable tumor types.
2:35 Potent and Selective Alpha-Amanitin-Antibody Conjugates
Brian Mendelsohn, Ph.D., Senior Scientist, ADC Chemistry Group Leader, Agensys, Inc.
We have developed a technology based on arming antibodies with derivatives of the rigid, water-soluble bicycle-octapeptide alpha-amanitin, a highly potent inhibitor of eukaryotic RNA polymerase II. We have shown in various in vitro and in vivo models, with antibodies to several different oncology-related antigens, the tumor-selective activity and high potency of these ADCs. We have explored and elucidated the in vivo metabolite-profiles, as well as performed toxicological studies.
3:05 Brain-Penetrant Peptide-ADCs Reduce Tumor Size and Increase Survival in Mice with HER2-Positive Brain Tumors
Jean Lachowicz, Ph.D., CSO, Angiochem, Inc.
Using a peptide recognized by the brain capillary endothelial cell receptor LRP1, peptide-mAb conjugates can access the brain. Applying this strategy to ADCs has produced the first examples of ADCs entering the brain by receptor-mediated transcytosis. Targeting the brain tumor cells, these therapeutic agents release their toxic payload, resulting in a significant decrease in tumor size and increase in survival.
3:35 Sponsored Presentation (Opportunity Available)
4:05 Refreshment Break
4:25 Plenary Keynote Session
5:45-7:00 Reception in the Exhibit Hall with Poster Viewing
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