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Cambridge Healthtech Institute’s 2nd Annual
Antibody-Drug Conjugates
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.


Day 1 | Day 2 | Download Brochure | Speaker Biographies 

Final Agenda


TUESDAY, JANUARY 20

1:30 pm Conference Registration


BUZZ Sessions png

2:00 BuzZ Session A

3:00 Refreshment Break in the Exhibit Hall with Poster Awards

3:45 BuzZ Session B
(More Details >>)


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


Moving ADCs Safely into the Clinic

8:15 Chairperson’s Opening Remarks

Trevor Hallam, Ph.D., CSO, Sutro Biopharma, Inc.


Keynote Presentation

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 RockDan 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 LindenLars 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


MODELING AND ENGINEERING BREAKTHROUGHS

10:50 Mechanistic Models for Designing Efficacious ADCs

Arijit ChakravartyArijit Chakravarty, Ph.D., Director, Modeling & Simulation, Takeda Pharmaceuticals International Co., Cambridge, MA

The process of creating novel ADCs is more akin to design than discovery, as there is an expectation of a rational linkage between design choices and outcomes. A critical step in rationalizing this process is to translate the impact on the therapeutic window of ADC design choices affecting pharmacokinetic (PK) and pharmacodynamic (PD) profiles. The approach in the field so far has been to hover at one of two extremes- either using an intuition-based approach, or using full blown mechanistic PK/PD models that are expensive and often tangential to the critical translational questions. This talk will outline the critical questions on the path to designing a novel antibody, and demonstrate practical strategies for building parsimonious models to answer these questions.        

11:20 Bioconjugation Strategies for Generating Serum-Stable Antibody Conjugates 

James PattersonJames T. Patterson, Ph.D., Scientist, Ferring Research Institute

Bioconjugation strategies commonly rely on maleimide linkers to react with cysteine thiols for the synthesis of antibody-drug conjugates. However, thioether exchange with serum proteins and other metabolites can compromise conjugate stability and in vivo efficacy. We have developed a phenyloxadiazole sulfone linker for the preparation of antibody conjugates. This sulfone linker site-specifically labeled engineered cysteine residues in THIOMABs and SELENOMABs as well as improved antibody conjugate stability in human plasma at sites previously shown to be labile for maleimide conjugates.

11:50 Novel Bifunctional Linkers for the Synthesis of Homogeneous ADCs

David JacksonDavid 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 Enjoy Lunch on Your Own

 


ADCs for Oncology

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. ThanosChristopher 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 MendelsohnBrian 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 LachowiczJean 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 INTERACTIVE PANEL DISCUSSION

Moderator:  Trevor Hallam, Ph.D., CSO, Sutro Biopharma, Inc. 

Panelists Include:
Jean Lachowicz, Ph.D., CSO, Angiochem, Inc.  
David Jackson, Ph.D., Principal Scientist, Igenica, Inc.
 
John Lambert, Ph.D., Executive Vice President and CSO, ImmunoGen, Inc.     

o     Overcoming Current Challenges  

o     Trends & Technologies  

o     The Future of ADC Development  

 

4:05 Refreshment Break


4:30 Plenary Keynote Session

From Yeast to the Brain: Advances in Proteomics (More Details >>

John YatesJohn R. Yates, Ph.D., Ernest W. Hahn Professor, Chemical Physiology and Molecular and Cellular Neurobiology, The Scripps Research Institute

 

5:30-7:00 Reception in the Exhibit Hall with Poster Viewing



Day 1 | Day 2 | Download Brochure | Speaker Biographies