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2014 Archived Content

Cambridge Healthtech Institute’s Inaugural
Antibody-Drug Conjugates
Engineering Targeted Therapeutics
January 15-16, 2014


Antibody-drug conjugates offer the promise of delivering more powerful tumor-killing activity while resulting in diminished side effects for cancer patients. ADCs are precise and selective by combining a targeted monoclonal antibody (or antibody fragment) linked to a potent anti-cancer therapeutic. This important meeting will bring together leaders in the world of ADCs who will share their case studies along with their preclinical and clinical data to illustrate how this form of empowered antibody is transforming next-generation antibody therapeutics. ADC leaders will also discuss analytical methods used to explore these complex therapies, as well as the lack of established regulation for ADCs, and where the field is headed. Please join this focused discussion on conquering cancer with antibody-drug conjugates.

Day 1 | Day 2 | Download Engineering Brochure | Speaker Biographies 

TUESDAY, JANUARY 14

1:30-2:00 pm Conference Registration



BUZZ Sessions png

2:00 BuzZ Session A (More Details >>)

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 (SC8-SC14) More Details >> 


WEDNESDAY, JANUARY 15

7:30 am Conference Registration & Morning Coffee

 

SAFETY AND DESIGN 

8:15 Chairperson’s Opening Remarks

Jean E. Lachowicz, Ph.D., CSO, Angiochem
 

Keynote Presentation

8:20 Antibody-Drug Conjugates: Another View of the Therapeutic Window

Robert KahnRobert S. Kahn, M.D., CPI, Safety Science Leader, Early Clinical Development, Global Safety Risk Management, Genentech, Inc.

Antibody drug-conjugates (ADCs) are constituted by a recombinant antibody covalently bound by a synthetic linker to a given cytotoxic chemical. The concept of an ADC is to improve the “therapeutic window” of cancer chemotherapy. This presentation will examine the therapeutic windows for representative ADCs in clinical development. A discussion of efficacy and toxic liabilities of specific ADCs will provide such a vision as we peer into the therapeutic window of such agents.


Featured Presentation

9:00 Antibody-Drug Conjugate Design and Optimization

Lioudmila TchistiakovaLioudmila Tchistiakova, Ph.D., Senior Director, Global Biotherapeutic Technologies, Pfizer BioTx

Antibody-drug conjugates (ADCs) represent a promising therapeutic modality for the clinical management of cancer. The optimal activity of ADCs requires engineering and optimization of each component: antibody vehicle, conjugation strategy, and chemistry of linker-payload. This presentation will feature some examples of ADC components optimization, focusing primarily on the consideration for therapeutic antibody selection.
 

9:30 The Role of Analytics in the Safety and Design of Antibody Drug Conjugates

Samadhi VitharanaSamadhi Vitharana, Ph.D., Senior Scientist, Core Sciences & Technology, Takeda

Monoclonal Antibodies (mAbs) linked to cytotoxic payloads known as antibody drug conjugates (ADC) represents an emerging technology in clinical oncology. ADCs utilize the specificity of a mAb to deliver a cytotoxic drug to targeted tumor cells. Chemistry of the linker, cytotoxic drug and sites of attachment often result in complex and heterogeneous drug product preparations. How analytics can shed light in evaluating different architectures of ADCs will be discussed.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing


Conjugation 

10:45 Location Matters: Site of Conjugation Modulates Stability and Pharmacokinetics of Antibody Drug Conjugates

Arvind RajpalArvind Rajpal, Ph.D., Vice President, Protein Engineering, Rinat Pfizer

To understand the role of conjugation sites, we developed an enzymatic method for site-specific antibody drug conjugation using microbial transglutaminase. 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.

11:15 Site-Specific Antibody Conjugates Created with an Expanded Genetic Code

Olivier Laurent, Ph.D., Vice President, CMC, Ambrx, Inc.

Compared to what a medicinal chemist might do when exploring the structure-activity relationships in a small molecule, bio-conjugation using the natural 20 amino acids is very limited. By lifting this constraint, it is possible to not only derive a better understanding of the relationship between ADC structure and function, but also to rationally optimize their performance. This talk will describe recent advances in using an expanded genetic code to systematically improve the efficacy and safety of ADCs.

11:45 A Universal Chemically Driven Approach for Constructing Homogeneous ADCs

David Y. JacksonDavid Y. Jackson, Ph.D., Principal 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 that enable the synthesis of homogeneous ADCs. The linkers are compatible with a variety of different ADC payloads and can be applied directly to any antibody without prior modification. Analytical data, functional activity, and efficacy of two novel homogeneous ADCs in different tumor models will be presented.

Catalent12:15 pm Optimized Solutions for Better ADC Design Through SMARTag™ Technology 

Bleck_GregGreg Bleck, Ph.D., R&D Platform Director, Biologics, Catalent Pharma Solutions

We will present the development of a novel technology platform that enables precise, programmable, site-specific chemical protein modification. Leveraging the target sequence of Formylglycine Generating Enzyme, via the SMARTag™ Technology, homogenous enhanced biotherapeutics can be engineered, including ADCs. Additionally, the presentation will discuss how the novel conjugation chemistry results in ADCs having enhanced stability while maintaining the potency of the cytotoxic payload.

12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own


CREATING NEXT-GENERATION ADCs 

2:00 Chairperson’s Remarks

Robert S. Kahn, M.D., CPI, Safety Science Leader, Early Clinical Development, Global Safety Risk Management, Genentech, Inc.

2:05 Creating Next-Generation ADCs: Enabling Higher Capacity for Payloads and Stabilization of Interchain Cysteines by Fleximer-Based Antibody Drug Conjugates

Peter ParkPeter Park, Ph.D., Vice President, Biology, Mersana Therapeutics

The application of bio-degradable, polyacetal polymers to antibody-drug conjugate design can provide numerous advantages, including significantly higher capacity for drug payload, utilization of alternative payloads not suitable for direct conjugation, improvement of physicochemical properties and utilization of protein recognition scaffolds beyond the commonly used IgGs. The polyacetal polymer conjugated via cysteines in the antibody hinge region stabilizes the resulting ADCs through the formation of inter-chain bridge structures. Benefits achieved using Mersana’s conjugation system to create next-generation ADCs will be presented.

2:35 Producing Homogeneous ADCs with Combination Warheads

Aaron SatoAaron K. Sato, Ph.D, Vice President, Research, Sutro Biopharma

Cell-free protein synthesis methods have been developed for production of homogeneous therapeutic proteins, including ADCs. Many variants can be expressed in hours and rapidly assessed for function. Within days, production of chosen variants can be scaled using the same platform to generate material for clinical studies. The power and utility of the platform to design and manufacture single species antigen-targeted combination warheads will be described.

3:05  Interactive Panel Discussion:  Promise and Challenges for Creating Next-Generation ADCs

Moderator:    
Robert S. Kahn, M.D., CPI, Safety Science Leader, Early Clinical Development, Global Safety Risk Management, Genentech, Inc.
Panelists:    
Lioudmila Tchistiakova, Ph.D., Senior Director, Global Biotherapeutic Technologies, Pfizer BioTx
Peter Park, Ph.D., Vice President, Biology, Mersana Therapeutics
Aaron K. Sato, Ph.D, Vice President, Research, Sutro Biopharma
 

3:50 Refreshment Break

4:15 The Probody Platform Enables Tumor-Specific Targeting of Widely Expressed Antigens by Probody Drug Conjugates (PDC)

James W. West, Ph.D., Director of Research, CytomX Therapeutics, Inc.

A Probody represents a fully recombinant pro-form of an antibody that has been engineered to be inert in healthy tissues and activated in the proteolytic tumor microenvironment. Tumor-specific activation enables targeting of widely expressed antigens, focusing antibody activity to tumors and sparing healthy tissues, thereby mitigating mechanism-based toxicities. Likewise, tumor-specific protease activity can be harnessed to enhance the specificity of a Probody drug conjugate (PDC) directed against tumor antigens also expressed in healthy tissues. 

4:45 A Peptide-Antibody-Drug Conjugate for Brain-Penetrant Targeted Cytotoxicity

Jean E. LachowiczJean E. Lachowicz, Ph.D., CSO, Angiochem

Angiochem has created brain-penetrant small molecules and biologics by conjugation with Angiopep-2 (AN2). This 19-mer peptide associates with the LRP1 receptor on blood-brain barrier capillary endothelial cells and enters the brain via receptor-mediated transcytosis. ANG4043, a conjugate of AN2 and an anti-HER2 mAb, has been shown to cross the blood-brain barrier, reduce tumor size and increase survival in mice with intracranial HER2-positive tumors. We have now produced a three-way conjugate of AN2, anti-HER2 mAb, and docetaxel, resulting in enhanced cytotoxicity.

5:15-6:30 Reception in the Exhibit Hall with Poster Viewing



Day 1 | Day 2 | Download Engineering BrochureSpeaker Biographies