PepTalk 2017
PepTalk 2017
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Cambridge Healthtech Institute’s Fourth Annual
Antibody-Drug Conjugates
Engineering for Clinical Success
January 10-11, 2017 | Hilton San Diego Bayfront | San Diego, CA


With more than 30 ADCs in clinical trials, and more on the way, antibody-drug conjugates have reached an exciting point in development, particularly with the current next-generation strategies. Cambridge Healthtech Institute’s Antibody-Drug Conjugates conference reveals the engineering that has brought about today’s revolution, and examines how to design safe and effective ADCs. In addition, strategies for advancing ADCs to the clinic will be discussed along with considerations for clinical trial design. Analyzing ADCs to explore conjugation, stability, payloads and tumor penetration will also be addressed in this leading ADC event.


Sunday, January 8

4:00 - 5:30 Short Course Registration

5:00 - 8:00 Dinner Short Courses*

Recommended Course: (SC1) Production Challenges for Complex Biologics: ADCs, Bispecifics and Fusion Proteins

* Separate registration required

TUESDAY, JANUARY 10

1:00 pm Conference Registration

1:30 Refreshment Break in the Exhibit Hall with Poster Viewing

ADCs TO FIGHT CANCER

2:00 Chairperson’s Opening Remarks

Vaughn Smider, Ph.D., Assistant Professor, Molecular Biology, Scripps Research Institute; CSO, Sevion Therapeutics


Keynote Presentation

2:05 Antibody-Drug Conjugate Therapeutics and Their Evolving Role in Oncology

Arvind_RajpalArvind Rajpal, Ph.D., Vice President, Protein Therapeutics, Bristol-Myers Squibb Co.

ADCs are a maturing therapeutic class with more than 50 candidates in clinical development and two approved molecules on the market. The emergent role of immunotherapy in oncology presents several challenges and opportunities for ADCs. Successful positioning of current and future ADC candidates, in light of these changes, will require strategic imperatives that enhance the complementary role of ADCs to immunotherapy.

2:45 The Multifacets and Potentials of ADC in the Era of Immune-Oncology

David Miao, Ph.D., CSO, Concortis Biotherapeutics

3:15 Sponsored Presentation (Opportunity Available)

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing

4:30 Leveraging Ultra-Potent Toxins in Novel ADCs for Highly Effective Anti-Tumor Therapy

Ulf_GrawunderUlf Grawunder, Ph.D., CEO & Founder, NBE-Therapeutics, Ltd.

The development of antibody-drug conjugates (ADCs) is associated with the challenge of selective delivery of highly potent toxins to tumors. ADC stability, homogeneity, binding specificity and the engagement of immune-mediated cell death (ICD) mechanisms are critical factors to achieve an optimal therapeutic index of ADCs, especially if ultra-potent toxic payloads are engaged. Data on the anti-tumor activity of novel, next-generation ADCs with ultra-potent toxins will be presented.

5:00 Antigen-Targeted Amanitin-Conjugates (ATACs) – Expanding the ADC Landscape with a New Payload Targeting RNA Polymerase II

Andreas_PahlAndreas Pahl, Ph.D., CSO, Heidelberg Pharma

Antigen-Targeted Amanitin-Conjugates (ATACs) represent a new class of ADCs using the payload Amanitin. This payload introduces a novel mode of action into oncology therapy, the inhibition of RNA polymerase II. The technology platform around ATACs includes Amanitin supply, site-specific conjugation, a demonstrated safety profile and a biomarker. A BCMA-ATAC has been selected based on favorable preclinical data to start the clinical development of the first ATAC.

5:30 Close of Day


5:30 - 5:45 Short Course Registration

5:45 - 8:45 Dinner Short Courses*

Recommended Course: (SC9) Troubleshooting and Engineering of Antibody Constructs - Detailed Agenda


* Separate registration required

WEDNESDAY, JANUARY 11

8:00 am Conference Registration and Morning Coffee

MOVING ADCs INTO THE CLINIC

8:30 Chairperson’s Remarks

Dorin Toader, Ph.D., Senior Scientist, Antibody Discovery and Protein Engineering, MedImmune LLC

8:35 Clinical Pharmacology of vc-MMAE Antibody-Drug Conjugates: Platform Approach to Characterize Pharmacokinetics and Peripheral Neuropathy

Chunze Li, Ph.D., Senior Scientist, Therapeutic Area Lead for ADCs, Clinical Pharmacology, Genentech

This presentation will provide clinical pharmacology learnings and challenges for vc-MMAE antibody-drug conjugates (ADCs), and describe the innovative platform approach to integrate clinical pharmacology data across vc-MMAE ADCs to inform clinical strategy. I will also discuss the clinical pharmacokinetic characteristics across several vc-MMAE ADCs, and the exposure response relationship and risk factors for peripheral neuropathy associated with the use of vc-MMAE ADCs in clinical testing.

9:05 Peripheral Neuropathy with Microtubule Inhibitor Containing Antibody-Drug Conjugates: Challenges and Perspectives in Translatability from Nonclinical Toxicology Studies to the Clinic

Nicola Stagg, Ph.D., Scientist/Toxicologist, Safety Assessment, Genentech

The valine citriline monomethyl auristatin E (vcMMAE) ADC platform has shown promising clinical activity in a variety of cancers, but peripheral neuropathy (PN) has been observed in the clinic that was not observed in nonclinical toxicology studies. We evaluated four possible hypotheses for the lack of translatability of PN. The ultimate goal is to be able to have a model to screen the next generation MTI ADCs for reduced incidence and severity of peripheral neuropathy.

9:35 Sponsored Presentation (Opportunity Available)

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

ANALYTICAL STRATEGIES

10:50 How in vivo & in vitro ADC Stability Data Is Used to Advance Projects at Pfizer

Anokha_RatnayakeAnokha Ratnayake, Ph.D., Principal Scientist, Medicine Design - ADC Oncology, Pfizer

The design and development of a successful ADC require identification and implementation of reliable analytical techniques and assays (such as LBA and DAR-based PK, plasma stability) at an early stage, to help drive decisions about project advancements. A fundamental understanding of ADC metabolism enables problem solving that may “rescue” payloads that were previously deprioritized. Site of conjugation can play a major role in ADC metabolism, hydrophobicity and PK.

11:20 An Integrated Multiplatform Bioanalytical Strategy for Antibody–Drug Conjugates: A Novel Case Study

Vangipuram_RanganVangipuram S. Rangan, Ph.D., Senior Director, Protein Chemistry, Bristol-Myers Squibb Co.

This talk describes the utilization of reagents specifically tailored to an ADC with a microtubule polymerization inhibitor payload and cathepsin B cleavable linker. The PK strategy includes the evaluation of physiological levels of total antibody, active ADC, total ADC, antibody-conjugated payload and unconjugated payload. These data are evaluated in the context of target and antidrug antibody levels to elucidate bioactive ADC.

11:50 Neutropenia Translation of ADC: Perspective from Mechanistic Modeling

Shangchiung Chen, Ph.D., Scientist, Clinical Pharmacology, Genentech

A quantitative preclinical/clinical translational model for neutropenia was developed using PK and PD data from multiple vc-MMAE ADCs. The translational PK/PD model can be used to predict potential risk of neutropenia based on preclinical observation in monkeys and facilitate dose/regimen selection.

12:20 pm Sponsored Presentation (Opportunity Available)

12:50 Session Break

1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

ADC PROMISE AND INNOVATION

2:00 Chairperson’s Remarks

Andreas Pahl, Ph.D., CSO, Heidelberg Pharma

FEATURED PRESENTATION

2:05 Challenges and Opportunities in Design and Development of Antibody-Drug Conjugates

John_LambertJohn M. Lambert, Ph.D., Executive Vice President & Distinguished Research Fellow, ImmunoGen, Inc.

ADCs with potent tubulin-acting and DNA-acting agents can be effective anti-cancer agents with good TI. However, not all cell-surface targets have proven susceptible to the development of effective ADCs utilizing first generation ADC chemistries. Lessons from the past 15 years of ADC preclinical and clinical experience have created new opportunities in design and development of ADCs to meet the challenges in creating successful ADCs, as illustrated with the progress of ImmunoGen’s advancing ADC.

2:35 MMETA – A Tubulysin Analog for Antibody-Drug Conjugates

Dorin Toader, Ph.D., Senior Scientist, Antibody Discovery and Protein Engineering, MedImmune LLC

Tubulysins are a class of naturally occurring highly cytotoxic peptides of fungal origin. The observed picomolar activity of tubulysins against a range of cancer cell lines makes them excellent candidates for targeted delivery as conjugates with monoclonal antibodies. This presentation describes the discovery and development of a fully synthetic tubulysin analog MMETA and its application to antibody-drug conjugates for oncology.

3:05 Multiparatopic and Multispecific Nanobody-Based Drug Conjugates

Carlo Boutton, Ph.D., Director, Technology & Information Management, Ablynx nv

The modularity of the Nanobody platform allows an easy generation of multivalent, multiparatopic and multispecific constructs. By combining several Nanobodies with similar or different functionalities, the properties of the proposed drug can be tuned. This is an extremely powerful platform to direct Nanobody-based drug conjugates to diseased cells.

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing

SITE-SPECIFIC CONJUGATION

4:30 Selecting the Optimal Cysteine Site for THIOMAB-Drug Conjugates

Hans_EricksonHans Erickson, Ph.D., Associate Director, Protein Chemistry, Genentech

Antibodies with cysteine mutations for conjugation are widely used for the preparation of homogeneous ADCs with defined molar ratios of the payload to the antibody (site-specific). The factors that drive stability are not well understood. I propose to describe how we have optimized our cysteine engineering (THIOMAB™) technology to build better ADCs and also share some of the research conducted to understand the factors that drive stability of protein conjugates using maleimide and disulfide-based attachment chemistries.

5:00 Pcl and PPTase – Two Innovative Methods for the Preparation of Homogenous ADCs

Bernhard_GeierstangerBernhard H. Geierstanger, Ph.D., Director, Protein Engineering, Genomics Institute of the Novartis Research Foundation

Pyrroline-carboxy-lysine (Pcl) is readily incorporated by the unmodified pyrrolysyl-tRNA/tRNA synthetase pair into proteins at TAG codons and reacts specifically with 2-amino-benzaldehyde reagents. Similarly, post-translational modification catalyzed by phosphopantetheinyl transferases (PPTases) can be used to site-specifically label proteins with structurally diverse molecules. Both methods can be used to efficiently prepare homogenous, site-specifically conjugated ADCs with excellent biophysical and PK characteristics, and high in vitro and in vivo potency.

Buzz Sessions5:35 BuzZ Session B

Join your peers and colleagues for interactive roundtable discussions.

6:20-7:20 Reception in the Exhibit Hall with Poster Viewing

7:20 Close of Conference