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Cambridge Healthtech Institute’s 6th Annual

Antibody-Drug Conjugates

Next-Gen Engineering

January 15-16, 2019

 

As more Antibody-Drug Conjugates head to market, the next-generation of ADCs looms on the horizon. Next-gen engineering requires designing an optimal antibody, payload, linker and conjugation method while ensuring stability, targeted delivery, and limited off-target effects. Cambridge Healthtech Institute’s Antibody-Drug Conjugates conference will explore the engineering finesse required to achieve the crucial balance between efficacy and safety, thus  leading the way to more potent and targeted molecules. Case Studies and data will be shared that exemplify the ongoing efforts to engineer ADCs, move them into the clinic, and fight cancer along with potentially non-oncological indications.

Final Agenda

TUESDAY, JANUARY 15

1:00 pm Registration (Sapphire West Foyer)

1:30 Refreshment Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)

Fighting Cancer with Antibody-Drug Conjugates
Aqua AB

2:00 Chairperson’s Opening Remarks

Marc Damelin, PhD, Senior Director, Biology, Mersana Therapeutics, Inc.


KEYNOTE PRESENTATION

 2:05 Advances in Next-Generation ADCs, Immunotherapies and Combinations in the War against Cancer

Rakesh Dixit, PhD, Vice President and Global Head, Translational Sciences-Biologics Safety Assessment, MedImmune, LLC

In my talk, I will discuss advances in next-generation ADCs that are meeting the challenges; some new, some old. One persistent challenge is mitigating dose-limiting toxicities of ADCs and improving therapeutic index. I will also address next-generation immunotherapies and their combinations, and synergies between ADCs and immunotherapies.

2:45 ADCs with IGN Payload in Hematologic Malignancies

Kovtun_YelenaYelena Kovtun, PhD, Associate Director, Pipeline Research and Development, ImmunoGen, Inc.

Several ADCs with mono-imine containing Indolinobenzodiazepine (IGN) payload entered the clinic recently, including IMGN779 and IMGN632, conjugates targeting CD33 and CD123 respectively. The strategy to select targets in hematologic malignancies, as well as to design optimal antibody, payload and conjugation method for IMGN779 and IMGN632 will be covered in the presentation.

Eisai 3:15 Simple and Efficient Production of Homogeneous, Site-Specific ADCs with Transglutaminase & RESPECT ®

Spidel_JaredJared Spidel,Senior Principal Scientist, Antibody Development, Oncology Biologics Laboratory, Eisai

RESPECT®-H is a transglutaminase-based site-specific conjugation technology that forms a stable isopeptide bond between a glutamine-based payload and a specific lysine on an antibody. We identified single lysine point mutations in IgG that can be efficiently conjugated to small glutamine-containing payloads. We further demonstrated their utility with desirable manufacturing and biophysical characteristics as a means to produce homogenous, site-specific, highly potent ADCs with equimolar potency to ADCs produced by a random conjugate strategy.

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)

Fighting Cancer with Antibody-Drug Conjugates Cont.
Aqua AB

4:30 Transvascular Pumping of ADC into Solid Tumors Boosts Drug Potency and Safety

Schnitzer_JanJan E. Schnitzer, MD, Director and Professor, Cellular & Molecular Biology, Proteogenomics Research Institute for Systems Medicine (PRISM)

Current ADCs can’t deliver drugs inside solid tumors specifically, rapidly or robustly. Near MTD doses required to drive ADCs passively across endothelial cell barriers are inadequate to unleash drug potency inside tumors. We circumvent this passive transvascular delivery paradigm by generating the first antibody to actively penetrate solid tumors. This enables precision tumor targeting and imaging within one hour, boosts therapeutic indices >100-fold and even eradicates multi-drug resistant tumors at doses well below MTD.

5:00 Antibody-Drug Conjugates Targeting Tumor Stromal Cells

Dimitrov_DimiterDimiter Dimitrov, PhD, Director, Center for Antibody Therapeutics, University of Pittsburgh Medical School

Targeting the tumor stromal cells in addition to tumor cells with ADCs is a promising anti-cancer strategy. CD276 and TEM8 are variably expressed in a variety of cancers and to different extents on tumor stromal cells and tumor cells. Both CD276-ADC-PBD and TEM8-ADC-MMAE eradicated large established tumors and metastases and improved long-term overall survival in several different mouse models of cancer. Data for ADCs targeting other cancer-related molecules will also be discussed.

5:30 Close of Day

5:30 - 5:45 Short Course Registration (Sapphire West Foyer)


5:45 - 8:45 Recommended Dinner Short Courses*

SC2: Structure-Based Optimization of Antibodies- Detailed Agenda

Click here for more details.

*Separate registration required

WEDNESDAY, JANUARY 16

7:45 am Registration and Morning Coffee (Sapphire West Foyer)

NEXT-GEN ENGINEERING STRATEGIES FOR ADCs
Aqua AB

8:15 Chairperson’s Remarks

Shalom Goldberg, PhD, Principal Scientist, Discovery Sciences, Janssen Research & Development/Johnson & Johnson

FEATURED PRESENTATION

8:20 Next-Generation ADCs: Considerations and Examples

Damelin_MarcMarc Damelin, PhD, Senior Director, Biology, Mersana Therapeutics, Inc.

In this case study, I will discuss key opportunities for the discovery and development of next-generation ADCs as informed by learnings from our collective experience. Topics will include molecular design, preclinical studies and development strategy. In this context, I will highlight the rationale and early data from selected technologies and clinical molecules.

8:50 Conjugated or Engineered Antibodies -- Benefits and Limits of Different Therapeutic Modalities

Schmidt_StefanStefan R. Schmidt, PhD, MBA, Head, Operations (COO), BioAtrium, AG

During the last decade, we could observe disruptive developments in antibody technologies. On the one hand, a broader understanding of drug conjugates and their optimization could be gained. On the other hand, protein engineering was massively applied to improve critical features of antibodies in general. In this talk, the different strategies will be discussed, comparing their benefits and limits and highlighting recent success stories of both therapeutic modalities in the context of functionality and manufacturing.

9:20 Amanitin-Based Antibody-Drug-Conjugates as New Therapeutic Modalities for Cancer Therapy

Badescu_GeorgeGeorge Badescu, PhD, Vice President, Scientific Affairs, Heidelberg Pharma AG

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 includes Amanitin supply, site-specific conjugation, demonstrated safety profile and biomarker.  HDP-101 is the first ATAC directed against BCMA entering Phase I trials by the end of 2019.

9:50 Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)

Honing In on ADC Targets
Aqua AB

10:35 Targeting of Tumor-Initiating Cell-Associated Antigens with Antibody-Drug Conjugates

Bankovich_AlexAlex Bankovich, PhD, Senior Director, Late Stage Research, Abbvie Stemcentrx, LLC

Tumor-initiating cells (TICs) will remain controversial until findings in the lab translate into drugs providing significant clinical benefit to patients. Antibody drug conjugates (ADCs) are a promising class of drugs able to target and reduce the frequency of TICs in patient-derived xenografts. My company has worked to discover TIC phenotypes and to utilize methods well-suited to specifically identify cell surface proteins targetable by specific ADCs. My talk expands on the drug development path we followed and provides some new insights.

11:05 Using Multi-Omics Data and Functional Screens to Select Antibody-Drug Conjugate Targets

Hill_JenniferJennifer Hill, PhD, Team Lead, MS & NMR Analytics, National Research Council Canada (NRC)

Antibody drug conjugates (ADCs) are a promising therapeutic class for cancer therapy. We describe our approach to identify new ADC targets, incorporating gene expression data mining and glycoproteomic profiling, followed by in vitro screening through a surrogate ADC assay. Based on these target selection methods, we are producing thousands of monoclonal and single-domain antibodies generated against a variety of cancer-associated targets and screening them for ADC activity, in vitro and in vivo.

11:35 SILAC-Based Proteomics Screen to Select Potential ADC Targets

Andreev_JulianJulian Andreev, PhD, Fellow Scientist, Oncology and Angiogenesis, Regeneron Pharmaceuticals

Rapid constitutive lysosomal internalization of Prolactin Receptor (PRLR) is the mechanism behind PRLR ADC efficacy. By bridging PRLR, or another high turnover protein, Amyloid Precursor-like Protein 2 (APLP2), with surface tumor target HER2 using bispecific antibodies, HER2 lysosomal degradation can be triggered, and HER2 ADC efficacy can be significantly improved. Our study opens up a possibility to exploit high turnover proteins such as PRLR and APLP2 in combination with bispecific antibodies to enhance efficacy of ADCs.

12:05 pm Session Break

Ajinomoto_NEW 12:15 Luncheon Presentation I: Technology of Site Specific Conjugation for Next Generation ADCs

Okuzumi_TatsuyaTatsuya Okuzumi, PhD, Associate General Manager, R&D, Planning Department, Ajinomoto Co., Inc.


12:45 Luncheon Presentation II (Sponsorship Opportunity Available)

1:15 Session Break


PLENARY KEYNOTE PANEL (Aqua Salon)

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PepTalk Perspectives: Point-Counterpoint Discussions

2:00 Plenary Keynote Introduction

Norman Packard, PhD, CEO, Daptics


2:10 Plenary Keynote Panel

Moderator:
Howard Levine, PhD, President and CEO, BioProcess Technology Consultants
Panelists:
George BadescuGeorge Badescu, PhD, Vice President, Scientific Affairs, Heidelberg Pharma AG
Cox ManonManon Cox, PhD, Co-Founder & CEO, NextWaveBio
Zhimei Du, PhD, Director, Bioprocess & Clinical Manufacturing, Merck
Paul Jorjorian, Vice President, BioProcess Sciences, Thermo Fisher Scientific
Marina Kirkitadze, PhD, Deputy Director, Head of Biophysics and Conformation Unit, Analytical R&D Biochemistry, Sanofi Pasteur, Canada
Stefan SchmidtStefan R. Schmidt, PhD, MBA, Head, Operations (COO), BioAtrium AG

 

3:05 Refreshment Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)

Improving Site-Specific Conjugation, Payloads & Scaffold Engineering
Aqua AB

4:00 Chairperson’s Remarks

Yelena Kovtun, PhD, Associate Director, Pipeline Research and Development, ImmunoGen, Inc.

4:05 NEW TALK TITLE:  Development of a Robust Site-Specific Conjugation Platform for Hybrid Molecules

Cheng_YuanYuan Cheng, PhD, Principal Scientist, Therapeutic Discovery, Amgen, Inc.

We developed a site-specific conjugation platform using cysteine-mutant antibody or protein. In this presentation, we describe the optimization of this platform by changing the disulfide caps to cysteamine, using a mild reducing agent, and monitoring individual reaction steps. The conjugation sites and linkers had a significant effect on conjugation efficiency, biological activity, and pharmacokinetic profiles. The platform allowed efficient SAR studies in a variety of research projects and demonstrated feasibility in multi-gram conjugation.

4:35 Highly Homogeneous Antibody-Drug Conjugates Based on Dual Variable Domains

Rader_ChristophChristoph Rader, PhD, Associate Professor, Immunology and Microbiology, The Scripps Research Institute

Homogeneous antibody-drug conjugates (ADCs) that use a highly reactive buried lysine residue embedded in a dual variable domain (DVD) format can be assembled with high precision and efficiency under mild conditions and reveal potent and specific tumor cell killing in vitro and in vivo. Building on this DVD-ADC platform, we have developed orthogonal conjugation strategies that enable the loading of two different payloads in a one-pot reaction.

5:05 Antibody PBD Conjugates

Howard_PhilipPhilip Howard, PhD, Senior Fellow, MedImmune, Inc.; CSO, Spirogen, Ltd.

Pyrrolobenzodiazepines (PBDs) have found extensive use in the field of antibody drug conjugates. PBD payloads have been studied in more than 20 clinical trials; currently these trials are dominated by tesirine and talirine payloads. This presentation will focus on the learnings from the clinical studies and development of the next generation of PBD payloads.

5:35 Design, Characterization, and LC/MS/MS Bioanalysis of Protein-Drug Conjugates

Goldberg_ShalomShalom Goldberg, PhD, Principal Scientist, Discovery Sciences, Janssen Research & Development/Johnson & Johnson

Antibody- and other protein-drug conjugates have multiple parameters that can be tailored to increase the therapeutic window. Here we describe the design and characterization of a drug conjugate using the Centyrin alternative scaffold, as well as the development of broadly-applicable methods for in vivo characterization using LC/MS/MS.

6:05 - 7:00 Networking Reception in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)

7:00 Close of Antibody-Drug Conjugates Conference