Cambridge Healthtech Institute’s 7th Annual

Antibody-Drug Conjugates

Next-Gen Engineering

January 21-22, 2020

Part of the Antibody Therapeutics pipeline

Antibody-Drug Conjugates have demonstrated their ability to deliver cytotoxic small-molecule drugs through a selective and targeted mechanism in the fight against cancer. In recent years, ADCs have entered almost 600 clinical trials with more than 60 distinct ADC molecules currently under development. Despite the enormous promise, a low therapeutic index has plagued ADC development, particularly for treating solid tumors.

Cambridge Healthtech Institute’s Antibody-Drug Conjugates conference explores 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 illustrate the ongoing efforts to engineer ADCs, move them into the clinic, and conquer cancer.

Final Agenda

Day 1 | Day 2 | Download Brochure

TUESDAY, JANUARY 21

1:00 pm Registration (Sapphire West Foyer)

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

THE PROMISE OF ADCs AND LESSONS LEARNED
Aqua c

2:00 Chairperson’s Opening Remarks

Ian Schwartz, MS, Global Technology Consultant, Bioconjugation, Sartorius Stedim North America, Inc.

KEYNOTE PRESENTATION

2:05 Learnings from Successes and Failures of ADCs and Cancer Immunotherapies

Rakesh Dixit, PhD, DABT, President & CEO, Bionavigen, LLC

Learning from failures & enabling innovations in ADCs and immunotherapies to fight against deadly cancers; what are common features among clinically successful ADCs and immunotherapies? What went wrong with some clinically unsuccessful ADCs? Why have some immunotherapies failed? Top five lessons learned from the development of ADCs and immunotherapies in the last two decades; next-generation ADCs and immunotherapies meeting the five rights; combination of immunotherapies and ADCs: a new frontier in the fight against cancers.

2:45 Antibody-Drug Conjugates: Progress, Pitfalls, and Promises

Mark Glassy, PhD, Chairman, Nascent Biotech, Inc.

Antibody-drug conjugates (ADCs) represent a promising and an efficient strategy for targeted cancer therapy. The therapeutic success of future ADCs is dependent on adherence to key requirements of their design and careful selection of the target antigen on cancer cells. The main components in the design of antibody-drug conjugates, improvements made, and lessons learned over two decades of research are discussed.

3:15  ADC Bioanalysis in Support of Exposure-Response (E-R) Relationships for ADC Clinical Development

Leo Kirkovsky, PhD, Director, Clinical Assay Group, Global Clinical Pharmacology, Pfizer, La Jolla

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

ADC Development Strategies
AQUA C

FEATURED PRESENTATION

4:30 Exploring the Bioanalytical Strategy for ADCs

Edit Tarcsa, PhD, Director and Research Fellow, Drug Metabolism & Pharmacokinetics, Abbvie Bioresearch Center, AbbVie

ADCs are complex therapeutic modalities with the possibility of forming multiple analytes in vivo. A wide variety of assays on multiple analytical platforms has been utilized for their characterization. How does one choose what is appropriate for decision making at the various project stages while balancing speed, quality, and reagent availability? A few case studies with bioanalytical decision trees will illustrate the issues and solutions.

5:00 NEW:  Speaker Cancelled -- Novel Approaches to Modeling Preclinical Activity of ADCs and Informing Biomarker Strategy

Tony D’Alessio, PhD, Senior Research Investigator, Oncology Biotherapeutics, Novartis Institutes for Biomedical Research

5:30 Close of Day

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

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

SC2: The Safety of Immunotherapy and ADCs: How to Mitigate Risk and Adverse Effects - Detailed Agenda

Instructors:

Rakesh Dixit, PhD, DABT, President & CEO, Bionavigen, LLC

George Octavian Badescu, PhD, Vice President, Scientific Affairs, Heidelberg Pharma AG

*Separate registration required

Day 1 | Day 2 | Download Brochure

WEDNESDAY, JANUARY 22

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

ADCs for Cancer Therapy
AQUA C

8:15 Chairperson’s Remarks

Edit Tarcsa, PhD, Director and Research Fellow, Drug Metabolism & Pharmacokinetics, Abbvie Bioresearch Center, AbbVie

8:20 Antibody-Drug Conjugates for Immunology (iADC)

Adrian Hobson, PhD, Research Fellow, Global Biologics – Antibody Drug Conjugates, AbbVie Bioresearch Center, AbbVie

Antibody-Drug Conjugates (ADC) combine the targeting of an antibody with the potency of a small molecule. Pioneered for oncology, there are 4 marketed oncology antibody-drug conjugates (oADC) and many in clinical development. This talk will describe the technology behind oADCs, then the efficacy and safety challenges faced when modifying these novel therapeutic agents for immunology to enable an immunology antibody-drug conjugate (iADC) to progress to the clinic.

8:50 Amanitin-Based Antibody-Drug Conjugates as New Therapeutic Modalities for Cancer Therapy

Stephanie Voss, PhD, Group Leader, Bioconjugation & Protein Chemistry, Heidelberg Pharma Research GmbH

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 in 2020.

9:20  Developing Site-Specifically Modified ADCs using a Chemoenzymatic Approach    

David Rabuka, PhD, CEO and President, Acrigen Biosciences, Inc.

We will present recent data on our SMARTagTM technology platform and its application to generating novel bioconjugates, including ADCs, utilizing our new conjugation chemistries and linkers.  The application of these chemistries to the generate site-specifically modified bioconjugates with improved efficacy against numerous targets and safety profiles will be presented. Additionally, we will highlight progress in developing conjugates with a focus on preclinical studies as well as highlight our progress with the SMARTagTM technology in the clinic.

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

Targeting Tumors in the Fight Against Cancer
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10:35 Peptide Nucleic Acid (PNA)-Mediated Pretargeting for Radionuclide Therapy

Amelie Eriksson Karlström, PhD, Professor, Protein Sciences, Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology

Radioimmunotherapy utilizes tumor-specific radiolabeled antibodies to deliver cytotoxic radiation to tumor cells. To avoid unwanted exposure of non-tumor organs, we use pretargeting to uncouple the tumor-targeting step from the delivery of the toxic radionuclide. We have developed and evaluated a system for pretargeting based on the high selectivity and high affinity of PNA:PNA (peptide nucleic acid) hybridization. The primary agent is administered first, and the secondary, radiolabeled agent is administered after the primary agent has accumulated in the tumor and cleared from non-tumor tissue.

11:05 Probody Therapeutics in the Treatment of Cancer

Siew Schleyer, PhD, Director, Oncology Research, CytomX Therapeutics, Inc.

ProbodyTM therapeutics are fully recombinant antibody-based prodrugs designed to remain largely inactive in circulation until proteolytically activated in the tumor microenvironment. They are designed to protect normal tissues while increasing the concentration of active antibody in tumors, thus widening the therapeutic index. Probody technology can be applied to multiple antibody-based therapies. Examples will include Probody therapeutics based on checkpoint inhibitor antibodies, T cell-engaging bispecifics, and will focus on antibody-drug conjugates.

11:35 NEW:  SELECTED POSTER PRESENTATION 

A Different "ADC": Albumin-Drug Conjugates with Controlled Loading for Improved Antitumor Efficacy

Debadyuti Rana Ghosh, PhD, Assistant Professor, Molecular Pharmaceutics & Drug Delivery, University of Texas at Austin

12:05 pm Session Break

12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Session Break

Aqua Salon

1:45 PLENARY KEYNOTE PANEL

R&D CHALLENGES IN AN ERA OF INNOVATION

The PepTalk Plenary Keynote Panel convenes a group of leading scientists working across novel therapeutic modalities and R&D technologies to explore the many challenges associated with discovering, developing, and advancing today’s novel biotherapeutics. The Panel, via a highly interactive format, encourages discussion among both the panelists and the audience members. Please come prepared with your questions and ideas for this spirited discussion.

• Advances and challenges in expression and production for novel modalities
• Implementing next-generation informatics: data collection, standardization, analysis, ML/AI, and considerations for IP landscape and protection
• Implementing R&D and production capacity for gene and cell therapies – where are we heading?
• Modality-specific challenges: multi-specifics for cancer, improving the ADC therapeutic window, improved safety and pharmacology, novel delivery/targeting
• Preclinical and clinical development of drug combinations with focus in IO: How do we select the right combination dose so we can accelerate clinical development?

Moderator:

Mohammad Tabrizi, PhD, Senior Director, Pharmacology, Ascendis Pharma A/S

PANELISTS

Edward Kraft, PhD, Senior Scientific Manager, Biomolecular Resources, Genentech

Ilya Shestopalov, PhD, Associate Director, Cell Analytics, bluebird bio

David E. Szymkowski, PhD, Vice President, Cell Biology, Xencor, Inc.

Alayna George Thompson, PhD, Senior Scientist I, Drug Discovery Science & Technology, AbbVie

3:05 Refreshment Break in the Exhibit Hall with Poster Viewing

Breakthrough Engineering & Design
AQUA C

4:00 Chairperson’s Remarks

Jonathan van Dyck, Scientist, Analytical Sciences, Seattle Genetics

4:05 Antibody-Drug Conjugates as Targeted Conditioning Agents for Bone Marrow Transplant Patients

Bradley Pearse, PhD, Director, Biotherapeutics, Magenta Therapeutics

Current regimens for patient preparation, or conditioning, prior to bone marrow transplant in malignant and non-malignant settings are non-selective and toxic, limiting the use of this curative procedure due to regimen-related morbidities and mortality. To address this, we developed antibody-drug conjugates (ADCs) that specifically deplete recipient target cell populations to enable robust donor cell engraftment. Thus, ADCs may enable curative treatment through safer and targeted conditioning prior to transplant.

4:35 Characterizing Antibody-Drug Conjugate CQAs Considering Multiple Mechanisms of Action

Jonathan van Dyck, Scientist, Analytical Sciences, Seattle Genetics

Defining and understanding the critical quality attributes (CQAs) of antibody-drug conjugates (ADCs) is a necessary and integral part of product development. This assessment is more complex when multiple mechanisms of action (MOA) are present, since quality attributes that impact safety and efficacy must be understood within the context of each MOA. Typically, ADCs are understood to act through cellular delivery of a cytotoxic small molecule payload via specific antibody/antigen interactions. However, additional MOAs driven by antibody effector function, such as ADCC and ADCP, may be present and quality attributes that influence them should be well understood and characterized. Here we present results from experiments to characterize how drug-load and N-glycan product variants impact the effector function and overall MOA of MMAE conjugates.

5:05 Identification of Engineered Methionines and Oxaziridines for Antibody-Drug Conjugates

Susanna Elledge, MSc, Scientist, Chemistry and Chemical Biology, University of California, San Francisco (UCSF)

In this presentation, we will discuss the systematic scan of methionines throughout the trastuzumab antibody scaffold for a new kind of site-specific antibody engineering and drug conjugation. We will describe how expression, labeling, and stability varied at each methionine site and discuss in vitro and in vivo potency of methionine-based antibody-drug conjugates.

5:35 Improved Tumor Growth Inhibition of Diabody-Drug Conjugates Achieved by Half-Life Extension

Qing Li, PhD, Scientist, Antibody Discovery & Protein Engineering, AstraZeneca

Half-life extension technologies, such as PEGylation and albumin-binding domains (ABDs), have been widely used to improve the pharmacokinetics of many different types of biologics. In this study, we used an anti-5T4 diabody conjugated with a highly potent cytotoxic pyrrolobenzodiazepine (PBD) warhead to assess and compare the effects of PEGylation and albumin binding on the in vivo efficacy of antibody fragment drug conjugates.

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

6:45 - 7:30 Focus on Women in Science

CHI celebrates the advancement of diversity in the life sciences. We recognize that barriers preventing women from fully participating in the sciences are not just barriers to equality, but also critically deter scientific advancement worldwide. We invite the entire scientific community to discuss these barriers, as we believe that all voices are necessary and welcome.

Women in Science: Finding your Voice of Confidence 
Interactive Discussion Group Moderated by:

Edit Tarcsa, PhD, Director and Research Fellow, Drug Metabolism & Pharmacokinetics, Abbvie Bioresearch Center, AbbVie

7:00 Close of Antibody-Drug Conjugates Conference

Day 1 | Day 2 | Download Brochure