Engineering Antibody-Drug Conjugates


A successful ADC requires the combination of the right target, right antibody, right linker and the right payload. Getting it right can create ADCs that have the potential to become a life-saving medicine for many diseases, especially cancer. At CHI's Engineering Antibody-Drug Conjugates, speakers will share their creative strategies, whether in altering the antibody effector moiety, testing new payloads, selecting novel targets, or reinventing conjugation technologies, and discuss their progress to-date.

Wednesday, September 2

PRECLINICAL OUTCOMES AND TRANSLATION TO CLINIC

12:40 pm

OPENING REMARKS & KEYNOTE PRESENTATION: Key Learnings from Successful and Failed ADCs

Rakesh Dixit, PhD, President & CEO, Bionavigen

With seven approved ADCs combined with the great potential of approval of at least 4 additional ADCs in the next 2 years, there is renewed enthusiasm and momentum in the world of oncolytic ADCs. However, the success in oncolytic ADCs has come with high failures. The presentation will provide a comprehensive review as follows:

  • What is common among clinically successful ADCs?
  • What went wrong with some clinically unsuccessful ADCs?
  • Top five lessons learned from the development of ADCs in the last two decades
  • Innovations in creating designer ADCs with fit-for-purpose

1:05 pm

Application of PK/PD M&S for Preclinical-to-Clinical Translation of ADCs

Dhavalkumar K. Shah, PhD, Associate Professor, Pharmaceutical Sciences, State University of New York at Buffalo

This talk will highlight how preclinical experiments can be used in conjunction with PK/PD modeling and simulation to support the discovery, development and preclinical-to-clinical translation of novel ADCs. The talk will also focus on novel P/PD-based strategies to improve the therapeutic index of ADCs.

1:25 pm

MGTA-117: An Anti-CD117 Antibody Drug Conjugate (ADC) Designed for Patient Conditioning for Stem Cell Transplant and Gene Therapy Provides a Broad Therapeutic Window Across Species

Rahul Palchaudhuri, PhD, Senior Scientist, Magenta Therapeutics

Patient outcomes can be greatly improved by a bone marrow transplant in multiple disease settings, including autoimmune diseases and hematologic disorders. Prior to transplant, patients are conditioned by removing their own bone marrow stem cells using poorly tolerated toxic, non-selective chemotherapy and radiation. This presentation will highlight preclinical proof of concept data demonstrating that antibody-drug conjugates may be safer, targeted agents for patient preparation with the aim of extending the use of curative bone marrow transplant and improving outcomes for patients.

1:45 pm LIVE:

Q&A and Session Wrap Up

Panel Moderator:
Dhavalkumar K. Shah, PhD, Associate Professor, Pharmaceutical Sciences, State University of New York at Buffalo
Panelists:
Rakesh Dixit, PhD, President & CEO, Bionavigen
Rahul Palchaudhuri, PhD, Senior Scientist, Magenta Therapeutics
2:10 pm Refresh Break - View our Virtual Exhibit Hall

NEW & SPECIALTY PAYLOADS

2:25 pm

Targeted C’Dot-Drug Conjugates for the Treatment of Cancer

Gregory P Adams, PhD, CSO, Elucida Oncology Inc

C’Dot Drug Conjugates (CDCs) are ultra-small (sub-10nm) targeted organic-silica hybrid bio-material nanodrug conjugates that have a payload capacity 10 times higher than antibodies. The ultra-small size of CDCs facilitates both effective tumor penetration, including the ability to mediate drug delivery across a disrupted blood brain barrier, and efficient systemic elimination which can reduce toxicities associated with prolonged residence in the circulation. Elucida Oncology developmental platform will be presented.

2:45 pm

IMB-213: A Novel Secretome-Targeted Biologic for the Selective Delivery of Immunomodulatory Payloads to Solid Tumors

Anton Neschadim, PhD, MBA, CEO & Director, ImmunoBiochem Corporation

Strategies harnessing the potential of the innate immune system in cancer therapy are yielding promising clinical results. To improve on the current approaches, the targeted delivery of immunomodulatory payloads, such agonists of the Stimulator of Interferon Genes (STING) pathway, could yield a tunable platform for achieving increased efficacy and safety. ImmunoBiochem is utilizing its cancer secretome-targeted biologics platform to deliver high-potency immunomodulatory payloads selectively to the immune cells and stroma within the tumor microenvironment.

Robyn Barfield, PhD, Group Leader, Chemical Biology, Catalent, Biology, Catalent

SMARTag™ technology uses a simple, robust manufacturing process to generate stable, site-specific ADCs. Our RED-106 noncleavable maytansine linker-payload is resistant to P-glycoprotein efflux, offering wider therapeutic windows as compared to other technologies. This advantage is illustrated by our anti-HER2 RED-106 ADC in comparison to the related drug, T-DM1.

 

3:30 pm LIVE Q&A:

Q&A and Session Wrap-Up

Panel Moderator:
Anton Neschadim, PhD, MBA, CEO & Director, ImmunoBiochem Corporation
Panelists:
Gregory P Adams, PhD, CSO, Elucida Oncology Inc
Robyn Barfield, PhD, Group Leader, Chemical Biology, Catalent, Biology, Catalent
3:50 pm Refresh Break - View Our Virtual Exhibit Hall
4:10 pm Problem Solving Breakout Discussions - Part A

This session provides the opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges.

TABLE 27: ADC Targets and Payloads: When Friends Become Foes

Rakesh Dixit, PhD, President & CEO, Bionavigen
  • ​Navigation of targets and payloads for ADCs
  • Wrong pairing of targets and payloads: turning friends into foes
  • Strategies for selection of targets and payload for improving the therapeutic index
  • Translational medicine strategies to maximize TI
4:40 pm Refresh Break - View Our Virtual Exhibit Hall
5:00 pm Problem Solving Breakout Discussions - Part B

TABLE 28: Antibody Engineering Approaches to Improve the Therapeutics Index of ADCs

Dhavalkumar K. Shah, PhD, Associate Professor, Pharmaceutical Sciences, State University of New York at Buffalo
  • Is 150 kDa size of mAb the best to conjugate drug molecules, or fragment-drug conjugates may provide more/different benefits?
  • What are different antibody engineering approaches evaluated to improve ADCs (e.g. bi-specific etc.), and which one seems more superior?
  • Does the site of drug conjugation (e.g. specific amino acid, glycan etc.) matter dramatically for ADCs?
  • What are learnings from application of ADCs beyond oncology? Is it a viable targeted drug delivery approach for other disorders?

 

5:30 pm Close of Day

Thursday, September 3

ENGINEERING THE ANTIBODY EFFECTOR MOIETY

9:05 am

Antibody Fragment Drug Conjugates (FDCs): Expanding the Target Repertoire

Mahendra P. Deonarain, PhD, Chief Executive and Science Officer, Antikor Biopharma Ltd.

Antikor is developing smaller-format ADCs that penetrate tissues more rapidly, clear faster from normal organs and are better-tailored for solid tumours. Our HER2 FDC (ANT-043) is in advanced development but our toolbox of antibody libraries and linker-payloads have yielded our second new FDC candidate (ANT-045). We will present compelling new discovery data that helps us understand the strengths of our novel platform and tumour cure efficacy data for ANT-045 for gastro-intestinal cancers, with uptake and imaging data to support our technological approach..

9:25 am

Engineered Avibodies (Enhanced Diabodies) Precisely Loaded with Novel ADC Payloads that Surpass IgG-ADCs in Cancer Therapy

Peter J. Hudson, PhD, Chief Scientist and CSO, Victorian Cancer Biologics Consortium, Avipep Pty Ltd.

Avibodies™ comprise unique surface disulphides for precise loading of drug payloads (auristatins, maytansinoids) with superior tumor xenograft regression compared to conventional IgGs (targeting CD30). PK has been demonstrated in a Phase 1 clinical trial. With TagWorks NV2, Avibodies pre-target and upload tumors with the ADC-drug subsequently released by a systemic activator. In summary, Avipep’s novel Avibody designs enable precise site-specific loading of drug and isotope payloads for cancer imaging and ADC therapy.

9:45 am

Antibody-Drug Conjugates (ADCs) and Small-Molecule Drug Conjugates (SMDCs): A Comparative Analysis

Dario Neri, PhD, Full Professor, Chemistry & Applied Biosciences, ETH Zurich

Antibody-drug conjugates (ADCs) and small-molecule drug conjugates (SMDCs) represent two conceptually related strategies for the targeted delivery of potent cytotoxic agents to various types of cancer. In this lecture, I will present a comparative analysis of therapy and biodistribution results in mouse models of cancer, as well as clinical data and information on how ADCs and SMDCs can be potentiated using targeted cytokine therapeutics.

10:10 am

Q&A and Session Wrap-Up

Panel Moderator:
Dario Neri, PhD, Full Professor, Chemistry & Applied Biosciences, ETH Zurich
Tony Joseph A. D'Alessio, PhD, Senior Research Investigator/Lab Head, Oncology Biotherapeutics, Novartis Institutes for BioMedical Research, Inc.
Panelists:
Peter J. Hudson, PhD, Chief Scientist and CSO, Victorian Cancer Biologics Consortium, Avipep Pty Ltd.
Mahendra P. Deonarain, PhD, Chief Executive and Science Officer, Antikor Biopharma Ltd.
10:30 am Coffee Break - View our Virtual Exhibit Hall

SITE-SPECIFIC CONJUGATION & LINKER TECHNOLOGIES

10:50 am

Conjugating Payloads to Native Antibodies without the Need of Any Prior Antibody Engineering in a Single or Two Steps

Philipp Spycher, PhD, CEO, Araris Biotech AG

We will introduce a new linker antibody-conjugation technology that enables site-specific payload attachment to native antibodies ‘off-the-shelf’ in one or two steps without prior engineering. We will show that our linkers enable the incorporation of various functional chemistries and a loading of 2, 4 drugs or even 2 different drugs in one ADC. We found that the resulting ADCs have favorable physicochemical properties and showed very efficient anti-tumor responses in efficacy studies compared to conventional ADCs used at the same dosing, payload and drug load.

11:10 am

UV-NBS Site-Specific Antibody Conjugation

Nathan J. Alves, PhD, Assistant Professor, Emergency Medicine, Indiana University

Antibody modification is often necessary to endow antibodies with non-native capabilities from antibody-drug conjugates (ADCs) for targeted therapeutics to fluorescent reporter molecules for use in diagnostic or imaging applications. This session will explore site-specific antibody modification through conjugation to the conserved antibody nucleotide binding site (NBS) and will demonstrate how various linkers and conjugation strategies can be utilized to leverage the UV-NBS technology for use in next-gen antibody pharmaceuticals.

11:30 am LIVE Q&A:

Q&A and Session Wrap-Up

Panel Moderator:
Tony Joseph A. D'Alessio, PhD, Senior Research Investigator/Lab Head, Oncology Biotherapeutics, Novartis Institutes for BioMedical Research, Inc.
Panelists:
Philipp Spycher, PhD, CEO, Araris Biotech AG
Nathan J. Alves, PhD, Assistant Professor, Emergency Medicine, Indiana University
11:50 am Close of Engineering Antibody-Drug Conjugates





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