Cambridge Healthtech Institute's 8th Annual

Engineering Antibody-Drug Conjugates

( 抗体薬物複合体のエンジニアリング )

次世代抗体薬物複合体の設計に向けたパラメーターの最適化

2018年5月2-3日 | World Trade Center | マサチューセッツ州ボストン

 

Making a successful ADC relies not only on the science - the understanding of the underlying mechanism of action of ADCs, but also on the art - the expert combination of the 3 components - antibody, linker and cytotoxic drug - to achieve efficacy and tolerability. By combining the selectivity of targeted treatment with the cytotoxic potency of chemotherapy drugs, ADCs hold the power to revolutionize disease treatment, especially for cancer.
 

However, every novel technology has its challenges. ADCs suffer from low therapeutic window, tumor non-specificity, off-target toxicity, lack of efficacy, to name just a few. At the 8th Annual Engineering Antibody-Drug Conjugates conference, scientists will present their research and explorations on using alternative scaffolds and new payloads to improve half-lives and specificity, optimizing linker-payload chemistry to enhance efficacy, as well as discuss strategies to expand therapeutic window and improve stability of their ADCs.

 

Final Agenda

Recommended Short Course(s)*

SC10: Critical Considerations for the Design and Development of Antibody-Drug Conjugates


*Separate registration required.

5月2日 (水)

7:30 am Registration and Morning Coffee

代替スキャフォルドと新たなペイロード

8:30 Chairperson's Remarks

Ravi Chari, PhD, Vice President, Chemistry & Biochemistry, ImmunoGen, Inc.

8:40 Abdurin-Drug Conjugates - Small Size and Long Half-Life to Improve Drug Concentration in the Target Tissue

Kurt_GehlsenKurt Gehlsen, PhD, Vice President & CSO, Therapeutics, Research Corporation Technologies, Inc.

Abdurins are a novel antibody-like scaffold that can be engineered to bind to targets of interest and due to an FcRn binding motif, Abdurins have a circulating half-life longer than any other protein scaffold of similar size. Abdurins can be fused with protein toxins, other binding domains and engineered to carry payloads. Abdurin-drug conjugates retained high affinity binding and had in vivo half-life up to 70 hours for certain conjugates.

9:10 Antibody Targeted Amanitin Conjugates (ATACs) - Expanding the ADC Landscape with a New Payload Targeting RNA Polymerase II

Andreas_PahlAndreas Pahl, PhD, 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 includes Amanitin supply, site-specific conjugation, demonstrated safety profile and biomarker. Improvements of the technology and an update of the development of HDP-101 will be presented. HDP-101 is the first ATAC directed against BCMA entering Phase I trials by the end of 2018.

9:40 Anthracycline-Based Antibody Drug Conjugates with Potent Immune-Stimulatory Functions

Roger_BeerliRoger Beerli, PhD, CSO, NBE-Therapeutics AG

We employed enzymatic, site-specific conjugation to generate homogenous ADCs based on a derivative of the highly potent anthracycline toxin PNU-159682 and a non-cleavable peptide linker, using the anti-HER-2 antibody trastuzumab (part of trastuzumab emtansine) and the anti-CD30 antibody cAC10 (part of brentuximab vedotin). Characterization of the resulting ADCs in vitro and in vivo showed that they were highly stable and exhibited potencies exceeding those of ADCs based on conventional tubulin-targeting payloads, such as trastuzumab emtansine and brentuximab vedotin.

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

10:55 Design of a Novel, Glycan Targeting Antimicrobial ADC as a New Therapeutic Strategy for the Treatment of P. aeruginosa Infection

Obadiah_PlanteObadiah J. Plante, PhD, Director, Research, Visterra, Inc.

This presentation will describe Visterra's approach to the development of a novel antibody-based therapeutic for the treatment of established P. aeruginosa infections. The antibody targets a core region of lipopolysaccharide present at high density on P. aeruginosa and common across serotypes. To provide direct bactericidal activity, we have designed potent anti-microbial peptides that rapidly kill bacteria when directly conjugated to our antibody in the form of an ADC.

11:25 The Development of Antibody Conjugates for Targeted Delivery of siRNA

Chawita_NetirojjanakulChawita Netirojjanakul, PhD, Scientist, Therapeutic Discovery, Amgen

Advances in small interfering RNA (siRNA) technology result in numerous RNAi-based therapies being pursued in clinical trials. However, several challenges including targeted delivery of siRNA have limited the use of siRNAs as therapeutics. Here, we established a method to prepare and characterize well-defined antibody-siRNA conjugates and demonstrated that using this platform, siRNA can be delivered into specific cells or tissues in vitro and in vivo.

11:55 Attachment Site Cysteine Thiol pKa is a Key Driver for Site-Dependent Stability of Disulfide & Maleimide-Linked THIOMAB(TM) Antibody-Drug Conjugates

Breanna_VollmarBreanna S. Vollmar, PhD, Senior Scientific Researcher, Protein Chemistry, Genentech, Inc.

We set out to understand the underlying mechanisms of site-dependent stability for our THIOMAB™ antibody drug conjugate (TDC) platform utilizing engineered cysteines at specific sites on the antibody. Our observations suggest that cysteine thiol pKa is a significant driver of the circulation stability of TDCs utilizing disulfide or maleimide attachment chemistry and represents a new parameter for the optimization of next generation ADCs utilizing engineered cysteines.

 

12:25 pm Presentation to be Announced

12:55 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on your Own

1:55 Session Break

リンカーとペイロードの化学的性質の最適化

2:10 Chairperson's Remarks

Kurt Gehlsen, PhD, Vice President & CSO, Therapeutics, Research Corporation Technologies, Inc.

2:15 Chemical Fusion: A General Method for Equimolar Linking of Proteins and Payloads

Alain_WagnerAlain Wagner, PhD, Research Director, Biofunctional Chemistry, Faculty of Pharmacy, University of Strasbourg

We have designed a general conjugation methodology that involves native protein and leads to single DAR conjugates. Our method applies with virtually no limitations to all types of proteins and payloads. It enables preparation of conjugate bearing one, two or more payloads, with precise control for each of them. Noteworthy the simple mono-conjugated DAR 1 opened interesting prospects as a building block to engineer precise protein-oligonucleotide, protein-protein, protein-nanoparticle constructs.

2:45 Enzymatic (Dual) Site-Specific Conjugation of Engineered and Native Antibodies

Philipp_SpycherPhilipp R. Spycher, PhD, Post-doctoral Researcher, Center for Radiopharmaceutical Sciences, Paul Scherrer Institut

We will show single and dual site-specific conjugation of engineered antibodies with various functional payloads as well as the controlled modification of antibody-fragments and other proteins using solid-phase immobilized microbial transglutaminase (MTG). Additionally, we will introduce a novel proprietary enzymatic conjugation technology that enables site-specific payload attachment to native antibodies, thus generating well-defined ADCs that have a native IgG antibody structure.

3:15 Sponsored Presentation (Opportunity Available)

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

4:45 Problem-Solving Breakout Discussions

5:45 Networking Reception in the Exhibit Hall with Poster Viewing

7:00 End of Day

5月3日 (木)

8:00 am Morning Coffee

8:30 Chairperson's Remarks

Alain Wagner, PhD, Research Director, Biofunctional Chemistry, Faculty of Pharmacy, University of Strasbourg


8:35 KEYNOTE PRESENTATION: Clinical and Technological Advances in ADCs

Dennis Benjamin, PhD, Senior Vice President, Translational Research, Seattle Genetics

新たな標的

9:05 A Novel Cell Surface Target on Cancer Cells and Development of a Targeted ADC

Ginette_SerreroGinette Serrero, PhD, CEO, A&G Pharmaceutical, Inc.

The key to the ADC approach is the development of an antibody against a desired target preferentially expressed on cancer cells, that results in the internalization of the payload and eventual death of the cell, while limiting the off-target side effects. The presentation will cover antibody development and subsequent conjugation and payload selection for initial proof of concept studies prior to moving the antibody into linker and payload preclinical studies, using a real example of a mAb against a novel CSP target.

Applied Biomath9:35 Presentation to be Announced


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

治療濃度域の拡大と安定性の強化

11:05 Expanding Therapeutic Windows of Tubulysin Antibody-Drug Conjugates with Stable Hydrophilic Linkers

Robert_ZhaoRobert Yongxin Zhao, PhD, CEO, Hangzhou DAC Biotech Co., Ltd.

To address the liver toxicity issue in our original anti-Her2-tubulysin ADC, we developed a novel stable hydrophilic linker which, while maintaining better efficacy than T-DM1 in xenograft mouse models, proved significantly less toxic than T-DM1 in mice and cynomolgus monkeys. The overall therapeutic window was 4-6 times wider than that of T-DM1. The most percentage of metabolite of tubulysin analog was found in urine of animals demonstrating a clear correlation between its much reduced side effect and the metabolic pathway.

11:35 IMGN632, A Novel ADC with Uniquely Wide Therapeutic Window in Preclinical Models of AML

Yelena_KovtunYelena Kovtun, Associate Director, Pipeline R&D, ImmunoGen, Inc.

IMGN632 is a novel conjugate of anti-CD123 antibody with mono-imine containing Indolinobenzodiazepine payload. Unlike other conjugates (including ADCs with proven clinical success), only IMGN632 demonstrated potent anti-leukemic activity at the concentrations 100-fold lower the levels that impact normal human cells. The strategy to select an optimal antibody, payload, linker and conjugation method to achieve this uniquely wide therapeutic window will be covered in the presentation.

12:05 pm ADC Pumping into Solid Tumors Boosts Drug Potency and Efficacy

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

Current ADC can't deliver drugs inside solid tumors specifically, rapidly or robustly. Near MTD doses required to drive ADC across endothelial barriers are inadequate to unleash drug potency solely inside tumors. Off-target toxicities minimize therapeutic indices. We circumvent this passive transvascular delivery paradigm by utilizing caveolae pumping and the first antibody to actively penetrate tumors. Immunoconjugates concentrate imaging and therapeutic agents inside resistant and metastatic tumors, enabling precise imaging within 1 hr and boosting therapeutic indices >100-fold (<<<MTD eradication).

12:35 End of Engineering Antibody-Drug Conjugates

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

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