Engineering Antibody-Drug Conjugates

- 抗体药物复合体工程 -


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.

Final Agenda

5月5日(二)

Recommended Short Course*

SC9: Introduction to Biophysical Analysis for Biotherapeutics: Development Applications

*Separate registration required.

5月6日(三)

7:15 am Registration and Morning Coffee

7:25 Women in Science Panel Discussion with Continental Breakfast

Moderator:
Rochard_LucieLucie Rochard, PhD, Liaison, Scientific & Entrepreneurial Initiatives; Director, Innovation Services, Massachusetts Biotechnology Council


Panelists:
Nora MinevaNora Mineva, PhD, CSO, Adecto Pharmaceuticals


Tina Liu, MBA, Co-Founder and CEO, Ally Therapeutics

Jennifer Chadwich, PhD, Vice President, Biologic Development, BioAnalytix, Inc.

ENGINEERING THE ANTIBODY EFFECTOR MOIETY

8:40 Chairperson’s Opening Remarks

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

8:50 Antibody-Drug Conjugates (ADCs) and Small-Molecule Drug Conjugates (SMDCs): A Comparative Analysis

Neri_DarioDario Neri, PhD, Professor, Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (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.

9:20 Targeted C’Dot-Drug Conjugates for the Treatment of Cancer

Adams_GregGreg 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.

9:50 Antibody Fragment Drug Conjugates (FDCs): Expanding the Target Repertoire

Deonarain_MahenraMahendra 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.

10:20 Coffee Break in the Exhibit Hall with Poster Viewing

10:30 Women in Science Speed Networking in the Exhibit Hall

ADCs TARGETING THE TUMOR MICROENVIRONMENT

11:00 Chairperson’s Opening Remarks

Anton Neschadim, PhD, MBA, CEO, ImmunoBiochem Corporation

11:05 Probody™ Therapeutics in the Treatment of Cancer

Schleyer_SiewSiew Schleyer, PhD, Director, Oncology Research, CytomX Therapeutics

Probody 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 and T cell-engaging bispecifics, with a focus on antibody-drug conjugates.

11:35 TM4SF1: An Attractive Vascular and Tumor Cell Target for Antibody-Drug Conjugate Therapy

Jaminet_ShouChingShou-Ching Jaminet, PhD, Founder & Head of Research, Angiex, Inc.

TM4SF1 was discovered as a tumor cell antigen and anti-TM4SF1 drugs were tested clinically in the 1990s. Angiex founders identified TM4SF1 as an endothelial biomarker with a novel internalization route and an essential role in angiogenesis. TM4SF1’s highly specific expression in tumor cells and angiogenic endothelial cells, and its unusual internalization biology, make it an attractive target for antibody-drug conjugate (ADC) therapy. Angiex’s anti-TM4SF1 ADC is currently in preclinical development with promising animal data.

12:05 pm IMB-213: A Novel Secretome-Targeted Biologic for the Selective Delivery of Immunomodulatory Payloads to Solid Tumors

Neschadim_AntonAnton Neschadim, PhD, MBA, CEO, 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.

12:35 Presentation to be Announced

1:05 Session Break

1:10 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

2:10 Session Break

SITE-SPECIFIC CONJUGATION AND LINKER TECHNOLOGIES

2:25 Chairperson’s Remarks

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

2:30 Conjugating Payloads to Native Antibodies without the Need of Any Prior Antibody Engineering in a Single or Two Steps

Spycher_PhilippPhilipp 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.

3:00 Linkers for Cysteine Based Site-Specific Preparation of Antibody Drug Conjugates with High Drug-to-Antibody Ratio

Kumar_AmitAmit Kumar, PhD, Scientist I, Antibody Discovery and Protein Engineering, AstraZeneca

First generation of cysteine-based site-specific antibody drug conjugates (ADCs) are limited to two drugs per antibody. However, there are applications that require high DAR, such as when using low potent payloads. Here, we describe the design and validation of multifunctional linkers that can be used for the preparation of ADCs with DAR of two, three and four in a site-specific manner per single cysteine conjugation site, resulting in site-specific ADCs with DAR of four, six and eight.

3:30 Sponsored Presentation (Opportunity Available)

4:00 Refreshment Break in the Exhibit Hall with Poster Viewing

5:00 Problem-Solving Breakout Discussions - View All Breakout Discussion Topics

TABLE: Understanding Heterogeneity of Antibody Distribution in Human Tumors and Implications for Antibody Drug Conjugates

Moderator: Eben Rosenthal, MD, Cancer Center Medical Director, Otolaryngology, Stanford University

  • What tumor-related biomarkers are associated with modulation of antibody delivery
  • How can interventions be designed to increase the delivery of antibodies and antibody drug conjugates to target site(s), but avoid off-target effects?
  • What is the relationship between tumor burden/size or vessel fraction with the antibody delivery?
  • What aspects of tumor heterogeneity are the most important to determining delivery of antibodies and antibody drug conjugates

TABLE: Antibody Engineering Approaches to Improve the Therapeutic Index of ADCs

Moderator: Dhaval K. Shah, PhD, Assoc Prof, Pharmaceutical Sciences, University of 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?

TABLE: ADC Targets and Payloads: When Friends Become Foes

Moderator: Rakesh Dixit, PhD, DABT, 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

6:00 Taste of New England Networking Reception in the Exhibit Hall with Poster Viewing

7:15 End of Day

5月7日(四)

8:00 am Registration and Morning Coffee

8:30 Chairperson’s Remarks

Robert Lutz, PhD, CSO, Iksuda


8:35 KEYNOTE PRESENTATION: Ugly Ducklings: Why Clinically Effective Antibody-Drug Conjugates May Not Look that Pretty (at First)…And How to Spot Them

Thurber_GregGreg Thurber, PhD, Associate Professor, Chemical Engineering and Biomedical Engineering, University of Michigan

The antibody drug conjugate (ADC) landscape has changed significantly as lessons from the clinic have returned to the bench. Here, I present a ‘systems’ approach for designing ADCs and describe when the most potent ADC in vitro, the most effective ADC in vivo, and/or the least toxic ADC in animal models may not be the most effective drug in the clinic. This ‘systems’ approach can help ensure the most clinically effective agents, often ‘ugly ducklings’ in the pipeline, thrive in the end.

NEW & SPECIALTY PAYLOADS

9:05 NBE-002, an Anthracycline-Based Immune-Stimulatory Antibody Drug Conjugate (iADC) Targeting ROR1 for the Treatment of Triple-Negative Breast Cancer

grawunder_UlfUlf Grawunder, PhD, CEO, NBE Therapeutics

We present NBE-002, a novel ROR1-targeting ADC based on Sortase A-mediated, site-specific conjugation of a derivative of the highly potent anthracycline PNU-159682. NBE-002 is a highly effective and promising targeted therapeutic for the treatment of ROR1-positive TNBC and other solid tumor indications, warranting clinical development. Due to the pronounced immune-modulatory functions of the PNU payload, NBE-002 is particularly well suited for combination therapy with immune checkpoint inhibitors.

9:35 Presentation to be Announced

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

11:05 Development of Novel Payloads for Next-Generation ADCs

Lutz_BobRobert Lutz, PhD, CSO, Iksuda

Tubulin inhibitor payloads have been the mainstay of ADC development over the history of this modality; however, despite favorable biophysical properties and intrinsic selectivity of these compounds for tumor cells, the early successes of brentuximab vedotin and trastuzumab emtansine have not foreshadowed a deluge of approvals using payloads targeting tubulin. New payloads, with alternate mechanisms of actions, have been of foremost focus for recent efforts, with successful clinical data emerging. Iksuda is developing a portfolio of novel payloads aiming to improve clinical outcomes for ADC-based therapies.

11:35 Engineered Avibodies (Enhanced Diabodies) Precisely Loaded with Novel ADC Payloads that Surpass IgG-ADCs in Cancer Therapy

Hudson_PeterPeter Hudson, FTSE, PhD, Chief Scientist and CSO, 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.

12:05 pm HDP-101: Overcome Resistance Mechanisms to Establish New Treatment Options for Difficult to Treat Cancers

Hechler_TorstenTorsten Hechler, PhD, Vice President, ADC Research, Biochemistry, Heidelberg Pharma

HDP-101 an antigen-targeted amanitin-conjugate (ATAC) directed against BCMA introduces a new mode of action into oncology therapy. The inhibition of RNA polymerase II facilitates killing of dormant tumor cells (CSCs, TICs) and offers new treatment options for difficult-to-treat cancers. The unique MoA in combination with a demonstrated safety profile and a biomarker for patient selection might pave the way for accelerated development & approval for patient groups with high therapeutic needs. HDP-101 represent a new class of ADCs using Amanitin and is the first ATAC of HDP’s technology platform entering Phase I trials by 2020.

12:35 End of Engineering Antibody-Drug Conjugates


Recommended Short Course*

SC13: Design Strategies and Development of ADCs

*Separate registration required.

* 活动内容有可能不事先告知作更动及调整。

Choose your language
Chinese
Japanese
Korean
English





显示切换



免费电子邮件通知服务