Next-Generation Antibody-Drug Conjugate banner

- 抗体药物复合体 -

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. The “Next-Generation Antibody-Drug Conjugates” conference explores the engineering finesse required to achieve improved therapeutics while adhering to the underlying biology that research has uncovered, showing the way to more potent and efficacious 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

MONDAY 12 NOVEMBER | 09:00 - 12:00 | MORNING

Recommended Short Course*

SC2: Making Antibody Libraries in Phage and Yeast

Andrew R.M. Bradbury, MB BS, PhD, CSO, Specifica, Inc.

In this short course, students will learn about antibody basics, including structure, genetics and the generation of diversity, as well as the creation of naive antibody libraries in the phage and yeast display formats. This will include a description of phage and yeast display technologies, the creation of naïve libraries from natural and synthetic sources. The seminar will be fully interactive with students provided ample opportunities to discuss technology with instructors.

*Separate registration required.

MONDAY 12 NOVEMBER

12:00 Conference Registration


FIGHTING CANCER WITH ADCs

13:30 Organizer’s Welcome

Mary Ruberry, Senior Conference Director, Cambridge Healthtech Institute

13:35 Chairperson’s Opening Remarks

Christian P. R. Hackenberger, PhD, Professor and Department Head, Chemical Biology II, Leibniz-Research Institute for Molecular Pharmacology (FMP) and Humboldt University Berlin

13:45 FEATURED PRESENTATION: Delineating the Role of Normal Tissue Target Expression on PK and Anti-Tumor Activity with a Mouse Cross-Reactive ADC

Pinkas_JanJan Pinkas, PhD, Vice President, Translational Research & Development, ImmunoGen, Inc.

We have developed a mouse cross-reactive ADC that we have employed to understand the role of normal tissue target expression on PK and anti-tumor activity. Our findings are broadly applicable to the development of ADCs for solid tumor targets. In this talk, I will share the data that has been generated.

14:15 Clinical and Preclinical Evaluation of Anti-Tumor Antibody-Toxin Fusion Proteins

Adams_GregGregory P. Adams, PhD, CSO, Eleven Biotherapeutics, Inc.

Anti-tumor antibody fragments genetically fused to protein toxins that block translation can overcome many of the limitations of current generation ADCs. Their ability to drive immunogenic cell death and potentially stimulate host anti-tumor immune responses also makes them attractive candidates for combination with immuno-oncology agents. Preliminary results from an ongoing mono therapy Phase III clinical trial in patients with high-grade non-muscle invasive bladder cancer will be presented along with preclinical results of earlier-stage agents.

14:45 Radionuclide Therapy Using Peptide Nucleic Acid (PNA)-Mediated Pretargeting of HER2-Expressing Tumors

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

In vivo pretargeting is a promising approach to reduce unfavorable biodistribution leading to side effects during treatment with radiolabeled tumor-targeting antibodies or alternative scaffold proteins. We have developed a concept where the primary, tumor-targeting agent is conjugated to a peptide nucleic acid (PNA) strand, which binds with high affinity to a secondary, radiolabeled, complementary PNA strand. We also applied the same pretargeting system to tumor targeting with the monoclonal antibody trastuzumab and demonstrated a high contrast between tumor and non-tumor tissue.

15:15 Sponsored Presentation (Opportunity Available)

15:45 Networking Refreshment Break



PLENARY KEYNOTE SESSION

16:15 Moderator’s Opening Remarks

Janine Schuurman, PhD, Corporate Vice President, Research & Innovation, Genmab BV

 

 

 

 

16:20 Bicycles and Bicycle Drug Conjugates

Sir Gregory Winter, PhD, FRS, Master, Trinity College and Co-Founder and Director, Bicycle Therapeutics

Bicycles® are a novel therapeutic class of constrained bicyclic peptides that combine antibody-like affinity and selectivity with small molecule-like tissue penetration, tunable exposure and chemical synthesis. They have potential in many indications, including oncology, where Bicycles’ unique properties have been used to develop Bicycle Drug Conjugates™ (BDCs), a novel toxin delivery platform which greatly improves toxin loading into tumour tissues. A BDC is expected to enter clinical trial in Q1 2018.

17:20 Paracrine Delivery: Therapeutic Biomolecules Produced in Situ

Andreas G. Plückthun, PhD, Professor and Director, Department of Biochemistry, University of Zürich

Cancer will have to be fought with cocktails of therapeutics acting locally, which may have to include therapeutic antibodies against receptors, checkpoint inhibitors, as well as cytokines to modify the tumor microenvironment. We have recently developed a technology of using non-replicative adenovirus carrying no viral genes, engineered to target desired cells and also to be shielded from the immune response, as a vehicle for simultaneous delivery of multiple genes of therapeutic proteins, produced and secreted by the infected cells.

18:20 Welcome Reception in the Exhibit Hall with Poster Viewing

19:30 End of Day

TUESDAY 13 NOVEMBER

07:45 Registration and Morning Coffee


THE NEXT GENERATION OF ADCs

08:30 Chairperson’s Remarks

Pedro M.S.D. Cal, PhD, Postdoctoral Investigator, Instituto de Medicina Molecular, University of Lisbon


08:35 KEYNOTE PRESENTATION: Strategies & Challenges for the Next Generation of ADCs

Beck_AlainAlain Beck, PhD, Senior Director, Analytical Chemistry, NBEs, Centre d’Immunologie Pierre Fabre; Associate Editor, mAbs

The development of ADCs has benefited from general improvements in the design of therapeutic mAbs and from specific improvements in methods for conjugate synthesis. Diversification of linking strategies and warheads has provided new opportunities to improve drug delivery to tumors while reducing drug exposure to normal tissues. Protein structural characterization tools such as mass spectrometry are allowing better understanding of ADC structures, stability and biotransformations. This knowledge contributes to the identification of early-developability criteria for all of the ADC components.

09:05 The Power of Chemoselectivity: Powerful Conjugation Technologies for Next-Generation ADCs

Hechler_TorstenChristian P. R. Hackenberger, PhD, Professor and Department Head, Chemical Biology II, Leibniz-Research Institute for Molecular Pharmacology (FMP) and Humboldt University Berlin

We develop novel protein functionalization technologies for the generation of site-specific conjugates with high stability and defined activities. With Tub-tag labeling, we recently introduced a novel and versatile chemoenzymatic method for the C-terminal functionalization of biomolecules. It is based on the microtubule modifying enzyme tubulin tyrosine ligase (TTL) and facilitates one- or two-step functionalization procedures. Moreover, we have developed a new thiol-selective protein conjugation chemistry, that is characterized by strongly increased conjugate stability compared to previous approaches. Both methods are applied for the generation of defined ADCs with improved stability and potent cytotoxicity.

09:35 Problem-Solving Breakout Discussions

10:30 Coffee Break in the Exhibit Hall with Poster Viewing


POTENT PAYLOAD DESIGN

11:15 New Payloads for Antibody-Drug Conjugates

Pillow_ThomasThomas Pillow, PhD, Senior Scientist, Discovery Chemistry, Genentech, Inc.

This presentation will highlight the most recent work on ADCs at Genentech. It will cover our newest effort to deliver targeted protein degraders as a new modality for ADCs as well as new linkers developed to enable this platform.


11:45 Preclinical Validation of Site-Specifically Conjugated ADCs with Potent Anthracycline Payloads in Solid and Hematologic Tumor Models

Rémy Gébleux, PhD, Scientist II, NBE-Therapeutics Ltd.

I will address next-generation ADC technology with an update on preclinical development of our program NBE002, targeting ROR1 in TNBC and lung adenocarcinoma. My talk will cover the validation of a novel ultra-potent anthracycline-toxin in ADCs, including validation of NBE’s lead ADCs in preclinical tumor models, and the characterization of the immuno-oncology function of NBE’s ADCs. The audience will gain insights into both a novel site-specific conjugation platform as well as a highly potent payload technology.

12:15 Sponsored Presentation (Opportunity Available)

12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

13:45 Dessert Break in the Exhibit Hall with Poster Viewing


BREAKTHROUGH ADC ENGINEERING

14:15 Chairperson’s Remarks

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

14:20 Antibody Targeted Amanitin Conjugates (ATACs) - Expanding the ADC Landscape with a New Payload Targeting RNA Polymerase II

Hechler_TorstenTorsten Hechler, PhD, Vice President ADC Research, 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. 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.

14:50 Taming Random Conjugation: A General Approach for Equimolar Linking of Proteins and Payloads

Kolodych_SergiiSergii Kolodych, PhD, CSO, Syndivia SAS

Multiple conjugation sites are usually available on a biomolecule. Upon conjugation, they produce a mixture of species having different degrees of conjugation (DoC). We report a general conjugation approach for achieving a defined DoC, which is virtually applicable to any biological macromolecule and payload. Applied to native antibodies, the method yields highly homogenous antibody-drug conjugates, antibody-oligonucleotide conjugates as well as bispecific scaffolds.

15:20 Utility of PK-PD Modeling and Simulation (M&S) in the Discovery and Development of Next-Generation Immunoconjugates (ICs) for Cancer Therapy

Singh_AmanAman P. Singh, PhD, PK-PD Scientist/Biologics Development Leader, Janssen Biotherapeutics

We have experienced an expeditious emergence in the development of novel immunoconjugates (ICs) in cancer therapy, including the success of Antibody-Drug Conjugates (ADCs), with more than 60 molecules currently in clinical development, where the payload is designed to either inhibit the growth of replicating tumor cells (e.g., microtubule inhibitors) or intercalate with the DNA (e.g., DNA damaging agents). A more emerging subcategory of ICs includes radio-immunoconjugates (RICs), where DNA damaging alpha or beta ray emitting radionuclides are conjugated to antibodies.

15:50 Sponsored Presentation (Opportunity Available)

16:20 Refreshment Break in the Exhibit Hall with Poster Viewing


BREAKTHROUGH ADC ENGINEERING (CONT.)

17:00 Functional Disulfide Re-Bridging Enables Native Full Antibody DAR 2, 4 & 8 Formation, Site-Selective Orthogonal Dual Modification and Homogeneous Fragment Drug Conjugates, as well as Bi- and Tri-Specific Scaffolds

Chudasama_VijayVijay Chudasama, PhD, Lecturer, Chemistry, University College London

Our latest data on next-generation maleimide (NGM) and pyridazinedione (PD) reagents for the site-selective modification of antibodies will be detailed (including robust serum stability, in vitro selectivity, in vivo efficacy with options for DAR 2, 4 & 8, dual drug conjugates and fragment drug conjugates). Also presented will be our latest work on using chemical linkers to form bi- and tri-specific scaffolds, as well as applications to nanoparticle modification.

17:30 Site-Specific Antibody Functionalization at the Antibody NBS

Alves_NathanNathan J. Alves, PhD, Assistant Professor, Emergency Medicine and Biomedical Engineering, Indiana University School of Medicine

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 as diagnostic or tracking tools. 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.

18:00 Generation of Potent Anti-HER1/2 Immunotoxins by Protein Ligation Using Split Inteins

Kolmar_HaraldHarald Kolmar, PhD, Professor and Head, Applied Biochemistry, Technical University of Darmstadt

We developed a route for the generation of immunotoxins based on full length antibodies using self-splicing split inteins and were able to generate a set of specific and highly potent conjugates. Our robust and generic method for generation of immunotoxins relies on protein conjugation via split intein ligation. This strategy overcomes notorious problems with immunotoxin production and the resulting conjugates with intrinsic bivalency and longer in vivo half-life display promising properties for further clinical development.

18:30 End of Next-Generation Antibody-Drug Conjugates

* 活动内容有可能不事先告知作更动及调整。

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