ADC


The complexity of antibody-drug conjugates with its many moving parts makes this field incredibly challenging yet full of potential for innovation. From novel targeting ligands to new conjugation methods, from multiple payloads to changing the drug-antibody ratio, all these are challenging the convention for the design and development of next-generation ADCs. At Antibody-Drug Conjugates I: New Ligands, Payloads and Alternative Formats, we invite scientists to present their new technologies and showcase how they are redefining the rules in the field of ADCs.

Continue your exploration of the antibody-drug conjugates field by attending the accompanying meeting, Antibody-Drug Conjugates II: Advancing toward the Clinic on April 28-29.

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WEDNESDAY, APRIL 27

7:00 am Registration and Morning Coffee

8:00 Chairperson’s Remarks

Christopher D. Thanos, Ph.D., Senior Director, Biotherapeutics Discovery, Halozyme Therapeutics, Inc.


8:10 KEYNOTE PRESENTATION:

Determination of Cellular Processing Rates Points to Key Parameters for Antibody-Drug Conjugate Design

K_Dane_WittrupK. Dane Wittrup, Ph.D., C.P. Dubbs Professor, Chemical Engineering & Biological Engineering, Associate Director, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology

Numerous processing steps occur before the active drug component of an ADC can reach its intracellular target. Increased understanding of ADC cellular processing may facilitate more rational design of ADCs. In this work, we present a generalizable method to determine kinetic parameters, which can be used in a basic model for cellular processing of ADCs and can be incorporated into larger scale pharmacokinetic/pharmacodynamic models.

8:40 KEYNOTE PRESENTATION:

Combining Antibody-Drug Conjugates and Immune-Mediated Cancer Therapy: What to Expect?

Hans-Peter GerberHans-Peter Gerber, Ph.D., Vice President, CSO, Bioconjugates Discovery & Development, Oncology Research Unit East, Pfizer Worldwide Research & Development

Toxins targeting DNA like anthracyclines or tubulin poisons like vinblastine can stimulate the innate immune system. When combined immuno-oncology (IO) compounds, both classes of toxins further enhanced the adaptive immune response and improved the anti-tumor responses. Therefore, identification of optimal combination regimens between ADCs employing different classes of toxins and IO compounds holds strong promise to overcome the key limitations of current immune checkpoint inhibitors, by increasing the recruitment and infiltration of CD8+ effector T cells to the tumor.


ALTERNATIVE FORMATS AND NEW TARGETING LIGANDS

9:10 Small Ligand-Targeted Drug Conjugates: An Alternative to ADCs

Phillip_LowPhilip S. Low, Ph.D., Director of the Purdue Center for Drug Discovery, Ralph C. Corley Distinguished Professor, Department of Chemistry, Purdue University

We have developed small molecule ligands for use in targeting attached drugs to pathologic cells, thereby avoiding collateral toxicity to healthy cells. We have also developed low molecular weight targeting ligands to deliver attached drugs selectively to cancers that over-express PSMA, CCK2 receptor, neurokinin 1 receptor, carbonic anhydrase IX , and several other tumor-specific receptors. Finally, ligand-targeted imaging and therapeutic agents for autoimmune, inflammatory, and infectious diseases (e.g. malaria, rheumatoid arthritis, multiple sclerosis, psoriasis, atherosclerosis, osteoarthritis, etc.) will also be described.

9:40 Targeted Protein Therapeutics (TPTs) for the Treatment of Cancer

Greg_AdamsGreg Adams, Ph.D., Chief Development Officer, Viventia Biotech

TPTs are fully biologic constructs containing antibody fragments and protein toxin payloads in a single engineered molecule. The preclinical/clinical development of TPTs employing fully deimmunized payloads for the treatment of systemic disease and non-deimmunized payloads for use in the treatment of loco regional disease will be discussed.

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

10:55 Development of Probody-Drug Conjugates Targeting Highly Expressed Tumor Antigens

Jon Terrett, Ph.D., Vice President, Oncology CytomX

PDCs are antibody prodrugs that are designed to be activated in tumors while avoiding binding to normal tissues. PDCs can safely enable targeting of antigens with broad, persistent & very high expression in cancer that are also expressed in normal tissues, and therefore cannot be approached with traditional Antibody-Drug Conjugates. Such targets can show >70% prevalence at 3+ expression in many cancer types. Preclinical proof of concept for safety, efficacy & developability of PDCs to high expression targets will be shown.

11:25 Immunomodulation by CO Delivered from Artificial Metalloproteins

Goncalo_BernardesGoncalo J.L. Bernardes, Ph.D., Chemistry, University of Cambridge

A new class of therapeutic metalloproteins allows for the controlled and targeted delivery of carbon monoxide (CO) into tumors. When administered into tumor bearing mice, the CO-releasing metalloproteins result in strong tumor growth retardation. The CO-mediated effect is due to the combined downregulation of important angiogenic factors as well as activation of CD8 cytotoxic T cells. Finally, when used in combination with current standard of care chemotherapeutic drugs, the novel CO immune-modulation treatment results in cancer cures in mice.

11:55 Drug Conjugation and Delivery Enabled by a Tumor-Targeting Peptide-Fc Fusion

Jennifer_ChochranJennifer Cochran, Ph.D., Associate Professor, Bioengineering, Stanford University

We are creating novel peptide-drug conjugates for targeted delivery of chemotherapeutic agents to tumors. As an example, an integrin targeted peptide-Fc fusion, conjugated to an auristatin derivative, was effective as a single agent at inducing regression and prolonged survival in tumor xenograft models. These studies provide proof-of-concept for further development of peptide-drug conjugates as attractive alternatives to ADCs for tumor targeting and drug delivery applications.

12:25pm Sponsored Presentation (Opportunity Available)

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

1:55 Session Break


NOVEL APPLICATIONS OF ADCS

2:10 Chairperson’s Remarks

Hans-Peter Gerber, Ph.D., Vice President and CSO, Bioconjugates Discovery & Development, Oncology Research Unit East, Pfizer Worldwide R&D

2:15 Development of a Novel Protease Cleavable Linker for Anti-Staphylococcus Aureus Antibody-Antibiotic Conjugates

Martine_DarwishMartine Darwish, MSc, Senior Scientific Researcher, Protein Chemistry, Genentech

Antibody-Antibiotic Conjugates (AACs) employ an antibody specific for cell wall components of Staphylococcus aureus conjugated with a potent antibiotic. We describe the development of a peptide linker that is cleaved by staphopain B, a secreted endopeptidase of S. aureus. The resultant AAC has demonstrated efficacy in in vitro and in vivo models of MRSA infection, providing a novel mechanism by which to target MRSA infections and release payload in a disease specific manner.  

2:45 Tau-Specific Single Domain Antibody-Nanoparticle Complex as Biomarker for Traumatic Brian Injury

Mehdi_ArabiGhahroudiMehdi Arbabi Ghahroudi, Ph.D., Research Officer/Research Scientist, Human Health Therapeutics, National Research Council Canada

Tau, a microtubule-associated protein, accumulates in the brain following traumatic brain injury and neurodegenerative diseases. We identified a single-domain antibody, specific for tau and its hyper-phosphorylated form. Here we demonstrate that this antibody fragment, conjugated to an MR visible nanoparticle, can cross the primary hippocampal neuronal membrane in vitro and bind to intracellular tau. This is the first step towards a new, non-invasive method of detecting tau deposition in patients.

3:15 Developing Site-Specifically Modified ADCs Using a Chemoenzymatic Approach

David Rabuka, Global Head, Research & Development, Chemical Biology, Catalent Pharma Solutions

Antibody-drug conjugates (ADCs) have become de rigueur for pharmaceutical oncology drug development pipelines. We have developed the SMARTagTM technology platform, which enables precise, programmable, site-selective chemical protein modification. We will highlight progress in developing these SMARTagTM ADCs with a focus on preclinical studies as well as highlight our progress in cell line development and manufacturing of bioconjugates using this chemoenzymatic approach.


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

4:45 Problem-Solving Breakout Discussions

  • The pros and cons of large and small molecular weight ligand-targeted drug conjugates
  • Philip S. Low, Ph.D., Director of the Purdue Center for Drug Discovery, Ralph C. Corley Distinguished Professor, Department of Chemistry, Purdue University

    • The large size of ADCs assures a large AUC but limits tumor penetration. Which property is most important for therapeutic efficacy? Is there an optimal ligand size that yields the best AUC and tumor penetration?
    • Is AUC important when the number of targeted receptors is limited? How does receptor recycling rate impact this answer?
    • Is there a relationship between targeted receptor number and the potency of the targeted cytotoxic drug required for therapeutic efficacy?
    • How can one design a linker in a ligand-targeted drug conjugate that is stable in circulation and cleavable upon endocytosis into the diseased cell?
  • ADCs : Past, Present and Future
  • Peter Hofland, Ph.D., Managing Partner, Publisher and Executive Editor, ADC Review

  • Topic to be Announced
  • Greg Adams, Ph.D., Chief Development Officer, Viventia Biotech

  • Topic to be Announced
  • Christopher D. Thanos, Ph.D., Senior Director, Biotherapeutics Discovery, Halozyme Therapeutics, Inc.

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

7:00 End of Day

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THURSDAY, APRIL 28

8:00 am Morning Coffee


ENGINEERING AND CONJUGATION CHEMISTRY TO IMPROVE PROPERTIES OF ADCs

8:30 Chairperson’s Remarks

Greg Adams, Ph.D., Chief Development Officer, Viventia Biotech

8:35 Engineering a Tumor-Specific, Next-Generation Anti-EGFR ADC Development Candidate

Chris_ThanosChristopher D. Thanos, Ph.D., Senior Director, Biotherapeutics Discovery, Halozyme Therapeutics, Inc.

 

 

 

9:05 HSP90 Inhibitor Drug Conjugates (HDCs): A Novel Conjugation Platform

Alan_RigbyAlan Rigby, Ph.D., CSO and Senior Vice President, Synta Pharmaceuticals

I will discuss an innovative strategy that utilizes HSP90 inhibitor-drug conjugates (HDC) for the purpose of directed intratumoral targeting of chemotherapeutic agents. STA-12-8666 is a first in class HDC that is comprised of an HSP90 inhibitor fused to SN-38, the active metabolite of irinotecan. We have observed intratumoral payload release by STA-12-8666 that contributed to a broad therapeutic window, sustained biomarker activity, and remarkable degree of efficacy and durability of response in multiple in vivo cell line and patient-derived xenograft models.

9:35 Sponsored Presentation (Opportunity Available)

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

11:05 A Plug-and-Play Approach to Antibody-Based Therapeutics via a Chemoselective “Dual Click” Strategy

Vijay_ChudasamaVijay Chudasama, Ph.D., MSc, Lecturer, Chemistry, University College London

There is a clear demand for the construction of novel antibody-drug conjugate (ADC) platforms that offer greater stability, homogeneity and flexibility. A significant step towards the ideal platform for next generation antibody-based therapeutics is presented. Our technology provides decorated antibody constructs that are highly stable, with complete retention of antibody binding/structure post-modification. It combines site-specific functionalisation with exceptional versatility via the functional re-bridging of interchain disulfide bonds native to antibodies.

11:35 Improving the Therapeutic Window of an Antibody-Drug Conjugate by a New Stable Conjugation Method

Sanghoon_LeeSang Hoon Lee, Ph.D., CEO and Founder, ABL BIO

To overcome the limitation of ADC due to off-target toxicity and narrow therapeutic window, we have developed s new conjugation technique that attaches drugs to N-terminal of an antibody through amine bond by reductive alkylation reaction (NTERM). NTERM ADC showed superior in vitro and in vivo stability as well as tolerability than commonly used thiol-conjugate and lysine conjugate. Therefore, NTERM can be a novel conjugation method to improve therapeutic window.

12:05 pm A Non-Genetic Approach to ADCs with Improved Therapeutic Index with GlycoConnect™ and HydraSpace™ Technology

Floris_vanDelftFloris van Delft, Ph.D., Co-Founder and CSO, Synaffix

GlycoConnect™ is a highly efficient technology to obtain, without protein engineering, antibody-drug conjugates (ADCs) in a two-stage process involving (a) enzymatic N-glycan remodeling and (b) copper-free click attachment of payload. Conjugation of highly hydrophobic payloads is accommodated with polar HydraSpace™ technology. Excellent in vivo efficacy and high tolerability is demonstrated, thus paving the way for the next generation of ADCs with an improved therapeutic index.

12:35 End of Antibody-Drug Conjugates I: New Ligands, Payloads and Alternative Formats

5:15 Registration for Dinner Short Courses


Recommended Dinner Short Course*

SC13: Critical Considerations for the Design and Development of Antibody-Drug Conjugates

*Separate registration required.


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