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From novel payloads to new linkers and conjugation methods, ADC development has reached a new height. Companies are pushing the envelope in ADC design and optimization to achieve the desired properties such as homogeneity and DAR, and to improve the therapeutic index. New formats such as alternate or non-antibody protein conjugates are also making headway into the next generation ADC space. This is the moment for ADC developers.

The goal of CHI’s Fifth Annual Engineering ADCs is to bring together these cutting-edge technologies, novel concepts and creative engineering that puts ADC on the map as one of the most promising therapeutics for this decade.


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Recommended Pre-Conference Short Course* 

SC12: Production Challenges for Complex Biologics - ADCs, Bispecifics & Fusion Proteins 

*Separate registration required.


WEDNESDAY, MAY 6

7:00 am Registration and Morning Coffee


Novel Payloads & Linkers 

8:00 Chairperson’s Remarks

Peter Park, Ph.D., Vice President, Biology, Mersana Therapeutics


8:10 KEYNOTE PRESENTATIONS

Lessons from Kadcyla™: The Future of ADCs in Oncology and Beyond

Fred Jacobson, Ph.D., Staff Scientist, Kadcyla™ Technical Development Leader, Protein Analytical Chemistry, Genentech, Inc.

 

8:40 Fleximer Next-Generation ADCs: Creating ADCs for Low Expression Targets and Improving Therapeutic Index

Timothy Lowinger, Ph.D., Senior Vice President and CSO, Mersana Therapeutics

Mersana has developed novel, next-generation antibody-drug conjugation platforms which enable the creation of highly differentiated ADCs for a variety of solid tumor targets and that overcome many of the limitations of existing ADC approaches. The development and application of Mersana’s Fleximer-based Dolaflexin ADC platform will be described, and its potential to address low-expression antigens and potentially improve clinical outcomes for a variety of cancer patients will be highlighted.

9:10 Drug and Cytokines: Synergistic Payloads for Monoclonal Antibodies

Dario Neri, Ph.D., Professor, Department of Chemistry and Applied Biosciences, Swiss Federal institute of Technology (ETH Zurich)

This presentation will illustrate preclinical and clinical experience, gained in collaboration with Philogen, related to the development of human antibodies which target components of the pathological extracellular matrix and which can be “armed” with cytotoxic drugs and/or with cytokines. A comparative analysis will be presented.

9:40 Cancer Stem Cell Targeting with Antibody-Drug Conjugate Payloads and Linker Technologies

Unpublished DataRiley Ennis, Ph.D., Thiel Fellow, Cell and Molecular Biology, Dartmouth College and Co-Founder, Oncolinx

A challenge with current antibody-drug conjugates (ADCs) is to improve patient outcomes by circumventing drug resistance, disease recurrence, and cancer stem cells. We explore a novel cytotoxic payload, Azonafides, that can be integrated into ADC platforms. This cytotoxin is more stable in circulation, has unique mechanisms of action, and is derived from natural products. Azonafides create an exciting clinical opportunity to improve the therapeutic window, efficacy, and safety of ADCs.

10:10 Homogeneous ADCs Bearing Two Different Payloads Show Strong Synergistic Killing Effect in vivo

Sean Hu, Ph.D., Senior Vice President, Biotherapeutics Discovery, Dophen Biomed

Two different toxins were conjugated site-specifically to the endogenous glutamine residues of one mAb molecule by engineered transglutaminase in a single step reaction at >95% yield. Such a homogeneous hybrid (ADC) displays strong synergy in tumor cell killing in both in vitro cell based assays and xenograft mice in comparison to ADCs with each toxin individually.

10:40 Coffee Break in the Exhibit Hall with Poster Viewing

11:25 A pH-Tunable Linker: The Next Generation of Versatile Linkers for ADC

Unpublished DataCindy Jan Choy, Ph.D., Postdoctoral Researcher, Chemistry, Washington State University

We have discovered a novel pH-sensitive chemical linker scaffold that can be tuned to release molecules at various pH values. The tunability of a pH-triggered phosphoramidate linker is advantageous for intracellular drug release because it allows the tailoring of the drug release profile to meet specific application needs; an attribute that is absent in current linker technologies. In addition, the pH-triggered phosphoramidate linker does not require intracellular enzymatic action to initiate drug release from the ADC.

11:55 Enabling Splicing Inhibitors as ADC Payloads

Chakrapani Subramanyam, Ph.D., Associate Research Fellow, Worldwide Medicinal Chemistry, Pfizer R&D

Antibody-drug conjugates (ADC’s) for the treatment of refractory malignancies is an area of intense focus across the pharma industry and to date more than 30 ADC’s are in clinical trials. A majority of these utilize microtubule inhibitors (MTI’s) such as Auristatin or Maytansine as the payload. Discovery of novel payload class to further advance this field would undoubtedly enhance the utility of the antibody-drug conjugate based anticancer drugs. This talk will focus on the discovery and enablement of a novel class of spliceostatin-based splicing inhibitors as ADC payloads.

12:25 pm Presentation to be Announced

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

1:55 Session Break


Site-Specific Conjugation Technologies 

2:10 Chairperson’s Remarks

David Rabuka, Global Head, R&D, Chemical Biology, Redwood Bioscience

2:15 New Site-Specific, Traceless Antibody Conjugation Methodology

Unpublished DataGonçalo Bernardes, Ph.D., Group Leader, Royal Society University Research Fellow, Department of Chemistry, University of Cambridge

Our work explores the interplay between effector molecules, targeting ligands and site-specific protein conjugation chemistry to create safer, more selective and efficient cancer therapeutics. This lecture will cover recent examples of emerging areas in our group in (i) site-specific modification of antibodies via Aza-Michael addition at chemically installed dehydroalanine residues – a new traceless drug-release strategy at slightly acidic pH and (ii) use of carbon monoxide (CO) as an immunomodulator signalling molecule for applications in cancer therapeutics.

2:45 Engineering Site-Specific ADCs

Pam Thompson, Ph.D., Scientist I, Antibody Discovery and Protein Engineering, MedImmune

Antibody-Drug Conjugates (ADCs) are commonly produced by conjugating cytotoxic drugs to antibodies through lysine side chains or native cysteine thiols, which yield heterogeneous conjugates with complex biophysical properties. To limit these liabilities, we have designed, characterized, and validated antibody variants which allow precise control of the site of conjugation. The strategies presented herein for engineering site-specific ADCs allow for controlled drug loads, optimal serum stability, and potentially decreased off-target toxicity.

3:15 Sponsored Presentation (Opportunity Available)

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

4:45 Site Specific ADC Generation Using SMARTag™ Technology

David Rabuka, Global Head, R&D, Chemical Biology, Redwood Bioscience

  • Enabling precise, and programmable, site-specific chemical protein modification
  • The development of novel conjugation chemistry resulting in ADCs with enhanced stability
  • Linker chemistry that optimises the potency of the cytotoxic payload

5:15 Site-Specific Conjugation by BTG Improves the Therapeutic Index of ADC In Vivo

Florence Lhospice, PharmD, Director, Pharmaceutical Operations, R&D, Innate Pharma

We describe the in vitro and in vivo characterization of four novel ADCs that are based on the anti-CD30 antibody cAC10, which has the same polypeptide backbone as ADCETRIS®, and compare the results with the latter. Bacterial transglutaminase (BTG) was exploited to site-specifically conjugate derivatives of monomethyl auristatin E (all comprising a cleavable linker) to the glutamines at position 295 and 297 of cAC10, thereby yielding homogeneous ADCs with a DAR of 4. The results suggest that homogenous BTG ADCs display improved pharmacokinetics and better therapeutic indexes compared to chemically modified ADCs with variable DARs.

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

7:00 End of Day


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THURSDAY, MAY 7

8:00 am Morning Coffee


ENGINEERING ADCs FOR IMPROVED PROPERTIES 

8:30 Chairperson’s Remarks

Andreas Pahl, Ph.D., CSO, Heidelberg Pharma

8:35 Engineering of Amanitin-Based ADCs to Improve the Therapeutic Index

Andreas Pahl, Ph.D., CSO, Heidelberg Pharma

Payloads of today’s ADCs are exclusively based on compounds acting on microtubules or DNA suffering from various limitations. New generations of payloads enter the field including Heidelberg Pharma’s amanitin, a highly effective inhibitor of the eukaryotic RNA Polymerase II. Due to its unique mode of action and its hydrophilicity this toxin differs from well-known payloads. We will present new developments on engineering amanitin-based ADCs to improve the tolerability thereby improving the therapeutic index.

9:05 An EGFR Targeting Antibody-Drug Conjugate Engineered for Increased Tumor Specificity

Unpublished DataChristopher Thanos, Ph.D., Director, New Molecular Entities, New Molecular Entities, Halozyme Therapeutics

Cancers with KRAS/BRAF mutations and EGFR+ genotypes are resistant to EGFR targeting agents and are a significant unmet medical need. We hypothesized that an anti-EGFR ADC could be active against these tumors. In an effort to eliminate the known dermal toxicity associated with anti-EGFR therapy, we engineered an EGFR targeting mAb with significant binding to EGFR+ tumors and attenuated binding to human skin in murine xenografts. The corresponding ADC demonstrated significant activity against multiple KRAS/BRAF mutated tumors in vivo, suggesting a possible new approach for treatment over a broad range of tumor types.


New Formats & Designs - Next Gen ADCs, Alternative and Non Antibody Protein Conjugates 

9:35 Meditopes: Development of Noncovalent Peptide-Fab Interaction to Rapidly and Specifically Add Functionality to mAbs

John C. Williams, Ph.D., Associate Professor, Molecular Medicine, Beckman Research Institute at City of Hope

mAbs require chemical conjugation and/or extensive re-engineering to deliver toxins, imaging agents and other functionalities to diseased tissues. Herein, we present the discovery of a novel cyclic peptide (aka a meditope) that binds to the cavity of cetuximab Fab. While this binding site is unique to cetuximab, it can be grafted on to mAbs. Studies will be presented highlighting the rapid and efficient functionalization of mAbs.

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

11:05 Peptide-ADCs Cross the Blood-Brain Barrier and Extend Survival in Mice with Intracranial HER2-Positive Tumors

Jean Lachowicz, Ph.D., CSO, R&D, Angiochem

ADC therapy for metastatic brain tumors requires that the mAb crosses the blood-brain barrier. We have successfully engineered peptides (Angiopeps) which utilize Receptor-mediated transcytosis to enter brain. A three-way conjugation between Angiopep, cytotoxic and mAb results in a targeted cytotoxic that can reach tumors in the brain. Survival studies in mice with brain-implanted tumor cells were conducted to select the optimal peptide/linker/payload combination, which resulted in significant improvement in survival.

11:35 OptiLinked Antibody Fragments for ADCs

Ioanna Stamati, Ph.D., Team Leader, Bioconjugation, Antikor Biophama Ltd.

Fragment based ADCs offer the prospect of a wider therapeutic window due to a controllable PK profile and better tumour penetration. Using OptiLinked anti-HER2 scFvs high DAR (=12) ADCs were synthesised using various payloads. These retained solubility and exhibited limited/no aggregation even at high DAR. This is further demonstrated by the in vivo PK profile of the ADCs which is similar or slower to that of the free antibody.

12:05 pm Presentation to be Announced

Volker Schellenberger, Ph.D., President and CEO, R&D and Strategy, Amunix, Inc.

12:35 End of Conference

5:15 Registration for Dinner Short Courses



Recommended Dinner Short Course* 

SC13: Physicochemical and Biophysical Characterization of Antibody-Drug Conjugates 

*Separate registration required


Day 1 | Day 2 | Download Brochure | Register