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Bioconjugates: From Targets to Therapeutics

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Transitioning Innovation into Viable Therapeutic Candidates

May 18-20, 2015 | Parc 55 Hilton | San Francisco, CA

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Agenda

Agenda

  Download the Agenda-at-a-Glance PDF, featuring all 3 co-located events

Monday, May 18, 2015

7:00
Registration and Coffee

8:00
Chairperson's Remarks
Jennifer R. Cochran, Ph.D., Associate Professor of Bioengineering and Chemical Engineering, Stanford University

Keynote Presentations

8:15
Peter Senter, Ph.D.
Potent Antibody Drug Conjugates for Cancer Therapy
Peter Senter, Ph.D., Vice President,Chemistry, Seattle Genetics

8:45
Paul J. Carter, Ph.D.
Bispecific Antibodies - Are We There Yet?
Bispecific antibodies are coming of age with 2 approved for human therapy and >30 more in clinical development. Efficient production of bispecific IgG in a single host cell is challenging because of many potential unwanted chain pairings. Engineered Fab pairs have been combined with knobs-into-holes Fc mutations for more efficient production of bispecific IgG in a single host cell.
Paul J. Carter, Ph.D., Staff Scientist and Senior Director, Antibody Engineering, Genentech, Inc.

9:15
Andreas Plückthun, Ph.D.
New Engineering and Application Perspectives of Scaffold Proteins
Andreas Plückthun, Ph.D., Director, Department of Biochemistry, University of Zurich, Switzerland

9:45
Networking Refreshment Break in Poster and Exhibit Hall

10:10
Chairperson's Remarks
Alan Wahl, Ph.D., Vice President, Research and Discovery, Ambrx, Inc.

Exploring Novel and Emerging Payloads

10:15
ADCs: Leveraging Shared Learnings to Enable Next Generation Success
Alan C. Rigby, Ph.D., Vice President, ADC Biology, Eli Lilly and Company

10:45
New Payloads for ADCs: Challenges and Advancements
A majority of ADCs currently in clinical trials use a tubulin interacting agent (maytansinoids or auristatins) as the payload. There is considerable interest in developing payloads with alternative mechanisms of cell killing. The key requirements and challenges for payload development for ADCs will be discussed. The current status of new payloads along with data that support their further advancement will be highlighted.
Ravi J. Chari, Ph.D., Executive Director, Chemistry and Biochemistry, ImmunoGen, Inc.

11:15
Tuning the Efficacy of Antibody Drug Conjugates via Site-Selective Conjugation
The random linkage of drugs to targeting proteins is now eclipsed by new chemistries allowing both a defined number of payloads and discrete drug positioning on the protein's surface. Production cell lines engineered to incorporate reactive, non-natural amino acids into selectable sites in the antibody structure yield homogeneous, readily linkable antibody. Combining medicinal chemistry to select for optimal surface placement, conditionally stable linker chemistry and disease-selective warhead, an ADC of superior stability, potency and tolerability can be realized.
Alan Wahl, Ph.D., Vice President, Research and Discovery, Ambrx, Inc.

Featured Presentation

11:45
Tumor-Targeted Drug Delivery Via XTEN™, A Protein-Polymer Offering Precisely Controlled Structure and Valency
Amunix developed a hydrophilic protein-polymer (XTEN™) with long half-life in circulation that is rapidly degraded upon internalization. XTEN facilitates the orthogonal conjugation of multiple toxins and targeting moieties with precisely controlled stoichiometry. The hydrophilic nature of XTEN allows high drug loads and reduces toxicity resulting from non-specific internalization. XTEN-drugs can be linked to many tumor-specific ligands such as peptides, scaffolds, and antibody fragments and full antibodies.
Volker Schellenberger, Ph.D., President and CEO, Amunix Operating Inc.

12:15
Networking Luncheon in Poster and Exhibit Hall

1:25
Chairperson's Remarks
Karyn O'Neil, Ph.D., Senior Director and Venture Leader, Centyrex, Janssen R&D

Advances in Bioconjugate Development and Design

1:30
Centyrin Conjugates for Targeted Delivery
Centyrins combine the binding and specificity properties of antibodies with the stability, solubility and tissue penetration properties of small molecules. The excellent biophysical properties of Centyrins make them ideal bioconjugate applications. The in vivo stability and tolerability properties of Centryins together with their excellent site specific conjugation efficiency can be used to address some of the outstanding challenges for targeted drug delivery.
Karyn O'Neil, Ph.D., Senior Director and Venture Leader, Centyrex, Janssen R&D

2:00
Cysteine Arylation Enables Facile and Robust Bioconjugation
Bradley L. Pentelute, Ph.D., Pfizer-Laubach Career Development, Professor, Associate Member, Broad Institute of Harvard and MIT, Member, Center for Environmental Health Sciences MIT, Massachusetts Institute of Technology

2:30
Serum Half-life Extension by Site-specific Conjugation to Albumin's Natural Free Cysteine 34
Serum half-life extension by fusion to human serum albumin has recently been validated in the clinic. To augment this chemical conjugation to the thiol of cysteine 34 of native and variant sequence recombinant human serum albumin will be presented. In particular, the advantage of mono-bromo-maleimide versus standard maleimide will be discussed.
Mikael Bjerg Caspersen, Ph.D., Senior Professional, Novozymes Biopharma

3:00
Networking Refreshment Break in Poster & Exhibit Hall

Breakthroughs in ADC Discovery and Development

3:30
Making Homogeneous and Site-specific ADCs Directly from mABs in Your Fridge
Homogeneous ADCs, where toxins are conjugated site-specifically to the endogenous glutamine residues of any IgG1, IgG2 and IgG4 in their Fc regions, are prepared in a single step reaction catalyzed by engineered transglutaminase at >95% yield. Such a simple and quick site-specific conjugation method has enabled us to make ADCs out of any given toxin with an amine group and any intact mAB without the need of antibody re-engineering. We were able to optimize linker, toxin, and drug to antibody ratio quickly for a given antibody. Herceptin ADC, made as a showcase, is far more stable and potent than TDM-1 in mouse xenografts of BT474, SK_OV3, N87 and HCC1954. We also developed a formulation for intra-tumoral injection, which shows fast tumor remission than iv injection.
Sean Hu, Ph.D., Senior Vice President, Dophen BioMed

4:00
A pH-Tunable Linker: The Next Generation Of Versatile Linkers For ADC
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. This chemical linker scaffold is superior to current linkers because the release of the drug is tunable and requires no enzymatic action.
Cindy Choy, Post-Doctoral Researcher, Washington State University

4:30
Early Phase Formulation Development of Antibody Drug Conjugates (ADC) and its Intermediate Drug Substance, mAb
ADCs are a group of novel anti-cancer bio-therapeutics which contain a small molecular cytotoxic drug covalently attached to a target specific mAb via a peptide linker. While most mAb and peptide linkers are hydrophilic, most of the small molecular anti-cancer drug molecules are hydrophobic. This complex and also heterogeneous nature of ADCs often results in poor solubility, aggregation/self-association through hydrophobic interactions and chemical instability, and may lead to immunogenicity and other toxicities and loss of efficacy. Therefore, development of a stable, efficacious and safe formulation for ADCs is critical and more challenging than the standard protein formulation development. Chemical and physical stability of all three components, the mAb, linker and the drug in final lyophilized ADC drug product as well as in the liquid bulk drug substance are equally important. Here, we discuss a semi platform approach for early phase formulation development for ADCs of lgG1 and lgG2.
Ananda K. Seneviratne, Ph.D., Principal Scientist, Analytical and Formulation Development, Agensys, Inc.

5:00
Networking Cocktail Reception in Poster and Exhibit Hall

6:00
Dinner Discussions
(Additional registration fee required - see registration page for details)
Please join us for this highly interactive 3 hour evening exchange in a roundtable format, which encourages participants to share their experiences and concerns amongst several discussion topics that include:
  • GPCRs, Ion Channels and Other Membrane Targets - The Next Hot Targets! Why? What are the Challenges?
    Moderator: Catherine Hutchings, Ph.D., Antibody Alliance Management & Strategic Partnering, Heptares Therapeutics Ltd., United Kingdom
  • Delivery Approaches for Intracellular Biologics
    Moderator: Paul Watt, Ph.D., Chief Scientific Officer, Phylogica Ltd., Australia
  • Strategies for Plasma Half-Life Extension of Biopharmaceuticals
    Moderator: Arne Skerra, Ph.D., Professor, Chief Scientific Officer, XL-protein GmbH, Germany
  • Non-Antibody Targeting Moieties
    Moderator: Robert Lutz, Ph.D., Vice President, Translational Research and Development, ImmunoGen, Inc.
  • Clinical Translatability of Current ADC Programs: Does Patient Selection/Tailoring Improve Success
    Moderator: Alan C. Rigby, Ph.D., Vice President, ADC Biology, Eli Lilly and Company
  • Site-Specific Conjugation and its Progress Towards Clinical Development
    Moderator: Jagath Reddy Junutula, Ph.D., Vice President, Antibody Discovery & Development, Cellerant Therapeutics, Inc.
  • CRISPR's Influence on Therapeutic Development
    Moderator: Ben Haley, Ph.D., Scientist, Genentech
  • What Technological Breakthroughs will Make a Difference to Cell line Development: Enthusiasm Tempered by Realism
    Moderator: Alan Dickson, Ph.D., Professor of Biotechnology, Director, Centre of Excellence in Biopharmaceuticals, Co-Director, BioProNET, The University of Manchester, United Kingdom
  • Cell Line Authentication
    Moderator: Leonard P. Freedman, Ph.D., President, Global Biological Standards Institute
  • Smart Polymers as Drug Linkers and to Extend Half-Life
    Moderator: Volker Schellenberger, Ph.D., President and CEO, Amunix Operating Inc.

Tuesday, May 19, 2015

7:30
Coffee

8:00
Chairperson's Remarks
Joseph G. Joyce, Ph.D., Director, Vaccine Process Development, Merck Research Laboratories

Advances in Conjugated Vaccines

8:15
V114: Development of a 15-Valent Pneumococcal Conjugate Vaccine
Joseph G. Joyce, Ph.D., Director, Vaccine Process Development, Merck Research Laboratories

8:45
Development of a Malaria Transmission Blocking Vaccine as a Chemically Conjugated Nanoparticle
The current control strategy for elimination of malaria will benefit from the development of an effective malaria vaccine. Our approach is to develop a well-characterized recombinant protein based, chemically conjugated transmission blocking malaria vaccine. The chemical conjugates comprised of Pfs25 and/or Pfs230 with a carrier form nanoparticles that significantly enhance immunogenicity in mice and humans and induce transmission blocking antibodies.
David Narum, Head of Process Development, NIH, NIAID

9:15
Dialing in the Molecular Attributes of a Therapeutic Vaccine Through Process Control, Characterization and In Vivo Testing
Justin Sperry, Group Leader, Senior Principal Scientist, Pfizer, Inc.

9:45
Networking Refreshment Break in Poster and Exhibit Hall

10:25
Chairperson's Remarks
Bo Arve, Executive Director, Pfizer, Inc.

Beyond ADCs - Assessing Other Areas for Breakthroughs in Bioconjugates

10:30
Site-Specific Techniques for the Rapid and Efficient Preparation of Nanoparticle Conjugates
In recent years, the value of functionalizing nanoparticles with targeting ligands has become increasingly apparent. However, the field of nanomedicine is still plagued by bioconjugation techniques that lead to sub-optimal performance and excessive costs. We have developed several strategies that combine chemical and biological bioconjugation techniques to enable the highly efficient, site-specific attachment of targeting ligands to nanoparticles.
Andrew Tsourkas, Ph.D., Associate Professor, Department of Bioengineering, University of Pennsylvania

11:00
Optimizing the Production and Quality Control of an ImmunoPET Clinical Imaging Agent
Herman Gill, Research Associate, Genentech

11:30
Technology Workshop Presentations

12:00
Networking Luncheon in Poster and Exhibit Hall

1:25
Chairperson's Remarks
Dimiter Dimitrov, Ph.D., Senior Investigator, Protein Interactions, National Cancer Institute, NIH

Site-Specific Conjugation Methods and Strategies

1:30
Overcome Key Challenges in Antibody Drug Conjugate Design through the SMARTag Technology Platform
  • Enabling precise & programmable site specific chemical protein modification
  • The development of novel conjugation chemistry resulting in ADCs with enhanced stability
  • Linker chemistry that optimizes the potency of the cytotoxic payload
Robyn Barfield, Ph.D., Group Leader, Bioconjugation, Catalent Pharma Solutions

2:00
De-risking ADC Development Through Cell-free Based Rapid Make-test Cycles
The cell-free Xpress CF+ platform offers the ability to rapidly generate 1000s of antibodies with site-specific chemical linkers in short timeframes. This in turn enables screening efforts to look at critical quality attributes of potential ADC drug candidates at a very early stage in microtiter formats; therefore either identifying viable drug candidates or informing re-engineering efforts of promising leads. Overall, aspects of developability and manufacturability testing can be incorporated during lead selection, allowing for early stage de-risking of ADC drug discovery efforts.
Alexander Steiner, M.S., Director, Protein Biochemistry, Sutro

2:30
Site-specific Conjugation Through Carbohydrates
Conjugation of antibodies with small molecules through glycans will be overviewed. A method based on naturally occurring N-linked glycans will be discussed in detail. This method was used for generation of antibody drug conjugates against cancer-related targets which were extensively characterized.
Dimiter Dimitrov, Ph.D., Senior Investigator, Protein Interactions, National Cancer Institute, NIH

3:00
Networking Refreshment Break and Last Chance for Poster and Exhibit Viewing

Next Generation Bioconjugates

Featured Presentation

3:45
Robert Lutz, Ph.D. Clinical Development of ADCs Lessons Learned and Where Do We Go From Here
A look at the successes and challenges encountered in the clinic with current ADC technologies and how this clinical experience is shaping future development efforts. Where will new technologies have impact? This talk will focus on where we have been and where we are going in the effort to improve ADC therapies.
Robert Lutz, Ph.D., Vice President, Translational Research and Development, ImmunoGen, Inc.

4:15
PEG Alternatives - New Applications of PASylation for Therapeutic Protein Development
PASylation is a biodegradable substitute with biophysical properties very similar to PEG. This technology allows the simple genetic fusion (or chemical coupling) of a therapeutic protein or peptide with a voluminous hydrophilic polypeptide composed of Pro, Ala, and/or Ser to retard kidney filtration. PASylation has been successfully applied to Fab fragments, cytokines, hormones, adipokines, incretins, lipocalins etc., leading to therapeutic drug candidates with increased bioactivity and prolonged action.
Arne Skerra, Ph.D., Professor, Chief Scientific Officer, XL-protein GmbH, Germany

4:45
Close of Tuesday Sessions

5:00
Join Us... Happy Hour @ Pier 39 Overlooking San Francisco Bay
This networking reception is at Players Sports Grill & Arcade, which has sweeping views of San Francisco Bay. Enjoy buffet finger food and drinks (beer, wine, soft drinks) plus arcade games and pool tables. Transportation will be provided. Limited tickets for this event remain for an additional $125 fee. If you want to register for this reception, please stop by the registration desk to reserve your spot.

Wednesday, May 20, 2015

7:30
Coffee

8:00
Chairperson's Remarks
Arne Skerra, Ph.D., Professor, Chief Scientific Officer, XL-protein GmbH, Germany

Keynote Presentations

8:15
Patrick Baeuerle
Development of Bite® Antibody Construct Blinatumomab - The First FDA-Approved Bispecific Antibody
Bispecific T cell-engaging (BiTE®) antibody constructs can transiently link tumor cells with otherwise inactive cytotoxic T cells for induction of potent redirected lysis of attached tumor cells. One example is blinatumomab (AMG 103), a CD19/-CD3-bispecific BiTE® antibody construct for the treatment of acute lymphocytic leukemia (ALL) and non-Hodgkin's lymphoma (NHL), which has been filed in the EU for treatment of relapsed/refractory ALL, and approved in the US by the FDA in December 2014. Two other BiTE® antibody constructs, called AMG 211/MEDI-565 (CEA/CD3-specific) and AMG 212/BAY2010112 (PSMA/CD3-bispecific) are in early clinical development for the treatment of solid tumors. A BiTE® antibody construct specific for CD33 and CD3, called AMG 330, is in formal preclinical development, and has shown high activity in ex-vivo experiments by redirecting autologous patient T cells for lysis of acute myelogenous leukemia (AML) blasts. Blinatumomab and all other BiTE® antibody constructs can activate T cells in a highly efficient manner that is strictly dependent on the presence of target cells, elicit serial lysis of target cells by T cells, induce T cell proliferation, and act at subnanomolar concentrations. In a Phase 1 dose escalation study, blinatumomab showed a complete (CR)/partial response (PR) rate of 68% at a target dose level of 60 micrograms/squaremeter/day in relapsed or refractory NHL patients with, for instance, follicular, mantle cell lymphoma, or diffuse large B cell lymphoma. Initial phase 2 studies investigating monotherapy with blinatumomab in patients with minimal residual disease (N=20) or relapsed/refractory (r/r) ALL (N= 36) revealed molecular/MRD response and complete hematologic response (CR and CRh) rates in the range of 69-80% at a target dose level of 15 micrograms/squaremeter/day. A larger phase 2 study in r/r ALL patients (N=189) at a fixed dose of 9 µg per day for one week and a maintenance dose of 28 µg per day for the remaining treatment period confirmed a CR/CRh rate of 43%. Clinically most relevant safety events were neurological. An overview of the clinical program and insights into the mode of action, immunopharmacology, safety profile, and clinical activity of blinatumomab will be provided.
Patrick Baeuerle, Vice President, Research; General Manager, Amgen Research GmbH, Germany

8:45
James A. Wells, Ph.D.
Engineered Proteins for Signaling
Jim Wells, Ph.D., Professor and Chair, Pharmaceutical Chemistry, UCSF

9:15
Mark S. Dennis
Receptor-Mediated Delivery of Bispecific Antibodies into the Primate Brain: Challenges and Safety Findings
Mark Dennis, Ph.D., Principal Scientist, Antibody Engineering, Genentech, Inc.

9:45
Networking Refreshment Break

Overcoming Challenges with Manufacturability

10:15
Integration of Discovery through Manufacture
Amar Parashad, Principle Scientist, Pfizer, Inc

10:45
Transitioning Radioimmunoconjugates from the Laboratory to the Clinic: Applying cGMPs to Translational Imaging Trials
Joseph McCann, Ph.D., General Manager, Radiopharmaceutical Operations, Centre for Probe Development and Commercialization

11:15
Advancing a New Payload Through Early Phase Development: Lessons from Process and Analytical Development
Robert Herbst, Scientist, ImmunoGen, Inc.

11:45
Technology Workshop Presentations

12:15
Lunch on your Own

1:25
Chairperson's Remarks
Mark Pozzo, Associate Research Fellow, Group Leader, Pfizer, Inc

Conjugation Reaction and Characterization Strategies

1:30
Orthogonal Determination of DAR and Conjugation Distribution for a Lysine Conjugated ADC
Jim Mo, Research Fellow, Pfizer, Inc

2:00
Modeling Conjugation Efficiency of Multimeric Proteins Using the Multinomial Distribution
The analysis of conjugation reactions involving multimeric proteins can be challenging for protein complexes linked by non-covalent interactions. In these cases, analysis under native conditions is not always possible and is limited to characterization of the composite subunits. This situation is frequently encountered in PEGylation, as analysis under native conditions is often insufficient to distinguish between molecules with similar degrees of conjugation. In this work we calculate the extent of PEGylation of a multimeric protein from the conjugation efficiency of the monomeric subunits using a multinomial distribution. This approach offers a number of advantages, including a high degree of model flexibility and an increased sensitivity to differences in conjugation efficiency at higher levels of functionalization. The conjugation reaction was optimized using the modeled functionalization of the multimer and the accuracy of the model was confirmed by multi-angle light scattering. This approach is applicable to a range of conjugation reactions involving multimeric biomolecules, particularly in the area of biotherapeutics. Application of this model can provide a better understanding of conjugation reactions and support more consistent manufacturing and product quality.
Chris Thompson, Associate Scientist, Purification Sciences, MedImmune

2:30
Use of Automation for Execution of DoE
Stephen Freese, Associate Research Fellow, Pfizer, Inc

3:00
Roundtable Discussions & Networking Refreshment Break

CMC Challenges and Regulatory Tactics

3:30
Title TBD
Fred Jacobsen, Ph.D., Principal Scientist, Genentech, Inc.

4:00
Successful CMC Development and Regulatory Strategies for ADCs
Nathan Ihle, Vice President, CMC Strategy and Management, Seattle Genetics

4:30
ADC Process Development Towards a Liquid Formulation
Chris Borths, Senior Scientist, Amgen

5:00
Close of Conferences

Antibody Engineering & Therapeutics China