- What are the key parameters?
5. Next-Generation Drug Conjugates: Non-Antibody Based Scaffolds
Moderator: Darrell Sleep, Ph.D., CSO, Albumedix Ltd.
- Advantages and disadvantages of non-antibody based scaffolds as novel therapeutic approaches
- Overcoming half-life shortcomings of non-antibody based scaffolds
- Clinical and manufacturing challenges of non-antibody based scaffolds
3:20 Refreshment Break in the Exhibit Hall with Poster Viewing
PLENARY KEYNOTE SESSION
4:00 Chairperson’s Remarks
4:10 The Promise of Cancer Immunotherapy: An Overview of Recent Advances and Jounce’s Approach to Delivering the Right Therapy to the Right Patient
Deborah Law, D. Phil. CSO Jounce Therapeutics, Inc.
As immunotherapies become an increasingly important component of cancer treatment the challenge will be to identify ways to provide the best therapy(s) to the individual. This presentation will provide an overview of current cancer
immunotherapies as well as highlight some of the challenges ahead including selection of optimal combinations, moving outside of T cell-directed approaches, and will highlight how Jounce Therapeutics is using its Translational
Science Platform as an approach to develop and deliver the right therapy to the right patient.
4:50 Antibody as Drugs: Then, Now and Tomorrow
Paul J. Carter, Ph.D., Senior Director and Staff Scientist, Antibody Engineering, Genentech
Antibodies have grown into a clinically and commercially important drug class with more than >45 antibodies marketed for imaging or therapy in the USA and/or Europe and with ~$63 billion in worldwide sales in 2013. This presentation
will highlight progress in developing antibody drugs and consider opportunities for future innovation.
5:30 Welcome Reception in the Exhibit Hall with Poster Viewing
6:45 End of Day
TUESDAY, APRIL 26
8:00 am Morning Coffee
8:25 Chairperson’s Remarks
Stefan Schmidt, Ph.D., MBA, Vice President, Process Science and Production, Rentschler Biotechnologie GmbH
8:30 Immunocytokines for the Therapy of Cancer and of Chronic Inflammation: From the Bench to Phase II Clinical Trials
Dario Neri, Ph.D., Professor, Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, ETH Zürich
Certain monoclonal antibodies can be used as vehicles for the selective pharmacodelivery of potent immunomodulatory payloads, including cytokines. In this lecture, I will review our work in the field and present the most recent clinical
data, originating from on-going Phase II clinical trials.
9:00 Combination Immunotherapy Enabled by a Tumor-Targeting Peptide-Fc Fusion
Jennifer R. Cochran, Ph.D., Associate Professor, Bioengineering and Chemical Engineering,
I will discuss an engineered peptide-Fc fusion protein that we have adapted for targeted delivery of chemotherapeutic agents, as well as recruitment of immune cell effector functions to tumors. The co-administration of peptide-Fc fusion
and an immune stimulating cytokine results in significant control of tumor growth in melanoma and colon carcinoma models, which is further enhanced by combination with checkpoint blockade inhibitors.
9:30 Diphtheria-Toxin Based Anti-Human CCR4 Immunotoxin for Targeting Human CCR4+ Tumors and Tregs
Zhirui Wang, Ph.D., Assistant Professor, Center for Transplantation Sciences, Massachusetts General Hospital
and Harvard Medical School
We have successfully developed an anti-human CCR4 immunotoxin using yeast Pichia Pastoris expression system. In vivo efficacy for targeting CCR4+ tumors was assessed using human CCR4+ tumor-bearing NSG mouse model. In vivo efficacy for depleting CCR4+ Tregs was characterized in two naïve cyno monkeys. This immunotoxin is a promising drug candidate for targeting human CCR4+ tumors and Tregs.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing and Poster Awards
10:50 Engineering of a GLP-1 Analogue Peptide in Fusion with a PCSK9 Antibody for Type 2 Diabetes Patients at High Cardiovascular Risk
Matthieu Chodorge, Ph.D., Senior Scientist, Antibody Discovery and Protein Engineering,
In addition to high blood glycose, Type 2 diabetic patients often have an impaired cholesterol balance and are at greater risk of cardiovascular disease. We have developed a GLP-1 receptor agonist peptide in fusion with a PCSK9 antibody
to provide glucose control and LDL cholesterol reduction in one molecule. Here we will present how the fusion has been exquisitely engineered to deliver optimum pharmacology on both axis and adequate manufacturability.
11:20 Apolipoprotein A-I as a Novel Scaffold for Protein Delivery
Pedro Berraondo, Ph.D., Researcher, Program of Immunology & Immunotherapy, University of Navarra
Clinical use of therapeutic proteins and peptides is limited by the short half-life in circulation and the absence of a specific targeting. Fusion to apolipoprotein A-I is a strategy to improve the pharmacokinetic and pharmacodynamics
properties: the half-life in circulation is improved, the fusion proteins are targeted to the liver and tumors, the blood brain passage is modified and the activity of the fused protein is modulated by the interaction with the scavenger
receptor class B type I.
11:50 Human Serum Albumin and p53-Derived Peptide Fusion Protein Promotes Cytotoxicity Irrespective of p53 Status in Cancer Cells
Zhiyu Li, Ph.D., Associate Professor, Pharmaceutical Sciences, Philadelphia College of Pharmacy
Human serum albumin (HSA) fusion protein is a feasible and effective approach to target and inhibit essential intracellular pathways. HSA and p53-derived peptide fusion protein (rHSA-p53i) binds to 4 intracellular proteins, including
MDM2, MDMX, BCL-XL, and Mcl-1. Therefore, rHSA-p53i is capable of promoting cytotoxicity irrespective of p53 status (wild type, mutation, and deficiency). Moreover, rHSA-p53i can carry fatty acid-modified chemotherapeutics for
synergistic therapeutic efficacy.
12:20 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on your Own
1:20 Ice Cream Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Remarks
Zhirui Wang, Ph.D., Assistant Professor, Center for Transplantation Sciences, Massachusetts General Hospital and Harvard Medical School
2:05 POSTER SPOTLIGHT
Increasing the Proteolytic Stability of Affibody Molecules by Intramolecular Cross-Linking
Anders Nilsson, Ph.D. Student, Biotechnology, Royal Institute of Technology (KTH)
2:35 A Novel Protease-Based Fusion Protein Platform with Utility across a Range of Disease Areas
Nathaniel Gordon, Ph.D., Senior Scientist, MedImmune, Ltd.
Proteases have a unique mechanism of action and could offer a number of therapeutic advantages relative to neutralizing monoclonal antibodies, however their practical realization is impeded by the difficulty in engineering protease
specificity. We have bypassed limitations in protease engineering by designing protease-fusion proteins with a modular, multi-domain architecture, in which specificity and hydrolytic activity are conferred by complementary domains.
Further engineering principles and therapeutic implications of our platform will be discussed.
3:05 Multiple Domain Challenges of Fc Fusions and Fab Fusion Bispecific Antibodies
Hua Tu, Ph.D., Chairman and CEO, LakePharma, Inc.
We will describe several fusion platform technologies, addressing challenges arising from the multiple domain nature of fusion protein therapeutics. Case studies showing successful engineering of Fc fusions and bispecific antibodies
will be presented, including applying integrated solutions to protein design and engineering, activity testing, bioanalytical characterization, and manufacturability assessment.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing
4:25 Target-Engaged Complementation: Replacing ELISA and Resurrecting ADEPT
Shawn Owen, Ph.D., Assistant Professor, Pharmaceutics and Pharmaceutical Chemistry, University of Utah
We are developing a technology, termed Target Engaged Complementation (TEC), which utilizes enzymes split into inactive components. Each fragment is fused to an individual antibody Fab; the binding of the Fabs forces the split enzyme
fragments into proximity where they refold to the active form. The activity of the split enzyme is used to activate luminescence for diagnostic applications or activate prodrug for therapeutic applications.
4:55 Therapeutic Strategies Combining Specificities on the Outside and Inside: Ligands Sneaking into Cells
Stefan Dübel, Ph.D., Director, Biotechnology, Technical University of Braunschweig
Our “Sneaking Ligand” fusion proteins provided a cell-specific delivery of an intracellular regulator of immune activation. The E-selectin–specific “Sneaking Ligand” fusion protein inhibited NF- κB
by interfering with endothelial IκB kinase 2 activity inside the cells in vitro and in vivo. The treatment drastically reduced the extravasation of inflammatory cells murine experimental peritonitis and significantly
ameliorated the disease course in murine models of rheumatoid arthritis.
5:25 End of Fusion Protein Therapeutics
5:30 Registration for Dinner Short Courses*
*Separate registration required