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Key Sessions

Sachdev Sidhu

Keynote Presentation: From Antibodies to Synthetic Proteins

University of Toronto

Martin Steegmaier, Ph.D.

From Format to Function - Engineering Transformative Antibody Therapeutics

Roche Innovation Center Munich

7:00am - 8:00am 60 mins
Breakfast & Registration
8:00am - 8:15am 15 mins
Chairperson’s Remarks
  • H. Kaspar Binz, Ph.D. - Vice President and Co-Founder, Molecular Partners AG
8:15am - 8:45am 30 mins
Info
Next Generation Protein Therapeutics Summit
Keynote Presentation: From Antibodies to Synthetic Proteins
  • Sachdev Sidhu - Professor, Department of Molecular Genetics, University of Toronto

Synthetic antibodies enable applications beyond the reach of natural antibodies.  Moreover, alternative scaffolds such as ubiquitin can be used to modulate proteins in live cells. In addition, small scaffolds that function like antibodies but are amenable to full chemical synthesis enable D-protein engineering. In sum, these advances greatly extend the applications of protein engineering in biological research and therapeutic development.

8:45am - 9:15am 30 mins
Info
Next Generation Protein Therapeutics Summit
Next Generation Protein Therapeutics for Treating Cancer
  • Jennifer Cochran - Shriram Chair of Bioengineering, Stanford University

We use natural ligands and receptors as scaffolds for protein engineering to leverage their inherent biophysical and biochemical properties. I will present our recent data on new therapeutic candidates engineered to possess high affinity and unique specificity for applications in oncology.

9:15am - 9:45am 30 mins
Info
Next Generation Protein Therapeutics Summit
Optimization of biologics using mRNA display and NGS
  • Julie Su - Senior Research Investigator II, Bristol-Myers Squibb

In this talk, I will describe library design, selection strategies, and data analysis using next generation sequencing (NGS) for discovery of biologic leads.

9:45am - 10:30am 45 mins
Next Generation Protein Therapeutics Summit
Networking Refreshment Break in the Exhibit Hall
10:30am - 11:00am 30 mins
Info
Next Generation Protein Therapeutics Summit
Automated Protein Production and Investigating FcRn Interaction with IgG and other Fc Biologics
  • Medha Tomlinson - Principal Research Scientist, Abbvie

Early stages of drug discovery require large amounts of protein for assays and proprietary therapeutic generation. Proteins are often needed to establish animal models. Automation plays a key role in efficient production to meet high demand. The ability to use these systems for other applications such as exploration of IgG-FcRn interactions will also be discussed.

11:00am - 11:30am 30 mins
Info
Next Generation Protein Therapeutics Summit
Protein Selections in the Absence of a Physical Genotype-Phenotype Linkage
  • Markus Seeger - Assistant Professor, University of Zurich

NestLink is a novel method that combines the benefits of selections and screens. In a novel process called library nesting, binder candidates are genetically fused to a peptide barcode library, which is designed for maximal detection efficiency in mass spectrometry. An in silico genotype-phenotype linkage is established by combining mass spectrometry and deep sequencing. This enables the biophysical characterization of several thousand individual proteins in one single experiment. The technology offers unprecedented selection pressures and deep mining of diverse binder pools and it paves the way for a paradigm shift in biopharmaceutical drug delivery testing.

11:30am - 12:00pm 30 mins
Info
Next Generation Protein Therapeutics Summit
From Format to Function - Engineering Transformative Antibody Therapeutics
  • Martin Steegmaier, Ph.D. - Head of Discovery, Large Molecule Research, Roche Pharma Research and Early Development, Roche Innovation Center Munich

Bi- and multi specific antibodies enable the exploration of new biological concepts and treatment strategies. Within Roche such next generation biologics have found broad application prospects in onco-immunological and anti-inflammatory approaches. But their use goes far beyond these established applications to convey unique mode of actions.

  • We have generated a portfolio of T cell bispecific antibodies and novel, engineered targeted checkpoint modulators that show promising pre-clinical and clinical activity as single agent or in combination with other cancer immunotherapy agents.
  • The CrossMAb technology has proven to be very versatile, allowing the generation of various bispecific antibody formats providing great opportunity to tackle novel biology and to convey superior efficacy.
  • The DutaFab technology platform brings forward a novel class of fully human Fab molecules that bind any two antigens with high affinity and specificity. This format of bispecific molecules is uniquely suited to be used for Ophthalmology indications.  
  • Examples will be given how antibody format fundamentally influences the mode of action and activity of these next generation antibody drugs.
12:00pm - 12:30pm 30 mins
Info
Next Generation Protein Therapeutics Summit
An Integrated Approach To Managing Immunogenicity Risk And Optimum Protein Design
  • Emilee Knowlton - Immunology Sales Specialist, ProImmune Inc.

Integrated platforms can be used to mitigate immunogenicity risk and characterize immune responses during the drug design and development stages.  ProImmune offers mutational activity mapping for optimal protein design,  DC-T/T cell proliferation assays for biologic lead selection/optimization, a Mass Spectrometry assay for characterization of antigen presentation; HLA-peptide binding assays to characterize individual epitopes & undiluted whole blood cytokine storm assays.

12:30pm - 1:45pm 75 mins
Next Generation Protein Therapeutics Summit
Luncheon in the Exhibit Hall
1:45pm - 2:15pm 30 mins
Info
Next Generation Protein Therapeutics Summit
ProTIA – Bispecific T Cell Engagers Designed for Local Activation in the Tumor Environment
  • Volker Schellenberger - CEO and President, Amunix
  • ProTIAs are highly potent bispecific T cell engagers
  • ProTIAs are administered to patients as inactive long half-life prodrugs
  • Activation by tumor-associated proteases occurs within tumor tissue
  • The released active form has a short circulation half-life to minimize the risk of systemic exposure
  • Amunix’ proprietary XTEN™ protein polymer provides half-life modulation, masking of binding sites, and facilitates manufacturing of ProTIA prodrugs
2:15pm - 2:45pm 30 mins
Info
Next Generation Protein Therapeutics Summit
A Novel T-Cell Engaging Bispecific Antibody Platform: In Vivo Tumor Clearance with Minimal Cytokine Release
  • Nathan Trinklein - Vice President, Teneobio, Inc.

Using transgenic rats and a unique discovery approach, we have created a large collection of fully human anti-CD3 antibodies with diverse T-cell agonist activities. Our novel discovery platform combines antibody repertoire deep sequencing, high-throughput gene assembly, and recombinant expression and allows us to identify antibodies with finely tuned functional activities. The collection of CD3 antibodies identified by our platform show diverse in vitro T-cell activation profiles measured by CD69 upregulation, IL2, and IFNg production. Using our discovery platform, we have also generated human domain antibodies targeting tumor antigens that may be combined with our unique CD3 antibodies to create multi-specific molecules that mediate redirected T-cell killing of tumor cells. As one example, we have created a CD3xBCMA bispecific antibody (TNB-383B) for the treatment of multiple myeloma. TNB-383B kills multiple myeloma cells in vitro and in vivo in a BCMA-dependent manner, and kills primary patient myeloma cells ex vivo. Futhermore, TNB-383B induces significantly reduced cytokine secretion by T-cells without reduction of efficacy in vivo or ex vivo. In summary, we have created a novel T-cell engaging bispecific antibody platform with tunable T-cell agonism that can be used to optimize the therapeutic index for a variety of tumor antigens.

2:45pm - 3:15pm 30 mins
Info
Next Generation Protein Therapeutics Summit
A MET x MET Bispecific Antibody That Induces Receptor Degradation Potently Inhibits The Growth of MET-Addicted Tumor Xenografts
  • John DaSilva - Scientist, Regeneron Pharmaceuticals

We have developed a novel bispecific antibody that binds to two distinct epitopes on MET.  The METxMET bispecific antibody blocks HGF binding and exhibits very low agonist activity Furthermore, the METxMET bispecific antibody effectively promotes MET degradation, thereby inhibiting ligand-independent signaling in MET-amplified tumor cells. The METxMET bispecific antibody exhibits strong anti-tumor efficacy in xenograft models harboring MET genetic alterations.

3:15pm - 3:45pm 30 mins
Next Generation Protein Therapeutics Summit
Networking Refreshment Break in the Exhibit Hall
3:45pm - 4:15pm 30 mins
Info
Next Generation Protein Therapeutics Summit
The CTLA-4 x OX40 Bispecific Antibody ATOR-1015 Induces Anti-Tumor Effects Trough Tumor-Directed Immune Activation
  • Christina Furebring - SVP Research, Alligator Bioscience

ATOR-1015 is a CTLA-4 x OX40 bispecific immune activating antibody developed for tumor-directed immunotherapy. ATOR-1015 binds both targets simultaneously, promoting cell-cell interactions expected to enhance the immuno-stimulating effect of the compound. The mode of action of ATOR-1015 is thought to be a combination of regulatory T cell (Treg) depletion and effector T cell activation. It can be seen as a next generation CTLA-4 antibody with tumor-directed activity and augmented Treg depletion.

ATOR-1015 is currently in pre-clinical development and clinical trials will start in the second half of 2018.

4:15pm - 4:45pm 30 mins
Info
Next Generation Protein Therapeutics Summit
Anchoring CD137 Activation to Tumor Antigens by Bispecific DART® and TRIDENT™ Molecules
  • Annie Lam - Scientist II, Antibody Engineering, MacroGenics

Targeting CD137 costimulatory pathway holds great promise for cancer immunotherapy. Systemic administration of agonistic antibodies, however, can be associated with significant safety concerns. To localize immune activation to tumor sites, while sparing normal tissues, we employed our DART and TRIDENT platforms to generate bispecific molecules that simultaneously engage a tumor antigen and CD137 receptors. This talk will focus on the format selection/optimization process to select a candidate that mediates optimal tumor antigen-dependent T-cell co-stimulatory activity.

4:45pm - 5:15pm 30 mins
Info
Next Generation Protein Therapeutics Summit
A Modular Single Domain Antibody Platform That Enables Generation of Optimized Biotherapeutics
  • Katelyn McCabe Willis - Cell Biology Group Leader, InhibRx

Inhibrx’s modular single domain antibody platform enables crafting of differentiated biotherapeutics with functionalities beyond what is achievable with conventional antibodies. Therapeutic formats include multivalent and multispecific therapeutics to appropriately interface with the biology of each target antigen. These biotherapeutics can be designed for enhanced signaling, antigen-dependent agonism and specific immune cell recruitment and activation.