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Emerging Antibody and Protein Engineering Partnering Forum 

OverviewDay 1 | Day 2

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Day 2: Sunday, April 29

9:00 am Chairperson's Opening Remarks

Phillips Kuhl, Co-Founder and President, Cambridge Healthtech Institute

9:10 Panel Discussion: Clinical Development of Antibodies and Antibody-like Proteins

 

ANTIBODY PRODUCTS IN DEVELOPMENT 

9:40 Clinical Development of Tanibirumab and its Next Generation Dual Specific Antibodies, DIG-KT and PIG-KM

Jin-San Yoo, Ph.D., Chief Executive Officer & President, PharmAbcine, Inc. (www.pharmabcine.com)

Novel anti-KDR neutralizing fully human IgG with cross-species crossreactivity, Tanibirumab is in Phase I and will be completed in this fall. DIG-KT is one of the leading pipeline from DIG-Body platform and it neutralize both VEGF-KDR and ANG-Tie2 pathways and performed synergistic value like overcome Avastin resistance issue. PIG-KM from PIG-Body neutralizes both VEGF-KDR and HGF-cMET pathways and also potential value.

9:55 Chemoenzymatic Site-Specific Antibody-Drug Conjugate Generation

David Rabuka, Ph.D., Chief Scientific Officer, Redwood Bioscience, Inc. (www.redwoodbioscience.com)

We have developed a technology platform that enables the chemical modification of proteins in a controlled, site-specific manner. Using this technology we are able to generate panels of modified recombinant IgGs that are site-specifically modified and are easy to chemically elaborate with toxic payloads. The resulting homogenous ADCs are loaded with a defined amount of drug placed at defined locations on the proteins.

10:10 Delenex: Changing the Game in Immuno-Inflammation

Titus Kretzschmar, Ph.D., Chief Scientific Officer, Delenex Therapeutics AG (www.delenex.com)

Delenex' proprietary PENTRA® antibody format has proven its drug-like characteristics (affinity, manufacturability, safety), and adds the unique combination of a short half-life and excellent tissue penetration. On this basis, Delenex will be running three PoM and PoC clinical trials in 2012, addressing the areas of dermatology, gastro-intestinal disease and acute inflammation.

10:25 Oral Antibody Therapeutics with Local Activity in the GI Tract

Barbara Fox, Ph.D., Chief Executive Officer, Avaxia Biologics, Inc. (www.avaxiabiologics.com)

Avaxia is developing orally delivered antibody therapeutics designed to work locally in the GI tract. The antibodies are bovine polyclonal antibodies isolated from the early milk (colostrum) of immunized cows. These antibodies are safe for oral administration and inherently stable to gastric digestion, making them ideally suited to oral delivery.

10:40 Development of ProbodiesTM-Proteolytically-active Antibodies for Therapy

Debajan Ray, Senior Director, Head of Business Development, CytomX Therapeutics, Inc. (www.cytomx.com)

CytmoX is developing masked antibodies, called ProbodiesTM, that are proteolytically activated. ProbodiesTM are inert until they are localized to the site of disease at which point they are activated into traditional antibodies. Since upregulation and disregulation of proteases is a common feature of most diseased tissue and tumors, ProbodiesTM have several potential applications, including significant increase in therapeutic index versus a given parental antibody, improved biodistribution, and development of drugs against targets that are deemed intractable because they are too widely dispersed. CytomX has recently generated in-vivo tumor model data with our platform that demonstrates Probodies are being activated site specifically and mimic the activity of parenteral antibodies at the site of disease, but are inert in circulation and other healthy tissue.

10:55 Networking Coffee Break

 

PROTEIN ENGINEERING-FUSION PROTEINS 

11:15 One Molecule – Six Binding Sites: A New Class of TRAIL-receptor Agonists for the Treatment of Solid Tumors

Oliver Hill, Ph.D., Vice President, Molecular Biology, Apogenix GmbH (www.apogenix.com)

Apogenix has designed a new class of modular TRAIL-receptor agonists suitable for biopharmaceutical development.  The main feature of these second generation pro-apoptotic receptor agonists (PARAs) is an Apo2L/TRAIL mimic combining three Apo2L/TRAIL protomer sub-sequences in one polypeptide chain, termed single-chain-TRAIL-receptor-binding-domain (scTRAIL-RBD).  The scTRAIL-RBD exposes, like its natural counterpart, three binding sites for the interaction with death inducing TRAIL-receptors (TRAIL-R1, TRAIL-R2).  By fusing the hinge and the CH2-CH3 segment of human IgG1 to the C-terminus of the scTRAIL-RBD module, a dimeric fusion protein comprising six binding sites per molecule (scTRAIL-RBD-Fc) with an overall antibody like shape and volume was generated.  The prototype of this engineering concept, APG350, distinguishes itself from current agonistic anti-TRAIL-R1 or TRAIL-R2 antibodies in clinical development by its ability to form “super-clusters” on target cells. In vivo, APG350 and its muteins with reduced or depleted Fc-gamma-Receptor binding ability showed similar anti-tumor efficacy in the Colo205 human colon xenograft tumor model.


11:30 Intracellular Delivery of Bio-therapeutics Utilizing a Novel Cell Penetrating Antibody Technology

Dustin Armstrong, Ph.D., Vice President, Research, 4s3 Bioscience (www.4S3bioscience.com)

4s3 Bioscience is an emerging science-driven company developing therapies based on a proprietary intracellular delivery platform. The 4s3 technology takes advantage of tissue targeting via a novel antibody (3E10) for which intracellular uptake is dependent on membrane expression of a nucleoside transporter (ENT2). Because the ENT2 transporter is naturally enriched in skeletal muscle fibers and elevated in certain cancers, 4s3 is able to generate proprietary product candidates utilizing substrates (fusion proteins, bi-specific antibodies, Oligos, etc.) not previously deliverable to target tissues (muscles and cancers); thereby, providing a novel way to treat a number of diseases with limited or no current therapeutic options.

11:45 Bispecific Fynomer-Antibody Fusions

Julian Bertschinger, Ph.D., Chief Executive Officer, Covagen (www.covagen.com)

Covagen is a pioneer in the development and commercialization of Fynomers as next generation protein drugs for the treatment of inflammatory diseases and cancer. Fynomers are small binding proteins derived from a fully human protein domain and have excellent biophysical properties. Fynomers can be used for the construction of multivalent and multispecific therapeutic proteins with a novel mode of action. Of particular interest are bispecific Fynomer-antibody fusion proteins, as Fynomers can be genetically fused to antibodies to enhance their potency and functionality without compromising their beneficial drug-like properties. Fynomer-antibody fusions represent a new generation of bispecific protein therapeutics which are based on clinically well validated antibodies. Data obtained from in vitro and in vivo characterization of a bispecific TNF/IL-17A inhibitor will be presented.

12:00pm Site-Specific Crosslinking of Proteins Using Swift Linkage Multivalent Technology

Allen Krantz, Ph.D., President and Chief Executive Officer, Advanced Proteome Therapeutics, Inc. (www.advancedproteome.com)

The trifecta of fusion proteins, antibody drug-conjugates, and polymer therapeutics comprise the bulk of the burgeoning protein therapeutics market. For each of these therapeutic types it is necessary to connect two or more entities to achieve viable drugs. Whereas antibody drug-conjugates, and polymer therapeutics require chemical methods to forge a bond between entities, the production of fusion proteins by recombinant methods has become an integral part of the repertoire of protein therapeutics. A major limitation in the production of homogeneous protein drugs of all types has been the lack of site-specific chemical methods designed to connect two entities at a single site on each of their surfaces. In fact, to date essentially no practical chemical methods have been developed for producing protein multimers to rival fusion proteins and expand the range of chemical functionalities beyond peptides. Advanced Proteome Therapeutics has introduced advanced chemical modification techniques to enable the linking of entities to diverse positions along the protein framework with crosslinks of variable chemical functionality. Advanced Proteome Therapeutics has developed Swift Linkage Multivalent Technology (SLMT) to rapidly link proteins, peptides and organic chemical pharmacophores to a target protein, site specifically. Using SLMT, protein dimers can be prepared within 24 hours, site-specifically, biologically active, and in good yield.

12:15 Networking Lunch, Discussion with Company Presenters

1:30 Chairperson's Remarks

1:40 Panel Discussion "Design and Selection of Improved Protein Therapeutics"

 

PROTEIN DIVERSITY 

2:10 Peptide and Protein Engineering Using CIS Display

Chris Ullman, Ph.D., Chief Scientific Officer, Isogenica Ltd. (www.isogenica.com)

CIS display is a cell-free display technology that is capable of displaying very large libraries (>10e13) of polypeptides. The technology uses DNA rather than RNA and is therefore different to phage, yeast and ribosome display. Through iterative rounds of selection, CIS display has yielded highly specific ligand-binding peptides, protein scaffolds and antibody fragments to a wide range of targets, such as kinases, growth factors, GPCRs and proteases. In this presentation, an overview of the technology will be provided including applications and examples.

2:25 Open Cell-free Protein Synthesis as a Viable Route for Rapid Design and Manufacturing of Novel Engineered Therapeutic Proteins

Lesley Stolz, Ph.D., Vice President, Business Development, Sutro Biopharma, Inc. (www.sutrobio.com)

Sutro has developed a scalable cell–free protein synthesis platform for the efficient production of complex or difficult to express therapeutic proteins, including full length IgGs and ADCs, bispecific antibodies, and other complex eukaryotic proteins. The system allows for a 1-2 week make test cycle that can produce hundreds of variants rapidly for activity and specificity testing. Because of its scalable nature, it is a rapid route to manufacturing once discovery has been finished. Sutro has a GMP facility that is capable of producing materials up through Phase I clinical trials.

2:40 Affilin: The Ubiquitin-based Therapeutic Drug Platform

Ulrich Haupts, Ph.D., Chief Scientific Officer, Affilin Technology, Scil Proteins GmbH (www scilproteins.com.)

Scil Proteins develops biotherapeutics based on Ubiquitin as a new scaffold. Ubiquitin is a small and highly stable human protein whose sequence is fully conserved across all mammalian species, simplifying pre-clinical development. Examples of Affilins engineered to picomolar affinity and high specificity, fusions with effector molecules or dimeric constructs and applications will be presented.

2:55 A Technology Platform for Rapid Discovery of Oral and Injectable Peptide Therapeutics

Dinesh Patel, Ph.D., Chief Executive Officer, Protagonist Therapeutics (www.protagonist-inc.com)

Disulfide Rich Peptides (DRPs) offer better stability & potency compared to conventional peptides. Protagonist's technology platform integrates computational, phage, and med chem drug discovery tools to discover well differentiated and superior DRPs against those targets and diseases wherein conventional small molecule and antibody approaches do not offer a satisfactory solution. Examples of application of DRP technology platform will be provided.

3:10 Accessing Extracellular and Intracellular Targets with the Next Generation of Protein Therapeutics: Alphabodies™

Mark Vaeck, Ph.D., Chief Executive Officer, Complix NV (www.complix.be)

Complix has demonstrated it can successfully discover Alphabodies™ against a variety of target classes – both extra-cellular and intracellular targets. Alphabodies™ can act on therapeutic targets that are difficult or impossible to address with other therapeutic classes (antibodies or small chemicals). This is due to their special structure and exceptional properties. In addition, Complix is presenting a new paradigm in protein drug discovery: Its break-through Alphabody™ discovery engine is based on i) the identification of a key functional epitope on the target structure, ii) the design of initial Alphabody™ hits through 3-D computer modeling, iii) the creation of optimized leads through "dedicated" library selection and iv) the iterative process of structure activity relation analysis resulting in the final product. Our process eliminates the "black box" of random selection from phage libraries or unpredictable outcome of animal immunizations.

3:25 Networking Refreshment Break

3:45 Better by Design: Creating Differentiated Protein Products by Engineering

Tom Barnes, Ph.D., Vice President, Discovery, Eleven Biotherapeutics, Inc. (www.elevenbio.com)

Eleven Biotherapeutics is a biopharmaceutical company focused on engineering and developing innovative protein-based therapeutics to improve human health and treat disease. By integrating a unique molecular-level understanding and structure-based design capabilities, Eleven Biotherapeutics has built a protein design product engine to create and develop best in class protein-based therapies. Our lead product in development, EBI-005, is a chimera of IL-1Ra and IL-1beta which combines the ideal properties of both, for the treatment of dry eye disease. IL-1 blockade has been recently shown to be a promising mechanism in dry eye therapy. We will describe the discovery, pre-clinical validation and process development of EBI-005, and preview salient aspects of Eleven's pipeline.

4:00 Celexion's Protein Engineering Platforms for the Discovery and Optimization of Therapeutics

Andrew Rakestraw, Ph.D., Head of Technical Operations, Protein Engineering, Celexion LLC (www.celexionbio.com)

Celexion is a biotechnology company focused on creating next-generation protein engineering tools to empower partners to push the boundaries of human therapeutics. Celexion's team of scientists has developed customizable platforms that enable partners to construct, discover, optimize and refine next-generation antibody and protein scaffolds (full-length IgG, tandem scFv, bi-specifics, non-antibody scaffolds, therapeutic proteins, etc.) for applications in de novo discovery, affinity maturation, protein expression improvement, and enzyme engineering. The platforms are comprised of the SECANT® yeast display system for library selections, a fully-human, naïve, full-length IgG library for de novo discovery of fully human antibodies, novel linker libraries for multi-domain scaffold construction, and tremendous know-how from helping partners achieve human therapeutic goals for a number of diseases. Celexion uses a flexible business model to make these technologies available to our partners through outlicensing and service arrangements.

4:15 Achieving Multi-Epitopic Multi-Specificity (MEMS) with a Single Highly Conserved Human Therapeutic Protein

Casey Logan, M.B.A., Senior Vice President, Business Development, Anaphone, Inc. (www.anaphone.com)

Anaphore is developing a new class of protein therapeutics targeting multiple epitopes on multiple targets using a single protein species. This new class of therapeutics has the potential to show advantages over other classes of biologics given the structural characteristics of the protein, its drug-like properties and its ability to drug multiple therapeutic targets of interest concurrently. Anaphore will be presenting new data highlighting its early efforts in the multi-specific space.

4:30 Speaker to be Announced

4:45 Networking Session, Discussion with Company Presenters

5:45 End of Forum


OverviewDay 1 | Day 2