TIDES: Oligonucleotide and Peptide® Research, Technology and Product Development
CSS
肽创药与开发
肽创药与开发
以治疗法的开发为目的的细胞内药、新的立足点、做为改良分子的肽之开发
Courses: 星期日 | Plenary Sessions: 星期一 | Main Conference: 星期二 | 星期三
8:15
Chairperson's Remarks
Peter Timmerman, Ph.D., Chief Technology Officer, Pepscan Therapeutics B.V., The Netherlands
Peter Timmerman, Ph.D., Chief Technology Officer, Pepscan Therapeutics B.V., The Netherlands
Cell-Penetrating Peptides with Intrinsic Functional Activity: New Targets and Disease Mechanisms
8:30
Structure-Activity Relationship of Cell Penetration: More Knobs to Turn
Considering the interest in the application of peptides, peptidomimetics and proteins for addressing the intracellular target space, the problem of intracellular delivery of these molecules is receiving increasing attention. Here, I will summarize data that extends the common sense of efficient uptake simply depending on positive charge and amphipathicity. Instead, minor structural modifications of peptides with similar charge can have a major impact on uptake illustrating the room for innovation in the identification of cell-penetrating molecules.
Roland Brock, Ph.D., Head, Department of Biochemistry, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, The Netherlands
Considering the interest in the application of peptides, peptidomimetics and proteins for addressing the intracellular target space, the problem of intracellular delivery of these molecules is receiving increasing attention. Here, I will summarize data that extends the common sense of efficient uptake simply depending on positive charge and amphipathicity. Instead, minor structural modifications of peptides with similar charge can have a major impact on uptake illustrating the room for innovation in the identification of cell-penetrating molecules.
Roland Brock, Ph.D., Head, Department of Biochemistry, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, The Netherlands
9:00
CPP-Conjugated Anti-Apoptotic Peptides Prevent Cardiac Ischemia-Reperfusion Injuries in vivo
We have focused on anti-apoptotic peptides: BH4 peptide, essential for Bcl2 proteins, and new peptides selected from SPOT libraries. Since peptides do not cross biological membranes, they were delivered with cell penetrating peptides (CPP) and their anti-apoptotic activity was first evaluated in primary cardiomyocytes. Importantly, selected CPP constructs were found active when injected systemically at a single low dose (1mg/kg) at the time of reperfusion in a murine model of ischemia/reperfusion thus providing a possible treatment of I/R injuries. More generally, screening chemically-synthesized libraries for peptides interfering with protein-protein interactions and delivering them with CPPs is an easy to implement strategy with many potential applications in fundamental and translational research.
Bernard Lebleu, Ph.D., Professor of Molecular Biology, University of Montpelier, France
We have focused on anti-apoptotic peptides: BH4 peptide, essential for Bcl2 proteins, and new peptides selected from SPOT libraries. Since peptides do not cross biological membranes, they were delivered with cell penetrating peptides (CPP) and their anti-apoptotic activity was first evaluated in primary cardiomyocytes. Importantly, selected CPP constructs were found active when injected systemically at a single low dose (1mg/kg) at the time of reperfusion in a murine model of ischemia/reperfusion thus providing a possible treatment of I/R injuries. More generally, screening chemically-synthesized libraries for peptides interfering with protein-protein interactions and delivering them with CPPs is an easy to implement strategy with many potential applications in fundamental and translational research.
Bernard Lebleu, Ph.D., Professor of Molecular Biology, University of Montpelier, France
9:30
Bioportide: An Emergent Class of Bioactive Cell Penetrating Peptide
The term bioportide is a useful descriptor of cell penetrating peptides that are intrinsically bioactive. Following their effective intracellular translocation, bioportides can specifically modulate intracellular signaling events to achieve a desirable biological outcome. Thus, bioportides represent an innovative generic class of bioactive agent.
John Howl, Ph.D., Professor of Molecular Pharmacology, University of Wolverhampton, United Kingdom
The term bioportide is a useful descriptor of cell penetrating peptides that are intrinsically bioactive. Following their effective intracellular translocation, bioportides can specifically modulate intracellular signaling events to achieve a desirable biological outcome. Thus, bioportides represent an innovative generic class of bioactive agent.
John Howl, Ph.D., Professor of Molecular Pharmacology, University of Wolverhampton, United Kingdom
10:00
Access to Novel Disease Mechanisms by Cell-Permeable Peptides
Novel technologies to access intractable target proteins have paved the way of cell-permeable peptide drugs into the clinic. This upcoming drug class allows the targeting of novel, and so far inaccessible disease mechanisms. The drugs in development are therefore associated with unique USPs. The talk will give an introduction to the field and current developments. In addition, novel ways to identify and further develop cell permeable peptide drug candidates will be presented. A case study regarding the development of cell-permeable peptide drug candidates in oncology (Wnt-pathway) will be discussed.
Hanjo Hennemann, Ph.D., Chief Scientific Officer, Nexigen GmbH, Germany
Novel technologies to access intractable target proteins have paved the way of cell-permeable peptide drugs into the clinic. This upcoming drug class allows the targeting of novel, and so far inaccessible disease mechanisms. The drugs in development are therefore associated with unique USPs. The talk will give an introduction to the field and current developments. In addition, novel ways to identify and further develop cell permeable peptide drug candidates will be presented. A case study regarding the development of cell-permeable peptide drug candidates in oncology (Wnt-pathway) will be discussed.
Hanjo Hennemann, Ph.D., Chief Scientific Officer, Nexigen GmbH, Germany
10:30
Networking Refreshment Break in Poster and Exhibit Hall
11:15
Novel Chemical Entities Introduced into Cells via a Bacterial Transporter
There are a number of methods to deliver bioactive peptides and proteins into mammalian cells for biotechnological purposes. However, most approaches do not allow for routine delivery of chemical entities such as peptidomimetics, mirror image peptides, cyclic peptides, and intrabodies. Here, I will present a macromolecular delivery platform based on a engineered bacterial transport machine that allows for facile delivery of bioactive peptide and protein variants to the cytosol of cells.
Brad L. Pentelute, Ph.D., Assistant Professor of Chemistry, MIT
There are a number of methods to deliver bioactive peptides and proteins into mammalian cells for biotechnological purposes. However, most approaches do not allow for routine delivery of chemical entities such as peptidomimetics, mirror image peptides, cyclic peptides, and intrabodies. Here, I will present a macromolecular delivery platform based on a engineered bacterial transport machine that allows for facile delivery of bioactive peptide and protein variants to the cytosol of cells.
Brad L. Pentelute, Ph.D., Assistant Professor of Chemistry, MIT
11:45
The Importance of Modulating Peptides in PKC-based Topical Drug Development
PKC, a family of serine/threonine kinases, plays fundamental roles in skin physiology and pathology. The presentation will focus on the properties of individual PKC isoforms and their distinct roles in skin cell signaling. Also, it will discuss approaches for developing selective PKC activity modulating peptides in topical drug development.
Liora Braiman-Wiksman, Ph.D., Vice President, R&D, HealOr Ltd., Israel
PKC, a family of serine/threonine kinases, plays fundamental roles in skin physiology and pathology. The presentation will focus on the properties of individual PKC isoforms and their distinct roles in skin cell signaling. Also, it will discuss approaches for developing selective PKC activity modulating peptides in topical drug development.
Liora Braiman-Wiksman, Ph.D., Vice President, R&D, HealOr Ltd., Israel
Innovations in Cell-Penetrating and Membrane-Permeating Peptides
12:15
EPiC Technology: Using Peptides to Physiologically Cross the BBB
Angiochem is utilizing its proprietary EPiC platform to create and develop drugs that physiologically cross the blood-brain barrier (BBB). The technology is based on proprietary sequences of amino acids called Angiopeps, engineered to specifically target LRP-1. EPiC drugs incorporate an Angiopep with a drug moiety to create new chemical entities (NCEs). The platform has been validated in human in two US clinical trials. Angiochem is developing its platform and its portfolio in wide varieties of indications including brain cancers, pain and others.
Jean-Paul Castaigne, M.D., CEO, Angiochem, Inc., Canada
Angiochem is utilizing its proprietary EPiC platform to create and develop drugs that physiologically cross the blood-brain barrier (BBB). The technology is based on proprietary sequences of amino acids called Angiopeps, engineered to specifically target LRP-1. EPiC drugs incorporate an Angiopep with a drug moiety to create new chemical entities (NCEs). The platform has been validated in human in two US clinical trials. Angiochem is developing its platform and its portfolio in wide varieties of indications including brain cancers, pain and others.
Jean-Paul Castaigne, M.D., CEO, Angiochem, Inc., Canada
12:45
Networking Luncheon in Poster and Exhibit Hall
Sponsored by
1:55
Chairperson's Remarks
Hanjo Hennemann, Ph.D., Chief Scientific Officer, Nexigen GmbH, Germany
Hanjo Hennemann, Ph.D., Chief Scientific Officer, Nexigen GmbH, Germany
2:00
Applications of Cell-Penetrating Peptides for Oligonucleotide Delivery
The technology for oligonucleotide transfection by cell-penetrating peptides is introduced. This technology enables the transfection of "difficult" cells with high efficacy and simple transfection protocol. Improved drug delivery by PepFects on the variety of different cargoes as well as the novel mechanism of uptake of PepFect/oligonucleotide nanoparticles is discussed.
Ulo Langel, Ph.D., Professor and Chairman, Department of Neurochemistry, Stockholm University, Sweden
The technology for oligonucleotide transfection by cell-penetrating peptides is introduced. This technology enables the transfection of "difficult" cells with high efficacy and simple transfection protocol. Improved drug delivery by PepFects on the variety of different cargoes as well as the novel mechanism of uptake of PepFect/oligonucleotide nanoparticles is discussed.
Ulo Langel, Ph.D., Professor and Chairman, Department of Neurochemistry, Stockholm University, Sweden
2:30
Innovations in Cell-Penetrating Peptides: Multi-Objective Optimization Strategies and CPPs with Intrinsic Activity
This presentation will highlight our research in the discovery of new cell-penetrating peptides (CPPs). Because CPPs comprise peptides from different classes, the focus will be especially on the importance of assessing the risk for potential liabilities within each class (i.e. cytotoxicity, mode of uptake, etc.). Examples will be presented of CPPs with intrinsic biological activity, as well as computational methods we are using to generate peptides that are cell-penetrating and non-cytotoxic, together with experimental results from these methods.
Francesca Milletti, Ph.D., Group Head, Cheminformatics & Statistics, Hoffmann-La Roche
This presentation will highlight our research in the discovery of new cell-penetrating peptides (CPPs). Because CPPs comprise peptides from different classes, the focus will be especially on the importance of assessing the risk for potential liabilities within each class (i.e. cytotoxicity, mode of uptake, etc.). Examples will be presented of CPPs with intrinsic biological activity, as well as computational methods we are using to generate peptides that are cell-penetrating and non-cytotoxic, together with experimental results from these methods.
Francesca Milletti, Ph.D., Group Head, Cheminformatics & Statistics, Hoffmann-La Roche
Peptide Generation, Lead Optimization and Candidate Selection
3:00
Creation of Chemically Constrained Peptides with High Potency and Selectivity using Bicycle Selection Technology
Bicycle technology applies principles of Darwinian selection to identify chemically constrained peptides with high target binding affinities and specificity. The technology allows the interrogation of chemical space not easily accessible by either small molecular weight drugs or antibodies and generates molecules which have many of the favourable characteristics of antibodies combined with the manufacturing simplicity and biophysical advantages of small molecules.
John Tite, Ph.D., CEO, Bicycle Therapeutics, United Kingdom
Bicycle technology applies principles of Darwinian selection to identify chemically constrained peptides with high target binding affinities and specificity. The technology allows the interrogation of chemical space not easily accessible by either small molecular weight drugs or antibodies and generates molecules which have many of the favourable characteristics of antibodies combined with the manufacturing simplicity and biophysical advantages of small molecules.
John Tite, Ph.D., CEO, Bicycle Therapeutics, United Kingdom
3:30
Networking Refreshment Break in Poster and Exhibit Hall
4:00
NextGen Venomics: Peptide Drug Discovery in Natural, Synthetic and Virtual Venoms
Venoms are made of hundreds of peptides and folded mini-proteins, highly potent and selective bioactives optimized by nature that have already led six drugs to market. Our original Venomics platform for lead discovery will be presented. It combines innovative delivery-oriented, bioactivity-guided (HTS of pre-fractionated Natural & Synthetic Venom libraries), structure-driven (venom proteomics, massive NextGen venom gland transcriptomics & targeted genomics) and biocomputing-assisted (proprietary databases & bioinformatic tools integrating Virtual Venoms) strategies.
Reto Stöcklin, Ph.D., President & CEO, Atheris Laboratories, Switzerland
Venoms are made of hundreds of peptides and folded mini-proteins, highly potent and selective bioactives optimized by nature that have already led six drugs to market. Our original Venomics platform for lead discovery will be presented. It combines innovative delivery-oriented, bioactivity-guided (HTS of pre-fractionated Natural & Synthetic Venom libraries), structure-driven (venom proteomics, massive NextGen venom gland transcriptomics & targeted genomics) and biocomputing-assisted (proprietary databases & bioinformatic tools integrating Virtual Venoms) strategies.
Reto Stöcklin, Ph.D., President & CEO, Atheris Laboratories, Switzerland
4:30
Therapeutic Peptide Lead Discovery & Lead Optimization
The lecture will discuss recent work from the Peptide Lead Discovery & Optimization Program at Pepscan Therapeutics. Making use of its high-throughput synthesis & screening facilities in combination with the proprietary CLIPS-technology, PEPSCAN has the ability to simultaneously and systematically produce binding data for thousands of 3D-structured peptides and derivatives, which can be used to affinity-mature lead peptides that need optimization in order to be therapeutically relevant. Latest data from this program will be discussed in detail.
Peter Timmerman, Ph.D., Chief Technology Officer, Pepscan Therapeutics B.V., The Netherlands
The lecture will discuss recent work from the Peptide Lead Discovery & Optimization Program at Pepscan Therapeutics. Making use of its high-throughput synthesis & screening facilities in combination with the proprietary CLIPS-technology, PEPSCAN has the ability to simultaneously and systematically produce binding data for thousands of 3D-structured peptides and derivatives, which can be used to affinity-mature lead peptides that need optimization in order to be therapeutically relevant. Latest data from this program will be discussed in detail.
Peter Timmerman, Ph.D., Chief Technology Officer, Pepscan Therapeutics B.V., The Netherlands
5:00
From Peptide Hits to Leads to Drug Candidates: The Impact of Medicinal Chemistry
The selection of the right drug candidate for clinical trials is pivotal to successful drug development. In vitro activity, efficacy, toxicology profiles, pharmacokinetics, and CMC aspects are crucial to minimize attrition in clinical development. It is 3B Pharmaceuticals' corporate objective to provide an integrated solution to this challenge. Our technology platform will be presented, including peptide medicinal chemistry and conjugation approaches. Selected projects from discovery to pre-clinical development illustrate successful peptide hit to lead optimization.
Ulrich Reineke, Ph.D., CEO and Co-Founder, 3B Pharmaceuticals, Germany
The selection of the right drug candidate for clinical trials is pivotal to successful drug development. In vitro activity, efficacy, toxicology profiles, pharmacokinetics, and CMC aspects are crucial to minimize attrition in clinical development. It is 3B Pharmaceuticals' corporate objective to provide an integrated solution to this challenge. Our technology platform will be presented, including peptide medicinal chemistry and conjugation approaches. Selected projects from discovery to pre-clinical development illustrate successful peptide hit to lead optimization.
Ulrich Reineke, Ph.D., CEO and Co-Founder, 3B Pharmaceuticals, Germany
5:30
Networking Reception and Booth Crawl in Poster and Exhibit Hall with Dedicated Poster Viewing
Poster presenters are requested to be available at their posters
Poster presenters are requested to be available at their posters
Courses: 星期日 | Plenary Sessions: 星期一 | Main Conference: 星期二 | 星期三
8:25
Chairperson's Remarks
Derek Maclean, Ph.D., Executive Director, Chemistry, KAI Pharmaceuticals
Derek Maclean, Ph.D., Executive Director, Chemistry, KAI Pharmaceuticals
Novel Peptide-Like Scaffolds and Peptide Discovery
8:30
Protein Epitope Mimetics - Highly Potent and Selective Modulators of Protein-Protein Interactions
Protein Epitope Mimetics (PEM) Technology has emerged as a powerful method to identify potent and selective modulators of protein-protein interactions (PPIs) [1]. PEM Technology has been clinically validated with two molecules (POL7080[2] and POL6326[1]) which are currently in clinical phase I and II, respectively. The presentation will explain the basic concept of PEM Technology and describe case studies of clinical relevance.
Daniel Obrecht, Ph.D., Chief Scientific Officer, Polyphor, Switzerland
Protein Epitope Mimetics (PEM) Technology has emerged as a powerful method to identify potent and selective modulators of protein-protein interactions (PPIs) [1]. PEM Technology has been clinically validated with two molecules (POL7080[2] and POL6326[1]) which are currently in clinical phase I and II, respectively. The presentation will explain the basic concept of PEM Technology and describe case studies of clinical relevance.
Daniel Obrecht, Ph.D., Chief Scientific Officer, Polyphor, Switzerland
9:00
Directed Peptide Optimization for Pharmacokinetic Enhancement through Incorporation of NMR and Proteolysis Mapping Data
PlGF-1 peptide antagonists, identified via phage peptide display, were rapidly inactivated in vivo, despite presentation as a CovX-Body. A series of NMR binding studies were conducted to understand the critical peptide components for PlGF-1 binding. In vitro peptide protease treatment and biotinylated-peptide in vivo cleavage mapping studies revealed an exo-cyclic C-terminal proteolytic hotspot of our lead peptide. This information facilitated systematic chemical modifications for pharmacokinetic enhancement. We will detail our efforts to optimize these peptides for in vivo stability.
Son Lam, Ph.D., Principal Scientist, Chemistry, CovX, Pfizer
PlGF-1 peptide antagonists, identified via phage peptide display, were rapidly inactivated in vivo, despite presentation as a CovX-Body. A series of NMR binding studies were conducted to understand the critical peptide components for PlGF-1 binding. In vitro peptide protease treatment and biotinylated-peptide in vivo cleavage mapping studies revealed an exo-cyclic C-terminal proteolytic hotspot of our lead peptide. This information facilitated systematic chemical modifications for pharmacokinetic enhancement. We will detail our efforts to optimize these peptides for in vivo stability.
Son Lam, Ph.D., Principal Scientist, Chemistry, CovX, Pfizer
9:30
Discovery of Bioactive Macrocyclic Peptides through DNA-Templated Synthesis and In Vitro Selection
In this lecture, I will describe the application of the powerful principles underlying biological evolution to the discovery of bioactive synthetic small molecules, resulting in new classes of potent and selective inhibitors of therapeutically relevant kinases and proteases.
David R. Liu, Ph.D., Professor of Chemistry and Chemical Biology, Howard Hughes Medical Institute Investigator, Harvard University
In this lecture, I will describe the application of the powerful principles underlying biological evolution to the discovery of bioactive synthetic small molecules, resulting in new classes of potent and selective inhibitors of therapeutically relevant kinases and proteases.
David R. Liu, Ph.D., Professor of Chemistry and Chemical Biology, Howard Hughes Medical Institute Investigator, Harvard University
10:00
Direct Selection of Cyclic Peptidomimetics from In Vitro Display Libraries
Peptide modifications aimed at enhancing bioavailability are typically added after a candidate sequence is isolated, often reducing potency and usually failing to generate high quality clinical leads. Ra Pharma's Extreme Diversity™ platform uses in vitro display technologies to create cyclic peptidomimetic libraries of up to 100 trillion members and directly select extremely rare compounds with desirable features. By incorporating unnatural side chains and N-substituted amino acids, Ra creates libraries that are highly enriched in sequences with drug-like properties.
Douglas A. Treco, Ph.D., President and CEO, Ra Pharmaceuticals, Inc.
Peptide modifications aimed at enhancing bioavailability are typically added after a candidate sequence is isolated, often reducing potency and usually failing to generate high quality clinical leads. Ra Pharma's Extreme Diversity™ platform uses in vitro display technologies to create cyclic peptidomimetic libraries of up to 100 trillion members and directly select extremely rare compounds with desirable features. By incorporating unnatural side chains and N-substituted amino acids, Ra creates libraries that are highly enriched in sequences with drug-like properties.
Douglas A. Treco, Ph.D., President and CEO, Ra Pharmaceuticals, Inc.
10:30
Networking Refreshment Break with Poster and Exhibit Viewing
11:15
Phylomer Libraries for the Discovery of Custom Scaffolds Tailored for Particular Intracellular Targets
Phylomers are a new class of peptide, derived from genomic fragments of biodiverse archael and bacterial species which encode structural motifs which have evolved within proteins. The hits from Phylomer peptide libraries are typically of higher quality and quantity than those from random combinatorial peptide libraries. Phylomer libraries can be used to identify new cell penetrating peptides for delivery of macromolecules into cells. Some of these cell penetrating Phylomers are specific for particular cell types and most belong to new families, including those with a net negative charge.
Paul Watt, Ph.D., CEO, Phylogica, Australia
Phylomers are a new class of peptide, derived from genomic fragments of biodiverse archael and bacterial species which encode structural motifs which have evolved within proteins. The hits from Phylomer peptide libraries are typically of higher quality and quantity than those from random combinatorial peptide libraries. Phylomer libraries can be used to identify new cell penetrating peptides for delivery of macromolecules into cells. Some of these cell penetrating Phylomers are specific for particular cell types and most belong to new families, including those with a net negative charge.
Paul Watt, Ph.D., CEO, Phylogica, Australia
New Approaches to Making Drug-Like Peptides
11:45
Cyclic Cell Penetrating Peptides (CCPPs): A New Class of Cell Penetrating Peptides
Disulfide-rich cyclic peptides occur naturally in a range of plants and animals and are notable for their exceptional resistance to proteolytic breakdown. We have discovered that several subclasses of these peptides interact with membranes and are able to penetrate cells. These peptides are amenable to chemical synthesis and can be re-engineered to deliver bioactive peptide cargoes into cells.
David Craik, Ph.D., Professor of Biomolecular Structure, University of Queensland, Australia
Disulfide-rich cyclic peptides occur naturally in a range of plants and animals and are notable for their exceptional resistance to proteolytic breakdown. We have discovered that several subclasses of these peptides interact with membranes and are able to penetrate cells. These peptides are amenable to chemical synthesis and can be re-engineered to deliver bioactive peptide cargoes into cells.
David Craik, Ph.D., Professor of Biomolecular Structure, University of Queensland, Australia
12:15
D-Peptide Inhibitors of HIV Entry
HIV entry inhibitors target key proteins on the viral or host cell surface to prevent viral entry. Using mirror-image phage display and structure-assisted design, we identified a protease-resistant D-peptide, PIE12-trimer, that potently inhibits diverse strains from all major HIV subtypes. PIE12-trimer's ultra-high target affinity provides a reserve of binding energy ("resistance capacitor") that yields a dramatically improved resistance profile compared to other entry inhibitors. We have also designed variants of PIE12-trimer with enhanced PK properties to support weekly dosing.
Michael S. Kay, M.D., Ph.D., Associate Professor of Biochemistry, University of Utah School of Medicine
HIV entry inhibitors target key proteins on the viral or host cell surface to prevent viral entry. Using mirror-image phage display and structure-assisted design, we identified a protease-resistant D-peptide, PIE12-trimer, that potently inhibits diverse strains from all major HIV subtypes. PIE12-trimer's ultra-high target affinity provides a reserve of binding energy ("resistance capacitor") that yields a dramatically improved resistance profile compared to other entry inhibitors. We have also designed variants of PIE12-trimer with enhanced PK properties to support weekly dosing.
Michael S. Kay, M.D., Ph.D., Associate Professor of Biochemistry, University of Utah School of Medicine
12:45
Networking Luncheon in Poster and Exhibit Hall
Last Chance for Poster and Exhibit Viewing
Last Chance for Poster and Exhibit Viewing
1:55
Chairperson's Remarks
David Tumelty, Ph.D., Associate Director Chemistry, BioTherapeutics R&D, CovX, Pfizer
David Tumelty, Ph.D., Associate Director Chemistry, BioTherapeutics R&D, CovX, Pfizer
2:00
Mirror Image Proteins as Novel Anti-Angiogenic Agents
Mirror image proteins are made entirely out of D-amino acids, making them metabolically inert and non-immunogenic. Reflexion's first product blocks VEGF-A, a hemangiogenic factor. VEGF-A blockade is used to treat a variety of cancers and ocular diseases by modulating new blood vessel growth. Reflexion's second product blocks the growth factor VEGF-D, a lymphangiogenic factor. Blocking VEGF-D may effectively treat a rare disease called lymphangioleimyomatosis, which primarily afflicts young women and currently has no effective treatment.
Dana Ault-Riché, Ph.D., CEO, Reflexion Pharmaceuticals
Mirror image proteins are made entirely out of D-amino acids, making them metabolically inert and non-immunogenic. Reflexion's first product blocks VEGF-A, a hemangiogenic factor. VEGF-A blockade is used to treat a variety of cancers and ocular diseases by modulating new blood vessel growth. Reflexion's second product blocks the growth factor VEGF-D, a lymphangiogenic factor. Blocking VEGF-D may effectively treat a rare disease called lymphangioleimyomatosis, which primarily afflicts young women and currently has no effective treatment.
Dana Ault-Riché, Ph.D., CEO, Reflexion Pharmaceuticals
2:30
Applying the DRP Platform to Overcome Challenges of Ion Channel Therapeutic Development.
Evolved proteolytic resistance of Disulfide-Rich Peptides (DRPs) has been harnessed by Protagonist in developing the DRP technology platform; validated through generation of IL-6 antagonists. Now we report on development of modulators of therapeutically-relevant ion channels; well acknowledged as challenging targets. With respect to Nav1.7, a target for chronic pain, the DRP platform addresses PK and selectivity issues of known peptide modulators. Expertise in multi-disulfide peptide chemistry and design-based scaffold manipulation has generated novel and improved agents of therapeutic potential.
Craig A. Murphy, Ph.D., Head of Discovery Research, Protagonist Therapeutics
Evolved proteolytic resistance of Disulfide-Rich Peptides (DRPs) has been harnessed by Protagonist in developing the DRP technology platform; validated through generation of IL-6 antagonists. Now we report on development of modulators of therapeutically-relevant ion channels; well acknowledged as challenging targets. With respect to Nav1.7, a target for chronic pain, the DRP platform addresses PK and selectivity issues of known peptide modulators. Expertise in multi-disulfide peptide chemistry and design-based scaffold manipulation has generated novel and improved agents of therapeutic potential.
Craig A. Murphy, Ph.D., Head of Discovery Research, Protagonist Therapeutics
Creative Strategies to Improve Peptide Drug Discovery and Expand Target Space
3:00
Multifunctional Antibody Conjugates (MAC): A Platform Peptide-Antibody Conjugate Technology
Over the past three years, a multi-disciplinary team at CovX/Pfizer has been developing a platform technology for the discovery and development of novel peptide-antibody conjugates, which we term MAC (Multi-functional Antibody Conjugate) Technology. This will be illustrated by discussion of a particular project that highlights the following areas: the MAC technology itself and site-directed conjugation, the peptide chemistry involved in the process, chemistry of the conjugation reaction and its analysis, and scale-up and analysis of the Reg Tox batch of activated peptide and MAC conjugate product.
David Tumelty, Ph.D., Associate Director Chemistry, BioTherapeutics R&D, CovX, Pfizer
Over the past three years, a multi-disciplinary team at CovX/Pfizer has been developing a platform technology for the discovery and development of novel peptide-antibody conjugates, which we term MAC (Multi-functional Antibody Conjugate) Technology. This will be illustrated by discussion of a particular project that highlights the following areas: the MAC technology itself and site-directed conjugation, the peptide chemistry involved in the process, chemistry of the conjugation reaction and its analysis, and scale-up and analysis of the Reg Tox batch of activated peptide and MAC conjugate product.
David Tumelty, Ph.D., Associate Director Chemistry, BioTherapeutics R&D, CovX, Pfizer
3:30
Networking Refreshment Break
4:00
Novel Dual-Acting Peptide Drugs for Treatment of Diabetes and Obesity
Many endogenous peptide hormones are involved in the metabolic and homeostatic processes that are involved in glucose metabolism and body weight dynamics. At Zealand Pharma, one core technological approach has been to design dual- and triple-acting peptides that seek to possess potency towards two or three discrete peptide receptors in the search for effective and safe novel drugs for metabolic diseases. Several of these dual and triple peptide agonist approaches will be reviewed including the ongoing programs on GLP-1 Glucagon (partnered with Boehringer Ingelheim) and GLP1-Gastrin.
Christian Grøndahl, Ph.D., Chief Scientific Officer, Zealand Pharma, Denmark
Many endogenous peptide hormones are involved in the metabolic and homeostatic processes that are involved in glucose metabolism and body weight dynamics. At Zealand Pharma, one core technological approach has been to design dual- and triple-acting peptides that seek to possess potency towards two or three discrete peptide receptors in the search for effective and safe novel drugs for metabolic diseases. Several of these dual and triple peptide agonist approaches will be reviewed including the ongoing programs on GLP-1 Glucagon (partnered with Boehringer Ingelheim) and GLP1-Gastrin.
Christian Grøndahl, Ph.D., Chief Scientific Officer, Zealand Pharma, Denmark
4:30
Degarelix - A Potent Peptidic Self-Assembling GnRH Receptor Blocker
Natural fibrils can perform vital beneficial functions in bacteria, fungi, and even in mammals and new research indicates that synthetic fibrils can be exploited medically. Degarelix is a peptide which functions as a depot product for treatment of prostate cancer. When degarelix is injected into the subcutis, functional fibrils are spontaneously formed and the peptide is released from these fibrils in a slow and controlled manner.
Tine E. Gottschalk, Ph.D., Senior Research Scientist, Ferring Pharmaceuticals, Denmark
Natural fibrils can perform vital beneficial functions in bacteria, fungi, and even in mammals and new research indicates that synthetic fibrils can be exploited medically. Degarelix is a peptide which functions as a depot product for treatment of prostate cancer. When degarelix is injected into the subcutis, functional fibrils are spontaneously formed and the peptide is released from these fibrils in a slow and controlled manner.
Tine E. Gottschalk, Ph.D., Senior Research Scientist, Ferring Pharmaceuticals, Denmark
5:00
Stapled Peptide Drugs: Overcoming Biophysical and Pharmacological Barriers
Stapled Peptides are a promising breakthrough therapeutic modality for the treatment of many diseases by modulating of intracellular or extracellular targets. Examples of Stapled Peptides demonstrating remarkable in vivo properties will be described. Such studies will further illustrate the multi-therapeutic propensity of this new class of drugs and how they have unique capabilities to overcome biophysical and pharmacological barriers.
Tomi K. Sawyer, Ph.D., Chief Scientific Officer and Senior Vice President, Aileron Therapeutics
Stapled Peptides are a promising breakthrough therapeutic modality for the treatment of many diseases by modulating of intracellular or extracellular targets. Examples of Stapled Peptides demonstrating remarkable in vivo properties will be described. Such studies will further illustrate the multi-therapeutic propensity of this new class of drugs and how they have unique capabilities to overcome biophysical and pharmacological barriers.
Tomi K. Sawyer, Ph.D., Chief Scientific Officer and Senior Vice President, Aileron Therapeutics
5:30
Close of Conference