By 2018, the global Peptide Therapeutics market is expected to reach over $25 billion. This dramatic market increase is driven by both growing incidences of cardiovascular and metabolic diseases, and technological enhancements in peptide
synthesis that include high-throughput approaches. Hybrid technology combining solid and liquid syntheses is also contributing to the growth of peptide therapeutics, as are novel modes of conjugation.
This meeting will explore the burgeoning world of Peptide Therapeutics and how peptides are being engineered to penetrate cancer tumors and conquer unmet medical needs. Improving peptide properties, such as stability and half-life, will also be discussed,
along with innovating routes of administration. Case studies will be presented that illustrate the progress made in developing efficacious peptide therapeutics, while leaders in the field point the way to the future for these promising drugs.
WEDNESDAY, MAY 6
7:00 am Registration and Morning Coffee
8:00 Chairperson’s Remarks
Volker Schellenberger, Ph.D., President and CEO, Discovery, Amunix, Inc.
8:10 KEYNOTE PRESENTATIONS
Development of Bicyclic Peptides for Therapeutic Application
Christian Heinis, Ph.D.,
Professor, Therapeutic Peptides and Proteins, École Polytechnique Fédéral de Lausanne (EPFL)
Bicyclic peptides have two macrocyclic rings that can bind to protein targets much like antibodies interact through CDRs, but they have around a 100-fold smaller mass. The small size allows chemical synthesis and brings advantages in therapeutic applications
as, for example, good tissue penetration. We have recently developed new bicyclic peptide formats that will be presented.
8:40 FEATURED PRESENTATION:
High Affinity Bicyclic Peptides: Application to Payloads in Oncology
Christophe Bonny, Ph.D., Chief Scientific Officer, Bicycle Therapeutics Limited
The Bicycle technology is based on repertoires of peptides that can be modified with organochemical scaffolds to create a diverse array of constrained peptides. The bicycle peptides show antibody-like properties such as low to sub-nanomolar affinities
and exquisite selectivity, but in a 100-fold smaller, chemically synthesized format. Bicycle Therapeutics will present in vivo POC data from its preclinical programs demonstrating the power of its technology to deliver cytotoxic payloads to tumor
cells.
A look back at the 2014 exclusive interview with Dr. Bonny
9:10 Peptide Therapeutics and the Quest for Differentiated Medicines
Maria Ufret, Ph.D., Group Leader, Chemistry, Ipsen Bioscience, Inc.
Peptides possess a unique potential to function as receptor agonists, targeting agents or bifunctional molecules, yet peptides remain an underrepresented modality in pharmaceutical development pipelines. Strategies that synergize both biological screening
tools along with chemical approaches to deliver peptide therapeutic leads against targets not readily addressed by small molecules or antibodies will be presented.
9:40 Understanding the Mechanism of Physical Instability of Peptide Pharmaceuticals
Karolina Zapadka, Ph.D.
Candidate, Formulation Group, MedImmune, LLC
Aggregation and amyloid fibril formation of peptides and proteins is a widespread and intensively studied problem. Hence, the ability to understand the formation and proliferation of aggregates under specific conditions is of critical importance along
with developing ways to control the process. This study has worked towards a better understanding of the mechanism of the aggregation and amyloid fibrillation of human GLP-1 as a model peptide.
10:10 Identifying Novel Drug Leads: Proteome-Wide Screening of Peptide Motifs that Inhibit Protein-Protein Interactions
Philip M. Kim, Ph.D., Associate Professor,
The Donnelly Centre for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, Molecular Genetics and Computer Science, University of Toronto
I will present our novel technology platform that allows us to screen all peptide motifs in the human proteome as inhibitors of protein-protein interactions. Briefly, we have devised a strategy that expresses each peptide motif intracellularly and can
monitor the phenotype it causes. We do so using a pooled strategy, and screen about 500,000 peptide motifs. We thereby identify many novel target interactions whose inhibition shows very strong and specific phenotypes in cell lines.
10:40 Coffee Break in the Exhibit Hall with Poster Viewing
11:25 Use of Cell Penetrating Peptides to Mute Physiologically Deleterious Signal Cascades
Jamie L. Wilson, Ph.D., Research Associate, Boston University School of Medicine
We are controlling signal transductions initiated by G-protein coupled and tyrosine kinase receptors by targeting receptor motifs which link to specific signal cascades with cell penetrating peptides (CPP). Similarly we are also controlling downstream
signal point. We have used the hypoxic rat model of Pulmonary Hypertension in vivo and human pulmonary artery smooth muscle cell migration in culture as physiologic targets to demonstrate the potential of control through the CPP.
11:55 Ligand-Independent Inhibitory Peptides (SCHOOL Peptides) in Medicine: Recent Advances and Future Perspectives
Alexander B. Sigalov,
Ph.D., President and Founder, SignaBlok, Inc.
New model of cell signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) model, and peptides that employ novel, ligand-independent mechanisms of receptor inhibition (SCHOOL peptides) will be briefly reviewed. As an exemplary use case, preclinical
studies of the SCHOOL peptide inhibitor of TREM-1 receptor in free and nanoparticle-bound forms in cells and animal models of cancer and sepsis will be presented.
12:25pm Enjoy Lunch on Your Own
2:10 Chairperson’s Remarks
Jeffrey Wang, Ph.D., Associate Professor, Pharmaceutical Sciences, Western University of Health Sciences
2:15 Role of Guanylate Cyclase Agonists in the Regulation of Gastrointestinal Function and Treatment of Gastrointestinal Diseases
Mark Currie, Ph.D., Senior Vice President, Chief Scientific Officer & President, R&D, Ironwood Pharmaceuticals, Inc.
In the current talk, we will focus on the actions of linaclotide, a synthetic 14-amino acid peptide GCC agonist, on animal models of abdominal pain and intestinal transit and the relationship of these actions for the treatment of intestinal dysfunction
in irritable bowel sydrome with constipation (IBS-C) and chronic constipation (CC) patients by examining the effect of linaclotide treatment on the abdominal symptoms associated with IBS-C, including abdominal pain.
2:45 Orally Stable Peptides for Gastrointestinal Diseases
Dinesh V. Patel, Ph.D., President
& CEO, Protagonist Therapeutics
Targeted therapy in the field of GI diseases is currently dominated by injectable antibodies. Protagonist is pursuing the discovery and development of orally stable peptides based NCEs as a safer and superior choice for targeted treatment of inflammatory
bowel diseases (IBD, Crohn’s and Ulcerative Colitis). R&D progress towards orally stable antagonists of alfa4beta7 integrin, a clinically validated IBD specific target, will be highlighted.
3:15 SELECTED POSTER PRESENTATION
B10: A Conjugation Approach to Produce a S. aureus Synbody with Bactericidal Activity in Serum
Chris W. Diehnelt, Assistant Research Professor, Center for Innovations in Medicine, Biodesign Institute, Arizona State University
3:45 Refreshment Break in the Exhibit Hall with Poster Viewing
4:45 Problem-Solving Breakout Discussions
How Can Disruptive Innovations in Drug Delivery be Integrated into Early Stage Development?
Moderator: Leila Hassani-Beniddir, PharmD & Ph.D., Scientist--Novel Drug delivery Technologies, Peptides Development--CMC, Ipsen
Oral Peptide Drugs
Moderator: Dinesh V. Patel, Ph.D., President & CEO, Protagonist Therapeutics
Generation of Long-Acting Biotherapeutics
Moderator: Volker Schellenberger, Ph.D., President and CEO, Discovery, Amunix, Inc.
- Methods to increase time action
- How to minimize product viscosity?
- Combining multiple actives into a single product
- Incorporation of synthetic payloads
5:45 Networking Reception in the Exhibit Hall with Poster Viewing
7:00 End of Day
THURSDAY, MAY 7
8:00 am Morning Coffee
8:30 Chairperson’s Remarks
Jamie L. Wilson, Ph.D., Research Associate, Boston University School of Medicine
8:35 Cysteine Perfluoroarylation and Ultra Rapid Peptide Synthesis
Bradley L. Pentelute, Ph.D., Pfizer-Laubach Career Development Assistant Professor, Chemistry, Massachusetts
Institute of Technology (MIT)
Here we report a novel and robust method for macrocyclization of unprotected peptides using cysteine arylation. This chemistry allowed for peptide modifications that imparted favorable cell penetration and proteolytic stability. In addition, we
describe a rapid flow solid phase peptide synthesis methodology that enables incorporation of an amino acid residue in 1.5 minutes. To demonstrate the broad applicability of this method, it was employed to synthesize hundreds of peptides and
proteins.
9:05 XTEN – A Biodegradable and Monodisperse PEG Alternative for Monthly Dosing of Peptides
Volker Schellenberger, Ph.D., President and CEO, Discovery, Amunix, Inc.
Amunix has developed XTEN, a protein-based polymer that mimics the biophysical properties of PEG. XTEN is monodisperse, extremely hydrophilic, and it contains conjugation sites in precisely controlled locations. XTEN is stable in circulation but
readily degraded upon internalization which eliminates the risk of long-term polymer accumulation associated with PEG. XTEN offers class-leading monthly dosing.
9:35 Targeted Peptide-Directed Ablation of Adipose Stromal Cells Suppresses Obesity and Cancer Progression in Animal Models
Mikhail Kolonin, Ph.D., Associate Professor and Director, Center For Metabolic and Degenerative Diseases, University of Texas Health Science Center
As shown by our studies, adipose stromal cells (ASC), not only serve as adipocyte progenitors, but also promote cancer through supporting vasculature. We recently characterized a peptide that specifically targets ASC (Daquinag et al. Cell Stem
Cell 2011) and used it to design a targeted pro-apoptotic peptide ablating ASC in vivo (Daquinag et al., in press). We show that in mice this compound suppresses overgrowth of white fat tissue and inhibits tumor growth.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
11:05 Patient-Focused Peptide Delivery
Leila Hassani-Beniddir, PharmD & Ph.D., Scientist--Novel Drug delivery Technologies, Peptides Development--CMC, Ipsen
The high potency and specificity of peptides have made them attractive drug candidates with several blockbuster molecules. Recent advances in peptide delivery technologies are opening up the possibility of developing oral, nasal, buccal, transdermal
and inhaled routes for a wider range of peptides, with many in late stage development and close to market. Recent developments in novel peptide delivery technologies will be reviewed with an emphasis on key factors that might determine their
success.
11:35 Lipid Conjugates for Peptide Drug Delivery
Jeffrey Wang, Ph.D., Associate Professor, Pharmaceutical Sciences, Western University of Health Sciences
The use of peptides as therapeutic drugs offers many advantages. However, the delivery of peptides often faces challenges due to their inherently unfavorable pharmacokinetic properties. Lipid conjugation is one of the practical approaches
to improve these properties and two lipid-peptide conjugates (recombinant insulin detemir and liraglutide) are approved for clinical use. This presentation will include a discussion of the rationale for lipid conjugation, along with several
case studies.
12:05 pm Sponsored Presentation (Opportunity Available)
12:35 End of Conference
5:15 Registration for Dinner Short Courses