Cambridge Healthtech Institute’s Second Annual

Peptide Discovery and Delivery

Developing the Next Generation of Targeted Peptide Therapeutics

March 26-27, 2018 | Boston Marriott Cambridge | Cambridge, MA

CHI’s Peptide Discovery and Delivery conference reveals the latest strategies at the forefront of peptide discovery, chemistry and delivery with in-depth sessions on new chemistries, novel delivery mechanisms and the most important preclinical and clinical updates, helping you develop the next-generation of peptides therapeutics, including latest developments in antimicrobial peptides, peptide vaccines and macrocyclic and constrained peptides.

Final Agenda

Monday, March 26

7:00 am Registration and Morning Coffee

New Peptide Discoveries and Chemistries

8:00 Welcome Remarks from Conference Director

Daniel Barry, Senior Conference Director, Cambridge Healthtech Institute

8:10 Chairperson’s Opening Remarks

Lex Van der Ploeg, PhD, CSO, Rhythm Pharmaceuticals


8:15 KEYNOTE PRESENTATION: Peptide Drug Hunter: An Extraordinary Trek into Intracellular Target Space

Tomi_SawyerTomi Sawyer, PhD, Distinguished Scientist, Discovery Chemistry Modalities, Merck Research Laboratories

A deeper understanding of peptide science and technology is driving a renaissance in peptide drug discovery. This presentation will highlight past achievements and future opportunities to advance novel peptide therapeutics in tackling intracellular target space and complex diseases thereof.

8:45 High-Throughput Selection of Peptides with Biological Function

Alex_BatchelorAlex Batchelor, PhD, CEO, Orbit Discovery

Peptide therapeutics has been greatly enhanced by the evolution of display technologies. These technologies enable the move from peptide discovery which uses endogenous peptides as a starting point to discovery which uses large, random libraries to identify novel structures. This means we can address targets for which there are no known peptide binder. Peptide display is used to present natural peptides to both purified and cell-surface targets.

9:15 Genetic Encoded Peptide Libraries, 48 Hours Hits Identification

Ratmir_DerdaRatmir Derda, PhD, Assistant Professor, University of Alberta

Genetically-encoded (GE) libraries of peptides are one of the major sources of discovery of biological drugs and development of ligands. We use GE libraries as starting materials for multi-step organic synthesis. Examples are N-terminal conjugation and cyclization of linear peptides with simultaneous introduction of glycan entities. We developed the Genetically-Encoded Fragment-Based Discovery (GE-FBD) platform, which combines >109 peptides with GE-modifications. The talk will describe the progress and challenges in application of GE-FBD platform.

9:45 Networking Coffee Break

Is Glucagon a Suitable Drug Target?

10:30 Is Glucagon a Suitable Drug Target?

Thomas_KruseThomas Kruse, PhD, Senior Principle Scientist, Novo Nordisk

The pharmaceutical industry has pursued glucagon as a drug target for years with no clear consensus on the way forward. Agonists or antagonists? Long-acting or short-acting? This talk summarizes the literature and the Novo Nordisk efforts to understand glucagon pharmacology in greater depth.

11:00 Identification of Long Acting GIP/GLP-1 Dual-Acting Peptide Hormones

Pernille_Tofteng_SheltonPernille Tofteng Shelton, PhD, Senior Scientist, Medicinal Chemistry, Zealand Pharma

Research showing beneficial metabolic effects of GIPR and GLP-1R co-activation in T2D patients has led to a renewed interest in GIP biology. Here we present the design and characterization of long acting novel balanced GLP-1-GIP receptor dual agonists. We will describe optimization of enzymatic stability, chemical and physical stability, and half-life extension through albumin binding with a Lys17 acylation. These novel potent dual-agonists have a significantly increased half-life and demonstrate pharmacodynamic effects in mice.

New Peptide Developments

11:30 FEATURED PRESENTATION: Setmelanotide for the Treatment of Severe Obesity Resulting from MC4-Pathway Deficiency

Lex_Van_der_PloegLex Van der Ploeg, PhD, CSO, Rhythm Pharmaceuticals

Setmelanotide is a once daily injectable cyclic octapeptide MC4R agonist that acts as a precision medicine ‘replacement’ therapy to compensate for the lack/reduction of endogenous MC4R-pathway activation, leading to re-establishing weight and appetite control. Setmelanotide is currently in Phase III trials for the treatment of POMC, PCSK1 and LEPR deficiency related obesity. Our epidemiological studies have unveiled the predicted prevalence of MC4R-pathway genetic deficiencies. We are currently addressing the position of other MC4R-pathway genes to identify additional at-need patient populations that could benefit from setmelanotide therapy.

12:00 pm Enjoy Lunch on Your Own

Macrocyclic and Constrained Peptides

1:25 Chairperson’s Remarks

Jean Chmielewski, PhD, AW Kramer Distinguished Professor, Department of Chemistry, Purdue University

1:30 Properties of Orally Bioavailable Peptide Macrocycles beyond the Rule-of-5

Alan_MathiowetzAlan Mathiowetz, PhD, Director, Discovery Network, Pfizer, Inc.

Peptidic macrocycles with properties beyond the Rule-of-5 (BRo5) have the potential to be effective modulators of difficult targets. Oral delivery of BRo5 molecules is challenging and requires a balance of competing properties such as permeability, clearance, and potency; macrocyclization has the potential to impact all of these properties. This talk provides an overview of structure/property trends we have found spanning multiple series of BRo5 peptidic macrocycles.

2:00 Macrocyclic Peptide Inhibitors of the Hedgehog Signaling Pathway

Rudi_FasanRudi Fasan, PhD, Associate Professor, Department of Chemistry, University of Rochester

The Hedgehog signaling pathway plays a central role during embryonic development and its aberrant activation has been implicated in the development and progression of several human cancers. This talk will describe the design and optimization of macrocyclic peptides capable of inhibiting the Hedgehog pathway by targeting and disrupting the Hedgehog protein/Patched interaction, the most upstream event in the ligand-induced activation of this cell signaling pathway.

2:30 Turning Full Circle from Linear to Cyclic Azapeptide Modulators of the Cluster of Differentiation 36 Receptor

William_LubellWilliam D. Lubell, PhD, Département de Chimie, Université de Montréal

Azacyclopeptides were identified that exhibited unprecedented CD36 binding affinity and ability to reduce the overproduction of nitric oxide, an important marker of inflammation produced by macrophages when stimulated by the Toll-like receptor-2 agonist fibroblast-stimulating lipopeptide. Our presentation will describe synthetic methods, structure-activity relationships and conformational analyses to provide understanding of the requirements for azacyclopeptide CD36 modulator activity.

3:00 Refreshment Break in the Exhibit Hall with Poster Viewing

3:45 Stalking Elusive Pathogenic Bacteria with Cationic Amphiphilic Polyproline Helices: Diving into Human Cells to Treat Infections

Jean Chmielewski, PhD, AW Kramer Distinguished Professor, Department of Chemistry, Purdue University

A number of pathogenic bacteria invade and reside within mammalian host cells. However, most commonly used antibiotics are unable to achieve therapeutic concentrations within these same cells. There is a great need, therefore, to develop antibiotics that enter mammalian cells and target intracellular pathogens. In this work we have developed cationic amphiphilic polyproline helical (CAPHs) peptides containing unnatural proline amino acids.

4:15 Targeting Intracellular Protein-Protein Interactions with Structure-Based Designed Macrocyclic Peptides

David_SpellmeyerDavid Spellmeyer, CSO, Circle Pharma

Circle Pharma deploys a structure-based design/synthetic chemistry platform for macrocycle therapeutic discovery that incorporates prediction of intrinsic cell permeability as a key step in the design workflow. While this platform is target-agnostic, Circle’s internal pipeline is directed to intracellular protein-protein interactions that are key drivers in oncology pathways, including p53:MDM2/4, MCL1:BH3, cyclinA:cdk2 and beta-catenin:TCF4. Examples of Circle’s development work will be presented.

4:45 Poster Presentation: Ni-Catalyzed Photoredox C-O Coupling, Accessing Proteolytically Stable and Permeable Peptides

Hyelee Lee, PhD., Post Doc, Merck

5:15 Welcome Reception in the Exhibit Hall with Poster Viewing

6:15 End of Day

Tuesday, March 27

7:30 am Breakfast Breakout Roundtable Discussions

Grab a cup of coffee and join a roundtable discussion. These are moderated discussions with brainstorming and interactive problem solving, allowing participants from diverse backgrounds to exchange ideas and experiences and develop future collaborations around a focused topic.

Balancing Cost and Risk in Peptide Manufacturing from Early Development through Late Stage clinical trials

Moderator: Dave Garman, PhD, CTO, NoNO, Inc.

  • Managing CMC development on limited budget
  • Selecting the appropriate manufacturing scales for early development
  • Analytical method development and validations – timing and risks vis a vis safety and clinical studies

Measuring and Optimizing Cell Penetration for Peptides and Macrocycles

Moderator: Joshua Kritzer, PhD, Associate Professor, Department of Chemistry, Tufts University

  • Advantages and disadvantages of current methods for measuring cell penetration
  • Success stories of cell-penetrant peptides and macrocycles, and what can be learned from them
  • Emerging guidelines for maximizing cell penetration

Peptides for Cancer - Vaccines and Conjugates

8:25 Chairperson’s Remarks

Jesse Dong, PhD, Vice President, Peptide Chemistry, Neon Therapeutics

8:30 Engineering Potent NaV1.7 Inhibitory Peptide-Antibody Conjugates

Justin_MurrayJustin Murray, PhD, Senior Scientist, Hybrid Modality Engineering, Amgen

We describe NaV1.7 inhibitory peptide-antibody conjugates for potential prolonged channel blockade. A GpTx-1 peptide was conjugated to a carrier monoclonal antibody, and variations in attachment site, linker, and peptide loading established design parameters for potency optimization. Antibody conjugation led to in vivo half-life extension by 130-fold relative to a nonconjugated GpTx-1 peptide. Further improvements in potency have been achieved through the conjugation of selective analogs of JzTx-V.

9:00 Development Strategies of Neo-Antigen-Based Personalized Cancer Vaccines

Jesse_DongJesse Dong, PhD, Vice President, Peptide Chemistry, Neon Therapeutics

Neon Therapeutics is pursuing an exciting clinical development program of a personalized cancer vaccine, NEO-PV-01, which targets patient-specific tumor neoantigens to engage the immune system to precisely and selectively attack tumors. Our objective is to create and deepen anti-tumor immune responses and broaden the range of cancers treatable via immuno-oncology approaches.

9:30 Nanofitin-Drug Conjugates for Solid Tumors: From Imaging to Treatment

Olivier_KittenOlivier Kitten, PhD, Founder & CEO, Affilogic

The putative advantage of small targeting scaffolds in comparison with antibodies lies in their small size, at the expense of a short plasma half-life. The 7 kDa, highly specific Nanofitins are protein scaffolds that exhibit high tumor invasion capability. This feature is conserved after addition of cytotoxic payloads and radiotracers. Combined with Nanofitin-based half-life extension moieties, these assemblies constitute a novel set of therapeutically relevant modalities that will be illustrated.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

Peptide Developments

10:30 Chairperson’s Remarks

Jesse Dong, PhD, Vice President, Peptide Chemistry, Neon Therapeutics

10:35 The Development of Stapled Peptide Therapeutics

Loren_WalenskyLoren D. Walensky, MD, PhD, Professor of Pediatrics, Investigator, Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute – Boston Children’s Hospital, Harvard Medical School

This presentation describe our 15 year experience in developing stapled peptides as research tools and prototype therapeutics, highlighting lessons learned, pitfalls to avoid, and keys to translational success. With stapled peptides having now traversed the arc from concept to clinical trials, a new generation of structured peptide therapeutics is emerging, with potential broad and transformational biomedical applications.

11:05 Preclinical Studies on P8, a Novel Disease-Modifying Peptide Drug Candidate for the Treatment of Alzheimer’s Disease

Nazneen_DewjiNazneen Dewji, PhD, Associate Adjunct Professor of Medicine, UCSD and President and CEO, Cenna Biosciences, Inc., USA

We previously demonstrated that two small, non-overlapping peptides, P4 and P8, from the PS-1 NH2-terminal domain, can substantially and specifically inhibit the production of total Aβ as well as Aβ40 and 42 in model systems of AD without affecting the catalytic activities of β- or γ-secretase, or the level of APP. These peptides and their derivatives offer new disease-modifying drug candidates for the treatment of AD. We now provide data on the preclinical development of the lead peptide drug candidate P8.

11:35 Networking Luncheon

12:30 Dessert Break in the Exhibit Hall with Poster Viewing


Improving Peptide Delivery

1:15 Chairperson’s Remarks

Jesse Dong, PhD, Vice President, Peptide Chemistry, Neon Therapeutics

1:20 How Can Nanosystems Help Address Present and Future Challenges in Peptide Delivery?

Hayat_OnyukselHayat Onyuksel, PhD, Professor, Department of Biopharmaceutical Sciences, University of Illinois, Chicago

Peptides, which have become very attractive drugs in the last decades, remain difficult-to-administer molecules, because they have a short plasma half-life and are very sensitive to enzymatic and pH-driven degradation. Moreover, they show a poor cellular membrane permeability. Then, nano-delivery systems can provide appropriate solutions to address present and future challenges of peptide delivery, especially stability, crossing cellular membrane and targeting diseased tissues.

1:50 Cell Penetration Profiling for Biotherapeutics

Joshua Kritzer, PhD, Associate Professor, Department of Chemistry, Tufts University

Several classes of biomolecules have emerged as exciting potential therapies, but their development has been impeded by imprecise measurements of intracellular delivery. The Kritzer lab has devised a new method for quantitating cell penetration, the ChloroAlkane Penetration Assay (CAPA). CAPA is inexpensive and high-throughput, and it can quantitate penetration to individual cellular compartments. We are using CAPA to comprehensively profile cell penetration for diverse biomolecules and drug delivery systems.

2:20 Poster Presentation: Binding Determinants and Inhibition of Trehalose-6-Phosphate Phosphatase

Christine Harvey, Student, Boston University

Xeris’ XeriSol™ formulation technologies allow for the subcutaneous (SC) and intramuscular (IM) delivery of highly-concentrated, non-aqueous, ready-to-use formulations. The XeriSol formulation technology platform is specifically designed to produce optimal stability and solubility with peptide-based drugs. This platform can achieve high solubility and room temperature stability for peptides currently encountering formulation challenges. Potential benefits include: Eliminating reconstitution, enabling long-term room-temperature stability, significantly reduced injection volume and enabling co-delivery/co-formulation of active pharmaceutical ingredients

2:35 Poster Presentation: A*STAR Peptide Engineering Programme (PEP) Technologies and Capability

Charles Johannes, PhD, Head, Organic Chemistry, Institute of Chemical and Engineering Sciences (ICES), Agency for Science, Technology and Research (A*STAR)

2:50 Refreshment Break in the Exhibit Hall with Poster Viewing

Peptide Stability and Manufacturing

3:35 Stable and Effective Formulations of Peptide Drugs in Phospholipid Micelles

Hayat_OnyukselHayat Onyuksel, PhD, Professor, Department of Biopharmaceutical Sciences, University of Illinois, Chicago

Poor stability of peptide drugs causes a major problem during manufacturing, storage and in vivo use. Stability of peptide drugs can significantly be improved when delivered in sterically stabilized phospholipid micelles (SSM). In this talk, using vasoactive intestinal peptide (VIP) as a model drug, data obtained with free peptide or in SSM on two disease models, RA and IBD, will be compared. Reasons for significant improvements in peptide drug stability, efficacy and safety when used as a nanomedicine (VIP-SSM) will be explained.

4:05 Transitioning Manufacturing Processes from Clinical Trial Supply to Registration and Pre-Commercial Readiness

Dave_GarmanDave Garman, PhD, CTO, NoNO, Inc.

There are vast differences in the manufacturing and testing requirements between supplying a drug for clinical trials and registering a drug for market access. For small to midsize companies, these development expenses are often pushed to late stages when the risk of failure in clinical studies is lower. We examine the transition to commercial development of drug substance and drug product manufacturing processes to mitigate risks of a FDA refusal to file in the context of our Phase III peptide therapeutic NA-1.

4:35 High Throughput Purification of Synthetic Peptides by Reversed Phase Chromatography

Mathias Schaffrath, PhD., Group Head, Sanofi-Aventis Deutschland GmbH

The purification of synthetic peptides (25-55 amino acids) is still a challenge. The unwanted by-products of these peptides are often peptides with only one wrong amino acid in the sequence. Therefore, the peptide and the by-products elute at the same time during the chromatographic separation. The reversed phase chromatography is in many cases the method of choice. Sometimes orthogonal reversed phase methods with two chromatographic steps and two different column selectivities are needed to increase the purity to more than 95%. Chromatographic experience, a thorough method development and up scaling is needed for successful separations. Partial automation of the process leads to a remarkable throughput, which is particularly important in the field of research.

5:05 Close of Conference