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

Sunday, March 25

4:30 pm Dinner Short Course and Pre-Conference Registration


5:00-8:00 SC1: Oligonucleotide Therapeutics: From Discovery to Manufacturing*

RNAi/antisense oligonucleotides can target virtually any disease-causing gene and promise to become a third major class of therapeutics (besides small molecules and biologics). For this to happen, however, several challenges have to be addressed. This course discusses considerations taken into account when selecting oligonucleotide therapeutic programs: from target and delivery selection to developmental and manufacturing particularities. Detailed discussion will focus on, but not be limited to, the tightly interconnected factors of therapeutic indication, delivery and targets, as well as chemistry manufacturing and controls (CMC), regulatory, cost, and intellectual property considerations. Developers who are seeking a comprehensive and up-to-date overview from recognized oligonucleotide development experts are highly encouraged to join.

Instructors:

Dmitry Samarsky, PhD, CSO, Silence Therapeutics


* Separate registration required.

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

 


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. Phage 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 Sponsored Presentation (Opportunity Available)

10:15 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 Session Break

12:10 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:40 Session Break

Macrocyclic and Constrained Peptides

1:25 Chairperson’s Remarks

 

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 Discovery and Development of Novel Macrocycle Drugs: Outer Membrane Protein Targeting Antibiotics (OMPTA), a New Class with a Novel Mode of Action

Daniel_OrbechtDaniel Obrecht, PhD, CSO & Co-Founder, Pharma, Polyphor Ltd

We have recently shown exceptional in vitro activity on the most recently emerging antibiotic-resistant strains, and in animal model studies we have shown excellent in vivo efficacy against relevant bacterial strains, including resistant strains. We will also give an update on our lead antibiotic Murepavadin (POL7080), which is a narrow-spectrum, targeted therapy for Pseudomonas infections in critically ill patients in the ICU. POL7080 has successfully completed Phase II and we are preparing the path forward for a Phase III registration trial.

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 Sponsored Presentation (Opportunity Available)

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



6:15 Dinner Short Course Registration


6:30-9:30 SC2: Overcoming Challenges with Peptide Delivery*

Peptides make attractive drug candidates due to their specificity, potency and low toxicity, but present particular challenges for their delivery to the site of action, due to their short half-life and susceptibility to proteolytic degradation. This short course reviews the latest challenges in peptide drug delivery and the various options available, including oral, transdermal and nanosystems. We also look at challenges around half-life, bioavailability, stability and formulation.

Instructor:

Joël Richard, PhD, Senior Vice President, Peptides Development, Ipsen


* Separate registration required.

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.

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 Sponsored Presentation (Opportunity Available)

11:50 Session Break

12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

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

Improving Peptide Delivery

1:15 Chairperson’s Remarks

Steve Prezstelski, PhD, CSO, Xeris Pharmaceuticals

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

Joël_RichardJoël Richard, PhD, Senior Vice President, Peptides Development, Ipsen

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, nanodelivery systems (e.g., nanotubes, nanoparticles) can provide appropriate solutions to address present and future challenges of peptide delivery, especially for sustained release, or to cross cellular membranes and target intracellular receptors.

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 Update on Xeris Peptide Development and Delivery

Steve Prezstelski, PhD, CSO, Xeris Pharmaceuticals

2:50 Sponsored Presentation (Opportunity Available)

3:05 Refreshment Break in the Exhibit Hall with Poster Viewing

Peptide Stability, Antimicrobials and Preparing for Commercialization

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

Hayat 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 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.

5:05 Close of Conference