OPT Congress
OPT Congress

Peptide Discovery and Development

With over 150 peptide therapeutics in clinical trials and 500 in preclinical development, the peptide area is thriving with new chemistries, designs and discoveries. However, challenges still remain in delivering peptides into patients and, more importantly, keeping them there.

Cambridge Healthtech Institute's Peptide Discovery and Development meeting brings you the latest findings in peptide chemistry, design, delivery, formulation and development, with in-depth case studies and scientific updates from industry's leading players and new, upcoming biotechs, helping you build the next generation of peptide therapeutics.

Final Agenda

Monday, March 27

7:00 am Registration and Morning Coffee

Challenges and Opportunities in Peptide Discovery and Development

8:00 Welcome Remarks from Conference Director

Daniel Barry, Senior Conference Director, Cambridge Healthtech Institute

8:10 Chairperson’s Opening Remarks

Waleed Danho, Ph.D., Distinguished Research Leader and Consultant for Peptides, Danho Associates, Inc., USA

8:15 FEATURED PRESENTATION: Peptide Drug Hunter: Breakthrough Medicines and Disruptive Innovation

Tomi_SawyerTomi Sawyer, Ph.D., 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 Strategy for Highly Efficient Synthesis of the Insulin Superfamily Peptides

Fa_LiuFa Liu, Ph.D., Director, Medicinal Chemistry, Novo Nordisk

Chemical synthesis of the insulin superfamily peptides presents unique challenges associated with peptide assembly and disulfide bond formation. We have established a general biomimetic strategy enabling high efficient synthesis exemplified by insulin, relaxin-2 and insulin-like peptide 5. The key steps involve a unique intermediary and temporary oxime-based ligation that enables high efficient formation of disulfide bonds, and two alkaline mediated degradative steps to yield native heterodimeric insulin-like peptides.

9:15 DNA-Encoded Libraries of Peptidomimetic Compounds as a Source of Probe Molecules and Drug Leads

Thomas_KodadekThomas Kodadek, Ph.D., Professor of Chemistry & Cancer Biology, Chair, Department of Cancer Biology, The Scripps Research Institute

We have collaborated with the laboratory of Brian Paegel at TSRI to develop efficient methods for the synthesis and production of novel DNA-encoded one bead one compound libraries. Unlike most DNA-encoded libraries, these are made by solid-phase synthesis on hydrophilic beads, which confers several advantages, including the ability to rigorously quality control the library. The synthesis and screening of these libraries will be described.

Forte Bio 9:45 Peptide-Based Nanodrugs: A Strategy to Improve Protein Nanoconjugate Efficacies

Paul Hubbard, Project Scientist, Department of Biomedical Sciences, Cedars-Sinai Medical Center

Reducing the size of conjugated nanotherapeutics is a simple strategy that aims to improve drug distribution and cellular uptake. We have taken a high-affinity trastuzumab-conjugated lead and reduced its size in part by exchanging the conjugated monoclonal antibody with a lower affinity 12-mer anti-HER2/neu peptide. Surface plasmon resonance shows that while conjugation reduces the peptide’s affinity for recombinant Her2 receptor, the off-rate is relatively unaffected, and in vivo efficacy is comparable to the antibody-conjugated form.

 10:15 Coffee Break in the Exhibit Hall with Poster Viewing

Peptide Design and Discovery

10:45 Discovery of Novel Ion Channel Modulators from Animal Venoms

Laurent_BialyLaurent Bialy, Ph.D., Section Head, R&D IDD Medicinal Chemistry, Research & Development Integrated Drug Discovery Medicinal Chemistry, Sanofi

Animal venoms are potentially a valuable resource for finding new drug candidates. Despite several examples in recent literature, only a minute fraction of animal toxins has been discovered so far. The structure elucidation and synthesis of new ion channel modulators identified from an animal venom screening campaign will be presented. First in vitro and SAR results will be discussed in the context of a recent drug discovery project.

11:15 Engineered Dengue EDIIIs as Broad Immunogens

Jonathan_LaiJonathan R. Lai, Ph.D., Associate Professor, Department of Biochemistry, Albert Einstein College of Medicine

Dengue virus is a flavivirus that causes hundreds of millions of infections world-wide each year. There are four serotypes of Dengue (DENV1-4) that co-circulate in hyperendemic regions. Primary infection by a single serotype results in febrile illness, but secondary infections by heterotypic serotypes can lead to severe disease. We will discuss structure-based protein design and phage display approaches to develop novel broad immunogens (subunit vaccines) against all four DENV serotypes.

11:45 Design, Synthesis and Affinity Selection of a DNA Encoded Cyclic Peptide Library

Chris Arico-Muendel, Ph.D., Manager, NCE Molecular Discovery, R&D Platform Technology and Sciences, GSK.

12:15 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

Peptides for CNS and Cardiovascular

1:55 Chairperson’s Remarks

Soumitra S. Ghosh, Ph.D., CSO, Avexegen Therapeutics, Inc.

2:00 The CS6253 ABCA1 Agonist Peptide Reverses apoE4 Alzheimer’s Disease

Jan_JohanssonJan Johansson, M.D., Ph.D., CEO & President, Artery Therapeutics, Inc.

Apolipoprotein E4 (apoE4) is the strongest risk factor for Alzheimer’s disease (AD) and no treatment is available. This presentation will show how we contrasted CS6253 peptide effects in apoE4 and apoE3 astrocytes (cholesterol efflux) and target replacement (TR) mice (brain phenotype and cognition). ABCA1 agonist treatment by CS653 resulted in improved apoE4 lipidation in cells and in mice. Six weeks of treatment counteracted apoE4-driven AD with regard to both phenotype and cognition.

2:30 NA-1: The Development of an Intracellular Peptide Therapeutic for Stroke from Animal Studies through the Late Stage Clinical Studies ESCAPE-NA1 and FRONTIER

Dave_GarmanDave Garman, Ph.D., CTO, NoNO, Inc.

NA-1 is a novel peptide therapeutic shown to reduce brain ischemia and improve neurological function in rodent and primate models of stroke. The FRONTIER trial is assessing the efficacy of administering NA-1 in the ambulance as soon as possible after the onset of stroke, and the ESCAPE-NA-1 trial is testing the effect of NA-1 in acute ischemic stroke patients who are candidates for endovascular reperfusion.

3:00 Discovery and Development of KISS1R Agonists as Clinical Peptide Therapeutics

Taiji_AsamiTaiji Asami, Ph.D., Associate Director, Medicinal Chemistry Research Laboratories, Pharmaceutical Research Division, Takeda

Kisspeptin (Kp) and its receptor KISS1R play critical roles in the regulation of the hypothalamic–pituitary–gonadal (HPG) axis. Highly potent and stable nonapeptides TAK-683 and TAK-448 were rationally designed and synthesized as analogues of the N-terminally truncated decapeptide of Kp. Continuous dosing of TAK-683 and TAK-448 effectively suppressed the HPG axis, which indicates the potential of these investigational drugs for sex-hormone-dependent diseases.

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

PeptideS for Gastrointestinal Disorders

4:00 A Novel Mucosal Healing Therapy for Inflammatory Gastrointestinal Disorders

Soumitra S. Ghosh, Ph.D., CSO, Avexegen Therapeutics, Inc.

Avexegen Therapeutics is developing Neuregulin-4 (NRG‐4), a naturally occurring constituent of human breast milk, as a novel mucosal healing peptide therapeutic for inflammatory disorders of the gastrointestinal tract. NRG-4 leverages physiological mechanisms to both directly protect the intestinal epithelium and to attenuate colonic macrophage-driven inflammatory cascade. These actions have been shown to promote mucosal healing and restoration of the damaged gut barrier in multiple experimental animal models of intestinal inflammation.

4:30 Evolving Clinical Profile of Linaclotide: Driving Innovation for Patients with Functional GI Disorders

Mark_CurrieMark G. Currie, Ph.D., President and CSO, Ironwood Pharmaceuticals

Linaclotide is a synthetic 14-amino acid peptide that is approved for treatment of adults with chronic constipation and irritable bowel with constipation (IBS-C). In animal models, linaclotide acts through stimulation of guanylate cyclase-C to decrease abdominal pain. Based on these findings, and our experience with decreasing pain in the IBS-C patients, we continue to study these actions as we seek to advance and expand the clinical profile of this peptide.

5:00 Optimizing Permeability and Bioavailability of Peptide Macrocyclics

David Price, Ph.D., Senior Director, Worldwide Medicinal Chemistry, Pfizer

OligoFactory5:30 Welcome Reception in the Exhibit Hall with Poster Viewing

 6:15 Short Course Registration

Tuesday, March 28

7:30 am Breakfast 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.

View Roundtable Discussions

Non-Invasive Peptide Delivery

8:25 Chairperson’s Remarks

Ved Srivastava, Ph.D., Vice President, Peptide Chemistry, Intarcia Therapeutics

8:30 FEATURED PRESENTATION: Delivery of Peptides by Non-Invasive Routes: Focus on Successful Oral Technologies Progressing in the Clinic and Future Challenges

Joel_RichardJoël Richard, Ph.D., Senior Vice President, Peptides Development, Ipsen

Injectable sustained-release peptide formulations based on biodegradable microparticles or implants have been very successful to enhance patient adherence and convenience, and increase safety and efficacy. They are likely to remain a significant and important part of the new peptide products coming to the market. However, the tremendous developments in alternative non-invasive routes of delivery are likely to result in more and more peptides being delivered by the transdermal, nasal, inhalation and oral routes. The main purpose of this talk will be to analyze and compare the various alternative non-invasive peptide delivery technologies progressing in the clinic, discussing the pros and cons of these technologies in regards to stability, bioavailability, safety/efficacy balance, impact on costs of goods and manufacturability.

9:00 Oral Bioavailability beyond the Rule of 5: Attempts at Oral Delivery of a Series of Short Unnatural Peptides

Claudio_MapelliClaudio Mapelli, Ph.D., Principal Scientist, Discovery Chemistry Modalities, Merck Research Laboratories

Cell membrane permeability and oral bioavailability of peptides remain a challenge, in spite of recent advances in peptide drug design and formulation methods. This presentation will focus on a number of approaches investigated to orally deliver a new class of re-designed GLP-1 peptides with improved stability. Key findings will be presented on how bioavailability was modulated using structural modifications and formulation methodologies. Lessons learned will be reviewed and utilized to define some of the challenges in oral delivery of rule of 5 breakers.

9:30 Oral Inhalation – A Simple Approach to Peptide Delivery

John_FreemanJohn Freeman, Ph.D., Principal Scientist, Formulations Development Department, Mannkind Corporation

Oral inhalation, a viable option for peptide drug delivery, provides benefits such as rapid onset of action, avoidance of first pass metabolism, and elimination of injections. While oral inhalation is the standard for treating pulmonary diseases, only within the last decade has it been applied to therapies requiring systemic exposure. Development of orally inhaled dry powders will be exemplified with non-clinical data in the therapeutic areas of diabetes, obesity, and pain.

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

Improving Peptide Delivery

10:40 Chairperson’s Remarks

Ved Srivastava, Ph.D., Vice President, Peptide Chemistry, Intarcia Therapeutics

10:45 Oral Insulin for Diabetes Treatment: Bypassing the Roadblock

Miriam_KidronMiriam Kidron, Ph.D., CSO and Director, Oramed Pharmaceuticals, Inc.

A novel platform for preserved bioavailability and effective delivery of protein and peptide therapeutics will be described. Results demonstrating applicability of this platform toward delivery of insulin and exenatide to manage diabetes, as assessed in animal models, healthy volunteers and in both type 1 and type 2 diabetes patients, will be presented. In addition, the physiological benefits of oral versus subcutaneous insulin delivery will be discussed.

11:15 Discussion Panel: Peptide Formulation: 

Ved Srivastava, Ph.D., Vice President, Peptide Chemistry, Intarcia Therapeutics


11:45 Sponsored Presentation (Opportunity Available)

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

Delivering Potent, Stable and Long-Lasting Peptides

1:25 Chairperson’s Remarks

Joël Richard, Ph.D., Senior Vice President, Peptides Development, Ipsen

1:30 FEATURED PRESENTATION: Strategies for Peptide Optimization and Sustain Delivery for Longer than Once a Week

Ved_SrivastavaVed Srivastava, Ph.D., Vice President, Peptide Chemistry, Intarcia Therapeutics

Peptide therapeutics continue to develop biopharmaceutical pipelines, and a number of GLP-1 analogs made remarkable commercial successes. Design and development strategies for a potent and stable peptide including longer duration of action are still challenging. In this presentation, we will discuss overcoming challenges from BID to once a year/half yearly delivery of GLP-1 agonist.

2:00 Harnessing Transthyretin to Enhance the Circulation Half-Life of Peptides

Mamoun_AlhamadshehMamoun Alhamadsheh, Ph.D., Associate Professor, Department of Pharmaceutics & Medicinal Chemistry, University of the Pacific

The tremendous therapeutic potential of peptides has not yet been fulfilled. A major challenge impeding the widespread use of peptides as therapeutics is their poor pharmacokinetic profile, due to short in vivo half-life. In this talk, we will discuss our effort in developing a fundamentally new approach for enhancing the in vivo half-life of peptides without affecting its biological activity, which could decrease dosing frequency and improve patient compliance.

2:30 Transdermal Approach to Peptide Delivery

Alan_SmithAlan Smith, Ph.D., Vice President and Co-Founder, 4P Therapeutics

Transdermal delivery offers a needle-free alternative to injection of peptides and avoids the disadvantages associated with the pulmonary/nasal and oral routes. Currently marketed transdermal products are limited to small lipophilic molecules that can penetrate the skin. Various approaches have been developed to overcome the skin barrier to enable peptide delivery at therapeutic levels in humans. An overview of the field will be presented and the limitations of the transdermal route and challenges for commercialization will be discussed.

3:00 Sponsored Presentation (Opportunity Available)

3:15 Refreshment Break in the Exhibit Hall with Poster Viewing

Manufacturing, Analytics and CMC Strategies

3:40 Chairperson’s Remarks

Waleed Danho, Ph.D., Distinguished Research Leader and Consultant for Peptides, Danho Associates, Inc., USA

3:45 Automated Flow Peptide Synthesis: Toward Amide Bonds at Nature’s Pace

Bradley_PenteluteBradley L. Pentelute, Ph.D., Professor Pfizer-Laubach Career Development, Department of Chemistry, Associate Member, Broad Institute of Harvard and MIT

This presentation describes a rapid flow solid phase peptide synthesis methodology that enables incorporation of an amino acid residue in 40 seconds with amide-bond formation taking only 5 seconds. To demonstrate the broad applicability of this method, it was employed to synthesize hundreds of peptides and proteins.

4:15Leveraging Biophysical Characterization in the Formulation Development of Multi-Dose Aggregation-Prone Peptides

Jingtao_ZhangJingtao Zhang, Ph.D., Principle Scientist, Merck

Synthetic peptides are conformationally more flexible than protein or other large biomacromolecules due to the relatively small size. As a result, the development of aggregation-prone peptides as a therapeutic could be highly challenging. The presentation will focus on the characterization of reversible and irreversible fibril aggregates in peptide formulations, biophysical assays that guide AME study design, and high resolution biophysical study to enable insights in formulation stabilization mechanism. Overall considerations on the development of multi-dose peptide formulations as well as strategies in overcoming the challenges will also be highlighted.

4:45 Close of Conference