Bridgewater Chapter Upcoming Events Join PCCI


The Wistar Institute

An early stage drug discovery company

Presenter: Troy Messick, Senior Staff Scientist


Monday, January 16, 2017

Embassy Suites, Chesterbrook, Pennsylvania (directions)




Unmet Medical Need

Epstein Barr Virus (EBV) is a human gamma-herpesvirus that infects over 90% of the adult population worldwide. EBV is causative of a number of neoplastic diseases, including nasopharyngeal carcinoma, Burkitt lymphoma, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, gastric carcinoma, and lymphoproliferative disorders in immunocompromised patients (HIV-associated or after solid organ transplant), such as hairy leukoplakia and central nervous system lymphomas.  Increasing evidence provide an association between EBV with a higher risk of certain autoimmune diseases, for example, multiple sclerosis.  200,000 cancer cases per year are attributable to EBV. The World Health Organization has classified EBV as a human class I carcinogen due to its association with 1-2% of all human cancers worldwide.


Therapeutic strategy

A consortium of academic and industrial partners has discovered novel inhibitors that are targeted toward therapeutic intervention of EBV-associated diseases. Epstein-Barr Nuclear Antigen 1 (EBNA1) is an ideal target for elimination of latent infection and treatment of EBV-associated disease as it is expressed in all EBV-positive tumors. EBNA1 is required for immortalization of primary B-lymphocytes and for the stable maintenance of the EBV genome in latently infected cells. The structure of EBNA1 contains a unique fold that has no homology to other proteins in the human proteome. By targeting a virally expressed protein with no known human orthologs, we have mitigated the potential risk of dose-limiting toxicity. The three-dimensional structure of EBNA1 bound to the inhibitors has been solved by X-ray crystallography and this has driven the chemical strategy.  We have developed an in depth understanding of the structure-activity relationship with over 70 high-resolution co-crystal structures and more than 1500 compounds synthesized and evaluated during the lead optimization phase of the program.  A portfolio of three non-overlapping patents has been filed to protect these chemically-unique EBNA1 inhibitors.


 Preclinical Development to Clinical Development

In conjunction with our clinical partners, we established a target product profile (TPP) to guide our preclinical development program.  Based on the TPP, we set rigorous, industry-accepted attributes that the drug candidate must possess to justify progression to IND-enabling studies. Our clinical candidate meets or exceeds those criteria, which includes standards for potency, selectivity, safety and tolerability.  Our clinical candidate shows excellent efficacy in 4 different EBV-dependent mouse models, including patient-derived xenograft studies with a >16-fold therapeutic window.  And we have performed validation studies to demonstrate in vivo target engagement.  Currently, we are performing solid-state analysis, salt selection, and formulation work.  IND-enabling studies including safety pharmacology and toxicology and GMP manufacturing will commence later this year with a projected First-In-Human clinical trial in H1 2018.  We anticipate that EBV plasma levels will be a useful surrogate biomarker that correlates with disease prognosis and progression.

In summary, our potent EBV-specific clinical candidate:

  • Represents a first-in-class oncology product that addresses an unmet medical need,
  • Possesses potent nanomolar activity, is selective and efficacious in animal models,
  • Should be more effective, better tolerated and safer than the current standard of care, and
  • Meets or exceeds industry-accepted criteria for drug suitability, safety and toxicology.
  • IND-enabling studies will begin later this year with a projected FIH clinical trial in H1 2018.
  • We have assembled a team that includes clinical investigators from Stanford, MSKCC and Chinese University of Hong Kong to conduct a Phase I clinical trial in NPC patients.



3 Major Issues


  1. Regulatory and clinical trial strategy:
    We are currently in the development phase of the program with a potential IND and start of the clinical trial in Q1/Q2 2018.  There are many diseases that are associated with EBV for which our drug could potentially be effective.  Each of these patient populations have advantages and risks.  For example, there is a high incidence of nasopharyngeal carcinoma (NPC) in southeast Asia including Hong Kong and a phase I clinical trial could be carried out there in 2 years in patients with recurrent or metastatic NPC.  An advantage of NPC is that there are plasma biomarkers available to monitor disease progression.  For a Phase II/III studies, one would probably have to involve China, which presents from a regulatory and commercial perspective.  Some have advised us to do a clinical trial in post transplant lymphoproliferative disease (PTLD) or EBV-postive lymphomas.  Because it’s an anti-EBV drug, others have advised us to do a phase I study in healthy volunteers.  Which strategy would you recommend that balances regulatory, clinical and commercial risks and benefits?
  2. Development partner strategy:
    Many potential investors or industrial partners on first pass dismiss this program as not having a large enough market.  Obviously, we disagree.  What can we be doing to bolster their interest?  Which companies should we be targeting?
  3. Funding strategy:
    We have been successful at attracting funding from government sources and the Wellcome Trust.  Current funding will support the program through filing the IND.  We are now, however, entering a new phase that requires funding for a clinical trial.  It presents a particular dilemma because this program has its roots in a non-profit institution and because of our natural inclination to preserve control over the program and the value of the asset.  What should our strategy be to raise funds for a clinical trial?





6:30 - Cocktails & Dinner (Cash bar and special 2-entree buffet menu)

8:00 - Troy Messick, Senior Staff Scientist, will deliver the Company's "Elevator" Pitch to the Group

8:20 - A Panel will address three major issues crucial to helping the Company reach the next level.

9:00 - Open discussion: members and guests



Available Media

Please note: All information obtained here is the property of those presenting and should not be copied or duplicated without written consent.



None available at this time


None available at this time


None available at this time


None available at this time



Contact Info:



Our Sponsors

EisnerAmperGlaxoSmithKlineKEH Insurance Agency
New Jersey Institute of Technology
Science CenterWhite and Williams


<Top of the page>





Questions or Coments?

Contact: Peter van der Kam, | (610) 296-8086




Good Company! Good Drink! Good Food! Good Program! Good Fun!


Site Navigation



Pharmaceutical Consulting Consortium International, Inc., or (610) 296-8086

Meetings Held at Embassy Suites - Valley Forge

888 Chesterbrook Blvd, Chesterbrook, Pennsylvania 19087

All content on this website is copyrighted and should not be reproduced without the consent of PCCI.

© Copyright 2016-2018



Tat Communication Inc