USA flag logo/image

An Official Website of the United States Government

Novel Methylenecyclopropane Analogues as Anti-Human Herpesvirus 6 and 8 Agents

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
Program Year/Program:
2012 / SBIR
Agency Tracking Number:
R44AI082799
Solicitation Year:
2012
Solicitation Topic Code:
NIAID
Solicitation Number:
PA10-123
Small Business Information
MICROBIOTIX, INC
ONE INNOVATION DR WORCESTER, MA -
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 2
Fiscal Year: 2012
Title: Novel Methylenecyclopropane Analogues as Anti-Human Herpesvirus 6 and 8 Agents
Agency: HHS
Contract: 2R44AI082799-03
Award Amount: $2,990,305.00
 

Abstract:

DESCRIPTION (provided by applicant): The human herpesviridae family contains eight members divided into three subfamilies, designated alpha, beta and gamma. The alpha herpes viruses include herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2) and varicella zoster virus (VZV). The beta herpes viruses include human cytomegalovirus (HCMV), two variants of human herpes virus 6 (HHV-6A, HHV-6B), and human herpes virus 7 (HHV-7). The gamma herpes viruses include Epstein-Barr virus (EBV) and human herpes virus 8 (HHV-8). Herpes virus infections are commonly acquired, and many present major health concerns, especially among immunocompromised patient populations (e.g., transplant recipients, AIDS patients, and the elderly). Because of the narrow spectrum of current therapeutics, emergence of resistant virus strains, and the limiting toxicities of current treatment options, there is a definite need for new agents that are effective and safe for treating herpes virus infections, particularly those caused by drug-resistant virus strains in the immunocompromised patient. We have previously identified the methylenecyclopropane nucleosides (MCPNs) as potent inhibitors of HCMV, HHV- 6 and HHV-8. The original goal of the SBIR Phase I proposal was to identify new MCPN analogs with even greater anti-HHV6/8 potency and efficacy, while maintaining HCMV activity. We have exceeded that SBIR Phase I goal, and have now identified novel MCPN analogs with a very unusual, broad anti-herpes spectrum of activity that includes the alpha-, beta- and gamma-herpes viruses, including ACV resistant strains. To our knowledge, this broad spectrum activity has not been seen with existing anti-herpes virus agents. The primary objective of this SBIR Phase II proposal is to evaluatea limited number of the most potent MCPNs in murine toxicity, PK/PD, and efficacy (HSV/CMV/VZV) in animal models to identify a final broad- spectrum anti-herpes virus preclinical candidate, and backup compound, to advance into IND enabling rat GLP toxicology and safety pharmacology studies. PUBLIC HEALTH RELEVANCE: The overall goal of the project is to develop a single agent active against all herpes viruses for use in the immunocompromised patient population. The primary objective of this SBIR Phase II proposal is to evaluate a limited number of the most potent MCPNs in murine toxicity, PK/PD, and efficacy (HSV/CMV/VZV) models to identify a final broad-spectrum anti-herpes virus preclinical candidate, and backup compound, to advance into IND-enabling rat GLP toxicology and safety pharmacology studies.

Principal Investigator:

Terry L. Bowlin
508-757-2800
tbowlin@microbiotix.com

Business Contact:

Kim L. Kapteyn
508-757-2800
kkapteyn@microbiotix.com
Small Business Information at Submission:

MICROBIOTIX, INC
ONE INNOVATION DR WORCESTER, MA -

EIN/Tax ID: 106153834
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No