SBIR and STTR Success Story for
SIGA Technologies, Inc.

(Information Posted/Updated on 01/31/2008)

SIGA Technologies, Inc.
4575 SW Research Way
Suite 230
Corvallis, OR  97333

Contact:    Melissa Lehew
Phone:      541-766-3740
Fax:          541-753-9999
Web Site:

Project Title:  Small Molecule Inhibitors of Smallpox Virus Replication
Related Award(s):  1 R43 AI056409-01, 2 R44 AI056409-02 - 06
Technology Developed:
The Phase I SBIR supported development of a validated virus-specific high throughput screening assay to identify specific inhibitors of variola virus. This assay was used to screen a proprietary chemically diverse library of over 400,000 small molecule compounds for inhibitors of orthopoxvirus-induced cytopathic effects. Inhibitor compounds were evaluated for chemical tractability, antiviral potency and spectrum and selectivity as well as activity against authentic variola virus in cell culture (performed through collaborating laboratories). Lead compounds were optimized and mechanism of antiviral action was determined.

The Phase II SBIR supported lead optimization, animal efficacy evaluations, and preclinical development of ST-246 the lead compound identified from the initial screen. This work resulted in a submission of an investigational new drug application (IND) with the FDA to support human clinical development of ST-246 for the treatment of pathogenic orthopoxvirus infections.

Key Words:  antiviral, smallpox, ST-246, egress inhibitor, biodefense, high throughput screen.
Uses of Technology/Products/Service:
The primary use of ST-246 is to treat and prevent diseases caused by pathogenic orthopoxvirus infections including smallpox and to prevent side-effects associated with the current smallpox vaccine.

While smallpox is no longer endemic it is considered a formidable biowarfare threat. ST-246 works by preventing egress of extracellular forms of virus thereby, blocking the ability of the virus to spread to other cells. This compound is well-tolerated and has been demonstrated to protect mice, rabbits, ground squirrels, and non-humam primates from lethal orthopoxvirus challenge. The compound is safe and well tolerated in humans with plasma drug exposure levels comparable to those that provide efficacy in animal models of orthopoxvirus disease. The FDA has designated ST-246 for “fast-track” status, creating a path for expedited FDA review and eventual regulatory approval. ST-246 can be used for the following indications:

• prophylaxis: preventing the orthopoxvirus disease in non-vaccinated individuals

• post-exposure therapeutic: treating disease in non-symptomatic people exposed to smallpox virus

• therapeutic: treating those with smallpox symptoms

• adjunct to vaccination: combining with smallpox vaccines to prevent disease and reduce vaccine-related complications.

Benefit to Company:
Prior to initiation of the biodefense-specific RFA, there was little financial incentive to develop therapeutics for biodefense applications. The SBIR program provided the impetus for establishing screening programs to identify inhibitors of category A biodefense pathogens. The success of these screening programs have lead to potential products that have created value through grants, contracts, and partnering opportunities with the ultimate goal of procurement to the Strategic National Stockpile for biodefense products. SBIR funding provided SIGA with the opportunity to utilize in-house expertise to develop a smallpox antiviral to fulfill this critical unmet need.

How Product Was Commercialized:
The primary customer for biodefense antiviral products will be U.S. government, and specifically the Strategic National Stockpile (SNS). In addition, many category A biowarfare agents are endemic and governments investing in public health will also serve as potential markets. Continued collaboration with the NIH and other government agencies involved in the development and procurement of biodefense products is the primary means to commercialize SIGA products.

Other Comments Related to Company's Success Story:
ST-246 is the first drug to demonstrate complete protection against death from variola and monkey pox. In 2007, SIGA was granted an emergency IND to treat a patient suffering from severe eczema vaccinatum with ST-246.

Estimated Future Annual R&D and/or Sales from this Project:   $100M