Soligenix, Inc., a development stage biopharmaceutical company, has submitted a full contract proposal to the Biomedical Advanced Research and Development Authority (BARDA) Division of Chemical, Biological, Radiological and Nuclear (CBRN) Medical Countermeasures. This submission supports a potential multi-year, multi-million dollar contract to develop OrbeShield (oral beclomethasone 17,21-dipropionate or oral BDP) as a medical countermeasure (MCM) for the treatment of gastrointestinal acute radiation syndrome (GI ARS).

Soligenix was invited to submit this proposal following a review of its white paper entitled "OrbeShield, oral beclomethasone 17,21-dipropionate (BDP), a candidate broad spectrum therapeutic countermeasure for GI ARS," to BARDA in response to a Broad Agency Announcement (BARDA-BAA-12-100-SOL-00011) for advanced research and development of MCMs for chemical, biological, radiological and nuclear threats. BARDA is interested in the advanced development and eventual licensure/approval of effective MCMs that mitigate, treat, affect, delay, or interrupt the progression of injuries resulting from acute exposure to radiation from a nuclear accident or attack.

In a canine model of GI ARS, OrbeShield demonstrated a statistically significant survival advantage in animals that received OrbeShield therapy up to 24 hours following exposure to lethal doses of total body irradiation when compared with placebo-control animals (p=0.04). Median survival following irradiation in the control group was eight days, compared to 87 days in the OrbeShield treated group. This work was largely supported by a $1 million grant to Soligenix's academic partner, the Fred Hutchinson Cancer Research Centre, from the National Institute of Allergy and Infectious Diseases (NIAID).

A subsequent study to replicate and expand upon the observations made in the canine model is ongoing and is supported by a $600,000 Small Business Innovation Research (SBIR) grant award from the NIAID.

"We are excited about the contract proposal submission to BARDA," stated Christopher J Schaber, PhD, president & chief executive officer of Soligenix. "Although there are no guarantees, we believe that we are well-positioned to receive BARDA development support for this indication allowing us to further demonstrate the growing body of compelling scientific evidence supporting OrbeShield's potential as a countermeasure for GI ARS. Having recently received Orphan Drug and Fast Track designations from the FDA, we look forward to continued productive interactions with BARDA, NIAID and FDA as we move the OrbeShield GI ARS development programme forward."

The submission of our proposal is non-binding and does not guarantee the award of a BARDA contract. The contract award will require a favorable technical and scientific review by BARDA followed by negotiation of fair and reasonable contract terms.

ARS occurs after toxic radiation exposure and involves several organ systems, notably the bone marrow the GI tract and later the lungs. In the event of a nuclear disaster or terrorist detonation of a nuclear bomb, casualties exposed to >2 Gy are at high risk for development of clinically significant ARS. Exposure to high doses of radiation exceeding 10-12 Gy causes acute GI injury which can result in death in 5-15 days. The GI tract is highly sensitive due to the requirement for incessant proliferation of crypt stem cells and production of mucosal epithelium. The extent of injury to the bone marrow and the GI tract are the principal determinants of survival after exposure to TBI. Although the hematopoietic syndrome can be rescued by bone marrow transplantation or growth factor administration, there is no established treatment or preventive measure for the GI damage that occurs after high-dose radiation. Therefore, there is an urgent need to develop specific MCMs against the lethal pathophysiological manifestations of radiation-induced GI injury.

OrbeShield is formulated for oral administration in GI ARS patients as a single product consisting of two tablets; one tablet releases BDP in the proximal portions of the GI tract and the other tablet releases BDP in the distal portions of the GI tract. BDP has been marketed in the United States and worldwide since the early 1970s as the active pharmaceutical ingredient in inhalation products for the treatment of patients with allergic rhinitis and asthma. Oral BDP may also have application in treating other GI disorders characterized by severe inflammation such as Crohn's disease and radiation enteritis.

The FDA has cleared the Investigational New Drug (IND) application for OrbeShield for the mitigation of morbidity and mortality associated with GI ARS. OrbeShield has also been granted Orphan Drug and Fast Track designations by the FDA for the prevention of death following a potentially lethal dose of total body irradiation during or after a radiation disaster.

Soligenix is a development stage biopharmaceutical company developing products to treat serious gastrointestinal diseases where there remains an unmet medical need, as well as developing several biodefense vaccines and therapeutics.