Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 600.00K | Year: 2012
DESCRIPTION (provided by applicant): This proposal concerns the use of beclomethasone dipropionate (BDP) as a post-exposure drug therapy having the potential to mitigate the gastrointestinal (GI) injury associated with acute radiation syndrome (ARS) following exposure to intense ionizing radiation. ARS occurs after toxic radiation exposure and involves at least several organ systems, primarily resulting in toxicity to the bone marrow (hematopoietic [HP] syndrome) and the GI (GI-ARS). In the event of a nuclear disaster or terrorist detonation of a nuclear bomb, casualties exposed to gt2 Gray (Gy) are at high risk for development of clinically significant ARS. Exposure to high doses of radiation exceeding 10-12 Gy causes acute gastrointestinal injury which canresult in death in 5-10 days. Thus, the extent of injury to the bone marrow and the GI tract are the principal determinants of survival after exposure to total- body irradiation (TBI). Although lethal hematopoietic injury can be rescued by bone marrow transplantation and several therapeutic drugs, there is no treatment or preventive measure for GI damage that occurs after high dose radiation. We evaluated an oral formulation of beclomethasone dipropionate (BDP), a mucosally active glucocorticoid, as a treatment of dogs to mitigate acute GI syndrome. The primary result that justifies further study of this drug in the GI-ARS is the survival benefit in dogs that have received BDP therapy starting 2 hours following lethal TBI. Preliminary results also suggest BDP efficacy starting at 24 hours after TBI. With this application, we are proposing further evaluation of the oral drug in beagle dogs with a focus on intervention at least 24 hours after TBI. The dog is one of the crucial large animal models that will aid in establishing efficacy of BDP (or other drugs) for eventual FDA licensure under the Animal Rule. We envision future studies that would occur in mouse models on refinement of the putative mechanisms of BDP in GI-ARS, as wells as studies of orally administered BDP in non-human primates. PUBLIC HEALTH RELEVANCE: This proposal concerns the use of beclomethasone dipropionate (BDP) as a post-exposure drug therapy having the potential to mitigate the gastrointestinal (GI) injury associated with acute radiation syndrome (ARS) following exposure to intense ionizing radiation. Exposure to high doses of radiation exceeding 10-12 Gy causes acute gastrointestinal injury which can result in death in 5-10 days. In this project, we are proposing evaluation of orally administered BDP in beagle dogs with a focus on intervention at least 24 hours after lethal total body irradiation (TBI).
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 300.00K | Year: 2012
DESCRIPTION (provided by applicant): Graft vs. Host Disease (GVHD) is an expensive life-threatening complication following allogeneic hematopoietic cell transplantation in some patients that receive this life-saving treatment for certain cancers. The proposed open-label, multi-center, two-part Phase 2 clinical study is designed to evaluate the potential of orBec(R), a novel formulation of oral beclomethasone 17,21- dipropionate (BDP), as a treatment for chronic gastrointestinal cGVHD. OrBec(R), as developed by Soligenix, is formulated as two separate drug products for oral administration as an immediate release and delayed release tablet, each containing 1 mg of BDP, a potent, locally-acting corticosteroid originally developed primarily for the prevention and treatment of acute gastrointestinal graft versus host disease (aGVHD). The reduced systemic bioavailability of oral BDP offers a major therapeutic advantage over systemic glucocorticoids such as prednisone and methylprednisolone, which have well-recognized adverse effects (e.g., development of glucose intolerance, Cushingoid habitus, muscle weakness and fatigue, bone demineralization, and increased risks of infections). Adverse effects of systemic glucocorticoid administration can be avoided by use of topically active glucocorticoids. The protocol for this Phase 2 CLINICAL STUDY was submitted to IND 20,212 June 24, 2011. To date, no additional FDA feedback on the study design has been noted by the FDA. We will conduct this Phase 2 clinical study with thefollowing specific goals, which form the Specific Aims of this proposal: To conduct a FDA reviewed and accepted Phase 2 clinical study: the study will be a point estimate design aimed at elucidating the dose response needed to define future placebo-controlled studies. The placebo-controlled study will be the Phase 3 clinical study that will be described in the Phase II SBIR proposal. This study will estimate the proportion of subjects who achieve a complete response (CR), partial response (PR) and overall response (OR) of GI GVHD signs and symptoms when treated with orBec(R), 2 mg four times a day (8 mg/day) for up to 16 weeks, in patients with cGVHD. The secondary objectives of this study are to determine the: i. proportion of subjects who experience a flare/worsening of GI GVHD; ii. time to flare/worsening of GI GVHD at each dose-level; iii. time to CR during the initial 16 weeks of orBec(R) treatment; and iv. time to flare/worsening of GI GVHD signs and symptoms during each of the planned orBec(R) dose reductions in Part 2 of the study. The safety objectives are to evaluate safety and tolerability of orBec(R) in subjects with cGVHD. Upon completion of the Phase 2 clinical study, Soligenix will be in a position to begin the process for a Phase 3 FDA reviewed and accepted clinical study, on the road to the first drug to be approved for treatment for cGVHD. PUBLIC HEALTH RELEVANCE: Currently there are no FDA approved therapies specifically for prevention or treatment of chronic GVHD (cGVHD). Furthermore, there are no FDA approved therapies for the prevention of the gastrointestinal manifestation of cGVHD. Off-label treatments (e.g., prednisone) are typically used; however, they can be associated with serious side effects that seriously diminish the quality of life for cancer survivors that have undergone life saving hematopoietic cell transplantation. More simply stated the underlying hematologic malignancy can be cured; however, the treatment utilized comes with its own set of negative consequences. This grant application requests funding to initiate (via a Phase 2 clinical study) the clinical evaluation of orBec(R), oral beclomethasone 17,21- dipropionate (BDP) for use in treating the gastrointestinal signs and symptoms associated with cGVHD. OrBec(R)is a two tablet system consisting of 1 delayed release and 1 immediate release tablet each containing 1mg BDP. The development of cGVHD and its GI complications significantly impacts the patient's quality of life and can in some cases be fatal. Based on previous clinical studies and the pharmacology of BDP, Soligenix and its medical advisors believe that orBec(R) has the potential to treat the GI manifestation of cGVHD, thereby improving the quality of life of cancer survivors as well as potentially impacting overall mortality. Upon completion of the proposed clinical study, Soligenix intends to evaluate the data generated with the intent of designing a placebo-controlled clinical study (e.g., Phase 3) to demonstrate both the safety and efficacy of orBec(R)for use in this indication.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 300.00K | Year: 2014
DESCRIPTION (provided by applicant): This proposal describes development of an immunomodulatory peptide that targets the host defense system for treatment of acute pneumonic melioidosis. The disease is caused by Burkholderia pseudomallei (Bps), a non-spore-forming motile saprophytic bacterium that can be transmitted from the soil to humans by inhalation, through cuts in the skin and by ingestion. Bps is classified as a category B biological threat agent by U.S. Department of Health and Human Services (DHHS) and in the 2012 Health Emergency Medical Countermeasure Enterprise (PHEMCE) Strategy document because of its infectivity by the aerosol route and environmental robustness. Furthermore, Bps is endemic in Southeast Asia, Brazil, Africa, the Middle East, and Northern Australia. Bps is intrinsically resistant to antibiotics normally used for first line treatment of Gram-negative septicemia, accounting for high mortality in endemic regions. Preventative or therapeutic vaccinations are not yet available, i
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 225.00K | Year: 2014
DESCRIPTION (provided by applicant): Oral mucositis has a significant impact on patient quality of life and outcomes during cancer therapy as well as having a significant pharmacoeconomic cost. There are no currently approved drugs to treat oral mucositisin patients with non-hematological malignancies, including head and neck cancer (HNC). Soligenix is developing a new compound, SGX942, a modulator of the innate defense system, which binds to the p62 protein. p62 is a key adaptor protein that functions downstream of key sensing receptors of the innate defense system. Preclinical studies with SGX942 revealed a significant reduction in both duration and peak intensity of oral mucositis in both a fractionated radiation-induced hamster model of oral mucositisand a chemotherapy- induced mouse model of oral (tongue) mucositis: there was ~50% reduction in the duration of severe mucositis. Efficacy was dose responsive and optimal at 25 mg/kg dosed every third day during fractionated radiation therapy. Based o
Soligenix | Date: 2015-10-21
The present invention provides a liquid formulation for the treatment of a skin condition associated with leukocyte accumulation in the skin, comprising a therapeutic compound selected to reduce leukocyte accumulation in the skin; and an aqueous solution of an organic solvent, wherein the organic solvent increases skin permeability. The present invention also provides a method of treating a skin condition associated with leukocyte accumulation in the skin, comprising the steps of applying topically a liquid formulation of a photosensitizer to a skin lesion of a patient afflicted with the skin condition; and exposing the skin lesion to a light source.
Soligenix | Date: 2014-10-24
Innate Defense Regulators (IDRs) interact with intracellular signaling events and modulate the innate defense response. Whereas much of the initial work with the IDRs focused on their role in fighting infection, recent results in animal models of chemotherapy- or radiation-induced mucositis and wound healing suggest that IDRs can be beneficial during the responses to a broader range of damage-inducing agents beyond pathogens. RIVPA (SEQ ID NO. 5), has demonstrated safety in humans and efficacy in animal models of fractionated radiation-induced and chemotherapy-induced oral mucositis, in models of chemotherapy induced damage to the gastro-intestinal tract and in models of local and systemic Gram-positive and Gram-negative infection in immunocompetent and immunocompromised hosts. Based on this information, we propose the use of RIVPA (SEQ ID NO. 5) and/or other IDRs (Table 1) as a novel treatment for Macrophage Activation Syndrome.
Soligenix | Date: 2015-08-05
The present invention features methods of delivering corticosteroids or metabolites thereof for treating and preventing tissue damage resulting from acute radiation injury in the gastrointestinal tract with locally effective therapeutic agents.
Soligenix | Date: 2014-08-11
Preclinical data obtained in models of chemotherapy-induced mucositis, radiation-induced mucositis, neutropenic infection and colitis indicate oral mucositis is a promising indication for Innate Defense Regulator (IDR) peptides. Preclinical efficacy results obtained with IDRs in mouse and hamster models of mucositis indicate that dosing every third day should be able to cover the mucositis window with seven to fourteen doses, depending on the duration of chemotherapy or radiation exposure. IDRs have also shown efficacy in mouse models of chemotherapy-induced oral and gastrointestinal mucositis, consistent with the response of the innate immune response to chemotherapy and/or radiation damage. IDRs are also effective at reducing bacterial burden and improve survival in the presence or absence of antibiotic treatment in various murine infection models.
Soligenix | Date: 2012-11-30
Results from two randomized trials have shown that oral beclomethasone dipropionate (BDP) is effective for treatment of acute gastrointestinal graft-versus-host disease (GVHD). Here, we report results of a double-blind, randomized placebo-controlled phase II study designed to test the hypothesis that acute GVHD could be prevented by administration of oral BDP, beginning before hematopoietic cell transplantation (HCT) and continuing until day 75 after HCT. Study drug (BDP or placebo) was administered as 1 mg immediate-release formulation plus 1 mg delayed-release formulation orally four times daily. According to the primary endpoint, systemic glucocorticoid treatment for GVHD was given to 60 of the 92 participants (65%) in the BDP arm, versus 31 of 46 participants (67%) in the placebo arm. The secondary efficacy endpoints showed no statistically significant differences between the two arms. The proportion of participants who took at least 90% of the prescribed study drug during the first 4 weeks after HCT was 54% overall. Lower severity of mucositis strongly correlated with higher adherence to the schedule of study drug administration. Inconsistent adherence related to mucositis during recovery after myeloablative conditioning may have obscured a beneficial therapeutic effect in the current study.
Soligenix | Date: 2015-07-09
Stable immunogenic composition capable of eliciting a robust and durable immune response yielding a measurable increase in neutralizing antibodies at least 200 days post-administration, comprising at least one antigen consisting of a ribosome inactivating protein and at least one antigen comprising a toxin derived from bacterial spores. Method making and using a stable immunogenic composition capable of eliciting a stable immune response yielding a measurable increase in neutralizing antibodies at least 200 days post-administration, comprising providing an immunogenic composition comprising at least one antigen comprising a ribosome inactivating protein and at least one antigen comprising a toxin derived from bacterial spores and administering the immunogenic composition to an individual.