Agency: NSF | Branch: Standard Grant | Program: | Phase: | Award Amount: 173.80K | Year: 2012
This Small Business Innovation Research (SBIR) Phase I project is a feasibility assessment of the ocular delivery of a synthetic peptide, ACT1, for the treatment of Age-Related Macular Degeneration (AMD). AMD is a retinal disease in patients who progressively lose their central vision through pathological and damaging conditions of the macula primarily by the development of leaky blood vessels in the retina of the eye. The objective is to determine whether ACT1 can be transported passively to the retinal epithelial cell layer, elicit a response consistently on blood vessel lesions of the macula, and slow the progression or restore visual functions in vivo as a milestone for the further development of a topical eye drop formulation.
The broader/commercial impacts of this research are manifold and foremost the potential commercialization of a much needed treatment option for patients suffering from AMD. AMD affects approximately 25 to 30 million people worldwide and is the leading cause of vision loss for Americans 60 years old or older, with close to 2 million people suffering in the United States. Current treatments of AMD require the use of drugs are administered chronically to patients by injections into the eyes that can be quite painful as well as eliciting further safety concerns, and are modestly effective in slowing the rate of vision loss. A topically delivered therapeutic may provide a variety of benefits including easier, faster, and cheaper treatments of patients, patient self-care, and potentially jumpstart a new industry for the optometric management of AMD.
Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 148.80K | Year: 2012
This Small Business Innovation Research (SBIR) Phase I project is a feasibility assessment of the ocular delivery of a synthetic peptide, ACT1, for the treatment of Age-Related Macular Degeneration (AMD). AMD is a retinal disease in patients who progressively lose their central vision through pathological and damaging conditions of the macula primarily by the development of leaky blood vessels in the retina of the eye. The objective is to determine whether ACT1 can be transported passively to the retinal epithelial cell layer, elicit a response consistently on blood vessel lesions of the macula, and slow the progression or restore visual functions in vivo as a milestone for the further development of a topical eye drop formulation. The broader/commercial impacts of this research are manifold and foremost the potential commercialization of a much needed treatment option for patients suffering from AMD. AMD affects approximately 25 to 30 million people worldwide and is the leading cause of vision loss for Americans 60 years old or older, with close to 2 million people suffering in the United States. Current treatments of AMD require the use of drugs are administered chronically to patients by injections into the eyes that can be quite painful as well as eliciting further safety concerns, and are modestly effective in slowing the rate of vision loss. A topically delivered therapeutic may provide a variety of benefits including easier, faster, and cheaper treatments of patients, patient self-care, and potentially jumpstart a new industry for the optometric management of AMD.
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 225.00K | Year: 2016
DESCRIPTION provided by applicant Transplantation is a widely accepted and highly successful therapy for end stage heart disease While success rates and survival have risen steadily since its inception almost years ago due largely to improved immunosuppression regimes there is a growing appreciate that factors associated with brain death organ donation procurement and storage prior to implantation greatly effect outcomes post transplantation Clinical data has demonstrated that recipients of hearts from living donors have significantly improved outcomes as compared to those from cadaveric sources These data suggest that insults to the donor organ induced by brain death and cold storage predispose to poorer post transplantation outcomes These injurious events are thought to initiate organ injury endothelial dysfunction and inflammation that are further exacerbated upon implantation and reperfusion and that primes the donor organ for alloimmune recognition Therefore strategies to minimize or switch off these injurious events are likely to improve graft outcomes Cold preservation has greatly facilitated the use of cadaveric hearts for transplantation but clearly damage occurs prior to storage from brain death and during both the preservation episode and the reperfusion phase While metabolic additives have been incorporated into preservation solutions to prolong storage times and improve organ viability no additives have been incorporated into the preservation solutions to minimize endothelial injury activation We hypothesize that brain death cold preservation and ischemia reperfusion injury induces cell junction damage which leads to inflammation heart damage and endothelial dysfunction upon reperfusion and that inclusion of a novel gap and tight junction stabilizing peptide ACT would preserve cell junctions during cold preservation and reduce graft damage and immunogenicity upon reperfusion PUBLIC HEALTH RELEVANCE The greatest rate limiting step to successful transplantation is the shortage of suitable organs for transplant Many candidate hearts are deemed unusable due to brain death induced injury BDI and hearts that are transplanted are often sub optimal due to endothelial activation and injury which promotes primary graft failure Here we explore ACT as a pharmacotherapy to minimize endothelial injury and improve post transplant outcomes
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 641.09K | Year: 2010
DESCRIPTION (provided by applicant): According to the American Diabetes Association, there are more than 16 million people in the United States with known diabetes. Diabetic patients commonly demonstrate impaired wound healing. Approximately 20 percent of patients with diabetes will develop foot ulceration in their lifetime. Diabetic foot ulceration (DFU) represents a major problem that can significantly impair the patient's quality of life, require prolonged hospitalization, and may involve infection, gangrene, and amputation. It has been estimated that for each new foot ulcer the attributable cost for a middle-aged diabetic man in the first two years is approximately 30,000. The cost of DFU to the healthcare system is over one billion dollars per year in the United States. A well- established reason as to why diabetic wounds are tough to heal is that they do not progress through the normal healing phases. Instead, it is thought that diabetic wounds are caught and remain trapped in the initial inflammatory phase of wound healing. FirstString Research, Inc. (FSR) is a biotech company located in Charleston, South Carolina. The founders of FSR, Drs. Robert Gourdie and Gautam Ghatnekar are co inventors of a class of novel bioengineered peptides - we refer to as ACT peptides. Phase I funded studies in the diabetic C57BL/KsJ-m+/+Leptdb (db+/db+) mouse model have provided strong evidence for efficacy and potential of the ACT1 peptide in the treatment of diabetic wounds. The peptide effects a significantly faster closure rate. Subjective parameters such as redness and overall appearance were also substantially improved in ACT1 treated wounds. ACT1 peptide did not show any adverse reactions or safety concerns in our Phase I SBIR studies, as evaluated by a complete necropsy and histopathological evaluation. Moreover, to enhance our ability to understand and anticipate issues associated with the safety and efficacy of ACT1peptide, we will also use gene microarray and computational approaches to analyze effects on key signaling pathways involved in wound healing. Of particular interest will be changes induced in angiogenic signaling that provide basic mechanistic insight into the regeneration of skin vascular pattern in wounds treated with ACT1 peptide. Our market research has indicated that present therapies and drugs for wound healing in diabetes and chronic wounds in general are predominantly symptomatic, empirical, unpredictable, and largely ineffective. Our ACT1 peptide potentially offers a mechanistically based solution to not just faster wound closure but also significant cost savings and more importantly improving the quality of life in diabetic patients. In this Phase II application, Dr. Paul Ehrlich, Director for the Wound Healing Research Laboratory in the Division of Plastic Surgery, Department of Surgery, Hershey Medical Center at Penn State University and Dr. Indu Parikh, President and CSO, BioMarck Pharmaceuticals, Durham, NC have agreed to assist us in achieving our aims. PUBLIC HEALTH RELEVANCE: Diabetes is a debilitating condition that threatens the quality of life of not just the people suffering from the disease but also family members and loved ones. Approximately 20 percent of patients with diabetes develop foot ulceration in their lifetime and they demonstrate impaired wound healing. A well-accepted reason for the poor healing of the diabetic or chronic wounds in general is that they are 'stuck' in the inflammatory phase. This technology provides promise for reduced inflammation and faster healing of diabetic wounds thereby improving the quality of life and saving millions of dollars in health care related costs.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 2.99M | Year: 2014
Project Summary/Abstract According to the ADA, 25.8 million children and adults have diabetes. Diabetics have an increased risk of complications such as heart disease and are prone to impaired wound healing. A major cause of morbidity and hospitalizationis diabetic foot ulceration (DFUs) that may result in infection, gangrene, amputations requiring prolonged hospitalization, costly treatments, and can significantly impair a patient's quality of life. The cost of DFU's to the US healthcare system is over10 Billion annually. Diabetic wounds tend to remain stalled in the initial inflammatory phase of wound healing and are generally unresponsive to conventional treatments. Current treatment approaches including debridement, pressure off-loading, infection control, negative pressure, and skin substitutes tend to have marginal efficacy and high cost. A large unmet need exists for an easier and more effective treatment. FirstString Research, Inc. (FSR), a clinical stage biotech company, is advancing the develo
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 232.76K | Year: 2012
DESCRIPTION (provided by applicant): According to the World Health Organization, at least 171 million people worldwide are living with diabetes and this figure is likely to more than double by the year 2030. Because of its chronic nature, the severity of its complications and the means required to control them, the economic burden is enormous not only to the individuals and families involved but also to the health system. Wound healing in diabetics, in general, is severely impaired, which has a great impacton the economic and social burden of our society. Diabetes is the leading cause of new cases of blindness among adults aged 20-74 years. Although retinopathy is the primary cause of blindness in these patients, in the past 3 decades it has been noted that47-64% of diabetic patients will manifest diabetic keratopathy or other corneal abnormalities, which are potentially sight threatening. Currently, therapies to treat these corneal epithelial wounds are very limited. FirstString Research, Inc is an early stage biotech company developing therapeutic peptides for applications in tissue engineering and regenerative medicine. FirstString's lead novel bioengineered peptide dubbed ACT1, is based on the C-terminal sequence of connexin 43 (Cx43), and shows great promise in modulating intercellular communication. ACT1 works by stabilizing gap junctions and maintaining intercellular communication between cells that is essential for wound repair or injury response. Preliminary data from our company has indicated that this peptide can effect accelerated wound healing, reduce inflammatory response, reduce scar formation and restore skin structure following acute injury in a diabetic mouse model system. Furthermore, ACT1 peptide has been shown to promote corneal wound closure following ethanol burn injuries to the rat cornea, compared with that of a control peptide. Based on these early findings we hypothesize that ACT1 peptide will increase corneal re-epithelialization and accelerate wound closure following injury to the corneas of diabetic rats as demonstrated by the aims outlined in this Phase I SBIR application. The completion of aims outlined in this project will set the stage for a future Phase II SBIR and could lead to a commercially viable therapeutic in the clinicalmanagement of diabetic keratopathy. PUBLIC HEALTH RELEVANCE: According to the World Health Organization, at least 171 million people worldwide are living with diabetes. Corneal disorders secondary to diabetes, such as diabetic keratopathy, are an increasing cause of morbidity associated with diabetes and affects 47-64% of diabetics during the course of their disease. Conventional therapies for the treatment of these corneal wounds have failed. FirstString Research Inc. has developed a novel therapeutic peptide that may promote re-epithelialization of the cornea, reduce scarring and inflammation and thereby prevent potential blindness in diabetics with such disorders.
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 225.00K | Year: 2015
DESCRIPTION provided by applicant Glioblastoma GBM is an incurable cancer even with aggressive therapies such as surgical resection followed by radiotherapy and chemotherapy using temozolomide TMZ Efforts to improve surgical resection or the efficacy of irradiation are limited by the potential damage these interventions cause to the brain In contrast sensitizing GBM to TMZ is an appealing strategy because TMZ has excellent brain penetration and a low toxicity profile Recent research has suggested that targeting the gap junction protein connexin Cx holds promise for enhancing TMZ sensitivity in GBM Dr Gourdieandapos s co Investigator laboratory has developed a synthetic peptide ACT which comprises the carboxy terminus of Cx and has demonstrated therapeutic effects in promoting healing of chronic wounds FirstString Research has licensed ACT for further development and clinical application and has advanced Granexin tm Gel the topical formulation of ACT peptide through three successfully completed Phase human clinical trials for scar reduction and the treatment of chronic wounds In collaboration with the Shengandapos s co Investigator laboratory we observed that Cx expression inversely correlates to TMZ sensitivity and GBM patient survival and demonstrated that ACT significantly increases TMZ sensitivity in vitro and in vivo thus encouraging us to further investigate its therapeutic potential in sensitizing GBM tumors to TMZ However intracranial delivery of this peptide is limited by its relatively short half life Therefre the overall objective of this application is to develop a novel delivery approach for ACT to treat GBM in vivo The use of biodegradable nanoparticles for peptide delivery is a powerful approach due to its high biocompatibility and sustained peptide release The rationale of this study is that ACT loaded nanoparticles ACT NP will efficiently deliver ACT into the brain by constantly and continuously supply GBM tumor cells with this peptide Our hypothesis is that ACT NP will sensitize GBM to TMZ which will then be tested in two specific aims to engineer ACT NP and optimize controlled delivery of ACT in vitro to assess in vivo the therapeutic potential of ACT NP in tandem with TMZ treatment of brain tumors We will first generate ACT NP in collaboration with Dr Foster co Investigator and his laboratory using poly lactic co glycolic acid PLGA copolymer After in vitro characterization of ACT NP and effect on human GBM cells we will intracranially inject ACT NP into the brains of GBM mice followed by TMZ treatment We will monitor the tumor growth using magnetic resonance imaging and analyze mice survival These results will validate the therapeutic effect of ACT in vivo We expect that this approach will efficiently deliver ACT in a sustained way and sensitize GBM tumors to TMZ The proposed research is significant because this innovative approach will not only allow us to develop novel combinational therapies for lethal GBM but also will lay foundation on potential clinical trials in newly diagnosed GBM patients in the near future Finally our new ACT NP may be scalable to other CNS diseases that could benefit from Cx targeting PUBLIC HEALTH RELEVANCE Glioblastoma is a very aggressive type of brain tumor and one of the most deadly diseases with no efficient therapy to cure it The proposed research aims at developing a new combinational therapy to enhance the effectiveness of temozolomide the front line chemotherapy for glioblastoma Therefore this work will have important impact on therapeutic intervention for glioblastoma and is relevant to public health and NIHandapos s mission
Agency: Department of Defense | Branch: Army | Program: SBIR | Phase: Phase I | Award Amount: 99.86K | Year: 2015
Ocular traumas resulting from explosive or incendiary devices are one of the most common injuries reported by our armed forces. Current standard of care protocols do not address the biological and molecular processes in corneal wound healing, and therapeutic failure is associated with corneal ulcers, scarring, and loss of vision. Ocular therapeutics that have regenerative healing properties, restore corneal biomechanical integrity and can be readily applied in the field will greatly enhance therapeutic outcome. FirstString Research has developed an ophthalmic eye-drop formulation containing the short regulatory peptide (ACT1) that possesses anti-inflammatory properties and enhances corneal regeneration via the stabilization of gap and tight junctions by modulating junctional protein interactions. The proposed Phase I SBIR will test the hypothesis that an ophthalmic ACT1 peptide formulation can accelerate corneal reepithelialization and restore corneal biomechanics, thus improving visual outcome. Using pre-clinical corneal injury models of blast and burn, our goal is to evaluate the therapeutic potential of an ACT1 ophthalmic formulation with respect to corneal and lentricular pharmacokinetics, corneal regeneration, corneal scarring, and corneal biomechanics. Successful completion of this study will demonstrate feasibility and will allow us to perform comprehensive translational technology development in a future Phase II effort.
News Article | June 24, 2015
SUMMERVILLE, S.C.--(BUSINESS WIRE)--SCRA Technology Ventures’ SC Launch Board recently finalized investments for two Charleston, S.C.-based companies. Charleston Pharma, who received board approval for investment in May 2015, and FirstString Research, who received board approval in March 2015 have now received funds from the program. Both companies will utilize the investment to expanded operations. Charleston Pharma is focused on developing innovative therapeutic antibodies and related diagnostic tests for cancer patients and healthcare providers. Research is done in laboratories at the SCRA MUSC Innovation Center and is designed to identify the most promising antibodies for studies that will establish preclinical efficacy and safety. Part of the SC Launch program since October 2010, Charleston Pharma has received a grant and two rounds of investment from the program. The most recent investment will be used to expand recombinant production efforts, explore antibody-drug conjugates and add animal efficacy studies. FirstString Research, an SC Launch company since 2006, is a privately held, clinical-stage biotechnology company that focuses on scar prevention, inflammation reduction, wound healing and complex tissue regeneration. This investment will be the fourth round of SC Launch funding for the company. “It is through the continued support and development of innovative companies like these that we are seeing the high-tech economy in South Carolina continue to grow,” said SCRA CEO Bill Mahoney. “We are delighted to support these companies and the great work they are doing in South Carolina.” SCRA Technology Ventures enables research commercialization and promotes the development of high tech industries, enhancing South Carolina’s technology-based economy. Through its flagship SC Launch program, this SCRA business sector makes investments in and offers support services to South Carolina’s early stage, start-up technology companies. Multiple economic impact studies show SCRA's cumulative output on South Carolina's economy to be over $18.1 billion, and that the company has helped create approximately 15,000 technology-related jobs in the state, with annual wages averaging between $55,000 and $79,000.
News Article | May 6, 2015
SUMMERVILLE, S.C.--(BUSINESS WIRE)--SCRA Technology Ventures' SC Launch Portfolio Company, FirstString Research, has recently signed a Cooperative Research and Development Agreement (CRADA) with the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health, through NCATS’ Bridging Interventional Development Gaps program. This agreement is based on the development of a connexin-based peptide therapeutic, ACT1, as a topical ophthalmic therapy for the treatment of diabetic keratopathy and persistent corneal defects. The goal is to develop an optimized ACT1 topical ophthalmic drug formulation, and conduct pre-clinical IND enabling studies in preparation for clinical trials. Diabetes is a leading cause of blindness and visual impairments, where diabetic keratopathy, characterized by corneal thinning and disorganization, presents in an estimated 47-64% of diabetic patients. Unlike in normoglycemic individuals, diabetic corneal defects are associated with abnormal corneal reepithelialization and individuals with diabetes present with persistent corneal wounds that are unresponsive to conventional treatment regimens. ACT1 is a peptide-based therapeutic based on the C-terminal sequence of connexin43 (Cx43) and is designed to competitively inhibit the binding of endogenous Cx43. Cx43 plays critical roles in multiple aspects of wound healing, including spread of injury signals, extravasations of immune cells, granulation tissue formation, and fibrosis. A topical gel formulation of ACT1 (Granexin) has completed several Phase II clinical trial studies for chronic wound healing and scar reduction. Topically applied ACT1 enhances corneal re-epithelialization and wound closure following corneal injury in diabetic models. “ACT1 peptide effectively targets the underlying molecular and cellular processes involved in corneal re-epithelialization by increasing coordination of cellular communication, and tempering inflammatory responses. The result is accelerated corneal reepithelialization and reduced scarring.” said Dr. Christina Grek, Director of Translational Research at FirstString Research. “We are excited to work with the project team at NCATS to further optimize our ophthalmic ACT1 formulation. The research completed under this CRADA will pave the way for human clinical evaluation and has the potential to address the medical needs of an expanding diabetic population.” said Dr. Gautam S. Ghatnekar, President and CEO of FirstString Research. “Furthermore, the resulting ACT1 formulation will be useful in the treatment of corneal injuries resulting from military engagement or corneal epithelial damage obtained during cataract or corneal refractive surgery.” "We are delighted to support FirstString as they continue their progress in the regenerative medicine market," said SCRA CEO Bill Mahoney. "It is promising emerging companies like FirstString that are shaping our state’s technology-base and job creation." SCRA Technology Ventures enables research commercialization and promotes the development of high tech industries, enhancing South Carolina’s technology-based economy. Through its flagship SC Launch program, this SCRA business sector makes investments in and offers supports services to South Carolina’s early stage, start-up technology companies. Multiple economic impact studies show SCRA's cumulative output on South Carolina's economy to be over $18.1 billion, and that the company has helped create approximately 15,000 technology-related jobs in the state, with annual wages averaging between $55,000 and $77,000. To keep up with our latest news, follow SCRA on Twitter or visit our blog.