Company

Portfolio Data

Back to Company Search

Inotek Pharmaceuticals Corporation

Address

100 Cummings Center Suite 419E
Beverly, MA, 01915
USA

UEI: N/A

Number of Employees: N/A

HUBZone Owned: No

Woman Owned: No

Socially and Economically Disadvantaged: No

SBIR/STTR Involvement

Year of first award: 1997

Phase I Awards

Phase II Awards

21.95%

Conversion Rate

$13,609,702

Phase I Dollars

$24,752,734

Phase II Dollars

$38,362,436

Total Awarded

Awards

Up to 10 of the most recent awards are being displayed. To view all of this company's awards, visit the Award Data search page.

Catalytic antioxidant for hemorrhagic shock

Amount: $978,243

DESCRIPTION (provided by applicant): This Phase II SBIR proposal is intended to further develop a new therapeutic approach to save the lives of severely injured trauma victims with hemorrhagic shock (HS). In a small proportion of trauma, a fatal outcome is assured due to the irreversible loss of vital functions or massive blood loss. Frequently, however, emergent resuscitation is possible. These victims survive to hospitalization and are able to receive the full benefits of modern intensive care and surgery. In spite of fluid resuscitation and surgery to repair vascular and parenchymal injuries, however, not all treated patients survive HS. The principal impediment to a successful outcome in this population is the development of cardiovascular failure, a condition in which HS results in profound hypotension refractory to fluid replacement and inotropic support. There is substantial evidence that HS - induced tissue injury is mediated by profound alterations in the biosynthesis of the free radicals nitric oxide and superoxide anion, and their reaction product peroxynitrite, a toxic oxidant. We are developing novel metalloporphyrin-based molecules that act as peroxynitrite decomposition catalysts. An early development compound, FP15, was protective in experimental models of ischemia-reperfusion injury. Based on these data, the central objective of the Phase I grant proposal was to establish that pharmacological peroxynitrite decomposition can improve hemodynamics, metabolic function, end-organ injury, and survival in a rodent model of hemorrhagic shock. We have addressed this objective by characterizing the pharmacodynamic profile of the catalysts in a rat model of severe fixed-pressure HS. The results of the Phase I application demonstrated the efficacy of WW-85, a next generation potent porphyrinic catalytic antioxidant, and thereby established the technical merit and feasibility of the current project. In the current Phase II grant application, we plan to conduct additional efficacy studies testing WW-85 in clinically relevant rodent and large animal models of uncontrolled hemorrhagic shock. Additional aims of the study include formulation and stability work, as well as pharmacokinetic and metabolic characterization of the compound, and toxicological evaluation, in order to advance the technology to the stage of human clinical testing.

SBIR

Phase II

2005

HHS

NIH

A nitric oxide synthase inhibitor for uveitis

Amount: $2,098,450

DESCRIPTION (provided by applicant): Steroid treatment of anterior uveitus is effective but frequently associated with cataract formation after prolonged use. Development of an effective substitute for steroids, free of these safety concerns, would be a substantial advance. In a Phase I SBIR, we proposed a novel therapeutic candidate for treatment of uveitus, based on the introduction of a proprietary novel inhibitor of the inducible nitric oxide (NO) synthase (iNOS), an enzyme whose de novo upregulated expression accounts for the release of injurious quantities of NO and produces inflammatory injury in uveitis. Our development candidate, GED (guanidinoethyldisulfide), selectively inhibits iNOS activity and scavenges peroxynitrate, a toxic oxidant formed from the reaction of NO and superoxide. In a rat model of endotoxin-induced uveitis (EIU), GED proved highly effective when administered either systemically of topically (as an 0.3% ophthalmac solution). We also carried out studies that suggest that GED therapy is safe, as evidenced by negative in vitro and in vivo genotoxicology assays, a NOEL in rats and dogs for systemic GED administration 100-fold greater than the potential absorbed drug from ophthlamic use, a lack of cytotoxicity in cultured epithelial cells, and absenceof ocular injury in rabbits challenged with a supratherapeutic (10%) GED ophthalmic solution. In the current Phase 2 SBIR, we will conduct safety and efficacy studies in order to move GED forward to the stage where human clinical testing can begin. To this end, we will first test GED in rabbits to establish the therapeutic window of opportunity in a classic model of uveitis and we will test the safety of the compound in 60 day and 6 month repeat dose studies. The latter study will be critical to establish that GED, in contrast to steroids, does not induce cataract formation. The results of the studies proposed in the current Phase III SBIR application will provide the basis for an FDA-approved IND to perform Phase I/II clinical trials.

SBIR

Phase II

2005

HHS

NIH

PARP inhibition for thoraco-abdominal aneurysm surgery

Amount: $191,048

DESCRIPTION (provided by applicant): Ischemia-reperfusion (I/R) produces tissue injury and systemic inflammatory response syndrome (SIRS). The mechanism by which oxidants effect these changes has recently been ascribed to their impact on genomic integrity. Oxidants rapidly induce DNA single strand breaks that activate the nuclear enzyme poly (ADPribose) polymerase ("PARP"). PARP in turn catalyses an energy-consuming polymerization of ADP-ribose, resulting in NAD consumption, ATP depletion, necrosis, and organ failure. PARP activation also strongly upregulates expression of pro-inflammatory cytokines, chemokines, and endothelial cell adhesion molecules. Blockade of PARP, or its genetic deletion, is profoundly protective in cell and animal models of reperfusion injury and inflammation, but there are no data on the clinical role of PARP. We now propose to test the hypothesis that PARP inhibition can beneficially influence the outcome of I/R injury and SIRS in man. To address this hypothesis, we will utilize a unique drug candidate (a novel nanomolar potent PARP inhibitor termed INO-1001) and a highly controlled period of I/R afforded by elective repair of thoracoabdominal aneurysm (TAA). This surgical procedure produces profound tissue injury that may result in renal and pulmonary insufficiency, paraplegia, and mortality. In the present PHASE I COMPONENT OF OUR FASTTRACK proposal, we will establish the safety profile and pharmacokinetics (PK) of INO-1001 in a population undergoing TAAA repair. We will address this objective by carrying out a prospective, double-blind, randomized, single-center investigation in n= 17 subjects. Administration of INO-1001 will be initiated preoperatively, i.e. prior to the onset of organ injury, and continued for 4 days, the critical period of reperfusion and induction of a systemic inflammatory response, administered in a repeated bolus dosing regimen (100 and 400 mg INO-1001 q12h). The primary clinical endpoints will be safety and pharmacokinetics. Safety studies will focus on biochemical, hematologic, and cardiovascular endpoints. Pharmacokinetic studies will establish whether the half-life and tissue distribution of INO-1001 differ from parameters defined in a healthy population. The FDA has granted Fast-Track IND approval to this investigation.

SBIR

Phase I

2005

HHS

NIH

Novel therapy for female sexual dysfunction

Amount: $1,463,180

DESCRIPTION (provided by applicant): Female sexual dysfunction is increasingly recognized as a significant and widespread abnormality, contributing to coital pain, decreased libido, and a loss of sexual pleasure. In contrast to the enormous scientific in

SBIR

Phase II

2004

HHS

NIH

Novel xanthine oxidase inhibitor for arthritis

Amount: $153,173

DESCRIPTION (provided by applicant): Xanthine oxidase (XO)-catalyzed generation of superoxide anion is thought to contribute to the pathogenesis of autoimmune arthritis. The relative importance of XO to the pathogenesis of arthritis is demonstrated in

SBIR

Phase I

2004

HHS

NIH

Organophosphate intoxication: effect of PARS inhibition

Amount: $240,309

DESCRIPTION (provided by applicant): Activation of poly (ADP)ribose synthetase (PARS) (also known as poly(ADP)ribose polymerase or PARP) is a novel mechanism of oxidant-induced neuroinjury. Triggered by DNA single strand breakage, PARS catalyzes an en

SBIR

Phase I

2004

HHS

NIH

A1 adenosine agonist: antinociceptive effects

Amount: $193,885

DESCRIPTION (provided by applicant): The current Phase I SBIR Grant application by Inotek Pharmaceuticals Corporation proposes to test the antinociceptive effect of a novel A1 receptor agonist in rat models. As preliminary data we present evidence in

SBIR

Phase I

2004

HHS

NIH

PARP inhibitor therapy for septic shock

Amount: $210,226

DESCRIPTION (provided by applicant): Progression of septic shock to multiple organ failure (MOF) is mediated by the activation of poly(ADP-ribose) polymerase ("PARP"), a nuclear cell death enzyme that catalyzes intracellular energetic failure and

SBIR

Phase I

2004

HHS

NIH

Poly(ADP-ribose)and diabetic erectile dysfunction

Amount: $372,288

DESCRIPTION (provided by applicant): The current application represents a Phase I SBIR Grant application by Inotek Corporation, proposing to establish a proof-of-concept of the involvement of poly (ADP-ribose) polymerase (PARP) activation in the patho

SBIR

Phase I

2004

HHS

NIH

Inosine pro-drug: novel therapy for arthritis

Amount: $1,396,710

DESCRIPTION (provided by applicant): Rheumatoid arthritis (RA) is mediated by articular expression of pro-inflammatory cytokines and chemokines. We have discovered that the purine degradation product inosine exerts multiple anti-inflammatory and immunomo

SBIR

Phase II

2004

HHS

NIH