While seeking additional assets to add to the Inotek program in ophthalmology, the Company is also looking for development partners for internal programs that address serious diseases with unmet medical needs but that are no longer part of the focused ophthalmology business strategy. If interested, please contact us at: busdev@inotekcorp.com. Our programs available for partnering include the following:

Anti-Flagellin Monoclonal Antibodies for Inflammatory Bowel Disease (IBD)
Many infectious bacteria achieve motility with the help of hair-like appendages called flagella. These flagella are made of a protein called flagellin, whose structure varies between species, but which also possesses a region of conserved structure. At low concentrations, flagellin has been shown to activate macrophages, monocytes and intestinal and pulmonary epithelial cells and induce the release of a variety of pro-inflammatory mediators. Inotek has developed a series of monoclonal antibodies (mAbs) targeted to the conserved region of the flagellin structure, giving them high affinity and a broad spectrum of activity against pathogenic bacteria.

Inotek has established preclinical validation of its lead monoclonal flagellin antibodies, INO-741 and INO-763, in several mouse models of IBD. Inotek believes that this series of mAbs represents a novel approach to the treatment of IBD in that they block the interaction between the TLR5 (Toll-like) receptor and flagellin. Because these mAbs act specifically at the point of presumed inflammatory stimuli, their localized effect may provide safety advantages relative to existing IBD therapeutics. Additionally, these mAbs may have broad applicability in the treatment of a variety of gram negative infections. Inotek is seeking a partner to further develop its anti-flagellin mAbs.

Peroxynitrite Decomposition Catalyst for the Prevention of Contrast-Induced Nephropathy
Oxidants such as peroxynitrite can stimulate inflammatory gene expression and have a profound effect on protein function. Inotek has discovered and developed a series of compounds representing a new class of metalloporphyrinic agents with broad and potent activity against oxidative cell damage. The lead candidate, INO-4885, is a clinical-stage peroxynitrite decomposition catalyst that protects against contrast-induced nephropathy by neutralizing toxic reactive oxygen species in the kidney.

A Phase 1 clinical trial in healthy volunteers has been completed and Maximal Tolerated Dose (MTD) determined for use in a planned Proof-of-Concept efficacy trial in patients undergoing contrast studies who are at high risk of kidney damage (e.g., diabetic patients). Preclinical studies supporting this product candidate include a rat model of contrast-induced renal injury in which INO-4885 was shown to be protective. Inotek is seeking a partner to further develop INO-4885 and this class of agents for the prophylactic treatment of contrast-induced nephropathy (CIN).

Poly (ADP ribose) polymerase (PARP) in Non-ophthalmic Indications:
Pharmacologic blockade of the PARP cell death pathway prevents oxidant-mediated cell death and organ dysfunction. Inotek's extensive portfolio of PARP inhibitors exhibit profiles suitable for both oral and intravenous administration in a variety of clinical indications, including cancer, ischemia/reperfusion injuries, inflammation, neurologic dysfunction and complications of diabetes. In extensive preclinical in vivo studies, Inotek's PARP inhibitors have consistently demonstrated the ability to block the enzymatic activity of PARP-1 and PARP-2. Multiple independent research groups, including Inotek, have unequivocally demonstrated a benefit of PARP inhibition in augmenting the effects of alkylating agents such as such as temozolomide (TMZ) and other cancer therapies (e.g., topoisomerase inhibitors, anthracyclines, cis-platinum). PARP has also been shown to mediate resistance of malignant tissue to TMZ. Additionally, in cases where tumors are deficient in BRCA1 or BRCA2, such as certain types of breast and ovarian cancer, a PARP inhibitor may be used alone to arrest the growth and potentially kill dividing tumor populations. Inotek is seeking a partner to further develop its PARP inhibitors in non-ophthalmic indications.