mechanism of action

NF-kB Technology: OT-551 and the OT-300 Series

Othera’s most advanced clinical-stage drug candidate, OT-551, is a proprietary small molecule that has application to age-related macular degeneration (AMD) through a novel, dual mechanism of action. OT-551's mechanism involves the oxidative stress pathways, as well the inflammatory / Nuclear Factor kappa B (NF-kB) pathway. OT-551 downregulates the overexpression of the protein complex NF-kB, a transcription factor that is highly activated in various disease states resulting in the overproduction of inflammatory cytokines. Through these dual pathways, OT-551 exhibits activity against oxidative stress, inflammation, and angiogenesis. A growing body of scientific literature points to these three factors as key targets for treating wet and dry age-related macular degeneration (AMD). OT-551 also possesses excellent bioavailability, penetrating tissues in both the front of the eye (cornea, conjunctiva, lens) and back of the eye (choroid, retina, vitreous).

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Building on our insights into OT-551’s mechanism of action, Othera is expanding its chemical library with the OT-300 series, orally-available compounds to address cancer-related and inflammatory diseases. The OT-300 series is comprised of a diverse set of compounds that exhibit similar activities to OT-551, including the downregulation of NF-kB overexpression. Among these compounds, Othera has identified a lead candidate, OT-304, which shows promising preclinical activity in cancer-associated thrombosis, as well as strong anti-tumor activity.

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The following diagram shows some of the effects of NF-kB overexpression in various disease states:

Oculoselective Beta-Blocker for Glaucoma: OT-730

OT-730 is a proprietary pro-drug that is converted by enzymes in the cornea into a novel small molecule antagonist of beta receptors for reducing the elevated intraocular pressure associated with glaucoma. It represents an entirely new class of beta blocker drugs - oculoselective agents. Applied topically via eye drop, this oculoselective beta blocker is active in the eye, yet rapidly metabolizes into inactive compounds once it reaches the bloodstream. Because OT-730 selectively targets ocular tissues only, it has the potential to be highly effective in treating glaucoma, without many of the side effects associated with current therapies.

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