OcuNexus Therapeutics, Inc.
|Stage of funding:||Current|
OcuNexus Therapeutics is a development stage biopharmaceutical company with novel, proven gap junction channel modulation technologies targeting unmet clinical needs in ophthalmology.
OcuNexus Therapeutics has highly differentiated, lead drug candidates based upon a novel mechanism of action called “Gap Junction Channel Modulation.” OcuNexus has potential treatments for multiple front- and back-of-the-eye diseases and disorders, and is developing unique, patented therapeutics to treat ophthalmic diseases with high unmet needs that offer the potential to alter the standard of care. In addition, the company's technologies are expected to be transferable to other acute and chronic disease indications.
Gap junctions are a class of transmembrane channel proteins that occur in all tissues in the body and allow adjacent cells in animal tissues to communicate with one another. They normally enable small molecules up to ~1000 Daltons and simple ions to flow between adjacent cells in a controlled manner. The six proteins that covalently bind to form gap junctions are called connexins. Six connexin proteins form a hemichannel which is a donut shaped hexagonal arrangement with a central channel which enters the cell membrane as a closed non-functional pore. This structure can migrate around the cell membrane until its extracellular protein loops “dock” to an analogous hemichannel structure on a neighboring cell to form the gap junction channel. This then establishes a direct communication channel between cells. In the normal state, gap junction hemichannels are closed and do not open until they dock with the hemichannel on an adjacent cell to allow cell-to-cell communication.
In the presence of pathological stimuli such as acute injury or chronic disease, the hemichannels open and release ATP into the extracellular milieu. The released ATP activates an inflammatory response which is mediated by the innate inflammasome pathway of inflammation. Simultaneously there is an upregulation of Connexin43, which is then overexpressed, further adding to the number of open gap junction hemichannels and creating a perpetual cycle of inflammation. This cycle continues to cause the release of ATP and inflammatory cytokines leading to significant tissue damage including microvascular leak, edema, microvascular dropout, ischemia and ultimately fibrosis.
The purpose of OcuNexus drug treatment is to break the cycle of activated inflammasome mediated inflammation. OcuNexus treatments either prevent pathological open hemichannels from being formed or close the hemichannels directly, returning them to a state of homeostasis.
OcuNexus Clinical Candidates and Indications
THERAPEUTIC TARGET AND BIOLOGICAL EFFECT
OcuNexus has identified 3 distinct Clinical Candidates based on robust and repeatable clinical and pre-clinical data.
The OcuNexus therapeutic target is the Connexin43 (Cx43) protein, a key component of the Gap Junction Hemichannel that under pathological conditions is upregulated and overexpressed in an injury or disease environment and perpetuates a cycle of inflammation through the activated inflammasome pathway. Depending on the drug being used, further formation of the open hemichannels is significantly inhibited or the hemichannel is directly closed. The biological effect is the shutting down of the cycle of inflammation otherwise perpetuated by the open pathological hemichannel pores in the cell membrane. Shutting down the inflammation and inflammatory cytokine production, provides the damaged ocular tissues the opportunity to repair and regenerate in an environment of physiological homeostasis. The pathology related to the continuing cycle of inflammation includes loss of vascular integrity, vascular leakage, edema, microvascular dropout, ischemia and ultimately neovascularization and fibrosis.