The Nicox expertise
NO is a well-known small naturally-occurring signaling molecule whose target is an intracellular enzyme, soluble guanylate cyclase (sGC), which converts guanosine triphosphate to the second messenger, cyclic guanosine monophosphate (cGMP). The NO stimulated increase in the concentration of cGMP in the trabecular meshwork leads to the sequestration of intracellular calcium, the relaxation of the trabecular meshwork and, consequently, an increase in the outflow of the aqueous humor from the anterior segment of the eye through the primary or conventional outflow pathway. All of the foregoing events are thought to lead to lowering of intraocular pressure (IOP).
NO lowers IOP via distinct cellular and molecular pathways compared to other pharmaceutical agents currently used to treat ocular diseases including glaucoma and ocular hypertension. By designing our proprietary molecules with a dual mechanism of action, we may be able to achieve increased IOP lowering efficacy compared to the molecules acting by a single mode of action. Based on this approach, our partnered approved product VYZULTA®, the only NO donating molecule approved for an ophthalmic indication in the U.S., and our product candidate NCX 470 currently in clinical development, are comprised of a parent prostaglandin analog (PGA) and a NO-donating moiety.
We have also explored NO-donating compounds of different chemical and pharmacological classes in order to combine the NO donation effects with other existing mechanism of action (MOA) and thus to potentially increase the overall IOP lowering potentials of the resulting new molecular entities. Our research program is focused on NO-donating PDE5 inhibitors (PDE5), fully owned by Nicox: PDE5 is a key enzyme that accelerates the degradation of the second messenger, cGMP produced by sGC following its stimulation by NO. By inhibiting PDE5 we may enhance and prolong the effect of NO on IOP reduction.