Our two lead product candidates, Rhopressa™ (netarsudil ophthalmic solution) 0.02% and Roclatan™ (netarsudil/latanoprost ophthalmic solution) 0.02%/0.005%, are currently in the late stages of development. The Company expects to resubmit an NDA for Rhopressa™ ophthalmic solution near the end of Q1-2017 upon notification from our finished product contract manufacturer of their readiness for pre-approval inspection by the FDA. If the current Phase 3 trials for Roclatan™ ophthalmic solution continue to be successful, the Company expects to file an NDA for this product candidate near year-end 2017.

*In addition to our primary product candidates, Rhopressa™ ophthalmic solution and Roclatan™ ophthalmic solution, we are in the preclinical development stage with AR-13533, our second-generation ROCK/NET inhibitor. AR-13533 does not require enzymatic conversion in the eye to deliver maximal ROCK inhibitor activity, and therefore AR-13533 may provide additional IOP-lowering effect in patients beyond that obtained with Rhopressa™ ophthalmic solution. We have not submitted an investigational new drug application, or IND, for AR-13533 to the FDA and there can be no assurance that an IND will be submitted.
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RhopressaTM Trials for Near End Q1-2017 NDA Resubmission

Additional Phase 3 Trials to be filed to RhopressaTM NDA as Supportive

Rhopressa (netarsudil ophthalmic solution) 0.02%

Rhopressa™ 1 2 3 (netarsudil ophthalmic solution) 0.02%, is a novel eye drop that we believe, if approved, would become the only once-daily product available that, based on Aerie’s preclinical studies, specifically targets the trabecular meshwork, the eye’s primary fluid drain and the diseased tissue responsible for elevated IOP in glaucoma. Preclinical studies have also demonstrated that Rhopressa™ ophthalmic solution lowers episcleral venous pressure, which contributes approximately half of IOP in healthy subjects. Further, based on Aerie’s preclinical studies, Rhopressa™ ophthalmic solution provides an additional mechanism that reduces fluid production in the eye and therefore lowers IOP. Biochemically, Rhopressa™ ophthalmic solution has been shown in Aerie studies to inhibit both Rho kinase (ROCK) and norepinephrine transporter (NET). Recent preclinical studies have also shown that Rhopressa™ ophthalmic solution may have disease-modifying properties, including an anti-fibrotic effect on the trabecular meshwork and the potential to increase perfusion of the trabecular meshwork. Further, in a Rhopressa™ ophthalmic solution 24-hour IOP pilot study, the product demonstrated similar levels of IOP lowering during nocturnal and diurnal periods reflecting higher levels of nocturnal IOP lowering compared to currently marketed products. Preclinical research is also currently underway to evaluate the potential neuroprotective benefits of Rhopressa™ ophthalmic solution. The results of two Phase 3 registration trials (Rocket 2 and Rocket 1) for Rhopressa™ ophthalmic solution will be included in the resubmission of the NDA filing expected near the end of Q1-2017. Rocket 2 represents the pivotal trial, and Rocket 1 is supportive. There are two additional Phase 3 trials currently underway for Rhopressa™ ophthalmic solution, named Rocket 3 and Rocket 4. Rocket 3 is a 12-month safety-only study in Canada that is not needed for the NDA filing. Rocket 4 is designed to provide adequate six-month safety data for regulatory filing purposes in Europe, and recent top line 90-day efficacy data from this clinical trial successfully demonstrated non-inferiority to timolol at its primary endpoint range. We expect to file the top line Rocket 4 data to the Rhopressa™ ophthalmic solution NDA as supportive.

Roclatan (netarsudil/latanoprost ophthalmic solution) 0.02% / 0.005%

Roclatan™ 1 2 4, (netarsudil/latanoprost ophthalmic solution) 0.02%/0.005% is a once-daily eye drop that combines Rhopressa™ ophthalmic solution, as described below, with latanoprost, a PGA that is the most widely prescribed glaucoma drug in the world. Based on our preclinical studies and clinical trials, we believe that Roclatan™ ophthalmic solution, if approved, would be the first glaucoma product to lower IOP through all known mechanisms: (i) increasing fluid outflow through the trabecular meshwork, the eye’s primary drain, (ii) increasing fluid outflow through the uveoscleral pathway, the eye’s secondary drain, (iii) reducing fluid production in the eye, and (iv) reducing episcleral venous pressure (EVP). By covering the full spectrum of known IOP-lowering mechanisms, Roclatan™ ophthalmic solution has the potential to provide a greater IOP-lowering effect than any currently approved glaucoma product. The first Phase 3 registration trial for Roclatan™ ophthalmic solution, named Mercury 1 is a 12-month safety trial in 718 patients with a 90-day efficacy readout. The topline efficacy readout from Mercury 1 demonstrated that Roclatan™ ophthalmic solution was statistically superior to each of its components with an IOP-lowering effect of up to 3 mmHg greater than each of its components. The second Phase 3 registration trial, named Mercury 2, is a 90-day efficacy trial that commenced in March 2016, and a third Phase 3 registration trial, named Mercury 3, is expected to commence in Europe in the first half of 2017. Mercury 3 is not necessary for approval in the U.S., but rather to facilitate regulatory approval and commercialization in Europe.

RoclatanTM Registration Trial Design

Roclatan Registration Trial Design

Mechanisms of Action

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References
  1. Wang RF, Williamson JE, Kopczynski C, Serle JB. Effect of 0.04% AR-13324, a ROCK, and norepinephrine transporter inhibitor, on aqueous humor dynamics in normotensive monkey eyes. J Glaucoma 2015. 24(1):51-4.
  2. Kiel JW, Kopczynski C. Effect of AR-13324 on Episcleral Venous Pressure (EVP) in Dutch Belted Rabbits. J Ocul Pharmacol Ther 2015; 31(3):146-151.
  3. Sturdivant JM,* Royalty SR, Lin CW, Moore LA, Yingling JD, Laethem CL, Sherman B, Heintzelman GR, Kopczynski CC, deLong M. Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma. Bioorg Med Chem Lett. 2016; 26:2475–2480.
  4. Xalatan® Package Insert Revised November 2014.