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 resubmitted an NDA for Rhopressa™ ophthalmic solution on February 28, 2017. In May 2017, we received notification from the FDA that the Rhopressa™ NDA is sufficiently complete to permit a substantive review. The PDUFA goal date for the completion of the FDA’s review of the Rhopressa™ NDA is set for February 28, 2018. 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 in the first half of 2018.

*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 February 28, 2017 NDA Resubmission

Additional Phase 3 Trials 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 and clinical studies, specifically targets the trabecular meshwork, the eye’s primary fluid drain and the diseased tissue responsible for elevated IOP in glaucoma. Preclinical and clinical 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 may provide an additional mechanism that reduces fluid production in the eye and therefore lowers IOP. Biochemically, the active ingredient in Rhopressa™ ophthalmic solution, netarsudil, 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 of netarsudil on trabecular meshwork cells and the potential to increase perfusion of the trabecular meshwork. The results of two Phase 3 registration trials (Rocket 2 and Rocket 1) for Rhopressa™ ophthalmic solution were included in the resubmission of the NDA filing on February 28, 2017. Rocket 2 represents the pivotal trial, and Rocket 1 is supportive. There were two additional Phase 3 trials for Rhopressa™, named Rocket 3 and Rocket 4. Rocket 3 was a small 12-month safety-only study in Canada that was not needed for the NDA filing and for which we have discontinued enrollment. Rocket 4, which was successfully completed in April 2017, was designed to generate adequate six-month safety data for European regulatory approval. In October 2016, topline 90-day efficacy data from this clinical trial successfully demonstrated non-inferiority to timolol at its primary endpoint range. This topline Rocket 4 data was also included in the resubmitted Rhopressa™ ophthalmic solution NDA as supportive. We expect to file for European regulatory approval of Rhopressa™ in the second half of 2018.

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 above, with latanoprost, a widely-prescribed PGA. Based on our preclinical studies and clinical trials to date, 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) potentially 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 was a 12-month safety trial, which had a successful 90-day efficacy readout in September 2016. The topline efficacy readout from Mercury 1 demonstrated that Roclatan™ ophthalmic solution was statistically superior to each of its components with IOP-lowering beyond the comparators in the range of 1 to 3 mmHg.5 The second Phase 3 registration trial, named Mercury 2, was a 90-day efficacy trial that was completed in May 2017. The study also achieved its primary efficacy endpoint demonstrating statistical superiority beyond the comparators in the range of 1 to 3 mmHg. A third Phase 3 registration trial, named Mercury 3, commenced in Europe in the third quarter of 2017. Mercury 3 is not necessary for approval in the U.S., but rather to facilitate regulatory approval and commercialization in Europe. Mercury 3 is designed to compare Roclatan™ to Ganfort®, a fixed-dose combination product of bimatoprost and timolol marketed in Europe, which if successful, is expected to improve our commercialization prospects in that region.

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.
  5. This topline Mercury 1 data was also included in the resubmitted Rhopressa ™ NDA as supportive