Retinal Disease Program OIS @ ASRS Presentation August 2017
Important Information Any discussion of the potential use or expected success of our product candidates is subject to our product candidates being approved by regulatory authorities. In addition, any discussion of clinical trial results for Rhopressa TM (netarsudil ophthalmic solution) 0.02% relate to the results in its first Phase 3 registration trials named Rocket 1 and Rocket 2, or Rocket 4 which will be used primarily for European regulatory filing purposes, and for Roclatan TM (netarsudil/latanoprost ophthalmic solution) 0.02%/0.005% relate to the results in its Phase 3 registration trials. The information in this presentation is current only as of its date and may have changed or may change in the future. We undertake no obligation to update this information in light of new information, future events or otherwise. We are not making any representation or warranty that the information in this presentation is accurate or complete. Certain statements in this presentation, including the updated guidance presented herein, are forward-looking statements within the meaning of the federal securities laws. Words such as may, will, should, would, could, believe, expects, anticipates, plans, intends, estimates, targets, projects, potential or similar expressions are intended to identify these forward-looking statements. These statements are based on the Company s current plans and expectations. Known and unknown risks, uncertainties and other factors could cause actual results to differ materially from those contemplated by the statements. In evaluating these statements, you should specifically consider various factors that may cause our actual results to differ materially from any forwardlooking statements. Any top line data presented herein is preliminary and based solely on information available to us as of the date of this document and additional information about the results may be disclosed at any time. In addition, the preclinical research discussed in this presentation is preliminary and the outcome of such preclinical studies may not be predictive of the outcome of later trials. Any future clinical trial results may not demonstrate safety and efficacy sufficient to obtain regulatory approval related to the preclinical research findings discussed in this presentation. These risks and uncertainties are described more fully in the quarterly and annual reports that we file with the SEC, particularly in the sections titled Risk Factors and Management s Discussion and Analysis of Financial Condition and Results of Operations. Such forward-looking statements only speak as of the date they are made. We undertake no obligation to publicly update or revise any forward-looking statements, whether because of new information, future events or otherwise, except as otherwise required by law. 2
Aerie Building a Major Ophthalmic Pharmaceutical Company Glaucoma/Ocular Hypertension Rhopressa (netarsudil ophthalmic solution) 0.02% Aerie-owned Rho kinase (ROCK) inhibitor targeting the diseased tissue PDUFA goal set for February 28, 2018; entering launch mode Roclatan (netarsudil/latanoprost ophthalmic solution) 0.02%/0.005% Two P3 s achieved primary efficacy endpoints; NDA preparation underway Retinal Diseases AR-13154 Pre-clinical ROCK/PKC inhibitor for wet AMD, diabetic retinopathy/dme Targets multiple disease processes Drug Delivery Technology Multi-month sustained delivery from injectable bioerodible implant 3
Rho Kinase (ROCK): A New Target for Treatment of Wet AMD and Diabetic Retinopathy (DR) ROCK is Ser/Thr kinase that regulates cell shape, contraction, motility 1 AMD ROCK inhibition targets multiple disease processes 2,3 Angiogenesis BRB breakdown/leakage Inflammation Fibrosis DR New Drugs Needed to Address Limitations of Current Anti-VEGF Therapy 4 1. Loirand, Pharmacol Rev. 67:1074-1095 (2015). 2. Bhutto and Lutty, Mol Aspects Med 33: 295-317 (2012) 3. Shin et al., J. Ophthalmic Vis Res 9: 362-373 (2014). 4. Yang et al., Drug Des Devel Ther 10: 1857-1867 (2016) 4
AR-13154 Selected from Aerie s Library of 3,000+ ROCK Inhibitors AR-13154 Single digit nanomolar potency at ROCK1 and ROCK2 ROCK Also potent inhibitor of PKC Favorable ocular PK/PD profile Relationship tree of human kinases. TK, TKL, STE, CK1, AGC, CAMK, CMGC, Other: Kinase superfamilies 5
AR-13154(S) Inhibits VEGF-induced Vessel Formation, Matrigel-induced Choroidal Angiogenesis VEGF-treated Vascular Endothelial Cells Increasing concentration of AR-13154(S) reduces VEGF-induced EC microvessel formation Choroid Explant Angiogenesis in Matrigel Control AR-13154(S) AR-13154(S) directly inhibits angiogenesis in vitro and ex vivo 6
AR-13154(S) Improves RPE Barrier Function In Vitro Transepithelial Resistance Measured in Primary Porcine RPE Cells RPE monolayer on trans-well filter Normalized TER + SD 3 2.5 2 1.5 1 0.5 0 PBS Sunitinib AR-13154(S) At 1 um, AR-13154(S) improved RPE barrier function by ~160% Dysfunction of RPE barrier leads to retinal edema in AMD, DR 7
AR-13154 Reduces CNV in Preclinical Model of Wet AMD um 2 Isolectin IB 4 (+SEM) 110000 100000 90000 80000 70000 60000 50000 40000 30000 20000 * p<0.05 vs. Saline ** p<0.001 Total CNV Lesion Area (Day 21) Saline n=49 0.06 ug/ml AR-13154 n=28 0.6 ug/ml AR-13154 n=25 ** 6 ug/ml AR-13154 n=25 * 800 ug/ml Eylea n=20 Laser-induced choroidal neovascularization (CNV) in rats Compounds delivered by intravitreal injection Confirms AR-13154 effectively inhibits angiogenesis in vivo Lin et al., ARVO 2016 Abstract 287 8
Percent of Control (+SEM) Sustained Delivery of AR-13154(S) Provides Added Efficacy in Proliferative DR Model 110% 100% 80% 60% 40% 20% 0% Vehicle Control (n=55) Total Neovascular Area -34% *** Eylea 1 mg/kg IP (n=26) -37% *** AR-13154(S) Topical (n=28) Mouse oxygen-induced retinopathy model AR-13154(S) delivered by 2 different methods: Intermittent delivery: topical eyedrop 3x daily Sustained delivery: single subconjunctival depot Greater efficacy achieved with sustained delivery of AR-13154(S) vs. 3x daily dosing -64% *** AR-13154(S) Subconj (n=10) 9
Aerie/DSM Collaboration: Sustained Delivery of Aerie Molecules from Bioerodible Implant DSM polymer: Amino acid based polyesteramides (PEA) Biocompatible and bioerodible Injectable by 27G needle 10
Unique Polymer Release and Degradation Profile PEA Polymer Degradation AR-13154(S)-PEA Drug Release Label Claim (%) Time 0 1 Month 3 Months Implant remains intact for >3 months Delayed polymer degradation allows zero-order drug release Duration of drug release ~4 months, implant degradation complete ~6 months 11
AR-13514: A First-in-Class ROCK/PKC Inhibitor for the Treatment of Wet AMD and DR Potential to improve outcomes by targeting multiple disease processes Monotherapy shows strong efficacy in preclinical models Effective as adjunct to anti-vegf therapy in preclinical models Expect durable treatment effect with injection frequency of once every 4 6 months Intravitreal sustained-release, bioerodible implant 12