![]() 1 Aerie Pharmaceuticals, Inc. Additional Rhopressa™ Rocket 1 Analyses and Path Forward May 7, 2015 Exhibit 99.2 |
![]() 2 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. 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 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 forward-looking statements. 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. |
![]() 3 Background There are three Phase 3 registration trials for Rhopressa™, • “Rocket 1,” a 90-day efficacy trial, the results of which were initially reported on April 23, 2015 and are further reported in this presentation, • “Rocket 2,” a 12-month safety trial with a 90-day interim efficacy readout expected third quarter 2015, and • “Rocket 3,” a safety-only study being conducted in Canada. Rocket 1 clinical trial evaluated • the ocular hypotensive efficacy of Rhopressa™ 0.02%, dosed QD, versus Timolol, 0.5%, dosed BID, in patients with elevated intraocular pressure (OAG and OHT) for 90 days • the ocular and systemic safety of Rhopressa™, 0.02% for 90 days |
![]() 4 4 Primary endpoint: Mean IOP at Weeks 2 and 6 and Day 90 Patients with open angle glaucoma (OAG) or ocular hypertension (OHT) with IOP >20 mmHg and < 27 mmHg N=411 randomized at 36 sites (370 subjects per protocol) Timolol 0.5% BID Rhopressa™ Rocket 1 Trial Design Rhopressa™ 0.02% QD (PM) Patients randomized 1:1 |
![]() 5 Number of Early Terminations – 44 (Total Rhopressa™ plus Timolol) 31 in Rhopressa™, 13 in Timolol Major Reasons for Early Termination (Total Rhopressa™ plus Timolol) * Adverse Events for Rhopressa™ included: Allergic conjunctivitis (2); Eyelid pruritus (2); Lacrimation increased (2); Angle closure glaucoma (1); Conj. hyperemia (1); Conj. edema (1); Conj. Vasc. Disorder (1); Eye irritation (1); Eye pain (1); Eye pruritus (1); Eyelid edema (1); Iris adhesions (1); Iris bombe (1); Vision blurred (1); Decreased visual acuity (1); Diarrhea (1); Dysphagia (1); Feel abnormal (1); Instill. site pain (1); Conjunctivitis (1); Hypersensitivity (1); Upper limb fracture (1); Corneal staining present (1); Prostate cancer (1); Dermatitis (1) Rocket 1 Trial Conduct Adverse events* (55%) Protocol violation (18%) Withdrawal of consent (11%) Lack of efficacy (7%) Investigator decision (4%) |
![]() 6 Rocket 1 Study Endpoints Efficacy: • • • IOP analysis stratified by baseline IOP above and below 24 mmHg • Mean change from baseline IOP • Mean percent change from diurnally adjusted baseline IOP • Mean diurnal and change from baseline diurnal IOP Safety: • The primary efficacy endpoint is the mean IOP at the following time points: 08:00, 10:00, and 16:00 at the Week 2, Week 6, and Day 90 visits Secondary efficacy endpoints include: Ocular and systemic safety measures |
![]() 7 Primary Endpoint: Topline Summary Per Protocol population (baseline IOP < 27 mmHg) Rhopressa™ did not meet criteria for non-inferiority to Timolol Rhopressa™ mean difference from Timolol ranged from –0.5 to +1.3 mmHg Inferiority was driven by a subset of Rhopressa™ patients losing efficacy over time (~ 20%) “Drifter” subset: Increase in IOP greater than 3 mmHg from week 2 to month 3 |
![]() 8 Summary Of Rhopressa™ Rocket 1 Efficacy Results Based On Different Baseline IOPs Baseline IOP (mmHg) Non-inferiority Numerical Superiority <27 Did not meet Met 2 time points <26 Met Met 4 time points <25 Met Met 7 time points <24 Met All (9 time points) <23 Met All (9 time points) <22 Insufficient power All (9 time points) |
![]() 9 Today’s Objectives Rhopressa™ IOP-lowering dynamics What happened between baseline IOP < 27 mmHg and 26 mmHg? Next steps for Rocket 2 Next steps for Rocket 4 Next steps for Roclatan™ |
![]() 10 Explanation of Increase in IOP Week 2 to Month 3 |
![]() 11 Baseline IOP < 24 mmHg (Pre-specified analysis) |
![]() 12 Rhopressa TM Efficacy In Subjects On PGA Prior To Study: Baseline IOP < 24 mmHg • Prior PGA use produced enhanced IOP-lowering with Rhopressa TM at weeks 2 and 6 • IOP lowering at month 3 equivalent to IOP lowering in non-PGA subjects • Prior PGA use had no effect on Timolol efficacy |
![]() 13 Rhopressa TM Efficacy In Subjects Not On PGA Prior To Study: Baseline IOP < 24 mmHg • No loss of efficacy seen from week 2 to month 3 for Rhopressa TM or Timolol |
![]() 14 Baseline IOP < 25 mmHg At All Time Points |
![]() 15 Baseline IOP < 25 mmHg At All Time Points -1.3, 0.0) (-1.6, -0.2) (- 1.7, -0.3) (-1.4, -0.3) -0.7, 0.7) -0.9, 0.5) (- 1.4, 0.0) -0.9, 0.3) (- 0.5, 0.9) -0.8, 0.7) -1.1, 0.3) -0.7, 0.5) ( ( ( ( ( ( ( Rhopressa – Timolol (95% CI) Mean Difference 95% CI 0.6 0.9 1.0 0.8 0.0 0.2 0.7 0.3 0.2 0.1 0.4 0.1 - - - - - - - - - - Mean IOP Rhopressa Timolol N=107 N=120 Baseline 8:00 AM 22.3 22.5 10:00 AM 21.2 21.0 4:00 PM 20.6 20.4 Mean Diurnal 21.4 21.3 Day 15 8:00 AM 17.2 17.8 10:00 AM 16.1 17.0 4:00 PM 16.2 17.2 Mean Diurnal 16.5 17.3 Day 43 8:00 AM 17.8 17.8 10:00 AM 16.8 17.0 4:00 PM 16.5 17.3 Mean Diurnal 17.1 17.4 Day 90 8:00 AM 18.1 18.0 10:00 AM 17.3 17.4 4:00 PM 17.0 17.4 Mean Diurnal 17.5 17.6 TM TM |
![]() 16 Rhopressa TM Efficacy In Subjects On PGA Prior To Study: Baseline IOP < 25 mmHg • Prior PGA use produced enhanced IOP-lowering with Rhopressa TM at weeks 2 and 6 • IOP lowering at month 3 equivalent to IOP lowering in non-PGA subjects • Prior PGA use had no effect on Timolol efficacy |
![]() 17 Rhopressa TM Efficacy In Subjects Not On PGA Prior To Study: Baseline IOP < 25 mmHg • No loss of efficacy seen from week 2 to month 3 for Rhopressa TM or Timolol |
![]() 18 Rhopressa TM IOP-lowering Effect Enhanced In Subjects On PGA Therapy Prior To Study Entry Prospective (pre-specified) analysis by pre-study medication status showed that prior PGA use enhanced Rhopressa TM IOP-lowering at week 2 (p=0.003) The PGA effect is lost over time, which we believe creates a false impression that Rhopressa TM loses efficacy over time The apparent PGA synergy with Rhopressa TM is greatest at week 2 and lessens over time in the absence of PGA dosing No evidence of enhanced efficacy in Timolol subjects on PGA therapy prior to study entry Retrospective analysis of Phase 2 trial results shows prior PGA use enhanced Rhopressa TM IOP-lowering by 1 mmHg (p=0.007) and 1.2 mmHg (p=0.002) at weeks 2 and 4, respectively, relative to subjects not previously on PGA |
![]() 19 What happened between baseline IOP of 26 mmHg and less than 27 mmHg? |
![]() 20 Rocket 1 Rhopressa TM Drifters IOP increase from week 2 to month 3 greater than 3 mmHg Correlation with entry baseline IOP • <27 mmHg – 36 drifters (n=182, 19.8%) • <26 mmHg – 18 drifters (n=133, 13.5%) • <25 mmHg – 12 drifters (n=107, 11%) • <24 mmHg – 5 drifters (n=76, 6.6%) |
![]() 21 Baseline IOP < 27 mmHg At All Time Points |
![]() 22 Baseline IOP < 27 mmHg – Drifters Removed |
![]() 23 • Higher baseline IOP and average duration of disease 3 years longer • Potential for more severely diseased trabecular meshwork • Highly variable IOP • 56% showed IOP decreases at week 2 of 5 – 11 mmHg • 31% showed decrease in IOP at week 2, an unusual IOP rise above baseline IOP at week 6, then IOP decreased again at month 3 • Variability of IOP between Rhopressa™ studies (Phase 2 vs. Rocket 1) • 22/36 (61%) drifters clustered at 5 (14%) study sites • Higher incidence (28%) of noncompliance compared to non-drifters • Impact of prior IOP lowering medication on week 2 IOP reading • 66% PGA • 34% None or Non-PGA Rhopressa™ Drifter Characteristics |
![]() 24 Variability of Baseline IOP Between Studies Phase 2 Max entry IOP <36 mmHg Rocket 1 Max entry IOP <27 mmHg Same subjects had baseline IOPs ~2 mmHg higher in previous Phase 2 studies vs. Rocket 1 study (n=71) Phase 2 studies Rocket-1 |
![]() 25 Rhopressa™ Dosing Compliance Week 6 to Month 3 Missed >35% of PM Doses Drifters Non-Drifters Number non-compliant 10/36 4/30 % Non-compliant 28% 13% Average days of dosing missed per non-compliant subject 28/47 21/47 Average % days of dosing missed per non-compliant subject 59% 45% Compliance with dosing determined by bottle weight Drifter subjects twice as likely to be non-compliant than non-drifters More doses missed by non-compliant drifters than non-compliant non-drifters |
![]() 26 Summary Of Rocket 1 Observations At baseline IOP <24 mmHg and <25 mmHg, Rhopressa™ subjects on non-PGA therapy or no therapy prior to study entry showed consistent IOP lowering over time (no drift) Prior PGA users showed a residual PGA effect that enhanced Rhopressa™ IOP lowering at week 2, creating a false impression of loss of Rhopressa™ efficacy by month 3 Rhopressa™ demonstrated equivalent IOP lowering at month 3 in prior PGA and non-PGA users at baseline IOP <24 mmHg and <25 mmHg At higher baseline IOPs, part of the reduced Rhopressa™ efficacy over time may be due to a minority of patients with severely diseased TM or non-dosing compliance, etc. The potential synergistic effect of PGA+Rhopressa™ is a positive for both Rhopressa™ and Roclatan™ |
![]() 27 Path Forward: Rocket 2 • FDA meeting to discuss changing the Rocket 2 IOP range for the primary endpoint to either baseline IOP < 24 mmHg or < 25 mmHg • Precedent for changing primary endpoint within ophthalmology: Zioptan – for treatment of glaucoma, approved February 2012 • Outcome dependent not only on FDA discussions but also the power adequacy at < 24 mmHg and < 25 mmHg based on patient enrollments • Aerie has the ability to increase patient enrollment if required because database is not locked • Expect Rocket 2 efficacy results in Q3 2015 assuming no increase in enrollment required – otherwise by year-end 2015 |
![]() 28 Path Forward: Additional Rhopressa™ Phase 3 Trial, “Rocket 4” • Rocket 4 planned for Q3 2015 • Primary endpoint: baseline IOP < 24 mmHg or < 25 mmHg at 9 time points through Day 90 • Secondary endpoints below 27 mmHg and potentially month 6 efficacy • Expect to file the Rhopressa™ NDA in the first half of 2016 if we don’t need additional patients in Rocket 2 or don’t need to wait for Rocket 4 results – otherwise by the end of 2016 |
![]() 29 Path Forward: Roclatan™ First Phase 3 registration trial “Mercury 1” to commence in Q3 2015 Final IOP range to be determined Trial design is superiority of Roclatan™ over each individual component Remaining Phase 3 trials (US+EU) to commence post-Rocket 2 topline results |
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