8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): May 7, 2015

Aerie Pharmaceuticals, Inc.

(Exact name of registrant as specified in its charter)

Delaware	001-36152	20-3109565
(State or other jurisdiction of incorporation)	(Commission File Number)	(I.R.S. Employer Identification Number)

2030 Main Street, Suite 1500

Irvine, California 92614

(Address of principal executive offices)(Zip code)

Registrant’s telephone number, including area code: (949) 526-8700

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Item 2.02. Results of Operations and Financial Condition.

On May 7, 2015, Aerie Pharmaceuticals, Inc. (the “Company”) issued a press release announcing its financial results for the first quarter ended March 31, 2015. A copy of the press release is furnished as Exhibit 99.1 hereto and is hereby incorporated by reference into this Item 2.02.

The information in this Item 2.02 (including Exhibit 99.1) shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended (the “Securities Act”), or the Exchange Act, except as expressly set forth by specific reference in such a filing.

Item 7.01. Regulation FD Disclosure.

On or after May 7, 2015, representatives of the Company may present to various investors the information about the additional analyses of the results from the Company’s first Phase 3 registration trial of Rhopressa^TM, named “Rocket 1,” as described in the slides attached to this report as Exhibit 99.2 hereto. Exhibit 99.2 is hereby incorporated by reference into this Item 7.01.

The information in this Item 7.01 (including Exhibit 99.2) is being furnished, not filed, pursuant to Regulation FD. Accordingly, the information in this Item 7.01 will not be incorporated by reference into any registration statement filed by the Company under the Securities Act unless specifically identified therein as being incorporated therein by reference. The furnishing of the information in this Item 7.01 is not intended to, and does not, constitute a determination or admission by the Company that this information is material or complete, or that investors should consider this information before making an investment decision with respect to any security of the Company.

Item 9.01. Financial Statements and Exhibits.

(d) Exhibits.

The following exhibits relating to Item 2.02 and Item 7.01 shall be deemed to be furnished, and not filed:

99.1 Press Release dated May 7, 2015.

99.2 Rhopressa^TM “Rocket 1” Additional Analyses dated May 7, 2015.

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

	AERIE PHARMACEUTICALS, INC.
Date: May 7, 2015	By:	/s/ Richard J. Rubino
		Richard J. Rubino
		Chief Financial Officer

EXHIBIT INDEX

Exhibit	Description
99.1	Press Release dated May 7, 2015.
99.2	RhopressaTM “Rocket 1” Additional Analyses dated May 7, 2015.

EX-99.1

Exhibit 99.1

Aerie Pharmaceuticals Reports First Quarter 2015 Financial Results and Provides Business and Strategic Update

Conference Call and Webcast Today, May 7, at 5:00 p.m. ET

Company to Review Additional Findings from Initial Rhopressa™ Phase 3 Registration Trial on Conference Call

IRVINE, Calif. & BEDMINSTER, N.J. & RESEARCH TRIANGLE PARK, N.C.—(BUSINESS WIRE)—Aerie Pharmaceuticals, Inc. (NASDAQ:AERI) (the “Company”), a clinical-stage pharmaceutical company focused on the discovery, development and commercialization of first-in-class therapies for the treatment of patients with glaucoma and other diseases of the eye, today reported financial results for the first quarter ended March 31, 2015. The Company will host a live conference call and webcast at 5:00 p.m. Eastern Time today to discuss the Company’s financial results and provide a general business and strategic update. On the call, the Company also will discuss additional findings from its initial Rhopressa^TM Phase 3 registration trial, “Rocket 1,” along with expected paths forward for both Rhopressa™ and Roclatan™.

Aerie Highlights

• At 5:00 p.m. Eastern Time today, the Company will discuss additional analyses of the Rocket 1 results and provide updates on its second Rhopressa^TM Phase 3 registration trial, “Rocket 2,” prospects for an additional Rhopressa^TM trial and the Roclatan™ Phase 3 clinical trials.

• As of March 31, 2015, the Company had $179.3 million in cash, cash equivalents and investments.

“We have been gaining valuable insights into the recently reported Rocket 1 results and plan to conduct further analyses over the next several weeks. We are in the process of defining our path forward for both Rhopressa^TM and Roclatan^TM and will discuss our perspective on our call today,” said Vicente Anido, Jr., Ph.D., Chairman and Chief Executive Officer.

Dr. Anido continued, “We raised an additional $35 million in first quarter 2015 through the at-the-market component of our shelf filing, and we believe the $179 million of cash and investments on our balance sheet provides a significant level of financial resources as we execute going forward.”

Triple-Action Rhopressa™

Aerie’s first-in-class product candidates are all single drop, once-daily medications that are well-tolerated and have shown no systemic drug-related adverse events.

Rhopressa^TM is a novel triple-action eye drop that we believe, if approved, would become the only once-daily product available that specifically targets the trabecular meshwork (TM), the eye’s primary fluid drain and the diseased tissue responsible for elevated intraocular pressure (IOP) in glaucoma. Preclinical results have demonstrated that Rhopressa^TM also lowers episcleral venous pressure (EVP), which contributes approximately half of IOP in healthy subjects. Further, Rhopressa^TM provides an additional mechanism that reduces fluid production in the eye and therefore lowers IOP. Biochemically, Rhopressa^TM is known to inhibit both Rho Kinase (ROCK) and norepinephrine transporter (NET).

There are three Phase 3 registration trials for Rhopressa^TM, “Rocket 1,” a 90-day efficacy trial, the results of which were initially reported on April 23, 2015, “Rocket 2,” a 12-month safety trial with a 90-day interim efficacy readout expected as early as the third quarter of 2015, and “Rocket 3,” a safety-only study being conducted in Canada. Pending successful results from the remaining Phase 3 registration trials and a potential additional Phase 3 registration trial for Rhopressa^TM, the Company expects to submit a New Drug Application filing by the end of 2016.

Quadruple-Action Roclatan™

Roclatan™ is a once-daily eye drop that combines our triple-action Rhopressa™ with latanoprost, a PGA that is the most widely prescribed glaucoma drug. If approved, we believe that Roclatan™ would be the first glaucoma product to lower IOP through all known mechanisms: (i) increasing fluid outflow through the TM, 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 EVP.

A successful 28-day Phase 2b clinical trial for Roclatan™ was completed in June 2014. Roclatan^TM achieved its primary efficacy endpoint on day 29 and demonstrated statistical superiority over the product’s individual components at all time points. We believe that Roclatan™, if approved, would be the only glaucoma product that covers the full spectrum of known IOP-lowering mechanisms, giving it the potential to provide a greater IOP-lowering effect than any currently approved glaucoma product. Therefore, we believe that Roclatan™, if approved, could compete in both the PGA and non-PGA markets and become the product of choice for patients requiring maximal IOP lowering, including those with IOPs in excess of 26 mmHg and those who present with significant disease progression despite currently available therapies. We expect the first Phase 3 registration trial, “Mercury 1,” to commence in the third quarter of 2015.

First Quarter 2015 Financial Results

As of March 31, 2015, the Company had cash, cash equivalents and investments of $179.3 million. For the first quarter ended March 31, 2015, the Company reported a net loss attributable to common stockholders, as measured in accordance with U.S. generally accepted accounting principles (“GAAP”), of $17.2 million, or $0.70 per share, compared to $6.7 million and $0.28 per share for the first quarter of 2014. The results also reflect proceeds of $2.9 million and $2.3 million for the first quarter of 2015 and 2014, respectively, from the sale of a New Jersey state tax benefit, which is recorded as a benefit in other income (expense), net. The weighted average number of shares of common stock outstanding utilized in the calculation of net loss per common share was 24,602,668 and 23,717,393 for the first quarter of 2015 and 2014, respectively. The increase in the weighted average number of shares of

common stock outstanding is mainly attributable to the exercise of stock options, vesting of restricted stock and the issuance and sale of common stock under the “at-the-market,” or ATM, sales agreement, pursuant to the Company’s shelf registration statement filed on Form S-3 on November 3, 2014. During the three months ended March 31, 2015, we issued and sold 1,204,248 shares of common stock under the ATM sales agreement.

The $17.2 million net loss attributable to common stockholders for the first quarter of 2015 includes $19.6 million in operating expenses, reflecting $11.6 million in research and development expenses and $8.0 million in general and administrative expenses. Included in the $19.6 million of operating expenses is $2.7 million of non-cash stock-based compensation expense. Excluding non-cash stock-based compensation expense, adjusted operating expenses for the first quarter of 2015 were $16.9 million include adjusted research and development expenses of $11.1 million and adjusted general and administrative expenses of $5.8 million. Total adjusted net loss for the first quarter of 2015 was $14.5 million and adjusted net loss per share was $0.59.

The $6.7 million net loss attributable to common stockholders for the first quarter of 2014 includes $9.0 million in operating expenses, reflecting research and development expenses of $5.4 million and general and administrative expenses of $3.6 million. Included in the $9.0 million of operating expenses is $1.9 million of non-cash stock-based compensation expense. Excluding non-cash stock-based compensation expense, adjusted operating expenses for the first quarter of 2014 were approximately $7.1 million, reflecting adjusted research and development expenses of $4.8 million and adjusted general and administrative expenses of $2.3 million. Total adjusted net loss for the first quarter of 2014 was $4.7 million and adjusted net loss per share was $0.20.

The higher operating expenses in the first quarter of 2015 as compared to the first quarter of 2014 primarily reflect increased clinical activities for Rhopressa™, increased non-clinical activities for Roclatan™ and increased activity related to supporting the growth in our operations.

Conference Call / Web Cast Information

The Company will host a live conference call and webcast at 5:00 p.m. Eastern Time today to discuss the Company’s financial results and provide a general business and strategic update. In addition, a presentation including additional findings from Rocket 1 will be discussed on the conference call and posted to the website.

The live webcast and a replay may be accessed by visiting the Company’s website at http://investors.aeriepharma.com. Please connect to the Company’s website at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast. Alternatively, please call (888) 734-0328 (U.S.) or (678) 894-3054 (international) to listen to the live conference call. The conference ID number for the live call is 1639305. Please dial in approximately 10 minutes prior to the call. Telephone replay will be available approximately two hours after the call. To access the replay, please call (855) 859-2056 (U.S.) or (404) 537-3406 (international). The conference ID number for the replay is 1639305. The telephone replay will be available until May 14, 2015.

About Aerie Pharmaceuticals, Inc.

Aerie is a clinical-stage pharmaceutical company focused on the discovery, development and commercialization of first-in-class therapies for the treatment of patients with glaucoma and other diseases of the eye. The Company is conducting a Phase 3 registration trial in the United States, named “Rocket 2,” where the primary efficacy endpoint will be to demonstrate non-inferiority of IOP lowering for Rhopressa^TM compared to timolol, along with a Phase 3 registration safety-only trial, named “Rocket 3,” in Canada. The Company recently completed its initial Phase 3 registration trial, “Rocket 1,” the three-month efficacy results of which were initially reported on April 23, 2015. The Company also completed in 2014 a Phase 2b clinical trial for Roclatan^TM.

Forward-Looking Statements

This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should,” “exploring,” “pursuing” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the success, timing and cost of our ongoing and anticipated preclinical studies and clinical trials for our current product candidates, including statements regarding the timing of initiation and completion of the studies and trials; our expectations regarding the clinical effectiveness of our product candidates and results of our clinical trials; the timing of and our ability to obtain and maintain U.S. Food and Drug Administration or other regulatory authority approval of, or other action with respect to, our product candidates; our expectations regarding the commercialization of our product candidates; our expectations related to the use of proceeds from our initial public offering, the issuance and sale of our senior secured convertible notes and the issuance and sale of shares of our common stock in connection with our “at-the-market” sales agreement; our estimates regarding anticipated capital requirements and our needs for additional financing; the potential advantages of our product candidates; our plans to pursue development of our product candidates for additional indications and other therapeutic opportunities; our plans to explore possible uses of our existing proprietary compounds beyond glaucoma; our ability to protect our proprietary technology and enforce our intellectual property rights; and our expectations regarding strategic operations, including our ability to in-license or acquire additional ophthalmic products or product candidates. By their nature, forward-looking statements involve risks and uncertainties because they relate to events, competitive dynamics and industry change, and depend on regulatory approvals and economic circumstances that may or may not occur in the future or may occur on longer or shorter timelines than anticipated. We discuss many of these risks in greater detail under the heading “Risk Factors” in the quarterly and annual reports that we file with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance and our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

Non-GAAP Financial Measures

To supplement our financial statements, which are prepared and presented in accordance with GAAP, we use the following non-GAAP financial measures, some of which are discussed above: adjusted net loss, adjusted operating expenses, adjusted research and development expenses, adjusted general and administrative expenses, adjusted other income (expense) and adjusted net loss per share. For a description of the adjusted calculations and reconciliation to the nearest GAAP measure, please see the “Reconciliation of GAAP Net Loss to Adjusted Net Loss” and “Reconciliation of GAAP Net Loss per Share to Adjusted Net Loss per Share” tables in this press release.

We believe these non-GAAP financial measures provide investors with useful supplemental information about the financial performance of our business, enable comparison of financial results between periods where certain items may vary independent of business performance, and allow for greater transparency with respect to key metrics used by management in operating our business.

The presentation of these financial measures is not intended to be considered in isolation from, or as a substitute for, financial information prepared and presented in accordance with GAAP. Investors are cautioned that there are material limitations associated with the use of non-GAAP financial measures as an analytical tool. In particular, the adjustments to our GAAP financial measures reflect the exclusion of non-cash stock-based compensation expense, which is recurring and will be reflected in our financial results for the foreseeable future. In addition, these measures may be different from non-GAAP financial measures used by other companies, limiting their usefulness for comparison purposes. We compensate for these limitations by providing specific information regarding the GAAP amounts excluded from these non-GAAP financial measures.

AERIE PHARMACEUTICALS, INC.

Consolidated Balance Sheets

(in thousands, except share and per share data)

	MARCH 31, 2015			DECEMBER 31, 2014
	(unaudited)
Assets
Current assets
Cash and cash equivalents	$	113,450		$	85,586
Short-term investments		56,286			54,339
Prepaid expenses and other current assets		1,219			1,122
Total current assets		170,955			141,047
Long-term investments		9,574			18,275
Furniture, fixtures and equipment, net		796			240
Other assets, net		13,872			1,523
Total assets	$	195,197		$	161,085
Liabilities and Stockholders’ Equity
Current liabilities
Accounts payable and other current liabilities	$	21,852		$	8,336
Interest payable		539			551
Total current liabilities		22,391			8,887
Convertible notes, net of discounts		124,187			124,156
Total liabilities		146,578			133,043
Commitments and contingencies
Stockholders’ Equity
Preferred stock, $0.001 par value; 15,000,000 shares authorized as of March 31, 2015 and December 31, 2014; None issued and outstanding		—			—
Common stock, $0.001 par value; 150,000,000 shares authorized as of March 31, 2015 and December 31, 2014; 25,275,672 and 24,018,577 shares issued and outstanding as of March 31, 2015 and December 31, 2014, respectively		25			24
Additional paid-in capital		209,092			171,326
Accumulated other comprehensive loss		(58	)		(107	)
Accumulated deficit		(160,440	)		(143,201	)
Total stockholders’ equity		48,619			28,042
Total liabilities and stockholders’ equity	$	195,197		$	161,085

AERIE PHARMACEUTICALS, INC.

Consolidated Statements of Operations and Comprehensive Loss

(Unaudited)

(in thousands, except share and per share data)

	THREE MONTHS ENDED MARCH 31,
	2015			2014
Operating expenses
General and administrative	$	(8,023	)	$	(3,612	)
Research and development		(11,618	)		(5,370	)
Loss from operations		(19,641	)		(8,982	)
Other income (expense), net		2,402			2,311
Net loss	$	(17,239	)	$	(6,671	)
Net loss attributable to common stockholders—basic and diluted	$	(17,239	)	$	(6,671	)
Net loss per share attributable to common stockholders—basic and diluted	$	(0.70	)	$	(0.28	)
Weighted average number of common shares outstanding—basic and diluted		24,602,668			23,717,393
Net loss		(17,239	)		(6,671	)
Unrealized loss on available-for-sale investments		49			(21	)
Comprehensive loss	$	(17,190	)	$	(6,692	)

Aerie Pharmaceuticals, Inc.

Reconciliation of GAAP Net Loss to Adjusted Net Loss

(Unaudited)

(in thousands)

	THREE MONTHS ENDED
	MARCH 31,
	2015			2014
Net loss attributable to common stockholders – basic and diluted:
Net loss attributable to common stockholders – basic and diluted (GAAP)	$	(17,239	)	$	(6,671	)
Adjustments:
Stock-based compensation (a)		2,741			1,922
Adjusted Net loss	$	(14,498	)	$	(4,749	)
Operating expenses:
General and administrative expense:
General and administrative expense (GAAP)	$	(8,023	)	$	(3,612	)
Adjustments:
Stock-based compensation (a)		2,230			1,307
Adjusted general and administrative expense	$	(5,793	)	$	(2,305	)
Research and development expense:
Research and development expense (GAAP)	$	(11,618	)	$	(5,370	)
Adjustments:
Stock-based compensation (a)		511			615
Adjusted research and development expense	$	(11,107	)	$	(4,755	)
Operating expenses (GAAP)	$	(19,641	)	$	(8,982	)
Adjustments:
Stock-based compensation (a)		2,741			1,922
Adjusted operating expenses	$	(16,900	)	$	(7,060	)
Other income (expense):
Other income (expense) (GAAP)	$	2,402		$	2,311
Adjustments:
		—			—
Adjusted other income (expense)	$	2,402		$	2,311

Aerie Pharmaceuticals, Inc.

Reconciliation of GAAP Net Loss Per Share to Adjusted Net Loss Per Share

(Unaudited)

	THREE MONTHS ENDED
	MARCH 31,
	2015			2014
Net loss per share attributable to common stockholders – basic and diluted:
Net loss per share attributable to common stockholders – basic and diluted (GAAP)	$	(0.70	)	$	(0.28	)
Adjustments:
Stock-based compensation (a)		0.11			0.08
Adjusted Net loss per share	$	(0.59	)	$	(0.20	)
Weighted average number of common shares outstanding – basic and diluted		24,602,668			23,717,393

Aerie is providing adjusted information that excludes certain items because of the nature of these items and the impact they have on the analysis of underlying business performance and trends. Management believes that providing this information enhances investors’ understanding of the Company’s performance. This information should be considered in addition to, but not in lieu of, information prepared in accordance with GAAP.

Explanation of adjustments:

(a) Stock-based compensation: Exclude the non-cash stock-based compensation.

Contacts

Aerie Pharmaceuticals

Richard Rubino, 908-947-3540

rrubino@aeriepharma.com

or

Burns McClellan, Inc., on behalf of Aerie Pharmaceuticals

Ami Bavishi, 212-213-0006

abavishi@burnsmc.com

EX-99.2

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

30