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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 10-K
(Mark One)
☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended December 31, 2019
or
◻ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from to
Commission file number 001-36554
Ocular Therapeutix, Inc.
(Exact name of registrant as specified in its charter)
Delaware
(State or other jurisdiction of
incorporation or organization)
24 Crosby Drive
Bedford, MA
(Address of principal executive offices)
20- 5560161
(I.R.S. Employer
Identification No.)
01730
(Zip Code)
(781) 357-4000
(Registrant’s telephone number, including area code)
Securities registered pursuant to Section 12(b) of the Act:
Title of each class
Common Stock, $0.0001 par value per share
Trading Symbol
OCUL
Name of each exchange on which registered
Nasdaq Global Market
Securities registered pursuant to Section 12(g) of the Act: None
Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. ◻ Yes ☒ No
Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. ◻ Yes ☒ No
Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934
during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing
requirements for the past 90 days. ☒ Yes ◻ No
Indicate by check mark whether the registrant has submitted electronically, every Interactive Data File required to be submitted pursuant to Rule 405 of
Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such
files). ☒ Yes ◻ No
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an
emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company” and “emerging growth company”
in Rule 12b-2 of the Exchange Act.
Large accelerated filer ◻
Non-accelerated filer
◻
(cid:0)
Accelerated filer
Smaller reporting company
Emerging growth company
☒
☒
(cid:0)
◻
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any
new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ◻
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). ◻ Yes ☒ No
As of June 28, 2019, the aggregate market value of the voting and non-voting common equity held by non-affiliates of the registrant was approximately
$169 million. The number of shares outstanding of the registrant’s class of common stock, as of March 2, 2020: 52,576,940.
DOCUMENTS INCORPORATED BY REFERENCE
Part III of this Annual Report incorporates by reference information from the definitive Proxy Statement for the registrant’s 2020 Annual Meeting of
Stockholders, which is expected to be filed with the Securities and Exchange Commission not later than 120 days after the registrant’s fiscal year ended
December 31, 2019.
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TABLE OF CONTENTS
PART I
Business
Item 1.
Item 1A. Risk Factors
Item 1B. Unresolved Staff Comments
Item 2.
Item 3.
Item 4. Mine Safety Disclosures
Properties
Legal Proceedings
PART II
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of
Equity Securities
Selected Financial Data
Item 6.
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations
Item 7A. Quantitative and Qualitative Disclosures About Market Risk
Financial Statements and Supplementary Data
Item 8.
Item 9.
Changes in and Disagreements with Accountants on Accounting and Financial Disclosure
Item 9A. Controls and Procedures
Item 9B. Other Information
PART III
Item 10. Directors, Executive Officers and Corporate Governance
Item 11. Executive Compensation
Item 12.
Item 13. Certain Relationships and Related Transactions, and Director Independence
Item 14.
Principal Accounting Fees and Services
Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
Item 15. Exhibits, Financial Statement Schedules
Item 16.
Form 10-K Summary
PART IV
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FORWARD-LOOKING STATEMENTS
This Annual Report on Form 10-K contains forward-looking statements that involve substantial risks and
uncertainties. All statements, other than statements of historical facts, contained in this Annual Report on Form 10-K,
including statements regarding our strategy, future operations, future financial position, future revenues, projected costs,
prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,”
“estimate,” “expect,” “intend,” “may,” “might,” “plan,” “predict,” “project,” “target,” “potential,” “goals,” “will,” “would,”
“could,” “should,” “continue” and similar expressions are intended to identify forward-looking statements, although not all
forward-looking statements contain these identifying words.
The forward-looking statements in this Annual Report on Form 10-K include, among other things, statements about:
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our commercialization efforts for our product DEXTENZA ;
®
our plans to develop and commercialize DEXTENZA for additional indications and our product candidates
based on our proprietary bioresorbable hydrogel technology platform;
our ability to manufacture DEXTENZA, ReSure Sealant and our product candidates in compliance with current
Good Manufacturing Practices, or cGMP;
our ability to manage a sales, marketing and distribution infrastructure to support the commercialization of
DEXTENZA;
the timing of and our ability to submit applications and obtain and maintain regulatory approvals for
DEXTENZA and our other product candidates;
our estimates regarding future revenue and expenses and the sufficiency of our cash resources, our ability to fund
our operating expenses, debt service obligations and capital expenditure requirements and our needs for
additional financing;
our plans to raise additional capital, including through equity offerings, debt financings, collaborations, strategic
alliances, licensing arrangements, royalty agreements and marketing and distribution arrangements;
our ongoing and planned clinical trials: including our Phase 3 clinical trials of DEXTENZA for the treatment of
ocular itching associated with allergic conjunctivitis; our Phase 1 clinical trial of OTX-TIC for the reduction of
intraocular pressure in patients with primary open-angle glaucoma or ocular hypertension; and our Phase 1
clinical trial of OTX-TKI for the treatment of wet age-related macular degeneration, or wet AMD;
our ability to resolve the U.S. Food and Drug Administration warning letter received with respect to ReSure
Sealant on October 18, 2018;
®
the potential advantages of DEXTENZA, ReSure Sealant, and our product candidates;
the rate and degree of market acceptance and clinical utility of our products;
our ability to secure and continue to maintain reimbursement for our products;
our estimates regarding the potential market opportunity for DEXTENZA, ReSure Sealant, OTX-TIC, OTX-TKI
and our other product candidates;
the preclinical development of our intravitreal depot with protein-based or small molecule drugs for the
treatment of wet AMD and other retinal diseases;
our strategic collaboration, option and license agreement with Regeneron Pharmaceuticals, Inc. under which we
are collaborating on the development of an extended-delivery formulation of the vascular endothelial
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growth factor, trap aflibercept, currently marketed under the brand name Eylea, for the treatment of wet AMD,
and other serious retinal diseases;
our capabilities and strategy related to, and the costs and timing of manufacturing, sales, marketing, distribution
and other commercialization efforts with respect to DEXTENZA, ReSure Sealant and any additional products
for which we may obtain marketing approval in the future;
our intellectual property position;
our ability to identify additional products, product candidates or technologies with significant commercial
potential that are consistent with our commercial objectives, including potential opportunities outside the field of
ophthalmology;
the impact of government laws and regulations;
the costs and outcomes of legal actions and proceedings;
our ability to continue as a going concern; and
our competitive position.
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We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and
you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially
from the plans, intentions and expectations disclosed in the forward-looking statements we make. We have included
important factors in the cautionary statements included in this Annual Report on Form 10-K, particularly in the “Risk
Factors” section, that could cause actual results or events to differ materially from the forward-looking statements that we
make. Our forward-looking statements do not reflect the potential impact of any future acquisitions, mergers, dispositions,
joint ventures or investments we may make.
You should read this Annual Report on Form 10-K and the documents that we have filed as exhibits to this Annual
Report on Form 10-K completely and with the understanding that our actual future results may be materially different from
what we expect. We do not assume any obligation to update any forward-looking statements, whether as a result of new
information, future events or otherwise, except as required by applicable law.
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Item 1.
Business
Overview of Ocular Therapeutix
LOCAL PPART I
We are a biopharmaceutical company focused on the formulation, development and commercialization of innovative
therapies for diseases and conditions of the eye using our proprietary, bioresorbable hydrogel platform technology. We use
this technology to tailor duration and amount of delivery of a range of therapeutic agents of varying duration in our product
candidates.
We are pursuing three overall strategic goals:
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To make prescription eye drops obsolete;
To make immediate release, back-of-the-eye injections obsolete; and
To extend our hydrogel platform technology for use beyond the eye to other areas of the body.
We currently incorporate therapeutic agents that have previously received regulatory approval from the U.S. Food
and Drug Administration, or FDA, including small molecules and proteins, into our hydrogel technology with the goal of
providing local programmed-release of drug to the eye. We believe that our local programmed-release drug delivery
technology has the potential to treat conditions and diseases of both the front and the back of the eye and can be
administered through a range of different modalities including intracanalicular inserts, intracameral implants and
intravitreal implants. We have products and product candidates in early commercial, clinical and preclinical development
applying this technology to treat post-surgical ocular inflammation and pain, ocular itching associated with allergic
conjunctivitis, dry eye disease, glaucoma and ocular hypertension, and wet age-related macular degeneration, or wet AMD,
among other conditions.
In November 2018, the FDA approved our new drug application, or NDA, for DEXTENZA (dexamethasone
ophthalmic insert) 0.4mg for intracanalicular use for the treatment of ocular pain following ophthalmic surgery. In June
2019, the FDA approved our supplemental new drug application, or sNDA, for DEXTENZA to treat post-surgical ocular
inflammation. On July 1, 2019, we commercially launched DEXTENZA in the United States for the treatment of post-
surgical ocular inflammation and pain. DEXTENZA is the first FDA-approved intracanalicular insert delivering
dexamethasone to treat post-surgical ocular inflammation and pain for up to 30 days with a single administration. We have
enrolled 96 patients in a pivotal Phase 3 clinical trial evaluating DEXTENZA for the treatment of ocular itching associated
with allergic conjunctivitis.
®
In May 2019, we announced the results of the Phase 3 clinical trial of our product candidate OTX-TP
(intracanalicular travoprost insert) for the reduction of intraocular pressure, or IOP, in patients with glaucoma and ocular
hypertension. Both DEXTENZA and OTX-TP are local programmed-release, drug-eluting, preservative-free
intracanalicular inserts that are placed into the canaliculus through a natural opening called the punctum located in the
portion of the lower eyelid near the nose. In October 2019, we announced that we had met with the FDA who determined
that the results did not achieve clinical meaningfulness for OTX-TP. As a result, we informed the market that we did not
intend to advance OTX-TP without a partner.
Our earlier stage assets include two development programs that have initiated clinical trials: OTX-TIC, an
intracameral travoprost implant for the reduction of IOP in patients with glaucoma and ocular hypertension when greater
IOP reduction is needed, and OTX-TKI, an intravitreal injection by fine gauge needle of a hydrogel, anti-angiogenic
formulation of a tyrosine kinase inhibitor, or TKI, for the treatment of wet AMD. We also have a collaboration with
Regeneron Pharmaceuticals, Inc., or Regeneron, for the development and potential commercialization of products
containing our local programmed-release hydrogel in combination with Regeneron’s VEGF inhibitor, aflibercept, currently
marketed under the brand name Eylea. We delivered an initial formulation to Regeneron in December 2017 that was
subsequently determined to not achieve the goals of the program. We are currently negotiating an amendment to the initial
collaboration to deliver additional formulations going forward.
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In addition to our ongoing drug product development, we currently market ReSure Sealant, a hydrogel ophthalmic
®
wound sealant approved by the FDA to seal corneal incisions following cataract surgery. ReSure Sealant is the first and
only surgical sealant to be approved by the FDA for ophthalmic use. We are also assessing the potential use of our
hydrogel platform technology in other areas of the body.
Front-of-the-Eye Programs: Intracanalicular Inserts
Poor patient compliance with eye drop regimens and the need for frequent administration of eye drops at high drug
concentrations due to rapid washout by the tears can create challenges in the successful management of ocular diseases and
conditions. For example, poor patient compliance can lead to diminished efficacy and disease progression and high drug
concentrations can create side effects. We are developing therapies to replace standard of care eye drop regimens with our
innovative local programmed-release, drug-eluting intracanalicular inserts. The goal for our intracanalicular insert product
candidates is to replace the management of many front-of-the-eye diseases and conditions using frequent, pulsed eye drop
therapy, characterized by significant variations in drug concentration over time, with longer term, local programmed-
release hydrogel-based therapeutic agents to improve patient outcomes.
DEXTENZA (dexamethasone ophthalmic insert)
®
DEXTENZA incorporates the FDA-approved corticosteroid dexamethasone as an active pharmaceutical ingredient
into a hydrogel, drug-eluting intracanalicular insert. In November 2018, the FDA approved our NDA for DEXTENZA for
the treatment of post-surgical ocular pain. In June 2019, the FDA approved our sNDA, for DEXTENZA to treat post-
surgical ocular inflammation. In connection with our July 1, 2019 commercial launch of DEXTENZA for post-surgical
ocular inflammation and pain, we have built our own highly targeted, key account manager, or KAM, sales force that
focuses on the ambulatory surgical centers, or ASCs, responsible for the largest volumes of cataract surgery. Since the
commercial launch of DEXTENZA, we have expanded our field sales team to a total of 30 KAMs. DEXTENZA is now
available through a network of distributors. Our initial commercial efforts are focused on the two million cataract
procedures performed annually under Medicare Part B. Following our receipt of FDA approval on November 30, 2018, we
submitted an application for a C-code for transitional pass-through payment status. On May 29, 2019, we received formal
notification from the Centers for Medicare and Medicaid Services, or CMS, that it had approved transitional pass-through
payment status and established a new reimbursement code for DEXTENZA. The code, C9048, became effective on July 1,
2019. On December 28, 2018, we submitted an application for a J-Code for permanent payment status. In July 2019, we
subsequently received a specific and permanent J-Code, J1096, that became effective October 1, 2019. A J-Code is a
permanent code used to report drugs that ordinarily cannot be self-administered. With the effectiveness of our permanent J-
Code as of October 1, 2019, our C-code is no longer in effect.
We have completed three Phase 3 clinical trials of DEXTENZA for the treatment of post-surgical ocular
inflammation and pain. The data from two of these three completed Phase 3 clinical trials and a prior Phase 2 clinical trial
were used to support our NDA for post-surgical ocular pain; data from a subsequent Phase 3 clinical trial was used to
support our subsequent sNDA for post-surgical ocular inflammation.
We have completed two Phase 3 clinical trials of DEXTENZA for the treatment of allergic conjunctivitis and are
currently conducting a third Phase 3 clinical trial. In October 2015, we announced topline results of our first Phase 3
clinical trial for the treatment of ocular itching and conjunctival redness associated with allergic conjunctivitis. In June
2016 we announced topline results of our second Phase 3 clinical trial for the treatment of ocular itching associated with
allergic conjunctivitis. In the first Phase 3 clinical trial, DEXTENZA achieved the co-primary endpoint of improvement in
ocular itching compared with placebo but failed to achieve on the co-primary endpoint of improvement in conjunctival
redness compared with placebo, in each case, at certain prespecified timepoints. For the second Phase 3 trial, DEXTENZA
failed to achieve the primary endpoint of improvement in ocular itching compared with placebo, at certain prespecified
timepoints. In the third quarter of 2019, we began dosing patients in pivotal Phase 3 clinical trial evaluating DEXTENZA
for the treatment of ocular itching associated with allergic conjunctivitis. A total of 96 patients were enrolled in this Phase
3 clinical trial, which is a U.S.-based, multi-center, 1:1 randomized, double-masked, placebo-controlled trial testing the
safety and efficacy of DEXTENZA (dexamethasone ophthalmic insert) 0.4 mg versus a placebo vehicle punctum plug
using the Ophthalmic Research Associates’ modified Conjunctival Allergen Challenge (Ora-Cac®) Model for the treatment
of ocular itching associated with allergic conjunctivitis. The trial is designed to assess the effect of DEXTENZA compared
with a placebo on allergic reactions using a series of successive allergen challenges over a 30-day period. The primary
efficacy endpoint being evaluated in the study is ocular itching one week following the insertion of DEXTENZA.
DEXTENZA is administered by a physician as a bioresorbable intracanalicular
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insert and designed for drug release to the ocular surface for up to 30 days. If this trial is successful, we plan to submit a
supplemental NDA to the FDA for the indication of ocular itching associated with allergic conjunctivitis. We recently
completed enrollment and topline results from this trial are anticipated to be reported in the second quarter of 2020.
We are also planning to evaluate DEXTENZA in pediatric subjects that are 0 to 3 years of age undergoing cataract
surgery beginning in the fourth quarter of 2020. The planned pediatric trial is a post-approval commitment to the
FDA. Additionally, we have initiated several investigator-initiated trials evaluating DEXTENZA in different clinical
situations.
We have also completed a small proof-of-concept Phase 2 clinical trial of DEXTENZA for the treatment of episodic
dry eye disease which suggests that DEXTENZA may have benefit in treating ocular surface disease.
OTX-TP (intracanalicular travoprost insert)
Our product candidate OTX-TP is an intracanalicular insert that delivers a preservative-free formulation of the drug
travoprost, an FDA approved prostaglandin analog, for the reduction of intraocular pressure, or IOP, in patients with
primary open-angle glaucoma or ocular hypertension. OTX-TP is designed to lower IOP for up to 90 days and to address
the poor adherence associated with chronic, daily eye drop regimens, the current standard of care.
On May 20, 2019, we reported topline results of a Phase 3 randomized, double blind, placebo-controlled clinical trial
that was conducted across more than 50 sites and enrolled 554 subjects with open-angle glaucoma or ocular hypertension in
the full analysis set, or FAS, population. The trial’s primary efficacy endpoint was an assessment of mean IOP at nine
different time points, three diurnal time points (8:00 a.m., 10:00 a.m., and 4:00 p.m.) at each of 2, 6, and 12 weeks
following insertion. The secondary endpoints included an evaluation of whether OTX-TP demonstrated a statistically
superior mean reduction of IOP from baseline for OTX-TP treated subjects compared with placebo insert treated subjects
(Table 1) compared with placebo insert treated subjects at the same nine time points. Topline results show that the trial did
not achieve its endpoint of statistically significant superiority in mean reduction of IOP compared with placebo at all nine
time points.
OTX-TP was generally well tolerated and no ocular serious adverse events were observed. The most common ocular
adverse events seen in the study eye were dacryocanaliculitis (approximately 7.0% in OTX-TP vs. 3.0% in placebo) and
lacrimal structure disorder (approximately 6.0% in OTX-TP vs. 4.0% in placebo).
We have met with the FDA to discuss data we reported in May 2019 from our completed Phase 3 trial. Our
conversation with the FDA was productive and involved a discussion around the importance of compliance and how a
product like OTX-TP could address the issue of non-compliance by delivering a prostaglandin analog formulated with our
local programmed-release hydrogel to lower intraocular pressure for up to 12 weeks with a single insert. While the FDA
did not feel that the data from this clinical trial met the standard of clinical meaningfulness in the population studied, there
were constructive discussions about potential pathways forward in specific patient populations for whom drops are
problematic. Based on the feedback following these discussions with the FDA, we do not intend to initiate a second Phase
3 clinical trial at this time without the assistance of a collaborative partner. We believe that if we were to find a partner for
our OTX-TP program, we or such partner could decide to conduct additional Phase 2 clinical trials to address feedback
from the FDA prior to another Phase 3 clinical trial. Given the potential use of OTX-TP as a chronic therapy, however, we
have decided to continue an ongoing open-label, one-year safety extension study, generating six-month and one-year safety
data for a limited number of subjects to support a potential future product registration. We anticipate data from this safety
study including pharmacokinetic data later this year.
Front-of-the-Eye Programs: Implants for Intracameral Injection
OTX-TIC (travoprost implant for intracameral injection)
OTX-TIC is our product candidate for glaucoma patients in need of a more significant reduction in IOP. OTX-TIC is
a bioresorbable hydrogel implant incorporating travoprost that is designed to be administered by a physician as an
intracameral injection with an initial target duration of drug release of four to six months. Preclinical studies to date have
demonstrated reduction of IOP and pharmacokinetics in the aqueous humor that suggest a pharmacodynamic response of
IOP reduction in humans. Our investigational new drug application, or IND, for our U.S. trial became effective in the first
quarter of 2018, and we dosed the first patient in May 2018. This clinical trial is a multi-center, open-label, dose-
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escalation, proof-of-concept study designed to evaluate the safety, biological activity, durability, and tolerability of OTX-
TIC in patients with primary open-angle glaucoma or ocular hypertension. We presented initial results from the first cohort,
comprised of five patients, in this clinical trial at the Association of Research and Vision of Ophthalmology (ARVO)
meeting in April 2019 and the American Society of Cataract and Refractive Surgery annual meeting in May 2019. We
subsequently presented results from the second cohort, comprised of four patients, at the Glaucoma 360 conference in
February 2020. These data demonstrated that, with a single implant, subjects were able to achieve IOP lowering from
baseline for up to eighteen months. In addition, the hydrogel carrier, as designed, biodegraded in approximately five to
seven months. There were no clinically meaningful changes in corneal health as measured by endothelial cell evaluation
and corneal pachymetry. Several subjects reported low grade inflammation and peripheral anterior synechiae that we
believe may be addressable with modifications to the implants.
We are currently collecting additional data from the first two cohorts and have begun enrolling a third and fourth
cohort to assess the impact of a faster degrading implant with the same therapeutic dose as administered in cohort one and a
fourth cohort to assess an additional formulation with a smaller implant of OTX-TIC. We expect to provide topline data for
the third and fourth cohorts in the second half of 2020.
Back-of-the-Eye Programs
We are engaged in the development of formulations of our hydrogel administered via intravitreal injection to address
the large and growing markets for diseases and conditions of the back of the eye. Our initial development efforts are
focused on the use of our extended-delivery hydrogel in combination with anti-angiogenic drugs, such as protein-based
anti-VEGF drugs, or small molecule drugs, such as TKIs, for the treatment of retinal diseases such as wet AMD, retinal
vein occlusion and diabetic macular edema. Our initial goal for these programs is to provide extended delivery over a four
to nine-month period thereby reducing the frequency of the current monthly or bi-monthly immediate release intravitreal
injection regimen for wet AMD and other retinal diseases.
OTX-TKI (tyrosine kinase inhibitor intravitreal implant containing axitinib)
OTX-TKI is a preformed, bioresorbable hydrogel fiber incorporating axitinib, a small molecule TKI with anti-
angiogenic properties delivered by intravitreal injection. TKIs have shown promise in the treatment of wet AMD. In May
2017, we reported data from preclinical studies evaluating the efficacy, tolerability and pharmacokinetics of OTX-TKI. In
this study, OTX-TKI was well-tolerated, and high levels of drug were maintained in the tissue for up to twelve months in
Dutch belted rabbits. In the first quarter of 2019, we began dosing patients in a Phase 1 clinical trial in Australia. This
clinical trial is a multi-center, open-label, dose escalation study designed to evaluate the safety, durability and tolerability
of OTX-TKI. We also plan to evaluate biological activity by following visual acuity over time and measuring retinal
thickness using standard optical coherence tomography. Two cohorts of six subjects each have been enrolled, a lower dose
cohort of 200 μg and a higher dose cohort of 400 μg. In these cohorts, OTX-TKI was generally well tolerated and observed
to have a favorable safety profile with no ocular serious adverse events noted. In the higher dose cohort, OTX-TKI showed
a decrease in central subfield retinal thickness as measured by mean changes in central subfield thickness values by
decreases in intraretinal and/or subretinal fluid in some subjects. We plan to continue long-term evaluation of these
cohorts. We plan to amend our current clinical trial protocol to enroll a third, higher-dose cohort. This Phase 1 clinical trial
is not powered to measure any efficacy endpoints with statistical significance.
OTX-IVT (intravitreal aflibercept implant) in Collaboration with Regeneron
In October 2016, we entered into a strategic collaboration, option and license agreement, or Collaboration
Agreement, with Regeneron for the development and potential commercialization of products using our hydrogel in
combination with Regeneron’s large molecule VEGF-targeting compounds for the treatment of retinal diseases, with the
initial focus on the VEGF trap aflibercept, currently marketed under the brand name Eylea. Under the terms of the
agreement, we granted Regeneron an option, or the Option, to enter into an exclusive, worldwide license under our
intellectual property to develop and commercialize products using our hydrogel in combination with Regeneron’s large
molecule VEGF-targeting compounds, or Licensed Products. The Collaboration Agreement does not cover the
development of any products that deliver small molecule drugs, including TKIs, for any target including VEGF, or any
products that deliver large molecule drugs other than those that target VEGF proteins. Under the terms of the Collaboration
Agreement, we and Regeneron have agreed to conduct a joint research program with the aim of developing an extended-
delivery formulation of aflibercept that is suitable for advancement into clinical development. We refer to the formulation
we are developing with Regeneron as OTX-IVT.
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Under the terms of the Collaboration Agreement, Regeneron is responsible for funding an initial preclinical
tolerability study. If the Option is exercised, Regeneron will conduct further preclinical development and an initial clinical
trial under a collaboration plan. We are obligated to reimburse Regeneron for certain development costs during the period
through the completion of the initial clinical trial, subject to a cap of $25 million, which cap may be increased by up to $5
million under certain circumstances. We do not expect our funding requirements under the collaboration to be material over
the next twelve months. If Regeneron elects to proceed with further development beyond the initial clinical trial, it will be
solely responsible for conducting and funding further development and commercialization of product candidates. If the
Option is exercised, Regeneron is required to use commercially reasonable efforts to research, develop and commercialize
at least one Licensed Product. Such efforts shall include initiating the dosing phase of a subsequent clinical trial within
specified time periods following the completion of the first-in-human clinical trial or the initiation of preclinical toxicology
studies, subject to certain extensions.
Under the terms of the Collaboration Agreement, Regeneron has agreed to pay us $10 million upon exercise of the
Option. We are also eligible to receive up to $145 million per Licensed Product upon the achievement of specified
development and regulatory milestones, including successful results from the first-in-human clinical trial, $100 million per
Licensed Product upon first commercial sale of such Licensed Product and up to $50 million based on the achievement of
specified sales milestones for all Licensed Products. In addition, we are entitled to tiered, escalating royalties, in a range
from a high-single digit to a low-to-mid teen percentage of net sales of Licensed Products.
In December 2017, we delivered to Regeneron a proposed final formulation for the initial preclinical tolerability
study. Regeneron initiated an initial preclinical tolerability study in early 2018. We and Regeneron have subsequently
reached an understanding that the proposed formulation did not meet the goals of the program, was not final and have
therefore ceased development of it. We are currently in discussions with Regeneron, in accordance with the terms of the
Collaboration Agreement, regarding the development of an alternative formulation.
ReSure Sealant
®
We commercially launched this product in the United States in 2014. ReSure Sealant is approved to seal corneal
incisions following cataract surgery. In the pivotal clinical trials that formed the basis for FDA approval, ReSure Sealant
provided superior wound closure and a better safety profile than sutured closure.
The FDA required two post-approval studies as a condition for approval of our premarket approval, or PMA,
application for ReSure Sealant. The first post-approval study, identified as the Clinical PAS, was to confirm that ReSure
Sealant can be used safely by physicians in a standard cataract surgery practice and to confirm the incidence of the most
prevalent adverse ocular events identified in our pivotal study in eyes treated with ReSure Sealant. We submitted the final
study report to the FDA in June 2016, and the FDA has confirmed the Clinical PAS has been completed. The second post-
approval study, identified as the Device Exposure Registry Study, is intended to link to the Medicare database to ascertain
if patients are diagnosed or treated for endophthalmitis within 30 days following cataract surgery and application of ReSure
Sealant. The Device Exposure Registry Study is required to include at least 4,857 patients. Due to difficulties in
establishing an acceptable way to link ReSure Sealant to the Medicare database and lack of investigator interest, we have
been unable to enroll trial sites and patients, collect patient data and report study data to the FDA. We have provided
regular periodic reports to the FDA on the progress of this post-approval study.
We received a warning letter from the FDA in October 2018 relating to our compliance with data collection and
information reporting obligations in the Device Exposure Registry Study. The FDA warning letter refers to a lack of
progress with the enrollment and related data collection and information reporting obligations for a required post-approval
trial. In November 2018, we appealed this warning letter. In December 2018, the FDA rejected our appeal. Failure by us to
conduct the required post-approval trial for ReSure Sealant to the FDA’s satisfaction may result in withdrawal of the FDA’s
approval of ReSure Sealant or other regulatory action.
A teleconference was held with the FDA in January 2019 resulting in tentative agreement on a proposed retrospective
registry study of endophthalmitis rates to satisfy the Device Exposure Registry Study requirements. In a letter dated June
7, 2019 from the FDA, the agency acknowledged receipt of a letter dated March 29, 2019 from us in which we proposed
conducting the proposed retrospective analysis of the IRIS Registry, comparing endophthalmitis rates from sites that
purchased ReSure versus those sites that did not purchase ReSure. If the rates are no different, the FDA has indicated that
it will consider the post-approval requirement to have been fulfilled. If there is a statistically significant increase in
endophthalmitis rates at sites purchasing ReSure compared with those not purchasing ReSure, a
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prospective study will be required. The FDA has indicated it will consider our response to the warning letter adequate once
it approves the study protocol for the retrospective analysis of the IRIS Registry and the outline of the prospective study. In
December 2019, we submitted the protocol for the agreed upon retrospective study and prospective study outline, as
required per the terms of the warning letter. We received feedback from the FDA in February 2020 and responded to the
FDA in March 2020. We expect a response from the FDA in the middle of 2020.
ReSure Sealant currently remains commercially available in the United States, though there is no sales support
provided to the product at this time. We have received only limited revenues from ReSure Sealant to date and anticipate
only limited sales for 2020.
Additional Potential Areas for Growth
We continue to leverage the potential of our hydrogel platform to explore areas for growth with our focus on
formulating, developing and commercializing innovative therapies for diseases and conditions of the eye.
We are also assessing the potential use of our hydrogel platform technology in other areas of the body and are
studying several localized delivery platforms including via wound inlays; sinus and ear inserts; and subcutaneous,
peripheral, and intra-articular injections. In September 2018, we entered into a second amended and restated license
agreement, or Second Amended Agreement, with Incept LLC, an intellectual property holding company, or Incept. The
Second Amended Agreement expands the scope of our intellectual property license to include products delivered for the
treatment of acute post-surgical pain or for the treatment of ear, nose and/or throat diseases or conditions, subject to
specified exceptions.
Market Background
Our clinical stage product candidates and our marketed product are based on a proprietary bioresorbable hydrogel
technology platform that uses polyethylene glycol, or PEG, as a key component. Bioresorbable materials gradually break
down in the body into non-toxic, water soluble compounds that are cleared by normal biological processes. PEG is used in
many pharmaceutical products and is widely considered to be safe and biocompatible. Our technology platform allows us
to tailor the physical properties, drug release profiles and bioresorption rates of our hydrogels to meet the needs of specific
clinical indications. We have used this platform to engineer each of our intracanalicular insert product candidates, our
intracameral product candidates, our intravitreal implant product candidates, and ReSure Sealant. Our technical capabilities
include a deep understanding of the polymer chemistry of PEG-based hydrogels and the design of the specialized
manufacturing processes required to achieve a reliable, preservative-free and high purity product.
Our product candidates target large and growing markets. Grand View Research estimates that the global ophthalmic
drugs market size was valued at approximately $30 billion in 2018 and is expected to grow at a CAGR of 4.5% from 2018
to 2026. Increased funding by public and private bodies for conducting research on ocular disorders along with the
presence of strong emerging pipeline drugs are among the key factors responsible for the growth of this market.
We have in-licensed a significant portion of the patent rights and the technology for ReSure Sealant and our hydrogel
platform technology product candidates from Incept, LLC, or Incept, an intellectual property holding company. Amarpreet
Sawhney, our former President and Chief Executive Officer and former Chairman of the Board of Directors, is a general
partner of Incept and has a 50% ownership stake in Incept.
Our founders and management team have significant experience in developing and commercializing medical
products for other companies using bioresorbable hydrogel technology, including FDA-approved and currently marketed
medical products such as SpaceOAR (marketed by Boston Scientific, Inc.), a hydrogel spacer used to reduce a common and
debilitating side effect that men may experience after receiving prostate cancer radiotherapy; DuraSeal Dural Sealant
(marketed by Integra Lifesciences, Inc.), a sealant for cranial and spine surgery; and Mynx (marketed by Cardinal Health,
Inc.), a sealant for femoral artery punctures after angiography and angioplasty.
®
®
Product Pipeline
The following table summarizes the status of our key product development programs and our marketed product. We
hold worldwide exclusive commercial rights to the core technology underlying all of our products in development
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and have not granted commercial rights to any marketing partners other than the Option on commercial rights we granted to
Regeneron for the delivery of protein-based anti-VEGF drugs in our hydrogel depot for the treatment of retinal diseases.
Our Strategy
We are pursuing three overall strategic goals: to make prescription eye drops obsolete; to make immediate release
back-of-the-eye injections obsolete; and to extend our hydrogel platform technology for use beyond the eye to other areas
of the body. The key tactics of our strategy to achieve these goals are:
·
·
®
Commercialize DEXTENZA (dexamethasone ophthalmic insert) 0.4mg for intracanalicular use for the
treatment of ocular pain following ophthalmic surgery. DEXTENZA is the first FDA-approved
intracanalicular insert delivering dexamethasone to treat post-surgical ocular inflammation and pain for up to
30 days with a single administration. We launched the commercialization of DEXTENZA in July of 2019 and
have built a commercial field force consisting of 30 key account managers, eight field reimbursement
specialists and five medical sales liaisons.
Create proprietary solutions for ophthalmic diseases and conditions based on our bioresorbable hydrogel and
complete clinical development of and seek marketing approval for other intracanalicular insert product
candidates and implants for intracameral injection for diseases and conditions of the front of the eye.
o Allergic Conjunctivitis.
§
In the first quarter of 2020, we completed enrollment of our pivotal Phase 3 clinical trial
evaluating DEXTENZA for the treatment of ocular itching in connection with allergic
conjunctivitis. A total of 96 patients were enrolled in this trial. This trial represents the third
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Phase 3 clinical trial in allergic conjunctivitis conducted by us and, if successful, we plan to
submit a supplemental NDA to the FDA for an indication of ocular itching associated with
allergic conjunctivitis. We recently completed enrollment and topline data from this trial is
anticipated to be reported in the second quarter of 2020.
o Glaucoma.
§ Our IND for our U.S. Phase 1 trial of OTX-TIC became effective in the first quarter of 2018,
and we dosed the first patient in May 2018. Data generated to date has demonstrated that, with
a single implant, subjects were able to achieve IOP lowering for up to eighteen months. In
addition, the hydrogel carrier, as designed, biodegraded in approximately five to seven months.
There were no clinically meaningful changes in corneal health as measured by slit lamp
examination, endothelial cell evaluation, and corneal pachymetry. We are currently collecting
additional data from the first two cohorts and have begun a third and fourth cohort to assess the
impact of a faster degrading implant with the same therapeutic dose as administered in cohort
one and a fourth cohort to assess an additional formulation with a smaller implant.
·
Pursue development of our intravitreal implant and other technologies for back-of-the-eye diseases and
conditions.
Wet AMD
§
·
In the first quarter of 2019, we began dosing patients in a Phase 1 clinical trial in Australia.
After review of data from the first cohort of patients in the Phase 1, the independent Data Safety
and Monitoring Committee recommended moving to a higher dose of OTX-TKI and we are
currently treating the next cohort of subjects. We have treated two cohorts of six subjects
each. Two cohorts have been enrolled, a lower dose cohort of 200 μg and a higher dose cohort
of 400 μg. In the first two fully enrolled cohorts to date, OTX-TKI was generally well tolerated
and observed to have a favorable safety profile with no ocular serious adverse events noted. In
the higher dose cohort, OTX-TKI showed a decrease in central subfield retinal thickness as
measured by mean central subfield thickness values by decreases in intraretinal and/or subretinal
fluid in some subjects. The Company plans to continue long-term evaluation of the first two
cohorts.
In December 2017, under the Collaboration Agreement with Regeneron, we delivered a
proposed final formulation of our extended-delivery hydrogel in combination with Regeneron’s
large molecule VEGF-targeting compound aflibercept, currently marketed under the brand name
Eylea, for an initial preclinical tolerability study by Regeneron. Regeneron initiated this
preclinical study in early 2018. We and Regeneron have subsequently reached an understanding
that the proposed formulation did not meet the goals of the program, was not final and have
therefore ceased development of it. We are currently in discussions with Regeneron, in
accordance with the terms of the Collaboration Agreement, regarding the development of an
alternative formulation.
·
Apply our local programmed-release intracanalicular insert technology for the treatment of additional diseases
and conditions of the front of the eye. We intend to apply our proprietary PEG-based bioresorbable hydrogel
technology platform to product candidates that are designed to provide local programmed-release of
therapeutic agents to the eye using active pharmaceutical ingredients that are currently used in ophthalmic
drugs approved by the FDA and that are or are expected to become available on a generic basis prior to
anticipated launch dates. By focusing on the development of products based on FDA-approved therapeutic
agents, we believe that we can advance potential products efficiently and predictably through the development
cycle based on well-defined clinical and regulatory approval pathways. We believe this strategy represents an
attractive risk-reward profile relative to new drug development.
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We currently have a number of preclinical programs that we have positioned for further development including
OTX-CSI for episodic dry eye, for which we filed an IND in the United States in December 2019 and intend to
initiate a Phase 1 clinical trial in the middle of 2020; OTX-BPI for acute ocular pain; and OTX-BDI for post-
operative inflammation, pain and bacterial infection.
·
Utilize our hydrogel platform to enable local programmed-release of therapeutics to areas of the body outside
the eye. In September 2018, we entered into the Second Amended Agreement with Incept to expand the scope
of our intellectual property license to include products delivered for the treatment of acute post-surgical pain or
for the treatment of ear, nose and/or throat diseases or conditions, subject to specified exceptions. We intend to
explore programs outside of the eye not only on our own but also potentially through partnerships or
collaborations with third parties who have expertise and experience with other therapeutics as well as other
areas of the body.
Eye Disease
The front of the human eye consists of the cornea on the surface of the eye, the lens and the aqueous humor, which is
a transparent fluid that fills the anterior chamber between the lens and the cornea. The tissue surrounding the eye also
serves important functions. There is a natural opening, called a punctum, located in the inner portion of each upper and
lower eyelid near the nose. The puncta open into nasolacrimal ducts, which collect and drain tears. The conjunctiva is the
membrane covering the inside of the eyelids and the white part of the eye, known as the sclera. It helps to protect the eye
from microbes and to lubricate the eye. The back of the eye contains the retina, which is the light sensing layer of tissue,
the vitreous humor, which is a transparent gel that fills the vitreous chamber between the lens and the retina, and the optic
nerve, which transmits visual information from the retina to the brain. Eye disease can be caused by many factors and can
affect both the front and back of the eye. Diseases and conditions affecting the front of the eye are generally treated either
with surgery or with medications delivered to the ocular surface by eye drops. Intravitreal injections or oral pills are
typically used to deliver medications to the back of the eye.
Cross Section of Eye
Tear Drainage System
Front-of-the-Eye Diseases and Conditions
Ocular Inflammation and Pain
Ocular inflammation and pain are common conditions caused by a variety of factors, including ophthalmic surgery,
allergic conjunctivitis and dry eye disease.
Post-Surgical Ocular Inflammation and Pain
Ocular inflammation and pain are common side effects following ophthalmic surgery. Frequently performed
ophthalmic surgeries include cataract, refractive, vitreoretinal, cornea, and glaucoma procedures. Physicians prescribe anti-
inflammatory drugs, such as corticosteroids, which are typically administered through eye drops multiple times per
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day, following ocular surgery as the standard of care. These drugs improve patient comfort and also accelerate recovery
through disruption of the inflammatory cascade resulting in decreased inflammation and reduced activity of the immune
system. Physicians also frequently prescribe non-steroidal anti-inflammatory drugs, or NSAIDs, as adjunctive or
combination therapy to supplement the use of corticosteroids. If left untreated, inflammation of the eye may result in
further ocular complications, including pain, scarring and vision loss. Market Scope has estimated that approximately
6.1 million ocular surgeries were to be performed in the United States in 2019.
Allergic Conjunctivitis
Allergic conjunctivitis is an inflammatory disease of the conjunctiva resulting primarily from a reaction to
allergy- causing substances such as pollen or pet dander. The primary sign of this inflammation is redness and the primary
symptom is acute itching. Allergic conjunctivitis ranges in clinical severity from relatively mild, common forms to more
severe forms that can cause impaired vision. According to a study on the management of seasonal allergic conjunctivitis
published in 2012 in the peer-reviewed journal Acta Ophthalmologica, allergic conjunctivitis affects 15% to 40% of the
U.S. population. The first line of defense against allergic conjunctivitis is avoidance of the allergen. If this is not successful,
physicians typically prescribe a combination of a topical mast cell stabilizer and anti-histamine. These treatments act to
reduce the signs and symptoms of the early phase allergic reaction. For the subset of patients with chronic or more severe
forms of allergic conjunctivitis, anti-histamines and mast cell stabilizers are often not sufficient to treat their signs and
symptoms. These refractory patients are frequently treated with topical corticosteroids administered by prescription eye
drops.
Dry Eye Disease
Dry eye disease affects the ocular surface and is characterized by dryness, inflammation, pain, discomfort and
irritation. The current standard of care for moderate to severe dry eye disease is the use of artificial tears and topical
anti- inflammatory and immune modulating drugs administered by prescription eye drops. The anti-inflammatory and
immune modulating prescription drug market for the treatment of moderate to severe dry eye disease consists of Restasis®,
for increasing tear production, marketed by Allergan; Cequa™ for increasing tear production, marketed by Sun
Ophthalmics in the United States; lifitegrast, for the treatment of the signs and symptoms of dry eye disease, marketed by
Novartis under the brand name Xiidra®; and off-label use of corticosteroids. Based on our review of industry sources, we
estimate that approximately 20 million people in the United States have dry eye disease, including approximately five
million people who suffer from moderate to severe dry eye disease.
Dry eye disease is a chronic, multifactorial disease affecting the tears and ocular surface that can result in tear film
instability, inflammation, discomfort, visual disturbance and ocular surface damage. Dry eye disease can have a significant
impact on quality of life and can potentially cause long‑term damage to the ocular surface. Due to the impact of dry eye
disease on tear film dynamics, the condition can affect performance of common vision‑related activities such as reading,
using a computer and driving, and can lead to complications associated with visual impairment. In addition, the vast
majority of dry eye patients experience acute episodic exacerbations of their symptoms, which are commonly referred to as
flares, at various times throughout the year. These flares can be triggered by numerous factors, including exposure to
allergens, pollution, wind and low humidity, intense visual concentration such as watching television and working at a
computer, hormonal changes, contact lens wear, smoking and sleep deprivation, which cause ocular surface inflammation
and impact tear production and/or tear film stability.
Based on third‑party academic research, we believe dry eye disease results in approximately $55 billion in direct and
indirect costs in the United States each year, of which approximately $3.8 billion are direct medical costs. The exact
prevalence of dry eye disease is unknown due to the difficulty in defining the disease and the lack of a single diagnostic test
to confirm its presence. The Beaver Dam Offspring Study, a major epidemiological study published in 2014 in
the American Journal of Ophthalmology, reported that in a cohort of over 3,000 patients, dry eye disease was self‑reported
by 14.5% of the patients. The prevalence of dry eye disease increases with age, and we expect that the number of dry eye
disease cases will increase as the U.S. population continues to age.
The most commonly used treatments for dry eye disease in the United States are over‑the‑counter eye drops, often
referred to as “artificial tears,” and three prescription pharmaceutical products, Restasis® Xiidra® and Cequa™. Artificial
tears are intended to be palliative in nature to supplement insufficient tear production or improve tear film instability, but do
not treat the underlying inflammation in dry eye disease. Restasis increases tear production and Xiidra treats the signs and
symptoms of dry eye disease, however, both Restasis and Xiidra are typically used chronically for dry eye patients
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who have continuous symptoms. Restasis had sales in 2018 of approximately $1.2 billion in the United States. Xiidra,
which was commercially launched in the United States in August 2016, had sales of approximately $255.1 million for the
nine-month period ended September 30, 2018. As each of Restasis and Xiidra have a relatively long onset of action, they
are not generally used for the short‑term treatment of episodic dry eye flares. In addition, they have significant issues with
stinging and burning.
Market Data
According to IMS Health data, approximately 20.0 million prescriptions were filled in the United States in 2019 for
anti-inflammatory drugs administered by prescription eye drops for ocular diseases and conditions, resulting in sales of
approximately $4.5 billion. These prescriptions consisted of approximately 8.3 million prescriptions and $752 million in
sales for single-agent corticosteroids, 3.2 million prescriptions and $366 million in sales for NSAIDs, 4.6 million
prescriptions and $294 million in sales for corticosteroid and antibiotic combination products and approximately
3.8 million prescriptions and $2.9 billion in sales of Restasis and Xiidra for dry eye disease. According to IMS Health data,
approximately 7.0 million anti-allergy eye drop prescriptions were filled in the United States in 2019, resulting in sales of
approximately $487 million. The steroid market for eye drops to treat ocular diseases and conditions consists of both
branded and generic products. Branded steroids include Lotemax and Alrex (loteprednol etabonate) marketed by Bausch &
Lomb, and Durezol (difluprednate) marketed by Alcon. Commonly used generic steroids include prednisolone,
dexamethasone and fluorometholone. In addition, an injectable suspension of dexamethasone, Dexycu, is commercially
available and approved for treatment of post-operative ocular inflammation.
Glaucoma
Glaucoma is a large market and a disease that is estimated to impact more than 2.7 million people age 40 or older in
the United States. The primary goal of glaucoma treatment is to slow the progression of this chronic disease by reducing
intraocular pressure, and many medications can accomplish this. Importantly, however, adherence to current topical
glaucoma therapies is known to be particularly poor with reported rates of non-adherence from 30% to 80%. These low
compliance rates may be associated with disease progression and loss of vision, and may be part of the reason that
glaucoma is a leading cause of blindness in people over 60 years of age.
Glaucoma is a progressive and highly individualized disease in which elevated levels of IOP are associated with
damage to the optic nerve, which results in irreversible vision loss. According to the World Health Organization, glaucoma
is the second leading cause of blindness in the world. Ocular hypertension is characterized by elevated levels of IOP
without any optic nerve damage. Patients with ocular hypertension are at high risk of developing glaucoma.
In a healthy eye, fluid is continuously produced and drained to maintain pressure equilibrium and provide nutrients to
the ocular tissue. Excess fluid production or insufficient drainage of fluid in the front of the eye or a combination of these
problems causes increased IOP. The increased IOP associated with uncontrolled glaucoma results in degeneration of the
optic nerve in the back of the eye and loss of peripheral vision. Once glaucoma develops, it is a chronic condition that
requires life-long treatment.
Prostaglandins are the most commonly used class of medications to treat patients with glaucoma and are
administered via daily eye drops as the current standard of care. The ability of patients to use and place daily eye drops is
challenging. The products that we are developing are designed to address the issue of compliance by delivering a
prostaglandin analog formulated with our programmed release hydrogel to lower intraocular pressure for several months
with a single insert.
Market Data
According to IMS Health data, approximately 35.6 million prescriptions were filled in the United States in 2019 for
drugs administered by eye drops for the treatment of glaucoma, resulting in sales of approximately $3.3 billion. A typical
prescription provides approximately one month of treatment. We expect prescription volume to grow, in large part as a
result of the aging population. According to IMS Health, PGAs accounted for approximately half of the prescription
volume in the glaucoma market in 2019. The market for drugs administered by eye drops for the treatment of glaucoma
consists of both branded and generic products. Branded products have maintained premium pricing and significant market
share. These products include Travatan Z (travoprost) marketed by Alcon and Lumigan (bimatoprost)
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marketed by Allergan. The relevant patents covering travoprost expired in December 2014. Commonly used generic drugs
include latanoprost and timolol.
The Use of Eye Drops and their Limitations
Eye drops are widely used to deliver medications directly to the ocular surface and to intraocular tissue in the front of
the eye. Eye drops are administrable by the patient or care provider, inexpensive to produce and treat the local tissue.
However, eye drops have significant limitations, especially when used for chronic diseases or when requiring frequent
administration, including:
·
·
·
·
Lack of patient compliance. Eye drops require frequent administration. For example, steroids for ophthalmic use
require administration as frequently as four to six times daily and require tapered dosing over the course of the
therapy. As a result, patient compliance with required dosing regimens frequently suffers. According to a
published third-party study, more than 50% of glaucoma patients are not compliant with their prostaglandin
therapy and do not refill prescriptions as required or do not follow the prescribed regimen within six months of
initiating therapy. Poor patient compliance can lead to diminished efficacy and disease progression.
Difficulty in administration. Eye drops are difficult to administer for many patients, in particularly the elderly,
due to physical or mental conditions such as arthritis or dementia. Difficulty in self-administering eye drops may
lead to bacterial contamination in the bottle resulting from incorrect usage, limited accuracy administering the
drops directly into the eye and the potential washout of drops from the eye. We believe that this also may play a
large role in lack of patient compliance and resulting diminished efficacy of treatment.
Need for high concentrations. After eye drops are administered to the ocular surface, the tear film rapidly
renews. Most topically applied solutions are washed away by new tear fluid within 15 to 30 seconds. Because
contact time with the ocular surface is short, less than 5% of the applied dose actually penetrates to reach
intraocular tissues. As a result, eye drops generally require frequent administration at high drug concentrations to
deliver a meaningful amount of drug to the eye. This pulsed therapy results in significant variations in drug
concentrations over a treatment period, which we refer to as peak and valley dosing. At peak levels, the high
concentrations can result in side effects, such as burning, stinging, redness of the clear membrane covering the
white part of the eye, referred to as hyperemia, and spikes in IOP, which may lead to drug induced glaucoma. At
low concentration levels, the drug may not be effective, thus allowing the disease to progress.
Side effects of preservatives. To guard against contamination, many eye drops are formulated with antimicrobial
preservatives, most commonly benzalkonium chloride, or BAK. Patients on long term or chronic therapy, such
as glaucoma patients, often suffer reactions, which have been linked to BAK, including burning, stinging,
hyperemia, irritation and eye dryness. Less frequently, conjunctivitis or corneal damage may result.
As a result of these limitations, eye drops are often suboptimal as a therapeutic option for the treatment of many
diseases and conditions of the front of the eye.
Back-of-the-Eye Diseases and Conditions
There are a range of back-of-the-eye diseases and conditions that adversely affect vision. One of the principal back-
of-the-eye conditions is wet AMD, a serious disease of the central portion of the retina, known as the macula that is
responsible for detailed central vision and color perception. Wet AMD is characterized by abnormal new blood vessel
formation, referred to as neovascularization, which results in blood vessel leakage and retinal distortion. If untreated,
neovascularization in wet AMD patients typically results in formation of a scar under the macular region of the retina. The
current standard of care for wet AMD are drugs that target VEGF, one of several proteins involved in neovascularization.
Wet AMD is the leading cause of blindness in people over the age of 55 in the United States and the European Union.
According to a study on the burden of AMD published in 2006 in the peer-reviewed journal Current Opinion in
Ophthalmology, approximately 1.2 million people in the United States suffer from wet AMD. In addition, AMD Alliance
International reported that approximately 200,000 new cases of wet AMD arise each year in the United States. The
incidence of wet AMD increases substantially with age, and we expect that the number of cases of wet AMD will
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increase with growth of the elderly population in the United States. The anti-VEGF market for the treatment of wet AMD
consists predominantly of three drugs that are approved for marketing and primarily prescribed for the treatment of wet
AMD; Lucentis marketed in the United States by Genentech; Eylea marketed in the United States by Regeneron; Beovu
marketed in the United States by Novartis; Avastin, a cancer treatment drug, marketed by Genetech, is also used off-label
for wet AMD. In 2019, sales of Lucentis and Eylea totaled approximately $6.5 billion in the United States and $11.4 billion
globally.
Because eye drops are unable to carry effective drug concentrations to the back-of-the-eye, intravitreal injections or
oral medications are used to deliver medications to this location. However, the frequency of intravitreal injection can be a
significant burden on patients, caregivers and clinicians. For example, the current treatment protocol for wet AMD involves
monthly or bi-monthly injections. Intravitreal injections can lead to patient discomfort, a transient increase in IOP, and
ocular inflammation and infection. Although serious adverse event rates after treatment with anti-VEGF compounds are
low, intravitreal injections can result in severe complications and damage to the retina and other structures of the eye, such
as ocular hemorrhage and tears in the retinal pigment epithelium.
Ocular Wound Closure
According to the World Health Organization, cataracts are the leading cause of visual impairment eventually
progressing to blindness. According to the American Academy of Ophthalmology Cataract and Anterior Segment Panel’s
2011 Preferred Practice Pattern Guidelines, cataract extraction is the most commonly performed eye surgery in the United
States. Market Scope has estimated that in 2019 there were to be approximately 4.3 million cataract extractions performed
in the United States.
A cataract is a clouding of the lens inside the front of the eye. During cataract surgery, a patient’s cloudy natural lens
is removed and replaced with a prosthetic intraocular lens. Clear corneal incision that allows entry to the eye is the typical
method for performing cataract surgery. The most common post-surgical approach is to allow the incisions to self-seal, or
close, through normal biological processes. However, self-sealing incisions can open spontaneously, especially within 12 to
24 hours following surgery, when IOP fluctuates or as a result of the application of external pressure or manipulation. In
addition, incisions that are left to self-seal may leak, which can sometimes result in complications. Complications from
fluid leakage include the development of hypotony, or low IOP, which can lead to corneal decompensation and vision loss,
as well as the potential for infection. The implanted intraocular lens also may shift in position due to hypotony, leading to
reduced visual outcomes following surgery.
Sutures are the most widely used alternative method of wound closure. However, sutures do not completely prevent
fluid leakage, are time-consuming to place and have been associated with patient discomfort, corneal distortion, and
shallowing of the interior chamber. An additional visit may be required to remove sutures, thus adding time, inconvenience
and expense to the surgical process. Sutures may also lead to astigmatism, a distortion of the cornea. These shortcomings
limit the use of sutures in ophthalmic surgery. In a 2012 survey of ophthalmologists in the United States conducted by
Lachman Consulting LLC, a healthcare consulting firm, respondents indicated that they use sutures in approximately 14%
of cataract surgeries.
The Ocular Therapeutix Approach
Our Hydrogel Technology Platform
We apply our expertise with an established bioresorbable hydrogel technology to the development of products for
local programmed-release of known, FDA-approved therapeutic agents for a variety of ophthalmic diseases and conditions
and to ophthalmic wound closure. Our founders used this same hydrogel technology to develop FDA-approved and
currently marketed medical products for other companies such as SpaceOAR (marketed by Boston Scientific, Inc.), a
hydrogel spacer used to reduce a common and debilitating side effect that men may experience after receiving prostate
cancer radiotherapy; DuraSeal Dural Sealant (marketed by Integra Lifesciences, Inc.), a sealant for cranial and spine
surgery, and Mynx (marketed by Cardinal Health), a sealant for femoral artery punctures after angiography and
angioplasty.
®
®
Our bioresorbable hydrogel technology is based on the use of a proprietary form of PEG. Our technical capabilities
include a deep understanding of the polymer chemistry of PEG-based hydrogels and the design of the highly specialized
manufacturing processes required to achieve a reliable, preservative free and pure product. We tailor the
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hydrogel to act as a vehicle for local programmed-release drug delivery to the eye and as an ocular tissue sealant. We have
used bioresorbable hydrogels to engineer each of our intracanalicular insert product candidates, our intracameral implant
product candidates, ReSure Sealant and our intravitreal implant product candidates.
We create our hydrogels by cross-linking PEG molecules to form a network that resembles a three-dimensional mesh
on a molecular level. Our PEG molecules are branched, with four to eight branches or arms. Each arm bears a reactive site
on its end. Our cross-linking chemistry uses a second molecule with four arms, bearing complimentary reactive sites on
each end, such that when combined with the PEG molecules, a network spontaneously forms. When swollen with water,
this molecular network forms a hydrogel. We design these hydrogels to slowly degrade in the presence of water, a process
called hydrolysis, by inserting a biodegradable linkage between the PEG molecule and the cross-linked molecule. By
appropriately selecting the number of arms of the PEG molecule and the biodegradable linkage, we can design hydrogels
with varying mechanical properties and bioresorption rates. Because the body has an abundance of water at a constant
temperature and pH level, hydrolysis provides a predictable and reproducible degradation rate. Our technology enables us
to make hydrogels that can bioresorb over days, weeks or several months. The figure below depicts the formation and
bioresorption of the hydrogel for ReSure Sealant.
Intracanalicular Insert-Based Local Programmed-Release Therapies for Front-of-the-Eye Diseases and Conditions
A punctum is a natural opening located in the inner portion of the eyelid near the nose. There is a punctum in each of
the lower eyelids and the upper eyelids. The puncta open into nasolacrimal ducts, which collect and drain tears produced by
the eyes’ lacrimal glands. Tears produced in the lacrimal glands sweep across the eye surface and drain through the puncta
to the nasal cavity. The section of the nasolacrimal duct immediately beyond the puncta is called the vertical canaliculus.
Intracanalicular inserts that do not contain an active drug are commonly used for treatment of dry eye disease by physically
blocking tear drainage. Because intracanalicular inserts stay in contact with the tear film, they are well suited for local
programmed-release of drug to the eye.
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Intracanalicular insert shown positioned in the vertical canaliculus
Our intracanalicular inserts utilize our proprietary hydrogel technology and are embedded with an active drug.
Following insertion through the punctum, our inserts swell in tear fluid to fill the vertical canaliculus, which secures the
inserts in place. We design our inserts to release drug in a programmed fashion, tailored to each disease state, back through
the punctum to the surface of the eye. Over time the inserts liquefy and are cleared through the nasolacrimal duct. If
necessary due to excessive tearing, discomfort or improper placement, a healthcare professional can remove an
intracanalicular insert by a process of pushing the soft insert back through the punctum.
Our inserts allow incorporation of a variety of drugs with a controllable range of delivery durations and delivery
rates. For acute conditions, such as post-surgical ocular inflammation and pain and ocular itching associated with allergic
conjunctivitis, we have designed our intracanalicular inserts to provide a local programmed-release of therapeutic levels of
drug for the duration of treatment. For chronic diseases, such as glaucoma, we have designed our intracanalicular inserts for
repeat administration with extended dosing periods. We are concentrating our initial development efforts on
intracanalicular inserts incorporating active pharmaceutical ingredients that are approved by the FDA for the targeted
indication and that satisfy other specific selection criteria that we have developed.
We manufacture our intracanalicular inserts from dried PEG-based hydrogel formed into tiny rods that hold an active
pharmaceutical ingredient in a preservative-free formulation. We embed the active pharmaceutical ingredient in the pre-
hydrogel liquid formulation, which then solidifies to form a hydrogel containing the drug within. The relative size of one of
our intracanalicular inserts is shown in the figure below.
We provide the intracanalicular insert as a thin dry rod to facilitate insertion through the narrow punctal opening.
Upon hydration with tear fluid, the insert swells, softens, and conforms to roughly the size and shape of the vertical
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canaliculus, to secure it in place. We incorporate the active pharmaceutical ingredient in the form of micronized particles
embedded directly in the hydrogel or as bioresorbable microspheres.
We have included a fluorescent label, or marker, in our intracanalicular insert hydrogel to serve as a visualization aid
for the healthcare professional to confirm the insert’s presence. The viewer applies a blue handheld light and a clear yellow
filter aid to see the insert in the eyelid as shown in the figure below.
Because intracanalicular inserts stay in contact with the tear film, other companies have pursued the development of
intracanalicular punctum plugs containing active drugs for local programmed release to the ocular surface. However, these
earlier product designs had significant limitations with respect to drug capacity, drug release kinetics and patient comfort
and used non-degradable punctum plugs with a clear silicone hard rubber shell containing only a core with active drug.
These plugs typically extended outside of the punctal opening and secured themselves in place with an external cap. The
external cap was in constant contact with the surface of the eye, which may cause irritation and discomfort in some cases.
In addition, some prior designs resorted to plugging both the upper and lower puncta, which could cause excessive tearing
and patient discomfort. These designs did not incorporate a visualization agent to allow the patient and physician to assess
the presence of the plug.
In contrast to these prior approaches, we have designed our intracanalicular inserts to:
·
·
incorporate the active pharmaceutical ingredient throughout the insert rather than just in a core to allow for
higher drug capacity and better control over drug release;
be bioresorbable so that removal is not required for acute conditions and required infrequently for chronic
conditions;
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·
·
be soft and to fit beneath the punctal opening for patient comfort; and
include a fluorescent label to allow the healthcare professional and patient to visualize and assess the presence of
the insert.
We select the active pharmaceutical ingredients for our local programmed-release drug delivery product candidates,
including our intracanalicular inserts, based on criteria we have developed through our extensive experience with hydrogel
insert systems. Our active pharmaceutical ingredient selection criteria include:
·
·
·
·
·
prior approval by the FDA for the targeted ophthalmic indication;
expiration of relevant patent protection prior to or within our anticipated development timeline;
high potency to minimize required drug load in the intracanalicular insert;
availability from a qualified supplier; and
compatibility with our drug delivery system.
Anticipated Benefits of Our Intracanalicular Inserts, Intracameral Implants and Intravitreal Implant Compared to Eye
Drops
We believe our intracanalicular insert, intracameral implants and intravitreal implant product candidates may offer a
range of favorable attributes as compared to eye drops, including:
·
·
·
·
Improved patient compliance. Our inserts and implants are placed by a healthcare professional and are designed
to provide local programmed-release of drug to the ocular surface. Because patients are not responsible for self-
administration of the drug and the inserts and implants dissipate over time and do not require removal for acute
conditions or frequent removal for chronic conditions, we believe our inserts and implants address the problem
of patient compliance.
Ease of administration. We have designed our inserts and implants to provide the entire course of medication
with a single administration by a healthcare professional for acute conditions or for several months for chronic
conditions. We believe this avoids the need for frequent administration and the potential complications that could
result if doses are missed.
Local programmed-release of drug. We have designed our inserts and implants to deliver drug in a programmed
fashion in order to avoid the peak and valley dosing and related side effects and spikes in IOP associated with
eye drops. We also believe programmed-release dosing may improve the therapeutic profile of the active
pharmaceutical ingredient because it eliminates periods of little or no drug presence between eye drop
administrations. Further, we are designing our product candidates so that their drug release profiles can be
tailored or programmed to match the treatment needs of the disease. For example, steroids for ophthalmic
purposes generally require administration over four weeks, with tapered dosing over this period. In contrast,
PGAs require administration in a steady fashion over the duration of treatment. Our inserts and implants are
designed to fully dissipate and can be removed if necessary by a healthcare professional.
Avoidance of preservative side effects. Our inserts and implants do not involve the use of preservatives, such as
BAK, which have been linked to side effects including burning, stinging, hyperemia, irritation, eye dryness and,
less frequently, conjunctivitis or corneal damage.
Intravitreal Implants for Back-of-the-Eye Diseases and Conditions
We are engaged in the clinical development of our hydrogel administered via intravitreal injection to address the
large and growing markets for diseases and conditions of the back of the eye. Our initial development efforts are focused
on the use of our programmed-release hydrogel in combination with anti-angiogenic drugs such as protein-based anti-
VEGF drugs or small molecule drugs, such as TKIs for the treatment of retinal diseases, including wet AMD, retinal
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vein occlusion and diabetic macular edema. Our initial goal for these programs is to provide extended delivery of a protein-
based large molecule or small molecule TKI drug targeting VEGF and other targets over a four to six month period
following administration of a bioresorbable hydrogel incorporating the drug by an injection into the vitreous humor,
thereby reducing the frequency of the current monthly or bi-monthly intravitreal injection regimen for wet AMD and other
retinal diseases and potentially providing a more consistent, uniform release of drug over the treatment period.
We are pursuing a multi-pronged strategy to seek to maximize the potential of this technology.
· We are researching the delivery of small molecule TKIs from our hydrogel implant and we initiated an open-
label, proof-of-concept Phase 1 clinical trial in Australia in the first quarter of 2019. This clinical trial is a multi-
center, open-label study designed to evaluate the safety, durability and tolerability of OTX-TKI for up to nine
months. We have conducted preclinical work on this compound and have achieved local programmed-release
and pharmacodynamic effect in vivo for up to twelve months. We believe this class of drugs is well suited for
use with our platform given its high potency, multi-target capability, and compatibility with a hydrogel vehicle.
In the absence of a sophisticated drug delivery system, these drugs have been difficult to deliver to the eye for
acceptable time frames at therapeutic levels without causing local and systemic toxicity due to low drug
solubility and very little short half-lives in solution. We believe our local drug delivery technology gives us
potential advantages in this regard. By selecting a compound that is compatible with our hydrogel platform
technology and that will have expiration of relevant patents within the timeline of our development program, we
avoid the need to license the TKI molecule, thus retaining full worldwide rights to any products we develop.
· We are also evaluating an intravitreal implant through our collaboration with Regeneron, consisting of a PEG-
based hydrogel matrix containing embedded micronized particles of aflibercept. Aflibercept is marketed by
Regeneron under the brand name Eylea. We designed the injection to be delivered to the vitreous chamber of the
eye using a fine gauge needle. We entered into the Collaboration Agreement with Regeneron in October 2016 for
the development and commercialization of protein-based anti-VEGF drugs, with the initial product candidate
incorporating the drug aflibercept into our hydrogel. As previously discussed, we are currently in discussions
with Regeneron regarding the development of an alternative formulation of a proposed product candidate.
Our intravitreal implant consists of a PEG-based hydrogel suspension, which contains embedded micronized protein
particles of an anti-angiogenic compound. We designed the intravitreal implant to be injected and retained in the vitreous
humor, as depicted in the figure below, to provide local programmed-release intravitreal delivery of anti-VEGF
compounds.
We have designed our intravitreal implant for delivery using typically available syringes and fine gauge needles
compatible with the current standard of care. Once in the vitreous humor, the hydrogel is designed to retain properties of
TKI and anti-VEGF compounds until they are released. We have designed the hydrogel to liquefy, dissolve and be
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cleared from the eye through hydrolysis over time. We design our hydrogels to control the hydrogel biodegradation rate
and, as a result, the timing of TKI and anti-VEGF compound release.
ReSure Sealant for Ocular Wound Closure
ReSure Sealant is our bioresorbable hydrogel product for wound closure following cataract surgery. A surgeon
applies ReSure Sealant as a liquid painted onto the corneal incision. Within about 15 seconds, the sealant cross-links and
transforms into a smooth, lubricious hydrogel that seals the wound. ReSure Sealant dissipates as healing progresses and
does not require removal. In the pivotal clinical trials that formed the basis for FDA approval, ReSure Sealant provided
superior wound closure and a better safety profile than sutured closure.
We commercially launched ReSure Sealant in February 2014 on a region-by-region basis in the United States
through a network of independent distributors. In early 2017, we terminated these distributors and hired a contract sales
force of four representatives to sell ReSure Sealant. In July 2017, in connection with a broader reduction in force, we
terminated these representatives. At this time, we have no sales support provided to ReSure Sealant. In the future we may
have our currently deployed Key Account Managers carry the product along with DEXTENZA. We also believe that the
market opportunity for a surgical sealant following cataract surgery may be modest because sutures are used in a minority
of cataract surgeries and, currently, there is no direct reimbursement for ReSure Sealant. As a result, we do not expect to
generate meaningful levels of revenue from the sale of ReSure in 2020.
Development Pipeline and Marketed Products
The following table summarizes important information about our key product development programs and our
marketed products, DEXTENZA and ReSure Sealant. We hold worldwide commercial rights to each of our product
candidates, DEXTENZA and ReSure Sealant.
Product / Program
Approved Product
DEXTENZA
Indication
Post-surgical
ocular
inflammation and
pain
Description
(Active Pharmaceutical
Ingredient)
Stage of
Development
Intracanalicular insert
(Dexamethasone)
Marketed
ReSure Sealant
Cataract incision
closure
Ocular sealant
Marketed
Late Stage Clinical
Product
Candidates
21
Status
Approved by the FDA in November
2018 for post-surgical pain and
approved by the FDA in June 2019
for inflammation; product
commercially launched in July 2019
upon the receipt of a C-code for
transitional pass through
payment; permanent J-Code
became effective as of October 1,
2019.
Approved by the FDA in January
2014; commercially launched in the
United States in February 2014. In
October 2018, we received a FDA
warning letter that we appealed in
November 2018. The appeal was
rejected in December 2018. In
December 2019, we submitted a
post-approval study protocol.
We received further feedback in
February 2020 from FDA and
responded in March 2020.
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Product / Program
DEXTENZA
Indication
Allergic
conjunctivitis
Description
(Active Pharmaceutical
Ingredient)
Stage of
Development
Intracanalicular insert
(Dexamethasone)
Phase 3
DEXTENZA
Episodic dry eye
disease
Intracanalicular insert
(Dexamethasone)
Phase 2
OTX-TP
Glaucoma
Intracanalicular insert
(Travoprost)
Phase 2
Early Stage Clinical
Product
Candidates
OTX-TIC
Glaucoma and
ocular
hypertension
Intracameral implant
(Travoprost)
Phase 1
OTX-CSI
Dry eye disease
Cyclosporine
IND filed
Status
Phase 2 trial completed in
November 2014; topline results
from the two Phase 3 trials; first
Phase 3 trial reported in October
2015 and second Phase 3 trial
reported in June 2016; a third Phase
3 trial commenced in the second
half of 2019, is fully enrolled as of
January 2020 and topline results are
expected in the second quarter 2020.
Results of Phase 2 trial reported in
December 2015; Phase 3 clinical
and regulatory pathways identified;
advancement subject to available
capital
Phase 2a trial completed in May
2014; Phase 2b topline results
reported in October 2015; topline
data from the first Phase 3 trial
reported in May 2019; the FDA
determined that the data was not
clinically meaningful in September
2019, program not anticipated to
move forward without a corporate
partner.
Initiated Phase 1 clinical trial in the
first half of 2018 in the U.S. with
initial results from cohort 1 reported
in April 2019 and initial results
from cohort 2 reported in February
2020. Topline data from cohorts
three and four expected in the
second half of 2020.
Ongoing preclinical studies; IND
filed in December 2019; planned
Phase 1 trial beginning in middle of
2020.
OTX-BPI
Acute ocular pain
Bupivicane
Preclinical
Ongoing preclinical studies
OTX-BDI
Post-operative
pain,
inflammation &
antibacterial
Besifloxicin and
dexamethasone
Preclinical
Ongoing preclinical studies
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Product / Program
Anti-
angiogenic hydrogel
implants
Indication
OTX-TKI
Wet AMD
Description
(Active Pharmaceutical
Ingredient)
Stage of
Development
Status
Phase 1
Intravitreal implant
(Tyrosine kinase
inhibitor anti-
angiogenic compound)
Initiated a Phase 1 clinical trial in
Australia in the second half of
2018. Interim data on first two
cohorts reported in March 2020.
OTX-IVT
Wet AMD DME
and RVO
Intravitreal implant
(Protein-based anti-
angiogenic compound)
Preclinical
Under negotiation with corporate
partner Regeneron to advance
preclinical studies with agreed
upon new formulations
DEXTENZA (dexamethasone ophthalmic insert)
®
DEXTENZA incorporates the FDA-approved corticosteroid dexamethasone as an active pharmaceutical ingredient
into a hydrogel, drug-eluting intracanalicular insert. We are commercializing DEXTENZA for the treatment of post-
surgical ocular inflammation and pain and are developing it for additional indications including ocular itching associated
with allergic conjunctivitis. We have designed DEXTENZA to deliver therapeutic levels of dexamethasone over a period of
approximately 30 days. The FDA approved the NDA for DEXTENZA for the treatment of post-surgical ocular pain in
November 2019 and subsequently the sNDA for inflammation in June 2019. We have also completed two Phase 3 clinical
trials for the treatment of allergic conjunctivitis with topline data reported out in 2015 and 2016, respectively. In the first
Phase 3 clinical trial, DEXTENZA achieved the co-primary endpoint of improvement in ocular itching compared with
placebo but failed to achieve on the co-primary endpoint of improvement in conjunctival redness compared with placebo,
in each case, at certain prespecified timepoints. For the second Phase 3 trial, DEXTENZA failed to achieve the primary
endpoint of improvement in ocular itching compared with placebo, at certain prespecified timepoints. We commenced a
third Phase 3 trial for the treatment of ocular itching associated with allergic conjunctivitis in the second half of 2019. We
have completed enrollment with topline results expected to be reported in the second quarter of 2020.
We selected dexamethasone as the active pharmaceutical ingredient for DEXTENZA because it:
·
·
·
·
·
is approved by the FDA and has a long history of ophthalmic use;
is available on a generic basis;
is highly potent and is typically prescribed for prevention of ocular inflammation and pain following ocular
surgery;
is available from multiple qualified suppliers; and
has physical properties that are well suited for incorporation within our hydrogel technology.
Embedded within our DEXTENZA intracanalicular insert are dexamethasone drug particles that gradually erode and
release the drug in a programmed fashion until the drug is depleted. As the dexamethasone drug particles erode and the
hydrogel degrades by hydrolysis, the intracanalicular insert softens, liquefies and is cleared through the nasolacrimal duct.
We provide the DEXTENZA drug product in a preservative-free formulation in a sterile, single use package.
The standard regimen for dexamethasone eye drops following cataract surgery is an initial administration of four
times daily for one week, with a gradual tapering in the number of eye drops over a four week period. Such a regimen is
often confusing to patients as they must remember to taper the number of times per day they administer the steroid, while
also taking multiple drops of other drugs, such as antibiotics and NSAIDs. We believe that local programmed-release of
drug to the eye may result in better control of ocular inflammation and pain as compared to prescription eye
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drops and that a low dose amount may provide enhanced safety by eliminating spikes in IOP associated with high dose
steroid eye drops.
Although dexamethasone is clinically effective in the treatment of late-phase inflammatory allergic reactions, the
safety limitations associated with eye drop administration, including the potential to generate spikes in IOP due to the high
levels of drug, have limited its widespread adoption as a treatment for the treatment of allergic conjunctivitis. These spikes
in IOP can lead to drug induced glaucoma, although the incidence is low. Further, use of oral anti-histamine medications as
well as anti-histamine eye drops for allergic conjunctivitis may dry out the eye and exacerbate the discomfort to some
patients. We believe, based on our clinical trial results to date, that periodic use of the DEXTENZA for allergic
conjunctivitis could create a low, tapered, consistent dose of dexamethasone, potentially minimizing or eliminating side
effects associated with the eye drop formulation, while retaining the drug’s anti-inflammatory effects.
One of the causes of dry eye disease is inflammation. Topical anti-inflammatory drugs are used as one of several
therapies to treat dry eye disease and are administered by eye drops. As the understanding of dry eye disease, specifically
the inflammatory components of dry eye disease, has evolved, the use of corticosteroids has become a standard to offer
short-term relief of signs and symptoms of the disease. Physicians typically prescribe a topical corticosteroid for a period of
two to four weeks, tapered over the course of delivery as the inflammation and symptoms subside. As with allergic
conjunctivitis, there are safety limitations associated with the use of corticosteroids for dry eye disease that have limited
wide spread adoption. We believe that DEXTENZA has potential as a short-term therapy for more severe cases of episodic
dry eye caused by inflammation, followed by the delivery of an immunosuppressant drug such as cyclosporine after the
inflammation has been reduced.
Overview of DEXTENZA Clinical Development
We are conducting clinical development of DEXTENZA for the treatment of post-surgical ocular inflammation and
pain and ocular itching associated with allergic conjunctivitis. The following summarizes our clinical development to date
for DEXTENZA.
·
In March and April 2015, we reported topline results from two Phase 3 clinical trials for the treatment of post-
surgical ocular inflammation and pain. In the first Phase 3 clinical trial, DEXTENZA met both primary efficacy
endpoints, absence of pain at day 8 and absence of inflammatory cells at day 14, with statistical significance. In
the second Phase 3 clinical trial, DEXTENZA met the primary efficacy endpoint for absence of pain at day 8
with statistical significance but did not meet the primary efficacy endpoint for absence of inflammatory cells at
day 14. We met with the FDA in April 2015 to discuss the path forward for seeking marketing approval of
DEXTENZA for the treatment of post-surgical ocular inflammation and pain. In this pre-NDA clinical meeting,
the FDA indicated that the existing data from our Phase 2 and two Phase 3 clinical trials are appropriate to
support an NDA submission for DEXTENZA for a post-surgical ocular pain indication. The FDA further
indicated that we would need additional data from a third Phase 3 clinical trial for the inflammation endpoint to
support the potential labeling expansion of DEXTENZA’s indications for use. We initiated a third Phase 3
clinical trial for DEXTENZA for the treatment of post-surgical ocular inflammation and pain in October 2015.
In September 2015, we submitted to the FDA an NDA for DEXTENZA for the treatment of post-surgical ocular
pain. In July 2016, we received a CRL from the FDA regarding our NDA for DEXTENZA. This CRL
pertained to deficiencies in manufacturing process and controls identified during a pre-NDA approval inspection
of our manufacturing facility. In January 2017, we resubmitted our NDA to the FDA. Following a re-inspection
of manufacturing operations by the FDA which was completed in May 2017, we received an FDA Form 483
containing inspectional observations focused on manufacturing processes and analytical testing related to the
manufacture of drug product for commercial production. In July 2017, we received a CRL from the FDA
regarding our NDA for DEXTENZA for the treatment of post-surgical ocular pain. The FDA concerns included
deficiencies in manufacturing processes and analytical testing related to manufacturing of drug product
identified during the pre-NDA approval inspection. We resubmitted our NDA for DEXTENZA for the treatment
of post-surgical ocular pain in June 2018. In November 2018, we received approval for the pain indication. In
June 2019, we received approval for the inflammation indication.
·
In November 2014, we completed a Phase 2 clinical trial evaluating the safety and efficacy of DEXTENZA for
the treatment of allergic conjunctivitis. Based upon the encouraging results of this Phase 2 clinical trial and a
subsequent meeting with the FDA, we began enrollment for an initial Phase 3 clinical trial of DEXTENZA
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for the treatment of ocular itching and conjunctival redness associated with allergic conjunctivitis in June 2015.
We announced topline results from this trial in October 2015. We initiated a second Phase 3 clinical trial of
DEXTENZA for the treatment of ocular itching associated with allergic conjunctivitis in November 2015. We
announced topline results for the second Phase 3 clinical trial in June 2016. In the third quarter of 2019, we
initiated a third Phase 3 clinical trial for the treatment of ocular itching associated with allergic
conjunctivitis. We completed enrollment and topline results from this trial are anticipated in the second quarter
of 2020.
·
In January 2015, we initiated a Phase 2 exploratory clinical trial of DEXTENZA for the treatment of episodic
dry eye disease. We reported topline results from this trial in December 2015.
· We are also planning to evaluate DEXTENZA in pediatric subjects that are 0 to 3 years of age undergoing
cataract surgery beginning in the fourth quarter of 2020. The planned pediatric trial is a post-approval
commitment to the FDA.
Clinical Trials for Post-Surgical Ocular Inflammation and Pain
Completed Phase 2 Clinical Trial
In 2013, we completed a prospective, randomized, parallel-arm, vehicle-controlled, multicenter, double-masked
Phase 2 clinical trial evaluating the safety and efficacy of DEXTENZA for the treatment of ocular inflammation and pain
following cataract surgery. We conducted this trial in 60 patients at four sites in the United States pursuant to an effective
IND. We randomized patients in a 1:1 ratio to receive either DEXTENZA or a placebo vehicle control intracanalicular
insert without active drug. One patient randomized into the DEXTENZA group was excluded from the trial because the
investigator was unable to insert the insert, resulting in 29 patients in the DEXTENZA group and 30 patients in the vehicle
control group. We evaluated patients in this trial at days 1, 4, 8, 11, 14 and 30 following surgery.
One of our goals for this trial was to determine the appropriate primary endpoints for a subsequent Phase 3 clinical
development program. The two primary efficacy measures in this trial were absence of inflammatory cells in the anterior
chamber of the study eye and absence of pain in the study eye. When viewed with a slit lamp biomicroscope, these
inflammatory cells, referred to as cells in a slit lamp examination, appear like dust specks floating in a projected light beam.
The presence of these cells in the anterior chamber indicates inflammation. In this trial, absence of pain was based on a
patient reported score of zero on a scale from zero to ten of ocular pain assessment. The first primary efficacy endpoint was
the difference in the proportion of patients in each treatment group with absence of cells in the anterior chamber of the
study eye at day 8 following surgery. The second primary efficacy endpoint was the difference in the proportion of patients
in each treatment group with absence of pain in the study eye at day 8 following surgery.
We evaluated as secondary measures the absence of flare in the anterior chamber of the study eye at each evaluation
date, absence of inflammatory cells in the anterior chamber of the study eye and absence of pain in the study eye at each
evaluation date other than day 8 and insert retention and visualization. Flare is a scattering of light in the aqueous humor
when viewed during a slit lamp biomicroscopic examination. Flare occurs when the protein content of the aqueous humor
increases due to intraocular inflammation.
We enrolled patients in this trial who were at least 21 years of age undergoing unilateral clear corneal cataract
surgery. We excluded patients from the trial if, among other reasons, they had intraocular inflammation or ocular pain in the
study eye at screening or had glaucoma or ocular hypertension.
Efficacy: In this trial, DEXTENZA met the primary efficacy endpoint with statistical significance for absence of
pain compared to the vehicle control at day 8 (p<0.0001). We determined statistical significance based on a widely used,
conventional statistical method that establishes the p-value of clinical results. Typically, a p-value of 0.05 or less represents
statistical significance. The differences between DEXTENZA and the vehicle control for absence of pain also were
statistically significant at each other evaluation date (p<0.0002). These results are shown in the graph below. In this
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graph and other graphs appearing further below, we use the abbreviation “N” to reference the number of patients in each
group.
In this trial, DEXTENZA did not meet the primary efficacy endpoint with statistical significance for absence of cells
in the anterior chamber compared to the vehicle control at day 8. However, there was a trend of improved absence of
anterior chamber cells at each evaluation date, with statistical significance at day 14 (p<0.0027) and day 30 (p< 0.0002).
These results are shown in the graph below.
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Based on post hoc analysis, DEXTENZA showed statistical significance for absence of flare compared to vehicle
control at each evaluation date. These results are shown in the graph below.
Safety: In this trial, there were three serious adverse events, none of which was considered related to the study
treatment. The trial investigator determined the relatedness of the serious adverse events to study treatment based on his or
her professional medical judgment and in accordance with the study protocol, which required the investigator to determine
that a reasonable possibility did not exist that the study treatment caused the adverse event. None of the three serious
adverse events: syncope, intracranial hemorrhage and cellulitis of the arm, were ocular in nature. In addition, there were a
variety of adverse events in both the DEXTENZA group and the vehicle control group, with the adverse events in the
vehicle control group outnumbering the adverse events in the DEXTENZA group. In the DEXTENZA group, the only
adverse event that occurred more than once was reduced visual acuity, which occurred twice. The most common adverse
events in the vehicle control group were reduced visual acuity, conjunctival hyperemia and corneal edema. Overall, 19
adverse events were noted in the DEXTENZA group and 30 adverse events were noted in the vehicle control group. All
adverse events were transient in nature and completely resolved by the end of the trial.
Completed Phase 3 Clinical Trials
In 2014, we initiated a pivotal clinical trial program that consisted of two prospective, randomized, parallel-arm,
vehicle-controlled, multicenter, double-masked Phase 3 clinical trials evaluating the safety and efficacy of DEXTENZA for
the treatment of ocular inflammation and pain following cataract surgery. We initiated the first of these Phase 3 clinical
trials in February 2014 and the second trial in April 2014. Patient enrollment was completed in September 2014, and the
topline efficacy data from these clinical trials was reported in March and April 2015. We initiated a third Phase 3 clinical
trial in the October 2015. Patient enrollment in the third Phase 3 clinical trial was completed in May 2016 and the topline
efficacy data was reported in November 2016.
We enrolled 247 patients at 16 sites in the first Phase 3 clinical trial, 241 patients at 16 sites in the second Phase 3
clinical trial and 438 patients at 21 sites in the third Phase 3 clinical trial in the United States pursuant to our effective IND.
We randomized patients in a 2:1 ratio in the first two Phase 3 clinical trials and in a 1:1 ratio in the third Phase 3 clinical
trial to receive either DEXTENZA or a placebo vehicle control intracanalicular insert without active drug. We evaluated
patients at days 2, 4, 8, 14, 30 and 60 following surgery in the first two Phase 3 trials and at days 2, 4, 8, 14, and 30 in the
third Phase 3 clinical trial.
The two primary efficacy measures in these trials were absence of inflammatory cells in the anterior chamber of the
study eye when measured with a slit lamp biomicroscope and absence of pain in the study eye. To meet the efficacy end
point for absence of inflammatory cells, there needed to be a complete absence of inflammatory cells. In these trials,
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absence of pain was based on a patient reported score of zero on a scale from zero to ten of ocular pain assessment. The
first primary efficacy endpoint for these trials was the difference in the proportion of patients in each treatment group with
absence of inflammatory cells in the anterior chamber of the study eye at day 14 following surgery. Pivotal clinical trials
for other ophthalmic steroid drugs approved by the FDA for marketing in the United States also have evaluated this
endpoint at day 14. The second primary efficacy endpoint for these trials was the difference in the proportion of patients in
each treatment group with absence of pain in the study eye at day 8 following surgery. For clarification of the endpoints,
the day of surgery and insertion of DEXTENZA or the placebo is considered to be day 1.
We evaluated as secondary efficacy measures the level of flare, an indicator of inflammation in the anterior chamber
of the study eye at each evaluation date until day 30 and absence of inflammatory cells in the anterior chamber of the study
eye and absence of pain in the study eye at each evaluation date other than the day used for the primary efficacy measure
until day 30. The secondary analyses on primary endpoints were intended to be exploratory assessments that can be used to
support the results from the primary endpoints. We enrolled patients in these two trials who were at least 18 years of age
undergoing unilateral clear corneal cataract surgery. We excluded patients from these trials if, among other reasons, they
had intraocular inflammation or ocular pain in the study eye at screening or had glaucoma or ocular hypertension.
We evaluated safety in all patients at each study visit with an assessment of general eye conditions, including visual
acuity and IOP, along with any adverse events.
Efficacy: In the first Phase 3 clinical trial, DEXTENZA met the primary efficacy endpoint with statistical
significance for the absence of cells in the anterior chamber compared to the vehicle control at day 14. 33.1% of
DEXTENZA treated patients showed an absence of inflammatory cells in the anterior chamber of the study eye on day 14
following drug product insertion, compared to 14.5% of those receiving placebo vehicle control intracanalicular inserts
(p=0.0018). DEXTENZA also met the primary efficacy endpoint with statistical significance for absence of pain compared
to the vehicle control at day 8. 80.4% of patients receiving DEXTENZA reported absence of pain in the study eye on day 8
following insertion of the drug product, compared to 43.4% of those receiving placebo vehicle control intracanalicular
inserts (p< 0.0001).
In the second Phase 3 clinical trial, DEXTENZA met the primary efficacy endpoint for absence of pain at day 8 with
statistical significance but did not meet the primary efficacy endpoint for absence of inflammatory cells at day 14. In the
second Phase 3 clinical trial, 77.5% of patients receiving DEXTENZA reported an absence of pain in the study eye on day
8 following insertion of the drug product, compared to 58.8% of those receiving placebo vehicle control intracanalicular
inserts, a difference which was statistically significant (p=0.0025). However, 39.4% of DEXTENZA treated patients
showed an absence of inflammatory cells in the anterior chamber of the study eye on day 14 following drug product
insertion, compared to 31.3% of those receiving placebo vehicle control intracanalicular inserts, a difference which was not
statistically significant (p=0.2182).
In the third Phase 3 clinical trial, DEXTENZA met the primary efficacy endpoint with statistical significance for the
absence of cells in the anterior chamber compared to the vehicle control at day 14. 52.1% of DEXTENZA treated patients
showed an absence of inflammatory cells in the anterior chamber of the study eye on day 14 following drug product
insertion compared to 31.2% of those receiving placebo vehicle control intracanalicular inserts (p< 0.0001). DEXTENZA
also met the primary efficacy endpoint with statistical significance for absence of pain compared to the vehicle control at
day 8. 79.3% of patients receiving DEXTENZA reported absence of pain in the study eye on day 8 following insertion of
the drug product, compared to 61.3% of those receiving placebo vehicle control intracanalicular inserts (p< 0.0001).
Secondary analyses on primary endpoints for the three Phase 3 clinical trials were also completed. In the first Phase 3
clinical trial, statistically significant differences were seen for absence of pain at all time points (days 2, 4, 8, 14, 30 and 60)
in the DEXTENZA treatment group compared to the vehicle control group. Statistically significant differences were seen
for the absence of inflammatory cells at day 30 in the DEXTENZA treatment group compared to the vehicle control group,
and there were no statistically significant differences seen at the other time points. Statistically significant differences
between the DEXTENZA treatment group and the vehicle control group were seen for flare at days 8, 14 and 30.
In the second Phase 3 clinical trial, statistically significant differences were seen for absence of pain at days 2, 4, 14
and 30 in the DEXTENZA treatment group compared to the vehicle control group. A similar proportion of patients in
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the DEXTENZA treatment group and the vehicle control group were observed to have an absence of inflammatory cells at
days 2, 4, 8, and 30. A statistically significant difference between treatment groups was not seen for the absence of
inflammatory cells until the day 60 visit, at which time a greater proportion of patients in the DEXTENZA treatment group
compared to the vehicle control group were observed to have an absence of inflammatory cells at day 60 (p=0.0012).
Statistically significant differences between the DEXTENZA treatment group and the vehicle control group were seen for
flare at days 14, 30 and 60.
In the third Phase 3 clinical trial, statistically significant differences were seen for absence of pain at all time points
(days 2,4, 14, and 30) in the DEXTENZA treatment group compared to the vehicle control group. Statistically significant
differences were seen for the absence of inflammatory cells at days 4, 8, and 30 but not seen at day 2. Statistically
significant differences between the DEXTENZA treatment group and the vehicle control group were seen for flare at all
measured time points (days 2, 4, 8, 14, and 30).
Safety: There were no ocular or treatment-related serious adverse events in the DEXTENZA treatment group in
either of the first two completed Phase 3 clinical trials. There was one ocular serious adverse event in the vehicle control
group in the first two completed Phase 3 clinical trials: hypopyon, or inflammatory cells in the anterior chamber. There
were two patients with three serious adverse events in the DEXTENZA treatment group in the first Phase 3 clinical trial
(1.2% incidence), compared with two patients with four serious adverse events in the vehicle control group (2.4%
incidence). There were two serious adverse events in the DEXTENZA treatment group in the second Phase 3 clinical trial
(1.3% incidence), compared with three serious adverse events in the vehicle control group (3.8% incidence). There were
three serious adverse events in the DEXTENZA treatment group in the third Phase 3 clinical trial (1.4% incidence),
compared with two serious adverse events in the vehicle control group (0.9% incidence). One serious adverse event in the
DEXTENZA group was ocular in nature (retinal detachment). None of the serious adverse events in either group were
deemed to be treatment-related.
Patients were randomized in a 2:1 ratio in the first two Phase 3 clinical trials and in a 1:1 ratio in the third Phase 3
clinical trial between the treatment group and the vehicle control group. In the first Phase 3 clinical trial, 98 adverse events
were noted in the DEXTENZA group and 59 adverse events were noted in the vehicle control group. In the second Phase 3
clinical trial, 74 adverse events were noted in the DEXTENZA group and 47 adverse events were noted in the vehicle
control group. In the third Phase 3 clinical trial, 91 adverse events were noted in the DEXTENZA group and 109 adverse
events were noted in the vehicle control group. All adverse events were either resolved or considered chronic/stable at the
time of subject exit from the study. We expect to be able to use the safety data from these Phase 3 trials to support our other
DEXTENZA clinical development programs, including for allergic conjunctivitis.
Regulatory Pathway
In September 2015, we submitted to the FDA an NDA for DEXTENZA for the treatment of post-surgical ocular
pain. In July 2016, we received a CRL from the FDA regarding our NDA for DEXTENZA pertaining to deficiencies in
manufacturing process and controls identified during a pre-NDA approval inspection. We resubmitted our NDA to the
FDA in January 2017. Following a re-inspection of manufacturing operations by the FDA which was completed in May
2017, we received an FDA Form 483 containing inspectional observations focused on manufacturing processes and
analytical testing related to the manufacture of drug product for commercial production. In July 2017, we received a CRL
from the FDA regarding our NDA for DEXTENZA for the treatment of post-surgical ocular pain, which states that the
FDA has determined that it cannot approve the NDA in its present form. In May 2017, we submitted our initial response to
the Form 483 and, in November 2017, we submitted our responses to the FDA’s remaining inspectional observations in an
effort to close out the items identified in the Form 483.
We resubmitted our NDA for DEXTENZA for the treatment of post-surgical ocular pain in June 2018. In November
2018, we received FDA approval for DEXTENZA for the pain indication. In January 2019, we submitted a sNDA for
DEXTENZA for the treatment of post-surgical ocular inflammation. In June 2019, we received FDA approval for
DEXTENZA for the inflammation indication. Although we conducted our Phase 3 clinical trials of DEXTENZA in
patients who have undergone cataract surgery, these trials were intended to support, and DEXTENZA ultimately received,
a label for patients who have undergone any ocular surgery.
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Clinical Trials for Allergic Conjunctivitis
Completed Phase 2 Clinical Trial
In November 2014, we completed a prospective, randomized, parallel-arm, vehicle-controlled, multicenter, double-
masked Phase 2 clinical trial evaluating the safety and efficacy of DEXTENZA for the treatment of allergic conjunctivitis.
We conducted this trial using a modified version of a controlled exposure model commonly used to assess anti-allergy
medications known as the Conjunctival Allergen Challenge model, or CAC , which is a proprietary model owned by ORA,
Inc., the clinical research organization we used to manage the trial. The modified CAC achieves a very high transient dose
exposure by placing allergen directly into the space between the eyelid and the surface of the eye of the patient. We initially
exposed patients to specified allergens to determine which allergens resulted in an allergic response for the patients. If
patient was responsive to a particular allergen, we continued to expose the patient to that same allergen prior to each
evaluation.
TM
We enrolled 68 patients at two sites in the United States. We randomized patients in a 1:1 ratio to receive either
DEXTENZA or a placebo vehicle control intracanalicular insert without active drug. We evaluated patients using three
allergen challenges in series for each of the two efficacy measures at 14, 28 and 42 days following placement of the
intracanalicular insert.
The primary efficacy measures for this trial were ocular itching graded by the patient and conjunctival redness graded
by the trial investigator, in each case based on a five point scale from zero to four. The primary efficacy measures were
differences between treatment groups of at least 0.5 units on the five point scale on day 14 for all three time
points measured in a day for both ocular itching and conjunctival redness and differences between treatment groups of at
least 1.0 unit for the majority of the three time points measured on 14 days post insertion for both ocular itching and
conjunctival redness. The secondary endpoints for this trial were similar to the primary efficacy endpoints, except that each
variable was assessed at 28 days and 42 days following placement of the intracanalicular insert.
We enrolled patients in this trial who were at least 18 years of age with a positive history of ocular allergies and a
positive skin test reaction to a perennial allergen and a seasonal allergen. We excluded patients from this trial if, among
other reasons, they had an active ocular infection or itching or conjunctival redness at screening.
We evaluated safety in all patients at each study visit with an assessment of general eye conditions, including visual
acuity and IOP, along with any adverse events.
Efficacy: In this trial, there was a statistically significant mean difference (p<0.05) between the DEXTENZA
treatment group and the vehicle group for both ocular itching and conjunctival redness at all three time points measured on
14, 28, and 42 days following placement of the intracanalicular insert. DEXTENZA met one of the two primary efficacy
endpoints. The DEXTENZA treatment group achieved a mean difference compared to the vehicle control group of more
than 0.5 units on a five point scale at 14 days post insertion for all three time points measured in a day for both ocular
itching and conjunctival redness. The DEXTENZA group did not achieve a mean difference compared to the vehicle
control group of 1.0 unit for the majority of the three time points measured on 14 days post insertion for either ocular
itching or conjunctival redness. However, in a pre-specified analysis group of a second site in the clinical trial, in which
DEXTENZA intracanalicular inserts were placed 48 to 72 hours following exposure to the allergen, rather than on the same
day, we observed a mean difference in ocular itching between the DEXTENZA group and the vehicle control group of
approximately 1.0 unit for the majority of three time points measured on 14 days.
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The results of this trial for each of the three time points on day 14 following the insertion of the intracanalicular insert
for the DEXTENZA group and the vehicle control group are shown in the table below:
Parameter
Ocular Itching
Conjunctival Redness
Time
Point
DEXTENZA
1.80 (1.068)
Vehicle
2.58 (0.823)
3 min
5 min
1.72 (0.998)
7 min
1.65 (0.989)
7 min
1.60 (0.753)
15 min
1.53 (0.753)
20 min
1.54 (0.739)
2.70 (0.865)
2.53 (0.880)
2.11 (0.727)
2.23 (0.708)
2.21 (0.696)
Treatment
Difference
(P-value)
-0.78
(0.0031)
-0.98
(0.0002)
-0.88
(0.0007)
-0.51
(0.0100)
-0.70
(0.0006)
-0.67
(0.0008)
Safety: In this trial, there was one serious adverse event in the treatment arm, which was depression. This event was
not suspected to be related to treatment. The serious adverse event was not ocular in nature. In addition, there were a
variety of adverse events in both the DEXTENZA group and the vehicle control group, with nine ocular adverse events and
two non-ocular related adverse events in the DEXTENZA group and eight ocular adverse events and two non-ocular
adverse events in the vehicle control group. In the DEXTENZA group, the only adverse events that occurred more than
once were reduction in visual acuity and increased IOP, both of which occurred twice. The most common adverse events in
the vehicle control group were erythema of the eyelid, discharge from the eye and an increase in lacrimation, all of which
occurred twice. All adverse events were transient in nature and completely resolved by the end of the trial.
Phase 3 Clinical Program
We met with the FDA in December 2014 to review the Phase 2 clinical trial results of DEXTENZA for the treatment
of allergic conjunctivitis and to discuss our planned Phase 3 clinical development program. Based on these discussions, we
have completed two Phase 3 clinical trials and initiated a third Phase 3 clinical trial in August 2019. Our first Phase 3
clinical trial assessed both ocular itching and conjunctival redness associated with allergic conjunctivitis. Our second and
third Phase 3 clinical trials have focused on the ocular itching indication.
First Phase 3 Clinical Trial
We initiated our first planned Phase 3 clinical trials in June 2015, and we reported topline efficacy results in October
2015. This first Phase 3 clinical trial was a prospective, randomized, parallel-arm, vehicle-controlled, multicenter, double-
masked trial. A total of 73 patients were enrolled in this trial and were randomized in a 1:1 ratio to receive either
DEXTENZA or a placebo vehicle control intracanalicular insert without active drug. This trial was conducted using the
modified CAC model. We evaluated patients using three allergen challenges in series for each of two efficacy measures at
days 7, 14 and 28 following placement of intracanalicular insert as described below. In this Phase 3 clinical trial, we placed
the intracanalicular inserts 48 to 72 hours after exposure to the allergen. In our completed Phase 2 clinical trial, we obtained
better efficacy results with this design protocol as noted in the description of the Phase 2 efficacy results above.
The primary efficacy measures for this trial were ocular itching graded by the patient and conjunctival redness graded
by the trial investigator, in each case based on a five point scale from zero to four. The primary efficacy endpoints were the
differences between the treatment group and the vehicle group of at least 0.5 units on the five point scale measured on 7
days post-insertion of the intracanalicular insert for all three time points measured for both ocular itching and conjunctival
redness and differences of at least 1.0 unit for the majority of the three time points measured on 7 days post-insertion of the
intracanalicular insert for both ocular itching and conjunctival redness. The secondary endpoints were similar to the
primary efficacy endpoints except that each variable was assessed at day 14 and day 28 following insertion of the
intracanalicular insert. The primary efficacy measure of conjunctival redness is typically included in Phase 3 trials for
allergic conjunctivitis but has not been required for FDA approval of drugs for allergic
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conjunctivitis. Most commercially available prescription medications for the treatment of allergic conjunctivitis have an
ocular itching indication only. As described below, ocular itching was the only primary efficacy endpoint in the second
Phase 3 trial of DEXTENZA for the treatment of allergic conjunctivitis, with conjunctival redness being moved to a
secondary efficacy endpoint.
We enrolled patients in this trial who were at least 18 years of age with a positive history of ocular allergies and a
positive skin test reaction to a perennial allergen and a seasonal allergen. We excluded patients from this trial if, among
other reasons, they had an active ocular infection or itching or conjunctival redness at screening.
We evaluated safety in all patients at each study visit with an assessment of general eye conditions, including visual
acuity and IOP, along with any adverse events.
Efficacy: In this trial, there was a statistically significant mean difference (p<0.0001) between the DEXTENZA
treatment group and the placebo vehicle group for ocular itching at all three time points measured on 7 days post-placement
of the intracanalicular insert. DEXTENZA also met the primary efficacy endpoint for ocular itching. The DEXTENZA
treatment group achieved a mean difference compared to the vehicle group of greater than 0.5 units on a five point scale on
7 days post-insertion at each time point and greater than 1.0 unit at a majority of the time points on 7 days post-insertion for
ocular itching. There was a statistically significant mean difference (p=0.01 or less) between the DEXTENZA treatment
group and the placebo vehicle group for conjunctival redness at all three time points measured on 7 days post-placement of
the intracanalicular insert. However, the DEXTENZA group did not achieve the pre-specified primary efficacy endpoints
on 7 days post-insertion with respect to conjunctival redness.
The results of this trial for each of the three time points on day 7 following placement of the intracanalicular insert
for the DEXTENZA group and the vehicle control group are shown in the table below:
Parameter
Ocular Itching
Time
Point
DEXTENZA
Vehicle
3 min 1.68 (1.032) 2.66 (0.861)
5 min
1.87 (1.04)
2.74 (0.69)
7 min 1.70 (0.938) 2.74 (0.679)
Conjunctival Redness
7 min 1.52 (0.641) 1.80 (0.764)
15 min 1.48 (0.698) 1.75 (0.786)
20 min 1.44 (0.710) 1.76 (0.766)
Treatment
Difference
(P-value)
-1.02
(<0.0001)
-0.87
(<0.0001)
-1.04
(0.0007)
-0.26
(0.1082)
-0.32
(0.0419)
-0.29
(0.0667)
Safety: There were no serious adverse events reported in this trial. There were a variety of adverse events in both the
DEXTENZA group and the vehicle control group, with three patients in the DEXTENZA treatment group with a total of
three ocular adverse events and one non-ocular adverse event and four patients in the vehicle control group with a total of
six ocular adverse events and one non-ocular adverse events. The most common ocular adverse event was increased
lacrimation, which was experienced by one patient in the DEXTENZA group and two patients in the vehicle control group.
Other treatment-related ocular adverse events included increased IOP in the DEXTENZA group, and blepharospasm in the
vehicle control group.
Second Phase 3 Clinical Trial
We initiated our second Phase 3 clinical trial of DEXTENZA for the treatment of allergic conjunctivitis in November
2015, and we reported topline efficacy results in June 2016. This second Phase 3 clinical trial was a prospective,
randomized, parallel-arm, vehicle-controlled, multicenter, double-masked trial. A total of 72 patients were enrolled in this
trial and randomized in a 1:1 ratio to receive either DEXTENZA or a placebo vehicle control intracanalicular insert without
active drug. This trial was conducted using the modified CAC model. Patients were evaluated using three allergen
challenges in series for each of two efficacy measures at days 7, 14 and 28 following
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insertion of the intracanalicular insert. In this Phase 3 clinical trial, we placed the intracanalicular inserts 48 to 72 hours
after exposure to the allergen.
The single primary efficacy measure for this trial was ocular itching graded by the patient based on a five point scale
from zero to four. The primary efficacy endpoints were the differences between the treatment group and the vehicle group
of at least 0.5 units on the five point scale 7 days post-insertion of the intracanalicular insert for all three time points
measured for ocular itching and differences of at least 1.0 unit for the majority of the three time points measured 7 days
post-insertion of the intracanalicular insert for ocular itching. The secondary endpoints for ocular itching were similar to
the primary efficacy endpoints except that each variable was assessed at day 14 and day 28 following placement of the
intracanalicular insert. The secondary endpoints for conjunctival redness were the differences between the treatment group
and the vehicle group of at least 0.5 units on the five point scale 7 days post-insertion of the intracanalicular insert for all
three time points measured and differences of at least 1.0 unit for the majority of the three time points measured 7 days
post-insertion of the intracanalicular insert.
We enrolled patients in this trial who are at least 18 years of age with a positive history of ocular allergies and a
positive skin test reaction to a perennial allergen and a seasonal allergen. We excluded patients from this trial if, among
other reasons, they had an active ocular infection or itching or conjunctival redness at screening.
We evaluated safety in all patients at each study visit with an assessment of general eye conditions, including visual
acuity and IOP, along with any adverse events.
Efficacy: In this trial, DEXTENZA did not meet the primary efficacy endpoint of ocular itching at the three time
points measured on day 7 post-placement of the intracanalicular insert. The mean difference in ocular itching in the
DEXTENZA treatment group compared to the placebo group measured 7 days following insertion of the inserts, at 3, 5,
and 7 minutes was -0.18, -0.29, and -0.29 units, respectively, on a five point scale and did not achieve statistical
significance. In addition, the trial did not achieve the requirement of at least a 0.5 unit difference at all three time points 7
days following insertion of the inserts and at least a 1.0 unit difference at a majority of the three time points between the
treatment group and the placebo group 7 days following insertion of the inserts.
The trial also assessed conjunctival redness as a secondary endpoint. The differences in the mean scores in
conjunctival redness between the DEXTENZA treatment group and the placebo group 7 days following insertion of the
inserts at 7, 15 and 20 minutes were -0.35, -0.39 and -0.42, respectively.
The results of this trial for each of the three time points on day 7 following placement of the intracanalicular insert
for the DEXTENZA group and the vehicle control group are shown in the table below:
Parameter
Ocular Itching
Time
Point
DEXTENZA
Vehicle
3 min 2.04 (1.088) 2.31 (1.115)
5 min
2.07 (1.1) 2.41 (1.039)
7 min 2.02 (1.131) 2.37 (1.129)
Treatment
Difference*
(P-value)
-0.18
(0.44)
-0.29
(0.223)
-0.29
(0.2611)
Safety: There were no serious adverse events reported in this trial. There were a variety of adverse events in both
the DEXTENZA group and the vehicle control group, with six patients in the DEXTENZA treatment group with a total of
six ocular and one non-ocular adverse events and 11 patients in the vehicle control group with a total of nine ocular and
eight non-ocular adverse events. The lower rate of ocular adverse events in the DEXTENZA group could potentially be due
to the presence of an anti-inflammatory active pharmaceutical ingredient. Ocular adverse events reported more than one
patient in either treatment group included increased IOP, which was experienced by two patients in the DEXTENZA group,
as well as dacryostenosis acquired and dacryocanaliculitis, each experienced by two patients in the vehicle control group.
Both cases of IOP increased were considered treatment related, as were both cases of dacrycanaliculitis and a single case of
dacryostenosis. All other ocular adverse events were reported by single patients in either the DEXTENZA or vehicle
control group, with most in the PV group considered treatment related.
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Third Phase 3 Clinical Trial - Ongoing
We initiated our third Phase 3 clinical trial of DEXTENZA for the treatment of allergic conjunctivitis in August
2019. We recently completed enrollment and expect to report topline efficacy results in the second quarter of 2020. This
third Phase 3 clinical trial is a prospective, randomized, parallel-arm, vehicle-controlled, multicenter, double-masked trial.
A total of 96 patients were enrolled in this trial and randomized in a 1:1 ratio to receive either DEXTENZA or a placebo
vehicle control intracanalicular insert without active drug. This trial was conducted using the modified CAC model.
Patients were evaluated using three allergen challenges in series for each of two efficacy measures at days 7 and 14
following insertion of the intracanalicular insert.
The single primary efficacy measure for this trial was ocular itching graded by the patient based on a five point scale
from zero to four. The primary efficacy endpoints were the differences between the treatment group and the vehicle group
of at least 0.5 units on the five point scale 7 days post-insertion of the intracanalicular insert for all three time points
measured for ocular itching and differences of at least 1.0 unit for the majority of the three time points measured 7 days
post-insertion of the intracanalicular insert for ocular itching. The secondary endpoints for ocular itching were similar to
the primary efficacy endpoints except that each variable was assessed at day 14 following placement of the intracanalicular
insert. The secondary endpoints for conjunctival redness were the differences between the treatment group and the vehicle
group of at least 0.5 units on the five point scale 7 days post-insertion of the intracanalicular insert for all three time points
measured and differences of at least 1.0 unit for the majority of the three time points measured 7 days post-insertion of the
intracanalicular insert.
We enrolled patients in this trial who are at least 18 years of age with a positive history of ocular allergies and a
positive skin test reaction to a perennial allergen and a seasonal allergen. We excluded patients from this trial if, among
other reasons, they had an active ocular infection or itching or conjunctival redness at screening.
We evaluated safety in all patients at each study visit with an assessment of general eye conditions, including visual
acuity and IOP, along with any adverse events.
Regulatory Pathway
We have completed two Phase 3 clinical trials evaluating DEXTENZA for the treatment of ocular itching associated
with allergic conjunctivitis and we are conducting a third Phase 3 clinical trial that commenced in the third quarter of
2019. Subject to obtaining favorable results from this third Phase 3 clinical trial, we plan to submit an sNDA to the FDA
for DEXTENZA for the treatment of ocular itching associated with allergic conjunctivitis. We expect that we would submit
this sNDA under Section 505(b)(2) of the FDCA. See “—Government Regulation—Section 505(b)(2) NDAs” for
additional information. Based on discussions with the FDA, we expect to use safety results from our Phase 3 clinical trials
of DEXTENZA for the treatment of post-surgical ocular inflammation and pain to support the sNDA for DEXTENZA for
the ocular itching indication.
Clinical Trial for Dry Eye
Phase 2 Clinical Trial
In January 2015, we initiated a prospective, randomized, parallel-arm, vehicle-controlled, multicenter, bilateral,
double-masked Phase 2 feasibility study evaluating the safety and efficacy of DEXTENZA for the treatment of episodic
dry eye disease. We enrolled 43 patients and evaluated 86 eyes at two sites in the United States pursuant to our effective
IND. The clinical trial was not powered for statistical significance. We randomized patients in a 1:1 ratio to receive either
DEXTENZA or a placebo vehicle control intracanalicular insert without active drug.
Designed as an exploratory study, patients were initially administered a placebo vehicle control intracanalicular insert
for 45 days to establish a baseline for the investigational drug treatment. Patients who responded to the placebo insert in
treatment of their dry eye disease were excluded from the trial. Patients who continued to exhibit symptoms of dry eye
disease during the initial 45 days, as indicated by a minimum threshold of signs of corneal staining, were qualified for
enrollment in the treatment phase of the trial. Qualified patients were then randomized to receive either DEXTENZA or a
placebo vehicle control intracanalicular insert. Primary efficacy measures included corneal and conjunctival staining, tear
osmolarity, tear film break-up time, presence of the insert, ease of product use and
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visualization, and resorption of the insert following therapy. We reported topline results for this clinical trial in December
2015.
In this exploratory Phase 2 clinical trial, patients were selected for a minimum threshold of signs of corneal staining
and were randomized to either treatment with DEXTENZA or a placebo vehicle insert. Patients were stratified into groups
based on the level of National Eye Institute aggregate corneal fluorescein staining score improvement and were then
randomized into the treatment or placebo vehicle insert group per a pre-determined randomization list to maintain masking.
DEXTENZA treated patients showed clinically meaningful benefits compared to patients receiving a placebo vehicle
control intracanalicular insert, with improvement in total and inferior corneal staining as well as conjunctival staining. Total
corneal staining at day 30 following randomization was significantly decreased from baseline in the DEXTENZA group
(-3.14) compared to placebo (-1.10) (p=0.018). Inferior staining showed clinically significant differences in the change
from baseline in the DEXTENZA treatment group compared to the placebo group (-0.44 and -0.45 at day 15 and day 30,
respectively). Corneal staining is a primary endpoint that has been used in recent Phase 3 dry eye clinical trials for dry eye
disease conducted by other ophthalmology companies. Supportive analyses of lissamine green staining also demonstrated a
clinically significant change in favor of DEXTENZA, where total staining was more than 1 point improved for the
DEXTENZA group compared to the placebo group.
This clinical trial was designed to evaluate a range of objective and subjective measures (signs and symptoms,
respectively) for DEXTENZA and was intended to explore which measures would be appropriate to include in the design
of future clinical trials of DEXTENZA or other molecules in a sustained-release product as a potential therapy for dry eye
disease. Our long term strategy for the treatment of dry eye may be to use DEXTENZA as a mode of therapy to reduce
inflammation in patients with acute dry eye conditions and pursue the development of an intracanalicular insert containing
an immunosuppressant drug such as cyclosporine to treat dry eye disease.
There was one serious adverse event in the DEXTENZA treatment group, myocardial infarction, that was not
deemed to be treatment related. There were 17 adverse events in the DEXTENZA group and 11 adverse events in the
vehicle control group. Eight patients in the DEXTENZA group reported 12 ocular related adverse events, and 4 patients in
the vehicle control group reported 5 ocular related adverse events. Four patients in the DEXTENZA group reported 5 non-
ocular related adverse events, and 5 subjects in the vehicle control group reported 6 non-ocular related adverse events. The
most frequently reported ocular treatment related ocular adverse event was increased lacrimation, which was reported in 4
patients in the DEXTENZA group and 1 subject in the vehicle control group. Three patients, all from the DEXTENZA
group, had a mild reduction in best corrected visual acuity, of which 2 were considered treatment related and 1 of these was
not resolved during the trial.
Regulatory Pathway
We are not currently pursuing DEXTENZA for the treatment of episodic dry eye disease but have identified clinical
and regulatory pathways for the program’s potential advancement. If we were to advance the program, we would expect to
initiate a Phase 2 clinical trial to evaluate DEXTENZA for the treatment of flares due to dry eye, which we refer to as
episodic dry eye disease. We would then be required to successfully complete two well-controlled Phase 3 clinical trials
conducted under an IND to obtain marketing approval from the FDA. If we were to obtain favorable results from these two
pivotal clinical trials, we would expect to submit an sNDA under Section 505(b)(2) of the FDCA. See “—Government
Regulation—Section 505(b)(2) NDAs” for additional information.
Clinical Trial for DEXTENZA in Pediatric Subjects
We are also planning to evaluate DEXTENZA in pediatric subjects that are 0 to 3 years of age undergoing cataract
surgery beginning in the second half of 2020. The planned pediatric trial is a post-approval commitment to the FDA.
Travoprost Intracanalicular Insert (OTX-TP)
Our OTX-TP product candidate incorporates the PGA travoprost as an active pharmaceutical ingredient in our
proprietary intracanalicular insert. We are developing OTX-TP for the treatment of glaucoma and ocular hypertension. We
have completed Phase 2a and Phase 2b clinical trials of OTX-TP, and we reported topline efficacy results of a Phase 3 trial
in May 2019.
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Travoprost is a synthetic PGA that reduces IOP by enhancing the clearance and drainage of ocular fluid.
We selected travoprost as the active pharmaceutical ingredient for OTX-TP because it:
·
·
·
·
·
is approved by the FDA for the treatment of glaucoma and ocular hypertension;
has relevant patent protection that expired in December 2014;
is a highly potent PGA molecule;
is available from multiple qualified suppliers; and
has physical properties that are well suited for incorporation within our hydrogel technology.
We have designed OTX-TP to deliver therapeutic levels of travoprost for up to three months. We have tested versions
of OTX-TP that are capable of local programmed-release over a one-month, a two-month and a three-month period. The
retention time of our intracanalicular inserts varies from patient-to-patient due to various physiological and anatomical
factors to which the intracanalicular inserts may be subjected. We have conducted a series of non-significant risk, or NSR,
investigational device exemption, or IDE, studies with improved product designs and placement procedures with the goal
of achieving higher retention rates. We have achieved successive improvements in retention, with as high as a 92%
retention rate at day 90 in one of these NSR studies. Our completed pilot studies evaluated one-month and two-month
versions of OTX-TP. In our Phase 2a clinical trial, we evaluated two-month and three-month versions of OTX-TP. In our
Phase 2b clinical trial, we evaluated an improved three-month version of OTX-TP. In our pilot studies, the OTX-TP inserts
we evaluated were violet to provide a visual assessment of insert position. In our subsequent Phase 2 clinical trials, we
switched to a fluorescent yellow color to improve visibility and are using this same fluorescent marker in our Phase 2b
clinical trial.
In addition to the PEG-based hydrogel, OTX-TP contains bioresorbable microparticles which contain encapsulated
travoprost. We designed OTX-TP to deliver travoprost at therapeutic levels for the duration of therapy as the microparticles
degrade. We provide OTX-TP in a sterile, single use package without any added preservatives.
Overview of OTX-TP Clinical Development
We are conducting clinical development of OTX-TP for glaucoma and ocular hypertension. Because OTX-TP
incorporates an active pharmaceutical ingredient already approved by the FDA for the treatment of glaucoma and ocular
hypertension, we did not need to conduct Phase 1 clinical trials for this product candidate. However, we did conduct two
pilot studies to assess safety and to obtain initial efficacy data. The following summarizes our clinical development to date
for OTX-TP.
·
·
·
In 2012, we conducted two pilot studies evaluating the safety and efficacy of two versions of OTX-TP for the
treatment of glaucoma and ocular hypertension over a 30 to 60 day period.
In 2014, we completed a Phase 2a clinical trial of two versions of OTX-TP for the treatment of glaucoma and
ocular hypertension to evaluate reduction in IOP over a 60 to 90 day period. This completed trial provided
important information regarding the effects in patients of the drug delivery rates for our inserts that informed the
design of the OTX-TP insert that we used in our Phase 2b clinical trial for this indication.
In the November 2014, we initiated a Phase 2b clinical trial of OTX-TP for the treatment of glaucoma and ocular
hypertension to evaluate reduction in IOP over a 60 to 90 day period. We reported topline efficacy results from
this trial in October 2015. There were no hyperemia-related adverse events noted in any of the patients treated
with OTX-TP. Further, there have been no serious adverse events observed to date in the Phase 2b trial. Adverse
events noted include punctal stenosis, punctal trauma and canaliculitis.
· We have conducted NSR studies on additional modified intracanalicular insert design. We met with the FDA in
the second quarter of 2016 to discuss alternative Phase 3 clinical trial designs and to formulate our plans for our
Phase 3 program.
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·
Based on feedback we received from the FDA, we initiated a Phase 3 clinical trial in September 2016. We
reported topline efficacy results from this trial in May 2019. No serious adverse events have been reported in
connection with this trial. Adverse events observed include dacryocanaliculitis and lacrimal structure disorder.
The trial design for the initial Phase 3 clinical trial includes an OTX-TP treatment arm and a placebo-controlled
comparator arm using a non-drug-eluting insert. No timolol comparator or validation arm will be required in the study
design and no eye drops, placebo or active, are being administered in either arm. We expect that the FDA will require that
OTX-TP show both a statistically superior reduction of IOP, when compared to the placebo, as a primary efficacy endpoint,
and a clinically meaningful reduction of IOP in the absolute. The primary efficacy endpoint will be evaluated at 2 weeks, 6
weeks and 12 weeks at 8:00 a.m., 10:00 a.m. and 4:00 p.m. at each of the three timepoints.
Clinical Trials for Glaucoma and Ocular Hypertension
Completed Singapore Pilot Study
In 2012, we completed a prospective, single arm, open-label pilot study evaluating the initial safety and efficacy of
the one-month version of OTX-TP for the treatment of glaucoma and ocular hypertension. We conducted this trial in 17
patients, and in 26 eyes, at two sites in Singapore.
We enrolled patients in this trial who were at least 21 years of age with a documented diagnosis of ocular
hypertension or open-angle glaucoma, baseline IOP within a specified range and a specified minimum level of visual acuity
in each eye. The trial protocol provided that if the participant’s IOP was high despite treatment with OTX-TP, rescue
medication would be made available to the patient. For patients who were currently under treatment for ocular hypertension
or glaucoma, we required a drug washout period for these medications between screening and first visit.
We evaluated patients at days 3, 10, 20 and 30 following insertion of the insert and made the following assessments:
· mean IOP at 8:00 a.m. at each evaluation date as measured in millimeters of mercury, or mmHg;
· mean IOP at 10:00 a.m. and 4:00 p.m. at days 10, 20 and 30;
·
·
change in mean IOP from baseline at each time point measured; and
retention of the insert in the canaliculus at days 10, 20 and 30.
We assessed IOP at multiple time points on each evaluation date because IOP naturally varies over the course of the
day.
For patients who are affected bilaterally, if both eyes met all eligibility criteria, both eyes were treated, but only the
eye with the higher mean IOP at baseline was included in the efficacy analysis.
Efficacy: On day 10, 100% of the inserts were visualized, on day 20, 88% of the inserts were visualized, and on
day 30, 79% of the inserts were visualized.
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We observed a clinically meaningful reduction in mean IOP over the 30 day trial period. For eyes that retained the
insert, from a mean baseline IOP of 27.2 mmHg, the mean IOP during treatment was maintained at or below 22 mmHg at
each evaluation date and time point. The mean reduction in IOP from baseline ranged from 5.3 mmHg (20%) to 8.2 mmHg
(30%) across all evaluation dates and time points. In studies conducted by third parties, a sustained 5.0 mmHg reduction in
IOP reduced risk of disease progression by approximately 50%. The results for change in mean IOP from baseline at 8:00
a.m. on each evaluation date are set forth in the graph below.
Safety: In this trial, there were no serious adverse events or unanticipated adverse events. There was only one
adverse event, bilateral epiphora, or excess tearing of both eyes, which was transient in nature and completely resolved
after insert removal. There were no significant changes in hyperemia scores from baseline through day 30. There were no
notable observations of clinical relevance among the slit lamp biomicroscopy assessments.
Completed South Africa Pilot Study
In 2012, we completed a prospective, single arm, open-label pilot study evaluating the initial safety and efficacy of
the two-month version of OTX-TP for the treatment of glaucoma and ocular hypertension. We conducted this trial in 20
patients, and in 36 eyes, at two sites in South Africa.
Enrollment criteria were comparable to our Phase 1 Singapore trial described above, except that the minimum patient
age was 18.
We evaluated patients at days 3, 15, 30, 45 and 60 following insertion of the insert and made the same assessments
with respect to mean IOP, change in mean IOP from baseline and retention of the insert in the canaliculus at each
evaluation date following day 3 as in our Phase 1 Singapore trial described above.
Efficacy: On day 15, 97% of the inserts were retained, on day 30, 92% of the inserts were visualized, on day 45,
78% of the inserts were retained, and on day 60, 59% of the inserts were retained. Because of the limitations of the
visualization of the violet color through pigmented eyelids, it is possible that intracanalicular inserts identified as not being
retained were in fact retained but not visible, particularly given the sustained reduction in IOP through day 60 described
below. We have since eliminated the violet colorant in favor of a fluorescent PEG hydrogel, resulting in greatly improved
visualization.
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We observed a clinically meaningful reduction in mean IOP over the 60 day trial period. For eyes that retained the
insert, from a mean baseline IOP of 28.7 mmHg, the mean IOP during treatment was maintained at or below 22.0 mmHg
beginning on day 15 and at all subsequent evaluation dates. The mean reduction in IOP from baseline ranged from 5.0
mmHg (18%) to 7.1 mmHg (25%) across all evaluation dates and time points. The results for change in mean IOP from
baseline at 8:00 a.m. on each evaluation date are set forth in the graph below for patients who retained the insert on such
date.
There were only two cases in which IOP remained high even though the insert was confirmed to be present. In each
of these cases, the investigator prescribed rescue medication at the end of the visit. It is possible that this elevated IOP was
the result of the participants not responding to travoprost.
Safety: In this trial, there were no serious adverse events or unanticipated adverse events. The most common adverse
event was inflammatory reaction, which was noted in three patients. All adverse events were transient in nature and
completely resolved by the end of the trial. There were no significant changes in hyperemia scores from baseline through
day 60. There were no notable observations of clinical relevance among the slit lamp biomicroscopy assessments.
Completed South Africa Phase 2a Clinical Trial
In May 2014, we completed a prospective, randomized, multi-arm, active-controlled, multicenter, double masked
Phase 2 clinical trial evaluating the safety and efficacy of two versions of OTX-TP for the treatment of glaucoma and
ocular hypertension. The OTX-TPa version was intended to release travoprost over a two-month period, and the OTX-TPb
version was intended to release travoprost at a slower rate over a three-month period. Based on in vitro testing, the OTX-
TPa version had an average daily drug delivery rate of 3.5 micrograms per day and the OTX-TPb version had an average
daily drug delivery rate of 2.8 micrograms per day. We conducted this trial in 41 patients at four sites in South Africa. In
this trial, we randomized 11 patients for treatment with OTX-TPa and placebo eye drops, 17 patients for treatment with
OTX-TPb and placebo eye drops and 13 patients for treatment with a placebo vehicle control intracanalicular insert without
active drug and timolol eye drops. One patient randomized into the timolol group was excluded from the trial because the
investigator was unable to insert the insert. We randomized more patients in the OTX-TPb group than in the OTX-TPa
group because we ceased enrolling patients in the OTX-TPa group during the trial based on an amendment to our trial
protocol intended to facilitate the completion of the trial and to allow us to evaluate a larger number of patients being
treated with a three-month version of the insert. Timolol is the most commonly prescribed non-PGA drug for the treatment
of glaucoma and has been used as a comparator drug in pivotal clinical trials for other approval glaucoma products.
The primary efficacy endpoints in this trial are differences between treatment groups in:
· mean change in IOP from baseline on each evaluation date and at each time point;
· mean percent change in IOP from baseline on each evaluation date and at each time point; and
· mean IOP on each evaluation date and at each time point.
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We designed our Phase 2a clinical trial to assess clinically meaningful response to treatment, and did not power the
trial to measure any efficacy endpoints with statistical significance. We also evaluated retention of the insert as a secondary
endpoint.
We enrolled patients in this trial who were at least 18 years of age with a documented diagnosis of ocular
hypertension or open-angle glaucoma, baseline IOP within a specified range and a specified minimum level of visual acuity
in each eye. We excluded patients from this trial if, among other reasons, they had a history of inadequate response to
treatment with prostaglandins or beta-blockers. For patients who were currently under treatment for ocular hypertension or
glaucoma, we required a drug washout period for these medications between screening and first visit.
We evaluated patients at days 3, 15, 30, 45, 60, 75 and 90 following insertion of the insert and made the following
assessments:
· mean IOP at 8:00 a.m. at each evaluation date;
· mean IOP at 12:00 p.m. and 4:00 p.m. at days 30, 60 and 90;
·
·
change in mean IOP from baseline at each time point measured; and
retention of the insert in the canaliculus at each evaluation date.
For patients who are affected bilaterally, if both eyes met all eligibility criteria, both eyes were treated, but only the
eye with the higher mean IOP at baseline was included in the primary efficacy analysis.
We evaluated safety in all patients at each study visit with an assessment of general eye conditions, including visual
acuity, along with any adverse events.
Efficacy: In the timolol group, for eyes that retained the insert, from a mean baseline IOP of 26.1 mmHg, the mean
IOP during treatment was maintained at or below 21.4 mmHg beginning on day 15 and at all subsequent evaluation dates
and time points. The mean reduction in IOP from baseline ranged from 3.2 mmHg (13%) to 6.4 mmHg (25%) across all
evaluation dates and time points through day 75.
In the OTX-TPa group, for eyes that retained the insert, from a mean baseline IOP of 25.8 mmHg, the mean IOP
during treatment was maintained at or below 21.0 mmHg beginning on day 15 and at all subsequent evaluation dates and
time points through day 75. The OTX-TPa formulation, originally intended to deliver drug over a two-month period,
exceeded our expectations, delivering drug for 75 days. The mean reduction in IOP from baseline ranged from 3.2 mmHg
(14%) to 6.0 mmHg (24%) across all evaluation dates and time points through day 75.
In OTX-TPb group, for eyes that retained the insert, from a mean baseline IOP of 26.4 mmHg, the mean IOP during
treatment was maintained at or below 22.2 mmHg beginning on day 15 and at all subsequent evaluation dates and time
points. The mean reduction in IOP from baseline ranged from 2.0 mmHg (9%) to 5.4 mmHg (20%) across all evaluation
dates and time points.
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The results for change in mean IOP for patients in the OTX-TPa group, for patients in the OTX-TPb group and for
patients in the timolol group from baseline at 8:00 a.m. on each applicable evaluation date are set forth in the graph below,
in each case for patients who retained the insert on such date. We believe that the lower average daily drug delivery rate in
the OTX-TPb group may have resulted in less reduction of mean IOP in this group as compared to the OTX-TPa group. As
discussed below, we evaluated an improved three-month version of OTX-TP in our Phase 2b clinical trial.
Safety: In this trial, there were no serious adverse events. The most common adverse event was inflammatory
reaction, which was noted in five patients. All adverse events were transient in nature and resolved by the end of the trial.
There were no significant changes in hyperemia scores from baseline through day 90. There were no notable observations
of clinical relevance among the slit lamp biomicroscopy assessments.
Completed U.S. Phase 2b Clinical Trial
In November 2014, we initiated a prospective, randomized, parallel-arm, active-controlled, multicenter, double-
masked Phase 2b clinical trial to evaluate the safety and efficacy of OTX-TP for the treatment of glaucoma and ocular
hypertension after submitting an IND to the FDA for this indication. We treated 73 patients at 11 sites in the United States
pursuant to our effective IND. We randomized patients in a 1:1 ratio to receive either OTX-TP and placebo eye drops or a
placebo vehicle control intracanalicular insert without active drug and eye drops containing timolol. Patients were
instructed to use the placebo drops or timolol drops twice daily for the duration of the trial. Based on the results of our
completed Phase 2a clinical trial, we designed the OTX-TP insert for use in our Phase 2b clinical trial to deliver drug over a
90 day period at the same daily rate as the OTX-TPa insert used in the Phase 2a clinical trial. To achieve this, we modified
the design of the OTX-TP insert to enlarge it in order to enable the insert to carry a greater amount of drug. These structural
changes were previously evaluated in NSR studies that we describe below.
The primary efficacy endpoint in this trial was the difference between treatment groups in the mean change in IOP
from baseline at day 60 following insertion of the intracanalicular insert, calculated by averaging the change from baseline
across the three time points at the assessment date, which is known as diurnal IOP. The secondary efficacy endpoints in this
trial were the difference between treatment groups in the mean change from baseline in average diurnal IOP at day 90, the
difference between treatment groups in the mean change from baseline in IOP at each individual time point at day 60 and
day 90, the difference between treatment groups in the mean change in average diurnal IOP and IOP at each individual time
point at day 60 and day 90, and the difference between treatment groups in the mean percent change from baseline in
average diurnal IOP and IOP at each individual time point at day 60 and 90. We designed our Phase 2b clinical trial to
assess clinically meaningful response to treatment, and did not power the trial to measure any efficacy endpoints with
statistical significance.
We enrolled patients in this trial who are at least 18 years of age with a documented diagnosis of ocular hypertension
or open-angle glaucoma, baseline IOP within a specified range and a specified minimum level of visual acuity in each eye.
We excluded patients from this trial if, among other reasons, they had a history of inadequate
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response to treatment with prostaglandins or beta-blockers. For patients under treatment for ocular hypertension or
glaucoma, we required a drug washout period for these medications between screening and first visit. We also evaluated the
effect of a four week versus a five week washout duration on the change in 8:00 a.m. IOP in both groups.
We evaluated patients at days 3, 15, 30, 45, 60, 75 and 90 (with insertion of the insert on day 1) and made the
following assessments:
· mean IOP and change in mean IOP from baseline at 8:00 a.m. at days 3, 15, 45 and 75; and
· mean IOP and change in mean IOP from baseline at 8:00 a.m., 12:00 p.m. and 4:00 p.m. at days 30, 60 and 90.
We also collected data on intracanalicular insert presence along with visualization of the insert by both the study
patient and the investigator. The patients were instructed to assess insert presence on a daily basis and report the absence of
an insert immediately. This data has provided a method for us to assess the accuracy of patient self-examination for insert
presence, and we expect that this will maximize the consistency of dosing.
We evaluated safety in all patients at each study visit with an assessment of general eye conditions, including visual
acuity, along with any adverse events.
Efficacy:
In this trial, the mean change from baseline IOP at 8:00 a.m. on day 30, 60, and 90 in the OTX-TP group was a
decrease of 4.5, 4.7, and 5.1 mm Hg, respectively.
In this trial, on day 60, the OTX-TP group experienced a mean diurnal IOP lowering effect of 3.3 mmHg compared
to baseline, versus mean diurnal IOP lowering of 5.9 mmHg compared to baseline for the timolol group. On day 90, the
OTX-TP group experienced a mean diurnal IOP lowering effect of 3.6 mmHg compared to baseline, versus mean diurnal
IOP lowering of 6.3 mmHg compared to baseline for the timolol group.
On day 60, the OTX-TP group experienced a mean IOP lowering effect compared to baseline of 4.7 mmHg at 8:00
a.m., 2.3 mmHg at 12:00 p.m. and 2.8 mmHg at 4:00 p.m., versus mean IOP lowering compared to baseline of 6.4 mmHg
at 8:00 a.m., 6.1 mmHg at 12:00 p.m. and 5.6 mmHg at 4:00 p.m. for the timolol group. On day 90, the OTX-TP group
experienced a mean IOP lowering effect compared to baseline of 5.1 mmHg at 8:00 a.m., 2.5 mmHg at 12:00 p.m. and 3.0
mmHg at 4:00 p.m., versus a mean IOP lowering effect compared to baseline of 7.2 mmHg at 8:00 a.m., 6.1 mmHg at
12:00 p.m. and 5.5 mmHg at 4:00 p.m. for the timolol group.
The mean IOP in the OTX-TP treatment group on day 60 was 21.73 mmHG at 8:00 a.m., 22.27 mmHg at 12:00 p.m.
and 21.42 mmHg at 4:00 p.m. In the timolol group, the mean IOP on day 60 was 20.74 mmHg at 8:00 a.m., 19.05 mmHg at
12:00 p.m. and 18.85 mmHg at 4:00 p.m. The mean IOP in the OTX-TP treatment group on day 90 was 21.33 mmHg at
8:00 a.m., 22.09 mmHg at 12:00 p.m. and 21.18 mmHg at 4:00 p.m. In the timolol group, the mean IOP on day 90 was
19.87 mmHg at 8:00 a.m., 19.08 mmHg at 12:00 p.m. and 18.95 mmHg at 4:00 p.m.
The mean diurnal IOP in the OTX-TP treatment group on day 60 was 21.81 mmHg. The mean diurnal IOP in the
timolol treatment group on day 60 was 19.54 mmHg.
The mean diurnal IOP in the OTX-TP treatment group on day 90 was 21.53 mmHg. The mean diurnal IOP in the
timolol treatment group on day 90 was 19.3 mmHg.
This Phase 2b glaucoma clinical trial was designed to evaluate the non-inferiority of OTX-TP compared to timolol
and to inform the further clinical development for OTX-TP. This trial was not powered to show statistical significance
between treatment groups. The OTX-TP treatment group included placebo eye drops that may have reduced the efficacy
measures for OTX-TP, by washing out drug eluted from the insert from the ocular surface, whereas the timolol group
included a placebo insert that may have improved the efficacy of timolol through occlusion of the punctum thereby
prolonging its retention on the ocular surface. Several peer-reviewed medical journals have reported studies in which an
additional IOP lowering effect of 1.32 to 1.80 mmHg was observed in patients taking timolol eye drops in combination
with a non-drug eluting punctum plug compared to those patients only taking timolol eye drops. These include studies
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reported in September 2011 in Clinical and Experimental Optometry, February 1989 in the American Journal of
Ophthalmology and August 1996 in Acta Ophthalmologica Scandinavica. The expected design for our Phase 3 clinical
trials of OTX-TP for the treatment of glaucoma and ocular hypertension is addressed below under “—Regulatory
Pathway”.
In the timolol group, the mean IOP at day 30, 60 and 90 at all time points ranged from 18.9 mmHg to 20.7 mmHg.
The mean reduction in IOP from baseline at day 30, 60 and 90 at all time points ranged from 5.3 mmHg to 7.3mmHg.
In the OTX-TP group, the mean IOP at day 30, 60 and 90 at all time points ranged from 21.0 mmHg to 22.3 mmHg.
The mean reduction in IOP from baseline at day 30, 60 and 90 at all time points ranged from 2.3 mmHg to 5.2 mmHg.
In our completed South Africa Phase 2a clinical trial in which OTX-TP intracanalicular inserts were inserted in 36
eyes in 20 patients with no placebo eye drops used, on day 30 we observed a reduction in IOP of 6.1 mmHg at 8:00 a.m.,
5.1 mmHg at 12:00 p.m. and 5.6 mmHg at 4:00 p.m. following insertion of the intracanalicular insert. In this trial, on day
60 we observed a reduction in IOP of 6.7 mmHg at 8:00 a.m., 5.1 mmHg at 12:00 p.m. and 4.3 mmHg at 4:00 p.m.
following insertion of the intracanalicular insert. The diurnal averages of the reduction in the IOP were 5.6 mmHg at day
30 and 5.4 mmHg at day 60 in this trial. We believe that the higher IOP reduction observed in this trial may be due in part
to the lack of placebo eye drops.
We performed additional post-hoc analyses that were not pre-specified in the trial protocol for the Phase 2b glaucoma
clinical trial to provide further insight on the performance of OTX-TP. Although post-hoc analyses performed using an
unlocked clinical trial database can result in the introduction of bias, we believe that these analyses provide important
information regarding our OTX-TP product candidate and are helpful in determining the study population and inclusion
and exclusion criteria for future clinical trials. When we excluded patients on more than one glaucoma medication and used
the baseline of five weeks of washout for comparisons of the OTX-TP group and the timolol group, the differences in mean
reduction in IOP between the OTX-TP treatment group and the timolol group at the 8:00 a.m. time point on day 30, 60 and
90 narrowed to an average of 1.1 mmHg from an average of 2.2 mmHg based on the pre-specified criteria. These results
are shown in the table below:
8:00 am Results for Intraocular Pressure (mmHg)
Intent to Treat
Population
Post-hoc analysis
Baseline of 5 weeks,
single drug only
Day 30
Day 60
Day 90
Average
Difference
OTX-TP Timolol OTX-TP Timolol
-6.2
-6.2
-7.2
-6.7
-4.5
-4.7
-5.1
-4.8
-4.9
-5.3
-5.7
-5.6
-6.6
-6.4
-7.3
-7.0
-2.2
-1.1
In this trial, inserts were found to be retained in 91% of patients at day 60, 88% of patients at day 75 and 48% of
patients at day 90, reflecting the corresponding absorption and clearance of the inserts with the duration of drug release.
Safety: In this trial, there were no serious adverse events. Adverse events noted to date including punctal stenosis,
punctal trauma and canaliculitis. The most common adverse event was inflammatory reaction of the lacrimal punctum
and/or canaliculus, which was noted in five patients. These adverse events were transient in nature and resolved by the end
of the trial. There were no significant changes in hyperemia scores from baseline through day 90 and there were no
hyperemia related adverse events. There were no notable observations of clinical relevance among the slit lamp
biomicroscopy assessments.
Non-Significant Risk Retention Studies
We conduct medical device NSR IDE studies on an ongoing basis for the purpose of refining our intracanalicular
insert product and placement procedure. We conduct these NSR studies under FDA IDE regulations, although no specific
FDA approval is required. We are able to conduct NSR studies because intracanalicular inserts without active drug are well
established ophthalmic medical devices. The NSR study process allows us to make relatively quick evaluations of our
intracanalicular insert design and placement procedure in human subjects.
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In a series of completed NSR studies, we have effected compositional and dimensional adjustments to our
intracanalicular insert to optimize retention. We have also used these studies to evaluate intracanalicular insert placement,
as well as removal and repeat placements and have seen a range of results in NSR studies to date, with the most recent
study achieving a retention rate of approximately 85-90% at day 90.
We are using an intracanalicular insert design in our Phase 3 clinical trials of OTX-TP for the treatment of glaucoma
and ocular hypertension that is slightly smaller than the plug design used in the Phase 2b clinical trial. We also plan to use
an intracanalicular insert design in these trials that has a rapidly dissolvable tip that enables greater ease of insertion of the
insert.
We believe that with the current level of retention with our intracanalicular insert design and given the ability of
patients to assess the presence of the insert as a result of the fluorescent label, our current product design offers a
potentially significant improvement over the current standard of care with patients receiving PGAs. The compliance rate
with PGA eye drops has been shown to be only approximately 50% after six months of therapy due to the challenges of
administration and side effects including hyperemia, or red eye.
Completed U.S. Phase 3 Clinical Trial
We initiated a randomized, double blind, placebo-controlled Phase 3 clinical trial in September 2016 based on
feedback following discussions with the FDA in the second quarter of 2016, using a protocol design that focused on a
comparison of the OTX-TP arm against a vehicle placebo arm. Patients were randomized in a 3:2 ratio to receive either
OTX-TP or a placebo vehicle control intracanalicular insert without active drug. No timolol comparator or validation arm
was required in the study design and no eye drops, placebo or active, were administered in either arm. In May 2019, we
reported topline results of the Phase 3 clinical trial that was conducted at 49 sites and enrolled 554 subjects with open-angle
glaucoma or ocular hypertension in the full analysis set, or FAS, population.
The trial’s primary efficacy endpoint was an assessment of mean IOP at nine different time points: three diurnal time
points (8:00 a.m., 10:00 a.m., and 4:00 p.m.) at each of 2, 6, and 12 weeks following insertion. The secondary endpoints
included an evaluation of whether OTX-TP demonstrated a statistically superior mean reduction of IOP from baseline for
OTX-TP treated-subjects compared with placebo insert-treated subjects (Table 1) at the same nine time points. Topline
results show that the trial did not achieve its endpoint of statistically significant superiority in mean reduction of IOP
compared with placebo at all nine time points.
We enrolled patients in this trial who are at least 18 years of age with a documented diagnosis of ocular hypertension
or open-angle glaucoma, baseline IOP within a specified range and a specified minimum level of visual acuity in each eye.
We excluded patients from this trial if, among other reasons, they had a history of inadequate response to treatment with
prostaglandins or beta-blockers. For patients under treatment for ocular hypertension or glaucoma, we required a drug
washout period for these medications between screening and first visit.
We evaluated patients at weeks 2, 4, 6, 8, 10 and 12 (with insertion of the insert on day 1) and made the following
assessments:
· mean IOP at 8:00 a.m., 10:00 a.m. and 4:00 p.m. at weeks 2, 6, and 12; and
· mean IOP at 8:00 a.m. at weeks 4, 8, and 10.
We also collected data on intracanalicular insert presence along with visualization of the insert by both the study
patient and the investigator.
We evaluated safety in all patients at each study visit with an assessment of general eye conditions, including visual
acuity, along with any adverse events.
Efficacy: Topline results show that the trial did not achieve its endpoint of statistically significant superiority in
mean reduction of IOP compared with placebo at all nine time points. OTX-TP treated subjects did have a greater reduction
in IOP from baseline relative to placebo insert at all nine time points (Table 2), and these differences were statistically
significant (p value < 0.05) for eight of the nine time points (Tables 2 and 3). The reductions from baseline
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for OTX-TP treated subjects in this trial ranged from 3.27-5.72 millimeters of mercury (mm Hg) across the nine time points
with higher levels of intraocular pressure reduction seen at the earlier time points in this trial (Table 3).
Table 1: Baseline Values
Baseline
8:00 AM
10:00 AM
4:00 PM
OTX-TP (mm Hg)
26.63
25.1
24.76
Placebo (mm Hg)
26.92
25.03
24.58
Table 2:
Mean Intraocular Pressure Values
2 Weeks
Diurnal
Time
points
8:00 AM
10:00 AM
4:00 PM
mm Hg
OTX-
TP
21.02
20.16
19.46
Placebo
22.86
21.92
21.51
LS
Mean
p-value
<.0001
<.0001
<.0001
FAS Population (OTX-TP=343 subjects, Placebo=211
subjects)
6 Weeks
mm Hg
OTX-
TP
21.93
21.05
20.53
Placebo
22.73
21.85
21.55
LS
Mean
p-value
0.0181
0.0077
0.0004
12 Weeks
mm Hg
OTX-
TP
22.83
21.74
21.41
Placebo
23.23
22.45
22.08
LS
Mean
p-value
0.2521
0.0234
0.0310
Table 3:
Reduction in Intraocular Pressure (Change from Baseline)
6 Week
2 Week
mm Hg
mm Hg
Diurnal
Time
points
8:00 AM
10:00 AM
4:00 PM
OTX-
TP
-5.72
-4.92
-5.22
Placebo
-3.88
-3.16
-3.18
FAS Population (OTX-TP=343 subjects, Placebo=211 subjects)
p-value
<.0001
<.0001
<.0001
OTX-
TP
-4.81
-4.03
-4.16
Placebo
-4.01
-3.23
-3.14
p-value
0.0181
0.0077
0.0004
OTX-
TP
-3.91
-3.34
-3.27
Placebo
-3.52
-2.63
-2.60
p-value
0.2521
0.0234
0.0310
Least Squares (LS) Means
Least Squares (LS) Means
12 Week
mm Hg
Safety: OTX-TP was generally well tolerated and no ocular serious adverse events were observed. The most
common ocular adverse events seen in the study eye were dacryocanaliculitis (approximately 7.0% in OTX-TP vs. 3.0% in
placebo) and lacrimal structure disorder (approximately 6.0% in OTX-TP vs. 4.0% in placebo).
Regulatory Pathway
In October 2019, we met with the FDA to discuss the topline data we reported from our completed Phase 3 trial. Our
conversation with the FDA was productive and involved a discussion around the importance of compliance and how a
product like OTX-TP could address the issue of non-compliance by delivering a prostaglandin analog formulated with our
programmed release hydrogel to lower intraocular pressure for up to 12 weeks with a single insert. While the FDA did not
feel that the data from this clinical trial met the standard of clinical meaningfulness in the population studied, there were
constructive discussions about potential pathways forward in specific patient populations for whom drops are problematic.
Based on feedback following discussions with the FDA in the fourth quarter of 2019, we do not intend to initiate the
second Phase 3 clinical trial at this time without the assistance of a collaborative partner. We believe that if we were to find
a partner for our OTX-TP program, we or such partner could decide to conduct additional Phase 2 clinical trials to address
feedback from the FDA prior to another Phase 3 clinical trial. Given the potential use of OTX-TP as a chronic therapy,
however, we have decided to continue an ongoing open-label, one-year safety extension study, generating six-month and
one-year safety data for a limited number of subjects to support a potential future product registration. We anticipate data
from this safety study including pharmacokinetic data later this year.
If we were to obtain favorable results from future Phase 3 clinical trials, we would plan to submit an NDA to the
FDA for marketing approval of OTX-TP for the treatment of glaucoma and ocular hypertension. We expect that we
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would submit this NDA under Section 505(b)(2) of the FDCA. See “—Governmental Regulation—Section 505(b)(2)
NDAs” for additional information.
Intracameral Glaucoma (OTX-TIC) Product Candidate
We are conducting an open-label, proof-of-concept Phase 1 clinical trial of OTX-TIC that we initiated in the second
quarter of 2018 for the treatment of patients with moderate to severe glaucoma and ocular hypertension. OTX-TIC
(extended-delivery travoprost) is a bioresorbable hydrogel implant incorporating travoprost that is designed to be an
intracameral injection into the anterior chamber of the eye with an initial target duration of drug release of four to six
months. Preclinical studies to date have demonstrated clinically meaningful IOP lowering and good pharmacokinetics in
the aqueous humor. We initiated a pilot clinical study outside the United States in the third quarter of 2017 to assess safety
and obtain initial efficacy data, but did not enroll any patients in this clinical trial and determined to close this trial. We
submitted an IND in the first quarter of 2018 and initiated a second Phase 1 trial in the United States in the second quarter
of 2018. The study is a prospective, multi-center, open-label, dose escalation study to evaluate the safety, biological
activity, durability and tolerability of OTX-TIC compared to topical travoprost (eye drops) in patients with open-angle
glaucoma or ocular hypertension. We presented initial results from the first cohort, comprised of five patients, in this
clinical trial at the Association of Research and Vision of Ophthalmology (ARVO) meeting in April 2019 and the American
Society of Cataract and Refractive Surgery annual meeting in May 2019. This data demonstrated that, with a single
implant, subjects were able to achieve IOP lowering for up to thirteen months at a level least as good as standard of care
topical eye drop that was placed in each subject’s non-study eye. In addition, the hydrogel carrier, as designed, biodegraded
in five to seven months. There were no clinically meaningful changes in corneal health as measured by endothelial cell
evaluation and corneal pachymetry. Several subjects reported low grade inflammation and peripheral anterior synechiae
that we believe may be addressable with modifications to the implants.
At the Glaucoma 360 meeting in February of 2020, we presented results from the first two of four patient cohorts in
the Phase 1 clinical trial. Data from the first two fully-enrolled cohorts (cohort 1 = 5 subjects, cohort 2 = 4 subjects) shows
a clinically meaningful reduction from baseline in mean IOP values at the 8 a.m. timepoint in patients treated with a single
insertion of OTX-TIC throughout the six-month study period. The data also shows that the mean IOP values at the 8 a.m.
timepoint remained decreased from the baseline values beyond the study period and, in one patient, for up to eighteen
months at the time of assessment.
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Cohort 1: Mean IOP Change from Baseline at 8:00 a.m.
Cohort 2: Mean IOP Change from Baseline at 8:00 a.m.
Overall, OTX-TIC was generally well-tolerated and observed to have a favorable safety profile, and no serious
adverse events were reported. No changes in corneal health were noted as measured by slit lamp examination, corneal
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pachymetry and endothelial cell count evaluation. Eight ocular adverse events were reported, with the most frequent being
iritis. The implant biodegraded consistently in approximately five to seven months.
We continue to collect additional data from the first two cohorts and have begun enrollment in the third and fourth
cohort to assess the impact of a faster degrading implant with the same therapeutic dose as administered in cohort one. We
have also developed an additional formulation to test a smaller implant of OTX-TIC and expect to evaluate this formulation
in a fourth cohort of this clinical trial in the future.
We are currently collecting additional data from the first two cohorts and have begun enrolling a third cohort to
assess the impact of a faster degrading implant with the same therapeutic dose as administered in cohort one. We have
developed an additional formulation to test a smaller implant of OTX-TIC and expect to evaluate this formulation in a
fourth cohort of this clinical trial in the future.
Regulatory Pathway
We anticipate that our ongoing Phase 1 clinical trial of OTX-TIC will provide important information to inform the
design of later stage clinical trials of this product candidate. If our Phase 1 clinical trial were successful, we would expect
to initiate a Phase 2 clinical trial to evaluate OTX-TIC for the treatment of open-angle glaucoma and ocular
hypertension. We would then be required to successfully complete two well controlled Phase 3 clinical trials conducted
under an IND to obtain marketing approval from the FDA. If we were to obtain favorable results from these two pivotal
clinical trials, we would plan to submit an NDA to the FDA for marketing approval of OTX-TIC for such indication. We
expect that we would submit this NDA under Section 505(b)(2) of the FDCA. See “—Government Regulation—Section
505(b)(2) NDAs.”
Intravitreal Implants for the Treatment of Back-of-the-Eye Diseases
We are engaged in a preclinical development program of our sustained-release hydrogel administered via intravitreal
injection to address the large and growing markets for diseases and conditions of the back of the eye. Our current
development efforts are focused on the use of our sustained-release hydrogel in combination with anti-angiogenic
compounds, including anti-VEGF compounds, for the treatment of wet AMD. Our initial implants have delivered both
small and large molecule anti-VEGF compounds in vitro over our targeted four to six month period, which we believe
could make it possible to reduce the frequency of the current monthly or bi-monthly intravitreal injection regimen for wet
AMD. In addition, our preclinical studies have demonstrated a sustained pharmacodynamic effect in vivo of up to six
months with a small molecule tyrosine kinase inhibitor (TKI). The two strategies being pursued are as follows:
· We are evaluating an intravitreal implant, in collaboration with Regeneron, consisting of a PEG-based hydrogel
matrix containing embedded micronized particles of aflibercept. Aflibercept is marketed by Regeneron under the
brand name Eylea. We refer to the formulation we are developing with Regeneron as OTX-IVT. We designed the
injection to be delivered to the vitreous chamber of the eye using a fine gauge needle. We entered into a strategic
collaboration with Regeneron in October 2016 for the development and commercialization of protein-based anti-
VEGF drugs, with the initial product candidate incorporating the drug aflibercept into our hydrogel.
In December 2017, we delivered to Regeneron a proposed final formulation for the initial preclinical tolerability
study. Regeneron initiated the preclinical study in early 2018. We and Regeneron have subsequently reached an
understanding that the proposed formulation was not final and have ceased development of it. We are currently
in discussions with Regeneron, in accordance with the terms of the Collaboration Agreement, regarding the
development of an alternative formulation.
· We have selected the TKI, axitinib, referred to as OTX-TKI, and advanced the product candidate into an initial
human clinical trial and dosed our first patient in Australia in February 2019. We have conducted preclinical
work on this compound and have achieved local programmed-release and pharmacodynamic effect in vivo for
six months. We believe this class of drugs is well suited for use with our platform given its high potency, multi-
target capability, and compatibility with a hydrogel vehicle. In the absence of a sophisticated drug delivery
system, these drugs have been difficult to deliver to the eye for acceptable time frames at
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therapeutic levels without causing local and systemic toxicity due to low drug solubility and very short half-lives
in solution. We believe our local programmed-release drug delivery technology gives us potential advantages in
this regard. By selecting a compound that is compatible with our hydrogel platform technology and that will
have expiration of relevant patents within the timeline of our development program, we avoid the need to license
the TKI molecule, thus retaining full worldwide rights to any products we develop.
In Vitro and Preclinical results
To date, in in vitro tests and preclinical studies, we have been able to incorporate antibody anti-VEGF drugs within
our hydrogels, and our collaborators have been testing release rates and the integrity and activity of their compounds. We
have achieved in vitro release over a four to six month duration. The released proteins have been stable, with no chemical
or functional changes observed.
Our hydrogel implants have shown initial tolerability and acceptable pharmacokinetics. We conducted an in vivo
study to measure ocular tissue concentrations of bevacizumab after injection with and without our sustained-release
hydrogel. The injection of a bevacizumab formulation without our hydrogel resulted in a first-order rate of drug clearance,
as expected. In addition, bevacizumab concentrations decreased in the ocular tissues with distance from the intravitreal
injection site. The injection of our hydrogel implant containing bevacizumab showed the same decrease of tissue
concentration of bevacizumab in successively distant tissues. However, the injection of our hydrogel implant containing
bevacizumab resulted in a sustained level of drug over the course of the 30 day study. Further, after injection of our
hydrogel implant containing bevacizumab, we observed levels of drug in ocular tissues over the course of the study that
were consistent with our in vitro release data. After two weeks, the drug concentrations of the implant exceeded those of
bevacizumab injected without our hydrogel. More recently, we have conducted a pharmacodynamic study in a rabbit
model, achieving activity against an intravitreal VEGF challenge injection after study duration of four months, compared to
less than six weeks for a 1.25 mg (human dose) bevacizumab intravitreal injection. Tolerability of bevacizumab-loaded
implants in rabbit eyes has been demonstrated through four months. In addition, there were no anti-drug antibodies
detected in these rabbits, even though bevacizumab is a recombinant humanized monoclonal antibody and therefore might
be expected to elicit an immune response in rabbits. This early feasibility study has provided us with initial encouraging
data for our sustained-release hydrogel implant with bevacizumab and its potential capability of delivering active drug to
ocular tissues in a local programmed-release fashion and informs the additional preclinical activities we plan to pursue.
Although these results have been encouraging, we will need to further optimize our hydrogels for aflibercept in our
collaboration with Regeneron. We believe we have demonstrated initial feasibility sufficient to support the continuing
preclinical development of this program and, if we obtain additional favorable preclinical results, advancement into Phase 1
clinical trials.
We have conducted in vivo pharmacokinetic and pharmacodynamic studies with hydrogels loaded with a small
molecule anti-angiogenic TKI compound injected intravitreally. Pharmacokinetic data showed retinal tissue drug
concentrations in excess of 3,000 times published IC50 after six months and pharmacodynamic results show sustained
efficacy for six months.
We also continue to conduct our own internal preclinical development program using TKIs. We also believe there are
other opportunities for targets beyond VEGF-related targets to utilize our hydrogel for back-of-the-eye diseases, and we
may pursue opportunities through internal research or in partnership with pharmaceutical companies.
Intravitreal wet AMD (OTX-TKI) Product Candidate
We are conducting an open-label, proof-of-concept Phase 1 clinical trial of OTX-TKI that was initiated in the second
quarter of 2018 for the treatment of patients with neovascular age related macular degeneration (wet AMD). OTX-TKI
(sustained-release tyrosine kinase inhibitor) is a bioresorbable hydrogel implant incorporating axitinib that is designed to be
an intravitreal injection into the inferior hemisphere of the vitreous humor of the eye with an initial target duration of drug
release for approximately 6-9 months. Preclinical studies to date have demonstrated suppression of vascular leakage and
good pharmacokinetics in the relevant ocular tissues. The Phase 1 study was submitted to Therapeutic Goods
Administration (TGA) in July 2018. The study is a prospective, multi-center study to evaluate the safety, biological activity,
durability and tolerability of OTX-TKI.
In the first quarter of 2019, we began dosing patients in a Phase 1 clinical trial in Australia. This clinical trial is a
multi-center, open-label, does escalation study designed to evaluate the safety, durability, tolerability, and biological
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activty of OTX-TKI. We are evaluating biological activity by following visual acuity over time and measuring retinal
thickness using standard optical coherence tomography. The independent Data Safety and Monitoring Committee met to
review the safety from the first cohort of subjects in the Phase 1 clinical trial and recommended moving to a higher dose of
OTX-TKI for the next cohort of subjects to be treated, as the first cohort of subjects reported no safety concerns. Two
cohorts of six subjects each have been enrolled, a lower dose cohort of 200 μg and a higher dose cohort of 400 μg. In the
first two fully enrolled cohorts, OTX-TKI was generally well tolerated and observed to have a favorable safety profile with
no ocular serious adverse events noted. In the higher dose cohort, OTX-TKI showed a decrease in central subfield retinal
thickness as measured by mean change in central subfield thickness values by decreases in intraretinal and/or subretinal
fluid in some subjects. We plan to continue long-term evaluation of the first two cohorts. We plan to amend our current
clinical trial protocol to enroll a third, higher-dose cohort. This Phase 1 clinical trial is not powered to measure any
efficacy endpoints with statistical significance.
Interim results from the Phase 1 trial were presented at the 40 Annual Cowen Health Care Conference on March 3,
th
2020. Slides covering Mean Change in Central Subfield Thickness Values by Cohort, Individual Subject Durability
Assessment and Safety Overview for Cohorts 1 & 2 are included below.
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Regulatory Pathway
In the second quarter of 2018 we initiated a Phase 1 clinical trial for the treatment of patients with neovascular age-
related macular degeneration (wet AMD) in Australia. If successful, we would plan for one Phase 2 clinical trial and two
Phase 3 clinical trials for the treatment of patients with neovascular age-related macular degeneration (wet AMD). If
successful, we would plan to submit an NDA under Section 505(b)(2) of the FDCA. See “—Government Regulation—
Section 505(b)(2) NDAs” for additional information.
ReSure Sealant
ReSure Sealant is a topical liquid hydrogel that creates a temporary, adherent, soft and lubricious sealant to prevent
post-surgical leakage from clear corneal incisions that are made during cataract surgery. The main components of ReSure
hydrogel are water and PEG. ReSure hydrogel is completely synthetic, with no animal or human derived components. The
FDA granted marketing approval for ReSure Sealant in January 2014. We commercially launched ReSure Sealant in the
United States in February 2014.
Product Design
A surgeon forms ReSure Sealant hydrogel by combining three components: PEG, a cross-linker and a diluent buffer
solution. The cross-linker interacts with the PEG molecules to form a molecular network that comprises the hydrogel. The
components are mixed to initiate the cross-linking reaction to form a biocompatible, resorbable hydrogel. The hydrogel is
approximately 90% water and is blue in color to help the surgeon visualize the sealant during application. The surgeon
applies the sealant to the corneal incision as a liquid using a soft foam-tipped applicator. The sealant forms a conformal
coating that adheres to the ocular tissue through mechanical interlocking of the hydrogel with
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the tissue surfaces. The blue color fades within a few hours following surgery. The soft, pliable hydrogel remains on the
corneal surface during the critical wound healing period of one to three days and provides a barrier to fluid leakage. ReSure
Sealant softens over time, detaches and is sloughed off in the tears as a liquid or extremely soft gel pieces. ReSure Sealant
is designed to completely liquefy over a five to seven day duration. Complete epithelial healing takes place over this time
period, providing long-term wound closure.
We provide ReSure Sealant in a sterile, single patient use package. The package contains a tray with two elongated
mixing wells. Each well contains dried deposits of reactants, separated within the well. The package also contains one
plastic dropper bottle filled with diluent solution and two applicators. The device is stored at room temperature for easy
access.
ReSure Sealant Clinical Development
We conducted a pivotal clinical trial evaluating the safety and effectiveness of ReSure Sealant compared to sutures
for preventing incision leakage from clear corneal incisions. In connection with FDA approval of ReSure Sealant in
January 2014, we have agreed to conduct two post-approval studies. The first post-approval registry study was designed to
confirm whether ReSure Sealant can be used safely by physicians in a standard cataract surgery practice and to confirm the
incidence of pre-specified adverse ocular events in eyes treated with ReSure Sealant. The second post-approval study is
designed to ascertain the incidence of endophthalmitis in patients treated with ReSure Sealant.
Pivotal Clinical Trial
In 2013, we completed a prospective, randomized, parallel-arm, controlled, multicenter, subject-masked pivotal
clinical trial evaluating the safety and effectiveness of ReSure Sealant. In this trial, we enrolled 488 patients at 24 sites
across the United States. One patient was excluded prior to treatment because the surgeon was unable to achieve a dry
ocular surface for application of ReSure Sealant. As a result, we randomized 304 patients for treatment with ReSure
Sealant and 183 patients for treatment with sutures. Based on the trial protocol, 295 patients treated with ReSure Sealant
and 176 patients treated with sutures completed study follow-up without a significant protocol deviation that directly
affected the primary efficacy endpoint.
The primary efficacy endpoint was non-inferiority of ReSure Sealant to sutures for preventing incision leakage from
clear corneal incisions within the first seven days following cataract surgery. A non-inferiority determination requires that
the test product is not worse than the comparator by more than a small pre-specified margin. The non-inferiority margin for
the ReSure Sealant pivotal clinical trial was a percentage difference in leak rates between ReSure Sealant and sutures of
5%.
We randomized patients in a 5:3 ratio to receive either ReSure Sealant or sutures. All patients received a standardized
self-sealing incision.
Surgeons assessed incision leakage during the operation and during follow-up visits on days 1, 3, 7 and 28 after the
procedure. During the pre-randomization intraoperative evaluation, the surgeons assessed whether there was any leakage
based on a standard test called a Seidel test in conjunction with an application of force near the incision using a
standardized tool and technique. The surgeon slowly applied force using the standardized tool that we provided until a leak
was observed or until a pre-specified maximum force of one ounce of force was reached. In the assessments
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conducted during the operation, approximately 50% of leaks occurred spontaneously without application of force and 76%
of leaks occurred with the application of 0.25 ounces of force or less.
Based on assessments conducted immediately following surgery, using the same standardized leak testing tool and
technique, eyes receiving sutures leaked more frequently than eyes sealed with ReSure Sealant by a statistically significant
margin of more than 8 to 1 (p<0.0001). In this trial, ReSure Sealant demonstrated both non-inferiority and superiority
relative to the suture control based on the proportion of eyes with leakage within the first seven days after surgery. These
results are shown in the figures below.
ReSure Sealant treated patients had significantly lower adverse event and device-related adverse event rates than
patients treated with suture wound closure. We determined statistical significance based on a widely used, conventional
statistical method that establishes the p-value of clinical results. Typically, a p-value of 0.05 or less represents statistical
significance. In adverse events related to the study device, ReSure Sealant had a lower occurrence rate by a statistically
significant margin of 1.6% for ReSure Sealant compared to 30.6% for sutures (p<0.0001). There were no significant or
clinically relevant differences in the other safety endpoints, including slit lamp examination findings, between ReSure
Sealant and suture patients, thus indicating that ReSure Sealant is well tolerated. Only one ReSure Sealant treated patient
out of 299 (0.3%) had a wound healing assessment characterized as outside of normal limits at the day 7 assessment due to
the presence of mild stromal edema. No ReSure Sealant treated subjects were outside of normal limits at the day 28
assessment. In this trial, surgeons rated ReSure Sealant as “easy” or “very easy” to use for 94.1% of patients treated with
ReSure Sealant.
Post-Approval Studies
ReSure Sealant is classified in the United States as a class III medical device subject to the rules and regulation of
premarket approval by the FDA. Following our submission of a PMA application to the FDA for review and during the
review process, the FDA completed compliance audits of our manufacturing facility and several of our pivotal clinical
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trial sites. Before granting approval of the PMA application, the FDA sought input from the Ophthalmic Devices Advisory
Committee, a panel of physicians charged with reviewing results from our pivotal clinical trial. The FDA approved our
PMA application for ReSure Sealant in January 2014. The FDA included two post-approval studies as a condition of the
PMA application approval.
The first post-approval study, identified as the Clinical PAS, is to confirm that ReSure Sealant can be used safely by
physicians in a standard cataract surgery practice and to confirm the incidence in eyes treated with ReSure Sealant of the
most prevalent adverse ocular events identified in our pivotal study of ReSure Sealant in eyes treated with ReSure Sealant.
The FDA has approved the protocol for the Clinical PAS, and we initiated enrollment in December 2014. Enrollment was
completed in December 2015 with 626 patients in 22 sites. We submitted the final study report to the FDA in June 2016,
and the FDA has subsequently confirmed the Clinical PAS has been completed.
The second post-approval study, identified as the Device Exposure Registry Study, is intended to link to the Medicare
database to ascertain if patients are diagnosed or treated for endophthalmitis within 30 days following cataract surgery and
application of ReSure Sealant. We initiated enrollment in this study in December 2016 and submitted our first progress
report to FDA in January 2017. The Device Exposure Registry Study is required to include at least 4,857 patients. Due to
difficulties in establishing an acceptable way to link ReSure Sealant to the Medicare database and lack of investigator
interest, we have been unable to enroll trial sites and patients, collect patient data and report study data to the FDA. We
have provided regular periodic reports to the FDA on the progress of this post-approval study.
We received a warning letter from the FDA in October 2018 relating to our compliance with data collection and
information reporting obligations in the Device Exposure Registry Study. The FDA warning letter refers to a lack of
progress with the enrollment and related data collection and information reporting obligations for a required post-approval
trial. Failure by us to conduct the required post-approval trial for ReSure Sealant to the FDA’s satisfaction may result in
withdrawal of the FDA’s approval of ReSure Sealant or other regulatory action.
In November 2018, we appealed this warning letter. In December 2018, the FDA rejected our appeal. A
teleconference was held with the FDA in January 2019 resulting in tentative agreement on a proposed retrospective registry
study of endophthalmitis rates to satisfy the Device Exposure Registry Study requirements. In a letter dated June 7, 2019
from the FDA, the agency acknowledged receipt of a letter dated March 29, 2019 from us in which we proposed
conducting the proposed retrospective analysis of the IRIS Registry, comparing endophthalmitis rates from sites that
purchased ReSure versus those sites that did not purchase ReSure. If the rates are no different, the FDA has indicated that
it will consider the post-approval requirement to have been fulfilled. If there is a statistically significant increase in
endophthalmitis rates at sites purchasing ReSure compared with those not purchasing ReSure, a prospective study will be
required. The FDA has indicated it will consider our response to the warning letter adequate once it approves the study
protocol for the retrospective analysis of the IRIS Registry and the outline of the prospective study. We submitted the
protocol for the agreed upon retrospective study and the prospective study outline, as required per the terms of the warning
letter in December 2019. We received feedback from the FDA in February 2020 and responded to the FDA in March
2020. We expect a response from the FDA in the middle of 2020.
ReSure Sealant currently remains commercially available in the United States, though there is no sales support
provided to the product at this time. We have received only limited revenues from ReSure Sealant to date and anticipate
receiving only limited revenues from the program in 2020.
Foreign Approvals
Outside the United States, we plan to assess whether to seek regulatory approval for ReSure Sealant in markets such
as the European Union, Australia and Japan based on the market opportunity, particularly pricing, and the requirements for
marketing approval. Given our prioritization of the clinical development of our sustained-release product candidates and
our planned commercialization efforts for our initial intracanalicular insert product candidates in the United States, we do
not currently plan to seek CE Mark approval to commercialize ReSure Sealant in the European Union. Outside of the
United States and the European Union, we will need to engage a third party to assist us in the approval process. If we
obtain regulatory approval to market and sell ReSure Sealant in international markets, we expect to utilize a variety of
types of collaboration, distribution and other marketing arrangements with one or more third parties to commercialize
ReSure Sealant. See “—Government Regulation—Review and Approval of Medical Devices in the European Union” for
additional information.
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Commercial Strategy
Our goals for ReSure Sealant are to provide a novel means of definitive wound closure in situations in which the
surgeon would otherwise use sutures and to increase the number of procedures in which surgeons close the wound
following cataract surgery, instead of leaving the wound to self-seal. The market opportunity for a surgical sealant
following cataract surgery may be modest. However, we believe ReSure Sealant offers important benefits over sutures,
including superior wound closure, a better safety profile and less follow-up. While ReSure Sealant remains commercially
available in the United States, there is no current sales support provided to the product at this time.
Sales, Marketing and Distribution
We plan to prioritize our commercialization efforts in the United States. We generally expect to retain commercial
rights in the United States to any of our local programmed-release drug delivery product candidates for front-of-the-eye
diseases and conditions for which we may receive marketing approvals and which we believe we can successfully
commercialize.
We commercially launched ReSure Sealant in the United States in February 2014. We initially sold ReSure Sealant
through a network of independent distributors across the United States. While ReSure Sealant remains commercially
available in the United States, there is no sales support provided to the product at this time. However, with the approval of
DEXTENZA, we expect to be able to sell ReSure Sealant with DEXTENZA with the current sales force if we choose to do
so in the future. Although we do not actively promote ReSure Sealant in terms of territory sales representatives, we
continue to sell it in the United States, and will resume a promotional presence for ReSure Sealant in the ophthalmic
marketplace at industry conventions, such as the American Society of Cataract and Refractive Surgery and the American
Academy of Ophthalmology, among others.
With the approval of DEXTENZA in November of 2018 for ocular pain, and in June 2019 for ocular inflammation,
we have built a highly targeted, key account sales force that focuses on the ambulatory surgical centers responsible for the
largest volumes of cataract surgery. Following our receipt of FDA approval on November 30, 2018, we submitted an
application for a C-code for transitional pass-through payment status. On May 29, 2019, we received formal notification
from the Centers for Medicare and Medicaid Services, or CMS, that it had approved transitional pass-through payment
status and established a new reimbursement code for DEXTENZA. The code, C9048, became effective on July 1,
2019. On December 28, 2018, we submitted an application for a J-Code for permanent payment status. In July 2019, we
subsequently received a specific and permanent J-Code, J1096, that became effective October 1, 2019. A J-Code is a
permanent code used to report drugs that ordinarily cannot be self-administered. With the effectiveness of our permanent J-
Code as of October 1, 2019, our C-code is no longer in effect. J-Codes are familiar to both medical practices and their
billing staffs, as well as Medicare (Part B and Part C) and commercial insurers. As a result, J-Codes allow for a simpler and
more convenient reimbursement process.
In connection with our July 1, 2019 commercial launch of DEXTENZA, we have built our own highly targeted, key
account manager, or KAM, sales force that focuses on the ambulatory surgical centers, or ASCs, responsible for the largest
volumes of cataract surgery. Since the commercial launch of DEXTENZA, we have expanded our field sales team by 50%
to a total of 30 KAMs. DEXTENZA is now available through a network of distributors. Our initial commercial efforts are
focused on the two million cataract procedures performed annually under Medicare Part B.
If we receive approval to market any of our product candidates in the United States, we plan to then evaluate the
regulatory approval requirements and commercial potential for any such product candidate in Europe, Japan and other
selected geographies. If we decide to commercialize our products outside of the United States, we expect to utilize a variety
of types of collaboration, distribution and other marketing arrangements with one or more third parties to commercialize
any product of ours that receives marketing approval. These may include independent distributors, pharmaceutical
companies or our own direct sales organization.
We have entered into a strategic collaboration with Regeneron for the commercialization of our intravitreal implant
for the delivery of protein-based anti-VEGF drugs for the treatment of back-of-the-eye diseases, including wet AMD. In
December 2017, we delivered to Regeneron a proposed final formulation for the initial preclinical tolerability
study. Regeneron initiated the preclinical study in early 2018. We and Regeneron have subsequently reached an
understanding that the proposed formulation was not final and have ceased development of it. We are currently in
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discussions with Regeneron, in accordance with the terms of the Collaboration Agreement, regarding the development of
an alternative formulation.
Manufacturing
We fabricate devices and drug products for use in our clinical trials, research and development and commercial
efforts for all of our therapeutic product candidates using current Good Manufacturing Practices, or cGMP, at our facility
located in Bedford, Massachusetts. In June 2016, we entered into a new lease agreement for approximately 71,000 square
feet of a new facility in Bedford, Massachusetts that will include additional manufacturing space. We are evaluating the
potential relocation of our manufacturing operations to the new leased premises. We plan to maintain our existing
manufacturing space of approximately 20,000 square feet and extended the operating lease until June 2023. We have a
one-time option to terminate the manufacturing space lease on July 2021, upon the delivery to the landlord on or before
July 2020 a termination notice and the payment to the landlord of a termination fee.
We purchase active pharmaceutical ingredient drug substance from independent suppliers on a purchase order basis
for incorporation into our drug product candidates. We purchase our PEG and other raw materials from different vendors
on a purchase order basis according to our specifications. Multiple vendors are available for each component we purchase.
We qualify vendors according to our quality system requirements. We do not have any long term supply agreements in
place for any raw materials or drug substances. We do not license any technology or pay any royalties to any of our drug or
raw material vendors for the front-of-the-eye products.
We believe that our strategic investment in manufacturing capabilities allows us to advance product candidates at a
more rapid pace and with more flexibility than a contract manufacturer, although we will continue to evaluate outsourcing
unit operations for cost advantages. Our manufacturing capability also enables us to produce products in a cost-effective
manner while retaining control over the process and prioritize the timing of internal programs.
Our manufacturing capabilities encompass the full manufacturing process through quality control and quality
assurance and are integrated with our project teams from discovery through development and commercial release. This
structure enables us to efficiently transfer research stage product concepts into manufacturing. We have designed our
manufacturing facility and processes to provide flexibility for the manufacture of different product candidates. We
outsource sterilization services for our products.
We believe that we can scale our manufacturing processes to support DEXTENZA and ReSure Sealant sales as well
as development of our drug product candidates and the potential commercialization of such product candidates.
Intellectual Property
Our success depends in part on our ability to obtain and maintain proprietary protection for our products, product
candidates, technology and know-how, to operate without infringing the proprietary rights of others and to prevent others
from infringing our proprietary rights. We rely on patent protection, trade secrets, know-how, continuing technological
innovation and in-licensing opportunities to develop and maintain our proprietary position.
We have in-licensed a significant portion of our patent rights from Incept. The license from Incept is limited to the
fields of human ophthalmic diseases and conditions, acute post-surgical pain and ear, nose and/or throat diseases or
conditions. As of March 2, 2020, we have licensed from Incept a total of 20 U.S. patents, 8 U.S. patent applications and
foreign counterparts of some of these patents and patent applications. Our license from Incept includes the following:
Intracanalicular Insert and Intracameral Implant Product Candidates
We have six U.S. patents that cover our intracanalicular insert and intracameral implant product candidates. Two
patents which have issued in the U.S. and Japan, and are pending in the European Union and elsewhere, which are expected
to expire in 2030 and cover compositions and methods of use of intracanalicular inserts. These patents are licensed
exclusively to us in the field of ophthalmology. Two U.S. patents which are expected to expire in 2020 and cover the
hydrogel composition of the intracanalicular inserts and methods of making and using hydrogel implants. These patents are
licensed exclusively to us in the field of ophthalmology. A U.S. patent which is expected to expire in 2024 that covers the
process of making the hydrogel composition of OTX-TP and OTX-MP and are non-exclusively
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licensed to us. A pending U.S. patent application that covers the hydrogel composition of DEXTENZA that, if granted, is
expected to expire in 2027.
ReSure Sealant
We have two U.S. patents that cover ReSure Sealant. A U.S. patent which is expected to expire in 2024 and which
covers the process of making and using hydrogel compositions. A U.S. patent which is expected to expire in 2032 and
which covers certain features of the ReSure Sealant package.
Intravitreal Injection
We have two U.S. patents that cover intravitreal injection product candidates. A U.S. patent that is expected to expire
in 2027 and patent applications which are pending in the European Union covering certain drug-release features of the
hydrogel implant in combination with its hydrogel composition and other proprietary technology relating to intravitreal
injections, and which, if granted, are expected to expire in 2027. A granted U.S. patent which is expected to expire in 2033
and pending patent applications in the European Union, Japan, U.S. and certain other jurisdictions covering the process of
making the hydrogel implant with its drug release features and the resultant compositions and other proprietary technology
that, if granted are expected to expire in 2032.
We have pending patent applications in the United States, European Union, and Japan directed to a drug delivery
vehicle and other proprietary technology that, if granted, are expected to expire in 2040.
The term of individual patents depends upon the legal term for patents in the countries in which they are granted. In
most countries, including the United States, the patent term is generally 20 years from the earliest claimed filing date of a
non-provisional patent application in the applicable country. In the United States, a patent’s term may, in certain cases, be
lengthened by patent term adjustment, which compensates a patentee for administrative delays by the United States Patent
and Trademark Office in examining and granting a patent, or may be shortened if a patent is terminally disclaimed over a
commonly owned patent or a patent naming a common inventor and having an earlier expiration date. The Drug Price
Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Act, permits a patent term extension of up to
five years beyond the expiration date of a U.S. patent as partial compensation for the length of time the drug is under
regulatory review while the patent is in force. A patent term extension cannot extend the remaining term of a patent beyond
a total of 14 years from the date of product approval, only one patent applicable to each regulatory review period may be
extended and only those claims covering the approved drug, a method for using it or a method for manufacturing it may be
extended.
Similar provisions are available in the European Union and certain other foreign jurisdictions to extend the term of a
patent that covers an approved drug. In the future, if and when our product candidates receive approval by the FDA or
foreign regulatory authorities, we expect to apply for patent term extensions on issued patents covering those products,
depending upon the length of the clinical trials for each drug and other factors. The expiration dates referred to above are
without regard to potential patent term extension or other market exclusivity that may be available to us.
We may rely, in some circumstances, on trade secrets to protect our technology. However, trade secrets can be
difficult to protect. We seek to protect our proprietary technology and processes, in part, by confidentiality agreements with
our employees, consultants, scientific advisors and contractors. We also seek to preserve the integrity and confidentiality of
our data.
Licenses
Incept, LLC
In January 2012, we entered into an amended and restated license agreement, which we refer to as either the Prior
Agreement or Original License, with Incept under which we hold an exclusive, worldwide, perpetual, irrevocable license
under specified patents and technology owned or controlled by Incept to make, have made, use, offer for sale, sell,
sublicense, have sublicensed, offer for sublicense and import, products delivered to or around the human eye for diagnostic,
therapeutic or prophylactic purposes relating to all human ophthalmic diseases or conditions. This license covers a
significant portion of the patent rights and the technology for ReSure Sealant and our hydrogel platform technology product
candidates. The agreement supersedes an April 2007 license agreement between us and Incept. Amar
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Sawhney, our former President and Chief Executive Officer and former Executive Chairman of the Board of Directors, is a
general partner of Incept.
On September 13, 2018, or the Effective Date, we entered into a second amended and restated license agreement, or
the Second Amended Agreement, with Incept. The Second Amended Agreement amends and restates in full the Prior
Agreement, to expand the scope of our intellectual property license and modify future intellectual property ownership and
other rights thereunder.
License Rights; Ownership of Intellectual Property. We and Incept have agreed to expand the field of use of the
exclusive, worldwide, perpetual, irrevocable license held by us under the Prior Agreement to include specified intellectual
property rights and technology owned or controlled by Incept to make, have made, use, offer for sale, sell, sublicense, have
sublicensed, offer for sublicense and import, (i) consistent with the Prior Agreement, products delivered to or around the
human eye for diagnostic, therapeutic or prophylactic purposes relating to all human ophthalmic diseases or conditions, or
the Ophthalmic Field of Use, and (ii) as a result of the expansion of the scope of the Original License, products delivered
for the treatment of acute post-surgical pain or for the treatment of ear, nose and/or throat diseases or conditions, subject to
specified exceptions, or the Additional Field of Use. We and Incept have further agreed to expand the field of use of the
Original License for certain patents, patent applications and other rights pertaining to shape-changing hydrogel
formulations thereunder, or the Shape-Changing IP, to include all fields except those involving the nerves and associated
tissues specified in the Second Amended Agreement.
We will solely own, without a license to Incept, all intellectual property rights conceived solely by one or more
individuals from our company, or the Company Individuals, after the Effective Date, subject to exceptions specified
therein. Subject to certain exceptions specified in the Second Amended Agreement, Incept will own and license to the us
(i) all intellectual property rights included in the Original License, or the Original IP, in the Ophthalmic Field of Use and
the Additional Field of Use, (ii) intellectual property rights in the field of drug delivery conceived solely by the Company
Individuals on or before the Effective Date, or Incept IP, and (iii) intellectual property rights in the field of drug delivery
conceived by one or more Company Individuals jointly with one or more individuals from Incept, including Dr. Sawhney,
or the Incept Individuals, after the Effective Date. These intellectual property rights are referred to as Joint IP, and,
collectively with the Original IP and the Incept IP, as the Licensed IP.
Financial Terms. We and any of our sublicensees are obligated to pay Incept royalties as follows under the
Agreement: (i) consistent with the Prior Agreement, a royalty equal to a low single-digit percentage of net sales by the us
or our affiliates of products, devices, materials, or components thereof, or Licensed Products, including or covered by
Original IP, excluding the Shape-Changing IP, in the Ophthalmic Field of Use; (ii) a royalty equal to a mid-single-digit
percentage of net sales by us or our affiliates of Licensed Products including or covered by Original IP, excluding the
Shape-Changing IP, in the Additional Field of Use; and (iii) a royalty equal to a low single-digit percentage of net sales by
us or our affiliates of Licensed Products including or covered by Incept IP or Joint IP in the field of drug delivery. Royalty
obligations under the Second Amended Agreement commence with the first commercial sale of a Licensed Product
described above and terminate upon the expiration of the last-to-expire patents included in the Licensed IP, as
applicable. Any sublicensee of us also will be obligated to pay Incept royalties on net sales of Licensed Products made by
it and will be bound by the terms of the Second Amended Agreement to the same extent as us. Additionally, at its sole
discretion, Incept may require, as a condition of any sublicense by us in the Additional Field of Use and in exchange for a
reduction in the royalties owed on net sales of Licensed Products described above, payments equal to a mid-teen percentage
of any upfront payment and, subject to certain conditions, other payments received by us from the sublicensee.
Patent Prosecution and Litigation. Incept will continue to have sole control and responsibility for ongoing
prosecution of patents included in the Original IP, and we will have sole control and responsibility for ongoing prosecution
of patents and patent applications included in or arising under the Incept IP or Joint IP. The parties have agreed to work
together in good faith to enter into a separate agreement under which, subject to certain limitations, we would assume
control of the prosecution of patents and patent applications included in or arising under the Shape-Changing IP. We have
the right, subject to certain conditions, to bring suit against third parties who infringe the patents included in the Original IP
in the Ophthalmic Field of Use or the Additional Field of Use, patents included in the Incept IP in the drug delivery filed,
patents included in the Joint IP in the drug delivery field, and patents included in the Shape-Changing IP in all fields except
as described above. We have also agreed, if requested by Incept, to enter into a joint defense and prosecution agreement for
the purpose of allowing the parties to share confidential and attorney-client
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privileged information regarding the possible infringement of one or more patents covered by the Second Amended
Agreement. We are responsible for all costs incurred in prosecuting any infringement action it brings.
Term and Termination. The Second Amended Agreement will expire on the later of (i) the expiration or disclaimer
by us of the last valid claim of an issued and unexpired patent included in the Licensed IP or (ii) the final unappealable
rejection or abandonment of the last pending patent application arising under the Licensed IP. Either party may terminate
the Second Amended Agreement in the event of the other party’s insolvency, bankruptcy or comparable proceedings, or if
the other party materially breaches the agreement and does not cure such breach during a specified cure period.
Regeneron Collaboration
In October 2016, we entered into the Collaboration Agreement with Regeneron for the development and
commercialization of products using our sustained-release hydrogel in combination with Regeneron’s large molecule
VEGF-targeting compounds to address conditions of the eye.
Under the terms of the Collaboration Agreement, we and Regeneron have agreed to conduct a joint research program
with the aim of developing an extended-delivery formulation of aflibercept that is suitable for advancement into clinical
development. We have granted Regeneron the Option to enter into an exclusive, worldwide license, with the right to
sublicense, under our intellectual property to develop and commercialize the Licensed Products. The Option is exclusive
until 12 months after Regeneron has received a product candidate in accordance with a collaboration plan, subject to certain
conditions, and non-exclusive for an additional six months following the end of the exclusive period. The field of this
license is limited to Licensed Products delivered by local administration to or around the eye for diagnostic, therapeutic or
prophylactic purposes relating to ophthalmic diseases or conditions. The Collaboration Agreement does not cover the
development of any products that deliver small molecule drugs, including TKIs, or deliver large molecule drugs other than
those that target certain specified VEGF proteins or their receptors. Under the terms of the Collaboration Agreement,
Regeneron is responsible for funding an initial preclinical tolerability study.
If the Option is exercised, Regeneron is to use commercially reasonable efforts to conduct further preclinical
development and an initial clinical trial under a collaboration plan. We are obligated to reimburse Regeneron for certain
development costs incurred by Regeneron under the collaboration plan during the period through the completion of the
initial clinical trial, subject to a cap of $25 million, which cap may be increased by up to $5 million under certain
circumstances. We are also responsible for paying our own costs associated with the activities conducted by us under the
collaboration plan. If Regeneron elects to proceed with further development following the completion of the collaboration
plan, it will be solely responsible for conducting and funding, and is to use commercially reasonable efforts with respect to,
further development and commercialization of product candidates.
Under the terms of the Collaboration Agreement, Regeneron has agreed to pay us $10 million upon exercise of the
Option. We are also eligible to receive up to $145 million per Licensed Product upon the achievement of specified
development and regulatory milestones, $100 million per Licensed Product upon first commercial sale of such Licensed
Product and up to $50 million based on the achievement of specified sales milestones for all Licensed Products. In addition,
we are entitled to tiered, escalating royalties, in a range from a high-single digit to a low-to-mid teen percentage of net sales
of Licensed Products, which royalties are subject to potential reductions in certain circumstances, subject to a minimum
royalty.
If Regeneron has not exercised the Option during the designated option period, the Collaboration Agreement will
expire. If Regeneron exercises the Option, the Collaboration Agreement will expire on a Licensed Product-by-Licensed
Product and country-by-by country basis upon the expiration of the later of 10 years from the date of first commercial sale
in such country or the expiration of all patent rights covering the Licensed Product in such country. Following expiration,
Regeneron will have a fully paid-up, non-exclusive license to continue to develop and commercialize Licensed
Products. The Collaboration Agreement may be terminated by Regeneron at any time after exercise of the Option upon 60
days’ prior written notice. Either party may, subject to a cure period, terminate the Collaboration Agreement in the event of
the other party’s uncured material breach, in addition to other specified termination rights.
In December 2017, we delivered to Regeneron the final formulation for Regeneron’s initial preclinical tolerability
study. Regeneron initiated the preclinical study in early 2018. We and Regeneron have subsequently reached an
understanding that the proposed formulation was not final and have ceased development of it. We are currently in
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discussions with Regeneron, in accordance with the terms of the Collaboration Agreement, regarding the development of
an alternative formulation.
Competition
The biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies, intense
competition and a strong emphasis on proprietary products. While we believe that our technologies, knowledge, experience
and scientific resources provide us with competitive advantages, we face potential competition from many different
sources, including major pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions and
governmental agencies and public and private research institutions. Any product candidates that we successfully develop
and commercialize will compete with existing therapies and new therapies that may become available in the future.
Our potential competitors include large pharmaceutical and biotechnology companies, specialty pharmaceutical and
generic drug companies, and compounding pharmacies. Potential competitors also include academic institutions,
government agencies and other public and private research organizations that conduct research, seek patent protection and
establish collaborative arrangements for research, development, manufacturing and commercialization. Many of our
potential competitors have significantly greater financial resources and expertise in research and development,
manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved
products than we do. These competitors also compete with us in recruiting and retaining qualified scientific and
management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring
technologies complementary to, or necessary for, our programs. Smaller or early stage companies may also prove to be
significant competitors, particularly through collaborative arrangements with large and established companies.
The key competitive factors affecting the success of each of our product candidates, if approved for marketing, are
likely to be efficacy, safety, method of administration, convenience, price, the level of generic competition and the
availability of coverage and adequate reimbursement from government and other third-party payors.
Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products
that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any
products that we may develop. Our competitors also may obtain FDA or other regulatory approval for their products more
rapidly than we may obtain approval for ours, which could result in our competitors’ establishing a strong market position
before we are able to enter the market. In addition, our ability to compete may be affected in many cases by insurers or
other third-party payors seeking to encourage the use of generic products.
Our product candidates target markets that are already served by a variety of competing products based on a number
of active pharmaceutical ingredients. Many of these existing products have achieved widespread acceptance among
physicians, patients and payors for the treatment of ophthalmic diseases and conditions. In addition, many of these products
are available on a generic basis, and our product candidates may not demonstrate sufficient additional clinical benefits to
physicians, patients or payors to justify a higher price compared to generic products. In many cases, insurers or other third-
party payors, particularly Medicare, seek to encourage the use of generic products. Given that we are developing products
based on FDA-approved therapeutic agents, our product candidates, if approved, will face competition from generic,
branded and compounded versions of existing drugs based on the same active pharmaceutical ingredients that are
administered in a different manner, typically through eye drops.
Because the active pharmaceutical ingredients in our product candidates are available on a generic basis, or are soon
to be available on a generic basis, competitors will be able to offer and sell products with the same active pharmaceutical
ingredient as our products so long as these competitors do not infringe the patents that we license. For example, our
licensed patents related to our intracanalicular insert product candidates largely relate to the hydrogel composition of the
intracanalicular inserts and certain drug-release features of the intracanalicular inserts. As such, if a third party were able to
design around the formulation and process patents that we license and create a different formulation using a different
production process not covered by our licensed patents or patent applications, we would likely be unable to prevent that
third party from manufacturing and marketing its product.
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Competitors of our Intracanalicular Insert Product Candidates
Several competitors are developing sustained drug release products for the same ophthalmic indications as our
intracanalicular insert product candidates, as set forth below.
Competitors of DEXTENZA
Icon Biosciences, Inc. received FDA approval of DEXYCU in February 2018. DEXYCU is an injection of
dexamethasone at the time of surgery into the posterior chamber of the eye (behind the iris) to treat inflammation
associated with cataract surgery. Icon Biosciences Inc. was subsequently bought by pSvidia Corporation in March 2018
and, at the same time, the new entity was renamed Eyepoint Pharmaceuticals, Inc., or Eyepoint. In January 2019, Eyepoint
announced that DEXYCU’s J-Code became effective and Eyepoint launched DEXYCU commercially in the first quarter of
2019.
Competitors of OTX-TIC
Allergan PLC, now owned by Abbvie, Inc., received approval in March 2020 of DURYSTA™, a biodegradable
intracameral implant consisting of a PGA and a biodegradable polymer matrix for the reduction of IOP in patients with
open-angle glaucoma or ocular hypertension. Allergan purchased ForSight VISION5 who was conducting a Phase 2
clinical development of the Helios insert, a sustained-release ocular insert placed below the eyelid that delivers bimatoprost
for the treatment of glaucoma. In addition, several other companies have announced their intention to develop products for
treatment of glaucoma using sustained-release therapy, although each of these is at an early stage of development. Mati
Therapeutics has conducted a Phase 2 clinical development of an intracanalicular insert for the treatment of glaucoma.
Competitors of our Intravitreal Implants
Our intravitreal implant for the treatment of wet AMD will compete with anti-VEGF compounds administered in
their current formulation and prescribed for the treatment of wet AMD as these agents can in some instances deliver one to
two months or more of therapeutic effect. They include Lucentis, Eylea, Beovu and off-label use of the cancer therapy
Avastin. Multiple companies, although all in early stages of development are exploring ways to deliver anti-VEGF products
in a sustained-release fashion, including Graybug Vision, Inc. which is pursuing a sustained-release microparticle depot
formulation to extend therapeutic drug levels in ocular tissue for up to six months.
Competitors of ReSure Sealant
ReSure Sealant is the first and only surgical sealant approved for ophthalmic use in the United States. Outside the
United States, Beaver Visitec is commercializing its product OcuSeal, which is designed to provide a protective hydrogel
film barrier to stabilize ocular wounds. This product has received a CE Mark in Europe but is not approved for use in the
United States. Sutures are the primary alternative for closing ophthalmic wounds. In addition, a technique called stromal
hydration, which involves the localized injection of a balanced salt solution at the wound edges, is often used to facilitate
the self-sealing of a wound.
Government Regulation
Government authorities in the United States, at the federal, state and local level, and in other countries and
jurisdictions, including the European Union, extensively regulate, among other things, the research, development, testing,
manufacture, quality control, clearance, approval, pricing, sales, reimbursement, packaging, storage, recordkeeping,
labeling, advertising, promotion, distribution, marketing, post-approval monitoring and reporting, and import and export of
pharmaceutical products and medical devices. The processes for obtaining regulatory approvals in the United States and in
foreign countries and jurisdictions, along with subsequent compliance with applicable statutes and regulations and other
regulatory authorities, require the expenditure of substantial time and financial resources.
Review and Approval of Drugs and Biologics in the United States
In the United States, the FDA approves and regulates drugs under the FDCA and related regulations. Drugs are also
subject to other federal, state and local statutes and regulations. Biological products are licensed for marketing under
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the Public Health Service Act, or PHSA, and subject to regulation under the FDCA and related regulations, and other
federal, state and local statutes and regulations.
An applicant seeking approval to market and distribute a new drug or biological product in the United States must
typically undertake the following:
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completion of preclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s
good laboratory practice, or GLP, regulations;
submission to the FDA of an IND, which must take effect before human clinical trials may begin;
approval by an independent institutional review board, or IRB, representing each clinical site before each clinical
trial may be initiated;
performance of adequate and well-controlled human clinical trials in accordance with Good Clinical Practices, or
GCP, to establish the safety and efficacy of the proposed drug product for each indication;
preparation and submission to the FDA of a new drug application, or NDA, for a drug candidate product and a
biological licensing application, or BLA, for a biological product requesting marketing for one or more proposed
indications;
review by an FDA advisory committee, where appropriate or if applicable;
satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities at which the
product, or components thereof, are produced to assess compliance with current Good Manufacturing Practices,
or cGMP, requirements and to assure that the facilities, methods and controls are adequate to preserve the
product’s identity, strength, quality and purity;
satisfactory completion of FDA audits of clinical trial sites to assure compliance with GCPs and the integrity of
clinical data;
payment of user fees and securing FDA approval of the NDA or BLA; and
compliance with any post-approval requirements, including the potential requirement to implement a Risk
Evaluation and Mitigation Strategy, or REMS, and the potential requirement to conduct post-approval studies.
Preclinical Studies
Preclinical studies include laboratory evaluation of the purity and stability of the manufactured drug substance or
active pharmaceutical ingredient and the formulated product, as well as in vitro and animal studies to assess the safety and
activity of the investigational product for initial testing in humans and to establish a rationale for therapeutic use. The
conduct of preclinical studies is subject to federal regulations and requirements, including GLP regulations. The results of
the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and
plans for clinical studies, among other things, are submitted to the FDA as part of an IND.
Companies usually must complete some long-term preclinical testing, such as animal tests of reproductive adverse
events and carcinogenicity, and must also develop additional information about the chemistry and physical characteristics
of the investigational product and finalize a process for manufacturing the product in commercial quantities in accordance
with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the
candidate product and, among other things, the manufacturer must develop methods for testing the identity, strength,
quality and purity of the final product. Additionally, appropriate packaging must be selected and tested and stability studies
must be conducted to demonstrate that the candidate product does not undergo unacceptable deterioration over its shelf life.
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The IND and IRB Processes
Clinical trials involve the administration of the investigational product to human subjects under the supervision of
qualified investigators in accordance with GCP requirements, which include, among other things, the requirement that all
research subjects provide their voluntary informed consent in writing before their participation in any clinical trial. Clinical
trials are conducted under written study protocols detailing, among other things, the inclusion and exclusion criteria, the
objectives of the study, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. A
protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of the IND.
An IND is an exemption from the FDCA that allows an unapproved product candidate to be shipped in interstate
commerce for use in an investigational clinical trial and a request for FDA authorization to administer an investigational
drug to humans. Such authorization must be secured prior to interstate shipment and administration of any new drug or
biologic that is not the subject of an approved NDA or BLA. In support of a request for an IND, applicants must submit a
protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of the
IND. In addition, the results of the preclinical tests, together with manufacturing information, analytical data, any available
clinical data or literature and plans for clinical trials, among other things, are submitted to the FDA as part of an IND. The
FDA requires a 30-day waiting period after the filing of each IND before clinical trials may begin. This waiting period is
designed to allow the FDA to review the IND to determine whether human research subjects will be exposed to
unreasonable health risks. At any time during this 30-day period, or thereafter, the FDA may raise concerns or questions
about the conduct of the trials as outlined in the IND and impose a clinical hold or partial clinical hold. In this case, the
IND sponsor and the FDA must resolve any outstanding concerns before clinical trials can begin. For our intracanalicular
insert product candidates, we have typically conducted our initial and earlier stage clinical trials outside the United States.
We generally plan to conduct our later stage and pivotal clinical trials of our intracanalicular insert product candidates in
the United States.
In addition to the foregoing IND requirements, an IRB representing each institution participating in the clinical trial
must review and approve the plan for any clinical trial before it commences at that institution, and the IRB must conduct
continuing review and reapprove the study at least annually. The IRB must review and approve, among other things, the
study protocol and informed consent information to be provided to study subjects. An IRB must operate in compliance with
FDA regulations. An IRB can suspend or terminate approval of a clinical trial at its institution, or an institution it
represents, if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the product candidate
has been associated with unexpected serious harm to patients.
The FDA’s primary objectives in reviewing an IND are to assure the safety and rights of patients and to help assure
that the quality of the investigation will be adequate to permit an evaluation of the drug’s effectiveness and safety and of
the biological product’s safety, purity and potency. The decision to terminate development of an investigational drug or
biological product may be made by either a health authority body such as the FDA, an IRB or ethics committee, or by us
for various reasons. Additionally, some trials are overseen by an independent group of qualified experts organized by the
trial sponsor, known as a data safety monitoring board or committee. This group provides authorization for whether or not a
trial may move forward at designated check points based on access that only the group maintains to available data from the
study. Suspension or termination of development during any phase of clinical trials can occur if it is determined that the
participants or patients are being exposed to an unacceptable health risk. Other reasons for suspension or termination may
be made by us based on evolving business objectives and/or competitive climate.
Information about clinical trials must be submitted within specific timeframes to the National Institutes of Health, or
NIH, for public dissemination on its ClinicalTrials.gov website. Similar requirements for posting clinical trial information
are present in the European Union (EudraCT) website: https://eudract.ema.europa.eu/ and other countries, as well.
Expanded Access to an Investigational Drug for Treatment Use
Expanded access, sometimes called “compassionate use,” is the use of investigational new drug products outside of
clinical trials to treat patients with serious or immediately life-threatening diseases or conditions when there are no
comparable or satisfactory alternative treatment options. The rules and regulations related to expanded access are intended
to improve access to investigational drugs for patients who may benefit from investigational therapies. FDA regulations
allow access to investigational drugs under an IND by the company or the treating physician for treatment
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purposes on a case-by-case basis for: individual patients (single-patient IND applications for treatment in emergency
settings and non-emergency settings); intermediate-size patient populations; and larger populations for use of the drug
under a treatment protocol or Treatment IND Application.
When considering an IND application for expanded access to an investigational product with the purpose of treating
a patient or a group of patients, the sponsor and treating physicians or investigators will determine suitability when all of
the following criteria apply: patient(s) have a serious or immediately life-threatening disease or condition, and there is no
comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition; the potential patient
benefit justifies the potential risks of the treatment and the potential risks are not unreasonable in the context or condition to
be treated; and the expanded use of the investigational drug for the requested treatment will not interfere initiation, conduct,
or completion of clinical investigations that could support marketing approval of the product or otherwise compromise the
potential development of the product.
On December 13, 2016, the 21st Century Cures Act established (and the 2017 Food and Drug Administration
Reauthorization Act later amended) a requirement that sponsors of one or more investigational drugs for the treatment of a
serious disease(s) or condition(s) make publicly available their policy for evaluating and responding to requests for
expanded access for individual patients. Although these requirements were rolled out over time, they have now come into
full effect. This provision requires drug and biologic companies to make publicly available their policies for expanded
access for individual patient access to products intended for serious diseases. Sponsors are required to make such policies
publicly available upon the earlier of initiation of a Phase 2 or Phase 3 study; or 15 days after the drug or biologic receives
designation as a breakthrough therapy, fast track product, or regenerative medicine advanced therapy.
In addition, on May 30, 2018, the Right to Try Act was signed into law. The law, among other things, provides a
federal framework for certain patients to access certain investigational new drug products that have completed a Phase 1
clinical trial and that are undergoing investigation for FDA approval. Under certain circumstances, eligible patients can
seek treatment without enrolling in clinical trials and without obtaining FDA permission under the FDA expanded access
program. There is no obligation for a drug manufacturer to make its drug products available to eligible patients as a result
of the Right to Try Act, but the manufacturer must develop an internal policy and respond to patient requests according to
that policy.
Human Clinical Studies in Support of an NDA or BLA
Clinical trials involve the administration of the investigational product to human subjects under the supervision of
qualified investigators in accordance with GCP requirements, which include, among other things, the requirement that all
research subjects provide their informed consent in writing before their participation in any clinical trial. Clinical trials are
conducted under written study protocols detailing, among other things, the inclusion and exclusion criteria, the objectives
of the study, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated.
A sponsor may choose, but is not required, to conduct a foreign clinical trial under an IND. When a foreign clinical
trial is conducted under an IND, all FDA IND requirements must be met unless waived. When a foreign clinical trial is not
conducted under an IND, the sponsor must ensure that the trial complies with certain regulatory requirements of the FDA
in order to use the trial as support for an IND or application for marketing approval. Specifically, the FDA requires such
trials to be conducted in accordance with GCP, including review and approval by an independent ethics committee and
informed consent from subjects. The GCP requirements encompass both ethical and data integrity standards for clinical
trials. The FDA’s regulations are intended to help ensure the protection of human subjects enrolled in non-IND foreign
clinical trials, as well as the quality and integrity of the resulting data. They further help ensure that non-IND foreign trials
are conducted in a manner comparable to that required for IND trials.
Human clinical trials are typically conducted in three sequential phases, which may overlap or be combined:
·
Phase 1: The drug or biologic is initially introduced into a small number of healthy human subjects or patients
with the target disease or condition and tested for safety, dosage tolerance, absorption, metabolism, distribution,
excretion and, if possible, to gain an early indication of its effectiveness and to determine optimal dosage.
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Phase 2: The drug or biologic is administered to a limited patient population to identify possible adverse effects
and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to
determine dosage tolerance and optimal dosage.
Phase 3: The drug or biologic is administered to an expanded patient population, generally at geographically
dispersed clinical trial sites, in well-controlled clinical trials to generate enough data to statistically evaluate the
efficacy and safety of the product for approval, to establish the overall risk-benefit profile of the product, and to
provide adequate information for the labeling of the product.
Phase 3 clinical trials are commonly referred to as “pivotal” trials, which typically denotes a trial which presents the
data that the FDA or other relevant regulatory agency will use to determine whether to approve a drug.
Progress reports detailing the safety results of the clinical trials must be submitted at least annually to the FDA and
more frequently if serious adverse events occur. In addition, IND safety reports must be submitted to the FDA for any of
the following: serious and unexpected suspected adverse reactions; findings from other studies or animal or in vitro testing
that suggest a significant risk in humans exposed to the product candidate; and any clinically important increase in the case
of a serious suspected adverse reaction over that listed in the protocol or investigator brochure. The FDA or the sponsor or
the data monitoring committee may suspend or terminate a clinical trial at any time on various grounds, including a finding
that the research subjects are being exposed to an unacceptable health risk. The FDA will typically inspect one or more
clinical sites to assure compliance with GCP and the integrity of the clinical data submitted.
Concurrent with clinical trials, companies often complete additional animal studies and must also develop additional
information about the chemistry and physical characteristics of the drug as well as finalize a process for manufacturing the
product in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of
consistently producing quality batches of the drug candidate and, among other things, must develop methods for testing the
identity, strength, quality, purity, and potency of the final drug. Additionally, appropriate packaging must be selected and
tested and stability studies must be conducted to demonstrate that the drug candidate does not undergo unacceptable
deterioration over its shelf life.
Review of an NDA or BLA by the FDA
In order to obtain approval to market a drug or biological product in the United States, a marketing application must
be submitted to the FDA that provides data establishing the safety and effectiveness of the proposed drug product for the
proposed indication, and the safety, purity and potency of the biological product for its intended indication. The application
includes all relevant data available from pertinent preclinical and clinical trials, including negative or ambiguous results as
well as positive findings, together with detailed information relating to the product’s chemistry, manufacturing, controls
and proposed labeling, among other things. Data can come from company-sponsored clinical trials intended to test the
safety and effectiveness of a use of a product, or from a number of alternative sources, including studies initiated by
investigators. To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the
safety and effectiveness of the investigational drug product and the safety, purity and potency of the biological product to
the satisfaction of the FDA.
The NDA and BLA are thus the vehicles through which applicants formally propose that the FDA approve a new
product for marketing and sale in the United States for one or more indications. Every new product candidate must be the
subject of an approved NDA or BLA before it may be commercialized in the United States. Under federal law, the
submission of most applications is subject to an application user fee, which for federal fiscal year 2020 is $2,943,965 for an
application requiring clinical data. The sponsor of an approved application is also subject to an annual program fee, which
for fiscal year 2020 is $325,424. Certain exceptions and waivers are available for some of these fees, such as an exception
from the application fee for product candidates with orphan designation and a waiver for certain small businesses.
Following submission of an NDA or BLA, the FDA conducts a preliminary review of the application generally
within 60 calendar days of its receipt and strives to inform the sponsor by the 74th day after the FDA’s receipt of the
submission to determine whether the application is sufficiently complete to permit substantive review. The FDA may
request additional information rather than accept the application for filing. In this event, the application must be
resubmitted with the additional information. The resubmitted application is also subject to review before the FDA accepts
it for filing. Once the submission is accepted for filing, the FDA begins an in-depth substantive review. The
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FDA has agreed to specified performance goals in the review process of NDAs and BLAs. Under that agreement, 90% of
applications seeking approval of New Molecular Entities, or NMEs, are meant to be reviewed within ten months from the
date on which FDA accepts the application for filing, and 90% of applications for NMEs that have been designated for
“priority review” are meant to be reviewed within six months of the filing date. For applications seeking approval of
products that are not NMEs, the ten-month and six-month review periods run from the date that FDA receives the
application. The review process and the Prescription Drug User Fee Act goal date may be extended by the FDA for three
additional months to consider new information or clarification provided by the applicant to address an outstanding
deficiency identified by the FDA following the original submission.
Before approving an application, the FDA typically will inspect the facility or facilities where the product is or will
be manufactured. These pre-approval inspections may cover all facilities associated with an NDA or BLA submission,
including drug component manufacturing (e.g., active pharmaceutical ingredients), finished drug product manufacturing,
and control testing laboratories. The FDA will not approve an application unless it determines that the manufacturing
processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the
product within required specifications. Additionally, before approving an NDA or BLA, the FDA will typically inspect one
or more clinical sites to assure compliance with GCP. Under the FDA Reauthorization Act of 2017, the FDA must
implement a protocol to expedite review of responses to inspection reports pertaining to certain applications, including
applications for products in shortage or those for which approval is dependent on remediation of conditions identified in the
inspection report.
In addition, as a condition of approval, the FDA may require an applicant to develop a REMS. REMS use risk
minimization strategies beyond the professional labeling to ensure that the benefits of the product outweigh the potential
risks. To determine whether a REMS is needed, the FDA will consider the size of the population likely to use the product,
seriousness of the disease, expected benefit of the product, expected duration of treatment, seriousness of known or
potential adverse events, and whether the product is a new molecular entity.
The FDA may refer an application for a novel product to an advisory committee or explain why such referral was not
made. Typically, an advisory committee is a panel of independent experts, including clinicians and other scientific experts,
that reviews, evaluates and provides a recommendation as to whether the application should be approved and under what
conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such
recommendations carefully when making decisions.
Accelerated Approval Pathway
The FDA may grant accelerated approval to a drug for a serious or life-threatening condition that provides
meaningful therapeutic advantage to patients over existing treatments based upon a determination that the drug has an
effect on a surrogate endpoint that is reasonably likely to predict clinical benefit. The FDA may also grant accelerated
approval for such a condition when the product has an effect on an intermediate clinical endpoint that can be measured
earlier than an effect on irreversible morbidity or mortality, or IMM, and that is reasonably likely to predict an effect on
irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the
condition and the availability or lack of alternative treatments. Drugs granted accelerated approval must meet the same
statutory standards for safety and effectiveness as those granted traditional approval.
For the purposes of accelerated approval, a surrogate endpoint is a marker, such as a laboratory measurement,
radiographic image, physical sign, or other measure that is thought to predict clinical benefit, but is not itself a measure of
clinical benefit. Surrogate endpoints can often be measured more easily or more rapidly than clinical endpoints. An
intermediate clinical endpoint is a measurement of a therapeutic effect that is considered reasonably likely to predict the
clinical benefit of a drug, such as an effect on IMM. The FDA has limited experience with accelerated approvals based on
intermediate clinical endpoints, but has indicated that such endpoints generally may support accelerated approval where the
therapeutic effect measured by the endpoint is not itself a clinical benefit and basis for traditional approval, if there is a
basis for concluding that the therapeutic effect is reasonably likely to predict the ultimate clinical benefit of a drug.
The accelerated approval pathway is most often used in settings in which the course of a disease is long and an
extended period of time is required to measure the intended clinical benefit of a drug, even if the effect on the surrogate or
intermediate clinical endpoint occurs rapidly. The accelerated approval pathway is usually contingent on a sponsor’s
agreement to conduct, in a diligent manner, additional post-approval confirmatory studies to verify and describe the
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drug’s clinical benefit. As a result, a product candidate approved on this basis is subject to rigorous post-marketing
compliance requirements, including the completion of Phase 4 or post-approval clinical trials to confirm the effect on the
clinical endpoint. Failure to conduct required post-approval studies, or confirm a clinical benefit during post-marketing
studies, would allow the FDA to withdraw the drug from the market on an expedited basis. All promotional materials for
product candidates approved under accelerated regulations are subject to prior review by the FDA.
The FDA’s Decision on an Application
On the basis of the FDA’s evaluation of the application and accompanying information, including the results of the
inspection of the manufacturing facilities, the FDA may issue an approval letter or a complete response letter. An approval
letter authorizes commercial marketing of the product with specific prescribing information for specific indications. A
complete response letter generally outlines the deficiencies in the submission and may require substantial additional testing
or information in order for the FDA to reconsider the application. If and when those deficiencies have been addressed to the
FDA’s satisfaction in a resubmission of the application, the FDA will issue an approval letter. The FDA has committed to
reviewing such resubmissions in two or six months depending on the type of information included. Even with submission
of this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for
approval.
If the FDA approves a product, it may limit the approved indications for use for the product, require that
contraindications, warnings or precautions be included in the product labeling, require that post‑approval studies, including
Phase 4 clinical trials, be conducted to further assess the product candidate’s safety after approval, require testing and
surveillance programs to monitor the product after commercialization, or impose other conditions, including distribution
restrictions or other risk management mechanisms, including REMS, which can materially affect the potential market and
profitability of the product. The FDA may prevent or limit further marketing of a product based on the results of
post‑market studies or surveillance programs. After approval, many types of changes to the approved product, such as
adding new indications, manufacturing changes and additional labeling claims, are subject to further testing requirements
and FDA review and approval.
Post-Approval Regulation
Drugs and biologics manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing
regulation by the FDA, including, among other things, requirements relating to recordkeeping, periodic reporting, product
sampling and distribution, advertising and promotion and reporting of adverse experiences with the product. After
approval, most changes to the approved product, such as adding new indications or other labeling claims, are subject to
prior FDA review and approval. There also are continuing, annual user fee requirements for any marketed products and the
establishments at which such products are manufactured, as well as new application fees for supplemental applications with
clinical data.
In addition, manufacturers and other entities involved in the manufacture and distribution of approved products are
required to register their establishments with the FDA and state agencies, and are subject to periodic unannounced
inspections by the FDA and these state agencies for compliance with cGMP requirements. Changes to the manufacturing
process are strictly regulated and often require prior FDA approval before being implemented. FDA regulations also
require investigation and correction of any deviations from cGMP and impose reporting and documentation requirements
upon the sponsor and any third-party manufacturers that the sponsor may decide to use. Accordingly, manufacturers must
continue to expend time, money, and effort in the area of production and quality control to maintain cGMP compliance.
A product may also be subject to official lot release, meaning that the manufacturer is required to perform certain
tests on each lot of the product before it is released for distribution. If the product is subject to official release, the
manufacturer must submit samples of each lot, together with a release protocol showing a summary of the history of
manufacture of the lot and the results of all of the manufacturer’s tests performed on the lot, to the FDA. The FDA may in
addition perform certain confirmatory tests on lots of some products before releasing the lots for distribution. Finally, the
FDA will conduct laboratory research related to the safety, purity, potency and effectiveness of pharmaceutical products.
Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory requirements and
standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously
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unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing
processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new
safety information; imposition of post-market studies or clinical trials to assess new safety risks; or imposition of
distribution or other restrictions under a REMS program. Other potential consequences include, among other things:
·
·
·
·
·
restrictions on the marketing or manufacturing of the product, suspension of the approval, complete withdrawal
of the product from the market or product recalls;
fines, warning letters or holds on post-approval clinical trials;
refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocation of
product license approvals;
product seizure or detention, or refusal to permit the import or export of products; or
injunctions or the imposition of civil or criminal penalties.
The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market.
Products may be promoted only for the approved indications and in accordance with the provisions of the approved label. If
a company is found to have promoted off-label uses, it may become subject to adverse public relations and administrative
and judicial enforcement by the FDA, the Department of Justice, or the Office of the Inspector General of the Department
of Health and Human Services, as well as state authorities. This could subject a company to a range of penalties that could
have a significant commercial impact, including civil and criminal fines and agreements that materially restrict the manner
in which a company promotes or distributes drug products.
In addition, the distribution of prescription pharmaceutical products is subject to the Prescription Drug Marketing
Act, or PDMA, and its implementing regulations, as well as the Drug Supply Chain Security Act, or DSCA, which regulate
the distribution and tracing of prescription drugs and prescription drug samples at the federal level, and set minimum
standards for the regulation of drug distributors by the states. The PDMA, its implementing regulations and state laws limit
the distribution of prescription pharmaceutical product samples, and the DSCA imposes requirements to ensure
accountability in distribution and to identify and remove counterfeit and other illegitimate products from the market.
Section 505(b)(2) NDAs
NDAs for most new drug products are based on two full clinical studies which must contain substantial evidence of
the safety and efficacy of the proposed new product. These applications are submitted under Section 505(b)(1) of the
FDCA. The FDA is, however, authorized to approve an alternative type of NDA under Section 505(b)(2) of the FDCA.
This type of application allows the applicant to rely, in part, on the FDA’s previous findings of safety and efficacy for a
similar product, or published literature. Specifically, Section 505(b)(2) applies to NDAs for a drug for which the
investigations made to show whether or not the drug is safe for use and effective in use and relied upon by the applicant for
approval of the application “were not conducted by or for the applicant and for which the applicant has not obtained a right
of reference or use from the person by or for whom the investigations were conducted.”
Thus, Section 505(b)(2) authorizes the FDA to approve an NDA based on safety and effectiveness data that were not
developed by the applicant. NDAs filed under Section 505(b)(2) may provide an alternate and potentially more expeditious
pathway to FDA approval for new or improved formulations or new uses of previously approved products. If the 505(b)(2)
applicant can establish that reliance on the FDA’s previous approval is scientifically appropriate, the applicant may
eliminate the need to conduct certain preclinical or clinical studies of the new product. The FDA may also require
companies to perform additional studies or measurements to support the change from the approved product. The FDA may
then approve the new drug candidate for all or some of the label indications for which the referenced product has been
approved, as well as for any new indication sought by the Section 505(b)(2) applicant.
If we obtain favorable results in our clinical trials, we plan to submit NDAs for our intracanalicular insert product
candidates under Section 505(b)(2).
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Abbreviated New Drug Applications for Generic Drugs
In 1984, with passage of the Hatch-Waxman Amendments to the FDCA, Congress authorized the FDA to approve
generic drugs that are the same as drugs previously approved by the FDA under the NDA provisions of the statute. To
obtain approval of a generic drug, an applicant must submit an abbreviated new drug application, or ANDA, to the agency.
In support of such applications, a generic manufacturer may rely on the preclinical and clinical testing previously
conducted for a drug product previously approved under an NDA, known as the reference listed drug, or RLD.
Specifically, in order for an ANDA to be approved, the FDA must find that the generic version is identical to the
RLD with respect to the active ingredients, the route of administration, the dosage form, and the strength of the drug. At the
same time, the FDA must also determine that the generic drug is “bioequivalent” to the innovator drug. Under the statute, a
generic drug is bioequivalent to an RLD if “the rate and extent of absorption of the drug do not show a significant
difference from the rate and extent of absorption of the listed drug.”
Upon approval of an ANDA, the FDA indicates whether the generic product is “therapeutically equivalent” to the
RLD in its publication “Approved Drug Products with Therapeutic Equivalence Evaluations,” also referred to as the
“Orange Book.” Physicians and pharmacists consider a therapeutic equivalent generic drug to be fully substitutable for the
RLD. In addition, by operation of certain state laws and numerous health insurance programs, the FDA’s designation of
therapeutic equivalence often results in substitution of the generic drug without the knowledge or consent of either the
prescribing physician or patient.
Under the Hatch-Waxman Amendments, the FDA may not approve an ANDA until any applicable period of non-
patent exclusivity for the RLD has expired. The FDCA provides a period of five years of non-patent data exclusivity for a
new drug containing a new chemical entity. An NCE is a drug that contains no active moiety that has previously been
approved by the FDA in any other NDA. An active moiety is the molecule or ion responsible for the physiological or
pharmacological action of the drug substance. In cases where such exclusivity has been granted, an ANDA may not be filed
with the FDA until the expiration of five years unless the submission is accompanied by a Paragraph IV certification, in
which case the applicant may submit its application four years following the original product approval. The FDCA also
provides for a period of three years of exclusivity if the NDA includes reports of one or more new clinical investigations,
other than bioavailability or bioequivalence studies, that were conducted by or for the applicant and are essential to the
approval of the application. This three-year exclusivity period often protects changes to a previously approved drug
product, such as a new dosage form, route of administration, combination or indication.
The FDCA also provides for a period of three years of exclusivity if the NDA includes reports of one or more new
clinical investigations, other than bioavailability or bioequivalence studies, that were conducted by or for the applicant and
are essential to the approval of the application. This three-year exclusivity period often protects changes to a previously
approved drug product, such as a new dosage form, route of administration, combination or indication. Three-year
exclusivity would be available for a drug product that contains a previously approved active moiety, provided the statutory
requirement for a new clinical investigation is satisfied. Unlike five-year NCE exclusivity, an award of three-year
exclusivity does not block the FDA from accepting ANDAs seeking approval for generic versions of the drug as of the date
of approval of the original drug product. The FDA typically makes decisions about awards of data exclusivity shortly
before a product is approved.
The FDA must establish a priority review track for certain generic drugs, requiring the FDA to review a drug
application within eight months for a drug that has three or fewer approved drugs listed in the Orange Book and is no
longer protected by any patent or regulatory exclusivities, or is on the FDA’s drug shortage list. The FDA is also authorized
to expedite review of “competitor generic therapies” or drugs with inadequate generic competition, including holding
meetings with or providing advice to the drug sponsor prior to submission of the application.
Hatch-Waxman Patent Certification and the 30-Month Stay
Upon approval of an NDA or a supplement thereto, NDA sponsors are required to list with the FDA each patent with
claims that cover the applicant’s product or an approved method of using the product. Each of the patents listed by the
NDA sponsor is published in the Orange Book. When an ANDA applicant files its application to the FDA, the applicant is
required to certify to the FDA concerning any patents listed for the reference product in the Orange Book, except for
patents covering methods of use for which the ANDA applicant is not seeking approval. To the extent that the
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Section 505(b)(2) applicant is relying on studies conducted for an already approved product, the applicant is required to
certify to the FDA concerning any patents listed for the approved product in the Orange Book to the same extent that an
ANDA applicant would.
Specifically, the applicant must certify with respect to each patent that:
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the required patent information has not been filed;
the listed patent has expired;
the listed patent has not expired, but will expire on a particular date and approval is sought after patent
expiration; or
the listed patent is invalid, unenforceable or will not be infringed by the new product.
A certification that the new product will not infringe the already approved product’s listed patents or that such patents
are invalid or unenforceable is called a Paragraph IV certification. If the applicant does not challenge the listed patents or
indicate that it is not seeking approval of a patented method of use, the ANDA application will not be approved until all the
listed patents claiming the referenced product have expired.
If the ANDA applicant or 505(b)(2) applicant has provided a Paragraph IV certification to the FDA, the applicant
must also send notice of the Paragraph IV certification to the NDA and patent holders once the ANDA has been accepted
for filing by the FDA. The NDA and patent holders may then initiate a patent infringement lawsuit in response to the notice
of the Paragraph IV certification. The filing of a patent infringement lawsuit within 45 days after the receipt of a Paragraph
IV certification automatically prevents the FDA from approving the ANDA until the earlier of 30 months after the receipt
of the Paragraph IV notice, expiration of the patent, or a decision in the infringement case that is favorable to the ANDA
applicant.
To the extent that the Section 505(b)(2) applicant is relying on trials conducted for an already approved product, the
applicant is required to certify to the FDA concerning any patents listed for the approved product in the Orange Book to the
same extent that an ANDA applicant would. As a result, approval of a Section 505(b)(2) NDA can be stalled until all the
listed patents claiming the referenced product have expired, until any non-patent exclusivity, such as exclusivity for
obtaining approval of a new chemical entity, listed in the Orange Book for the referenced product has expired, and, in the
case of a Paragraph IV certification and subsequent patent infringement suit, until the earlier of 30 months, settlement of
the lawsuit or a decision in the infringement case that is favorable to the Section 505(b)(2) applicant.
Biosimilars
The 2010 Patient Protection and Affordable Care Act, which was signed into law on March 23, 2010, or ACA,
included a subtitle called the Biologics Price Competition and Innovation Act of 2009 or BPCIA. That Act established a
regulatory scheme authorizing the FDA to approve biosimilars and interchangeable biosimilars. As of January 1, 2020, the
FDA has approved 26 biosimilar products for use in the United States. No interchangeable biosimilars, however, have
been approved. The FDA has issued several guidance documents outlining an approach to review and approval of
biosimilars. Additional guidance is expected to be finalized by FDA in the near term.
Under the BPCIA, a manufacturer may submit an application for licensure of a biologic product that is “biosimilar
to” or “interchangeable with” a previously approved biological product or “reference product.” In order for the FDA to
approve a biosimilar product, it must find that there are no clinically meaningful differences between the reference product
and proposed biosimilar product in terms of safety, purity, and potency. For the FDA to approve a biosimilar product as
interchangeable with a reference product, the agency must find that the biosimilar product can be expected to produce the
same clinical results as the reference product, and for products administered multiple times that the biologic and the
reference biologic may be switched after one has been previously administered without increasing safety risks or risks of
diminished efficacy relative to exclusive use of the reference biologic.
Under the BPCIA, an application for a biosimilar product may not be submitted to the FDA until four years
following the date of approval of the reference product. The FDA may not approve a biosimilar product until 12 years from
the date on which the reference product was approved. Even if a product is considered to be a reference product
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eligible for exclusivity, another company could market a competing version of that product if the FDA approves a full BLA
for such product containing the sponsor’s own preclinical data and data from adequate and well-controlled clinical trials to
demonstrate the safety, purity and potency of their product. The BPCIA also created certain exclusivity periods for
biosimilars approved as interchangeable products. At this juncture, it is unclear whether products deemed
“interchangeable” by the FDA will, in fact, be readily substituted by pharmacies, which are governed by state pharmacy
law.
Pediatric Studies and Exclusivity
Under the Pediatric Research Equity Act of 2003, an NDA or supplement thereto must contain data that are adequate
to assess the safety and effectiveness of the drug product for the claimed indications in all relevant pediatric
subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and
effective. With enactment of the Food and Drug Administration Safety and Innovation Act, or FDASIA, in 2012, sponsors
must also submit pediatric study plans prior to the assessment data. Those plans must contain an outline of the proposed
pediatric study or studies the applicant plans to conduct, including study objectives and design, any deferral or waiver
requests, and other information required by regulation. The applicant, the FDA, and the FDA’s internal review committee
must then review the information submitted, consult with each other, and agree upon a final plan. The FDA or the applicant
may request an amendment to the plan at any time. Unless otherwise required by regulation, the pediatric data requirements
do not apply to products with orphan designation.
The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of some or all
pediatric data until after approval of the product for use in adults, or full or partial waivers from the pediatric data
requirements. Additional requirements and procedures relating to deferral requests and requests for extension of deferrals
are contained in FDASIA. In addition, products that have received orphan designation are exempt from the requirements
of the Pediatric Research Equity Act.
Pediatric exclusivity is another type of non-patent marketing exclusivity in the United States and, if granted, provides
for the attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity,
including the non-patent exclusivity. This six-month exclusivity may be granted if an NDA sponsor submits pediatric data
that fairly respond to a written request from the FDA for such data. The data do not need to show the product to be
effective in the pediatric population studied; rather, if the clinical trial is deemed to fairly respond to the FDA’s request, the
additional protection is granted. If reports of requested pediatric studies are submitted to and accepted by the FDA within
the statutory time limits, whatever statutory or regulatory periods of exclusivity or patent protection cover the product are
extended by six months. This is not a patent term extension, but it effectively extends the regulatory period during which
the FDA cannot approve another application. With regard to patents, the six‑month pediatric exclusivity period will not
attach to any patents for which an ANDA or 505(b)(2) applicant submitted a paragraph IV patent certification, unless the
NDA sponsor or patent owner first obtains a court determination that the patent is valid and infringed by the proposed
product.
Patent Term Restoration and Extension
A patent claiming a new drug product may be eligible for a limited patent term extension under the Hatch-Waxman
Act, which permits a patent restoration of up to five years for patent term lost during product development and the FDA
regulatory review. The restoration period granted is typically one-half the time between the effective date of an IND and the
submission date of an NDA, plus the time between the submission date of an NDA and the ultimate approval date. Patent
term restoration cannot be used to extend the remaining term of a patent past a total of 14 years from the product’s approval
date. Only one patent applicable to an approved drug product is eligible for the extension, and the application for the
extension must be submitted prior to the expiration of the patent in question. A patent that covers multiple drugs for which
approval is sought can only be extended in connection with one of the approvals. The United States Patent and Trademark
Office reviews and approves the application for any patent term extension or restoration in consultation with the FDA.
Review and Approval of Medical Devices in the United States
Medical devices in the United States are strictly regulated by the FDA. Under the FDCA, a medical device is defined
as an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article,
including a component part, or accessory which is, among other things: intended for use in the diagnosis
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of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals; or
intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary
intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon
being metabolized for the achievement of any of its primary intended purposes. This definition provides a clear distinction
between a medical device and other FDA regulated products such as drugs. If the primary intended use of the product is
achieved through chemical action or by being metabolized by the body, the product is usually a drug. If not, it is generally a
medical device.
Unless an exemption applies, a new medical device may not be marketed in the United States unless and until it has
been cleared through filing of a 510(k) premarket notification, or 510(k), or approved by the FDA pursuant to a PMA
application. The information that must be submitted to the FDA in order to obtain clearance or approval to market a new
medical device varies depending on how the medical device is classified by the FDA. Medical devices are classified into
one of three classes on the basis of the controls deemed by the FDA to be necessary to reasonably ensure their safety and
effectiveness.
Class I devices are low risk devices for which reasonable assurance of safety and effectiveness can be provided by
adherence to the FDA’s general controls for medical devices, which include applicable portions of the FDA’s Quality
System Regulation, or QSR, facility registration and product listing, reporting of adverse medical events and malfunctions
and appropriate, truthful and non-misleading labeling, advertising and promotional materials. Many Class I devices are
exempt from premarket regulation; however, some Class I devices require premarket clearance by the FDA through the
510(k) premarket notification process.
Class II devices are moderate risk devices and are subject to the FDA’s general controls, and any other special
controls, such as performance standards, post-market surveillance, and FDA guidelines, deemed necessary by the FDA to
provide reasonable assurance of the devices’ safety and effectiveness. Premarket review and clearance by the FDA for
Class II devices are accomplished through the 510(k) premarket notification procedure, although some Class II devices are
exempt from the 510(k) requirements. Premarket notifications are subject to user fees, unless a specific exemption applies.
Class III devices are deemed by the FDA to pose the greatest risk, such as those for which reasonable assurance of
the device’s safety and effectiveness cannot be assured solely by the general controls and special controls described above
and that are life-sustaining or life-supporting. A PMA application must provide valid scientific evidence, typically
extensive preclinical and clinical trial data and information about the device and its components regarding, among other
things, device design, manufacturing and labeling. PMA applications (and supplemental PMA applications) are subject to
significantly higher user fees than are 510(k) premarket notifications.
510(k) Premarket Notification
To obtain 510(k) clearance, a manufacturer must submit a premarket notification demonstrating that the proposed
device is “substantially equivalent” to a predicate device, which is a previously cleared 510(k) device or a pre-amendment
device that was in commercial distribution before May 28, 1976, for which the FDA has not yet called for the submission
of a PMA application. The FDA’s 510(k) clearance pathway usually takes from three to 12 months from the date the
application is submitted and filed with the FDA, but it can take significantly longer and clearance is never assured. The
FDA has issued guidance documents meant to expedite review of a 510(k) and facilitate interactions between applicants
and the agency. To demonstrate substantial equivalence, a manufacturer must show that the device has the same intended
use as a predicate device and the same technological characteristics, or the same intended use and different technological
characteristics and does not raise new questions of safety and effectiveness than the predicate device.
Most 510(k)s do not require clinical data for clearance, but the FDA may request such data.
The FDA seeks to review and act on a 510(k) within 90 days of submission, but it may take longer if the agency finds
that it requires more information to review the 510(k). If the FDA determines that the device is substantially equivalent to a
predicate device, the subject device may be marketed. However, if the FDA concludes that a new device is not substantially
equivalent to a predicate device, the new device will be classified in Class III and the manufacturer will be required to
submit a PMA application to market the product. Devices of a new type that the FDA has not previously classified based
on risk are automatically classified into Class III by operation of section 513(f)(1) of the
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FDCA, regardless of the level of risk they pose. To avoid requiring PMA review of low- to moderate-risk devices classified
in Class III by operation of law, Congress enacted section 513(f)(2) of the FDCA. This provision allows the FDA to
classify a low- to moderate-risk device not previously classified into Class I or II, a process known as the de novo process.
A company may apply directly to the FDA for classification of its device as de novo or may submit a de novo petition
within 30 days of receiving a not substantially equivalent determination.
Modifications to a 510(k)-cleared medical device may require the submission of another 510(k). Modifications to a
510(k)-cleared device frequently require the submission of a traditional 510(k), but modifications meeting certain
conditions may be candidates for FDA review under a Special 510(k). If a device modification requires the submission of a
510(k), but the modification does not affect the intended use of the device or alter the fundamental technology of the
device, then summary information that results from the design control process associated with the cleared device can serve
as the basis for clearing the application. A Special 510(k) allows a manufacturer to declare conformance to design controls
without providing new data. When the modification involves a change in material, the nature of the “new” material will
determine whether a traditional or Special 510(k) is necessary.
Any modification to a 510(k)-cleared product that would constitute a major change in its intended use or any change
that could significantly affect the safety or effectiveness of the device may, in some circumstances, requires the submission
of a PMA application, if the change raises complex or novel scientific issues or the product has a new intended use. A
manufacturer may be required to submit extensive pre-clinical and clinical data depending on the nature of the changes.
The FDA requires every manufacturer to make the determination regarding the need for a new 510(k) submission in
the first instance, but the FDA may review any manufacturer’s decision. If the FDA disagrees with the manufacturer’s
determination and requires new 510(k) clearances or PMA application approvals for modifications to previously cleared
products for which the manufacturer concluded that new clearances or approvals are unnecessary, the manufacturer may be
required to cease marketing or distribution of the products or to recall the modified product until it obtains clearance or
approval, and the manufacturer may be subject to significant regulatory fines or penalties. In addition, the FDA is currently
evaluating the 510(k) process and may make substantial changes to industry requirements.
Premarket Approval Application
The PMA application process for approval to market a medical device is more complex, costly, and time- consuming
than the 510(k) clearance procedure. A PMA application must be supported by extensive data, including technical
information regarding device design and development, preclinical studies, clinical trials, manufacturing and controls
information and labeling information that demonstrate the safety and effectiveness of the device for its intended use. After
a PMA application is submitted, the FDA has 45 days to determine whether it is sufficiently complete to permit a
substantive review. If the PMA application is complete, the FDA will file the PMA application. If the FDA accepts the
application for filing, the agency will begin an in-depth substantive review of the application. By statute, the FDA has 180
days to review the application although, generally, review of the application often takes between one and three years, and
may take significantly longer. If the FDA has questions, it will likely issue a first major deficiency letter within 150 days of
filing. It may also refer the PMA application to an FDA advisory panel for additional review, and will conduct a
preapproval inspection of the manufacturing facility to ensure compliance with the QSR, either of which could extend the
180-day response target. In addition, the FDA may request additional information or request the performance of additional
clinical trials in which case the PMA application approval may be delayed while the trials are conducted and the data
acquired are submitted in an amendment to the PMA. Even with additional trials, the FDA may not approve the PMA
application.
If the FDA’s evaluations of both the PMA application and the manufacturing facilities are favorable, the FDA will
either issue an approval letter authorizing commercial marketing or an approvable letter that usually contains a number of
conditions that must be met in order to secure final approval. If the FDA’s evaluations are not favorable, the FDA will deny
approval of the PMA application or issue a not approvable letter. The PMA application process, including the gathering of
clinical and nonclinical data and the submission to and review by the FDA, can take several years, and the process can be
expensive and uncertain. Moreover, even if the FDA approves a PMA application, the FDA may approve the device with
an indication that is narrower or more limited than originally sought. The FDA can impose post-approval conditions that it
believes necessary to ensure the safety and effectiveness of the device, including, among other things, restrictions on
labeling, promotion, sale and distribution. After approval of a PMA application, a new PMA application or PMA
application supplement may be required for a modification to the device, its labeling, or its manufacturing
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process. PMA application supplements often require submission of the same type of information as an initial PMA
application, except that the supplement is limited to information needed to support any changes from the device covered by
the approved PMA application and may or may not require as extensive technical or clinical data or the convening of an
advisory panel. The time for review of a PMA application supplement may vary depending on the type of change, but it can
be lengthy. In addition, in some cases the FDA might require additional clinical data.
PMA applications are subject to an application fee. For federal fiscal year 2020, the standard fee is $340,995 and the
small business fee is $85,249.
Investigational Device Exemption
A clinical trial is typically required for a PMA application and, in a small percentage of cases, the FDA may require a
clinical study in support of a 510(k) submission. A manufacturer that wishes to conduct a clinical study involving the
device is subject to the FDA’s IDE regulation. The IDE regulation distinguishes between significant and non-significant
risk device studies and the procedures for obtaining approval to begin the study differ accordingly. Also, some types of
studies are exempt from the IDE regulations. A significant risk device presents a potential for serious risk to the health,
safety, or welfare of a subject. Significant risk devices are devices that are substantially important in diagnosing, curing,
mitigating, or treating disease or in preventing impairment to human health. Studies of devices that pose a significant risk
require both FDA and an IRB approval prior to initiation of a clinical study. Non-significant risk devices are devices that do
not pose a significant risk to the human subjects. A non-significant risk device study requires only IRB approval prior to
initiation of a clinical study.
An IDE application must be supported by appropriate data, such as animal and laboratory testing results, showing
that it is safe to test the device in humans and that the testing protocol is scientifically sound. An IDE application is
considered approved 30 days after it has been received by the FDA, unless the FDA otherwise informs the sponsor prior to
30 calendar days from the date of receipt, that the IDE is approved, approved with conditions, or disapproved. The FDA
typically grants IDE approval for a specified number of subjects to be enrolled at specified study centers. The clinical trial
must be conducted in accordance with applicable regulations, including but not limited to the FDA’s IDE regulations and
GCP. The investigators must obtain subject informed consent, rigorously follow the investigational plan and study protocol,
control the disposition of investigational devices, and comply with all reporting and record keeping requirements. A
clinical trial may be suspended or terminated by the FDA, the IRB or the sponsor at any time for various reasons, including
a belief that the risks to the study participants outweigh the benefits of participation in the trial. Approval of an IDE does
not bind the FDA to accept the results of the trial as sufficient to prove the product’s safety and efficacy, even if the trial
meets its intended success criteria.
Post-Marketing Restrictions and Enforcement
After a device is placed on the market, numerous regulatory requirements apply. These include but are not limited to:
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submitting and updating establishment registration and device listings with the FDA;
compliance with the QSR, which require manufacturers to follow stringent design, testing, control,
documentation, record maintenance, including maintenance of complaint and related investigation files, and
other quality assurance controls during the manufacturing process;
unannounced routine or for-cause device inspections by the FDA, which may include our suppliers’ facilities
labeling regulations, which prohibit the promotion of products for uncleared or unapproved or “off-label” uses
and impose other restrictions on labeling; and
post-approval restrictions or conditions, including requirements to conduct post-market surveillance studies to
establish continued safety data or tracking products through the chain of distribution to the patient level.
Under the FDA medical device reporting, or MDR, regulations, medical device manufacturers are required to report
to the FDA information that a device has or may have caused or contributed to a death or serious injury or has
malfunctioned in a way that would likely cause or contribute to death or serious injury if the malfunction of the device or
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a similar device of such manufacturer were to recur. The decision to file an MDR involves a judgment by the manufacturer.
If the FDA disagrees with the manufacturer’s determination, the FDA can take enforcement action.
Additionally, the FDA has the authority to require the recall of commercialized products in the event of material
deficiencies or defects in design or manufacture. The authority to require a recall must be based on an FDA finding that
there is reasonable probability that the device would cause serious injury or death. Manufacturers may, under their own
initiative, recall a product if any material deficiency in a device is found. The FDA requires that certain classifications of
recalls be reported to the FDA within 10 working days after the recall is initiated.
The failure to comply with applicable regulatory requirements can result in enforcement action by the FDA, which
may include any of the following sanctions:
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untitled letters, warning letters, fines, injunctions or civil penalties;
recalls, detentions or seizures of products;
operating restrictions;
delays in the introduction of products into the market;
total or partial suspension of production;
delay or refusal of the FDA or other regulators to grant 510(k) clearance or PMA application approvals of new
products;
withdrawals of 510(k) clearance or PMA application approvals; or
in the most serious cases, criminal prosecution.
To ensure compliance with regulatory requirements, medical device manufacturers are subject to market surveillance
and periodic, pre-scheduled and unannounced inspections by the FDA, and these inspections may include the
manufacturing facilities of subcontractors.
Review and Approval of Combination Products in the United States
Certain products may be comprised of components that would normally be regulated under different types of
regulatory authorities, and frequently by different Centers at the FDA. These products are known as combination products.
Specifically, under regulations issued by the FDA, a combination product may be:
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a product comprised of two or more regulated components that are physically, chemically, or otherwise
combined or mixed and produced as a single entity;
two or more separate products packaged together in a single package or as a unit and comprised of drug and
device products;
a drug or device packaged separately that according to its investigational plan or proposed labeling is intended
for use only with an approved individually specified drug or device where both are required to achieve the
intended use, indication, or effect and where upon approval of the proposed product the labeling of the approved
product would need to be changed, e.g., to reflect a change in intended use, dosage form, strength, route of
administration, or significant change in dose; or
any investigational drug or device packaged separately that according to its proposed labeling is for use only
with another individually specified investigational drug, device, or biological product where both are required to
achieve the intended use, indication, or effect.
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Under the FDCA, the FDA is charged with assigning a center with primary jurisdiction, or a lead center, for review
of a combination product. That determination is based on the “primary mode of action” of the combination product. Thus,
if the primary mode of action of a device-drug combination product is attributable to the drug product, the FDA Center
responsible for premarket review of the drug product would have primary jurisdiction for the combination product. The
FDA has also established an Office of Combination Products to address issues surrounding combination products and
provide more certainty to the regulatory review process. That office serves as a focal point for combination product issues
for agency reviewers and industry. It is also responsible for developing guidance and regulations to clarify the regulation of
combination products, and for assignment of the FDA center that has primary jurisdiction for review of combination
products where the jurisdiction is unclear or in dispute.
Review and Approval of Drug Products in the European Union
In order to market any product outside of the United States, a company must also comply with numerous and varying
regulatory requirements of other countries and jurisdictions regarding quality, safety and efficacy and governing, among
other things, clinical trials, marketing authorization, commercial sales and distribution of drug products. Whether or not it
obtains FDA approval for a product, the company would need to obtain the necessary approvals by the comparable foreign
regulatory authorities before it can commence clinical trials or marketing of the product in those countries or jurisdictions.
The approval process ultimately varies between countries and jurisdictions and can involve additional product testing and
additional administrative review periods. The time required to obtain approval in other countries and jurisdictions might
differ from and be longer than that required to obtain FDA approval. Regulatory approval in one country or jurisdiction
does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country or
jurisdiction may negatively impact the regulatory process in others.
Clinical Trial Approval
Pursuant to the European Clinical Trials Directive, a system for the approval of clinical trials in the European Union
has been implemented through national legislation of the member states. Under this system, an applicant must obtain
approval from the competent national authority of a European Union member state in which the clinical trial is to be
conducted. Furthermore, the applicant may only start a clinical trial after a competent ethics committee has issued a
favorable opinion. Clinical trial application must be accompanied by an investigational medicinal product dossier with
supporting information prescribed by the European Clinical Trials Directive and corresponding national laws of the
member states and further detailed in applicable guidance documents.
In April 2014, the EU adopted a new Clinical Trials Regulation, which is set to replace the current Clinical Trials
Directive. The new Clinical Trials Regulation will be directly applicable to and binding in all 28 EU Member States
without the need for any national implementing legislation. Under the new coordinated procedure for the approval of
clinical trials, the sponsor of a clinical trial will be required to submit a single application for approval of a clinical trial to a
reporting EU Member State (RMS) through an EU Portal. The submission procedure will be the same irrespective of
whether the clinical trial is to be conducted in a single EU Member State or in more than one EU Member State. The
Clinical Trials Regulation also aims to streamline and simplify the rules on safety reporting for clinical trials.
As of January 1, 2020, the website of the European Commission reported that the implementation of the Clinical
Trials Regulation was dependent on the development of a fully functional clinical trials portal and database, which would
be confirmed by an independent audit, and that the new legislation would come into effect six months after the European
Commission publishes a notice of this confirmation. The website indicated that the audit was expected to commence in
December 2020.
Marketing Authorization
To obtain marketing approval of a drug under European Union regulatory systems, an applicant must submit a
marketing authorization application, or MAA, either under a centralized or decentralized procedure. The centralized
procedure provides for the grant of a single marketing authorization by the European Commission that is valid for all
European Union member states. The centralized procedure is compulsory for specific products, including for medicines
produced by certain biotechnological processes, products designated as orphan medicinal products, advanced therapy
products and products with a new active substance indicated for the treatment of certain diseases. For products with a new
active substance indicated for the treatment of other diseases and products that are highly innovative or for which a
centralized process is in the interest of patients, the centralized procedure may be optional.
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Under the centralized procedure, the Committee for Medicinal Products for Human Use, or the CHMP, established at
the European Medicines Agency, or EMA, is responsible for conducting the initial assessment of a drug. The CHMP is also
responsible for several post-authorization and maintenance activities, such as the assessment of modifications or extensions
to an existing marketing authorization. Under the centralized procedure in the European Union, the maximum timeframe
for the evaluation of an MAA is 210 days, excluding clock stops, when additional information or written or oral
explanation is to be provided by the applicant in response to questions of the CHMP. Accelerated evaluation might be
granted by the CHMP in exceptional cases, when a medicinal product is of major interest from the point of view of public
health and in particular from the viewpoint of therapeutic innovation. In this circumstance, the EMA ensures that the
opinion of the CHMP is given within 150 days.
The decentralized procedure is available to applicants who wish to market a product in various European Union
member states where such product has not received marketing approval in any European Union member states before. The
decentralized procedure provides for approval by one or more other, or concerned, member states of an assessment of an
application performed by one member state designated by the applicant, known as the reference member state. Under this
procedure, an applicant submits an application based on identical dossiers and related materials, including a draft summary
of product characteristics, and draft labeling and package leaflet, to the reference member state and concerned member
states. The reference member state prepares a draft assessment report and drafts of the related materials within 210 days
after receipt of a valid application. Within 90 days of receiving the reference member state’s assessment report and related
materials, each concerned member state must decide whether to approve the assessment report and related materials.
If a member state cannot approve the assessment report and related materials on the grounds of potential serious risk
to public health, the disputed points are subject to a dispute resolution mechanism and may eventually be referred to the
European Commission, whose decision is binding on all member states.
Regulatory Data Protection in the European Union
In the EU, innovative medicinal products approved on the basis of a complete independent data package qualify for
eight years of data exclusivity upon marketing authorization and an additional two years of market exclusivity pursuant to
Directive 2001/83/EC. Regulation (EC) No 726/2004 repeats this entitlement for medicinal products authorized in
accordance the centralized authorization procedure. Data exclusivity prevents applicants for authorization of generics of
these innovative products from referencing the innovator’s data to assess a generic (abridged) application for a period of
eight years. During an additional two-year period of market exclusivity, a generic marketing authorization application can
be submitted and authorized, and the innovator’s data may be referenced, but no generic medicinal product can be placed
on the EU market until the expiration of the market exclusivity. The overall ten-year period will be extended to a maximum
of 11 years if, during the first eight years of those ten years, the marketing authorization holder obtains an authorization for
one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to
bring a significant clinical benefit in comparison with existing therapies. Even if a compound is considered to be a new
chemical entity so that the innovator gains the prescribed period of data exclusivity, another company nevertheless could
also market another version of the product if such company obtained marketing authorization based on an MAA with a
complete independent data package of pharmaceutical tests, preclinical tests and clinical trials.
Periods of Authorization and Renewals
A marketing authorization has an initial validity for five years in principle. The marketing authorization may be
renewed after five years on the basis of a re-evaluation of the risk-benefit balance by the EMA or by the competent
authority of the EU Member State. To this end, the marketing authorization holder must provide the EMA or the competent
authority with a consolidated version of the file in respect of quality, safety and efficacy, including all variations introduced
since the marketing authorization was granted, at least six months before the marketing authorization ceases to be valid.
The European Commission or the competent authorities of the EU Member States may decide, on justified grounds relating
to pharmacovigilance, to proceed with one further five-year period of marketing authorization. Once subsequently
definitively renewed, the marketing authorization shall be valid for an unlimited period. Any authorization which is not
followed by the actual placing of the medicinal product on the European Union market (in case of centralized procedure) or
on the market of the authorizing EU Member State within three years after authorization ceases to be valid (the so-called
sunset clause).
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Regulatory Requirements after a Marketing Authorization has been Obtained
In case an authorization for a medicinal product in the EU is obtained, the holder of the marketing authorization is
required to comply with a range of requirements applicable to the manufacturing, marketing, promotion and sale of
medicinal products. These include:
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Compliance with the EU’s stringent pharmacovigilance or safety reporting rules must be ensured. These rules
can impose post-authorization studies and additional monitoring obligations.
The manufacturing of authorized medicinal products, for which a separate manufacturer’s license is mandatory,
must also be conducted in strict compliance with the applicable EU laws, regulations and guidance, including
Directive 2001/83/EC, Directive 2003/94/EC, Regulation (EC) No 726/2004 and the European Commission
Guidelines for Good Manufacturing Practice. These requirements include compliance with EU cGMP standards
when manufacturing medicinal products and active pharmaceutical ingredients, including the manufacture of
active pharmaceutical ingredients outside of the EU with the intention to import the active pharmaceutical
ingredients into the EU.
The marketing and promotion of authorized drugs, including industry-sponsored continuing medical education
and advertising directed toward the prescribers of drugs and/or the general public, are strictly regulated in the EU
notably under Directive 2001/83EC, as amended, and EU Member State laws. Direct-to-consumer advertising
of prescription medicines is prohibited across the EU.
Review and Approval of Medical Devices in the European Union
The European Union has adopted numerous directives and standards regulating, among other things, the design,
manufacture, clinical trials, labeling, approval and adverse event reporting for medical devices. In the EU, medical devices
must comply with the Essential Requirements in Annex I to the EU Medical Devices Directive (Council Directive
93/42/EEC), or the Essential Requirements. Compliance with these requirements is a prerequisite to be able to affix the CE
Mark of Conformity to medical devices, without which they cannot be marketed or sold in the European Economic Area, or
EEA, comprised of the European Union member states plus Norway, Iceland, and Liechtenstein. Actual implementation of
these directives, however, may vary on a country-by-country basis.
To demonstrate compliance with the Essential Requirements a manufacturer must undergo a conformity assessment
procedure, which varies according to the type of medical device and its classification. Except for low risk medical devices,
where the manufacturer can issue a CE Declaration of Conformity based on a self-assessment of the conformity of its
products with the Essential Requirements, a conformity assessment procedure requires the intervention of a third-party
organization designated by competent authorities of a European Union country to conduct conformity assessments, or a
Notified Body. Notified Bodies are independent testing houses, laboratories, or product certifiers typically based within the
European Union and authorized by the European member states to perform the required conformity assessment tasks, such
as quality system audits and device compliance testing. The Notified Body would typically audit and examine the product’s
Technical File and the quality system for the manufacture, design and final inspection of the product before issuing a CE
Certificate of Conformity demonstrating compliance with the relevant Essential Requirements.
Medical device manufacturers must carry out a clinical evaluation of their medical devices to demonstrate conformity
with the relevant Essential Requirements. This clinical evaluation is part of the product’s Technical File. A clinical
evaluation includes an assessment of whether a medical device’s performance is in accordance with its intended use, and
that the known and foreseeable risks linked to the use of the device under normal conditions are minimized and acceptable
when weighed against the benefits of its intended purpose. The clinical evaluation conducted by the manufacturer must also
address any clinical claims, the adequacy of the device labeling and information (particularly claims, contraindications,
precautions and warnings) and the suitability of related Instructions for Use. This assessment must be based on clinical
data, which can be obtained from clinical studies conducted on the devices being assessed, scientific literature from similar
devices whose equivalence with the assessed device can be demonstrated or both clinical studies and scientific literature.
With respect to implantable devices or devices classified as Class III in the European Union, the manufacturer must
conduct clinical studies to obtain the required clinical data, unless relying on existing clinical data from similar
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devices can be justified. As part of the conformity assessment process, depending on the type of devices, the Notified Body
will review the manufacturer’s clinical evaluation process, assess the clinical evaluation data of a representative sample of
the device’s subcategory or generic group, or assess all the clinical evaluation data, verify the manufacturer’s assessment of
that data and assess the validity of the clinical evaluation report and the conclusions drawn by the manufacturer.
Even after a manufacturer receives a CE Certificate of Conformity enabling the CE mark to be placed on it products
and the right to sell the products in the EEA countries, a Notified Body or a competent authority may require post-
marketing studies of the products. Failure to comply with such requirements in a timely manner could result in the
withdrawal of the CE Certificate of Conformity and the recall or withdrawal of the subject product from the European
market.
A manufacturer must inform the Notified Body that carried out the conformity assessment of the medical devices of
any planned substantial changes to the devices which could affect compliance with the Essential Requirements or the
devices’ intended purpose. The Notified Body will then assess the changes and verify whether they affect the product’s
conformity with the Essential Requirements or the conditions for the use of the devices. If the assessment is favorable, the
Notified Body will issue a new CE Certificate of Conformity or an addendum to the existing CE Certificate of Conformity
attesting compliance with the Essential Requirements. If it is not, the manufacturer may not be able to continue to market
and sell the product in the EEA.
In the European Union, medical devices may be promoted only for the intended purpose for which the devices have
been CE marked. Failure to comply with this requirement could lead to the imposition of penalties by the competent
authorities of the European Union Member States. The penalties could include warnings, orders to discontinue the
promotion of the medical device, seizure of the promotional materials and fines. Promotional materials must also comply
with various laws and codes of conduct developed by medical device industry bodies in the European Union governing
promotional claims, comparative advertising, advertising of medical devices reimbursed by the national health insurance
systems and advertising to the general public.
Additionally, all manufacturers placing medical devices in the market in the European Union are legally bound to
report any serious or potentially serious incidents involving devices they produce or sell to the competent authority in
whose jurisdiction the incident occurred. In the European Union, manufacturers must comply with the EU Medical Device
Vigilance System. Under this system, incidents must be reported to the relevant authorities of the European Union
countries, and manufacturers are required to take Field Safety Corrective Actions, or FSCAs, to reduce a risk of death or
serious deterioration in the state of health associated with the use of a medical device that is already placed on the market.
An incident is defined as any malfunction or deterioration in the characteristics and/or performance of a device, as well as
any inadequacy in the labeling or the instructions for use which, directly or indirectly, might lead to or might have led to
the death of a patient or user or of other persons or to a serious deterioration in their state of health. An FSCA may include
the recall, modification, exchange, destruction or retrofitting of the device. FSCAs must be communicated by the
manufacturer or its European Authorized Representative to its customers and to the end users of the device through Field
Safety Notices. In September 2012, the European Commission adopted a proposal for a regulation which, if adopted, will
change the way that most medical devices are regulated in the European Union, and may subject products to additional
requirements.
Brexit and the Regulatory Framework in the United Kingdom
On June 23, 2016, the electorate in the United Kingdom voted in favor of leaving the European Union, commonly
referred to as Brexit. Following protracted negotiations, the United Kingdom left the European Union on January 31, 2020.
Under the withdrawal agreement, there is a transitional period until December 31, 2020 (extendable up to two years).
Discussions between the United Kingdom and the European Union have so far mainly focused on finalizing withdrawal
issues and transition agreements but have been extremely difficult to date. To date, only an outline of a trade agreement has
been reached. Much remains open but the Prime Minister has indicated that the United Kingdom will not seek to extend
the transitional period beyond the end of 2020. If no trade agreement has been reached before the end of the transitional
period, there may be significant market and economic disruption. The Prime Minister has also indicated that the UK will
not accept high regulatory alignment with the EU.
Since the regulatory framework for medical products in the United Kingdom covering quality, safety, and efficacy of
medical products, clinical trials, marketing authorization, commercial sales, and distribution of medical products is
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derived from European Union directives and regulations, Brexit could materially impact the future regulatory regime that
applies to products and the approval of product candidates in the United Kingdom. Any delay in obtaining, or an inability
to obtain, any marketing approvals, as a result of Brexit or otherwise, may force us to restrict or delay efforts to seek
regulatory approval in the United Kingdom and/or European Union for our product candidates, which could significantly
and materially harm our business.
General Data Protection Regulation
The collection, use, disclosure, transfer, or other processing of personal data regarding individuals in the EU,
including personal health data, is subject to the EU General Data Protection Regulation, or GDPR, which became effective
on May 25, 2018. The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process
personal data, including requirements relating to processing health and other sensitive data, obtaining consent of the
individuals to whom the personal data relates, providing information to individuals regarding data processing activities,
implementing safeguards to protect the security and confidentiality of personal data, providing notification of data
breaches, and taking certain measures when engaging third-party processors. The GDPR also imposes strict rules on the
transfer of personal data to countries outside the EU, including the United States, and permits data protection authorities to
impose large penalties for violations of the GDPR, including potential fines of up to €20 million or 4% of annual global
revenues, whichever is greater. The GDPR also confers a private right of action on data subjects and consumer associations
to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting
from violations of the GDPR. Compliance with the GDPR will be a rigorous and time-intensive process that may increase
the cost of doing business or require companies to change their business practices to ensure full compliance.
Pharmaceutical Coverage, Pricing and Reimbursement
Significant uncertainty exists as to the coverage and reimbursement status of products approved by the FDA and
other government authorities. Sales of products will depend, in part, on the extent to which the costs of the products will be
covered by third-party payors, including government health programs in the United States such as Medicare and Medicaid,
commercial health insurers and managed care organizations. The process for determining whether a payor will provide
coverage for a product may be separate from the process for setting the price or reimbursement rate that the payor will pay
for the product once coverage is approved. Third-party payors may limit coverage to specific products on an approved list,
or formulary, which might not include all of the approved products for a particular indication. Additionally, the
containment of healthcare costs has become a priority of federal and state governments, and the prices of drugs have been a
focus in this effort. The U.S. government, state legislatures and foreign governments have shown significant interest in
implementing cost-containment programs, including price controls, restrictions on reimbursement and requirements for
substitution of generic products. Adoption of price controls and cost-containment measures, and adoption of more
restrictive policies in jurisdictions with existing controls and measures, could further limit our net revenue and results.
In order to secure coverage and reimbursement for any product that might be approved for sale, a company may need
to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of the
product, in addition to the costs required to obtain FDA or other comparable regulatory approvals. A payor’s decision to
provide coverage for a product does not imply that an adequate reimbursement rate will be approved. Third-party
reimbursement may not be sufficient to maintain price levels high enough to realize an appropriate return on investment in
product development.
Section 1833(t)(6) of the Social Security Act provides for temporary additional payments or “transitional pass-
through payments” for certain drugs and biological agents. As originally enacted by the Balanced Budget Refinement Act
of 1999, this provision required Centers for Medicare & Medicaid Services, or CMS, to make additional payments to
hospitals for current orphan drugs, as designated under section 526 of the FDCA; current drugs and biological agents and
brachytherapy sources used for the treatment of cancer; and current radiopharmaceutical drugs and biological products.
Transitional pass-through payments are also provided for certain new drugs, devices and biological agents that were not
paid for as a hospital outpatient department service as of December 31, 1996, and whose cost is “not insignificant” in
relation to the Outpatient Prospective Payment System payment for the procedures or services associated with the new
drug, device, or biological. Under the statute, transitional pass-through payments can be made for at least two years but not
more than three years.
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We applied for a transitional pass-through reimbursement status, or C-code, on November 30, 2018 for DEXTENZA
from the Centers for Medicare and Medicaid Services, or CMS. In May 2019, we received formal notification from CMS
that it had approved transitional pass-through payment status and established a new C-Code for DEXTENZA that
subsequently became effective on July 1, 2019. We expected pricing for DEXTENZA while in pass-through status to be
approximately $538 per surgery, and we expected pass-through status would remain in effect for up to three years from the
effective date of the C-code, or July 1, 2019. We also submitted an application to the CMS for a J-Code for DEXTENZA
on December 28, 2018, and received a specific and permanent J-Code in July 2019 which became effective on October 1,
2019. With the effectiveness of our permanent J-Code as of October 1, 2019, our C-code is no longer in effect.
In the European Union, pricing and reimbursement schemes vary widely from country to country. Some countries
provide that drug products may be marketed only after a reimbursement price has been agreed. Some countries may require
the completion of additional studies that compare the cost-effectiveness of a particular product candidate to currently
available therapies. For example, the European Union provides options for its member states to restrict the range of drug
products for which their national health insurance systems provide reimbursement and to control the prices of medicinal
products for human use. European Union member states may approve a specific price for a drug product or it may instead
adopt a system of direct or indirect controls on the profitability of the company placing the drug product on the market.
Other member states allow companies to fix their own prices for drug products, but monitor and control company profits.
The downward pressure on health care costs in general, particularly prescription drugs, has become intense. As a result,
increasingly high barriers are being erected to the entry of new products. In addition, in some countries, cross-border
imports from low-priced markets exert competitive pressure that may reduce pricing within a country. Any country that has
price controls or reimbursement limitations for drug products may not allow favorable reimbursement and pricing
arrangements.
Healthcare Law and Regulation
Healthcare providers, physicians and third-party payors play a primary role in the recommendation and prescription
of drug products that are granted marketing approval. Arrangements with providers, consultants, third-party payors and
customers are subject to broadly applicable fraud and abuse and other healthcare laws and regulations. Such restrictions
under applicable federal and state healthcare laws and regulations, include the following:
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the federal Anti-Kickback Statute prohibits, among other things, persons from knowingly and willfully
soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or
reward either the referral of an individual for, or the purchase, order or recommendation of, any good or service,
for which payment may be made, in whole or in part, under a federal healthcare program such as Medicare and
Medicaid;
the federal False Claims Act imposes civil penalties, and provides for civil whistleblower or qui tam actions,
against individuals or entities for knowingly presenting, or causing to be presented, to the federal government,
claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an
obligation to pay money to the federal government;
the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes criminal and civil
liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to
healthcare matters;
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act and its
implementing regulations, including the Final Omnibus Rule published in January 2013, also imposes
obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and
transmission of individually identifiable health information;
the federal false statements statute prohibits knowingly and willfully falsifying, concealing or covering up a
material fact or making any materially false statement in connection with the delivery of or payment for
healthcare benefits, items or services;
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the Foreign Corrupt Practices Act, or FCPA, which prohibits companies and their intermediaries from making, or
offering or promising to make improper payments to non-U.S. officials for the purpose of obtaining or retaining
business or otherwise seeking favorable treatment;
the federal transparency requirements under the ACA, known as the federal Physician Payments Sunshine Act,
will require certain manufacturers of drugs, devices, biologics and medical supplies to report to CMS within the
Department of Health and Human Services information related to payments and other transfers of value to
physicians and teaching hospitals and physician ownership and investment interests held by physicians and their
immediate family members; and
analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, may apply to
sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-
governmental third-party payors, including private insurers.
Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary
compliance guidelines and the relevant compliance guidance promulgated by the federal government in addition to
requiring drug manufacturers to report information related to payments to physicians and other health care providers or
marketing expenditures. State and foreign laws also govern the privacy and security of health information in some
circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus
complicating compliance efforts.
Healthcare Reform
A primary trend in the United States healthcare industry and elsewhere is cost containment. There have been a
number of federal and state proposals during the last few years regarding the pricing of pharmaceutical and
biopharmaceutical products, limiting coverage and reimbursement for drugs and other medical products, government
control and other changes to the healthcare system in the United States.
In March 2010, the United States Congress enacted the Patient Protection and Affordable Care Act, or ACA, which,
among other things, includes changes to the coverage and payment for products under government health care programs.
Among the provisions of ACA of importance to potential drug candidates are:
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an annual, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs and
biologic agents, apportioned among these entities according to their market share in certain government
healthcare programs, although this fee would not apply to sales of certain products approved exclusively for
orphan indications;
expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid
coverage to certain individuals with income at or below 133% of the federal poverty level, thereby potentially
increasing a manufacturer’s Medicaid rebate liability;
expanded manufacturers’ rebate liability under the Medicaid Drug Rebate Program by increasing the minimum
rebate for both branded and generic drugs and revising the definition of “average manufacturer price,” or AMP,
for calculating and reporting Medicaid drug rebates on outpatient prescription drug prices and extending rebate
liability to prescriptions for individuals enrolled in Medicare Advantage plans;
addressed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate
Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected;
expanded the types of entities eligible for the 340B drug discount program;
established the Medicare Part D coverage gap discount program by requiring manufacturers to provide a 50%
point-of-sale-discount off the negotiated price of applicable brand drugs to eligible beneficiaries during their
coverage gap period as a condition for the manufacturers’ outpatient drugs to be covered under Medicare Part D;
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a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative
clinical effectiveness research, along with funding for such research;
the Independent Payment Advisory Board, or IPAB, which has authority to recommend certain changes to the
Medicare program to reduce expenditures by the program that could result in reduced payments for prescription
drugs. However, the IPAB implementation has been not been clearly defined. ACA provided that under certain
circumstances, IPAB recommendations will become law unless Congress enacts legislation that will achieve the
same or greater Medicare cost savings; and
established the Center for Medicare and Medicaid Innovation within CMS to test innovative payment and
service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug
spending. Funding has been allocated to support the mission of the Center for Medicare and Medicaid
Innovation from 2011 to 2019.
Other legislative changes have been proposed and adopted in the United States since ACA was enacted. For example,
in August 2011, the Budget Control Act of 2011, among other things, created measures for spending reductions by
Congress. A Joint Select Committee on Deficit Reduction, tasked with recommending a targeted deficit reduction of at
least $1.2 trillion for the years 2012 through 2021, was unable to reach required goals, thereby triggering the legislation’s
automatic reduction to several government programs. This includes aggregate reductions of Medicare payments to
providers of up to 2% per fiscal year, which went into effect in April 2013 and will remain in effect through 2024 unless
additional Congressional action is taken. In January 2013, President Obama signed into law the American Taxpayer Relief
Act of 2012, which, among other things, further reduced Medicare payments to several providers, including hospitals,
imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover
overpayments to providers from three to five years. These laws may result in additional reductions in Medicare and other
healthcare funding and otherwise affect the prices we may obtain for any of our product candidates for which we may
obtain regulatory approval or the frequency with which any such product candidate is prescribed or used.
Since enactment of the ACA, there have been numerous legal challenges and Congressional actions to repeal and
replace provisions of the law. For example, with enactment of the Tax Cuts and Jobs Act of 2017, which was signed by the
President on December 22, 2017, Congress repealed the “individual mandate.” The repeal of this provision, which requires
most Americans to carry a minimal level of health insurance, will become effective in 2019. According to the
Congressional Budget Office, the repeal of the individual mandate will cause 13 million fewer Americans to be insured in
2027 and premiums in insurance markets may rise. Additionally, on January 22, 2018, President Trump signed a
continuing resolution on appropriations for fiscal year 2018 that delayed the implementation of certain ACA-mandated
fees, including the so-called “Cadillac” tax on certain high cost employer-sponsored insurance plans, the annual fee
imposed on certain health insurance providers based on market share, and the medical device excise tax on non-exempt
medical devices. Further, the Bipartisan Budget Act of 2018, among other things, amends the ACA, effective January 1,
2019, to increase from 50 percent to 70 percent the point-of-sale discount that is owed by pharmaceutical manufacturers
who participate in Medicare Part D and to close the coverage gap in most Medicare drug plans, commonly referred to as
the “donut hole”.
The Trump Administration has also taken executive actions to undermine or delay implementation of the ACA.
Since January 2017, President Trump has signed two Executive Orders designed to delay the implementation of certain
provisions of the ACA or otherwise circumvent some of the requirements for health insurance mandated by the ACA. One
Executive Order directs federal agencies with authorities and responsibilities under the ACA to waive, defer, grant
exemptions from, or delay the implementation of any provision of the ACA that would impose a fiscal or regulatory burden
on states, individuals, healthcare providers, health insurers, or manufacturers of pharmaceuticals or medical devices. The
second Executive Order terminates the cost-sharing subsidies that reimburse insurers under the ACA. Several state
Attorneys General filed suit to stop the administration from terminating the subsidies, but their request for a restraining
order was denied by a federal judge in California on October 25, 2017. In addition, CMS has recently proposed regulations
that would give states greater flexibility in setting benchmarks for insurers in the individual and small group marketplaces,
which may have the effect of relaxing the essential health benefits required under the ACA for plans sold through such
marketplaces. Further, on June 14, 2018, U.S. Court of Appeals for the Federal Circuit ruled that the federal government
was not required to pay more than $12 billion in ACA risk corridor payments to third-party payors who argued were owed
to them. The effects of this gap in reimbursement on third-party payors, the viability of the ACA marketplace, providers,
and potentially our business, are not yet known.
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In addition, on December 14, 2018, a U.S. District Court judge in the Northern District of Texas ruled that the
individual mandate portion of the ACA is an essential and inseverable feature of the ACA, and therefore because the
mandate was repealed as part of the Tax Cuts and Jobs Act, the remaining provisions of the ACA are invalid as well. The
Trump administration and CMS have both stated that the ruling will have no immediate effect, and on December 30, 2018
the same judge issued an order staying the judgment pending appeal. The Trump Administration recently represented to the
Court of Appeals considering this judgment that it does not oppose the lower court’s ruling. On July 10, 2019, the Court of
Appeals for the Fifth Circuit heard oral argument in this case. On December 18, 2019, that court affirmed the lower court’s
ruling that the individual mandate portion of the ACA is unconstitutional and it remanded the case to the district court for
reconsideration of the severability question and additional analysis of the provisions of the ACA. On January 21, 2020, the
U.S. Supreme Court declined to review this decision on an expedited basis. Litigation and legislation over the ACA are
likely to continue, with unpredictable and uncertain results.
Further, there have been several recent U.S. congressional inquiries and proposed federal and proposed and enacted
state legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between
pricing and manufacturer patient programs, reduce the costs of drugs under Medicare and reform government program
reimbursement methodologies for drug products. For example, there have been several recent U.S. congressional inquiries
and proposed federal and proposed and enacted state legislation designed to, among other things, bring more transparency
to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the costs of drugs under
Medicare and reform government program reimbursement methodologies for drug products. At the federal level, Congress
and the Trump administration have each indicated that it will continue to seek new legislative and/or administrative
measures to control drug costs. For example, on May 11, 2018, the Administration issued a plan to lower drug
prices. Under this blueprint for action, the Administration indicated that the Department of Health and Human Services
(HHS) will: take steps to end the gaming of regulatory and patent processes by drug makers to unfairly protect monopolies;
advance biosimilars and generics to boost price competition; evaluate the inclusion of prices in drug makers’ ads to
enhance price competition; speed access to and lower the cost of new drugs by clarifying policies for sharing information
between insurers and drug makers; avoid excessive pricing by relying more on value-based pricing by expanding outcome-
based payments in Medicare and Medicaid; work to give Part D plan sponsors more negotiation power with drug makers;
examine which Medicare Part B drugs could be negotiated for a lower price by Part D plans, and improving the design of
the Part B Competitive Acquisition Program; update Medicare’s drug-pricing dashboard to increase transparency; prohibit
Part D contracts that include “gag rules” that prevent pharmacists from informing patients when they could pay less out-of-
pocket by not using insurance; and require that Part D plan members be provided with an annual statement of plan
payments, out-of-pocket spending, and drug price increases. In addition, on December 23, 2019, the Trump Administration
published a proposed rulemaking that, if finalized, would allow states or certain other non-federal government entities to
submit importation program proposals to FDA for review and approval. Applicants would be required to demonstrate their
importation plans pose no additional risk to public health and safety and will result in significant cost savings for
consumers. At the same time, FDA issued draft guidance that would allow manufacturers to import their own FDA-
approved drugs that are authorized for sale in other countries (multi-market approved products).
At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations
designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints,
discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some
cases, designed to encourage importation from other countries and bulk purchasing. In addition, regional health care
authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products
and which suppliers will be included in their prescription drug and other health care programs. These measures could
reduce the ultimate demand for our products, once approved, or put pressure on our product pricing. We expect that
additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts
that federal and state governments will pay for healthcare products and services, which could result in reduced demand for
our product candidates or additional pricing pressures.
Employees
As of March 2, 2020, we had 161 full-time employees. Of these full-time employees, 71 employees are primarily
engaged in research and development activities. None of our employees are represented by labor unions or covered by
collective bargaining agreements. We consider our relationship with our employees to be good.
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Our Corporate Information
We were incorporated under the laws of the State of Delaware in 2006. Our principal executive offices are located at
24 Crosby Drive, Bedford, MA 01730, and our telephone number is (781)357-4000. Our manufacturing is located at 36
Crosby Drive, Suite 101, Bedford, MA 01730 and our research and development operations are located at 15 Crosby Drive,
Bedford, MA 01730. Our website address is www.ocutx.com.
Available Information
We make available free of charge through our website our annual report on Form 10-K, quarterly reports on Form 10-
Q, current reports on Form 8-K and amendments to those reports filed or furnished pursuant to Sections 13(a) and 15(d) of
the Securities Exchange Act of 1934, as amended, or the Exchange Act. We make these reports available through our
website as soon as reasonably practicable after we electronically file such reports with, or furnish such reports to, the SEC.
We also make available, free of charge on our website, the reports filed with the SEC by our executive officers, directors
and 10% stockholders pursuant to Section 16 under the Exchange Act as soon as reasonably practicable after copies of
those filings are provided to us by those persons. The information contained on, or that can be access through, our website
is not a part of or incorporated by reference in this Annual Report on Form 10-K.
Item 1A.
Risk Factors
The following risk factors and other information included in this Annual Report on Form 10-K should be carefully
considered. The risks and uncertainties described below are not the only ones we face. Additional risks and uncertainties
not presently known to us or that we presently deem less significant may also impair our business operations. Please see
page 1 of this Annual Report on Form 10-K for a discussion of some of the forward-looking statements that are qualified by
these risk factors. If any of the following risks occur, our business, financial condition, results of operations and future
growth prospects could be materially and adversely affected.
Risks Related to Our Financial Position and Need for Additional Capital
We have incurred significant losses since our inception. We expect to incur losses over the next several years and may
never achieve or maintain profitability.
Since inception, we have incurred significant operating losses. Our net losses were $63.4 million for the year ended
December 31, 2017, $60.0 million for the year ended December 31, 2018, and $86.4 million for the year ended
December 31, 2019. As of December 31, 2019, we had an accumulated deficit of $383.6 million. Through December 31,
2019, we have financed our operations primarily through private placements of our preferred stock, public offerings of our
common stock, private placements of our convertible notes and borrowings under credit facilities. We have devoted
substantially all of our financial resources and efforts to research and development, including preclinical studies and
clinical trials, commercialization of ReSure Sealant and the commercial launch of DEXTENZA for the treatment of ocular
inflammation and pain following ophthalmic surgery in July 2019. Although we expect to generate revenue from sales of
DEXTENZA, we expect to continue to incur significant expenses and operating losses over the next several years. Our net
losses may fluctuate significantly from quarter to quarter and year to year.
®
We anticipate we will incur substantial expenses if and as we:
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continue to commercialize DEXTENZA in the United States;
continue to develop and expand our sales, marketing and distribution capabilities for DEXTENZA and any of
our product candidates;
continue to pursue the clinical development of DEXTENZA for additional indications;
continue clinical trials of our product candidates OTX-TIC and OTX-TKI;
conduct joint research and development under our strategic collaboration with Regeneron, for the development
and potential commercialization of products containing our extended-delivery hydrogel
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formulation in combination with Regeneron’s large molecule, VEGF-targeting compounds to treat retinal
diseases;
continue the research and development of our other product candidates;
seek to identify and develop additional product candidates, including through additional preclinical development
activities associated with our intracanalicular insert and back-of-the-eye programs and potential opportunities
outside the field of ophthalmology;
seek marketing approvals for any of our product candidates that successfully complete clinical development;
scale up our manufacturing processes and capabilities to support sales of commercial products, our ongoing
clinical trials of our product candidates and commercialization of any of our product candidates for which we
obtain marketing approval, and expand our facilities to accommodate this scale up and any corresponding
growth in personnel;
renovate our new facility including research and development laboratories, manufacturing space and office
space;
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· maintain, expand and protect our intellectual property portfolio;
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expand our operational, financial and management systems and personnel, including personnel to support our
clinical development, manufacturing and commercialization efforts and our operations as a public company;
defend ourselves against legal proceedings;
increase our product liability and clinical trial insurance coverage as we expand our clinical trials and
commercialization efforts; and
continue to operate as a public company.
Because of the numerous risks and uncertainties associated with pharmaceutical product development, we are unable
to accurately predict the timing or amount of increased expenses or when, or if, we will be able to achieve profitability. Our
expenses will increase if:
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we are required by the FDA or the European Medicines Agency, or EMA, to perform trials or studies in addition
to those currently expected;
there are any delays in receipt of regulatory clearance to begin our planned clinical programs; or
there are any delays in enrollment of patients in or completing our clinical trials or the development of our
product candidates.
Prior to our commercial launch of DEXTENZA in July 2019, ReSure Sealant was our only source of revenue from
product sales. However, sales of ReSure Sealant have not generated significant revenue. For us to become and remain
profitable, we will need to succeed in developing and commercializing DEXTENZA and potentially other products with
significant market potential. This will require us or our current or future collaborators to be successful in a range of
challenging activities, including:
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successfully commercializing DEXTENZA in the United States, including by further developing our sales force,
marketing and distribution capabilities;
successfully completing clinical development of our product candidates, including DEXTENZA for additional
indications;
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obtaining marketing approval for these product candidates;
· manufacturing at commercial scale, marketing, selling and distributing DEXTENZA or those products for which
we obtain marketing approval;
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achieving an adequate level of market acceptance of and obtaining and maintaining coverage and adequate
reimbursement from third-party payors for our products; and
protecting our rights to our intellectual property portfolio.
Our ability to generate revenue from operations will depend, in part, on the timing and success of commercial sales
of DEXTENZA. However, the successful commercialization of DEXTENZA in the United States is subject to many
risks. DEXTENZA is our first significant product launch, and we may not be able to commercialize DEXTENZA
successfully. There are numerous examples of unsuccessful product launches and failures to meet expectations of market
potential, including by pharmaceutical companies with more experience and resources than we have. We do not anticipate
revenue from sales of DEXTENZA for the treatment of ocular inflammation and pain following ophthalmic surgery will be
sufficient for us to become profitable for several years, if ever. Furthermore, if we are unable to achieve our revenue
estimates for DEXTENZA, our ability to raise additional capital may be impacted.
We may never succeed in our commercialization efforts and may never generate revenue that is sufficient or great
enough to achieve profitability. Even if we do achieve profitability, we may not be able to sustain or increase profitability
on a quarterly or annual basis. Our failure to become and remain profitable would depress the value of our company and
could impair our ability to raise capital, expand our business, maintain our research and development efforts, diversify our
product offerings or even continue our operations. A decline in the value of our company could also cause our stockholders
to lose all or part of their investment.
We will need substantial additional funding. If we are unable to raise capital when needed, we could be forced to delay,
reduce or eliminate our product development programs or commercialization efforts.
We expect to devote substantial financial resources to our ongoing and planned activities, particularly as we continue
to commercialize DEXTENZA for the treatment of ocular inflammation and pain following ophthalmic surgery, including
expanding our product manufacturing, sales, marketing and distribution capabilities. We also expect to devote substantial
financial resources as we conduct late stage clinical trials for our local programmed-release drug delivery product
candidates, in particular DEXTENZA for additional indications including ocular itching associated with allergic
conjunctivitis, and seek marketing approval for any such product candidate for which we obtain favorable pivotal clinical
results. In addition, we plan to devote significant financial resources to conducting research and development and
potentially seeking regulatory approval for our other product candidates. Accordingly, we will need to obtain substantial
additional funding to fully support our continuing operations and the planned commercial launch of DEXTENZA. If we are
unable to raise capital when needed or on attractive terms, we could be forced to delay, reduce or eliminate our research
and development programs or any future commercialization efforts.
As of December 31, 2019, we had cash and cash equivalents of $54.4 million, outstanding debt of $25.0 million, net
of unamortized discount and $37.5 million aggregate principal amount of senior subordinated convertible notes
plus accrued interest of $1.8 million. Based on our current plans and forecasted expenses, which includes estimates related
to anticipated cash inflows from DEXTENZA and ReSure Sealant product sales and cash outflows from operating
expenses, we believe that our existing cash and cash equivalents, as of December 31, 2019, together with the first quarter
net proceeds through March 10, 2020 from the sales of our common stock pursuant to the 2019 Sales Agreement discussed
in Note 22 of our consolidated financial statements, will enable us to fund our planned operating expenses, debt service
obligations and capital expenditure requirements into the first quarter of 2021. This estimate is subject to a number of
assumptions related to the revenues and expenses associated with the commercialization of DEXTENZA as well as the
pace of our research and clinical development programs, and other aspects of our business. DEXTENZA has only recently
launched and anticipated cash flows are subject to uncertainty. These assumptions may prove to be wrong, and we could
use our capital resources sooner than we currently expect. Our future capital requirements will depend on many factors,
including :
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our ability to successfully commercialize and sell DEXTENZA in the United States;
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the costs, timing and outcome of regulatory review of our product candidates by the FDA, the EMA or other
regulatory authorities;
the level of product sales from DEXTENZA and any additional products for which we obtain marketing
approval in the future;
the costs of manufacturing, sales, marketing, distribution and other commercialization efforts with respect to
DEXTENZA and any additional products for which we obtain marketing approval in the future;
the costs of expanding our facilities to accommodate our manufacturing needs and headcount;
the progress, costs and outcome of the clinical trials of our extended-delivery drug delivery product candidates,
in particular DEXTENZA for additional indications, OTC-TIC for glaucoma and ocular hypertension, and OTX-
TKI for wet age-related macular degeneration, or wet AMD;
the progress and status of our collaboration with Regeneron, including any development costs for which we
reimburse Regeneron, the potential exercise by Regeneron of its option for a license for the development and
potential commercialization of products containing our extended-delivery hydrogel formulation in combination
with Regeneron’s large molecule VEGF-targeting compounds, and our potential receipt of future milestone
payments from Regeneron;
the scope, progress, costs and outcome of preclinical development and clinical trials of our other product
candidates;
the extent of our debt service obligations;
the extent to which we choose to establish additional collaboration, distribution or other marketing arrangements
for our products and product candidates;
the costs and outcomes of legal actions and proceedings, including the current lawsuits described under “Part I,
Item 3—Legal Proceedings”;
the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our
intellectual property rights and defending any intellectual property-related claims; and
the extent to which we acquire or invest in other businesses, products and technologies.
Conducting preclinical testing and clinical trials, seeking market approvals and commercializing products are time-
consuming, expensive and uncertain process that takes years to complete. We may never generate the necessary data or
results required to obtain regulatory approval of products with the market potential sufficient to enable us to achieve
profitability. We may not generate significant revenue from sales of any product for several years, if at all. Accordingly,
we will need to obtain substantial additional financing to achieve our business objectives. Adequate additional financing
may not be available to us on acceptable terms, or at all. In addition, we may seek additional capital due to favorable
market conditions or strategic considerations, even if we believe we have sufficient funds for our current or future
operating plans.
We have included a paragraph relating to our ability to continue as a going concern in the footnotes of our audited
consolidated financial statements included in this Annual Report on Form 10-K.
Our audited consolidated financial statements for the period ended December 31, 2019 include a paragraph stating
that our losses from operations and need for additional funding to finance our operations raise substantial doubt about our
ability to continue as a going concern. If we are unable to obtain sufficient funding, our business, prospects, financial
condition and results of operations will be materially and adversely affected and we may be unable to continue as a going
concern. If we are unable to continue as a going concern, we may have to liquidate our assets and may receive less than the
value at which those assets are carried on our consolidated financial statements, and it is likely that investors will lose all or
a part of their investment. If we seek additional financing to fund our business activities in the future and
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there remains substantial doubt about our ability to continue as a going concern, investors or other financing sources may
be unwilling to provide additional funding to us on commercially reasonable terms or at all.
Raising additional capital may cause dilution to our stockholders, restrict our operations or require us to relinquish
rights to our technologies or products or product candidates.
Until such time, if ever, as we can generate product revenues sufficient to achieve profitability, we expect to finance
our cash needs through equity offerings, debt financings, collaborations, strategic alliances, licensing arrangements, royalty
agreements, and marketing and distribution arrangements. We do not have any committed external source of funds,
although our collaboration agreement with Regeneron provides for the potential receipt of option exercise, development,
regulatory and sales milestones and royalty payments. To the extent that we raise additional capital through the sale of
equity, preferred equity or convertible debt securities, our stockholders’ ownership interests will be diluted, and the terms
of these securities may include liquidation or other preferences that adversely affect our existing stockholders’ rights as
holders of our common stock. Debt financing and preferred equity financing, if available, may involve agreements that
include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making
capital expenditures or declaring dividends. Our pledge of our assets as collateral to secure our obligations under our
Credit Facility may limit our ability to obtain additional debt financing. If we are unable to raise additional funds through
equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or
future commercialization efforts or grant rights to develop and market products or product candidates that we would
otherwise prefer to develop and market ourselves.
If we raise additional funds through collaborations, strategic alliances, licensing arrangements, royalty agreements, or
marketing and distribution arrangements, we may have to relinquish valuable rights to our technologies, future revenue
streams, research programs, products or product candidates or grant licenses on terms that may not be favorable to us.
Our substantial indebtedness may limit cash flow available to invest in the ongoing needs of our business.
We have a significant amount of indebtedness. Under our Credit Facility, we had $25.0 million, net of unamortized
discount, of outstanding principal indebtedness. Under the accompanying Credit Agreement, we are permitted to make
interest-only payments until January 1, 2021, subject to potential extension to January 1, 2022 if net sales of DEXTENZA
exceed $40.0 million in the aggregate during any trailing twelve-month period. Our obligations under the Credit
Agreement are secured by all of our assets, including our intellectual property. The Credit Agreement also includes
customary affirmative and negative covenants, including limitations on dispositions, mergers or acquisitions; incurring
indebtedness, liens or encumbrances; paying dividends; making certain investments; and engaging in certain other business
transactions. In March 2019, we issued $37.5 million aggregate principal amount of Convertible Notes. The Convertible
Notes mature on March 1, 2026 and interest on the Convertible Notes is payable at maturity or if earlier converted,
repurchased or redeemed pursuant to their terms. We could in the future incur additional indebtedness beyond such
amounts, including by potentially amending our Credit Agreement.
Our substantial debt combined with our other financial obligations and contractual commitments could have
significant adverse consequences, including:
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requiring us to dedicate a substantial portion of cash and cash equivalents and marketable securities to the
payment of interest on, and principal of, our debt, which will reduce the amounts available to fund working
capital, commercialization expenditures associated with DEXTENZA, capital expenditures, product
development efforts and other general corporate purposes;
obligating us to negative covenants restricting our activities, including limitations on dispositions, mergers or
acquisitions, encumbering our intellectual property, incurring indebtedness or liens, paying dividends, making
investments and engaging in certain other business transactions;
limiting our flexibility in planning for, or reacting to, changes in our business and our industry; and
placing us at a competitive disadvantage compared to our competitors that have less debt or better debt servicing
options.
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We intend to satisfy our current and future debt service obligations with our existing cash and cash equivalents,
anticipated product revenue from DEXTENZA and funds from external sources. However, we may not have sufficient
funds or may be unable to arrange for additional financing to pay the amounts due under our existing debt. Funds from
external sources may not be available on acceptable terms, if at all. In addition, a failure to comply with the conditions of
our Credit Agreement or the Convertible Notes could result in an event of default under those instruments. In the event of
an acceleration of amounts due under our Credit Agreement or the Convertible Notes as a result of an event of default,
including upon the occurrence of an event that would reasonably be expected to have a material adverse effect on our
business, operations, properties, assets or condition or a failure to pay any amount due, we may not have sufficient funds or
may be unable to arrange for additional financing to repay our indebtedness or to make any accelerated payments, and the
lenders could seek to enforce security interests in the collateral securing such indebtedness. In addition, the covenants
under our existing Credit Agreement and the pledge of our assets, including our intellectual property, as collateral limit our
ability to obtain additional debt financing.
The elimination of LIBOR could adversely affect our business, results of operations or financial condition.
In July 2017, the head of the United Kingdom Financial Conduct Authority announced plans to phase out the use
of LIBOR by the end of 2021. Although the impact is uncertain at this time, the elimination of LIBOR could have an
adverse impact on our business, results of operations, or financial condition. We may incur significant expenses to amend
our LIBOR-indexed loans and other applicable financial or contractual obligations, including our Credit Facility, to a new
reference rate, which may differ significantly from LIBOR. Accordingly, the use of an alternative rate could result in
increased costs, including increased interest expense on our credit facilities, and increased borrowing and hedging costs in
the future. At this time, no consensus exists as to what rate or rates may become acceptable alternatives to LIBOR and we
are unable to predict the effect of any such alternatives on our business, results of operations or financial condition.
Our limited operating history may make it difficult for our stockholders to evaluate the success of our business to date
and to assess our future viability.
We are an early-stage company. Our operations to date have been limited to organizing and staffing our company,
acquiring rights to intellectual property, business planning, raising capital, developing our technology, identifying potential
product candidates, undertaking preclinical studies and clinical trials, manufacturing initial quantities of our products and
product candidates, commercializing ReSure Sealant, and, since July 2019, commercializing DEXTENZA for the treatment
of ocular inflammation and pain following ophthalmic surgery. We have a limited history of commercializing products. We
commercially launched DEXTENZA on July 1, 2019 and, to date, have not generated material revenue from the sale of
DEXTENZA. Consequently, any predictions about our future success or viability may not be as accurate as they could be if
we had a longer operating history.
In addition, as a new business, we may encounter unforeseen expenses, difficulties, complications, delays and other
known and unknown factors. We are in early stages of the process of transitioning from a company with a research and
development focus to a company capable of supporting commercial activities. We may not be successful in such a
transition.
We expect our financial condition and operating results to continue to fluctuate significantly from quarter-to-quarter
and year-to-year due to a variety of factors, many of which are beyond our control. Accordingly, our stockholders should
not rely upon the results of any quarterly or annual periods as indications of future operating performance.
We have broad discretion in the use of our available cash and other sources of funding and may not use them
effectively.
Our management has broad discretion in the use of our available cash and other sources of funding and could spend
those resources in ways that do not improve our results of operations or enhance the value of our common stock. The
failure by our management to apply these funds effectively could result in financial losses that could cause the price of our
common stock to decline and delay the development of our product candidates. Pending their use, we may invest our
available cash in a manner that does not produce income or that loses value.
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Risks Related to Product Development
We depend heavily on the success of DEXTENZA and our product candidates. Clinical trials of our product candidates
may not be successful. If we are unable to successfully complete clinical development of and obtain marketing approvals
for our product candidates, or experience significant delays in doing so, or if after obtaining marketing approvals, we
fail to maintain marketing approval or fail to commercialize these product candidates, our business will be materially
harmed.
We have devoted a significant portion of our financial resources and business efforts to the development of our drug-
eluting intracanalicular insert products and product candidates for diseases and conditions of the front of the eye. In
particular, we are investing substantial resources to complete the development of DEXTENZA for allergic conjunctivitis,
OTX-TIC for glaucoma and ocular hypertension and OTX-TKI for wet AMD. We cannot accurately predict when or if any
of our product candidates will prove effective or safe in humans or whether our products and product candidates will
receive marketing approval or reach successful commercialization. In addition, in November 2019 we announced that we
would defer certain development programs as part of an initiative to reduce expenses and prioritize our resources to focus
on commercializing DEXTENZA for post-surgical ocular inflammation and pain as well as completing the ongoing Phase
3 clinical trial of DEXTENZA for the treatment of ocular itching associated with allergic conjunctivitis, a Phase 1 clinical
trial of OTX-TIC for the treatment of glaucoma and ocular hypertension and a Phase 1 clinical trial of OTX-TKI for the
treatment of wet age-related macular degeneration. Our ability to generate product revenues sufficient to achieve
profitability will depend heavily on our commercialization of DEXTENZA for the treatment of ocular inflammation and
pain following ophthalmic surgery and our obtaining marketing approval for and commercializing other products with
significant market potential, including DEXTENZA for additional indications.
The commercial success of our product DEXTENZA and our product candidates will depend on many factors,
including the following:
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successful completion of preclinical studies and clinical trials;
applying for and receiving and maintaining marketing approvals from applicable regulatory authorities for our
product candidates;
scaling up our manufacturing processes and capabilities to support additional or larger clinical trials of our
product candidates and commercialization of DEXTENZA or any of our product candidates for which we obtain
marketing approval;
developing, validating and maintaining a commercially viable manufacturing process that is compliant with
current good manufacturing practices, or cGMP;
developing our sales, marketing and distribution capabilities and launching commercial sales of our products and
product candidates, if and when approved, whether alone or in collaboration with others;
partnering successfully with our current and future collaborators, including Regeneron;
gaining acceptance of our products, if and when approved, by patients, the medical community and third-party
payors;
effectively competing with other therapies;
· maintaining a continued acceptable safety profile of our products following approval;
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obtaining and maintaining coverage and adequate reimbursement from third-party payors;
obtaining and maintaining patent and trade secret protection and regulatory exclusivity; and
protecting our rights in our intellectual property portfolio.
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In certain cases, such as in our collaboration with Regeneron, many of these factors may be beyond our control,
including clinical development and sales, marketing and distribution efforts. If we or our collaborators do not achieve one
or more of these factors in a timely manner or at all, we could experience significant delays or an inability to successfully
commercialize our products and product candidates, which would materially harm our business.
If clinical trials of our intracanalicular insert product candidates or any other product candidate that we develop fail to
demonstrate safety and efficacy to the satisfaction of the FDA, the EMA or other regulatory authorities or do not
otherwise produce favorable results, we may incur additional costs or experience delays in completing, or ultimately be
delayed or unable to complete, the development and commercialization of such product candidate.
Before obtaining marketing approval from regulatory authorities for the sale of any product candidate, including our
intracanalicular insert product candidates, we must complete preclinical development and then conduct extensive clinical
trials to demonstrate the safety and efficacy of our product candidates in humans. Clinical testing is expensive, difficult to
design and implement, can take many years to complete and is uncertain as to outcome. A failure of one or more clinical
trials can occur at any stage of testing. The outcome of preclinical testing and early clinical trials may not be predictive of
the success of later stage clinical trials, interim results of a clinical trial do not necessarily predict final results and results
from one completed clinical trial may not be replicated in a subsequent clinical trial with a similar study design. Some of
our completed studies were conducted with small patient populations, making it difficult to predict whether the favorable
results that we observed in such studies will be repeated in larger and more advanced clinical trials. Moreover, preclinical
and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their
product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain
marketing approval of their products.
In general, the FDA requires two adequate and well-controlled clinical trials to support the effectiveness of a new
drug for marketing approval. In a Phase 2 clinical trial of DEXTENZA that we completed in 2013 in which we were
evaluating DEXTENZA for post-surgical ocular inflammation and pain following cataract surgery, DEXTENZA did not
meet the primary efficacy endpoint for inflammation with statistical significance at the pre-specified time point at day
8. However, we did achieve statistical significance for this inflammation endpoint at days 14 and 30. Accordingly, we
measured the primary efficacy endpoint for inflammation in our completed Phase 3 clinical trials of DEXTENZA at day
14. In the first and third Phase 3 clinical trials, DEXTENZA met both primary endpoints for post-surgical ocular
inflammation and pain following cataract surgery with statistical significance. However, in the second Phase 3 clinical
trial, DEXTENZA met only one of the two primary efficacy endpoints with statistical significance. In this second trial,
DEXTENZA did not meet the primary endpoint relating to absence of inflammatory cells in the study eye at day 14.
We announced topline results from a third Phase 3 clinical trial of DEXTENZA for post-surgical ocular inflammation
and pain in November 2016, which we used to support the potential labeling expansion of DEXTENZA’s indications for
use. We modified the design of this third Phase 3 clinical trial compared to our two previous Phase 3 clinical trials of
DEXTENZA based on our learnings from these trials. In this trial, DEXTENZA successfully met its two primary efficacy
endpoints for inflammation and pain, achieving statistically significant differences between the treatment group and the
placebo group for the absence of inflammatory cells on day 14 and the absence of pain on day 8, respectively. Secondary
analyses on the primary efficacy measures have also been completed. DEXTENZA achieved each of the secondary
endpoints related to absence of inflammatory cells, absence of pain, and absence of anterior chamber flare with statistical
significance compared to placebo at each of the pre-specified time points, with the exception of the endpoint for the
absence of inflammatory cells at day 2 (which is the day following surgery). Based on the results of our third Phase 3
clinical trial of DEXTENZA and subsequent approval in November 2018 for the pain indication pursuant to the initial
NDA, we submitted an NDA supplement, or sNDA, for DEXTENZA for the treatment of post-surgical ocular
inflammation in January 2019, and the FDA approved the sNDA in June 2019.
In our first Phase 3 clinical trial of DEXTENZA for allergic conjunctivitis, for which we announced topline results in
October 2015, DEXTENZA met one of the two primary endpoints. DEXTENZA achieved the primary endpoint for ocular
itching associated with allergic conjunctivitis but not the primary endpoint for conjunctival redness, in each case measured
on day 7 after insertion of the insert. The difference in the mean scores for ocular itching between the DEXTENZA group
and the placebo group was greater than 0.5 units on a five point scale at all time points on day 7 post-insertion and was
greater than 1.0 unit at a majority of the time points on day 7 post-insertion. The DEXTENZA group did not achieve these
pre-specified endpoints on day 7 post-insertion with respect to conjunctival redness. In our second Phase 3 clinical trial of
DEXTENZA for allergic conjunctivitis, for which we announced topline results in June 2016, DEXTENZA did not meet
the sole primary endpoint for ocular itching. The single primary endpoint of the second
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Phase 3 clinical trial was the difference in the mean scores in ocular itching between the treatment group and the placebo
comparator group at three time points on day 7 following insertion of the inserts. While mean ocular itching was seen to be
numerically lower (more favorable) in the DEXTENZA treatment group compared to the placebo group measured at each
of the three specified times on day 7 following insertion of the inserts, at 3, 5, and 7 minutes by -0.18, -0.29, and -0.29
units, respectively, on a five point scale, this difference did not reach statistical significance. In addition, the trial did not
achieve the requirement of at least a 0.5 unit difference at all three time points on day 7 following insertion of the inserts
and at least a 1.0 unit difference at the majority of the three time points between the treatment group and the placebo group
on day 7 following insertion of the inserts. Further, in our prior Phase 2 clinical trial of DEXTENZA in which we were
evaluating DEXTENZA for allergic conjunctivitis, DEXTENZA met one of the two primary efficacy measures. The
DEXTENZA treatment group achieved a mean difference compared to the vehicle control group of more than 0.5 units on
a five point scale on day 14 for all three time points measured in a day for both ocular itching and conjunctival
redness. The DEXTENZA group did not achieve a mean difference compared to the vehicle control group of 1.0 unit for
the majority of the three time points measured on day 14 for either ocular itching or conjunctival redness. Even if we
obtain favorable clinical trial results in an additional Phase 3 clinical trial of DEXTENZA for allergic conjunctivitis, such
as our ongoing third Phase 3 clinical trial, including meeting all primary efficacy measures, we may not obtain approval for
DEXTENZA to treat allergic conjunctivitis or ocular itching associated with allergic conjunctivitis, or the FDA may
require that we conduct additional clinical trials. Post-hoc analyses that we performed on the results of our two completed
Phase 3 clinical trials for allergic conjunctivitis may not be predictive of success in any future Phase 3 clinical
trial. Although we believe that these analyses provide important information regarding DEXTENZA and are helpful in
understanding the results of this trial and determining the appropriate criteria for future clinical trials, post-hoc analyses
performed using an unlocked clinical trial database can result in the introduction of bias and are given less weight by
regulatory authorities than pre-specified analyses.
We designed our Phase 2 clinical trials of OTX-TP for the treatment of glaucoma and ocular hypertension to assess
response to treatment, and did not power these trials to measure any efficacy endpoints with statistical significance. We
reported topline efficacy results from our Phase 2b clinical trial of OTX-TP for the treatment of glaucoma and ocular
hypertension in October 2015. OTX-TP did not achieve non-inferiority to timolol drops in our Phase 2b clinical trial. In
this trial, on day 60 at the 8:00 a.m. time point, the OTX-TP group experienced a mean intraocular pressure, or IOP,
lowering effect of 4.7 mmHg, compared with IOP lowering of 6.4 mmHg for the timolol arm. On day 90 at the 8:00 a.m.
time point, the OTX-TP group experienced an IOP lowering effect of 5.1 mmHg, compared with an IOP lowering effect of
7.2 mmHg in the timolol arm. Also in this trial, on day 60, the OTX-TP group experienced a mean diurnal IOP lowering
effect of 3.3 mmHg compared to baseline 6.1 mmHg compared for the timolol group. On day 90, the OTX-TP group
experienced a mean diurnal IOP, or IOP, lowering effect of 3.6 mmHg compared to baseline, versus 6.3 mmHg for the
timolol group.
We completed an End‑of‑Phase 2 review with the FDA in April 2016 and initiated our first planned Phase 3 clinical
trials of OTX‑TP in September 2016. Based on discussions with the FDA, the Phase 3 clinical trial design has significant
differences as compared to our completed Phase 2 clinical trials. In particular, the most notable changes from our first
Phase 2 clinical trial to our first Phase 3 clinical trial were that our first Phase 3 clinical trial enrolled more subjects at a
greater number of sites, had a different randomization, measured the primary efficacy endpoints on different days and at
different time points, and had a longer washout period. As a result, the first Phase 3 clinical trial of OTX-TP was a
randomized, double blind, placebo-controlled clinical trial conducted across more than 50 sites, and it enrolled 554 subjects
with open-angle glaucoma or ocular hypertension in the full analysis set population. The trial’s primary efficacy endpoint
was to evaluate the mean IOP at three diurnal time points (8 a.m., 10 a.m., and 4 p.m.) at each of 2, 6, and 12 weeks
following insertion for OTX-TP treated subjects compared with placebo insert treated subjects. The trial’s secondary
efficacy endpoints included the evaluation of the mean reduction and mean percent reduction of IOP from baseline for
OTX-TP treated subjects compared with placebo insert treated subjects at the same time points. Topline results from this
trial show that OTX-TP did not achieve its primary and secondary endpoints of statistically significant superiority in mean,
mean reduction, or mean percentage reduction of IOP compared with placebo at all nine time points. OTX-TP treated
subjects did have a lower mean IOP and a greater reduction in IOP from baseline relative to placebo insert at all nine time
points, but these differences were statistically significant (p value < 0.05) for only eight of the nine time points. We do not
intend to initiate a second Phase 3 clinical trial at this time without a collaborative partner. If we do not achieve our primary
endpoint in an additional Phase 3 clinical trial with statistical significance, assuming we conduct such clinical trials, or do
not achieve a clinically meaningful reduction in IOP, we may not obtain marketing approval for OTX-TP.
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In addition, post-hoc analyses that we performed on the results of our completed Phase 2b clinical trial may not be
predictive of success in our planned Phase 3 clinical trials, including as a result of differences in trial design. Post-hoc
analyses performed using an unlocked clinical trial database can result in the introduction of bias and are given less weight
by regulatory authorities than pre-specified analyses.
The success of our intracanalicular insert product candidates is dependent upon retention during the course of
intended therapy. As such, we may conduct non-significant risk investigational device exemption, or IDE, medical device,
or NSR, studies in the United States for our extended-delivery intracanalicular insert in an effort to increase the rate of
retention. All NSR studies that we have performed to date have involved placebo vehicle control intracanalicular inserts
without active drug. If we determine to make any future changes to the design or composition of our inserts, such changes
could affect the outcome of any subsequent clinical trials using these updated inserts. For example, in our Phase 2b clinical
trial of OTX-TP, we used a different version of intracanalicular insert than either of the inserts that we used in our Phase 2a
clinical trial of OTX-TP. Based on the results of our completed Phase 2a clinical trial, we designed the OTX-TP insert that
was used in our Phase 2b clinical trial to deliver drug over a 90 day period at the same daily rate as the two-month version
of the insert used in the Phase 2a clinical trial. To achieve this, we modified the design of the OTX-TP insert to enlarge it
in order to enable the insert to carry a greater amount of drug. In addition, we incorporated minor structural changes to
improve retention rates. In our Phase 2b clinical trials, OTX-TP inserts could be visualized in approximately 88% of eyes
by the day 60 visit. By the day 90 visit, the ability to visualize OTX-TP had declined to approximately 42% of eyes as the
hydrogel softened, liquefied and had either advanced further down in the canaliculus or had cleared through the
nasolacrimal duct. We are conducting additional NSR studies on additional modified insert designs, including a
polyethylene glycol, or PEG, tip on the proximal end of the insert that have been incorporated into the design of the first
Phase 3 trial of OTX-TP. If in our Phase 3 clinical trials the retention rates for our inserts are inadequate to ensure that the
patient is receiving appropriate therapy, we may not be able to obtain regulatory approvals or, even if approved, achieve
market acceptance of our local programmed-release drug delivery products. As part of our restructuring plan announced in
November 2019, we have paused further activities in connection with our OTX-TP program for the treatment of primary
open-angle glaucoma or ocular hypertension, other than the ongoing open-label safety extension study.
The protocols for our clinical trials and other supporting information are subject to review by the FDA and regulatory
authorities outside the United States. For our intracanalicular insert product candidates, we have typically conducted our
initial and earlier stage clinical trials outside the United States. We generally plan to conduct our later stage and pivotal
clinical trials of our intracanalicular insert product candidates in the United States. The FDA, however, could require us to
conduct additional studies or require us to modify our planned pivotal clinical trials to receive clearance to initiate such
trials in the United States or to continue such trials once initiated. The FDA is not obligated to comment on our trial
protocols within any specified time period or at all or to affirmatively clear or approve our planned pivotal clinical
trials. Subject to a waiting period of 30 days, we could choose to initiate our pivotal clinical trials in the United States
without waiting for any additional period for comments from the FDA.
We have conducted, and may in the future conduct, clinical trials for product candidates at sites outside the United
States, and the FDA may not accept data from trials conducted in such locations.
We have conducted, and may in the future choose to conduct, one or more of our clinical trials outside the United
States. We have often conducted our initial and earlier stage clinical trials for our product candidates, including our
intracanalicular insert product candidates, outside the United States. We are currently conducting a Phase 1 clinical trial for
our product candidate OTX-TKI for the treatment of wet AMD in Australia. We generally plan to conduct our later stage
and pivotal clinical trials of our product candidates in the United States.
Although the FDA may accept data from clinical trials conducted outside the United States, acceptance of this data is
subject to conditions imposed by the FDA. For example, the clinical trial must be well designed and conducted and
performed by qualified investigators in accordance with ethical principles. The trial population must also adequately
represent the U.S. population, and the data must be applicable to the U.S. population and U.S. medical practice in ways that
the FDA deems clinically meaningful. In addition, while these clinical trials are subject to the applicable local laws, FDA
acceptance of the data will depend on its determination that the trials also complied with all applicable U.S. laws and
regulations. If the FDA does not accept the data from any trial that we conduct outside the United States, it would likely
result in the need for additional trials, which would be costly and time-consuming and would delay or permanently halt our
development of the applicable product candidates.
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Other risks inherent in conducting international clinical trials include:
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foreign regulatory requirements that could restrict or limit our ability to conduct our clinical trials
administrative burdens of conducting clinical trials under multiple sets of foreign regulations;
failure of enrolled patients to adhere to clinical protocols as a result of differences in healthcare services or
cultural customs;
foreign exchange fluctuations;
diminished protection of intellectual property in some countries; and
political and economic risks relevant to foreign countries.
If we experience any of a number of possible unforeseen events in connection with our clinical trials, potential
marketing approval or commercialization of our product candidates could be delayed or prevented.
We may experience numerous unforeseen events during, or as a result of, clinical trials that could delay or prevent
our ability to receive marketing approval or commercialize our extended-delivery drug delivery product candidates or any
other product candidates that we may develop, including:
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clinical trials of our product candidates may produce negative or inconclusive results, and we may decide, or
regulators may require us, to conduct additional clinical trials or abandon product development programs;
the number of patients required for clinical trials of our product candidates may be larger than we anticipate,
enrollment in these clinical trials may be slower than we anticipate or participants may drop out of these clinical
trials at a higher rate than we anticipate;
our third-party contractors may fail to comply with regulatory requirements or meet their obligations to us in a
timely manner, or at all;
regulators or institutional review boards may not authorize us or our investigators to commence a clinical trial or
conduct a clinical trial at a prospective trial site;
we may experience delays in reaching, or fail to reach, agreement on acceptable clinical trial contracts or clinical
trial protocols with prospective trial sites;
we may decide, or regulators or institutional review boards may require us, to suspend or terminate clinical
research for various reasons, including noncompliance with regulatory requirements or a finding that the
participants are being exposed to unacceptable health risks;
the cost of clinical trials of our product candidates may be greater than we anticipate; and
the supply or quality of our product candidates or other materials necessary to conduct clinical trials of our
product candidates may be insufficient or inadequate.
For example, we applied for a deferral from the FDA for the requirement to conduct pediatric studies for
DEXTENZA for the treatment of post-surgical ocular inflammation and pain following cataract surgery until after approval
of such product in adult populations for that indication. While the FDA ultimately approved our request, if the FDA had
required us to conduct pediatric studies in advance of FDA approval in adult populations, we would have experienced
significant delays in our ability to obtain marketing approval for DEXTENZA for these indications, particularly in light of
our decision announced in November 2019 to postpone our clinical trial to evaluate DEXTENZA in pediatric subjects
following cataract surgery until the fourth quarter of 2020. We will face a similar risk if we seek a comparable deferral for
other product candidates or indications.
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If we are required to conduct additional clinical trials or other testing of our product candidates beyond those that we
currently contemplate, if we are unable to successfully complete clinical trials of our product candidates or other testing, if
the results of these trials or tests are not favorable or are only modestly favorable or if there are safety concerns, we may:
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be delayed in obtaining or unable to obtain marketing approval for our product candidates;
obtain approval for indications or patient populations that are not as broad as intended or desired;
obtain approval with labeling that includes significant use or distribution restrictions or safety warnings;
be subject to additional post-marketing testing requirements; or
have the product removed from the market after obtaining marketing approval.
Our product development costs will also increase if we experience delays in testing or marketing approvals. We do
not know whether any of our preclinical studies or clinical trials will begin as planned, will need to be restructured or will
be completed on schedule, or at all. Significant preclinical or clinical trial delays also could shorten any periods during
which we may have the exclusive right to commercialize our product candidates or allow our competitors to bring products
to market before we do and impair our ability to successfully commercialize our product candidates.
If we experience delays or difficulties in the enrollment of patients in clinical trials, our receipt of necessary regulatory
approvals could be delayed or prevented.
We may not be able to initiate or continue clinical trials for our local programmed-release drug delivery product
candidates or our other product candidates that we may develop if we are unable to locate and enroll a sufficient number of
eligible patients to participate in these trials as required by the FDA, the EMA or similar regulatory authorities outside the
United States. Although there is a significant prevalence of disease in the areas of ophthalmology in which we are focused,
we may nonetheless experience unanticipated difficulty with patient enrollment. For example, in the third quarter of 2017,
we initiated a Phase 1 clinical trial of OTX-TIC outside the United States. After several months, after not enrolling any
patients, we closed this trial in the second quarter of 2018. Additionally, we intended to initiate a Phase 1 clinical trial of
OTX-TKI outside the United States in 2018, but we were unable to start dosing patients until the first quarter of 2019.
A variety of factors affect patient enrollment, including:
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the prevalence and severity of the ophthalmic disease or condition under investigation;
the eligibility criteria for the study in question;
the perceived risks and benefits of the product candidate under study;
the efforts to facilitate timely enrollment in clinical trials;
the patient referral practices of physicians;
the ability to monitor patients adequately during and after treatment;
the proximity and availability of clinical trial sites for prospective patients;
actual or threatened public health emergencies or outbreaks of disease (including, for example, the recent
coronavirus outbreak);
the conduct of clinical trials by competitors for product candidates that treat the same indications as our product
candidates; and
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the lack of adequate compensation for prospective patients.
Our Phase 3 clinical trial of OTX-TP exceeded its target enrollment of 550 patients at approximately 49 sites in the
United States and is the largest clinical trial we have conducted to date. While now complete, enrollment in this trial was
slower than projected. Our inability to enroll a sufficient number of patients in any of our other clinical trials would result
in significant delays, could require us to abandon one or more clinical trials altogether and could delay or prevent our
receipt of necessary regulatory approvals. Enrollment delays in our clinical trials may result in increased development
costs for our product candidates, which would cause the value of our company to decline and limit our ability to obtain
additional financing.
If serious adverse or unacceptable side effects are identified during the development or commercialization of our
extended-delivery drug delivery products or product candidates or any other product candidates that we may develop, we
may need to abandon or limit our development of such products or product candidates.
If DEXTENZA or any of our local programmed-release drug delivery product candidates or other product candidates
are associated with serious adverse events or undesirable side effects in clinical trials or have characteristics that are
unexpected, we may need to abandon their development or limit development to more narrow uses or subpopulations in
which the serious adverse events, undesirable side effects or other characteristics are less prevalent, less severe or more
acceptable from a risk-benefit perspective. In each of our first two Phase 3 clinical trials of DEXTENZA for the treatment
of post-surgical ocular inflammation and pain following cataract surgery, there were two subjects that experienced serious
adverse events in the DEXTENZA group in each trial, none of which were ocular in nature or considered by the
investigator to be related to the study treatment. In our third Phase 3 clinical trial of DEXTENZA for the treatment of post-
surgical ocular inflammation and pain, there were three subjects that experienced serious adverse events in the
DEXTENZA group, one of which was ocular in nature and none of which were considered by the investigator to be related
to the study treatment. There was one ocular serious adverse event in the vehicle control group in the three completed
Phase 3 clinical trials, which was hypopyon, or inflammatory cells in the anterior chamber. In our earlier Phase 2 clinical
trial of DEXTENZA for the same indication, there were three serious adverse events, none of which was considered by the
investigator to be related to the study treatment. In the DEXTENZA group of this Phase 2 clinical trial of DEXTENZA,
the only adverse event that occurred more than once for the same subject was reduced visual acuity, which occurred twice
but was not considered by the investigator to be related to the study treatment.
In our two pilot studies of OTX-TP for the treatment of glaucoma and ocular hypertension and our Phase 2a clinical
trial of OTX-TP for the same indication, the most common adverse event was inflammatory reaction of the eyelids and
ocular surface, which was noted in three patients in our pilot studies and in five patients in our Phase 2a clinical trial. No
hyperemia-related adverse events were noted in any of the patients treated with OTX-TP in our Phase 2b clinical
trial. There were no serious adverse events reported in our Phase 2b clinical trial; however, two OTX‑TP subjects and two
timolol subjects discontinued study participation due to ocular adverse events. Ocular adverse events were reported for
39.4% and 37.5% of subjects in the OTX-TP and timolol groups, respectively. The most frequently reported ocular adverse
events were dacryocanaliculitis, or inflammation of the lacrimal ducts, acquired dacryostenosis, or closing of the tear ducts,
and eyelid edema. In the Phase 2b clinical trial, inflammatory reaction at the administration site (punctal area) and lacrimal
structure injury were each noted in one OTX-TP subject as compared to higher percentages in prior trials. In the Phase 2b
trial, the majority of ocular adverse events, including the most frequently reported adverse events, were assessed by the
investigators as treatment related. In the Phase 3 clinical trial, no ocular serious adverse events were observed. The most
common ocular adverse events seen in the clinical trial were dacryocanaliculitis (approximately 7% in OTX-TP vs. 3% in
placebo) and lacrimal structure disorder (approximately 6% in OTX-TP vs. 4% in placebo).
Many compounds that initially showed promise in clinical or early stage testing for treating ophthalmic disease have
later been found to cause side effects that prevented further development of the compound. In addition, adverse events
which had initially been considered unrelated to the study treatment may later be found to be caused by the study
treatment.
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We may not be successful in our efforts to develop products and product candidates based on our bioresorbable hydrogel
technology platform other than DEXTENZA and ReSure Sealant or expand the use of our bioresorbable hydrogel
technology for treating additional diseases and conditions.
We are currently directing most of our development efforts towards applying our proprietary, bioresorbable hydrogel
technology platform to products and product candidates that are designed to provide local programmed-release hydrogel
based therapeutic agents to the eye using active pharmaceutical ingredients that are currently used in FDA-approved
ophthalmic drugs. We have a number of products and product candidates at various stages of development based on our
bioresorbable hydrogel technology platform and are exploring the potential use of our platform for other front-of-the-eye
diseases and conditions. We are also developing hydrogel drug delivery implants designed to release therapeutic
antibodies and small molecules such as TKIs to modulate the biological activity of VEGF over a sustained period following
administration by an intravitreal injection for the treatment of diseases and conditions of the back of the eye, including wet
AMD. In October 2016, we entered into a collaboration with Regeneron for the development and potential
commercialization of products containing our extended-delivery hydrogel formulation in combination with Regeneron’s
large molecule VEGF-targeting compounds for the treatment of retinal diseases. Our existing product candidates and any
other potential product candidates that we or our collaborators identify may not be suitable for continued preclinical or
clinical development, including as a result of being shown to have harmful side effects or other characteristics that indicate
that they are unlikely to be products that will receive marketing approval and achieve market acceptance. We are also
considering the future growth potential of the hydrogel platform technology in new areas of the body. If we do not
successfully develop and commercialize our products and product candidates that we or our current or future collaborators
develop based upon our technological approach, we will not be able to obtain substantial product revenues or revenue from
collaboration agreements, including our collaboration with Regeneron, in future periods.
We may expend our limited resources to pursue a particular product, product candidate or indication and fail to
capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of
success.
Because we have limited financial and managerial resources, we focus on research programs and product candidates
that we identify for specific indications. As a result, we may forego or delay pursuit of opportunities with other product
candidates or for other indications that later prove to have greater commercial potential. Our resource allocation decisions
may cause us to fail to capitalize on viable commercial products or profitable market opportunities. As part of our
restructuring plan announced in November 2019, we have decided to defer certain development programs as part of an
initiative to reduce expenses and prioritize our resources to focus on commercializing DEXTENZA for post-surgical ocular
inflammation and pain as well as completing the ongoing Phase 3 clinical trial of DEXTENZA for the treatment of ocular
itching associated with allergic conjunctivitis, a Phase 1 clinical trial of OTX-TIC for the treatment of glaucoma and ocular
hypertension, and a Phase 1 clinical trial of OTX-TKI for the treatment of wet age-related macular degeneration. Our
spending on current and future research and development programs and product candidates for specific indications may not
yield any commercially viable products. If we do not accurately evaluate the commercial potential or target market for a
particular product or product candidate, we may relinquish valuable rights to that product or product candidate through
collaboration, licensing or other royalty arrangements in cases in which it would have been more advantageous for us to
retain sole development and commercialization rights to such products or product candidate.
Risks Related to Manufacturing
We will need to upgrade and expand our manufacturing facility or relocate to another facility and to augment our
manufacturing personnel and processes in order to meet our business plans. If we fail to do so, we may not have
sufficient quantities of our products or product candidates to meet our commercial and clinical trial requirements.
We manufacture DEXTENZA, ReSure Sealant and our product candidates for use in clinical trials, research and
development and commercial efforts at our facility located in Bedford, Massachusetts. In order to meet our business plan,
which contemplates our scaling up manufacturing processes to support our product candidate development programs and
the potential commercialization of these products and product candidates, we will need to upgrade and expand our existing
manufacturing facility, or relocate to another manufacturing facility, add manufacturing personnel and ensure that validated
processes are consistently implemented in our facility or facilities. The upgrade and expansion of our facility, or the
relocation to an additional facility, will require additional regulatory approvals. In addition, it will be costly and time-
consuming to expand our facility or relocate to another facility and recruit necessary additional
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personnel. If we are unable to expand our manufacturing facility or relocate to another facility in compliance with
regulatory requirements or to hire additional necessary manufacturing personnel, we may encounter delays or additional
costs in achieving our research, development and commercialization objectives, including obtaining regulatory approvals of
our product candidates and meeting customer demand for our products, which could materially damage our business and
financial position.
We must comply with federal, state and foreign regulations, including quality assurance standards applicable to
medical device and drug manufacturers, such as cGMP, which is enforced by the FDA through its facilities inspection
program and by similar regulatory authorities in other jurisdictions where we do business. These requirements include,
among other things, quality control, quality assurance and the maintenance of records and documentation. For example,
between March 2015 and May 2018, we received several Form 483s from the FDA containing inspectional observations
relating to inadequate procedures for documenting follow-up information pertinent to the investigation of complaints and
for evaluation of complaints for adverse event reporting; process controls, analytical testing and physical security
procedures related to manufacture of our drug product for stability and commercial production purposes; and procedures
for manufacturing processes and analytical testing related to the manufacture of drug product for commercial
production. In each of July 2016 and July 2017, we also received a Complete Response Letter, or CRL, from the FDA
regarding our NDA for DEXTENZA pertaining to, among other things, the deficiencies in manufacturing processes,
controls, and analytical testing identified during pre-NDA approval inspections of our manufacturing facility documented
on Form 483s. We may be subject to similar inspections and requirements in connection with subsequent applications for
other product candidates or DEXTENZA for additional indications.
The FDA or similar foreign regulatory authorities at any time also may implement new standards, or change their
interpretation and enforcement of existing standards, for the manufacture, packaging or testing of our products. Any failure
to comply with applicable regulations may result in fines and civil penalties, suspension of production, product seizure or
recall, imposition of a consent decree, or withdrawal of product approval, and would limit the availability of DEXTENZA,
ReSure Sealant and our product candidates that we manufacture.
Any manufacturing defect or error discovered after products have been produced and distributed also could result in
significant consequences, including costly recall procedures, re-stocking costs, damage to our reputation and potential for
product liability claims.
If our sole clinical manufacturing facility is damaged or destroyed or production at this facility is otherwise interrupted,
our business and prospects would be negatively affected.
If our manufacturing facility or the equipment in it is damaged or destroyed, we may not be able to quickly or
inexpensively replace our manufacturing capacity or replace it at all. In the event of a temporary or protracted loss of this
facility or equipment, we might not be able to transfer manufacturing to another facility or to a third party. Even if we
could transfer our manufacturing to another facility or a third party, the shift would likely be expensive and time-
consuming, particularly since any new facility would need to comply with the necessary regulatory requirements and to be
inspected and qualified. We would also need FDA approval before any products manufactured at that facility could be used
for clinical or commercial supply. Such an event could delay our clinical trials or reduce our product sales.
Currently, we maintain insurance coverage against damage to our property and equipment in the amount of up to
$26.2 million and to cover business interruption and research and development restoration expenses in the amount of up to
$2.8 million. However, our insurance coverage may not reimburse us, or may not be sufficient to reimburse us, for any
expenses or losses we may suffer. We may be unable to meet our requirements for DEXTENZA, ReSure Sealant, or any of
our product candidates if there were a catastrophic event or failure of our current manufacturing facility or processes.
We expect to continue to contract with third parties for at least some aspects of the production of our products and
product candidates. This increases the risk that we will not have sufficient quantities of our products or product
candidates or such quantities at an acceptable cost, which could delay, prevent or impair our development or
commercialization efforts.
We currently rely on third parties for some aspects of the production of DEXTENZA, ReSure Sealant and our
product candidates for commercialization and preclinical testing and clinical trials, including supply of active
pharmaceutical ingredient drug substance, PEG, the molecule that forms the basis of our hydrogels, and other raw
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materials and for sterilization of the finished product. In addition, while we believe that our existing manufacturing facility,
or additional facilities that we will be able to build, will be sufficient to meet our requirements for manufacturing
DEXTENZA, ReSure Sealant and any of our product candidates for which we obtain marketing approval, we may in the
future need to rely on third-party manufacturers for some aspects of the manufacture of our products or product candidates.
We do not have any long-term supply agreements in place for the clinical or commercial supply of any drug
substances or raw materials for DEXTENZA, ReSure Sealant or any of our product candidates. We purchase drug
substance and raw materials, including the chemical constituents for our hydrogel, from independent suppliers on a
purchase order basis. Any performance failure or refusal to supply drug substance or raw materials on the part of our
existing or future suppliers could delay clinical development, marketing approval or commercialization of our products. If
our current suppliers do not perform as we expect, we may be required to replace one or more of these suppliers. In
particular, we depend on a sole source supplier for the supply of our PEG. This sole source supplier may be unwilling or
unable to supply PEG to us reliably, continuously and at the levels we anticipate or are required by the market. Although
we believe that there are a number of potential long-term replacements to our suppliers, including our PEG supplier, we
may incur added costs and delays in identifying and qualifying any such replacements.
Reliance on third parties for aspects of the supply of our products and product candidates entails additional risks,
including:
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reliance on the third party for regulatory compliance and quality assurance;
the possible misappropriation of our proprietary information, including our trade secrets and know-how;
the possible breach of an agreement by the third party; and
the possible termination or nonrenewal of an agreement by the third party at a time that is costly or inconvenient
for us.
Third-party suppliers or manufacturers may not be able to comply with quality assurance standards, cGMP
regulations or similar regulatory requirements outside the United States. Our failure, or the failure of our third parties, to
comply with applicable regulations could result in sanctions being imposed on us, including clinical holds, fines,
injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of product
candidates or products, operating restrictions and criminal prosecutions, any of which could significantly and adversely
affect supplies of our products and product candidates.
Our potential future dependence upon others for the manufacture of our products and product candidates may
adversely affect our future profit margins and our ability to commercialize any products that receive regulatory approval on
a timely and competitive basis.
Risks Related to Commercialization
Even though DEXTENZA and ReSure Sealant have received marketing approval from the FDA and even if any of our
product candidates receives marketing approval, any of these products may fail to achieve the degree of market
acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial
success, and the market opportunity for these products may be smaller than we estimate.
DEXTENZA, ReSure Sealant, or any of our product candidates that receives marketing approval may fail to gain
market acceptance by physicians, patients, third-party payors and others in the medical community. We commercially
launched ReSure Sealant in the first quarter of 2014 and DEXTENZA for the treatment of post-surgical ocular
inflammation and pain in July 2019 and cannot yet accurately predict whether either product will gain market acceptance
and become commercially successful. For example, we previously commenced commercialization in Europe of an earlier
version of ReSure Sealant that was approved and marketed as an ocular bandage. We recognized $0.1 million of revenue
from the commercialization of this product through 2012. However, we ceased our commercialization of the product in
2012 to focus on the ongoing clinical development of ReSure Sealant pursuant to FDA requirements. If our products do
not achieve an adequate level of acceptance, we may not generate significant product revenue and we may not become
profitable.
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The degree of market acceptance of DEXTENZA, ReSure Sealant, or any product candidate for which we obtain
marketing approval will depend on a number of factors, including:
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the efficacy and potential advantages compared to alternative treatments;
our ability to offer our products for sale at competitive prices, particularly in light of the lower cost of alternative
treatments;
the clinical indications for which the product is approved;
the convenience and ease of administration compared to alternative treatments, including the intracanalicular
insert retention rate for our intracanalicular insert products and product candidates;
the willingness of the target patient population to try new therapies and of physicians to prescribe these
therapies;
the strength of our marketing and distribution support;
timing of market introduction of competitive products;
the availability of third-party coverage and adequate reimbursement and, for DEXTENZA and ReSure Sealant,
the lack of separate reimbursement when used as part of a cataract surgery procedure;
the prevalence and severity of any side effects; and
any restrictions on the use of our products together with other medications.
For example, because we have not conducted any clinical trials to date comparing the effectiveness of DEXTENZA
directly to currently approved alternative treatments for either post-surgical ocular inflammation and pain following
cataract surgery or allergic conjunctivitis, it is possible that the market acceptance of DEXTENZA could be less than if we
had conducted such trials. Although market research we have commissioned indicates that a majority of ophthalmologists
believe DEXTENZA could become a new standard of care due to its potential ability to improve compliance with limited
toxicity concerns, market acceptance for DEXTENZA could be substantially less than such research indicates, and we may
not be able to achieve the market share we anticipate.
Our assessment of the potential market opportunity for DEXTENZA, ReSure Sealant and our product candidates is
based on industry and market data that we obtained from industry publications and research, surveys and studies conducted
by third parties. Industry publications and third-party research, surveys and studies generally indicate that their information
has been obtained from sources believed to be reliable, although they do not guarantee the accuracy or completeness of
such information. While we believe these industry publications and third-party research, surveys and studies are reliable,
we have not independently verified such data. If the actual market for DEXTENZA, ReSure Sealant or any of our product
candidates is smaller than we expect, our product revenue may be limited and it may be more difficult for us to achieve or
maintain profitability.
If we are unable to establish and maintain adequate sales, marketing and distribution capabilities, we may not be
successful in commercializing DEXTENZA, ReSure Sealant, or any product candidates if and when they are approved.
We have limited experience in the sale, marketing and distribution of drug and device products. To achieve
commercial success for DEXTENZA, ReSure Sealant, and any product candidate for which we obtain marketing approval,
we will need to establish and maintain adequate sales, marketing and distribution capabilities, either ourselves or through
collaborations or other arrangements with third parties. We have built our own highly targeted, key account sales force for
DEXTENZA that focuses on ambulatory surgical centers responsible for the largest volumes of cataract
surgery. Previously, we commercially launched ReSure Sealant in February 2014 on a region by region basis in the United
States through a network of independent distributors. In early 2017, we terminated these distributors and hired a
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contract sales force of four representatives to sell ReSure Sealant. We have subsequently terminated the agreement with
the contract sales force to sell ReSure Sealant.
If we decide to commercialize any of our products outside of the United States, we would expect to utilize a variety
of collaboration, distribution and other marketing arrangements with one or more third parties to commercialize any
product that receives marketing approval. We expect that a direct sales force will be required to effectively market and sell
OTX-TP, if approved for marketing. We also intend to rely on Regeneron to commercialize our extended-delivery
hydrogel formulation in combination with Regeneron’s large molecule VEGF-targeting compounds. Because we have not
historically evaluated whether to seek regulatory approval for any of our products or product candidates outside of the
United States, pending potential receipt of regulatory approval for the applicable product candidate in the United States, at
this time we cannot be certain when, if ever, we will recognize revenue from commercialization of our products or product
candidates in any international markets. If we decide to commercialize our products outside of the United States, we
expect to utilize a variety of types of collaboration, distribution and other marketing arrangements with one or more third
parties to commercialize any product of ours that receives marketing approval. These may include independent
distributors, pharmaceutical companies or our own direct sales organization.
There are risks involved with both establishing our own sales, marketing and distribution capabilities and with
entering into arrangements with third parties to perform these services. We may not be successful in entering into
arrangements with third parties to sell, market and distribute our products or may be unable to do so on terms that are most
beneficial to us. Such third parties may have interests that differ from ours. We likely will have little control over such
third parties, and any of them may fail to devote the necessary resources and attention to market, sell and distribute our
products effectively. Our product revenues and our profitability, if any, under third-party collaboration, distribution or
other marketing arrangements, including our collaboration with Regeneron, may also be lower than if we were to sell,
market and distribute a product ourselves. On the other hand, recruiting and training a sales force is expensive and time-
consuming and could delay any product launch. If the commercial launch of any product or product candidate for which
we recruit a sales force and establish marketing capabilities is delayed or does not occur for any reason, we would have
prematurely or unnecessarily incurred these commercialization expenses. This may be costly, and our investment would be
lost if we cannot retain or reposition our sales and marketing personnel.
Other factors that may inhibit our efforts to commercialize products on our own include:
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our inability to recruit, train and retain adequate numbers of effective sales and marketing personnel;
the inability of sales personnel to obtain access to physicians or lack of adequate number of physicians to use or
prescribe our products;
the lack of complementary products to be offered by sales personnel, which may put us at a competitive
disadvantage relative to companies with more extensive product lines; and
unforeseen costs and expenses associated with creating an independent sales and marketing organization.
If we do not establish sales, marketing and distribution capabilities successfully, either on our own or in collaboration
with third parties, we will not be successful in commercializing DEXTENZA, ReSure Sealant or any of our product
candidates.
We face substantial competition, which may result in others discovering, developing or commercializing products before
or more successfully than we do.
The development and commercialization of new drug and device products is highly competitive. We face
competition with respect to our products and product candidates, and will face competition with respect to any other
product candidates that we may seek to develop or commercialize in the future, from major pharmaceutical companies,
specialty pharmaceutical companies and biotechnology companies worldwide. Potential competitors also include academic
institutions, government agencies and other public and private research organizations that conduct research, seek patent
protection and establish collaborative arrangements for research, development, manufacturing and commercialization.
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Our products and product candidates target markets that are already served by a variety of competing products based
on a number of active pharmaceutical ingredients. Many of these existing products have achieved widespread acceptance
among physicians, patients and payors for the treatment of ophthalmic diseases and conditions. In addition, many of these
products are available on a generic basis, and our products and product candidates may not demonstrate sufficient
additional clinical benefits to physicians, patients or payors to justify a higher price compared to generic products. In many
cases, insurers or other third-party payors, particularly Medicare, encourage the use of generic products. Given that we are
developing products based on FDA-approved therapeutic agents, our products and product candidates, if approved, will
face competition from generic and branded versions of existing drugs based on the same active pharmaceutical ingredients
that are administered in a different manner, typically through eye drops or intravitreal injections.
Because the active pharmaceutical ingredients in our products and product candidates, other than those developed
under the Regeneron collaboration, are available on a generic basis, or are soon to be available on a generic basis,
competitors will be able to offer and sell products with the same active pharmaceutical ingredient as our products so long
as these competitors do not infringe the patents that we license. For example, our licensed patents related to our
intracanalicular insert products and product candidates largely relate to the hydrogel composition of the intracanalicular
inserts and certain drug-release features of the inserts. As such, if a third party were able to design around the formulation
and process patents that we license and create a different formulation using a different production process not covered by
our licensed patents or patent applications, we would likely be unable to prevent that third party from manufacturing and
marketing its product.
Icon Biosciences, Inc. received FDA approval of DEXYCU in February 2018. DEXYCU is an injection of
dexamethasone into the anterior chamber of the eye to treat inflammation associated with cataract surgery. Other
companies have also advanced into Phase 3 clinical development biodegradable, programmed-release drug delivery
product candidates that could compete with our intracanalicular insert products and product candidates. ReSure Sealant is
the first and only surgical sealant approved for ophthalmic use in the United States, but will compete with sutures as an
alternative method for closing ophthalmic wounds. Multiple companies, including our collaborator Regeneron, are
exploring in early stage development alternative means to deliver anti-VEGF and TKI products in an extended-delivery
fashion to the back of the eye.
Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products
that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than our
products. Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than we may
obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to
enter the market.
Many of the companies against which we are competing or against which we may compete in the future have
significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing,
conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. Mergers and
acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated
among a smaller number of our competitors. Smaller and other early stage companies may also prove to be significant
competitors, particularly through collaborative arrangements with large and established companies. These third parties
compete with us in recruiting and retaining qualified scientific and management personnel, establishing clinical trial sites
and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our
programs.
DEXTENZA, ReSure Sealant and any product candidates for which we obtain marketing approval may become subject
to unfavorable pricing regulations, third-party coverage or reimbursement practices or healthcare reform initiatives,
which could harm our business.
Our ability to commercialize DEXTENZA, ReSure Sealant or any product candidates that we may develop
successfully will depend, in part, on the extent to which coverage and adequate reimbursement for these products and
related treatments will be available from government healthcare programs, private health insurers, managed care plans and
other organizations. Government authorities and third-party payors, such as private health insurers and health maintenance
organizations, decide which medications they will pay for and establish reimbursement levels. A primary trend in the U.S.
healthcare industry and elsewhere is cost containment. Government authorities and third-party payors have attempted to
control costs by limiting coverage and the amount of reimbursement for particular
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medications. Increasingly, third-party payors are requiring that drug and device companies provide them with
predetermined discounts from list prices and are challenging the prices charged for medical products. Coverage and
reimbursement may not be available for DEXTENZA, ReSure Sealant or any other product that we commercialize and,
even if they are available, the level of reimbursement may not be satisfactory.
Inadequate reimbursement may adversely affect the demand for, or the price of, DEXTENZA, ReSure Sealant or any
product candidate for which we obtain marketing approval. Obtaining and maintaining adequate reimbursement for our
products may be difficult. We may be required to conduct expensive pharmacoeconomic studies to justify coverage and
reimbursement or the level of reimbursement relative to other therapies. If coverage and adequate reimbursement are not
available or reimbursement is available only to limited levels, we may not be able to successfully commercialize
DEXTENZA, ReSure Sealant or any product candidates for which we obtain marketing approval.
There may be significant delays in obtaining coverage and reimbursement for newly approved drugs and devices, and
coverage may be more limited than the indications for which the drug is approved by the FDA or similar regulatory
authorities outside the United States. Moreover, eligibility for coverage and reimbursement does not imply that a drug will
be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution
expenses. Interim reimbursement levels for new drugs, if applicable, may also not be sufficient to cover our costs and may
not be made permanent. Reimbursement rates may vary according to the use of the drug and the clinical setting in which it
is used, may be based on reimbursement levels already set for lower cost drugs and may be incorporated into existing
payments for other services. Net prices for drugs may be reduced by mandatory discounts or rebates required by
government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of
drugs from countries where they may be sold at lower prices than in the United States. Third-party payors often rely upon
Medicare coverage policy and payment limitations in setting their own reimbursement policies. Our inability to promptly
obtain coverage and adequate reimbursement rates from both government-funded and private payors for any FDA-
approved products that we develop would compromise our ability to generate revenues and become profitable.
The regulations that govern marketing approvals, pricing, coverage and reimbursement for new drug and device
products vary widely from country to country. Current and future legislation may significantly change the approval
requirements in ways that could involve additional costs and cause delays in obtaining approvals. Some countries require
approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins after
marketing or product licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains
subject to continuing governmental control even after initial approval is granted. As a result, we might obtain marketing
approval for a product in a particular country, but then be subject to price regulations that delay our commercial launch of
the product, possibly for lengthy time periods, and negatively impact the revenues we are able to generate from the sale of
the product in that country. To obtain reimbursement or pricing approval in some countries, we may be required to conduct
a clinical trial that compares the cost-effectiveness of our product or product candidate to other available
therapies. Adverse pricing limitations may hinder our ability to recoup our investment in one or more products or product
candidates, even if our product candidates obtain marketing approval.
DEXTENZA, ReSure Sealant or any product candidate for which we obtain marketing approval in the United States
or in other countries may not be considered medically reasonable and necessary for a specific indication, may not be
considered cost-effective by third-party payors, coverage and an adequate level of reimbursement may not be available, and
reimbursement policies of third-party payors may adversely affect our ability to sell our products and product candidates
profitably. ReSure Sealant is not separately reimbursed when used as part of a cataract surgery procedure, which could
limit the degree of market acceptance of this product by surgeons. In addition, while DEXTENZA may be considered a
post-surgical product in the same fashion as eye drops, it may instead be categorized as an inter-operative product. If
DEXTENZA is categorized as an inter-operative product, it will not be subject to separate reimbursement, which could
likewise limit its market acceptance.
We applied for a transitional pass-through reimbursement status, or C-code, on November 30, 2018 for DEXTENZA
from the Centers for Medicare and Medicaid Services, or CMS. In May 2019, we received formal notification from CMS
that it had approved transitional pass-through payment status and established a new C-Code for DEXTENZA that
subsequently became effective on July 1, 2019. Pricing for DEXTENZA while in pass-through status to be approximately
$538 per surgery, and we expected pass-through status would remain in effect for up to three years from the effective date
of the C-code. We also submitted an application to the CMS for a J-Code for DEXTENZA on December 28, 2018, and
received a specific and permanent J-Code in July 2019 which became effective on October 1,
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2019. With the effectiveness of our permanent J-Code as of October 1, 2019, our C-code is no longer in effect. There are
no assurances that we will be successful in obtaining and retaining reimbursement for our products and product candidates.
Product liability lawsuits against us could cause us to incur substantial liabilities and to limit commercialization of any
products that we develop.
We face an inherent risk of product liability exposure related to the use of our product candidates that we develop in
human clinical trials. We face an even greater risk for any products we develop and commercially sell, including
DEXTENZA and ReSure Sealant. If we cannot successfully defend ourselves against claims that our product candidates or
products caused injuries, we will incur substantial liabilities. Regardless of merit or eventual outcome, liability claims may
result in:
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decreased demand for any product candidates or products that we develop;
injury to our reputation and significant negative media attention;
withdrawal of clinical trial participants;
significant costs to defend the related litigation;
substantial monetary awards to trial participants or patients;
loss of revenue;
reduced time and attention of our management to pursue our business strategy; and
the inability to commercialize any products that we develop.
We currently hold $10.0 million in U.S. product liability insurance coverage in the aggregate, with a per incident
limit of $10.0 million and approximately $15.0 million in product liability insurance in another jurisdiction in which we
operate, with a per incident liability limit of approximately $15.0 million. These policies may not be adequate to cover all
liabilities that we may incur. We will need to increase our insurance coverage as we expand our clinical trials and our sales
of DEXTENZA, ReSure Sealant and any product candidates for which we obtain marketing approval.
We will need to further increase our insurance coverage if we commence commercialization of any of our product
candidates for which we obtain marketing approval. Insurance coverage is increasingly expensive. We may not be able to
maintain insurance coverage at a reasonable cost or in an amount adequate to satisfy any liability that may arise.
Risks Related to Our Dependence on Third Parties
We will depend heavily on our collaboration with Regeneron for the success of our extended-delivery hydrogel
formulation in combination with Regeneron’s large molecule VEGF-targeting compounds. If Regeneron does not
exercise its option, terminates our collaboration agreement or is unable to meet its contractual obligations, it could
negatively impact our business.
In October 2016, we entered into a strategic collaboration, option and license agreement, or Collaboration
Agreement, with Regeneron for the development and potential commercialization of products containing our extended-
delivery hydrogel formulation in combination with Regeneron’s large molecule VEGF-targeting compounds. Our ability to
generate revenues from the Collaboration Agreement will depend on our and Regeneron’s abilities to successfully perform
the functions assigned to each of us under the Collaboration Agreement. We did not receive any upfront payment under the
Collaboration Agreement, although Regeneron has an option to enter into an exclusive, worldwide license, with the right to
sublicense, under our intellectual property to develop and commercialize products containing our extended-delivery
hydrogel formulation in combination with Regeneron’s large molecule VEGF-targeting compounds. Regeneron has agreed
to pay us $10 million upon exercise of the option. The option is exclusive until 12 months after Regeneron has received a
product candidate in accordance with a collaboration plan and non-
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exclusive for an additional six months following the end of the exclusive period. In December 2017, we delivered to
Regeneron what we believed to be the final formulation for Regeneron’s initial preclinical tolerability study. Regeneron
initiated the preclinical study in early 2018. We and Regeneron have subsequently reached an understanding that the
proposed formulation was not final and have ceased development of it and the corresponding option period under the
Collaboration Agreement for the initial proposed formulation has stopped. We are currently in discussions with Regeneron,
in accordance with the terms of the Collaboration Agreement, regarding the development of an alternative formulation and
the related impact on the designated option period. Although we are engaged in ongoing discussions with Regeneron,
Regeneron has not informed us of its decision to exercise the option. While we await a decision from Regeneron, we are
not actively pursuing further formulation development or other preclinical testing under the Collaboration
Agreement. Under the Collaboration Agreement, we are obligated to reimburse Regeneron for certain development costs
incurred by Regeneron under the collaboration plan during the period through the completion of the initial clinical trial,
subject to a cap of $25 million, which cap may be increased by up to $5 million under certain circumstances. We are also
entitled to receive under the terms of the Collaboration Agreement specified development, regulatory and sales milestone
payments, as well as royalty payments.
If Regeneron exercises the option, the Collaboration Agreement will expire on a licensed product-by-licensed
product and country-by-country basis upon the expiration of the later of 10 years from the date of first commercial sale in
such country or the expiration of all patent rights covering the licensed product in such country. Regeneron may terminate
the Collaboration Agreement at any time after exercise of the option upon 60 days’ prior written notice. Either party may,
subject to a cure period, terminate the Collaboration Agreement in the event of the other party’s uncured material breach, in
addition to other specified termination rights.
If we are unable to achieve the preclinical milestones set forth in the collaboration plan, Regeneron may not exercise
the option, in which case we would not receive the $10 million payment in connection with such option and would have
incurred significant development expenses. Even if Regeneron does exercise its option, we or Regeneron may not be
successful in achieving the necessary preclinical, clinical, regulatory and sales milestones in connection with the
collaboration. Further, if Regeneron were to breach or terminate the Collaboration Agreement or if Regeneron elects not to
exercise the option we granted it and not to proceed in the collaboration, we may not be able to obtain, or may be delayed
in obtaining, marketing approvals for intravitreal implant product candidates developed pursuant to the Collaboration
Agreement and will not be able to, or may be delayed in our efforts to, successfully commercialize our intravitreal implant
product candidates. We may not be able to seek and obtain a viable, alternative collaborator to partner with for the
development and commercialization of the licensed products on similar terms or at all.
We have entered into collaborations with third parties to develop certain product candidates, and in the future may enter
into collaborations with third parties for the commercialization of DEXTENZA, ReSure Sealant or the development or
commercialization of our product candidates. If our collaborations are not successful, we may not be able to capitalize
on the market potential of these products or product candidates.
We have in the past entered into collaboration agreements with third parties, including our collaboration with
Regeneron, and expect to utilize a variety of types of collaboration, distribution and other marketing arrangements with
third parties to commercialize DEXTENZA, ReSure Sealant, or any of our product candidates for which we obtain
marketing approval in markets outside the United States. We also may enter into arrangements with third parties to
perform these services in the United States if we do not establish our own sales, marketing and distribution capabilities in
the United States for our products and product candidates or if we determine that such third-party arrangements are
otherwise beneficial. We also may seek additional third-party collaborators for development and commercialization of
other product candidates, such as OTX-TP. Our likely collaborators for any sales, marketing, distribution, development,
licensing or broader collaboration arrangements include large and mid-size pharmaceutical companies, regional and
national pharmaceutical companies and biotechnology companies. Other than our collaboration with Regeneron, we are
not currently party to any such arrangement. Our ability to generate revenues from these arrangements will depend on our
collaborators’ abilities and efforts to successfully perform the functions assigned to them in these arrangements.
Our collaboration with Regeneron poses, and any future collaborations likely will pose a number of risks, including
the following:
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collaborators have significant discretion in determining the amount and timing of efforts and resources that they
will apply to these collaborations;
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collaborators may not perform their obligations as expected;
collaborators may not pursue development and commercialization of our products or product candidates that
receive marketing approval or may elect not to continue or renew development or commercialization programs
based on results of clinical trials or other studies, changes in the collaborators’ strategic focus or available
funding, or external factors, such as an acquisition, that divert resources or create competing priorities;
collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical
trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a
product candidate for clinical testing;
collaborators could independently develop, or develop with third parties, products that compete directly or
indirectly with our products or product candidates if the collaborators believe that competitive products are more
likely to be successfully developed or can be commercialized under terms that are more economically attractive
than ours;
product candidates discovered in collaboration with us may be viewed by our collaborators as competitive with
their own product candidates or products, which may cause collaborators to cease to devote resources to the
commercialization of our product candidates;
a collaborator with marketing and distribution rights to one or more of our product candidates that achieve
regulatory approval may not commit sufficient resources to the marketing and distribution of such product or
products;
disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or the
preferred course of development, might cause delays or termination of the research, development or
commercialization of products or product candidates, might lead to additional responsibilities for us with respect
to products or product candidates, or might result in litigation or arbitration, any of which would divert
management attention and resources, be time-consuming and expensive;
collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary
information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or
proprietary information or expose us to potential litigation;
collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and
potential liability; and
collaborations may be terminated for the convenience of the collaborator and, if terminated, we could be
required to raise additional capital to pursue further development or commercialization of the applicable
products or product candidates.
Collaboration agreements may not lead to development or commercialization of products or product candidates in the
most efficient manner, or at all. If any collaborations that we enter into do not result in the successful development and
commercialization of products or if one of our collaborators terminates its agreement with us, we may not receive any
future research funding or milestone or royalty payments under the collaboration. If we do not receive the funding we
expect under these agreements, our development of our products or product candidates could be delayed and we may need
additional resources to develop our products or product candidates. All of the risks relating to product development,
regulatory approval and commercialization described in this prospectus supplement also apply to the activities of our
collaborators.
Additionally, subject to its contractual obligations to us, if a collaborator of ours were to be involved in a business
combination, it might deemphasize or terminate the development or commercialization of any product or product candidate
licensed to it by us. If one of our collaborators terminates its agreement with us, we may find it more difficult to attract
new collaborators and our perception in the business and financial communities could be harmed.
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If we are not able to establish additional collaborations, we may have to alter our development and commercialization
plans and our business could be adversely affected.
For some of our other product candidates, we may decide to collaborate with pharmaceutical, biotechnology and
medical device companies for the development and potential commercialization of those product candidates. We face
significant competition in seeking appropriate collaborators. Whether we reach a definitive agreement for a collaboration
will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and
conditions of the proposed collaboration and the proposed collaborator’s evaluation of a number of factors. Those factors
may include the design or results of clinical trials, the likelihood of approval by the FDA or similar regulatory authorities
outside the United States, the potential market for the subject product candidate, the costs and complexities of
manufacturing and delivering such product candidate to patients, the potential of competing products, the existence of
uncertainty with respect to our ownership of technology, which can exist if there is a challenge to such ownership without
regard to the merits of the challenge, and industry and market conditions generally. The collaborator may also consider
alternative product candidates or technologies for similar indications that may be available to collaborate on and whether
such a collaboration could be more attractive than the one with us for our product candidate. We may also be restricted
under future license agreements from entering into agreements on certain terms with potential
collaborators. Collaborations are complex and time-consuming to negotiate and document. In addition, there have been a
significant number of recent business combinations among large pharmaceutical companies that have resulted in a reduced
number of potential future collaborators.
We have conducted preclinical testing of protein-based anti-VEGF compounds in collaboration with Regeneron to
explore the feasibility of delivering their drugs in combination with our hydrogel. The initial drug selected for preclinical
testing under this collaboration was aflibercept, marketed under the brand name Eylea. We may explore broader
collaborations for the development and potential commercialization of our hydrogel technology in combination with other
large molecules with targets other than VEGF for the treatment of back-of-the-eye diseases and conditions.
If we are unable to reach agreements with suitable collaborators on a timely basis, on acceptable terms, or at all, we
may have to curtail the development of a product candidate, reduce or delay its development program or one or more of our
other development programs, delay its potential commercialization or reduce the scope of any sales or marketing activities,
or increase our expenditures and undertake development or commercialization activities at our own expense. If we elect to
fund and undertake development or commercialization activities on our own, we may need to obtain additional expertise
and additional capital, which may not be available to us on acceptable terms or at all. If we fail to enter into collaborations
and do not have sufficient funds or expertise to undertake the necessary development and commercialization activities, we
may not be able to further develop our product candidates or bring them to market or continue to develop our product
platform.
Although the majority of our clinical development is administered and managed by our own employees, we have relied,
and may continue to rely, on third parties for certain aspects of our clinical development, and those third parties may
not perform satisfactorily, including failing to meet deadlines for the completion of such trials.
Our employees have administered and managed most of our clinical development work, including our clinical trials
for ReSure Sealant and our clinical trials for DEXTENZA for the treatment of post-surgical ocular inflammation and pain
following cataract surgery. However, we have relied and may continue to rely on third parties, such as contract research
organizations, or CROs, to conduct future clinical trials of our product candidates, including DEXTENZA for the treatment
of ocular itching associated with allergic conjunctivitis. If we deem necessary, we may engage third parties, such as CROs,
clinical data management organizations, medical institutions and clinical investigators, to conduct or assist in our clinical
trials or other clinical development work. If we are unable to enter into an agreement with a CRO or other service provider
when required, our product development activities would be delayed.
Our reliance on third parties for research and development activities reduces our control over these activities but does
not relieve us of our responsibilities. For example, we remain responsible for ensuring that each of our clinical trials is
conducted in accordance with the general investigational plan and protocols for the trial. Moreover, the FDA requires us to
comply with standards, commonly referred to as good clinical practices for conducting, recording and reporting the results
of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity and
confidentiality of trial participants are protected. We are also required to register ongoing clinical trials and post the results
of completed clinical trials on a government-sponsored database, ClinicalTrials.gov, within specified timeframes. Failure
to do so can result in fines, adverse publicity and civil and criminal sanctions. If we engage third
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parties and they do not successfully carry out their contractual duties, meet expected deadlines or conduct our clinical trials
in accordance with regulatory requirements or our stated protocols, we will not be able to obtain, or may be delayed in
obtaining, marketing approvals for our product candidates and will not be able to, or may be delayed in our efforts to,
successfully commercialize our product candidates.
The novel coronavirus outbreak may affect our ability to recruit or retain patients for our clinical trials, disrupt our
supply chains or have other adverse effects on our business and operations.
In December 2019, an outbreak of respiratory illness caused by a novel coronavirus began in Wuhan, China. As of March
2020, that outbreak has led to more than a hundred thousand confirmed cases worldwide, with many countries throughout
the world confirming cases. The World Health Organization has declared the outbreak a global public health emergency. In
addition to those who have been directly affected, millions more have been affected by government efforts in China and
around the world to slow the spread of the outbreak through quarantines, travel restrictions, heightened border scrutiny and
other measures. The outbreak and government measures taken in response have also had significant direct and indirect
impacts on businesses and commerce as worker shortages have occurred; supply chains have been disrupted; facilities and
production have been suspended; and demand for certain goods and services, such as medical services and supplies, has
spiked, while demand for other goods and services, such as travel, has fallen.
The future progression of the outbreak and its effects on our business and operations are highly uncertain and cannot be
predicted. As we seek to enroll patients for our clinical trials at sites located both in the United States and internationally,
we may face difficulties recruiting or retaining patients if patients are affected by the virus or are fearful of traveling to our
clinical trial sites because of the outbreak. We and our third-party contract manufacturers, CROs and clinical sites may also
face disruptions in procuring items that are essential for our research and development activities that are sourced from
abroad or for which there are shortages because of ongoing efforts to address the outbreak, including, for example, raw
materials used in the manufacture of our product candidates; medical and laboratory supplies used in our clinical trials or
preclinical studies; or animals that are used for preclinical testing.
Risks Related to Our Intellectual Property
We may be unable to obtain and maintain patent protection for our technology and products, or the scope of the patent
protection obtained may not be sufficiently broad, such that our competitors could develop and commercialize
technology and products similar or identical to ours, and our ability to successfully commercialize our technology and
products may be impaired.
Our success depends in large part on our and our licensor’s ability to obtain and maintain patent protection in the
United States and other countries with respect to our proprietary technology and products. We and our licensor have sought
to protect our proprietary position by filing patent applications in the United States and abroad related to our novel
technologies, products and product candidates. Some of our licensed patents that we believe are integral to our hydrogel
technology platform have terms that extend through at least 2024. However, other broader patents within our patent
portfolio expire have already expired. Given the amount of time required for the development, testing and regulatory
review of new product candidates, patents protecting our candidates might expire before or shortly after such candidates are
commercialized. As a result, our patent portfolio would be less effective in excluding others from commercializing
products similar or identical to ours. The patent prosecution process is expensive and time-consuming, and we may not
have filed or prosecuted and may not be able to file and prosecute all necessary or desirable patent applications at a
reasonable cost or in a timely manner. It is also possible that we will fail to identify patentable aspects of our research and
development output before it is too late to obtain patent protection.
In some circumstances, we do not have the right to control the preparation, filing and prosecution of patent
applications, or to enforce or maintain the patents, covering technology that we license from third parties. In particular, the
license agreement that we have entered into with Incept LLC, or Incept, an intellectual property holding company, which
covers a significant portion of the patent rights and the technology for ReSure Sealant and our product candidates, provides
that, with limited exceptions, Incept has sole control and responsibility for ongoing prosecution for certain patents covered
by the license agreement. In addition, although we have a right under the Incept license to bring suit against third parties
who infringe such licensed patents in our fields, other Incept licensees may also have the right to enforce these patents in
their own respective fields without our oversight or control. Those other licensees may choose to enforce our licensed
patents in a way that harms our interest, for example, by advocating for claim
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interpretations or agreeing on invalidity positions that conflict with our positions or our interest. For example, three of our
licensed patents related to ReSure Sealant were invalidated and rendered unenforceable following their assertion by Integra
LifeSciences Holdings Corporation, another licensee of Incept. We also have no right to control the defense of
such licensed patents if their validity or scope is challenged before the U.S. Patent and Trademark Office, or USPTO,
European Patent Office, or other patent office or tribunal. Instead, we would essentially rely on our licensor to defend such
challenges, and it may not do so in a way that would best protect our interests. Therefore, certain of our licensed patents
and applications may not be prosecuted, enforced, defended or maintained in a manner consistent with the best interests of
our business. If Incept fails to prosecute, enforce or maintain such patents, or loses rights to those patents, our licensed
patent portfolio may be reduced or eliminated.
The patent position of pharmaceutical, biotechnology and medical device companies generally is highly uncertain,
involves complex legal and factual questions and has in recent years been the subject of much litigation. As a result, the
issuance, scope, validity, enforceability and commercial value of our patent rights, including our licensed patent rights, are
highly uncertain. Our and our licensor’s pending and future patent applications may not result in patents being issued
which protect our technology or products or which effectively prevent others from commercializing competitive
technologies and products. In addition, the laws of foreign countries may not protect our rights to the same extent as the
laws of the United States. For example, unlike patent law in the United States, European patent law precludes the
patentability of methods of treatment of the human body and imposes substantial restrictions on the scope of claims it will
grant if broader than specifically disclosed embodiments. Moreover, we have no patent protection and likely will never
obtain patent protection for ReSure Sealant outside the United States and Canada. We have only three issued patents
outside of the United States that cover all three intracanalicular insert products and product candidates. We have three
licensed patent families in Europe and certain other parts of the world for our intravitreal drug delivery product candidates,
but only one patent issuance to date outside of the United States. Patents might not be issued and we may never obtain any
patent protection or may only obtain substantially limited patent protection outside of the United States with respect to our
products.
Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications
in the United States and other jurisdictions are typically not published until 18 months after filing, or in some cases not at
all. Therefore, we cannot know with certainty whether we or our licensor were the first to make the inventions claimed in
our licensed patents or pending patent applications, or that we or our licensors were the first to file for patent protection of
such inventions. Databases for patents and publications, and methods for searching them, are inherently limited so it is not
practical to review and know the full scope of all issued and pending patent applications. As a result, the issuance, scope,
validity, enforceability and commercial value of our licensed patent rights are uncertain. Our pending and future patent
applications may not result in patents being issued which protect our technology or products, in whole or in part, or which
effectively prevent others from commercializing competitive technologies and products. In particular, during prosecution
of any patent application, the issuance of any patents based on the application may depend upon our ability to generate
additional preclinical or clinical data that support the patentability of our proposed claims. We may not be able to generate
sufficient additional data on a timely basis, or at all. Moreover, changes in either the patent laws or interpretation of the
patent laws in the United States and other countries may diminish the value of our patents or narrow the scope of our patent
protection.
Recent patent reform legislation could increase the uncertainties and costs surrounding the prosecution of our patent
applications and the enforcement or defense of our issued patents. The Leahy-Smith America Invents Act, or the Leahy-
Smith Act, includes a number of significant changes to United States patent law. These include provisions that affect the
way patent applications are prosecuted and may also affect patent litigation. The USPTO recently developed new
regulations and procedures to govern administration of the Leahy-Smith Act, and many of the substantive changes to patent
law associated with the Leahy-Smith Act, and in particular, the first to file provisions, only became effective on March 16,
2013. The first to file provisions limit the rights of an inventor to patent an invention if not the first to file an application
for patenting that invention, even if such invention was the first invention. Accordingly, it is not clear what, if any, impact
the Leahy-Smith Act will have on the operation of our business. However, the Leahy-Smith Act and its implementation
could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or
defense of our issued patents. For example, the Leahy-Smith Act provides a new administrative tribunal known as the
Patent Trial and Appeals Board, or PTAB, that provides a venue for companies to challenge the validity of competitor
patents at a cost that is much lower than district court litigation and on timelines that are much faster. Although it is not
clear what, if any, long term impact the PTAB proceedings will have on the operation of our business, the initial results of
patent challenge proceedings before the PTAB since its inception in 2013 have resulted in the invalidation of many U.S.
patent claims. The availability of the PTAB as a lower-cost, faster and potentially more
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potent tribunal for challenging patents could therefore increase the likelihood that our own licensed patents will be
challenged, thereby increasing the uncertainties and costs of maintaining and enforcing them. Moreover, if such challenges
occur, as indicated above, we have no right to control the defense. Instead, we would essentially rely on our licensor to
consider our suggestions and to defend such challenges, with the possibility that it may not do so in a way that best protects
our interests.
We may be subject to a third-party preissuance submission of prior art to the USPTO, or become involved in other
contested proceedings such as opposition, derivation, reexamination, inter partes review, post-grant review or interference
proceedings challenging our patent rights or the patent rights of others. An adverse determination in any such submission,
proceeding or litigation could reduce the scope of, or invalidate, our patent rights, allow third parties to commercialize our
technology or products and compete directly with us, without payment to us, or result in our inability to manufacture or
commercialize products without infringing third-party patent rights. In addition, if the breadth or strength of protection
provided by our patents and patent applications is threatened, it could dissuade companies from collaborating with us to
license, develop or commercialize current or future products.
In the United States, the FDA does not prohibit physicians from prescribing an approved product for uses that are not
described in the product’s labeling. Although use of a product directed by off-label prescriptions may infringe our method-
of-treatment patents, the practice is common across medical specialties, particularly in the United States, and such
infringement is difficult to detect, prevent or prosecute. In addition, patents that cover methods of use for a medical device
cannot be enforced against the party that uses the device, but rather only against the party that makes them. Such indirect
enforcement is more difficult to achieve.
The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our licensed
patents may be challenged in the courts or patent offices in the United States and abroad. Such challenges may result in
loss of exclusivity or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, which could
limit our ability to stop others from using or commercializing similar or identical technology and products, or limit the
duration of the patent protection of our technology and products. Given the amount of time required for the development,
testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly
after such candidates are commercialized. As a result, our patent portfolio may not provide us with sufficient rights to
exclude others from commercializing products similar or identical to ours.
Because the active pharmaceutical ingredients in our products and product candidates are available on a generic
basis, or are soon to be available on a generic basis, competitors will be able to offer and sell products with the same active
pharmaceutical ingredient as our products so long as these competitors do not infringe our patents or any patents that we
license. These patents largely relate to the hydrogel composition of our intracanalicular inserts and the drug-release design
scheme of our inserts. As such, if a third party were able to design around the formulation and process patents that we
license and create a different formulation using a different production process not covered by our patents or patent
applications, we would likely be unable to prevent that third party from manufacturing and marketing its product.
If we are not able to obtain patent term extensions in the United States under the Hatch-Waxman Act and in foreign
countries under similar legislation, thereby potentially extending the term of our marketing exclusivity for our product
and product candidates, our business may be impaired.
Depending upon the timing, duration and specifics of FDA marketing approval of our product candidates, one of the
U.S. patents covering each of such product candidates or the use thereof may be eligible for up to five years of patent term
restoration under the Hatch-Waxman Act. The Hatch-Waxman Act allows a maximum of one patent to be extended per
FDA-approved product. Patent term extension also may be available in certain foreign countries upon regulatory approval
of our product candidates. Nevertheless, we may not be granted patent term extension either in the United States or in any
foreign country because of, for example, failing to apply within applicable deadlines, failing to apply prior to expiration of
relevant patents or otherwise failing to satisfy applicable requirements. Moreover, the term of extension, as well as the
scope of patent protection during any such extension, afforded by the governmental authority could be less than we
request.
Further, our license from Incept does not provide us with the right to control decisions by Incept or its other licensees
on Orange Book listings or patent term extension decisions under the Hatch-Waxman Act. Thus, if one of our important
licensed patents is eligible for a patent term extension under the Hatch-Waxman Act, and it covers a product
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of another Incept licensee in addition to our own product candidate, we may not be able to obtain that extension if the other
licensee seeks and obtains that extension first.
If we are unable to obtain patent term extension or restoration, or the term of any such extension is less than we
request, the period during which we will have the right to exclusively market our product may be shortened and our
competitors may obtain approval of competing products following our patent expiration sooner, and our revenue could be
reduced, possibly materially.
We may become involved in lawsuits to protect or enforce our licensed patents or other intellectual property, which
could be expensive, time-consuming and unsuccessful.
Competitors may infringe our licensed patents or other intellectual property. As a result, to counter infringement or
unauthorized use, we may be required to file infringement claims, which can be expensive and time-consuming. Under the
terms of our license agreement with Incept, we have the right to initiate suit against third parties who we believe infringe
on the patents subject to the license. Any claims we assert against perceived infringers could provoke these parties to assert
counterclaims against us alleging that we infringe their patents. In addition, in a patent infringement proceeding, a court
may decide that a patent we have rights to is invalid or unenforceable, in whole or in part, construe the patent’s claims
narrowly or refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover
the technology in question. An adverse result in any litigation proceeding could put one or more of our patents at risk of
being invalidated or interpreted narrowly. Furthermore, because of the substantial amount of discovery required in
connection with intellectual property litigation, there is a risk that some of our confidential information could be
compromised by disclosure during this type of litigation.
Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the
outcome of which would be uncertain and could have a material adverse effect on the success of our business.
Our commercial success depends upon our ability to develop, manufacture, market and sell our products and product
candidates and use our proprietary technologies without infringing the proprietary rights of third parties. There is
considerable intellectual property litigation in the biotechnology, medical device, and pharmaceutical industries. We may
become party to, or threatened with, infringement litigation claims regarding our products and technology, including claims
from competitors or from non-practicing entities that have no relevant product revenue and against whom our own patent
portfolio may have no deterrent effect. Moreover, we may become party to future adversarial proceedings or litigation
regarding our patent portfolio or the patents of third parties. Such proceedings could also include contested post-grant
proceedings such as oppositions, inter partes review, reexamination, interference or derivation proceedings before the
USPTO or foreign patent offices. The legal threshold for initiating litigation or contested proceedings is low, so that even
lawsuits or proceedings with a low probability of success might be initiated and require significant resources to
defend. Litigation and contested proceedings can also be expensive and time-consuming, and our adversaries in these
proceedings may have the ability to dedicate substantially greater resources to prosecuting these legal actions than we or
our licensor can. The risks of being involved in such litigation and proceedings may increase as our products or product
candidates near commercialization and as we gain the greater visibility associated with being a public company. Third
parties may assert infringement claims against us based on existing patents or patents that may be granted in the future. We
may not be aware of all such intellectual property rights potentially relating to our products or product candidates and their
uses, or we may incorrectly determine that a patent is invalid or does not cover a particular product or product
candidate. Thus, we do not know with certainty that DEXTENZA, ReSure Sealant or any of our product candidates, or our
commercialization thereof, does not and will not infringe or otherwise violate any third party’s intellectual property.
We are also aware of a U.S. patent with an expiration in 2020 with claims directed to formulations of hydrogels and
which could be alleged to cover the hydrogel formulations used in our product candidates OTX-TP and OTX-MP. Based on
the specifications and file history of that patent, we believe its claims should be construed with a scope that does not cover
our product candidates. We also believe that such claims, if and to the extent they were asserted against our product
candidates, would be subject to a claim of invalidity. Further, we have been made aware by a third party of three patents
relating to intracanalicular inserts that may relate to, and potentially could be asserted against our intracanalicular insert
product and product candidates, including DEXTENZA. We believe that DEXTENZA does not infringe the claims of one
of more of these patents. We also believe that such claims, if and to the extent they were asserted against our product
candidates, would be subject to a claim of invalidity. We initiated legal proceedings against one of these patents and
administrative proceedings against the other two patents in order to show that DEXTENZA
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does not infringe the claims of these patents or that these patents are invalid. We have settled the legal proceedings related
to one of these patents. The USPTO has decided to proceed with the administrative proceeding related to one of the patents
while declining to do so for the other. We continue to believe that DEXTENZA does not infringe the claims of these
patents and that, if and to the extent they were asserted against DEXTENZA, they would be subject to a claim of
invalidity.
If we are found to infringe a third party’s intellectual property rights, we could be required to obtain a license from
such third party to continue developing and marketing our products and technology. However, we may not be able to
obtain any required license on commercially reasonable terms or at all. Even if we were able to obtain a license, it could be
non-exclusive, thereby giving our competitors access to the same technologies licensed to us. We could be forced,
including by court order, to cease commercializing the infringing technology or product. In addition, we could be found
liable for monetary damages, including treble damages and attorneys’ fees if we are found to have willfully infringed a
patent and could be forced to indemnify our customers or collaborators. A finding of infringement could also result in an
injunction that prevents us from commercializing our products or product candidates or forces us to cease some of our
business operations. In addition, we may be forced to redesign our products or product candidates, seek new regulatory
approvals and indemnify third parties pursuant to contractual agreements. Claims that we have misappropriated the
confidential information or trade secrets of third parties could have a similar negative impact on our business.
If we fail to comply with our obligations in our intellectual property licenses and funding arrangements with third
parties, we could lose rights that are important to our business.
Our license agreement with Incept, under which we license a significant portion of our patent rights and the
technology for DEXTENZA, ReSure Sealant and our product candidates, imposes royalty and other financial obligations
and other substantial performance obligations on us. We also may enter into additional licensing and funding arrangements
with third parties that may impose diligence, development and commercialization timelines and milestone payment,
royalty, insurance and other obligations on us. If we fail to comply with our obligations under current or future license and
collaboration agreements, our counterparties may have the right to terminate these agreements, in which event we might
not be able to develop, manufacture or market any product that is covered by these agreements or may face other penalties
under the agreements. Such an occurrence could diminish the value of our product. Termination of these agreements or
reduction or elimination of our rights under these agreements may result in our having to negotiate new or reinstated
agreements with less favorable terms, or cause us to lose our rights under these agreements, including our rights to
important intellectual property or technology.
Under the terms of our license agreement with Incept, we have agreed to assign to Incept our rights in certain patent
applications filed at any time in any country for which one or more inventors are under an obligation of assignment to
us. These assigned patent applications and any resulting patents are included within the specified patents owned or
controlled by Incept to which we receive a license under the agreement. Incept has retained rights to practice the patents
and technology licensed to us under the agreement for all purposes other than for researching, designing, developing,
manufacturing and commercializing products that are delivered to or around the human eye for diagnostic, therapeutic or
prophylactic purposes relating to ophthalmic diseases or conditions. As a result, termination of our agreement with Incept,
based on our failure to comply with this or any other obligation under the agreement, would cause us to lose a significant
portion of our rights to important intellectual property or technology upon which our business depends. Additionally, the
field limit of the license and the requirement that we assign to Incept our rights in certain patent applications may restrict
our ability to use certain of our licensed rights to expand our business outside of the specified fields. If we determine to
pursue a strategy of expanding the use of the hydrogel technology outside of the specified fields, we would need to
negotiate and enter into an amendment to our existing license agreement with Incept or a new license agreement with
Incept covering one or more additional such fields of use or utilize technologies that do not infringe on such licensed
rights. We may not be able to obtain any such required amendment or new license or to invent or otherwise access other
technology on commercially reasonable terms or at all.
We may be subject to claims by third parties asserting that our employees or we have misappropriated their intellectual
property, or claiming ownership of what we regard as our own intellectual property.
Many of our employees were previously employed at universities or other biotechnology, medical device or
pharmaceutical companies, including our competitors or potential competitors. Although we try to ensure that our
employees do not use the proprietary information or know-how of others in their work for us, we may be subject to claims
that these employees or we have used or disclosed intellectual property, including trade secrets or other
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proprietary information, of any such employee’s former employer. Litigation may be necessary to defend against these
claims.
In addition, while it is our policy to require our employees and contractors who may be involved in the development
of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in
executing such an agreement with each party who in fact develops intellectual property that we regard as our own. Our and
their assignment agreements may not be self-executing or may be breached, and we may be forced to bring claims against
third parties, or defend claims they may bring against us, to determine the ownership of what we regard as our intellectual
property.
If we fail in prosecuting or defending any such claims, in addition to paying monetary damages, we may lose
valuable intellectual property rights or personnel. Even if we are successful in prosecuting or defending against such
claims, litigation could result in substantial costs and be a distraction to management.
Intellectual property litigation could cause us to spend substantial resources and distract our personnel from their
normal responsibilities.
Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause
us to incur significant expenses and could distract our technical and management personnel from their normal
responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim
proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a
substantial adverse effect on the price of our common stock. Such litigation or proceedings could substantially increase our
operating losses and reduce the resources available for development activities or any future sales, marketing or distribution
activities. We may not have sufficient financial or other resources to conduct such litigation or proceedings
adequately. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively
than we can because of their greater financial resources. Uncertainties resulting from the initiation and continuation of
patent litigation or other proceedings could compromise our ability to compete in the marketplace.
If we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be
harmed.
In addition to seeking patents for our technology, products and product candidates, we also rely on trade secrets,
including unpatented know-how, technology and other proprietary information, to maintain our competitive position. We
seek to protect these trade secrets, in part, by entering into non-disclosure and confidentiality agreements with parties who
have access to them, such as our employees, corporate collaborators, outside scientific collaborators, contract
manufacturers, consultants, advisors and other third parties. We also enter into confidentiality and invention or patent
assignment agreements with our employees and consultants. Despite these efforts, any of these parties may breach the
agreements and disclose our proprietary information, including our trade secrets, and we may not be able to obtain
adequate remedies for such breaches. Enforcing a claim that a party illegally disclosed or misappropriated a trade secret is
difficult, expensive and time-consuming, and the outcome is unpredictable. In addition, some courts inside and outside the
United States are less willing or unwilling to protect trade secrets. If any of our trade secrets were to be lawfully obtained
or independently developed by a competitor, we would have no right to prevent them, or those to whom they communicate
it, from using that technology or information to compete with us. If any of our trade secrets were to be disclosed to or
independently developed by a competitor, our competitive position would be harmed.
Risks Related to Regulatory Approval and Marketing of Our Product Candidates and Other Legal Compliance
Matters
Even if we complete the necessary preclinical studies and clinical trials, the regulatory approval process is expensive,
time-consuming and uncertain and may prevent us from obtaining approvals for the commercialization of some or all of
our product candidates. If we or any current or future collaborator of ours is not able to obtain, or if there are delays in
obtaining, required regulatory approvals, we or they will not be able to commercialize our product candidates, and our
ability to generate revenue will be materially impaired.
The activities associated with the development and commercialization of our products and product candidates,
including design, testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion,
sale and distribution, are subject to comprehensive regulation by the FDA and other regulatory agencies in
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the United States and by the EMA and similar regulatory authorities outside the United States. Failure to obtain marketing
approval for a product candidate will prevent us from commercializing the product candidate. We have only received
approval to market DEXTENZA and ReSure Sealant in the United States, and have not received approval to market any of
our product candidates or to market DEXTENZA or ReSure Sealant in any jurisdiction outside the United States. Further,
we have only received approval to market DEXTENZA for the treatment of ocular inflammation and pain following
ophthalmic surgery and have not received approval to market DEXTENZA for any other indications. We may determine to
seek a CE Certificate of Conformity, which demonstrates compliance with relevant requirements and provides approval to
commercialize ReSure Sealant in the European Union. If we are unable to obtain a CE Certificate of Conformity for
DEXTENZA, ReSure Sealant, or any of our product candidates for which we seek European regulatory approval, we will
be prohibited from commercializing such product or products in the European Union and other places which require the CE
Certificate of Conformity. In such a case, the potential market to commercialize our products may be significantly smaller
than we currently estimate.
The process of obtaining marketing approvals, both in the United States and abroad, is expensive and may take many
years, especially if additional clinical trials are required, if approval is obtained at all. Securing marketing approval
requires the submission of extensive preclinical and clinical data and supporting information to regulatory authorities for
each therapeutic indication to establish the product candidate’s safety and purity. Securing marketing approval also
requires the submission of information about the product manufacturing process to, and inspection of manufacturing
facilities by, the regulatory authorities. The FDA, the EMA or other regulatory authorities may determine that our product
candidates are not safe or effective, are only moderately effective or have undesirable or unintended side effects, toxicities
or other characteristics that preclude our obtaining marketing approval or prevent or limit commercial use. In addition,
while we have had general discussions with the FDA concerning the design of some of our clinical trials, we have not
discussed with the FDA the specifics of the regulatory pathways for our product candidates.
As part of its review of the NDA for DEXTENZA for post-surgical ocular pain, the FDA completed inspections of
three sites from our two completed Phase 3 clinical trials for compliance with the study protocol and Good Clinical
Practices. During the first of these inspections, the FDA identified storage temperature excursions for the investigational
product that is labeled to be stored in a refrigerated condition between two degrees and eight degrees Celsius. We also had
previously addressed a minor temperature deviation report during the conduct of the Phase 3 trials and communicated a
response to the trial sites. In addition, while investigating the report stemming from the FDA inspection, several more
noteworthy temperature excursions were found to have occurred that had not been fully reported. Because of the limited
nature of the temperature excursions and historical product testing, including testing on product stored at elevated
temperatures, we believe it is unlikely that drug product performance was significantly impacted. We have also
implemented a corrective action plan to address clinical compliance and prevent recurrence in other clinical studies.
The FDA also completed two inspections of our manufacturing facility in connection with our NDA for DEXTENZA
for the treatment of post-surgical ocular pain. After each inspection, we received a Form 483 from the FDA pertaining to
deficiencies in our manufacturing processes identified during such inspection. After we responded to the issues which had
been identified with corrective action plans, we subsequently received CRLs from the FDA. We may be subject to similar
inspections in the future for DEXTENZA or for other product candidates for which we seek FDA approval. If we are
unable to address any identified issues successfully or if the FDA determines that the actions we take to remediate any
identified issues to be inadequate, our ability to commercialize any products could be limited, which could adversely affect
our ability to achieve or sustain profitability.
Changes in marketing approval policies during the development period, changes in or the enactment of additional
statutes or regulations, or changes in regulatory review for each submitted product application, may cause delays in the
approval or rejection of an application. The FDA, the EMA and regulatory authorities in other countries have substantial
discretion in the approval process and may refuse to accept any application or may decide that our data is insufficient for
approval and require additional preclinical, clinical or other studies. In addition, varying interpretations of the data
obtained from preclinical and clinical testing could delay, limit or prevent marketing approval of a product candidate. Any
marketing approval we or any current or future collaborator of ours ultimately obtains may be limited or subject to
restrictions or post-approval commitments that render the approved product not commercially viable.
Accordingly, if we or any current or future collaborator of ours experiences delays in obtaining approval or if we or
they fail to obtain approval of our product candidates, the commercial prospects for our product candidates may be harmed
and our ability to generate revenues will be materially impaired.
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Failure to obtain marketing approval in foreign jurisdictions would prevent our products or product candidates from
being marketed abroad.
In order to market and sell DEXTENZA, ReSure Sealant or our product candidates in the European Union and many
other jurisdictions, we or our third-party collaborators must obtain separate marketing approvals and comply with
numerous and varying regulatory requirements. The approval procedure varies among countries and can involve additional
testing. The time required to obtain approval may differ substantially from that required to obtain FDA approval. The
regulatory approval process outside the United States generally includes all of the risks associated with obtaining FDA
approval. In addition, in many countries outside the United States, it is required that the product be approved for
reimbursement before the product can be sold in that country. We or our collaborators may not obtain approvals from
regulatory authorities outside the United States on a timely basis, if at all. Approval by the FDA does not ensure approval
by regulatory authorities in other countries or jurisdictions, and approval by one regulatory authority outside the United
States does not ensure approval by regulatory authorities in other countries or jurisdictions or by the FDA. However, a
failure or delay in obtaining regulatory approval in one country may have a negative effect on the regulatory approval
process in other countries. We may not be able to file for marketing approvals and may not receive necessary approvals to
commercialize our products in any market.
Additionally, on June 23, 2016, the electorate in the United Kingdom voted in favor of leaving the European Union,
commonly referred to as Brexit Following protracted negotiations, the United Kingdom left the European Union on January
31, 2020. Under the withdrawal agreement, there is a transitional period until December 31, 2020 (extendable up to two
years). Discussions between the United Kingdom and the European Union have so far mainly focused on finalizing
withdrawal issues and transition agreements but have been extremely difficult to date. To date, only an outline of a trade
agreement has been reached. Much remains open but the Prime Minister has indicated that the United Kingdom will not
seek to extend the transitional period beyond the end of 2020. If no trade agreement has been reached before the end of the
transitional period, there may be significant market and economic disruption. The Prime Minister has also indicated that
the UK will not accept high regulatory alignment with the EU.
Since a significant proportion of the regulatory framework in the United Kingdom is derived from European Union
directives and regulations, Brexit could materially impact the regulatory regime with respect to the approval of our
products or product candidates in the United Kingdom or the European Union. Any delay in obtaining, or an inability to
obtain, any marketing approvals, as a result of Brexit or otherwise, would prevent us from commercializing our products or
product candidates in the United Kingdom and/or the European Union and restrict our ability to generate revenue and
achieve and sustain profitability. If any of these outcomes occur, we may be forced to restrict or delay efforts to seek
regulatory approval in the United Kingdom and/or European Union for our product candidates, which could significantly
and materially harm our business.
Even if we, or any current or future collaborators, obtain marketing approvals for our product candidates, the terms of
approvals, ongoing regulations and post-marketing restrictions for our products may limit how we manufacture and
market our products, which could materially impair our ability to generate revenue.
Once marketing approval has been granted, an approved product and its manufacturer and marketer are subject to
ongoing review and extensive regulation. We, and any current or future collaborators, must therefore comply with
requirements concerning advertising and promotion for any of our products for which we or our collaborators obtain
marketing approval. Promotional communications with respect to drug products, biologics, and medical devices are
subject to a variety of legal and regulatory restrictions and must be consistent with the information in the product’s
approved labeling. Thus, if any of our product candidates receives marketing approval, the accompanying label may limit
the approved use of our product, which could limit sales of the product.
The FDA required two post-approval studies as a condition for approval of our premarket approval application for
ReSure Sealant. The first post-approval study, identified as the Clinical PAS, was to enroll at least 598 patients to confirm
that ReSure Sealant can be used safely by physicians in a standard cataract surgery practice and to confirm the incidence of
the most prevalent adverse ocular events identified in our pivotal study of ReSure Sealant in eyes treated with ReSure
Sealant. We submitted the final study report of the Clinical PAS to the FDA in June 2016, and the FDA has confirmed the
Clinical PAS has been completed. The second post-approval study, identified as the Device Exposure Registry Study, is
intended to link to the Medicare database to ascertain if patients are diagnosed or treated for endophthalmitis within 30
days following cataract surgery and application of ReSure Sealant. The Device Exposure Registry Study is required to
include at least 4,857 patients. In December 2015, the CMS denied our application for a
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tracking or research code for ReSure Sealant commercial use. In July 2016, the FDA approved the Device Exposure
Registry Study protocol. We are required to provide periodic reports to the FDA on the progress of this post-approval
study until it is completed. We initiated enrollment in this study in December 2016 and submitted our first progress report
to FDA in January 2017. Due to difficulties in establishing an acceptable way to link ReSure Sealant to the Medicare
database and lack of investigator interest, we have been unable to enroll trial sites and patients, collect patient data and
report study data to the FDA. On October 18, 2018, we received a warning letter from the FDA, dated October 17, 2018,
relating to our compliance with data collection and information reporting obligations in this study. We appealed the
warning letter from the FDA. In December 2018, the FDA rejected our appeal. A teleconference was held with the FDA in
January 2019 resulting in tentative agreement on a proposed retrospective registry study of endophthalmitis rates to satisfy
the Device Exposure Registry Study requirements. In December 2019, we submitted the protocol for the agreed-upon
retrospective study and the prospective study outline, as required per the terms of the warning letter. We received feedback
from the FDA in February 2020 and responded to the FDA in March 2020. We expect a response from the FDA in the
middle of 2020.
We are working with the registry vendor to finalize a formal study protocol which we intend to submit to the FDA for
comment before the study is conducted. Following review of the results from these post-approval studies, any concerns
with respect to endophthalmitis that we are unable to address due to the lack of completion of the study would negatively
affect our ability to commercialize ReSure Sealant. Failure by us to conduct the Device Exposure Registry Study to the
FDA’s satisfaction may result in withdrawal of the FDA’s approval of ReSure Sealant or other regulatory action.
In addition, manufacturers of approved products and those manufacturers’ facilities are required to comply with
extensive FDA requirements, including ensuring that quality control and manufacturing procedures conform to cGMPs
applicable to drug and biologic manufacturers or quality assurance standards applicable to medical device manufacturers,
which include requirements relating to quality control and quality assurance as well as the corresponding maintenance of
records and documentation and reporting requirements. We, any contract manufacturers we may engage in the future, our
current or future collaborators and their contract manufacturers will also be subject to other regulatory requirements,
including submissions of safety and other post-marketing information and reports, registration and listing requirements,
requirements regarding the distribution of samples to physicians, recordkeeping, and costly post-marketing studies or
clinical trials and surveillance to monitor the safety or efficacy of the product such as the requirement to implement a risk
evaluation and mitigation strategy.
Accordingly, assuming we, or any current or future collaborators, receive marketing approval for one or more of our
product candidates, we, and any current or future collaborators, and our and their contract manufacturers will continue to
expend time, money and effort in all areas of regulatory compliance, including manufacturing, production, product
surveillance and quality control. If we, and any current or future collaborators, are not able to comply with post-approval
regulatory requirements, we, and any current or future collaborators, could have the marketing approvals for our products
withdrawn by regulatory authorities and our, or any current or future collaborators’, ability to market any products could be
limited, which could adversely affect our ability to achieve or sustain profitability. Further, the cost of compliance with
post-approval regulations may have a negative effect on our operating results and financial condition.
We may be subject to substantial penalties if we fail to comply with regulatory requirements or if we experience
unanticipated problems with our products.
Violations of the United States Federal Food, Drug, and Cosmetic Act, or the FDCA, relating to the promotion or
manufacturing of drug products, biologics or medical devices may lead to investigations by the FDA, Department of
Justice, or DOJ, and state attorneys general alleging violations of the FDCA, federal and state healthcare fraud and abuse
laws, as well as state consumer protection laws. In addition, later discovery of previously unknown adverse events or other
problems with our products, manufacturers or manufacturing processes, or failure to comply with regulatory requirements,
may yield various results, including:
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restrictions on such products, manufacturers or manufacturing processes;
restrictions on the labeling or marketing of a product;
restrictions on product distribution or use of a product;
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·
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requirements to conduct post-marketing studies or clinical trials;
warning letters or untitled letters;
withdrawal of the products from the market;
refusal to approve pending applications or supplements to approved applications that we submit;
recall of products;
fines, restitution or disgorgement of profits or revenues;
suspension or withdrawal of marketing approvals;
refusal to permit the import or export of our products;
product seizure or detention;
injunctions or the imposition of civil or criminal penalties;
damage to relationships with any potential collaborators;
unfavorable press coverage and damage to our reputation; or
litigation involving patients using our products.
Non-compliance with European Union requirements regarding safety monitoring or pharmacovigilance, and with
requirements related to the development of products for the pediatric population, can also result in significant financial
penalties. Similarly, failure to comply with the European Union’s requirements regarding the protection of personal
information can also lead to significant penalties and sanctions.
Our relationships with healthcare providers, physicians and third-party payors will be subject, directly or indirectly, to
applicable anti-kickback, fraud and abuse and other healthcare laws and regulations, which, in the event of a violation,
could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm and diminished profits
and future earnings.
Healthcare providers, physicians and third-party payors will play a primary role in the recommendation and
prescription and use of DEXTENZA, ReSure Sealant and any product candidates for which we obtain marketing
approval. Our future arrangements with healthcare providers, physicians and third-party payors may expose us to broadly
applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial
arrangements and relationships through which we market, sell and distribute any products for which we obtain marketing
approval. Restrictions under applicable federal and state healthcare laws and regulations include the following:
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the federal Anti-Kickback Statute prohibits, among other things, persons from knowingly and willfully
soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or
reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation or
arranging of, any good or service, for which payment may be made under a federal healthcare program such as
Medicare and Medicaid;
the federal False Claims Act imposes criminal and civil penalties, including through civil whistleblower or qui
tam actions, against individuals or entities for, among other things, knowingly presenting, or causing to be
presented, false or fraudulent claims for payment by a federal healthcare program or making a false statement or
record material to payment of a false claim or avoiding, decreasing or concealing an obligation to pay money to
the federal government, with potential liability including mandatory treble damages and significant per-claim
penalties, currently set at $5,500 to $11,000 per false claim;
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the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes criminal and civil
liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to
healthcare matters;
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act and its
implementing regulations, also imposes obligations, including mandatory contractual terms, with respect to
safeguarding the privacy, security and transmission of individually identifiable health information;
the federal Physician Payments Sunshine Act requires applicable manufacturers of covered products to report
payments and other transfers of value to physicians and teaching hospitals, with data collection beginning in
August 2013; and
analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws and
transparency statutes, may apply to sales or marketing arrangements and claims involving healthcare items or
services reimbursed by non-governmental third-party payors, including private insurers.
Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary
compliance guidelines and the relevant compliance guidance promulgated by the federal government and may require
product manufacturers to report information related to payments and other transfers of value to physicians and other
healthcare providers or marketing expenditures. State and foreign laws also govern the privacy and security of health
information in some circumstances, many of which differ from each other in significant ways and often are not preempted
by HIPAA, thus complicating compliance efforts.
If our operations or the operations of our present and future collaborators are found to be in violation of any of the
laws described above or any governmental regulations that apply to us or them, we or they may be subject to penalties,
including civil and criminal penalties, damages, fines and the curtailment or restructuring of our operations. Any penalties,
damages, fines, curtailment or restructuring of our operations could adversely affect our or their financial results. We are
developing and implementing a corporate compliance program designed to ensure that we will market and sell any future
products that we successfully develop from our product candidates in compliance with all applicable laws and regulations,
but we cannot guarantee that this program will protect us from governmental investigations or other actions or lawsuits
stemming from a failure to be in compliance with such laws or regulations. If any such actions are instituted against us and
we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our
business, including the imposition of significant fines or other sanctions.
Efforts to ensure that our business with third parties will comply with applicable healthcare laws and regulations will
involve substantial costs. We do not have a fully developed compliance program and will need to establish a more robust
compliance infrastructure to address our needs in this area. We may fail to establish appropriate compliance measures, and
even with a stronger program in place, it is possible that governmental authorities will conclude that our business practices
may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other
healthcare laws and regulations. If our operations are found to be in violation of any of these laws or any other
governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties,
damages, fines, imprisonment, exclusion of products from government funded healthcare programs, such as Medicare and
Medicaid, and the curtailment or restructuring of our operations. If any of the physicians or other healthcare providers or
entities with whom we expect to do business is found to be not in compliance with applicable laws, they may be subject to
criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.
The provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation,
endorsement, purchase, supply, order or use of medicinal products is also prohibited in the European Union. The provision
of benefits or advantages to physicians is governed by the national anti-bribery laws of European Union Member States,
such as the U.K. Bribery Act 2010. Infringement of these laws could result in substantial fines and imprisonment.
Payments made to physicians in certain European Union Member States must be publicly disclosed. Moreover,
agreements with physicians often must be the subject of prior notification and approval by the physician’s employer, his or
her competent professional organization and/or the regulatory authorities of the individual European Union Member States.
These requirements are provided in the national laws, industry codes or professional codes of conduct, applicable
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in the European Union Member States. Failure to comply with these requirements could result in reputational risk, public
reprimands, administrative penalties, fines or imprisonment.
The collection, use, disclosure, transfer, or other processing of personal data regarding individuals in the European
Union, including personal health data, is subject to the European Union General Data Protection Regulation, or GDPR,
which became effective on May 25, 2018. The GDPR is wide-ranging in scope and imposes numerous requirements on
companies that process personal data, including requirements relating to processing health and other sensitive data,
obtaining consent of the individuals to whom the personal data relates, providing information to individuals regarding data
processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing
notification of data breaches, and taking certain measures when engaging third-party processors. The GDPR also imposes
strict rules on the transfer of personal data to countries outside the European Union, including the United States, and
permits data protection authorities to impose large penalties for violations of the GDPR, including potential fines of up to
€20 million or 4% of annual global revenues, whichever is greater. The GDPR also confers a private right of action on data
subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain
compensation for damages resulting from violations of the GDPR. Compliance with the GDPR will continue to be a
rigorous and time-intensive process that may increase our cost of doing business or require us to change our business
practices, and despite those efforts, there is a risk that we may be subject to fines and penalties, litigation, and reputational
harm in connection with our European activities.
Under the Cures Act and the Trump Administration’s regulatory reform initiatives, the FDA’s policies, regulations and
guidance may be revised or revoked in a manner that could prevent, limit or delay regulatory approval of our product
candidates, which would impact our ability to generate revenue.
In December 2016, the 21st Century Cures Act, or Cures Act, was signed into law. The Cures Act, among other
things, is intended to modernize the regulation of drugs and spur innovation, but its ultimate implementation is unclear. If
we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we
are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained and we
may not achieve or sustain profitability, which would adversely affect our business, prospects, financial condition and
results of operations.
We also cannot predict the likelihood, nature or extent of government regulation that may arise from future
legislation or administrative or executive action, either in the United States or abroad. For example, certain policies of the
Trump administration may impact our business and industry. Namely, the Trump administration has taken several executive
actions, including the issuance of a number of Executive Orders, that could impose significant burdens on, or otherwise
materially delay, the FDA’s ability to engage in routine regulatory and oversight activities such as implementing statutes
through rulemaking, issuance of guidance, and review and approval of marketing applications. An under‑staffed FDA
could result in delays in the FDA’s responsiveness or in its ability to review submissions or applications, issue regulations
or guidance, or implement or enforce regulatory requirements in a timely fashion or at all. Moreover, on January 30, 2017,
President Trump issued an Executive Order, applicable to all executive agencies, including the FDA, which requires that
for each notice of proposed rulemaking or final regulation to be issued in fiscal year 2017, the agency shall identify at least
two existing regulations to be repealed, unless prohibited by law. These requirements are referred to as the “two‑for‑one”
provisions. This Executive Order includes a budget neutrality provision that requires the total incremental cost of all new
regulations in the 2017 fiscal year, including repealed regulations, to be no greater than zero, except in limited
circumstances. For fiscal years 2018 and beyond, the Executive Order requires agencies to identify regulations to offset any
incremental cost of a new regulation and approximate the total costs or savings associated with each new regulation or
repealed regulation. In interim guidance issued by the Office of Information and Regulatory Affairs within OMB on
February 2, 2017, the administration indicates that the “two‑for‑one” provisions may apply not only to agency regulations,
but also to significant agency guidance documents. In addition, on February 24, 2017, President Trump issued an executive
order directing each affected agency to designate an agency official as a “Regulatory Reform Officer” and establish a
“Regulatory Reform Task Force” to implement the two‑for‑one provisions and other previously issued executive orders
relating to the review of federal regulations, however it is difficult to predict how these requirements will be implemented,
and the extent to which they will impact the FDA’s ability to exercise its regulatory authority. If these executive actions
impose constraints on the FDA’s ability to engage in oversight and implementation activities in the normal course, our
business may be negatively impacted.
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Current and future legislation may increase the difficulty and cost for us and any current or future collaborators to
obtain marketing approval of and commercialize our products or product candidates and affect the prices we, or they,
may obtain.
In the United States and some foreign jurisdictions, there have been a number of legislative and regulatory changes
and proposed changes regarding the healthcare system that could, among other things, prevent or delay marketing approval
of our drug candidates, restrict or regulate post-approval activities and affect our ability, or the ability of any future
collaborators, to profitably sell any drugs for which we, or they, obtain marketing approval. We expect that current laws, as
well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria
and in additional downward pressure on the price that we, or any future collaborators, may receive for any approved drugs.
Among the provisions of the Patient Protection and Affordable Care Act, or ACA, of potential importance to our
business and our drug candidates are the following:
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an annual, non-deductible fee on any entity that manufactures or imports specified branded prescription drugs
and biologic agents;
an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate
Program;
expansion of healthcare fraud and abuse laws, including the civil False Claims Act and the federal Anti-
Kickback Statute, new government investigative powers and enhanced penalties for noncompliance;
a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 50% point-
of-sale discounts off negotiated prices to eligible beneficiaries during their coverage gap period, as a condition
for the manufacturer’s outpatient drugs to be covered under Medicare Part D;
extension of manufacturers’ Medicaid rebate liability;
expansion of eligibility criteria for Medicaid programs;
expansion of the entities eligible for discounts under the Public Health Service pharmaceutical pricing program;
new requirements to report certain financial arrangements with physicians and teaching hospitals;
a new requirement to annually report drug samples that manufacturers and distributors provide to physicians;
and
a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative
clinical effectiveness research, along with funding for such research.
Other legislative changes have been proposed and adopted since the ACA was enacted. These changes include the
Budget Control Act of 2011, which, among other things, led to aggregate reductions to Medicare payments to providers of
up to 2% per fiscal year that started in 2013 and will stay in effect through 2024 unless additional Congressional action is
taken, and the American Taxpayer Relief Act of 2012, which, among other things, reduced Medicare payments to several
types of providers and increased the statute of limitations period for the government to recover overpayments to providers
from three to five years. These new laws may result in additional reductions in Medicare and other healthcare funding and
otherwise affect the prices we may obtain for any of our product candidates for which we may obtain regulatory approval
or the frequency with which any such product candidate or product is prescribed or used. Further, there have been several
recent U.S. congressional inquiries and proposed state and federal legislation designed to, among other things, bring more
transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the costs
of drugs under Medicare and reform government program reimbursement methodologies for drug products.
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We expect that these healthcare reforms, as well as other healthcare reform measures that may be adopted in the
future, may result in additional reductions in Medicare and other healthcare funding, more rigorous coverage criteria, new
payment methodologies and additional downward pressure on the price that we receive for any approved product and/or the
level of reimbursement physicians receive for administering any approved product we might bring to market. Reductions in
reimbursement levels may negatively impact the prices we receive or the frequency with which our products are prescribed
or administered. Any reduction in reimbursement from Medicare or other government programs may result in a similar
reduction in payments from private payors.
With enactment of the Tax Cuts and Jobs Act of 2017, or the 2017 Tax Act, which was signed by President Trump on
December 22, 2017, Congress repealed the “individual mandate.” The repeal of this provision, which requires most
Americans to carry a minimal level of health insurance, has become effective. According to the Congressional Budget
Office, the repeal of the individual mandate will cause 13 million fewer Americans to be insured in 2027 and premiums in
insurance markets may rise.
Furthermore, since January 2017, President Trump has signed two Executive Orders designed to delay the
implementation of certain provisions of the ACA or otherwise circumvent some of the requirements for health insurance
mandated by the ACA. One Executive Order directs federal agencies with authorities and responsibilities under the ACA to
waive, defer, grant exemptions from, or delay the implementation of any provision of the ACA that would impose a fiscal
or regulatory burden on states, individuals, healthcare providers, health insurers, or manufacturers of pharmaceuticals or
medical devices. The second Executive Order terminates the cost-sharing subsidies that reimburse insurers under the ACA.
Several state Attorneys General filed suit to stop the administration from terminating the subsidies, but their request for a
restraining order was denied by a federal judge in California on October 25, 2017. The loss of the cost share reduction
payments is expected to increase premiums on certain policies issued by qualified health plans under the ACA. Further, on
June 14, 2018, the United States Court of Appeals for the Federal Circuit ruled that the federal government was not
required to pay more than $12 billion in ACA risk corridor payments to third-party payors who argued were owed to them.
The effects of this gap in reimbursement on third-party payors, the viability of the ACA marketplace, providers, and
potentially our business, are not yet known.
In addition, on December 14, 2018, a U.S. District Court judge in the Northern District of Texas ruled that the
individual mandate portion of the ACA is an essential and inseverable feature of the ACA, and therefore because the
mandate was repealed as part of the Tax Cuts and Jobs Act, the remaining provisions of the ACA are invalid as well. The
Trump administration and CMS have both stated that the ruling will have no immediate effect, and on December 30, 2018
the same judge issued an order staying the judgment pending appeal. The Trump Administration recently represented to the
Court of Appeals considering this judgment that it does not oppose the lower court’s ruling. On July 10, 2019, the Court of
Appeals for the Fifth Circuit heard oral argument in this case. On December 18, 2019, that court affirmed the lower court’s
ruling that the individual mandate portion of the ACA is unconstitutional and it remanded the case to the district court for
reconsideration of the severability question and additional analysis of the provisions of the ACA. On January 21, 2020, the
U.S. Supreme Court declined to review this decision on an expedited basis.
In addition, the CMS has recently proposed regulations that would give states greater flexibility in setting
benchmarks for insurers in the individual and small group marketplaces, which may have the effect of relaxing the essential
health benefits required under the ACA for plans sold through such marketplaces. On November 30, 2018, CMS
announced a proposed rule that would amend the Medicare Advantage and Medicare Part D prescription drug benefit
regulations to reduce out of pocket costs for plan enrollees and allow Medicare plans to negotiate lower rates for certain
drugs. Among other things, the proposed rule changes would allow Medicare Advantage plans to use pre authorization, or
PA, and step therapy, or ST, for six protected classes of drugs, with certain exceptions, permit plans to implement PA and
ST in Medicare Part B drugs; and change the definition of “negotiated prices” while adding a definition of “price
concession” in the regulations. It is unclear whether these proposed changes we be accepted, and if so, what effect such
changes will have on our business. Litigation and legislation over the ACA are likely to continue, with unpredictable and
uncertain results.
We will continue to evaluate the effect that the ACA and its possible repeal and replacement could have on our
business. It is possible that such initiatives, if enacted into law, could ultimately result in fewer individuals having health
insurance coverage or in individuals having insurance coverage with less generous benefits. While the timing and scope of
any potential future legislation to amend the ACA is highly uncertain in many respects, it is also possible that some of the
ACA provisions that generally are not favorable for the research‑based pharmaceutical industry could also be repealed
along with ACA coverage expansion provisions. Accordingly, such reforms, if enacted, could have an adverse
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effect on anticipated revenue from product candidates that we may successfully develop and for which we may obtain
marketing approval and may affect our overall financial condition and ability to develop or commercialize product
candidates.
The costs of prescription pharmaceuticals in the United States has also been the subject of considerable discussion in
the United States, and members of Congress and the Administration have stated that they will address such costs through
new legislative and administrative measures. The pricing of prescription pharmaceuticals is also subject to governmental
control outside the United States. In these countries, pricing negotiations with governmental authorities can take
considerable time after the receipt of marketing approval for a product. To obtain reimbursement or pricing approval in
some countries, we may be required to conduct a clinical trial that compares the cost effectiveness of our product
candidates to other available therapies. If reimbursement of our products is unavailable or limited in scope or amount, or if
pricing is set at unsatisfactory levels, our ability to generate revenues and become profitable could be impaired.
In addition, on May 11, 2018, the Administration issued a plan to lower drug prices. Under this blueprint for action,
the Administration indicated that the Department of Health and Human Services, or the HHS, will: take steps to end the
gaming of regulatory and patent processes by drug makers to unfairly protect monopolies; advance biosimilars and generics
to boost price competition; evaluate the inclusion of prices in drug makers’ ads to enhance price competition; speed access
to and lower the cost of new drugs by clarifying policies for sharing information between insurers and drug makers; avoid
excessive pricing by relying more on value-based pricing by expanding outcome-based payments in Medicare and
Medicaid; work to give Part D plan sponsors more negotiation power with drug makers; examine which Medicare Part B
drugs could be negotiated for a lower price by Part D plans, and improving the design of the Part B Competitive
Acquisition Program; update Medicare’s drug-pricing dashboard to increase transparency; prohibit Part D contracts that
include “gag rules” that prevent pharmacists from informing patients when they could pay less out-of-pocket by not using
insurance; and require that Part D plan members be provided with an annual statement of plan payments, out-of-pocket
spending, and drug price increases.
At the same time, the Trump administration’s budget proposal for fiscal year 2020 contains further drug price control
measures that could be enacted during the 2019 budget process or in other future legislation, including, for example,
measures to permit Medicare Part D plans to negotiate the price of certain drugs under Medicare Part B, to allow some
states to negotiate drug prices under Medicaid, and to eliminate cost sharing for generic drugs for low-income patients. It is
unclear what, if any, of these measures will be enacted during the Congressional session. Additionally, the Trump
administration released a “Blueprint” to lower drug prices and reduce out of pocket costs of drugs that contains additional
proposals to increase manufacturer competition, increase the negotiating power of certain federal healthcare programs,
incentivize manufacturers to lower the list price of their products and reduce the out of pocket costs of drug products paid
by consumers. While any proposed measures will require authorization through additional legislation to become effective,
Congress and the Trump administration have each indicated that it will continue to seek new legislative and/or
administrative measures to control drug costs. For example, on December 23, 2019, the Trump Administration published a
proposed rulemaking that, if finalized, would allow states or certain other non-federal government entities to submit
importation program proposals to FDA for review and approval. Applicants would be required to demonstrate their
importation plans pose no additional risk to public health and safety and will result in significant cost savings for
consumers. At the same time, FDA issued draft guidance that would allow manufacturers to import their own FDA-
approved drugs that are authorized for sale in other countries (multi-market approved products).
At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations
designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints,
discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some
cases, designed to encourage importation from other countries and bulk purchasing. In addition, regional health care
authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products
and which suppliers will be included in their prescription drug and other health care programs. These measures could
reduce the ultimate demand for our products, once approved, or put pressure on our product pricing. We expect that
additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts
that federal and state governments will pay for healthcare products and services, which could result in reduced demand for
our product candidates or additional pricing pressures.
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Legislative and regulatory proposals have been made to expand post‑approval requirements and restrict sales and
promotional activities for pharmaceutical products. We cannot be sure whether additional legislative changes will be
enacted, or whether the FDA regulations, guidance or interpretations will be changed, or what the impact of such changes
on the marketing approvals of our product candidates, if any, may be. Increased scrutiny by the U.S. Congress of the FDA’s
approval process may significantly delay or prevent marketing approval, as well as subject us to more stringent product
labeling and post‑marketing testing and other requirements.
Governments outside the United States tend to impose strict price controls, which may adversely affect our revenues, if
any.
In some countries, such as the countries of the European Union, the pricing of prescription pharmaceuticals is subject
to governmental control and access. In these countries, pricing negotiations with governmental authorities can take
considerable time after the receipt of marketing approval for a product. To obtain reimbursement or pricing approval in
some countries, we, or any current or future collaborators, may be required to conduct a clinical trial that compares the
cost-effectiveness of our product to other available therapies. If reimbursement of our products is unavailable or limited in
scope or amount, or if pricing is set at unsatisfactory levels, our business could be materially harmed.
Laws and regulations governing any international operations we may have in the future may preclude us from
developing, manufacturing and selling certain products outside of the United States and require us to develop and
implement costly compliance programs.
If we expand our operations outside of the United States, we must dedicate additional resources to comply with
numerous laws and regulations in each jurisdiction in which we plan to operate. The Foreign Corrupt Practices Act, or
FCPA, prohibits any U.S. individual or business from paying, offering, authorizing payment or offering of anything of
value, directly or indirectly, to any foreign official, political party or candidate for the purpose of influencing any act or
decision of the foreign entity in order to assist the individual or business in obtaining or retaining business. The FCPA also
obligates companies whose securities are listed in the United States to comply with certain accounting provisions requiring
the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including
international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international
operations.
Compliance with the FCPA is expensive and difficult, particularly in countries in which corruption is a recognized
problem. In addition, the FCPA presents particular challenges in the pharmaceutical industry, because, in many countries,
hospitals are operated by the government, and doctors and other hospital employees are considered foreign
officials. Certain payments to hospitals in connection with clinical trials and other work have been deemed to be improper
payments to government officials and have led to FCPA enforcement actions.
Various laws, regulations and executive orders also restrict the use and dissemination outside of the United States, or
the sharing with certain non-U.S. nationals, of information classified for national security purposes, as well as certain
products and technical data relating to those products. If we expand our presence outside of the United States, it will
require us to dedicate additional resources to comply with these laws, and these laws may preclude us from developing,
manufacturing, or selling certain products and product candidates outside of the United States, which could limit our
growth potential and increase our development costs.
The failure to comply with laws governing international business practices may result in substantial civil and
criminal penalties and suspension or debarment from government contracting. The Securities and Exchange Commission
also may suspend or bar issuers from trading securities on U.S. exchanges for violations of the FCPA’s accounting
provisions.
Our employees may engage in misconduct or other improper activities, including noncompliance with regulatory
standards and requirements.
We are exposed to the risk of employee fraud or other misconduct. Misconduct by employees could include
intentional failures to comply with FDA regulations, to provide accurate information to the FDA, to comply with
manufacturing standards we have established, to comply with federal and state health-care fraud and abuse laws and
regulations, to report financial information or data accurately or to disclose unauthorized activities to us. In particular,
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sales, marketing and business arrangements in the healthcare industry are subject to extensive laws and regulations
intended to prevent fraud, kickbacks, self-dealing and other abusive practices. These laws and regulations may restrict or
prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs
and other business arrangements. Employee misconduct could also involve the improper use of information obtained in the
course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation. We have adopted a
code of business conduct and ethics, but it is not always possible to identify and deter employee misconduct, and the
precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or
losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in
compliance with such laws or regulations. If any such actions are instituted against us, and we are not successful in
defending ourselves or asserting our rights, those actions could have a significant impact on our business, including the
imposition of significant fines or other sanctions.
If we, our collaborators or any third-party manufacturers we engage in the future fail to comply with environmental,
health and safety laws and regulations, we could become subject to fines or penalties or incur significant costs.
We, our collaborators and any third-party manufacturers we may engage in the future are subject to numerous
environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling,
use, storage, treatment and disposal of hazardous materials and wastes. From time to time and in the future, our operations
may involve the use of hazardous materials, including chemicals and biological materials, and produce hazardous waste
products. We generally contract with third parties for the disposal of these materials and wastes. We cannot eliminate the
risk of contamination or injury from these materials. In the event of contamination or injury resulting from our use of
hazardous materials, we could be held liable for any resulting damages, and any liability could exceed our resources. We
also could incur significant costs associated with civil or criminal fines and penalties for failure to comply with such laws
and regulations.
Although we maintain general liability insurance as well as workers’ compensation insurance to cover us for costs
and expenses we may incur due to injuries to our employees resulting from the use of hazardous materials, this insurance
may not provide adequate coverage against potential liabilities. We do not maintain insurance for environmental liability or
toxic tort claims that may be asserted against us in connection with our storage or disposal of biological, hazardous or
radioactive materials.
In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety
laws and regulations. These current or future laws and regulations may impair our research, development or production
efforts. Our failure to comply with these laws and regulations also may result in substantial fines, penalties or other
sanctions.
Further, with respect to the operations of any current or future collaborators or third-party contract manufacturers, it
is possible that if they fail to operate in compliance with applicable environmental, health and safety laws and regulations
or properly dispose of wastes associated with our products, we could be held liable for any resulting damages, suffer
reputational harm or experience a disruption in the manufacture and supply of our product candidates or products.
The comprehensive tax reform bill enacted in 2017 could adversely affect our business and financial condition.
On December 22, 2017, President Trump signed the 2017 Tax Act into law, which significantly revised the Internal
Revenue Code of 1986, as amended. The 2017 Tax Act, among other things, contains significant changes to corporate
federal income taxation, including the reduction of the corporate tax rate from a top marginal rate of 35% to a flat rate of
21%, the limitation of the tax deduction for net interest expense to 30% of adjusted earnings (except for certain small
businesses), the limitation of the deduction for net operating losses to 80% of current year taxable income and elimination
of net operating loss carrybacks, in each case, for losses arising in taxable years beginning after December 31, 2017
(though any such net operating losses may be carried forward indefinitely), the one-time taxation of offshore earnings at
reduced rates regardless of whether they are repatriated, the elimination of U.S. tax on foreign earnings (subject to certain
important exceptions), immediate deductions for certain new investments instead of deductions for depreciation expense
over time, and modification or repeal many business deductions and credits. Notwithstanding the reduction in the corporate
income tax rate, the overall impact of the 2017 Tax Act is uncertain and our business and financial condition could be
adversely affected. In addition, it is uncertain how various states will respond to the 2017 Tax Act. The impact of the 2017
Tax Act on holders of our common stock is also uncertain and
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could be adverse. We urge our stockholders to consult with their legal and tax advisors with respect to the 2017 Tax Act
and the potential tax consequences of investing in or holding our common stock.
We might not be able to utilize a significant portion of our net operating loss carryforwards and research and
development tax credit carryforwards.
As of December 31, 2019, we had federal and state net operating loss carryforwards of $274.3 million, of which
$126.1 million begin to expire in 2026 . We also have state net operating loss carryforwards of $219.4 million, which
begin to expire in 2026. As of December 31, 2019, we also had federal research and development tax credit carryforwards
of $8.2 million and state research and development tax credit carryforwards $4.3 million, which begin to expire in 2026
and 2025, respectively. These net operating loss and tax credit carryforwards could expire unused and be unavailable to
offset our future income tax liabilities. Under the 2017 Tax Act, federal net operating losses incurred in 2018 and in future
years may be carried forward indefinitely, but the deductibility of such federal net operating losses is limited. It is uncertain
how various states will respond to the 2017 Tax Act. If our ability to use our historical net operating loss and tax credit
carryforwards is materially limited, it would harm our future operating results by effectively increasing our future tax
obligations.
Risks Related to Employee Matters and Managing Growth
Our future success depends on our ability to retain key executives and to attract, retain and motivate qualified
personnel.
We remain highly dependent on the research and development, clinical and business development expertise of our
principal members of our management, scientific and clinical team, including Antony Mattessich, our President and Chief
Executive Officer. Although we have entered into employment agreements with our executive officers, each of them may
terminate their employment with us at any time. We do not maintain “key person” insurance for any of our executives or
other employees.
Recruiting and retaining qualified scientific, clinical, manufacturing and sales and marketing personnel will also be
critical to our success. The loss of the services of our executive officers or other key employees could impede the
achievement of our research, development and commercialization objectives and seriously harm our ability to successfully
implement our business strategy. Furthermore, replacing executive officers and key employees may be difficult and may
take an extended period of time because of the limited number of individuals in our industry with the breadth of skills and
experience required to successfully develop, gain regulatory approval of and commercialize products. Competition to hire
from this limited pool is intense, and we may be unable to hire, train, retain or motivate these key personnel on acceptable
terms given the competition among numerous pharmaceutical and biotechnology companies for similar personnel. We also
experience competition for the hiring of scientific and clinical personnel from universities and research institutions. In
addition, we rely on consultants and advisors, including scientific and clinical advisors, to assist us in formulating our
research and development and commercialization strategy. Our consultants and advisors may be employed by employers
other than us and may have commitments under consulting or advisory contracts with other entities that may limit their
availability to us. If we are unable to continue to attract and retain high quality personnel, our ability to pursue our growth
strategy will be limited.
We have recently reduced the size of our organization, and we may encounter difficulties in managing our business as a
result of this reduction, or the attrition that may occur following this reduction, which could disrupt our operations. In
addition, we may not achieve anticipated benefits and savings from the reduction.
In November 2019, our board of directors approved an operational restructuring to eliminate a portion of the
Company’s workforce as part of an initiative to reduce expenses and prioritize our resources to focus on commercializing
DEXTENZA for post-surgical ocular inflammation and pain as well as completing the ongoing clinical trials for our
product candidates. Under this plan, we reduced our workforce by 55 employees, representing approximately 22% of our
workforce, effective November 8, 2019. We also eliminated an additional 31 positions that were vacant. We completed the
restructuring and recorded the restructuring charges in the fourth quarter of 2019. This reduction in force, and the attrition
that may occur following this reduction, will result in the loss of institutional knowledge and expertise and the reallocation
and combination of certain roles and responsibilities across the organization, all of which could adversely affect our
operations.
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The restructuring and additional measures we might take to reduce costs could divert management attention, yield
attrition beyond our intended reduction if force, reduce employee morale, or cause us to delay, limit, reduce or eliminate
certain product development plans.
We expect to expand our development, regulatory and manufacturing capabilities and potentially implement sales,
marketing and distribution capabilities, and as a result, we may encounter difficulties in managing our growth, which
could disrupt our operations.
Although we had a reduction in workforce in 2019, we expect our drug development, clinical, regulatory affairs,
manufacturing and our sales and marketing capabilities in the longer term to grow as we commercialize DEXTENZA and
any product candidates that may receive marketing approval. To manage our anticipated future growth, we must continue to
implement and improve our managerial, operational and financial systems, expand our facilities and continue to recruit and
train additional qualified personnel. We relocated our corporate headquarters to 24 Crosby Drive, Bedford, Massachusetts
to accommodate our growth. We are evaluating expanding our manufacturing operations into 15 Crosby Drive, Bedford,
Massachusetts while maintaining our existing operations located at 36 Crosby Drive, Bedford, Massachusetts. Due to our
limited financial resources and our limited experience in managing such anticipated growth, we may not be able to
effectively manage the expansion of our operations, or recruit and train additional qualified personnel. The expansion of
our operations may lead to significant costs and may divert our management and business development resources. Any
inability to manage growth could delay the execution of our business plans or disrupt our operations.
Our internal computer systems, or those of our collaborators or other contractors or consultants, may fail or suffer
security breaches, which could result in a material disruption of our product development programs.
Our internal computer systems and those of our current and any future collaborators, contractors or consultants are
vulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication
and electrical failures. While we have not experienced any such material system failure, accident or security breach to date,
if such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our
development programs and our business operations, whether due to a loss of our trade secrets or other proprietary
information or other similar disruptions. For example, the loss of clinical trial data from completed or future clinical trials
could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the
data. To the extent that any disruption or security breach were to result in a loss of, or damage to, our data or applications,
or inappropriate disclosure of confidential or proprietary information, we could incur liability, our competitive position
could be harmed and the further development and commercialization of our products and product candidates could be
delayed.
Risks Related to Our Common Stock
Our executive officers, directors and principal stockholders, if they choose to act together, have the ability to control all
matters submitted to stockholders for approval.
Our executive officers, directors and principal stockholders, in the aggregate, beneficially own a large portion of our
capital stock. As a result, if these stockholders were to choose to act together, they would be able to control all matters
submitted to our stockholders for approval, as well as our management and affairs. For example, these persons, if they
choose to act together, would control the election of directors and approval of any merger, consolidation or sale of all or
substantially all of our assets.
This concentration of voting power may:
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delay, defer or prevent a change in control;
entrench our management and the board of directors; or
delay or prevent a merger, consolidation, takeover or other business combination involving us on terms that other
stockholders may desire.
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Provisions in our corporate charter documents and under Delaware law could make an acquisition of our company,
which may be beneficial to our stockholders, more difficult and may prevent attempts by our stockholders to replace or
remove our current management.
Provisions in our certificate of incorporation and our bylaws may discourage, delay or prevent a merger, acquisition
or other change in control of our company that stockholders may consider favorable, including transactions in which our
stockholders might otherwise receive a premium for their shares. These provisions could also limit the price that investors
might be willing to pay in the future for shares of our common stock, thereby depressing the market price of our common
stock. In addition, because our board of directors is responsible for appointing the members of our management team,
these provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current management
by making it more difficult for stockholders to replace members of our board of directors. Among other things, these
provisions:
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provide for a classified board of directors such that only one of three classes of directors is elected each year;
allow the authorized number of our directors to be changed only by resolution of our board of directors;
limit the manner in which stockholders can remove directors from our board of directors;
provide for advance notice requirements for stockholder proposals that can be acted on at stockholder meetings
and nominations to our board of directors;
require that stockholder actions must be effected at a duly called stockholder meeting and prohibit actions by our
stockholders by written consent;
limit who may call stockholder meetings;
authorize our board of directors to issue preferred stock without stockholder approval, which could be used to
institute a “poison pill” that would work to dilute the stock ownership of a potential hostile acquirer, effectively
preventing acquisitions that have not been approved by our board of directors; and
require the approval of the holders of at least 75% of the votes that all our stockholders would be entitled to cast
to amend or repeal specified provisions of our certificate of incorporation or bylaws.
Moreover, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the
Delaware General Corporation Law, which prohibits a person who owns in excess of 15% of our outstanding voting stock
from merging or combining with us for a period of three years after the date of the transaction in which the person acquired
in excess of 15% of our outstanding voting stock, unless the merger or combination is approved in a prescribed manner.
We are currently subject to legal proceedings related to the decline in our stock price, which could distract our
management and could result in substantial costs or large judgments against us.
In July 2017, we experienced a decline in our stock price following our announcement that we had received notice of
the FDA’s determination that it could not approve our NDA for DEXTENZA in its then present form. In addition, the
market prices of securities of companies in the biotechnology and pharmaceutical industry have been extremely volatile
and have experienced fluctuations that have often been unrelated or disproportionate to the operating performance of these
companies. These fluctuations could adversely affect the market price of our common stock. In the past, securities class
action litigation has often been brought against companies following periods of volatility in the market prices of their
securities. In July and August 2017, class action lawsuits were filed against us and certain of our current and former
executive officers in the United States District Court for the District of New Jersey, which were transferred to the United
States District Court for the District of Massachusetts at our request and were subsequently consolidated. The court
dismissed the consolidated cases in April 2019; that dismissal has been appealed. In addition, in July 2017, shareholder
derivative actions were filed against certain of our current and former executive officers, certain of our current and former
board members, and two of our investors and against the company as a nominal defendant, in the United States District
Court for the District of Massachusetts and in Massachusetts Superior Court (Suffolk County). These actions
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were re-filed in October and December 2017, were consolidated by court order in January 2018, and are now pending
under one docket in Massachusetts Superior Court (Suffolk County). In January 2018, a third shareholder derivative action
was filed against us, certain of our current and former executive officers, and certain of our current and former board
members in the United States District Court for the District of Massachusetts. In February 2018, a fourth shareholder
derivative action was filed against us, certain of our current and former executive officers, certain of our current and former
board members, and two of our investors in the United States District Court for the District of Delaware. We also received
subpoenas from the SEC in December 2017 and August 2018 seeking documents and information concerning
DEXTENZA, including related communications with the FDA and investors. In May 2019, the SEC notified us that the
SEC had concluded its investigation. Due to the volatility in our stock price, we may be the target of similar proceedings in
the future.
In connection with such legal proceedings, we could incur substantial costs and such costs and any related
settlements or judgments may not be covered by insurance. We could also suffer an adverse impact on our reputation and a
diversion of management’s attention and resources, which could cause serious harm to our business, operating results and
financial condition.
An active trading market for our common stock may not be sustained.
Our shares of common stock began trading on the Nasdaq Global Market on July 25, 2014. Given the limited trading
history of our common stock, there is a risk that an active trading market for our shares will not be sustained, which could
put downward pressure on the market price of our common stock and thereby affect the ability of our stockholders to sell
their shares.
The price of our common stock may be volatile and fluctuate substantially, which could result in substantial losses for
holders of our common stock.
Our stock price may be volatile. The stock market in general and the market for smaller biopharmaceutical
companies in particular have experienced extreme volatility that has often been unrelated to the operating performance. As
a result of this volatility, our stockholders may not be able to sell their common stock at or above the price at which they
purchased it. The market price for our common stock may be influenced by many factors, including:
·
·
·
·
·
·
·
·
·
·
our success in commercializing DEXTENZA, ReSure Sealant and any product candidates for which we obtain
marketing approval;
the success of competitive products or technologies;
results of clinical trials of our product candidates;
results of clinical trials of product candidates of our competitors;
regulatory or legal developments in the United States and other countries;
developments or disputes concerning patent applications, issued patents or other proprietary rights;
the recruitment or departure of key scientific or management personnel;
the level of expenses related to any of our product candidates or clinical development programs;
the results of our efforts and the efforts of our current and future collaborators to discover, develop, acquire or
in-license additional products, product candidates or technologies for the treatment of ophthalmic diseases or
conditions, the costs of commercializing any such products and the costs of development of any such product
candidates or technologies;
actual or anticipated changes in estimates as to financial results, development timelines or recommendations by
securities analysts;
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·
·
·
variations in our financial results or those of companies that are perceived to be similar to us;
the ability to secure third-party reimbursement for our products or product candidates;
changes in the structure of healthcare payment systems;
· market conditions in the pharmaceutical and biotechnology sectors;
·
·
general economic, industry and market conditions; and
the other factors described in this “Risk Factors” section.
In the past, following periods of volatility in the market price of a company’s securities, securities class-action
litigation has often been instituted against that company. We also may face securities class-action litigation if we cannot
obtain regulatory approvals for or if we otherwise fail to commercialize DEXTENZA or our other product candidates. As
described in “Part I, Item 3— Legal Proceedings,” we and certain of our current and former executive officers and current
and former board members have been named as defendants in purported class action lawsuits and derivative
lawsuits. These proceedings and other similar litigation, if instituted against us, could cause us to incur substantial costs to
defend such claims and divert management’s attention and resources.
Sales of a substantial number of shares of our common stock in the public market could cause our stock price to fall.
Persons who were our stockholders prior to our initial public offering continue to hold a substantial number of shares
of our common stock. If such persons sell, or indicate an intention to sell, substantial amounts of our common stock in the
public market, the trading price of our common stock could decline.
In addition, shares of common stock that are either subject to outstanding options or reserved for future issuance
under our stock incentive plans will become eligible for sale in the public market to the extent permitted by the provisions
of various vesting schedules and Rule 144 and Rule 701 under the Securities Act of 1933, as amended, and, in any event,
we have filed a registration statement permitting shares of common stock issued on exercise of options to be freely sold in
the public market. If these additional shares of common stock are sold, or if it is perceived that they will be sold, in the
public market, the trading price of our common stock could decline.
Certain holders of our common stock have rights, subject to specified conditions, to require us to file registration
statements covering their shares or, along with certain holders of shares of our common stock issuable upon exercise of
warrants issued to lenders, to include their shares in registration statements that we may file for ourselves or other
stockholders. Any sales of securities by these stockholders could have a material adverse effect on the trading price of our
common stock.
We are a “smaller reporting company” and the reduced disclosure requirements applicable to such companies may
make our common stock less attractive to investors.
We are a “smaller reporting company,” as defined in Rule 12b-2 under the Securities Exchange Act of 1934, as
amended. We would cease to be a smaller reporting company if we have a non-affiliate public float in excess of $250
million and annual revenues in excess of $100 million, or a non-affiliate public float in excess of $700 million, determined
on an annual basis. As a smaller reporting company, we are permitted and intend to rely on exemptions from certain
disclosure requirements that are applicable to other public companies that are not smaller reporting companies. These
exemptions include:
·
·
being permitted to provide only two years of audited consolidated financial statements in this Annual Report on
Form 10-K, with correspondingly reduced “Management's Discussion and Analysis of Financial Condition and
Results of Operations” disclosure;
reduced disclosure obligations regarding executive compensation;
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·
·
not being required to furnish a contractual obligations table in “Management's Discussion and Analysis of
Financial Condition and Results of Operations”; and
not being required to furnish a stock performance graph in our annual report.
We expect to continue to take advantage of some or all of the available exemptions until we cease to be a smaller
reporting company.
We cannot predict whether investors will find our common stock less attractive if we rely on these exemptions. If
some investors find our common stock less attractive as a result, there may be a less active trading market for our common
stock and our stock price may be more volatile.
We incur increased costs as a result of operating as a public company, and our management is now required to devote
substantial time to new compliance initiatives and corporate governance practices.
As a public company, and particularly since January 1, 2020, when we ceased to be an “emerging growth company,”
as defined in the Jumpstart Our Business Startups Act of 2012, we incur and will continue to incur significant legal,
accounting and other expenses that we did not incur as a private company. The Sarbanes-Oxley Act of 2002, the Dodd-
Frank Wall Street Reform and Consumer Protection Act, the listing requirements of The Nasdaq Global Market and other
applicable securities rules and regulations impose various requirements on public companies, including establishment and
maintenance of effective disclosure and financial controls and corporate governance practices. Our management and other
personnel devote a substantial amount of time to these compliance initiatives. Moreover, these rules and regulations have
increased our legal and financial compliance costs and will make some activities more time-consuming and costly.
Pursuant to Section 404 of the Sarbanes-Oxley Act of 2002, or Section 404, we are required to furnish a report by
our management on our internal control over financial reporting. As of January 1, 2020, we are also required to include an
attestation report on internal control over financial reporting issued by our independent registered public accounting firm
because we are no longer an emerging growth company. To maintain compliance with Section 404, we will continue to
document and evaluate our internal control over financial reporting, which is both costly and challenging. In this regard,
we will continue to dedicate internal resources, potentially engage outside consultants and adopt a detailed work plan to
assess and document the adequacy of internal control over financial reporting, continue steps to improve control processes
as appropriate, validate through testing that controls are functioning as documented and implement a continuous reporting
and improvement process for internal control over financial reporting. Despite our efforts, there is a risk that neither we
nor our independent registered public accounting firm will be able to conclude, within the prescribed timeframe or at all,
that our internal control over financial reporting is effective as required by Section 404. If we or our independent registered
public accounting firm identify one or more material weaknesses in our internal control over financial reporting, it could
result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of our consolidated
financial statements.
Because we do not anticipate paying any cash dividends on our capital stock in the foreseeable future, capital
appreciation, if any, will be our stockholders’ sole source of gain.
We have never declared or paid cash dividends on our capital stock. We currently intend to retain all of our future
earnings, if any, to finance the growth and development of our business. In addition, the terms of our Credit Agreement
and any future debt agreements that we may enter into, may preclude us from paying dividends without the lenders’
consent or at all. As a result, capital appreciation, if any, of our common stock will be our stockholders’ sole source of gain
for the foreseeable future.
Item 1B.
Unresolved Staff Comments
None.
Item 2.
Properties
Our facilities consist of leased office space, laboratory space and manufacturing facilities in Bedford, Massachusetts.
We occupy approximately 121,000 square feet of space. The lease for approximately 71,000 square feet
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of space expires in July 2027, the lease for approximately 30,000 square feet of space expires in 2024, and the lease for
approximately 20,000 square feet of space expires in 2023. We believe that our current facilities are suitable and adequate
to meet our current needs.
Item 3.
Legal Proceedings
On July 7, 2017, a putative class action lawsuit was filed against us and certain of our current and former executive
officers in the United States District Court for the District of New Jersey, captioned Thomas Gallagher v. Ocular
Therapeutix, Inc, et al., Case No. 2:17-cv-05011. The complaint purports to be brought on behalf of shareholders who
purchased our common stock between May 5, 2017 and July 6, 2017. The complaint generally alleges that we and certain
of our current and former officers violated Sections 10(b) and/or 20(a) of the Securities Exchange Act of 1934, or the
Exchange Act, and Rule 10b-5 promulgated thereunder by making allegedly false and/or misleading statements concerning
the Form 483 issued by the FDA related to DEXTENZA and our manufacturing operations for DEXTENZA. The
complaint seeks unspecified damages, attorneys’ fees, and other costs. On July 14, 2017, an amended complaint was filed;
the amended complaint purports to be brought on behalf of shareholders who purchased our common stock between May 5,
2017 and July 11, 2017, and otherwise includes allegations similar to those made in the original complaint.
On July 12, 2017, a second putative class action lawsuit was filed against us and certain of our current and former
executive officers in the United States District Court for the District of New Jersey, captioned Dylan Caraker v. Ocular
Therapeutix, Inc., et al., Case No. 2:17-cv-05095. The complaint purports to be brought on behalf of shareholders who
purchased our common stock between May 5, 2017 and July 6, 2017. The complaint includes allegations similar to those
made in the Gallagher complaint and seeks similar relief.
On August 3, 2017, a third putative class action lawsuit was filed against us and certain of our current and former
executive officers in the United States District Court for the District of New Jersey, captioned Shawna Kim v. Ocular
Therapeutix, Inc., et al., Case No. 2:17-cv-05704. The complaint purports to be brought on behalf of shareholders who
purchased our common stock between March 10, 2016 and July 11, 2017. The complaint includes allegations similar to
those made in the Gallagher complaint and seeks similar relief.
On October 27, 2017, a magistrate judge for the United States District Court for the District of New Jersey granted
the defendants’ motion to transfer the above-referenced Gallagher, Caraker, and Kim litigations to the United States
District Court for the District of Massachusetts. These matters were assigned the following docket numbers in the District
of Massachusetts: 1:17-cv-12288 (Gallagher), 1:17-cv-12146 (Caraker), and 1:17-cv-12286 (Kim).
On March 9, 2018, the court consolidated the three actions and appointed co-lead plaintiffs and co-lead counsel for
the consolidated action. On May 7, 2018, co-lead plaintiffs filed a consolidated amended class action complaint. The
amended complaint makes allegations similar to those in the original complaints, against the same defendants, and seeks
similar relief on behalf of shareholders who purchased our common stock between March 10, 2016 and July 11, 2017. The
amended complaint generally alleges that defendants violated Sections 10(b) and/or 20(a) of the Exchange Act and Rule
10b-5 promulgated thereunder. On July 6, 2018, defendants filed a motion to dismiss the consolidated amended
complaint. Plaintiffs filed an opposition to the motion to dismiss on September 4, 2018, and defendants filed a reply on
October 4, 2018. The court held oral argument on the motion to dismiss on February 6, 2019. By order dated April 30,
2019, the court granted defendants’ motion to dismiss. On May 31, 2019, the plaintiffs filed a notice of appeal to the United
States Court of Appeals for the First Circuit regarding the District Court’s opinion and order of dismissal of the Complaint.
The plaintiffs/appellants filed their opening brief on the appeal on October 23, 2019. Defendants/appellees filed their
response on November 22, 2019. Plaintiffs/appellants filed their reply brief on December 13, 2019. The First Circuit
held an oral argument on the appeal on February 4, 2020, and took the matter under advisement.
We deny any allegations of wrongdoing and intend to vigorously defend against these lawsuits.
Shareholder Derivative Litigation
On July 11, 2017, a purported shareholder derivative lawsuit was filed against certain of our current and former
executive officers, certain current and former board members, and us as a nominal defendant, in the United States District
Court for the District of Massachusetts, captioned Robert Corwin v. Sawhney et al., Case No. 1:17-cv-11270.
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The complaint generally alleged that the individual defendants breached fiduciary duties owed to us by making allegedly
false and/or misleading statements concerning the Form 483 related to DEXTENZA and our manufacturing operations for
DEXTENZA. The complaint purported to assert claims against the individual defendants for breach of fiduciary duty, and
sought to recover on behalf of us for any liability we incur as a result of the individual defendants’ alleged
misconduct. The complaint also sought contribution on behalf of us from all individual defendants for their alleged
violations of Sections 10(b) and/or 20(a) of the Exchange Act and Rule 10b-5 promulgated thereunder. The complaint
sought declaratory, equitable, and monetary relief, an unspecified amount of damages, with interest, and attorneys’ fees and
costs. On September 20, 2017, counsel for the plaintiff filed a notice of voluntary dismissal, stating that the plaintiff
wished to coordinate his efforts and proceed in a consolidated fashion with the plaintiff in a similar derivative suit that was
pending in the Superior Court of Suffolk County of the Commonwealth of Massachusetts captioned Angel Madera v.
Sawhney et al., Case. No. 17-2273 (which is discussed in the paragraph immediately below) by filing an action in that court
subsequent to the dismissal of this lawsuit. The Corwin lawsuit was dismissed without prejudice on September 21,
2017. On October 24, 2017, the plaintiff filed a new derivative complaint in Massachusetts Superior Court (Suffolk
County), captioned Robert Corwin v. Sawhney et al., Case No. 17-3425 (BLS2). The new Corwin complaint includes
allegations similar to those made in the federal court complaint and asserts a derivative claim for breach of fiduciary duty
against certain of our current and former officers and directors. The complaint also asserts an unjust enrichment claim
against two additional defendants, SV Life Sciences Fund IV, LP and SV Life Sciences Fund IV Strategic Partners,
LP. The complaint also names us as a nominal defendant.
On July 19, 2017, a second purported shareholder derivative lawsuit was filed against certain of our current and
former executive officers, all current board members, one former board member, and us as a nominal defendant, in the
Superior Court of Suffolk County of the Commonwealth of Massachusetts, captioned Angel Madera v. Sawhney et al.,
Case. No. 17-2273. The complaint included allegations similar to those made in the Corwin complaint. The complaint
purported to assert derivative claims against the individual defendants for breach of fiduciary duty, unjust enrichment,
abuse of control, gross mismanagement, and waste of corporate assets, and sought to recover on behalf of us for any
liability we incur as a result of the individual defendants’ alleged misconduct. The complaint sought declaratory, equitable,
and monetary relief, an unspecified amount of damages, with interest, and attorneys’ fees and costs. On November 6, 2017,
the court dismissed this action without prejudice due to plaintiff’s failure to complete service of process within the time
permitted under applicable court rules. On December 21, 2017, the same plaintiff filed a new derivative complaint in the
same court, captioned Angel Madera v. Sawhney et al., Case. No. 17-4126 (BLS2). The new Madera complaint is
premised on substantially similar allegations as the previous complaint and purports to assert derivative claims against
certain current and former executive officers and board members for breach of fiduciary duty, unjust enrichment, and waste
of corporate assets, and names the company as a nominal defendant. Like the new Corwin complaint, the new Madera
complaint also asserts an unjust enrichment claim against two additional defendants, SV Life Sciences Fund IV, LP and SV
Life Sciences Fund IV Strategic Partners, LP.
By order dated January 29, 2018, the court consolidated the state court Corwin and Madera complaints under the
Corwin docket and appointed lead counsel for plaintiffs. On February 28, 2018, plaintiffs filed a consolidated amended
complaint. The consolidated complaint names substantially the same defendants and is premised on substantially similar
allegations as the previous Corwin and Madera complaints, asserting claims for breach of fiduciary duty against the
individual defendants and unjust enrichment against the two SV entity defendants. On April 17, 2018, all defendants
served a motion to dismiss the consolidated amended complaint. On June 22, 2018, plaintiffs served their opposition to the
motion to dismiss and a cross-motion to stay the proceedings pending a decision on the motion to dismiss in the above-
referenced securities class action in the District of Massachusetts. On July 30, 2018, the parties filed a joint motion to stay
the proceedings pending a decision on the motion to dismiss in the above-referenced securities class action in the District of
Massachusetts. On August 3, 2018, the court granted the motion to stay.
On January 31, 2018, a third purported shareholder derivative suit was filed against certain of our current and former
executive officers, certain current and former board members, and us as a nominal defendant, in the United States District
Court for the District of Massachusetts, captioned Brian Robinson v. Sawhney et al., Case. No. 1:18-cv-10199. The
complaint includes allegations similar to those made in the Corwin and Madera complaints. The complaint does not name
either SV Life Sciences Fund, IV, LP or SV Life Sciences Fund IV Strategic Partners, LP as defendants, and adds two
former officers as defendants. The complaint purports to assert derivative claims against the individual defendants for
breach of fiduciary duty, waste of corporate assets, and unjust enrichment, and seeks to recover on behalf of us for any
liability we incur as a result of the individual defendants’ alleged misconduct. The complaint seeks declaratory, equitable,
and monetary relief, an unspecified amount of damages, with interest, and attorneys’ fees and costs. On April 30, 2018, all
defendants filed a motion to dismiss or stay the complaint. Plaintiff filed his opposition on June 22, 2018.
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On July 26, 2018, the parties filed a joint motion to extend the deadline for defendants to file their reply brief pending the
potential substitution of the named shareholder plaintiff. On August 20, 2018, the parties filed a joint stipulation and
proposed order regarding plaintiff’s unopposed request to substitute a new shareholder plaintiff and the parties’ joint
request that the court stay the proceedings pending a decision on the motion to dismiss in the above-referenced securities
class action in the District of Massachusetts. On September 4, 2018, the court entered the requested order substituting the
named plaintiff and staying the matter.
On February 16, 2018, a fourth purported shareholder derivative suit was filed against certain of our current and
former executive officers, certain current and former board members, and us as a nominal defendant, in the United States
District Court for the District of Delaware, captioned Terry Kelly v. Sawhney et al., Case. No. 1:18-cv-00277. The
complaint includes allegations similar to those made in the Corwin and Madera complaints. The complaint purports to
assert derivative claims against the individual defendants for breach of fiduciary duty, unjust enrichment, and waste of
corporate assets, and seeks to recover on behalf of us for any liability we incur as a result of the individual defendants’
alleged misconduct. The complaint also asserts an unjust enrichment claim against SV Life Sciences Fund IV, LP and SV
Life Sciences Fund IV Strategic Partners, LP. The complaint seeks declaratory, equitable, and monetary relief, an
unspecified amount of damages, with interest, and attorneys’ fees and costs. On June 11, 2018, the parties filed a stipulation
staying the lawsuit pending final judgment in the consolidated derivative action pending in Massachusetts state court under
the Corwin docket, described above. The court entered an order staying the case on June 12, 2018.
We deny any allegations of wrongdoing and intend to vigorously defend against these lawsuits.
In addition, we received a subpoena from the SEC, dated December 15, 2017, requesting documents and information
concerning DEXTENZA (dexamethasone insert) 0.4mg, including related communications with the U.S. Food and Drug
Administration, investors and others. We received a second subpoena from the SEC on August 21, 2018, requesting
documents and information concerning its participation in two investor conferences in June 2017. By letter dated May 2,
2019, the SEC notified us that the SEC had concluded its investigation and did not intend to recommend an enforcement
action against us or any individuals.
We are unable to predict the outcome of these lawsuits or proceedings at this time. Moreover, any conclusion of these
matters in a manner adverse to us and for which we incur substantial costs or damages not covered by our directors’ and
officers’ liability insurance would have a material adverse effect on our financial condition and business. In addition, the
proceedings could adversely impact our reputation and divert management’s attention and resources from other priorities,
including the execution of business plans and strategies that are important to our ability to grow our business, any of which
could have a material adverse effect on our business.
Item 4.
Mine Safety Disclosures
None.
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PART II
Item 5.
Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer’s Purchases of
Equity Securities
Our common stock has been publicly traded on the Nasdaq Global Market under the symbol “OCUL” since July 25,
2014.
Holders
As of March 1, 2020, there were approximately 29 holders of record of our common stock. This number does not
include beneficial owners whose shares are held by nominees in street name.
Dividends
We have never declared or paid cash dividends on our common stock, and we do not expect to pay any cash
dividends on our common stock in the foreseeable future. In addition, the terms of our existing credit facility preclude us
from paying cash dividends without the consent of our lenders.
Recent Sales of Unregistered Securities
We did not sell any shares of our common stock, shares of our preferred stock or warrants to purchase shares of our
stock, or grant any stock options or restricted stock awards, during the year ended December 31, 2019 that were not
registered under the Securities Act of 1933, as amended, or the Securities Act, and that have not otherwise been described
in an Annual Report on Form 10-K or a Quarterly Report on Form 10-Q.
Purchase of Equity Securities
We did not purchase any of our registered equity securities during the period covered by this Annual Report on Form
10-K.
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Item 6.
Selected Financial Data
The following selected financial data should be read together with our consolidated financial statements and the
related notes appearing elsewhere in this Annual Report on Form 10-K and the “Management’s Discussion and Analysis of
Financial Condition and Results of Operations” section of this Annual Report on Form 10-K. We have derived the
statements of operations data for the years ended December 31, 2019, 2018, and 2017, and the balance sheet data as of
December 31, 2019 and 2018 from our audited consolidated financial statements included elsewhere in this Annual Report
on Form 10-K. We have derived the statements of operations data for the years ended December 31, 2016 and 2015 and
the balance sheet data as of December 31, 2017, 2016 and 2015 from our audited consolidated financial statements not
included in this Annual Report on Form 10-K. Our historical results for any prior period are not necessarily indicative of
results to be expected in any future period.
2019
Year Ended
December 31,
2017
(in thousands, except per share data)
2018
2016
2015
Statement of Operations Data:
Revenue:
Product revenue, net
Collaboration revenue
Total revenue
Costs and operating expenses:
Cost of product revenue
Research and development
Selling and marketing
General and administrative
Total costs and operating expenses
Loss from operations
Other income (expense):
Interest income
Interest expense
Change in fair value of derivative liability
Other income (expense), net
Total other expense, net
Net loss
Net loss per share attributable to common stockholders, basic
and diluted
Weighted average common shares outstanding, basic and
diluted
$ 4,227 $ 1,990 $ 1,923 $ 1,845 $ 1,354
396
1,750
42
1,887
—
4,227
—
1,990
—
1,923
2,325
41,091
24,491
22,122
90,029
(85,802)
465
36,915
4,942
18,786
61,108
(59,118)
457
30,880
17,000
15,509
63,846
(61,923)
443
27,065
6,701
11,004
45,213
(43,326)
319
26,611
3,852
9,165
39,947
(38,197)
1,229
(6,101)
4,310
(8)
(570)
(86,372)
879
(1,739)
—
—
(860)
(59,978)
424
(1,892)
—
5
(1,463)
(63,386)
304
(1,680)
—
(1)
(1,377)
(44,703)
166
(1,724)
—
7
(1,551)
(39,748)
$
(1.91) $
(1.57) $
(2.20) $
(1.80) $
(1.71)
45,273
38,115
28,818
24,816
23,244
2019
2018
As of December 31,
2017
(in thousands)
2016
2015
Balance Sheet Data:
Cash, cash equivalents and marketable securities
Working capital
Operating lease assets
Total assets
Operating lease liabilities, including current portion
Long-term debt, net of discount, including current portion
Total stockholders’ equity (deficit)
(1)
(1)
(1)
(1)
$ 54,437 $ 54,062 $ 41,538 $ 68,145 $ 105,064
101,605
—
110,306
—
15,272
89,588
29,913 61,598
—
55,431 74,939
—
18,016 15,643
26,147 52,008
48,141
6,655
78,740
10,031
49,312
(3,630)
47,034
—
73,043
—
24,788
35,875
—
—
(1) Amounts prior to 2019 do not reflect the impact of the adoption of Accounting Standards Update (ASU) 2016-02,
Leases (Topic 842), in the first quarter of 2019 under the modified retrospective transition method. See Note 2 -
Summary of Significant Accounting Policies to the consolidated financial statements included elsewhere in this
Annual Report on 10-K for additional information.
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Item 7.
Management’s Discussion and Analysis of Financial Condition and Results of Operations
The following discussion and analysis of our financial condition and results of operations should be read together
with our consolidated financial statements and related notes appearing elsewhere in this Annual Report on Form 10-K.
Some of the information contained in this discussion and analysis or set forth elsewhere in this Annual Report on Form 10-
K, including information with respect to our plans and strategy for our business and related financing, includes forward-
looking statements that involve risks and uncertainties and should be read together with the “Risk Factors” section of this
Annual Report on Form 10-K for a discussion of important factors that could cause actual results to differ materially from
the results described in or implied by the forward-looking statements contained in the following discussion and analysis.
Overview
We are a biopharmaceutical company focused on the formulation, development and commercialization of innovative
therapies for diseases and conditions of the eye using our proprietary, bioresorbable hydrogel platform technology. We use
this technology to tailor duration and amount of delivery of a range of therapeutic agents of varying duration in our product
candidates.
We currently incorporate therapeutic agents that have previously received regulatory approval from the U.S. Food
and Drug Administration, or FDA, including small molecules and proteins, into our hydrogel technology with the goal of
providing local programmed-release of drug to the eye. We believe that our local programmed-release drug delivery
technology has the potential to treat conditions and diseases of both the front and the back of the eye and can be
administered through a range of different modalities including intracanalicular inserts, intracameral implants and
intravitreal implants. We have products and product candidates in early commercial, clinical and preclinical development
applying this technology to treat post-surgical ocular inflammation and pain, ocular itching associated with allergic
conjunctivitis, dry eye disease, glaucoma and ocular hypertension, and wet age-related macular degeneration, or wet AMD,
among other conditions.
In November 2018, the FDA approved our new drug application, or NDA, for DEXTENZA (dexamethasone
ophthalmic insert) 0.4mg for intracanalicular use for the treatment of ocular pain following ophthalmic surgery. In June
2019, the FDA approved our supplemental new drug application, or sNDA, for DEXTENZA to treat post-surgical ocular
inflammation. On July 1, 2019, we commercially launched DEXTENZA in the United States for the treatment of post-
surgical ocular inflammation and pain. DEXTENZA is the first FDA-approved intracanalicular insert delivering
dexamethasone to treat post-surgical ocular inflammation and pain for up to 30 days with a single administration. We have
also initiated a pivotal Phase 3 clinical trial evaluating DEXTENZA for the treatment of ocular itching associated with
allergic conjunctivitis.
®
In May 2019, we announced the results of the Phase 3 clinical trial of our product candidate OTX-TP
(intracanalicular travoprost insert) for the reduction of intraocular pressure, or IOP, in patients with glaucoma and ocular
hypertension. Both DEXTENZA and OTX-TP are local programmed-release, drug-eluting, preservative-free
intracanalicular inserts that are placed into the canaliculus through a natural opening called the punctum located in the
portion of the lower eyelid near the nose. In October 2019, we announced that we had met with FDA who determined that
the results did not achieve clinical meaningfulness for OTX-TP. As a result, we informed the market that we did not intend
to advance OTX-TP without a partner.
Our earlier stage assets include two development programs that have initiated clinical trials: OTX-TIC, an
intracameral travoprost implant for the reduction of IOP in patients with glaucoma and ocular hypertension when greater
IOP reduction is needed, and OTX-TKI, an intravitreal injection by fine gauge needle of a hydrogel, anti-angiogenic
formulation of a tyrosine kinase inhibitor, or TKI, for the treatment of wet AMD. We also have a collaboration with
Regeneron Pharmaceuticals, Inc., or Regeneron, for the development and potential commercialization of products
containing our local programmed-release hydrogel in combination with Regeneron’s VEGF inhibitor, aflibercept, currently
marketed under the brand name Eylea. We delivered an initial formulation to Regeneron in late 2018 that was subsequently
determined to not achieve the goals of the program. We are currently negotiating an amendment to the initial collaboration
to deliver additional formulations going forward.
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In addition to our ongoing drug product development, we currently market ReSure Sealant, a hydrogel ophthalmic
®
wound sealant approved by the FDA to seal corneal incisions following cataract surgery. ReSure Sealant is the first and
only surgical sealant to be approved by the FDA for ophthalmic use. We are also assessing the potential use of our hydrogel
platform technology in other areas of the body.
Inflammation and Pain after Ocular Surgery
DEXTENZA (dexamethasone ophthalmic insert)
®
DEXTENZA incorporates the FDA-approved corticosteroid dexamethasone as an active pharmaceutical ingredient
into a hydrogel, drug-eluting intracanalicular insert. In November 2018, the FDA approved our NDA for DEXTENZA for
the treatment of post-surgical ocular pain. In June 2019, the FDA approved our sNDA, for DEXTENZA to treat post-
surgical ocular inflammation. In connection with our July 1, 2019 commercial launch of DEXTENZA for post-surgical
ocular inflammation and pain, we have built our own highly targeted, key account manager, or KAM, sales force that
focuses on the ambulatory surgical centers, or ASCs, responsible for the largest volumes of cataract surgery. Since the
commercial launch of DEXTENZA, we have expanded our field sales team to a total of 30 KAMs. DEXTENZA is now
available through a network of distributors. Our initial commercial efforts are focused on the two million cataract
procedures performed annually under Medicare Part B. Following our receipt of FDA approval on November 30, 2018, we
submitted an application for a C-code for transitional pass-through payment status. On May 29, 2019, we received formal
notification from the Centers for Medicare and Medicaid Services, or CMS, that it had approved transitional pass-through
payment status and established a new reimbursement code for DEXTENZA. The code, C9048, became effective on July 1,
2019. On December 28, 2018, we submitted an application for a J-Code for permanent payment status. In July 2019, we
subsequently received a specific and permanent J-Code, J1096, that became effective October 1, 2019. A J-Code is a
permanent code used to report drugs that ordinarily cannot be self-administered. With the effectiveness of our permanent J-
Code as of October 1, 2019, our C-code is no longer in effect.
We have completed three Phase 3 clinical trials of DEXTENZA for the treatment of post-surgical ocular
inflammation and pain. The data from two of these three completed Phase 3 clinical trials and a prior Phase 2 clinical trial
were used to support our NDA for post-surgical ocular pain; data from a subsequent Phase 3 clinical trial was used to
support our subsequent sNDA for post-surgical ocular inflammation. In June 2019, the FDA approved the sNDA. We have
also completed two Phase 3 clinical trials of DEXTENZA for the treatment of allergic conjunctivitis and a Phase 2 clinical
trial of DEXTENZA for the treatment of episodic dry eye disease.
In the third quarter of 2019, we began dosing patients in an 80-subject, pivotal Phase 3 clinical trial evaluating
DEXTENZA for the treatment of ocular itching associated with allergic conjunctivitis. This Phase 3 clinical trial is a U.S.-
based, multi-center, 1:1 randomized, double-masked, placebo-controlled trial that intends to enroll approximately 96
subjects, testing the safety and efficacy of DEXTENZA (dexamethasone ophthalmic insert) 0.4 mg versus a placebo
vehicle punctum plug using the Ophthalmic Research Associates’ modified Conjunctival Allergen Challenge (Ora-Cac®)
Model for the treatment of ocular itching associated with allergic conjunctivitis. The trial is designed to assess the effect of
DEXTENZA compared with a placebo on allergic reactions using a series of successive allergen challenges over a 30-day
period. The primary efficacy endpoint being evaluated in the study is ocular itching one week following the insertion of
DEXTENZA. DEXTENZA is administered by a physician as a bioresorbable intracanalicular insert and designed for drug
release to the ocular surface for up to 30 days. Previously, we completed two Phase 3 clinical trials, in which DEXTENZA
for the treatment of ocular itching associated with allergic conjunctivitis. In the first Phase 3 clinical trial, DEXTENZA
achieved the co-primary endpoint of improvement in ocular itching compared with placebo but failed to achieve on the co-
primary endpoint of improvement in conjunctival redness compared with placebo, in each case, at certain prespecified
timepoints. For the second Phase 3 trial, DEXTENZA failed to achieve the primary endpoint of improvement in ocular
itching compared with placebo, at certain prespecified timepoints. This trial represents the third Phase 3 clinical trial in
allergic conjunctivitis conducted by us and, if successful, we plan to submit a supplemental NDA to the FDA for ocular
itching associated with allergic conjunctivitis. We have recently completed enrollment and topline results from this trial are
anticipated to be reported in the second quarter of 2020.
We are also planning to evaluate DEXTENZA in pediatric subjects that are 0 to 3 years of age undergoing cataract
surgery beginning in the second half of 2020. The planned pediatric trial is a post-approval commitment to the
FDA. Additionally, we have received proposals for, and plan to support, several investigator-initiated trials evaluating
DEXTENZA in different clinical situations.
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Glaucoma Programs
Glaucoma is a large market and a disease that is estimated to impact more than 2.7 million people age 40 or older in
the U.S. The primary goal of glaucoma treatment is to slow the progression of this chronic disease by reducing intraocular
pressure, and many medications can accomplish this. Importantly, however, adherence to current topical glaucoma
therapies is known to be particularly poor with reported rates of non-adherence from 30% to 80%. These low compliance
rates may be associated with disease progression and loss of vision, and may be part of the reason that glaucoma is a
leading cause of blindness in people over 60 years of age.
Prostaglandins are the most commonly used class of medications to treat patients with glaucoma and are
administered via daily eye drops as the current standard of care. The ability of patients to use and place daily eye drops is
challenging. The products that we are developing are designed to address the issue of compliance by delivering a
prostaglandin analog formulated with our programmed release hydrogel to lower intraocular pressure for several months
with a single insert.
OTX-TIC (travoprost implant for intracameral injection)
OTX-TIC is our product candidate for glaucoma patients in need of a significant reduction in IOP and ocular
hypertension. OTX-TIC is a bioresorbable hydrogel implant incorporating travoprost that is designed to be administered by
a physician as an intracameral injection with an initial target duration of drug release of four to six months. Preclinical
studies to date have demonstrated reduction of IOP and pharmacokinetics in the aqueous humor that suggest a
pharmacodynamic response of IOP reduction in humans. Our investigational new drug application, or IND, for our U.S.
trial became effective in the first quarter of 2018, and we dosed the first patient in May 2018. This clinical trial is a multi-
center, open-label, dose-escalation, proof-of-concept study designed to evaluate the safety, durability, tolerability, and
biological activity of OTX-TIC in patients with primary open-angle glaucoma or ocular hypertension. We presented initial
results from the first cohort, comprised of five patients, in this clinical trial at the Association of Research and Vision of
Ophthalmology (ARVO) meeting in April 2019 and the American Society of Cataract and Refractive Surgery annual
meeting in May 2019. This data demonstrated that, with a single implant, subjects were able to achieve IOP lowering for
up to thirteen months at a level least as good as standard of care topical eye drop that was placed in each subject’s non-
study eye. In addition, the hydrogel carrier, as designed, biodegraded in five to seven months. There were no clinically
meaningful changes in corneal health as measured by endothelial cell evaluation and corneal pachymetry. Several subjects
reported low grade inflammation and peripheral anterior synechiae that we believe may be addressable with modifications
to the implants. We are currently collecting additional data from the first two cohorts and have begun enrollment in a third
and fourth cohort to assess the impact of a faster degrading implant with the same therapeutic dose as administered in
cohort one. We have developed an additional formulation to test a smaller implant of OTX-TIC and expect to evaluate this
formulation in a fourth cohort of this clinical trial in the future.
OTX-TP (intracanalicular travoprost insert)
Our product OTX-TP is an intracanalicular insert that delivers a preservative-free formulation of the drug travoprost
for the reduction of intraocular pressure, or IOP, in patients with primary open-angle glaucoma or ocular hypertension.
OTX-TP is designed to lower IOP for up to 90 days and to address the poor adherence associated with chronic, daily eye
drop regimens, the current standard of care.
On May 20, 2019, we reported topline results of the Phase 3 randomized, double blind, placebo-controlled clinical
trial that was conducted across more than 50 sites and enrolled 554 subjects with open-angle glaucoma or ocular
hypertension in the full analysis set, or FAS, population. The trial’s primary efficacy endpoint was an assessment of mean
IOP at nine different time points, three diurnal time points (8:00 a.m, 10:00 a.m. and 4:00 p.m.) at each of 2, 6, and 12
weeks following insertion. The secondary endpoints included an evaluation of whether OTX-TP demonstrated a
statistically superior mean reduction of IOP from baseline for OTX-TP treated subjects compared with placebo insert
treated subjects (Table 1) compared with placebo insert treated subjects at the same nine time points. Topline results show
that the trial did not achieve its endpoint of statistically significant superiority in mean reduction of IOP compared with
placebo at all nine time points.
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OTX-TP was generally well tolerated and no ocular serious adverse events were observed. The most common ocular
adverse events seen in the study eye were dacryocanaliculitis (approximately 7.0% in OTX-TP vs. 3.0% in placebo) and
lacrimal structure disorder (approximately 6.0% in OTX-TP vs. 4.0% in placebo).
We have met with the FDA to discuss data we reported in May 2019 from our completed phase three trial. Our
conversation with the FDA was productive and involved a discussion around the importance of compliance and how a
product like OTX-TP could address the issue of non-compliance by delivering a prostaglandin analog formulated with our
programmed release hydrogel to lower intraocular pressure for up to 12 weeks with a single insert. While the FDA did not
feel that the data from this clinical trial met the standard of clinical meaningfulness in the population studied, there were
constructive discussions about potential pathways forward in specific patient populations for whom drops are problematic.
Therefore, we do not intend to initiate a second Phase 3 clinical trial at this time without the assistance of a collaborative
partner. We believe that if we were to partner OTX-TP, we may choose to conduct additional Phase 2 clinical trials to
address feedback from the FDA. Given the anticipated use of OTX-TP as a chronic therapy, however, we generated six-
month and one year safety data on a limited number of subjects in an open-label one year safety extension study to support
a potential future product registration.
Back-of-the-Eye Programs
We are engaged in the development of formulations of our hydrogel administered via intravitreal injection to address
the large and growing markets for diseases and conditions of the back of the eye. Our initial development efforts are
focused on the use of our extended-delivery hydrogel in combination with anti-angiogenic drugs, such as protein-based
anti-VEGF drugs, or small molecule drugs, such as TKIs, for the treatment of retinal diseases such as wet AMD, retinal
vein occlusion and diabetic macular edema. Our initial goal for these programs is to provide extended delivery over a four
to nine month period thereby reducing the frequency of the current monthly or bi-monthly immediate release intravitreal
injection regimen for wet AMD and other retinal diseases.
OTX-TKI (tyrosine kinase inhibitor intravitreal impaling containing axitinib)
OTX-TKI is a preformed, bioresorbable hydrogel fiber incorporating axitinib, a small molecule TKI with anti-
angiogenic properties delivered by intravitreal injection. TKIs have shown promise in the treatment of wet AMD. In May
2017, we reported data from preclinical studies evaluating the efficacy, tolerability and pharmacokinetics of OTX-TKI. In
this study, OTX-TKI was well-tolerated, and high levels of drug were maintained in the tissue for up to twelve months in
Dutch belted rabbits. In the first quarter of 2019, we began dosing patients in a Phase 1 clinical trial in Australia. This
clinical trial is a multi-center, open-label, dose escalation study designed to evaluate the safety, durability and tolerability of
OTX-TKI. We also plan to evaluate biological activity by following visual acuity over time and measuring retinal thickness
using standard optical coherence tomography. The independent Data Safety and Monitoring Committee met to review the
safety from the first cohort of subjects in the Phase 1 clinical trial and recommended moving to a higher dose of OTX-TKI
for the next cohort of subjects to be treated, as the first cohort of subjects reported no safety concerns. Two cohorts of six
subjects each have been enrolled, a lower dose cohort of 200 μg and a higher dose cohort of 400 μg. In the first two fully
enrolled cohorts, OTX-TKI was generally well tolerated and observed to have a favorable safety profile with no ocular
serious adverse events noted. In the higher dose cohort, OTX-TKI showed a decrease in central subfield retinal thickness as
measured by mean change in central subfield thickness by decreases in intraretinal and/or subretinal fluid in some subjects.
The Company plans to continue long-term evaluation of the first two cohorts. We plan to amend our current trial protocol
to enroll a third, higher-dose cohort. This Phase 1 clinical trial is not powered to measure any efficacy endpoints with
statistical significance.
OTX-IVT (intravitreal aflibercept implant) in collaboration with Regeneron
In October 2016, we entered into a strategic collaboration, option and license agreement, or Collaboration
Agreement, with Regeneron for the development and potential commercialization of products using our hydrogel in
combination with Regeneron’s large molecule VEGF-targeting compounds for the treatment of retinal diseases, with the
initial focus on the VEGF trap aflibercept, currently marketed under the brand name Eylea. Under the terms of the
agreement, we granted Regeneron an option, or the Option, to enter into an exclusive, worldwide license under our
intellectual property to develop and commercialize products using our hydrogel in combination with Regeneron’s large
molecule VEGF-targeting compounds, or Licensed Products. The Collaboration Agreement does not cover the
development of any products that deliver small molecule drugs, including TKIs, for any target including VEGF, or any
products that deliver large molecule drugs other than those that target VEGF proteins. Under the terms of the
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Collaboration Agreement, we and Regeneron have agreed to conduct a joint research program with the aim of developing
an extended-delivery formulation of aflibercept that is suitable for advancement into clinical development. We refer to the
formulation we are developing with Regeneron as OTX-IVT.
Under the terms of the Collaboration Agreement, Regeneron is responsible for funding an initial preclinical
tolerability study, which it initiated in early 2018. If the Option is exercised, Regeneron will conduct further preclinical
development and an initial clinical trial under a collaboration plan. We are obligated to reimburse Regeneron for certain
development costs during the period through the completion of the initial clinical trial, subject to a cap of $25 million,
which cap may be increased by up to $5 million under certain circumstances. We do not expect our funding requirements
under the collaboration to be material over the next twelve months. If Regeneron elects to proceed with further
development beyond the initial clinical trial, it will be solely responsible for conducting and funding further development
and commercialization of product candidates. If the Option is exercised, Regeneron is required to use commercially
reasonable efforts to research, develop and commercialize at least one Licensed Product. Such efforts shall include
initiating the dosing phase of a subsequent clinical trial within specified time periods following the completion of the first-
in-human clinical trial or the initiation of preclinical toxicology studies, subject to certain extensions.
Under the terms of the Collaboration Agreement, Regeneron has agreed to pay us $10 million upon exercise of the
Option. We are also eligible to receive up to $145 million per Licensed Product upon the achievement of specified
development and regulatory milestones, including successful results from the first-in-human clinical trial, $100 million per
Licensed Product upon first commercial sale of such Licensed Product and up to $50 million based on the achievement of
specified sales milestones for all Licensed Products. In addition, we are entitled to tiered, escalating royalties, in a range
from a high-single digit to a low-to-mid teen percentage of net sales of Licensed Products.
In December 2017, we delivered to Regeneron a proposed final formulation for the initial preclinical tolerability
study. Regeneron initiated the preclinical study in early 2018. We and Regeneron have subsequently reached an
understanding that the proposed formulation was not final and have ceased development of it. We are currently in
discussions with Regeneron, in accordance with the terms of the Collaboration Agreement, regarding the development of
an alternative formulation.
ReSure Sealant
®
Following our receipt of FDA approval for ReSure Sealant, we commercially launched this product in the United
States in 2014. ReSure Sealant is approved to seal corneal incisions following cataract surgery and is the first and only
surgical sealant to be approved by the FDA for ophthalmic use. In the pivotal clinical trials that formed the basis for FDA
approval, ReSure Sealant provided superior wound closure and a better safety profile than sutured closure. While ReSure
Sealant remains commercially available in the United States, there is no sales support currently provided to the product. We
have received only limited revenues from ReSure Sealant to date and anticipate only limited sales for 2020.
The FDA required two post-approval studies as a condition for approval of our premarket approval, or PMA,
application for ReSure Sealant. The first post-approval study, identified as the Clinical PAS, was to enroll at least 598
patients to confirm that ReSure Sealant can be used safely by physicians in a standard cataract surgery practice and to
confirm the incidence of the most prevalent adverse ocular events identified in our pivotal study in eyes treated with
ReSure Sealant. We submitted the final study report of the Clinical PAS to the FDA in June 2016, and the FDA has
confirmed the Clinical PAS has been completed. The second post-approval study, identified as the Device Exposure
Registry Study, is intended to link to the Medicare database to ascertain if patients are diagnosed or treated for
endophthalmitis within 30 days following cataract surgery and application of ReSure Sealant. The Device Exposure
Registry Study is required to include at least 4,857 patients. Due to difficulties in establishing an acceptable way to link
ReSure Sealant to the Medicare database and lack of investigator interest, we have been unable to enroll trial sites and
patients, collect patient data and report study data to the FDA. We have provided regular periodic reports to the FDA on the
progress of this post-approval study.
We received a warning letter from the FDA in October 2018 relating to our compliance with data collection and
information reporting obligations in the Device Exposure Registry Study. The FDA warning letter refers to a lack of
progress with the enrollment and related data collection and information reporting obligations for a required post-approval
trial. In November 2018, we appealed this warning letter. In December 2018, the FDA rejected our appeal. Failure by us to
conduct the required post-approval trial for ReSure Sealant to the FDA’s satisfaction may result in withdrawal of the FDA’s
approval of ReSure Sealant or other regulatory action.
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A teleconference was held with the FDA in January 2019 resulting in tentative agreement on a proposed retrospective
registry study of endophthalmitis rates to satisfy the Device Exposure Registry Study requirements. In a letter dated June
7, 2019 from the FDA, the agency acknowledged receipt of a letter dated March 29, 2019 from us in which we proposed
conducting the proposed retrospective analysis of the IRIS Registry, comparing endophthalmitis rates from sites that
purchased ReSure versus those sites that did not purchase ReSure. If the rates are no different, the FDA has indicated that
it will consider the post-approval requirement to have been fulfilled. If there is a statistically significant increase in
endophthalmitis rates at sites purchasing ReSure compared with those not purchasing ReSure, a prospective study will be
required. The FDA has indicated it will consider our response to the warning letter adequate once it approves the study
protocol for the retrospective analysis of the IRIS Registry and the outline of the prospective study. We submitted the
protocol for the agreed-upon retrospective study and prospective study outline, as required per the terms of the warning
letter in December 2019. We have received feedback from the FDA in February 2020 and we responded to the FDA in
March 2020. We expect a response from the FDA in the middle of 2020.
ReSure Sealant currently remains commercially available in the United States, though there is no sales support
provided to the product at this time. We have received only limited revenues from ReSure Sealant to date and anticipate
only limited sales for 2020.
Additional Potential Areas for Growth
We continue to leverage the potential of our hydrogel platform to explore areas for growth with our focus on
formulating, developing and commercializing innovative therapies for diseases and conditions of the eye.
We are also assessing the potential use of our hydrogel platform technology in other areas of the body and are
studying several localized delivery platforms including via wound inlays; sinus and ear inserts; and subcutaneous,
peripheral, and intra-articular injections. In September 2018, we entered into a second amended and restated license
agreement, or Second Amended Agreement, with Incept LLC, an intellectual property holding company, or Incept. The
Second Amended Agreement expands the scope of our intellectual property license to include products delivered for the
treatment of acute post-surgical pain or for the treatment of ear, nose and/or throat diseases or conditions, subject to
specified exceptions.
Financial Position
We have generated limited revenue to date. All of our local programmed-release drug delivery products are in various
phases of early commercial, clinical and preclinical development. Our ability to generate product revenues sufficient to
achieve profitability will depend heavily on our commercialization of DEXTENZA for the treatment of ocular
inflammation and pain following ophthalmic surgery and our obtaining marketing approval for and commercializing other
products with significant market potential, including DEXTENZA for additional indications, OTX-TIC for glaucoma and
ocular hypertension, and OTX-TKI for wet AMD. Since inception, we have incurred significant operating losses. Our net
losses were $86.4 million, $60.0 million and $63.4 million for the years ended December 31, 2019, 2018 and 2017,
respectively. As of December 31, 2019, we had an accumulated deficit of $383.6 million.
Our total cost and operating expenses were $90.0 million, $61.1 million and $63.8 million for the years ended
December 31, 2019, 2018 and 2017, respectively, including $8.8 million, $7.5 million and $7.3 million, respectively, in
non-cash stock-based compensation expense. Our operating expenses have grown as we prepared for the commercial
launch of DEXTENZA in July 2019; continue to pursue the clinical development OTX-TIC, OTX-TKI and DEXTENZA
for additional indications; continue the internal development of our intravitreal hydrogel formulation for the local
programmed-release of protein-based or small molecule anti-angiogenic drugs, such as OTX-IVT for the treatment of wet
AMD and other back-of-the-eye diseases; continue the research and development of our other product candidates; and seek
marketing approval for any such product candidate for which we obtain favorable pivotal clinical trial results. We expect to
incur substantial sales and marketing expenses in connection with the ongoing DEXTENZA commercial launch and that of
any of our other product candidates. In addition, we will continue to incur additional costs associated with operating as a
public company, including legal costs associated with any pending legal proceedings.
Although we expect to generate revenue from sales of DEXTENZA and potentially ReSure Sealant, we will need to
obtain substantial additional funding to support our continuing operations and the commercialization of DEXTENZA.
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If we are unable to raise capital or access our borrowing capacity when needed or on attractive terms, we could be forced to
delay, reduce or eliminate our research and development programs or any future commercialization efforts or to relinquish
valuable rights to our technologies, future revenue streams, research programs or product candidates or grant licenses on
terms that may not be favorable to us.
Through December 31, 2015, we raised $132.0 million through the sale of common stock in various offerings. In
November 2016, we entered into a Controlled Equity Offering Sales Agreement, or the 2016 Sales Agreement with Cantor
Fitzgerald & Co., or Cantor, under which we could offer and sell our common stock having aggregate proceeds of up to
$40.0 million from time to time. Through February 26, 2019, we sold an aggregate of 6,330,222 shares of common stock
under the 2016 Sales Agreement resulting in net proceeds of approximately $38.4 million after commission and other
offering expenses. On February 28, 2019, pursuant to the 2016 Sales Agreement, we delivered a termination notice to
Cantor, terminating the 2016 Sales Agreement.
In January 2017, we completed a follow-on offering of our common stock at a public offering price of $7.00 per
share. The offering consisted of 3,571,429 shares of common stock sold by us. We received net proceeds from the follow-
on offering of approximately $23.3 million after deducting underwriting discounts, commissions and expenses.
In January 2018, we completed a follow-on offering of our common stock at a public offering price of $5.00 per
share. The offering consisted of 7,475,000 shares of common stock sold by us, including those shares sold in connection
with the exercise by the underwriter of its option to purchase additional shares. We received net proceeds from the follow-
on offering of approximately $35.1 million after deducting underwriting discounts and commissions.
On March 1, 2019, we issued $37.5 million of unsecured senior subordinated convertible notes, or the 2026
Convertible Notes. The 2026 Convertible Notes accrue interest at an annual rate of 6% of its outstanding principal amount,
payable at maturity, on March 1, 2026, unless earlier converted, repurchased or redeemed. The holders of the 2026
Convertible Notes may convert all or part of the outstanding principal amount of their 2026 Convertible Notes into shares
of our common stock, par value $0.0001 per share, prior to maturity and provided that no conversion results in a holder
beneficially owning more than 19.99% of our issued and outstanding common stock. The conversion rate is initially
153.8462 shares of our common stock per $1,000 principal amount of the 2026 Convertible Notes, which is equivalent to
an initial conversion price is $6.50 per share. The conversion rate is subject to adjustment in customary circumstances such
as stock splits or similar changes to our capitalization.
On April 5, 2019, we entered into an Open Market Sale Agreement
SM
, or the 2019 Sales Agreement, with Jefferies
LLC, or Jefferies, under which we may offer and sell shares of our common stock having an aggregate offering price of up
to $50.0 million from time to time through Jefferies, acting as agent. In the twelve months ended December 31, 2019, the
Company sold 7,337,459 shares of common stock under the 2019 Sales Agreement, resulting in net proceeds of
approximately $32.7 million, respectively, after commissions and expenses. From inception to March 10, 2020, we have
sold 9,556,973 shares of common stock under the 2019 Sales Agreement, resulting in net proceeds of approximately $43.3
million after commissions and expenses.
On August 2, 2019, we entered into the Second Amendment of our Third Amended and Restated Credit and Security
Agreement, between us and our senior note lenders MidCap Financial and Silicon Valley Bank, whereby the lenders agreed
to remove the restrictions on the $5.0 million of restricted cash required under the Third Amended and Restated Credit and
Security Agreement as of June 30, 2019.
Based on our current plans and forecasted expenses, which includes estimates related to anticipated cash inflows
from DEXTENZA and ReSure Sealant product sales and cash outflows from operating expenses, we believe that our
existing cash and cash equivalents, as of December 31, 2019, together with the first quarter net proceeds through March 10,
2020 from sales of our common stock pursuant to the 2019 Sales Agreement discussed in Note 22 of our consolidated
financial statements, will enable us to fund our planned operating expenses, debt service obligations and capital
expenditure requirements into the first quarter of 2021. We have based this estimate on assumptions that may prove to be
wrong, and we could use our capital resources sooner than we currently expect. See “—Liquidity and Capital Resources.”
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Financial Operations Overview
Revenue
From our inception through December 31, 2019, we have generated limited amounts of revenue from the sales of our
products. We began to recognize limited product revenue from DEXTENZA during the second quarter of 2019 with the
first commercial shipments to customers in June 2019. Our ReSure Sealant product received premarket approval, or PMA,
from the FDA in January 2014. We commenced sales of ReSure Sealant in the first quarter of 2014, have received only
limited revenues from ReSure Sealant to date and anticipate only limited sales for 2020. Until June 2019, ReSure Sealant
was our only source of revenue from product sales. We may generate revenue in the future if we successfully
commercialize DEXTENZA and develop and commercialize one or more of our product candidates and receive marketing
approval for any such product candidate or if we enter into longer-term collaboration agreements with third parties.
For the year ended December 31, 2019, two individual customers accounted for 27% and 11% of our total revenue
and three customers accounted for 39%, 18% and 11% of our total accounts receivable. No other customer accounted for
more than 10% of total revenue or accounts receivable for the year ended December 31, 2019.
Operating Expenses
Cost of Product Revenue
Cost of product revenue consists primarily of costs of DEXTENZA, for 2019, and ReSure product revenue , which
include:
·
·
Direct materials costs;
Direct labor, which includes employee-related expenses, including salaries, related benefits and payroll taxes,
travel and stock-based compensation expense for employees engaged in the production process;
· Manufacturing overhead costs, which includes rent, depreciation, and indirect labor costs associated with the
production process;
·
·
Transportation costs; and
Cost of scrap material.
Research and Development Expenses
Research and development expenses consist primarily of costs incurred for the development of our product
candidates, which include:
·
·
·
·
employee-related expenses, including salaries, related benefits and payroll taxes, travel and stock-based
compensation expense for employees engaged in research and development, clinical and regulatory and other
related functions;
expenses incurred in connection with the clinical trials of our product candidates, including with the
investigative sites that conduct our clinical trials and under agreements with contract research organizations, or
CROs;
expenses relating to regulatory activities, including filing fees paid to the FDA for our submissions for product
approvals;
expenses associated with developing our pre-commercial manufacturing capabilities and manufacturing clinical
study materials;
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·
·
·
·
ongoing research and development activities relating to our core bioresorbable hydrogel technology and
improvements to this technology;
facilities, depreciation and other expenses, which include direct and allocated expenses for rent and maintenance
of facilities, insurance and supplies;
costs relating to the supply and manufacturing of product inventory, prior to approval by the FDA or other
regulatory agencies of our products; and
expenses associated with preclinical development activities.
We expense research and development costs as incurred. We recognize external development costs based on an
evaluation of the progress to completion of specific tasks using information provided to us by our vendors and our clinical
investigative sites.
Our direct research and development expenses are tracked on a program-by-program basis and consist primarily of
external costs, such as fees paid to investigators, consultants, central laboratories and CROs in connection with our clinical
trials and regulatory fees. We do not allocate employee and contractor-related costs, costs associated with our platform
technology, costs related to manufacturing or purchasing clinical trial materials, and facility expenses, including
depreciation or other indirect costs, to specific product development programs because these costs are deployed across
multiple product development programs and, as such, are not separately classified. We use internal resources in
combination with third-party CROs, including clinical monitors and clinical research associates, to manage our clinical
trials, monitor patient enrollment and perform data analysis for many of our clinical trials. These employees work across
multiple development programs and, therefore, we do not track their costs by program.
The table below summarizes our research and development expenses incurred by product development program:
Year Ended December 31,
2019
2018
(in thousands)
2017
ReSure Sealant
DEXTENZA for post-surgical ocular inflammation and pain
DEXTENZA for allergic conjunctivitis
DEXTENZA for dry eye disease
OTX-TP for glaucoma and ocular hypertension
OTX-TIC for glaucoma and ocular hypertension
OTX-TKI for Wet AMD
Preclinical programs
Unallocated expenses
Total research and development expenses
$
153 $
189 $
126
1,319
1,085
621
20
6
—
5,288
5,305
—
—
—
—
—
—
23,520
30,316
$41,091 $36,915 $30,880
1,039
2,060
—
1,558
726
1,013
1,645
32,897
We expect that our expenses will increase in connection with our ongoing activities. We estimate that in 2020, we
will incur approximately $15.0 million to $22.0 million of research and development expenses, including costs related to
clinical trials and other research and development activities. Of this amount, we estimate we will incur approximately $5.0
million to $10.0 million of external research and development expenses related to clinical trial and regulatory costs for
DEXTENZA, OTX-TP, OTX-TKI, OTX-TIC and other product candidates and approximately $10.0 million to $12.0
million of other research and development activities that we do not expect to track by program
We estimate that we will incur external research and development expenses for 2020, as follows:
·
·
·
approximately $1.0 million to $2.0 million for OTX-TP and OTX-TIC for glaucoma and ocular hypertension;
approximately $2.0 million to $4.0 million for OTX-TKI for Wet AMD; and
approximately $2.0 million to $4.0 million for other external research and development activities.
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The successful development and commercialization of our products or product candidates is highly uncertain. This is
due to the numerous risks and uncertainties associated with product development and commercialization, including the
uncertainty of:
·
·
·
·
·
the scope, progress, outcome and costs of our clinical trials and other research and development activities;
the timing, receipt and terms of any marketing approvals;
the efficacy and potential advantages of our products or product candidates compared to alternative treatments,
including any standard of care;
the market acceptance of our products or product candidates; and
significant and changing government regulation.
Any changes in the outcome of any of these variables with respect to the development of our product candidates in
clinical and preclinical development could mean a significant change in the costs and timing associated with the
development of these product candidates. For example, if the FDA or another regulatory authority were to require us to
conduct clinical trials or other testing beyond those that we currently expect or if we experience significant delays in
enrollment in any of our clinical trials, we could be required to expend significant additional financial resources and time
on the completion of clinical development of that product candidate.
General and Administrative Expenses
General and administrative expenses consist primarily of salaries and related costs, including stock-based
compensation, for personnel in executive, finance, information technology, human resources and administrative functions.
General and administrative expenses also include insurance, facility-related costs and professional fees for legal, patent,
consulting and accounting and audit services.
We anticipate that our general and administrative expenses will increase in the future as we support our continued
development and commercialization of our product candidates. We also anticipate that we will continue to incur increased
accounting, audit, legal, regulatory, compliance, director and officer insurance costs as well as investor and public relations
expenses associated with being a public company.
Selling and Marketing Expenses
Selling and marketing expenses consist primarily of salaries and related costs for personnel in selling and marketing
functions as well as consulting and advertising and promotion costs. During the years ended December 31, 2019, 2018 and
2017, we incurred limited marketing expenses in connection with ReSure Sealant, which we began commercializing in
2014, while selling and marketing expenses in connection with the commercial launch of DEXTENZA in July 2019. We
anticipate that our selling and marketing expenses associated with DEXTENZA will continue to increase.
Other Income (Expense)
Interest Income. Interest income consists primarily of interest income earned on cash and cash equivalents. In each
of 2019, 2018, and 2017, our interest income has not been significant due to the low rates of interest being earned on our
invested balances.
Interest Expense. Interest expense consists of interest expense on our debt. We borrowed $15.0 million in aggregate
principal amount in April 2014. In December 2015, we amended our credit and security agreement, or as amended, our
Credit Agreement, in connection with our credit facility, or our Credit Facility, to increase the aggregate principal amount
to $15.6 million, extend the interest-only payment period through December 2016, and extend the maturity date to
December 1, 2019. In March 2017, we amended our Credit Agreement to increase the aggregate principal amount under
our Credit Facility to $18.0 million, extend the interest-only payment period through February 2018, and extend the
maturity date to December 1, 2020. In December 2018, we amended the Credit Agreement to
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increase the aggregate principal amount to $25.0 million, extend the interest-only payment period through December 2020,
and extend the maturity date to December 2023. On March 1, 2019, we issued $37.5 million of unsecured senior
subordinated convertible notes, or the 2026 Convertible Notes. The 2026 Convertible Notes accrue interest at an annual
rate of 6% of the outstanding principal amount, payable at maturity, on March 1, 2026, unless earlier converted,
repurchased or redeemed.
Change in Fair Value of Derivative Liability. In 2019, in connection with the issuance of our 2026 Convertible Notes,
we identified an embedded derivative liability, which we are required to measure at fair value at inception and then at the
end of each reporting period until the embedded derivative is settled. The changes in fair value are recorded through the
statement of operations and comprehensive loss and are presented under the caption change in fair value of derivative
liability.
Critical Accounting Policies and Significant Judgments and Estimates
Our consolidated financial statements are prepared in accordance with generally accepted accounting principles in
the United States of America. The preparation of our consolidated financial statements and related disclosures requires us
to make estimates, assumptions and judgments that affect the reported amounts of assets, liabilities, revenue, costs and
expenses, and the disclosure of contingent assets and liabilities in our consolidated financial statements. On an ongoing
basis, we evaluate our estimates and judgments, including those related to revenue recognition, accrued research and
development expenses and stock-based compensation. We base our estimates on historical experience, known trends and
events and various other factors that we believe are reasonable under the circumstances, the results of which form the basis
for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources.
Actual results may differ from these estimates under different assumptions or conditions.
While our significant accounting policies are described in more detail in the notes to our consolidated financial
statements appearing elsewhere in this annual report, we believe the following accounting policies to be most critical to the
judgments and estimates used in the preparation of our consolidated financial statements.
Revenue Recognition
We recognize product revenue from DEXTENZA for the treatment of post-surgical ocular inflammation and pain,
which we began selling to customers in June 2019, and ReSure Sealant. We have generated limited revenues from ReSure
Sealant to date and do not expect significant future sales.
In November 2018, the FDA approved DEXTENZA for the treatment of ocular pain following ophthalmic surgery.
We entered into a limited number of arrangements with specialty distributors in the United States to distribute
DEXTENZA. Topic 606 applies to all contracts with customers, except for contracts that are within the scope of other
standards, such as leases, insurance arrangements and financial instruments. Under Topic 606, an entity recognizes revenue
when its customer obtains control of promised goods or services, in an amount that reflects the consideration which the
entity expects to be entitled to in exchange for those goods or services.
To determine revenue recognition for arrangements that an entity determines are within the scope of Topic 606, the
entity performs the following five steps: (i) identify the contract(s) with a customer, (ii) identify the performance
obligations in the contract, (iii) determine the transaction price, (iv) allocate the transaction price to the performance
obligations in the contract, and (v) recognize revenue when (or as) the entity satisfies a performance obligation. We only
apply the five-step model to arrangements that meet the definition of a contract with a customer under Topic 606, including
when it is probable that we will collect the consideration we are entitled to in exchange for the goods or services we
transfer to the customer. At contract inception, once the contract is determined to be within the scope of Topic 606, we
assess the goods or services promised within each contract, determines those that are performance obligations, and assesses
whether each promised good or service is distinct. We then recognize as revenue the amount of the transaction price that is
allocated to the respective performance obligation when (or as) the performance obligation is satisfied. For a complete
discussion of accounting for product revenue, see Product Revenue, Net (below).
Product Revenue, Net— We derive our product revenues from the sale of DEXTENZA in the United States to
customers, which includes a limited number of specialty distributors, who then subsequently resell DEXTENZA to
physicians, clinics and certain medical centers or hospitals. In addition to distribution agreements with customers, we
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enter into arrangements with government payers that provide for government mandated rebates and chargebacks with
respect to the purchase of DEXTENZA.
We recognize revenue on product sales when the customer obtains control of our product, which occurs at a point in
time (upon delivery to the customer). We have determined that the delivery of DEXTENZA to our customers constitutes a
single performance obligation. There are no other promises to deliver goods or services beyond what is specified in each
accepted customer order. We have assessed the existence of a significant financing component in the agreements with our
customers. The trade payment terms with our customers do not exceed one year and therefore we have elected to apply the
practical expedient and no amount of consideration has been allocated as a financing component. Product revenues are
recorded net of applicable reserves for variable consideration, including discounts and allowances.
Transaction Price, including Variable Consideration— Revenues from product sales are recorded at the net sales
price (transaction price), which includes estimates of variable consideration for which reserves are established.
Components of variable consideration include trade discounts and allowances, product returns, government chargebacks,
discounts and rebates, and other incentives, such as voluntary patient assistance, and other fee-for-service amounts that are
detailed within contracts between us and our customers relating to our sale of DEXTENZA. These reserves, as detailed
below, are based on the amounts earned, or to be claimed on the related sales, and are classified as reductions of accounts
receivable (if the amount is payable to the customer) or a current liability (if the amount is payable to a party other than a
customer). These estimates take into consideration a range of possible outcomes which are probability-weighted in
accordance with the expected value method in Topic 606 for relevant factors such as current contractual and statutory
requirements, specific known market events and trends, industry data, and forecasted customer buying and payment
patterns. Overall, these reserves reflect our best estimates of the amount of consideration to which we are entitled based on
the terms of the respective underlying contracts.
The amount of variable consideration which is included in the transaction price may be constrained, and is included
in the net sales price, only to the extent that it is probable that a significant reversal in the amount of the cumulative
revenue recognized under the contract will not occur in a future period. Actual amounts of consideration ultimately
received may differ from our estimates. If actual results in the future vary from our original estimates, we will adjust these
estimates, which would affect net product revenue and earnings in the period such variances become known.
Trade Discounts and Allowances—We compensate (through trade discounts and allowances) our customers for sales
order management, data, and distribution services. However, we have determined such services received to date are not
distinct from our sale of products to the customer and, therefore, these payments have been recorded as a reduction of
revenue within the statement of operations and comprehensive loss, as well as a reduction to trade receivables, net on the
consolidated balance sheets.
Product Returns— Consistent with industry practice, we generally offers customers a limited right of return for
product that has been purchased from us in certain circumstances as further discussed below. We estimate the amount of
our product sales that may be returned by our customers and record this estimate as a reduction of revenue in the period the
related product revenue is recognized, as well as within accrued expenses and other current liabilities, in the accompanying
consolidated balance sheets. We currently estimate product return reserves using available industry data and our own sales
information, including its visibility into the inventory remaining in the distribution channel. We have received no returns to
date and believe the returns of DEXTENZA will be minimal.
Our limited right of return allows for eligible returns of DEXTENZA in the following circumstances:
·
·
·
·
Shipment errors that were the result of an error by us;
Quantity delivered that is greater or less than the quantity ordered;
Product distributed by us that is damaged in transit prior to receipt by the customer;
Product from physicians, clinics, medical centers and hospitals that was not administered to the patient that is
rendered non-unusable due to spoilage or mishandling;
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·
·
·
Expired product, previously purchased directly from us, that is returned during the period beginning six months
prior to the product’s expiration date and ending twelve months after the product’s expiration date;
Product subject to a recall; and
Product that we, at our sole discretion, have specified to be returned.
Government Chargebacks— Chargebacks for fees and discounts to qualified government healthcare providers
represent the estimated obligations resulting from contractual commitments to sell products to qualified U.S. Department of
Veterans Affairs hospitals and 340B entities at prices lower than the list prices charged to customers who directly purchase
the product from us. The 340B Drug Discount Program is a U.S. federal government program created in 1992 that requires
drug manufacturers to provide outpatient drugs to eligible health care organizations and covered entities at significantly
reduced prices. Customers charge us for the difference between what they pay for the product and the statutory selling
price to the qualified government entity. These reserves are established in the same period that the related revenue is
recognized, resulting in a reduction of product revenue and trade receivables, net. Chargeback amounts are generally
determined at the time of resale to the qualified government healthcare provider by customers, and we generally issue
credits for such amounts within a few weeks of the customer’s notification to us of the resale. Reserves for chargebacks
consist of credits that we expect to issue for units that remain in the distribution channel inventories at each reporting
period-end that we expect will be sold to qualified healthcare providers, and chargebacks that customers have claimed, but
for which we have not yet issued a credit.
Government Rebates— We are subject to discount obligations under state Medicaid programs and Medicare. These
reserves are recorded in the same period the related revenue is recognized, resulting in a reduction of product revenue and
the establishment of a current liability which is included in accrued expenses and other current liabilities on the
consolidated balance sheets. For Medicare, we also estimate the number of patients in the prescription drug coverage gap
for whom we will owe an additional liability under the Medicare Part D program. For Medicaid programs, we estimate the
portion of sales attributed to Medicaid patients and record a liability for the rebates to be paid to the respective state
Medicaid programs. Our liability for these rebates consists of invoices received for claims from prior quarters that have not
been paid or for which an invoice has not yet been received, estimates of claims for the current quarter, and estimated
future claims that will be made for product that has been recognized as revenue, but which remains in the distribution
channel inventories at the end of each reporting period.
Other Incentives— Other incentives which we offer include voluntary patient assistance programs, such as the co-
pay assistance program, which are intended to provide financial assistance to qualified commercially-insured patients with
prescription drug co-payments required by payers. The calculation of the accrual for co-pay assistance is based on an
estimate of claims and the cost per claim that we expect to receive associated with product that has been recognized as
revenue, but remains in the distribution channel inventories at the end of each reporting period. The adjustments are
recorded in the same period the related revenue is recognized, resulting in a reduction of product revenue and the
establishment of a current liability which is included as an accrued expenses and other current liabilities on the
consolidated balance sheets.
Derivative Liability
The 2026 Convertible Notes allow the holders to convert all or part of the outstanding principal of their 2026
Convertible Notes into shares our common stock provided that no conversion results in a holder beneficially owning more
than 19.99% of our issued and outstanding common stock. The entire embedded conversion option is required to be
separated from the 2026 Convertible Notes and accounted for as a freestanding derivative instrument subject to derivative
accounting. Therefore, the entire conversion option is bifurcated from the underlying debt instrument and accounted for
and valued separately from the host instrument. We measure the value of the embedded conversion option at its estimated
fair value and recognize changes in the estimated fair value in other income (expense), net in the consolidated statements of
operations and comprehensive loss during the period of change. The embedded conversion is recognized as a derivative
liability in our consolidated balance sheet.
Smaller Reporting Company Status
As of January 1, 2020, we are no longer an “emerging growth company,” as defined in the Jumpstart Our Business
Startups Act of 2012, or the JOBS Act. However, we remain a “smaller reporting company,” as defined in Rule 12b-2
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under the Securities Exchange Act of 1934, as amended. We would cease to be a smaller reporting company if we have a
non-affiliate public float in excess of $250 million and annual revenues in excess of $100 million, or a non-affiliate public
float in excess of $700 million, determined on an annual basis. Even though we no longer qualify as an emerging growth
company, we may still qualify as a smaller reporting company. As a smaller reporting company, we are permitted and
intend to rely on exemptions from certain disclosure requirements that are applicable to other public companies that are not
smaller reporting companies. These exemptions include:
·
·
·
·
being permitted to provide only two years of audited consolidated financial statements in this Annual Report on
Form 10-K, with correspondingly reduced “Management's Discussion and Analysis of Financial Condition and
Results of Operations” disclosure;
reduced disclosure obligations regarding executive compensation; and
not being required to furnish a contractual obligations table in “Management's Discussion and Analysis of
Financial Condition and Results of Operations”; and
not being required to furnish a stock performance graph in our annual report.
We expect to continue to take advantage of some or all of the available exemptions.
Results of Operations
Comparison of the Years Ended December 31, 2019 and December 31, 2018
The following table summarizes our results of operations for the years ended December 31, 2019 and 2018:
Year Ended
December 31,
2019
2018
(in thousands)
Increase
(Decrease)
Revenue:
Product revenue, net
Total revenue, net
Costs and operating expenses:
Cost of product revenue
Research and development
Selling and marketing
General and administrative
Total costs and operating expenses
Loss from operations
Other income (expense):
Interest income
Interest expense
Change in fair value of derivative liability
Other income (expense), net
Total other income (expense), net
Net loss
Revenue
$
4,227 $
4,227
1,990 $
1,990
2,237
2,237
2,325
41,091
24,491
22,122
90,029
(85,802)
465
36,915
4,942
18,786
61,108
(59,118)
1,860
4,176
19,549
3,336
28,921
(26,684)
1,229
(6,101)
4,310
(8)
(570)
350
(4,362)
4,310
(8)
290
$ (86,372) $ (59,978) $ (26,394)
879
(1,739)
—
—
(860)
We generated $4.2 million of revenue during the year ended December 31, 2019 from sales of our DEXTENZA and
ReSure Sealant products. We generated $2.0 million of product revenue during the year ended December 31, 2018, from
sales of our ReSure Sealant product. Because we began to recognize product revenue from DEXTENZA during the second
quarter of 2019 with the first commercial shipments to customers in June 2019, we did not recognize product revenue from
DEXTENZA in 2018.
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Research and Development Expenses
Year Ended
December 31,
2019
2018
(in thousands)
Increase
(Decrease)
Direct research and development expenses by program:
ReSure Sealant
DEXTENZA for post-surgical ocular inflammation and
pain
DEXTENZA for allergic conjunctivitis
OTX-TP for glaucoma and ocular hypertension
OTX-TIC for glaucoma and ocular hypertension
OTX-TKI for wet AMD
Preclinical activities
$
153 $
189 $
(36)
1,039
2,060
1,558
726
1,013
1,645
1,085
20
5,305
—
—
—
(46)
2,040
(3,747)
726
1,013
1,645
Unallocated expenses:
Personnel costs
All other costs
Total research and development expenses
20,068
12,829
2,362
17,706
219
12,610
$41,091 $36,915 $ 4,176
Research and development expenses were $41.1 million for the year ended December 31, 2019, compared to $36.9
million for the year ended December 31, 2018. The increase of $4.2 million was primarily due to an increase of $2.6
million in unallocated expenses and $1.5 million in clinical trial expenses.
For the year ended December 31, 2019, we incurred $7.5 million in direct research and development expenses for our
intracanalicular insert product candidates, including $1.0 million for DEXTENZA for the treatment of post-surgical ocular
inflammation and pain, $2.1 million for DEXTENZA for the treatment of ocular itching associated with allergic
conjunctivitis, $1.5 million for our OTX-TP product candidate for the treatment of glaucoma and ocular hypertension
which was in Phase 3 clinical trials, $0.7 million for OTX-TIC for glaucoma and ocular hypertension, and $1.0 million for
OTX-TKI for wet AMD. In comparison, for the year ended December 31, 2018, we incurred $6.4 million in direct research
and development expenses for our intracanalicular insert product candidates, including $5.3 million for clinical trials of
OTX-TP for glaucoma and ocular hypertension which was in Phase 3 clinical trials, and $1.1 million for DEXTENZA for
ocular inflammation and pain following cataract surgery. Unallocated research and development costs increased $2.6
million for the year ended December 31, 2019, compared to the year ended December 31, 2018 primarily due to an increase
in unallocated personnel costs of $2.4 million.
Selling and Marketing Expenses
Personnel related (including stock-based compensation)
Professional fees
Facility related and other
Total selling and marketing expenses
Year Ended
December 31,
Increase
(Decrease)
2019
2018
(in thousands)
$ 12,382 $ 1,732 $ 10,650
6,524
2,563
2,375
647
$ 24,491 $ 4,942 $ 19,549
9,087
3,022
Selling and marketing expenses were $24.5 million for the year ended December 31, 2019, compared to $4.9 million
for the year ended December 31, 2018. The increase of $19.5 million was primarily due to an increase of $10.7 million in
personnel costs, including stock-based compensation, $6.5 million in professional fees including consulting, trade shows,
marketing material and conferences and $2.4 million in facility related and other costs as we continued the support of the
launch of DEXTENZA.
We expect our selling and marketing expenses to increase in 2020 and beyond, as we continue to support the
commercial launch of DEXTENZA.
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General and Administrative Expenses
Personnel related (including stock-based compensation)
Professional fees
Facility related and other
Total general and administrative expenses
Year Ended
December 31,
Increase
(Decrease)
2019
2018
(in thousands)
$ 11,352 $ 8,367 $ 2,985
(504)
855
$ 22,122 $ 18,786 $ 3,336
8,257
2,513
8,761
1,658
General and administrative expenses were $22.1 million for the year ended December 31, 2019, compared to $18.8
million for the year ended December 31, 2018. The increase of $3.3 million was primarily due to an increase of $3.0
million in personnel costs, including stock-based compensation.
Other Income (Expense), Net
Other expense, net was $0.6 million for the year ended December 31, 2019, compared to $0.9 million for the year
ended December 31, 2018. The change of $0.3 million, was due to higher interest expense of $6.1 million associated with
the 2026 Convertible Notes and the Credit Agreement, partially offset by an unrealized gain of $4.3 million on the change
in fair value of the derivative liability associated with the 2026 Convertible Notes. The change in fair value of the
derivative liability was a gain in the amount of $4.3 million during the year ended December 31, 2019 due changes in the
underlying assumptions of the derivative liability, primarily related to a decline in our common stock price between the
date of issuance of the 2026 Convertible Notes and December 31, 2019. We expect the change in fair value of the
derivative liability will continue to fluctuate until it is settled based on the extent changes occur in the underlying
assumptions. There was no change in fair value of derivative liability during the year ended December 31, 2018 as there
were no embedded derivatives during that period.
Comparison of the Years Ended December 31, 2018 and December 31, 2017
The following table summarizes our results of operations for the years ended December 31, 2018 and 2017:
Year Ended
December 31,
2018
2017
(in thousands)
Increase
(Decrease)
Revenue:
Product revenue
Collaboration revenue
Total revenue
Costs and operating expenses:
Cost of product revenue
Research and development
Selling and marketing
General and administrative
Total costs and operating expenses
Loss from operations
Other income (expense):
Interest income
Interest expense
Other income (expense), net
Total other expense, net
Net loss
152
$
1,990 $
—
1,990
1,923 $
—
1,923
67
—
67
465
36,915
4,942
18,786
61,108
(59,118)
457
30,880
17,000
15,509
63,846
(61,923)
8
6,035
(12,058)
3,277
(2,738)
2,805
879
(1,739)
—
(860)
424
(1,892)
5
(1,463)
$ (59,978) $ (63,386) $
455
153
(5)
603
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Revenue
We generated $2.0 and $1.9 million of product revenue during the years ended December 31, 2018 and December 31,
2017, respectively, from sales of our ReSure Sealant product. The increase in revenue was related to an increase in the total
number of units shipped in 2018.
Research and Development Expenses
Year Ended
December 31,
2018
2017
(in thousands)
Increase
(Decrease)
Direct research and development expenses by program:
ReSure Sealant
DEXTENZA for post-surgical ocular inflammation and
pain
DEXTENZA for allergic conjunctivitis
DEXTENZA for dry eye disease
OTX-TP for glaucoma and ocular hypertension
$
189 $
126 $
63
1,085
20
—
5,305
1,319
621
6
5,288
(234)
(601)
(6)
17
Unallocated expenses:
Personnel costs
All other costs
Total research and development expenses
17,706
12,610
2,495
4,301
$36,915 $30,880 $ 6,035
15,211
8,309
Research and development expenses were $36.9 million for the year ended December 31, 2018, compared to $30.9
million for the year ended December 31, 2017. The increase of $6.0 million was primarily due to an increase of $6.8
million in unallocated expenses offset by decreases in clinical trial expenses of $0.8 million. Clinical trial expenses
decreased in the year ended December 31, 2018, compared to the year ended December 31, 2017, primarily due to the
timing and number of clinical trials conducted for DEXTENZA for the treatment of post-surgical ocular inflammation and
pain, allergic conjunctivitis and episodic dry eye disease, partially offset by increases in clinical trial expenses related to
OTX-TP for the treatment of glaucoma and ocular hypertension.
For the year ended December 31, 2018, we incurred $6.4 million in direct research and development expenses for our
intracanalicular insert product candidates, including $1.1 million for DEXTENZA for the treatment of post-surgical ocular
inflammation and pain, and $5.3 million for our OTX-TP product candidate for the treatment of glaucoma and ocular
hypertension which was in Phase 3 clinical trials. In comparison, for the year ended December 31, 2017, we incurred $7.2
million in direct research and development expenses for our intracanalicular insert product candidates, including $5.3
million for clinical trials of OTX-TP for glaucoma and ocular hypertension which was in Phase 3 clinical trials, $0.6
million for DEXTENZA for the treatment of allergic conjunctivitis which was in Phase 3 clinical trials and $1.3 million for
DEXTENZA for ocular inflammation and pain following cataract surgery which was in Phase 3 clinical trials. Unallocated
research and development costs increased $6.8 million for the year ended December 31, 2018, compared to the year ended
December 31, 2017 primarily due to an increase in unallocated personnel costs of $2.5 million, relating to an increase of
$2.5 million from additional hiring primarily in our clinical, regulatory and quality department, a $2.1 million increase in
professional services, and an increase in facility related costs of $1.8 million.
Selling and Marketing Expenses
Year Ended December 31,
2018
2017
(in thousands)
Increase
(Decrease)
Personnel related (including stock-based compensation)
Professional fees
Facility related and other
Total selling and marketing expenses
$
$
1,732 $
2,563
647
5,715 $ (3,983)
(7,733)
10,296
(342)
989
4,942 $ 17,000 $ (12,058)
Selling and marketing expenses were $4.9 million for the year ended December 31, 2018, compared to $17.0 million
for the year ended December 31, 2017. The decrease of $12.1 million was primarily due to a decrease of $4.0 million in
personnel costs, a decrease of $7.7 million in professional fees due to decreased spending on external costs
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and $0.3 million in facility-related and other costs. The decrease overall was driven by a delay in the anticipated 2017
launch of DEXTENZA that occurred in mid-2019.
In August 2017, we reorganized our DEXTENZA commercial plans and realized savings in operating expenses,
including reduced personnel costs, as a result of streamlining headcount, as part of an initiative to enhance operations and
reduce expenses.
General and Administrative Expenses
Year Ended December 31,
2018
2017
(in thousands)
Increase
(Decrease)
Personnel related (including stock-based compensation)
Professional fees
Facility related and other
Total general and administrative expenses
$
8,367 $
8,761
1,658
14
3,298
(35)
$ 18,786 $ 15,509 $ 3,277
8,353 $
5,463
1,693
General and administrative expenses were $18.8 million for the year ended December 31, 2018, compared to $15.5
million for the year ended December 31, 2017. The increase of $3.3 million was primarily due to an increase of $3.3
million in professional fees related to our defense in legal proceedings.
Other Income (Expense), Net
Other expense, net was $0.9 million for the year ended December 31, 2018, compared to $1.5 million for the year
ended December 31, 2017.
Liquidity and Capital Resources
Since inception, we have incurred significant operating losses. Our net losses were $86.4 million, $60.0 million and
$63.4 million for the years ended December 31, 2019, 2018 and 2017, respectively. As of December 31, 2019, we had an
accumulated deficit of $383.6 million.
We have generated limited revenue to date. In 2014, we began recognizing revenue from sales of ReSure Sealant.
We commercially launched DEXTENZA for post-surgical ocular inflammation and pain in July 2019. All of our other
sustained drug delivery products are in various phases of pre-commercial, clinical and preclinical development. Our ability
to generate product revenues sufficient to achieve profitability will depend heavily on our commercialization of
DEXTENZA for the treatment of ocular inflammation and pain following ophthalmic surgery and our obtaining marketing
approval for and commercializing other products with significant market potential, including DEXTENZA for additional
indications, OTX-TIC for glaucoma and ocular hypertension, and OTX-TIC for wet AMD.
Through December 31, 2019, we have financed our operations primarily through private placements of our preferred
stock, public offerings of our common stock, private placements of our convertible notes and borrowings under credit
facilities, which has resulted in net proceeds of $ 412.6 million to us.
In April 2019, we entered into the 2019 Sales Agreement with Jefferies, acting as agent, for the issuance of up to
$50.0 million of our common stock. Through March 10, 2020, we have sold 9,566,973 shares of common stock under the
2019 Sales Agreement, resulting in net proceeds of approximately $43.4 million after commissions and expenses. We have
$5.2 million available for issuance as of March 10, 2020.
On March 2019, we issued $37.5 million of unsecured senior subordinated convertible notes, or the 2026 Convertible
Notes. The 2026 Convertible Notes accrue interest at an annual rate of 6% of its outstanding principal amount, payable at
maturity, on March 1, 2026, unless earlier converted, repurchased or redeemed. The holders of the 2026 Convertible Notes
may convert all or part of the outstanding principal amount of their 2026 Convertible Notes into shares of our common
stock, par value $0.0001 per share, prior to maturity and provided that no conversion results in a holder beneficially owning
more than 19.99% of our issued and outstanding common stock. The conversion rate is initially 153.8462 shares of our
common stock per $1,000 principal amount of the 2026 Convertible Notes, which is
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equivalent to an initial conversion price is $6.50 per share. The conversion rate is subject to adjustment in customary
circumstances such as stock splits or similar changes to our capitalization.
In April 2014, we borrowed $15.0 million in aggregate principal amount under a new credit facility and used $1.9
million of this amount to repay $1.7 million aggregate principal amount of indebtedness and pay $0.2 million of other
amounts due in connection with our termination of a prior credit facility. In December 2015, we amended the Credit
Agreement to increase the aggregate principal amount to $15.6 million, extend the interest-only payment period through
December 2016, and extend the maturity date to December 1, 2019. In March 2017, we amended the Credit Agreement to
increase the total indebtedness to $18.0 million and extend the interest only period through February 1, 2018 and extend the
maturity date to February 1, 2020. In December 2018, we amended the Credit Agreement to increase the total indebtedness
to $25.0 million and extend the interest-only payment period through December 2020 and extend the to maturity to date to
December 2023. See “—Contractual Obligations and Commitments” for additional information.
As of December 31, 2019, we had cash and cash equivalents of $54.4 million, notes payable of $25.0 million face
value and senior subordinated convertible notes of $37.5 million par value, plus accrued interest of $1.9 million.
Cash Flows
Based on our current plans and forecasted expenses, which includes estimates related to anticipated cash inflows
from DEXTENZA and ReSure Sealant product sales and cash outflows from operating expenses, we believe that our
existing cash and cash equivalents, as of December 31, 2019, together with the first quarter net proceeds through March 10,
2020 from sales of our common stock pursuant to the 2019 Sales Agreement discussed in Note 22 of our consolidated
financial statements, will enable us to fund our planned operating expenses, debt service obligations and capital
expenditure requirements into the first quarter of 2021. We have based this estimate on assumptions that may prove to be
wrong, and we could use our capital resources sooner than we currently expect. These factors, and the factors described
above, continue to raise substantial doubt about our ability to continue as a going concern.
The following table summarizes our sources and uses of cash for each of the periods presented:
Year Ended December 31,
Cash used in operating activities
Cash provided by (used in) investing activities
Cash provided by financing activities
Net increase in cash and cash equivalents
2019
2017
2018
(in thousands)
$ (77,578) $ (49,227) $ (50,473)
27,067
32,008
8,602
$ (4,475) $ 17,524 $
(2,238)
75,341
(1,889)
68,640
Operating activities. Net cash used in operating activities was $77.6 million for the year ended December 31, 2019,
primarily resulting from our net loss of $86.4 million, partially offset by non-cash charges of $10.7 million and cash
provided by changes in our operating assets and liabilities of $1.9 million. Our net loss was primarily attributed to research
and development activities, selling and marketing costs and our general and administrative expenses partially offset by $4.2
million of revenue in the period. Our net non-cash charges during the year ended December 31, 2019 primarily consisted of
$8.8 million of stock-based compensation expense, $2.5 million of depreciation expense and non-cash interest expense
partially offset by the change in fair value of the derivative liability of $4.3 million. Net cash provided by changes in our
operating assets and liabilities during the year ended December 31, 2019 consisted primarily of a $1.7 million increase in
accrued expenses and deferred rent and an $2.3 million increase in accounts receivables.
Net cash used in operating activities was $49.2 million for the year ended December 31, 2018, primarily resulting
from our net loss of $60.0 million, partially offset by non-cash charges of $10.2 million and cash provided by changes in
our operating assets and liabilities of $0.6 million. Our net loss was primarily attributed to research and development
activities and our general and administrative expenses partially offset by $2.0 million of revenue in the period. Our net non-
cash charges during the year ended December 31, 2018 primarily consisted of $7.5 million of stock-based compensation
expense and $2.3 million of depreciation expense. Net cash provided by changes in our operating assets and liabilities
during the year ended December 31, 2018 consisted primarily of a $1.7 million increase in accrued expenses and deferred
rent and a $0.8 million decrease in accounts payable, which was due to the timing of vendor invoicing and payments.
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Net cash used in operating activities was $50.5 million for the year ended December 31, 2017, primarily resulting
from our net loss of $63.4 million, partially offset by non-cash charges of $9.4 million and cash provided by changes in our
operating assets and liabilities of $3.6 million. Our net loss was primarily attributed to research and development activities
and our general and administrative expenses partially offset by $1.9 million of revenue in the period. Our net non-cash
charges during the year ended December 31, 2017 primarily consisted of $7.3 million of stock-based compensation
expense and $1.6 million of depreciation expense. Net cash provided by changes in our operating assets and liabilities
during the year ended December 31, 2017 consisted primarily of a $2.6 million increase in accrued expenses and deferred
rent and a $0.9 million increase in accounts payable, which was due to the timing of vendor invoicing and payments.
Investing activities. Net cash used in investing activities was $2.2 million for the year ended December 31, 2019,
consisting of cash used to purchase property and equipment of $2.2 million. Net cash used in investing activities was $1.9
million for the year ended December 31, 2018, consisting of cash used to purchase property and equipment of $1.9
million. Net cash provided by investing activities was $27.1 million for the year ended December 31, 2017 consisted of
maturities of marketable securities of $38.2 million offset by cash used to purchase property and equipment of $8.3 million
and cash used to purchase marketable securities of $3.0 million.
Financing activities. Net cash provided by financing activities for 2019 was $75.3 million and consisted primarily of
proceeds from the 2026 Convertible Notes of $37.3 million and the 2016 Sales Agreement of $4.9 million, net of
commissions and other offering expenses and the 2019 Sales Agreement of $32.6 million, net of commissions and other
offering expenses. Net cash provided by financing activities for 2018 was $68.6 million and consisted primarily of
proceeds from our follow-on offering in January 2018 of $34.7 and the 2016 Sales Agreement of $26.9 million, net of
commissions and other offering expenses, $6.4 million (net) in borrowings under our amended credit facility, proceeds
from the exercise of common stock options of $0.4 million; and proceeds from issuance of common stock pursuant to our
employee stock purchase plan of $0.3 million. Net cash provided by financing activities for 2017 was $32.0 million and
consisted primarily of proceeds from our follow-on offering in January 2017 of $23.3 and the 2016 Sales Agreement of
$5.9 million, net of commissions and other offering expenses, $2.4 million (net) in borrowings under our amended credit
facility, proceeds from the exercise of common stock options of $0.7 million; and proceeds from issuance of common stock
pursuant to our employee stock purchase plan of $0.3 million partially offset by payments of $0.6 million for insurance
costs financed by a third party.
Funding Requirements
We expect to continue to incur losses in connection with our ongoing activities, particularly as we advance the
clinical trials of our products in development and increase our sales and marketing resources to support the DEXTENZA
launch and the potential launch of our product candidates, subject to receiving FDA approval.
We anticipate we will incur substantial expenses if and as we:
·
·
·
·
·
·
continue to commercialize DEXTENZA in the United States;
continue to develop and expand our sales, marketing and distribution capabilities for DEXTENZA and any of
our product candidates;
continue to pursue the clinical development of DEXTENZA for additional indications;
continue clinical trials of our product candidates OTX-TIC and OTX-TKI;
conduct joint research and development under our strategic collaboration with Regeneron, for the development
and potential commercialization of products containing our extended-delivery hydrogel formulation in
combination with Regeneron’s large molecule, VEGF-targeting compounds to treat retinal diseases;
continue the research and development of our other product candidates;
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·
·
·
·
seek to identify and develop additional product candidates, including through additional preclinical development
activities associated with our intracanalicular insert and back-of-the-eye programs and potential opportunities
outside the field of ophthalmology;
seek marketing approvals for any of our product candidates that successfully complete clinical development;
scale up our manufacturing processes and capabilities to support sales of commercial products, our ongoing
clinical trials of our product candidates and commercialization of any of our product candidates for which we
obtain marketing approval, and expand our facilities to accommodate this scale up and any corresponding
growth in personnel;
renovate our new facility including research and development laboratories, manufacturing space and office
space;
· maintain, expand and protect our intellectual property portfolio;
·
·
·
·
expand our operational, financial and management systems and personnel, including personnel to support our
clinical development, manufacturing and commercialization efforts and our operations as a public company;
defend ourselves against legal proceedings;
increase our product liability and clinical trial insurance coverage as we expand our clinical trials and
commercialization efforts; and
continue to operate as a public company.
Based on our current plans and forecasted expenses, which includes estimates related to anticipated cash inflows
from DEXTENZA and ReSure Sealant product sales and cash outflows from operating expenses, we believe that our
existing cash and cash equivalents, as of December 31, 2019, together with the first quarter net proceeds through March 10,
2020 from sales of our common stock pursuant to the 2019 Sales Agreement discussed in Note 22 of our consolidated
financial statements, will enable us to fund our planned operating expenses, debt service obligations and capital
expenditure requirements into the first quarter of 2021. We have based this estimate on assumptions that may prove to be
wrong, and we could use our capital resources sooner than we currently expect. Our future capital requirements will
depend on many factors, including:
·
·
·
·
·
·
·
our ability to successfully commercialize and sell DEXTENZA in the United States;
the costs, timing and outcome of regulatory review of our product candidates by the FDA, the EMA or other
regulatory authorities;
the level of product sales from DEXTENZA and any additional products for which we obtain marketing
approval in the future;
the costs of manufacturing, sales, marketing, distribution and other commercialization efforts with respect to
DEXTENZA and any additional products for which we obtain marketing approval in the future;
the costs of expanding our facilities to accommodate our manufacturing needs and headcount;
the progress, costs and outcome of the clinical trials of our extended-delivery drug delivery product candidates,
in particular DEXTENZA for additional indications, OTX-TIC for glaucoma and ocular hypertension, and OTX-
TKI for wet AMD;
the progress and status of our collaboration with Regeneron, including any development costs for which we
reimburse Regeneron, the potential exercise by Regeneron of its option for a license for the development and
potential commercialization of products containing our extended-delivery hydrogel formulation in
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combination with Regeneron’s large molecule VEGF-targeting compounds, and our potential receipt of future
milestone payments from Regeneron;
the scope, progress, costs and outcome of preclinical development and clinical trials of our other product
candidates;
the extent of our debt service obligations;
the extent to which we choose to establish additional collaboration, distribution or other marketing arrangements
for our products and product candidates;
the costs and outcomes of legal actions and proceedings, including the current lawsuits described under “Part I,
Item 3 — Legal Proceedings”;
the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our
intellectual property rights and defending any intellectual property-related claims; and
the extent to which we acquire or invest in other businesses, products and technologies.
·
·
·
·
·
·
Until such time, if ever, as we can generate product revenues sufficient to achieve profitability, we expect to finance
our cash needs through equity offerings, debt financings, government or other third-party funding, collaborations, strategic
alliances, licensing arrangements, royalty agreements and marketing and distribution arrangements. We do not have any
committed external source of funds, although our collaboration agreement with Regeneron provides for the potential
receipt of option exercise, development, regulatory and sales milestone payments and royalties. To the extent that we raise
additional capital through the sale of equity or convertible debt securities, each security holder’s ownership interest will be
diluted, and the terms of these securities may include liquidation or other preferences that adversely affect each security
holder’s rights as a common stockholder. Debt financing and preferred equity financing, if available, may involve
agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional
debt, making capital expenditures or declaring dividends. The covenants under our existing Credit Agreement, the pledge
of our assets as collateral and the negative pledge of intellectual property limit our ability to obtain additional debt
financing. If we raise additional funds through government or other third-party funding, collaborations, strategic alliances,
licensing arrangements, royalty agreements or marketing and distribution arrangements, we may have to relinquish
valuable rights to our technologies, future revenue streams, research programs or product candidates or grant licenses on
terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings when
needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization
efforts or grant rights to develop and market products or product candidates that we would otherwise prefer to develop and
market ourselves.
As discussed in Note 1 of the Notes to the Consolidated Financial Statements under Accounting Standards Update, or
ASU, 2014-15, Presentation of Financial Statements—Going Concern (Subtopic 205-40), or, ASC 205-40, we have the
responsibility to evaluate whether conditions or events raise substantial doubt about our ability to meet our future financial
obligations as they become due within one year after the date the financial statements are issued. Under ASC 205-40, this
evaluation initially cannot take into consideration the potential mitigating effects of plans that have not been fully
implemented as of the date the financial statements are issued. Since we currently anticipate that our existing capital
resources and anticipated cash inflows from DEXTENZA and ReSure Sealant product sales and cash outflows from
operating expenses, will enable us to meet our planned operational expenses, debt service obligations, and capital
expenditures, based on our current operating plans, into the first quarter of 2021, we have determined that this cash runway
of less than 12 months along with our accumulated deficit, history of losses, and future expected losses meet the ASC 205-
40 standard for raising substantial doubt about our ability to continue as a going concern within one year of the issuance
date of these financial statements. While we have plans in place to mitigate this risk, which primarily consist of raising
additional capital through a combination of equity or debt financings, and, depending on the availability and level of
additional financings, potentially new collaborations and reducing cash expenditures, there is no guarantee that we will be
successful in these mitigation efforts
Since our inception in 2006, we have not recorded any U.S. federal or state income tax benefits for the net losses we
have incurred in each year or our earned research and development tax credits, due to our uncertainty of realizing a benefit
from those items. As of December 31, 2019, we had federal net operating loss carryforwards of $274.3 million,
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of which $126.1 million begin to expire in 2026, and $148.2 are not subject to expiration. We also have state net operating
loss carryforwards of $219.4 million, which begin to expire in 2029. As of December 31, 2019, we also had federal
research and development tax credit carryforwards of $8.2 million and state research and development tax credit
carryforwards $4.3 million, which begin to expire in 2026 and 2025, respectively. We have not completed a study to assess
whether an ownership change, generally defined as a greater than 50% change (by value) in the equity ownership of our
corporate entity over a three-year period, has occurred or whether there have been multiple ownership changes since our
inception, due to the significant costs and complexities associated with such studies. Accordingly, our ability to utilize our
tax carryforwards may be limited. Additionally, U.S. tax laws limit the time during which these carryforwards may be
utilized against future taxes. As a result, we may not be able to take full advantage of these carryforwards for federal and
state tax purposes.
Contractual Obligations and Commitments
The following table summarizes our contractual obligations at December 31, 2019 and the effects such obligations
are expected to have on our liquidity and cash flow in future periods:
Total
Less Than
1 to 3
1 Year Years
3 to 5
Years
More than
5 Years
(in thousands)
Operating lease commitments
Purchase commitments
Debt obligations including interest
2026 Convertible Notes
Total
$ 15,202 $ 2,432 $ 5,032 $ 3,925 $ 3,813
—
—
53,469
$ 103,780 $ 7,065 $ 25,790 $ 13,643 $ 57,282
2,152 $
2,481
—
2,945
32,164
53,469
20,030
—
9,653
—
728 $
65 $
In the table above, we set forth our enforceable and legally binding obligations and future commitments at
December 31, 2019, as well as obligations related to contracts that we are likely to continue, regardless of the fact that they
may be cancelable at December 31, 2019. Some of the figures that we include in this table are based on management’s
estimates and assumptions about these obligations, including their duration, and other factors. Because these estimates and
assumptions are necessarily subjective, the obligations we will actually pay in future periods may vary from those reflected
in the table.
Operating lease commitments represent payments due under our leases of office, laboratory and manufacturing space
in Bedford, Massachusetts and certain office equipment under operating leases that expire in July 2023, March 2024 and
July 2027.
In June 2016, we entered into a lease agreement for approximately 70,712 square feet of general office, research and
development and manufacturing space. The lease term commenced on February 1, 2017 and expires on July 31, 2027. No
base rent was due under the lease until August 1, 2017. The initial annual base rent is approximately $1.2 million and will
increase annually beginning on February 1 of each year. We are obligated to pay all real estate taxes and costs related to
the premises, including costs of operations, maintenance, repair, and replacement and management of the new leased
premises. We posted a customary letter of credit in the amount of $1.5 million as a security deposit. We relocated our
corporate headquarters to the new leased premises in June 2017. The lease agreement allowed for a construction allowance
not to exceed approximately $2.8 million to be applied to the total construction costs of the new leased premises. The
construction allowance had to be used before December 31, 2017, or it would be deemed forfeited with no further
obligation by the landlord of the new leased premises. As of December 31, 2017, we billed the landlord for $2.7 million
and subsequently, we have received payments of $2.7 million from the landlord. We forfeited $0.1 million under the
construction allowance.
On October 10, 2017, we entered into an amendment to the lease agreement for our laboratory and manufacturing
space located at 34 Crosby Drive and 36 Crosby Drive, each in Bedford, Massachusetts, which we refer to as the Second
Amendment. The Second Amendment extends the term of our lease for 36 Crosby Drive from June 30, 2018 to July 31,
2023. Further, the Second Amendment acknowledges that we have previously vacated and surrendered, and the lease has
expired with regards to 34 Crosby Drive, reducing the total laboratory and manufacturing space subject to the lease to
20,445 square feet. Accordingly, the Second Amendment reduces the required security deposit under the lease from $0.2
million to $0.1 million. Under the Second Amendment, the annual base rent for 36 Crosby Drive shall be approximately
$0.5 million until June 30, 2018, shall be $0 from July 1, 2018 to July 31, 2018, and shall be
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approximately $0.5 million from August 1, 2018 to July 31, 2019. The annual base rent shall increase annually
thereafter. The Second Amendment also provides us a one-time option to terminate the Lease on July 31, 2021, upon the
delivery to the landlord on or before July 31, 2020, of a termination notice and the payment to the landlord of a termination
fee of approximately $0.3 million.
On April 4, 2019, we entered into a sublease agreement for approximately 30,036 square feet of general office space
located at 24 Crosby Drive in Bedford, Massachusetts. The lease term commenced on April 4, 2019 and expires on March
31, 2024. No base rent was due under the lease until July 2019. The initial annual base rent is approximately $0.6 million
and will increase annually beginning on April 1 of each year. We are obligated to pay all real estate taxes and costs related
to the premises. We posted a customary letter of credit in the amount of approximately $0.2 million as a security
deposit. These rent payments have not been included in the table of contractual obligations and commitments above. We
relocated our corporate headquarters to the new leased premises in August 2019.
Purchase commitments represent non-cancelable contractual commitments associated with certain clinical trial
activities with our CROs.
Manufacturing commitments generally provide for termination on notice, and therefore are cancelable contracts but
are contracts that we are likely to continue, regardless of the fact that they are cancelable.
We enter into contracts in the normal course of business to assist in the performance of our research and development
activities and other services and products for operating purposes. These contracts generally provide for termination on
notice, and therefore are cancelable contracts and not included in the table of contractual obligations and commitments.
In April 2014, we entered into the Credit Agreement to establish the Credit Facility with Silicon Valley Bank and
MidCap Financial SBIC, LP, pursuant to which we were able to borrow an aggregate principal amount of up to $20.0
million, of which we borrowed $15.0 million. We did not borrow the remaining $5.0 million, and this amount is no longer
available to us. The Credit Facility carried a fixed annual interest rate of 8.25% on outstanding borrowings.
In December 2015, we amended the Credit Agreement to increase the aggregate principal amount to $15.6 million to
capitalize certain accrued interest. The Credit Agreement provided for monthly, interest-only payments on outstanding
borrowings through December 2016. Thereafter, we were required to pay thirty-six consecutive, equal monthly installments
of principal and interest through December 1, 2019. In March 2017, we further amended the Credit Agreement to increase
the aggregate principal amount under the Credit Facility to $18.0 million. The interest-only payment period was extended
through February 1, 2018. There were no financial covenants associated with the Credit Agreement.
In December 2018, we further amended the Credit Agreement to increase the aggregate principal amount borrowed
under the Credit Facility to $25.0 million. The interest-only payment period was extended through December
2020. Commencing in January 2021, we are required to make 36 equal monthly installments of principal in the amount of
$0.7 million, plus interest, through December 2023. Under the December 2018 amendment, we became obligated maintain
a minimum of $5.0 million of cash and/or cash equivalents on hand as a financial covenant to the borrowing arrangement.
On August 2, 2019, we entered into a second amendment to the Credit Agreement in which the lenders agreed to remove
the financial covenant requiring us to maintain a minimum of $5.0 million of cash on hand. There are no other financial
covenants associated with the Credit Agreement; however, there are negative covenants restricting our activities, including
limitations on dispositions, mergers or acquisitions; incurring indebtedness, liens or encumbrances; paying dividends;
making certain investments; and engaging in certain other business transactions. The obligations under the Credit
Agreement are subject to acceleration upon the occurrence of specified events of default, including a material adverse
change in our business, operations or financial or other condition. The debt is collateralized by a first-priority lien on all of
our assets, including our intellectual property.
In connection with our entry into the Purchase Agreement, as described below, in February 2019, we further
amended the Credit Agreement to permit our issuance and sale of the 2026 Convertible Notes in March 2019. The
February amendment added, among other provisions, a negative covenant restricting us from paying the holders of the
2026 Convertible Notes ahead in priority to the senior lenders, for so long as indebtedness remains outstanding under the
Credit Agreement, and a cross-default provision to establish that an event of default under the Purchase Agreement also
constituted an event of default under the Credit Agreement. In August 2019, we entered into the Second Amendment to
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the Credit Agreement to further amended the Credit Agreement to remove restrictions on us to maintain a minimum of $5.0
million of cash on hand as a financial covenant.
We have in-licensed a significant portion of our intellectual property from Incept, an intellectual property holding
company, under an amended and restated license agreement, or the License Agreement, that we entered into with Incept in
January 2012, which was most recently amended in September 2018. We are obligated to pay Incept a royalty equal to a
low-single-digit percentage of net sales made by us or our affiliates of any products, devices, materials, or components
thereof, or the Licensed Products, including or covered by Original IP (as defined in the License Agreement), excluding the
Shape-Changing IP (as defined in the License Agreement), in the Ophthalmic Field of Use (as defined in the License
Agreement). We are obligated to pay Incept a royalty equal to a mid-single-digit percentage of net sales made by us or our
affiliates of any Licensed Products including or covered by Original IP, excluding the Shape-Changing IP, in the Additional
Field of Use (as defined in the License Agreement). We are obligated to pay Incept a royalty equal to a low-single-digit
percentage of net sales made by us or our affiliates of any Licensed Products including or covered by Incept IP (as defined
in the License Agreement) or Joint IP (as defined in the License Agreement) in the field of drug delivery. Any sublicensee
of ours also will be obligated to pay Incept a royalty on net sales of Licensed Products made by it and will be bound by the
terms of the agreement to the same extent as we are. We are obligated to reimburse Incept for our share of the reasonable
fees and costs incurred by Incept in connection with the prosecution of the patent applications licensed to us under the
agreement. Our share of these fees and costs is equal to the total amount of such fees and costs divided by the total number
of Incept’s exclusive licensees of the patent application. We have not included in the table above any payments to Incept
under this license agreement as the amount, timing and likelihood of such payments are not known.
In October 2016, we entered into the Collaboration Agreement with Regeneron. If the Option is exercised,
Regeneron will conduct further preclinical development and an initial clinical trial under a collaboration plan. We are
obligated to reimburse Regeneron for certain development costs during the period through the completion of the initial
clinical trial, subject to a cap of $25.0 million, which cap may be increased by up to $5.0 million under certain
circumstances. We have not included in the table above any payments to Regeneron under this Collaboration Agreement as
the timing of such payments are not known. Regeneron will be responsible for funding an initial preclinical tolerability
study, which Regeneron initiated in early 2018. We do not expect our funding requirements under our collaboration with
Regeneron to be material over the next twelve months. If Regeneron elects to proceed with further development beyond the
initial clinical trial, it will be solely responsible for conducting and funding further development and commercialization of
product candidates.
On March 2019, we issued the 2026 Convertible Notes pursuant to a note purchase agreement, or the Purchase
Agreement with Cap 1 LLC, an affiliate of Summer Road LLC to issue and sell the 2026 Convertible Notes. The 2026
Convertible Notes accrue interest at an annual rate of 6% of its outstanding principal amount, payable at maturity, on
March 1, 2026, unless earlier converted, repurchased or redeemed. The holders of the 2026 Convertible Notes may convert
all or part of the outstanding principal amount of their 2026 Convertible Notes into shares of our common stock, par value
$0.0001 per share, prior to maturity and provided that no conversion results in a holder beneficially owning more than
19.99% of our issued and outstanding common stock. The conversion rate is initially 153.8462 shares of our common stock
per $1,000 principal amount of the 2026 Convertible Notes, which is equivalent to an initial conversion price is $6.50 per
share. The conversion rate is subject to adjustment in customary circumstances such as stock splits or similar changes to
our capitalization. At our election, we may choose to make such conversion payment in cash, in shares of common stock,
or in a combination thereof. Upon any conversion of any 2026 Convertible Note, we are obligated to make a cash payment
to the holder of such 2026 Convertible Note for any interest accrued but unpaid on the principal amount converted. Upon
the occurrence of a Corporate Transaction (as defined in the 2026 Convertible Notes), the holder of a 2026 Convertible
Note is entitled, at such holder’s option, to convert all of the outstanding principal amount of the 2026 Convertible Note in
accordance with the foregoing and receive an additional, “make-whole” cash payment in accordance with a table set forth
in each 2026 Convertible Note.
Upon the occurrence of a Corporate Transaction, each holder of a 2026 Convertible Note has the option to require us
to repurchase all or part of the outstanding principal amount of such 2026 Convertible Note at a repurchase price equal to
100% of the outstanding principal amount of the 2026 Convertible Note to be repurchased, plus accrued and unpaid interest
to, but excluding, the repurchase date.
On or after March 1, 2022, if the last reported sale price of the common stock has been at least 130% of the
conversion rate then in effect for twenty of the preceding thirty trading days (including the last trading day of such
161
Table of Contents
period), we are entitled, at our option, to redeem all or part of the outstanding principal amount of the 2026 Convertible
Notes, on a pro rata basis, at an optional redemption price equal to 100% of the outstanding principal amount of the 2026
Convertible Notes to be redeemed, plus accrued and unpaid interest to, but excluding, the optional redemption date.
The Purchase Agreement contains customary representations and warranties by us and the noteholder. The Purchase
Agreement does not include any financial covenants. Our obligations under the Purchase Agreement and the 2026
Convertible Notes are subject to acceleration upon the occurrence of specified events of default, including a default or
breach of certain contracts material to us and the delisting and deregistration of our common stock.
Off-Balance Sheet Arrangements
We did not have during the periods presented, and we do not currently have, any off-balance sheet arrangements, as
defined in the rules and regulations of the Securities and Exchange Commission, such relationships with unconsolidated
entities or financial partnerships, which are often referred to as structured finance or special purpose entities, established for
the purpose of facilitating financing transactions that are not required to be reflected on our balance sheets.
Recently Issued Accounting Pronouncements
Information regarding new accounting pronouncements is included in Note 2 – Summary of Significant Accounting
Policies to the current period’s consolidated financial statements.
Item 7A.
Quantitative and Qualitative Disclosures About Market Risk
We are exposed to market risk related to changes in interest rates. As of December 31, 2019, we had cash and cash
equivalents of $54.4 million, which consisted of money market funds. We have policies requiring us to invest in high-
quality issuers, limit our exposure to any individual issuer, and ensure adequate liquidity. Our primary exposure to market
risk is interest rate sensitivity, which is affected by changes in the general level of U.S. interest rates, particularly because
our investments are in short-term securities. Due to the short-term duration of our investment portfolio and the low risk
profile of our investments, an immediate 100 basis point change in interest rates would not have a material effect on the fair
market value of our portfolio.
Item 8.
Financial Statements and Supplementary Data
Our consolidated financial statements, together with the report of our independent registered public accounting firm,
appear on pages F-1 through F-28 of this Annual Report on Form 10-K.
Item 9.
Changes in and Disagreements with Accountants on Accounting and Financial Disclosure
None.
Item 9A.
Controls and Procedures
Evaluation of Disclosure Controls and Procedures
Our management, with the participation of our Chief Executive Officer and Chief Financial Officer, evaluated the
effectiveness of our disclosure controls and procedures as of December 31, 2019. The term “disclosure controls and
procedures,” as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as amended, or the
Exchange Act, means controls and other procedures of a company that are designed to ensure that information required to
be disclosed by a company in the reports that it files or submits under the Exchange Act is recorded, processed,
summarized and reported, within the time periods specified in the Securities and Exchange Commission’s rules and forms.
Disclosure controls and procedures include, without limitation, controls and procedures designed to ensure that information
required to be disclosed by a company in the reports that it files or submits under the Exchange Act is accumulated and
communicated to the company’s management, including its principal executive and principal financial officers, as
appropriate to allow timely decisions regarding required disclosure. Management recognizes that any controls and
procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving their objectives
and management necessarily applies its judgment in evaluating the cost-benefit relationship of possible
162
Table of Contents
controls and procedures. Based on the evaluation of our disclosure controls and procedures as of December 31, 2019, our
Chief Executive Officer and Chief Financial Officer concluded that, as of such date, our disclosure controls and procedures
were effective at the reasonable assurance level.
Management’s Annual Report on Internal Control Over Financial Reporting
Our management is responsible for establishing and maintaining adequate internal control over financial reporting for
the company. Internal control over financial reporting is defined in Rules 13a-15(f) and 15d-15(f) promulgated under the
Exchange Act as a process designed by, or under the supervision of, the company’s principal executive and principal
financial officers and effected by the company’s board of directors, management and other personnel, to provide reasonable
assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in
accordance with generally accepted accounting principles and includes those policies and procedures that:
·
·
·
Pertain to the maintenance of records that in reasonable detail accurately and fairly reflect the transactions and
dispositions of the assets of the company;
Provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial
statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the
company are being made only in accordance with authorizations of management and directors of the company;
and
Provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use or
disposition of the company’s assets that could have a material effect on the financial statements.
Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements.
Also, projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become
inadequate because of changes in conditions, or that the degree of compliance with the policies or procedures may
deteriorate.
Our management, including our Chief Executive Officer and Chief Financial Officer, assessed the effectiveness of
our internal control over financial reporting as of December 31, 2019. In making this assessment, management used the
criteria set forth by the Committee of Sponsoring Organizations of the Treadway Commission (COSO) in Internal Control
—Integrated Framework (2013). Based on that assessment, our management concluded that, as of December 31, 2019, our
internal control over financial reporting was effective.
The effectiveness of our internal control over financial reporting as of December 31, 2019, has been audited by
PricewaterhouseCoopers LLP, an independent registered public accounting firm, as stated in their report, which is included
herein.
Changes in Internal Control Over Financial Reporting
No change in our internal control over financial reporting (as defined in Rules 13a-15(f) and 15d-15(f) under the
Exchange Act) occurred during the three months ended December 31, 2019 that has materially affected, or is reasonably
likely to materially affect, our internal control over financial reporting.
Item 9B.
Other Information
None.
163
Table of Contents
Item 10.
Directors, Executive Officers and Corporate Governance
Directors and Executive Officers
PART III
The information required by this item will be set forth in our Proxy Statement for the 2020 Annual Meeting of
Stockholders and is incorporated in this Annual Report on Form 10-K by reference.
Delinquent Section 16(a) Reports
The information required by this item will be set forth in our Proxy Statement for the 2020 Annual Meeting of
Stockholders, if applicable, and is incorporated in this Annual Report on Form 10-K by reference.
Code of Ethics
We have adopted a code of business conduct and ethics that applies to our directors and officers (including our
principal executive officer, principal financial officer, principal accounting officer or controller, or persons performing
similar functions) as well as our other employees. A copy of our code of business conduct and ethics is available on our
website. We intend to post on our website all disclosures that are required by applicable law, the rules of the Securities and
Exchange Commission or the Nasdaq Global Market concerning any amendment to, or waiver of, our code of business
conduct and ethics.
Director Nominees
The information required by this item will be set forth in our Proxy Statement for the 2020 Annual Meeting of
Stockholders and is incorporated in this Annual Report on Form 10-K by reference.
Audit Committee
We have separately designated a standing Audit Committee established in accordance with Section 3(a)(58)(A) of the
Securities Exchange Act of 1934, as amended, or the Exchange Act. Additional information regarding the Audit Committee
that is required by this item will be set forth in our Proxy Statement for the 2020 Annual Meeting of Stockholders and is
incorporated in this Annual Report on Form 10-K by reference.
Audit Committee Financial Expert
Our board of directors has determined that Bruce Peacock is the “audit committee financial expert” as defined by
Item 407(d)(5) of Regulation S-K of the Exchange Act and is “independent” under the rules of the Nasdaq Global Market.
Item 11.
Executive Compensation
The information required by this item will be set forth in our Proxy Statement for the 2020 Annual Meeting of
Stockholders and is incorporated in this Annual Report on Form 10-K by reference.
Item 12.
Security Ownership of Certain Beneficial Owners and Management and Related Stockholder
Matters
The information required by this item will be set forth in our Proxy Statement for the 2020 Annual Meeting of
Stockholders and is incorporated in this Annual Report on Form 10-K by reference.
164
Table of Contents
Securities Authorized for Issuance under Equity Compensation Plans
The information required by this item will be set forth in our Proxy Statement for the 2020 Annual Meeting of
Stockholders and is incorporated in this Annual Report on Form 10-K by reference.
Item 13.
Certain Relationships and Related Transactions, and Director Independence
The information required by this item will be set forth in our Proxy Statement for the 2020 Annual Meeting of
Stockholders and is incorporated in this Annual Report on Form 10-K by reference.
Item 14.
Principal Accounting Fees and Services
The information required by this item will be set forth in our Proxy Statement for the 2020 Annual Meeting of
Stockholders and is incorporated in this Annual Report on Form 10-K by reference.
165
Table of Contents
Item 15.
Exhibits, Financial Statement Schedules
PART IV
The following financial statements are filed as part of this Annual Report on Form 10-K:
Report of Independent Registered Public Accounting Firm
Consolidated Balance Sheets
Consolidated Statements of Operations and Comprehensive Loss
Consolidated Statements of Changes in Stockholders’ Equity
Consolidated Statements of Cash Flows
Notes to Consolidated Financial Statements
Page
F-2
F-4
F-5
F-6
F-7
F-8
No financial statement schedules have been filed as part of this Annual Report on Form 10-K because they are not
applicable, not required or because the information is otherwise included in our consolidated financial statements or notes
thereto.
The exhibits filed as part of this Annual Report on Form 10-K are set forth on the Exhibit Index immediately
following Item 16. The Exhibit Index is incorporated herein by reference.
Item 16.
Form 10-K Summary
None.
166
Table of Contents
EXHIBIT INDEX
Exhibit
Number
3.1
Description of Exhibit
Restated Certificate of Incorporation of
Form
8-K
File Number
001-36554
Date of
Filing
7/30/2014
Exhibit
Number
3.1
Filed
Herewith
Incorporated by Reference
the Registrant
3.2
Amended and Restated Bylaws of the
8-K
001-36554
7/30/2014
3.2
Registrant
4.1
Specimen Stock Certificate evidencing
S-1/A
333-196932
7/11/2014
4.1
the shares of common stock
4.2
Registration Rights Agreement, dated as
of March 1, 2019, by and among the
Registrant and the Purchasers identified
therein
4.3
Description of Securities Registered under
Section 12 of the Exchange Act
10-K
001-36554
3/7/2019
4.2
X
10.1+ 2006 Stock Incentive Plan, as amended
10.2+ Form of Stock Option Agreement under
2006 Stock Incentive Plan
10.3+ Form of Restricted Stock Agreement
under 2006 Stock Incentive Plan
S-1
S-1
S-1
333-196932
6/20/2014 10.1
333-196932
6/20/2014 10.2
333-196932
6/20/2014 10.3
10.4+ 2014 Stock Incentive Plan
S-1/A
333-196932
7/11/2014 10.4
10.5+ Form of Incentive Stock Option
S-1/A
333-196932
7/11/2014 10.5
Agreement under 2014 Stock Incentive
Plan
10.6+ Form of Non-statutory Stock Option
S-1/A
333-196932
7/11/2014 10.6
Agreement under 2014 Stock Incentive
Plan
10.7+ Form of Restricted Stock Agreement
S-1/A
333-196932
7/11/2014 10.7
under 2014 Stock Incentive Plan
10.8+ 2019 Inducement Stock Incentive Plan
10-Q
001-036554
11/12/2019 10.1
10.9+ Form of Non-statutory Stock Option
10-Q
001-036554
11/12/2019 10.2
Agreement under 2019 Inducement Stock
Incentive Plan
10.10† Amended and Restated License
S-1
333-196932
6/20/2014 10.8
Agreement, dated January 27, 2012,
between the Registrant and Incept LLC
10.11 Lease Agreement dated September 2,
S-1
333-196932
6/20/2014 10.9
2009, by and between the Registrant and
RAR2-Crosby Corporate Center QRS,
Inc., as amended.
167
Table of Contents
Incorporated by Reference
Exhibit
Number
10.12+ 2014 Employee Stock Purchase Plan
Description of Exhibit
Form
S-1/A
File Number
333-196932
Date of
Filing
Exhibit
Number
7/11/2014 10.10
Filed
Herewith
10.13 Form of Indemnification Agreement by
S-1
333-196932
6/20/2014 10.12
and between the Registrant and each of its
directors and executive officers
10.14+ Transition, Separation and Release of
8-K
001-36554
5/30/2019 10.1
Claims Agreement by and between the
Registrant and Dr. Amarpreet S. Sawhney
dated as of May 29, 2019
10.15 Lease Agreement dated June 17, 2016
between the WS NF 15 Crosby Drive,
LLC and the Registrant
10-Q
001-36554
8/9/2016 10.1
10.16† Collaboration, Option and License
10-Q
001-36554
11/9/2016 10.1
Agreement between the Registrant and
Regeneron Pharmaceuticals, Inc. dated
October 10, 2016
10.17 Open Market Sales Agreement
SM
, dated as
8-K
001-36554
4/5/2019
1.1
of April 5, 2019, by and between the
Registrant and Jefferies LLC
10.18 Second Amended and Restated Credit and
10-Q
001-36554
5/5/2017 10.1
Security Agreement, dated March 7,
2017, by and among MidCap Financial
Trust, the Registrant and the Lenders
listed therein
10.19+ Consulting Agreement by and between
8-K
001-36554
5/30/2019 10.2
the Registrant and Dr. Amarpreet S.
Sawhney, dated as of May 29, 2019
10.20+ Employment Agreement, by and between
the Registrant and Antony C. Mattessich,
dated as of June 20, 2017
8-K
001-36554
6/22/2017 10.2
10.21+ Non-Statutory Stock Option Agreement,
8-K
001-36554
6/22/2017 10.3
by and between the Registrant and
Antony C. Mattessich dated as of June 20,
2017
10.22+ Transition, Separation and Release of
8-K
001-36554
8/3/2017 10.1
Claims Agreement by and between the
Registrant and Eric Ankerud, dated as of
July 31, 2017
10.23 Consulting Agreement by and between
8-K
001-36554
8/3/2017 10.2
the Registrant and Anchor Biotech
Consulting, LLC dated as of July 31, 2017
168
Table of Contents
Exhibit
Number
10.24+ Employment Agreement, by and between
the Registrant and Donald Notman, dated
as of September 25, 2017
Description of Exhibit
Incorporated by Reference
Form
8-K
File Number
001-36554
Date of
Filing
Exhibit
Number
Filed
Herewith
9/25/2017 10.1
10.25 Second Amendment to Lease, by and
8-K
001-36554
10/16/2017 10.1
between the Registrant and CCC Investors
LLC, dated October 10, 2017
10.26+ Transition, Separation and Release of
8-K
001-36554
10/13/2017 10.1
Claims Agreement by and between the
Registrant and James Fortune, dated as of
October 13, 2017
10.27+ Separation and Release of Claims
Agreement by and between the Registrant
and Daniel Bollag, dated December 2,
2019
X
10.28+ Employment Agreement, by and between
10-K
001-36554
3/8/2018 10.30
the Registrant and Michael Goldstein,
dated as of September 25, 2017
10.29+ Transition, Separation and Release of
10-Q
001-36554
8/7/2019 10.6
Claims Agreement by and between the
Registrant and Kevin Hanley, dated
August 2, 2019
10.30† Second Amended and Restated License
8-K
001-36554
9/19/2018 10.1
Agreement, dated September 13, 2018, by
and between the Registrant and Incept
LLC
10.31 Third Amended and Restated Credit and
Security Agreement dated December 21,
2018 by and among MidCap Financial
Trust, as administrative agent, the
Registrant, and the Lenders listed therein
10.32 First Amendment to Third Amended and
Restated Credit and Security Agreement,
dated as of February 21, 2019, by and
among the Registrant, MidCap Financial
Trust, as administrative agent, and the
Lenders listed therein
8-K
001-36554
12/28/2018 10.1
8-K
001-36554
2/22/2019 10.3
10.33 Second Amendment to Third Amended
10-Q
001-36554
8/7/2019 10.5
and Restated Credit and Security
Agreement, by and among the Registrant,
MidCap Financial Trust, as administrative
agent, and the Lenders listed therein
169
Table of Contents
Exhibit
Number
Description of Exhibit
10.34 Subordination Agreement, dated as of
February 21, 2019, by and among the
Registrant, MidCap Financial Trust, as
administrative agent, and the Lenders
listed therein
Incorporated by Reference
Form
8-K
File Number
001-36554
Date of
Filing
Exhibit
Number
Filed
Herewith
2/22/2019 10.4
10.35 Note Purchase Agreement (including
8-K
001-36554
2/22/2019 10.1
Form of Senior Subordinated Convertible
Note), dated as of February 21, 2019, by
and among the Registrant and the
Purchasers listed therein
10.36+ Consulting Agreement by and between
10-Q
001-36554
8/7/2019 10.7
the Registrant and Kevin Hanley, dated as
of August 2, 2019
10.37 Sublease, dated as of April 4, 2019, by
10-Q
001-36554
5/10/2019 10.4
and among Ocular Therapeutix, Inc. and
Holcim (US) Inc.
21.1
Subsidiaries of the Registrant
23.1
Consent of PricewaterhouseCoopers LLP
X
X
31.1
Certification of principal executive officer pursuant to Rule 13a-14(a)/15d-14(a) of the Securities
X
Exchange Act of 1934, as amended
31.2
Certification of principal financial officer pursuant to Rule 13a-14(a)/15d-14(a) of the Securities
X
Exchange Act of 1934, as amended
32.1
Certification of principal executive officer pursuant to 18 U.S.C. §1350, as adopted pursuant to
X
Section 906 of the Sarbanes-Oxley Act of 2002
32.2
Certification of principal financial officer pursuant to 18 U.S.C. §1350, as adopted pursuant to
X
Section 906 of the Sarbanes-Oxley Act of 2002
101.INS XBRL Instance Document
101.SCH XBRL Taxonomy Extension Schema Document
101.CAL XBRL Taxonomy Calculation Linkbase Document
101.DEF XBRL Taxonomy Extension Definition Linkbase Document
101.LAB XBRL Taxonomy Label Linkbase Document
101.PRE XBRL Taxonomy Presentation Linkbase Document
X
X
X
X
X
X
† Confidential treatment has been granted as to certain portions, which portions have been omitted and separately filed
with the Securities and Exchange Commission.
+ Management contract or compensatory plan or arrangement filed in response to Item 15(a)(3) of the Instructions to the
Annual Report on Form 10-K.
170
Table of Contents
SIGNATURES
Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has duly
caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
Date: March 12, 2020
OCULAR THERAPEUTIX, INC.
By:/s/ Donald Notman
Donald Notman
Chief Financial Officer
(Principal Financial and Accounting Officer)
Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed by the following
persons on behalf of the registrant in the capacities and on the dates indicated.
Signature
Title
Date
/s/ Antony Mattessich
Antony Mattessich
/s/ Donald Notman
Donald Notman
/s/ Charles Warden
Charles Warden
/s/ Jeffrey S. Heier, M.D.
Jeffrey S. Heier, M.D.
/s/ Seung Suh Hong, PH.D.
Seung Suh Hong, PH.D.
/s/ Richard L. Lindstrom, M.D.
Richard L. Lindstrom, M.D.
/s/ Bruce A. Peacock
Bruce A. Peacock
/s/ Leslie Williams
Leslie Williams
President and Chief Executive Officer
(Principal Executive Officer)
Chief Financial Officer
(Principal Financial and Accounting Officer)
March 12, 2020
March 12, 2020
Chairman of the Board
March 12, 2020
Director
Director
Director
Director
Director
March 12, 2020
March 12, 2020
March 12, 2020
March 12, 2020
March 12, 2020
Table of Contents
OCULAR THERAPEUTIX, INC.
INDEX TO CONSOLIDATED FINANCIAL STATEMENTS
Report of Independent Registered Public Accounting Firm
Consolidated Balance Sheets
Consolidated Statements of Operations and Comprehensive Loss
Consolidated Statements of Changes in Stockholders’ Equity(Deficit)
Consolidated Statements of Cash Flows
Notes to Consolidated Financial Statements
F-1
Page
F-2
F-4
F-5
F-6
F-7
F-8
Table of Contents
Report of Independent Registered Public Accounting Firm
To the Board of Directors and Stockholders of Ocular Therapeutix, Inc.
Opinions on the Financial Statements and Internal Control over Financial Reporting
We have audited the accompanying consolidated balance sheets of Ocular Therapeutix, Inc. and its subsidiary (the
“Company”) as of December 31, 2019 and 2018, and the related consolidated statements of operations and comprehensive
loss, of changes in stockholders’ equity (deficit) and of cash flows for each of the three years in the period ended December
31, 2019, including the related notes (collectively referred to as the “consolidated financial statements”). We also have
audited the Company's internal control over financial reporting as of December 31, 2019, based on criteria established in
Internal Control - Integrated Framework (2013) issued by the Committee of Sponsoring Organizations of the Treadway
Commission (COSO).
In our opinion, the consolidated financial statements referred to above present fairly, in all material respects, the financial
position of the Company as of December 31, 2019 and 2018, and the results of its operations and its cash flows for each of
the three years in the period ended December 31, 2019 in conformity with accounting principles generally accepted in the
United States of America. Also in our opinion, the Company maintained, in all material respects, effective internal control
over financial reporting as of December 31, 2019, based on criteria established in Internal Control - Integrated Framework
(2013) issued by the COSO.
Substantial Doubt About the Company’s Ability to Continue as a Going Concern
The accompanying consolidated financial statements have been prepared assuming that the Company will continue as a
going concern. As discussed in Note 1 to the consolidated financial statements, the Company has incurred losses and
negative cash flows from operations since its inception that raise substantial doubt about its ability to continue as a going
concern. Management’s plans in regard to these matters are also described in Note 1. The consolidated financial statements
do not include any adjustments that might result from the outcome of this uncertainty.
Change in Accounting Principle
As discussed in Note 2 to the consolidated financial statements, the Company changed the manner in which it accounts for
leases in 2019.
Basis for Opinions
The Company's management is responsible for these consolidated financial statements, for maintaining effective internal
control over financial reporting, and for its assessment of the effectiveness of internal control over financial reporting,
included in Management’s Annual Report on Internal Control Over Financial Reporting appearing under Item 9A. Our
responsibility is to express opinions on the Company’s consolidated financial statements and on the Company's internal
control over financial reporting based on our audits. We are a public accounting firm registered with the Public Company
Accounting Oversight Board (United States) (PCAOB) and are required to be independent with respect to the Company in
accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange
Commission and the PCAOB.
We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and
perform the audits to obtain reasonable assurance about whether the consolidated financial statements are free of material
misstatement, whether due to error or fraud, and whether effective internal control over financial reporting was maintained
in all material respects.
Our audits of the consolidated financial statements included performing procedures to assess the risks of material
misstatement of the consolidated financial statements, whether due to error or fraud, and performing procedures that
respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and
disclosures in the consolidated financial statements. Our audits also included evaluating the accounting principles used and
significant estimates made by management, as well as evaluating the overall presentation of the consolidated financial
statements. Our audit of internal control over financial reporting included obtaining an understanding of internal control
over financial reporting, assessing the risk that a material weakness exists, and testing and evaluating the
F-2
Table of Contents
design and operating effectiveness of internal control based on the assessed risk. Our audits also included performing such
other procedures as we considered necessary in the circumstances. We believe that our audits provide a reasonable basis for
our opinions.
Definition and Limitations of Internal Control over Financial Reporting
A company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the
reliability of financial reporting and the preparation of financial statements for external purposes in accordance with
generally accepted accounting principles. A company’s internal control over financial reporting includes those policies and
procedures that (i) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the
transactions and dispositions of the assets of the company; (ii) provide reasonable assurance that transactions are recorded
as necessary to permit preparation of financial statements in accordance with generally accepted accounting principles, and
that receipts and expenditures of the company are being made only in accordance with authorizations of management and
directors of the company; and (iii) provide reasonable assurance regarding prevention or timely detection of unauthorized
acquisition, use, or disposition of the company’s assets that could have a material effect on the financial statements.
Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also,
projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate
because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.
/s/ PricewaterhouseCoopers LLP
Boston, Massachusetts
March 12, 2020
We have served as the Company’s auditor since 2008.
F-3
Table of Contents
OCULAR THERAPEUTIX, INC.
CONSOLIDATED BALANCE SHEETS
(In thousands, except share and per share data)
Assets
Current assets:
Cash and cash equivalents
Accounts receivable, net
Inventory
Prepaid expenses and other current assets
Total current assets
Property and equipment, net
Restricted cash
Operating lease assets
Total assets
Liabilities and Stockholders’ Equity (Deficit)
Current liabilities:
Accounts payable
Accrued expenses and other current liabilities
Operating lease liabilities
Total current liabilities
Other liabilities
Operating lease liabilities, net of current portion
Derivative liability
Notes payable, net of discount
2026 convertible notes, net
Total liabilities
Commitments and contingencies (Note 15)
Stockholders’ equity:
December 31,
December 31,
2019
2018
$
$
$
54,437 $
2,548
954
2,231
60,170
10,151
1,764
6,655
78,740 $
3,268 $
7,635
1,126
12,029
—
8,905
12,124
25,007
24,305
82,370
54,062
201
217
1,713
56,193
10,236
6,614
—
73,043
2,965
6,194
—
9,159
3,221
—
—
24,788
—
37,168
Preferred stock, $0.0001 par value; 5,000,000 shares authorized and no shares issued
or outstanding at December 31, 2019 and December 31, 2018, respectively
Common stock, $0.0001 par value; 100,000,000 shares authorized and 50,333,559
and 41,518,091 shares issued and outstanding at December 31, 2019 and
December 31, 2018, respectively
Additional paid-in capital
Accumulated deficit
Total stockholders’ equity (deficit)
Total liabilities and stockholders’ equity (deficit)
—
—
5
379,980
(383,615)
(3,630)
78,740 $
4
333,114
(297,243)
35,875
73,043
$
The accompanying notes are an integral part of these consolidated financial statements.
F-4
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OCULAR THERAPEUTIX, INC.
CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS
(In thousands, except share and per share data)
Revenue:
Product revenue, net
Total revenue, net
Costs and operating expenses:
Cost of product revenue
Research and development
Selling and marketing
General and administrative
Total costs and operating expenses
Loss from operations
Other income (expense):
Interest income
Interest expense
Change in fair value of derivative liability
Other income (expense), net
Total other income (expense), net
Net loss and comprehensive loss
Net loss per share, basic and diluted
Weighted average common shares outstanding, basic and diluted
Comprehensive loss:
Net loss
Other comprehensive loss:
Unrealized gain on marketable securities
Total other comprehensive income
Total comprehensive loss
Year Ended December 31,
2018
2017
2019
$
4,227 $
4,227
1,990 $
1,990
1,923
1,923
2,325
41,091
24,491
22,122
90,029
(85,802)
1,229
(6,101)
4,310
(8)
(570)
(86,372) $
(1.91) $
$
$
465
36,915
4,942
18,786
61,108
(59,118)
457
30,880
17,000
15,509
63,846
(61,923)
879
(1,739)
—
—
(860)
(59,978) $
(1.57) $
424
(1,892)
—
5
(1,463)
(63,386)
(2.20)
28,818,196
45,273,231
38,115,142
$
(86,372) $
(59,978) $
(63,386)
—
—
(86,372) $
—
—
(59,978) $
5
5
(63,381)
$
The accompanying notes are an integral part of these consolidated financial statements.
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Table of Contents
CONSOLIDATED STATEMENTS OF CHANGES IN STOCKHOLDERS’ EQUITY (DEFICIT)
OCULAR THERAPEUTIX, INC.
(In thousands, except share data)
Common Stock
Additional
Paid-in
Par Value Capital
Accumulated
Other
Accumulated Comprehensive
Deficit
Loss
Shares
25,024,100 $
220,520
3 $ 225,889 $ (173,879) $
—
685
—
Balances at December 31, 2016
Issuance of common stock upon exercise of stock options
Issuance of common stock in connection with employee stock
purchase plan
Issuance of common stock upon public offering, net of issuance
costs
Unrealized gain on marketable securities
Stock-based compensation expense
Net loss
Balances at December 31, 2017
Issuance of common stock upon exercise of stock options
Issuance of common stock in connection with employee stock
purchase plan
Issuance of common stock upon public offering, net of issuance
costs
Stock-based compensation expense
Net loss
Balances at December 31, 2018
Issuance of common stock upon exercise of stock options
Issuance of common stock in connection with employee stock
purchase plan
Issuance of common stock upon public offering, net of issuance
costs
Stock-based compensation expense
Net loss
Balances at December 31, 2019
53,662
4,359,920
—
—
—
29,658,202
182,261
81,455
11,596,173
—
—
41,518,091
28,583
130,945
8,655,940
—
—
50,333,559 $
—
—
—
—
—
3
—
—
1
—
—
4
—
—
276
—
29,238
—
7,321
—
263,409
397
—
—
—
(63,386)
(237,265)
—
297
—
61,528
7,483
—
333,114
78
—
—
(59,978)
(297,243)
—
451
—
1
—
—
5 $ 379,980 $ (383,615) $
—
—
(86,372)
37,578
8,759
—
The accompanying notes are an integral part of these consolidated financial statements.
F-6
Total
Stockholders’
Equity
(Deficit)
(5) $
—
52,008
685
—
—
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
— $
276
29,238
5
7,321
(63,386)
26,147
397
297
61,529
7,483
(59,978)
35,875
78
451
37,579
8,759
(86,372)
(3,630)
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OCULAR THERAPEUTIX, INC.
CONSOLIDATED STATEMENTS OF CASH FLOWS
(In thousands)
Year Ended December 31,
2018
2017
2019
Cash flows from operating activities:
Net loss
Adjustments to reconcile net loss to net cash used in operating activities
Stock-based compensation expense
Non-cash interest expense
Change in fair value of derivative liability
Depreciation and amortization expense
(Gain)/loss on disposal of property and equipment
Purchase of premium on marketable securities
Amortization of premium on marketable securities
Changes in operating assets and liabilities:
Accounts receivable
Prepaid expenses and other current assets
Inventory
Operating lease assets
Accounts payable
Accrued expenses and deferred rent
Operating lease liabilities
Net cash used in operating activities
Cash flows from investing activities:
Purchases of property and equipment
Proceeds from sale of property and equipment
Purchases of marketable securities
Proceeds from maturities of marketable securities
Net cash (used in) provided by investing activities
Cash flows from financing activities:
Proceeds from issuance of notes payable
Proceeds from issuance of 2026 convertible notes, net of issuance costs
Proceeds from exercise of stock options
Proceeds from issuance of common stock pursuant to employee stock purchase plan
Proceeds from issuance of common stock offering, net
Payments of insurance costs financed by a third party
Repayment of notes payable
Net cash provided by financing activities
Net increase (decrease) in cash, cash equivalents and restricted cash
Cash, cash equivalents and restricted cash at beginning of period
Cash, cash equivalents and restricted cash at end of period
Supplemental disclosure of cash flow information:
Cash paid for interest
Supplemental disclosure of non-cash investing and financing activities:
Additional right of use asset and related lease liability
Additions to property and equipment included in accounts payable and accrued expenses
at balance sheet dates
Derivative liability in connection with issuance of 2026 convertible notes
Public offering costs included in accounts payable and accrued expenses at balance sheet
dates
$ (86,372) $ (59,978) $ (63,386)
8,759
3,683
(4,310)
2,530
7
—
—
7,483
397
—
2,286
—
—
—
7,321
408
—
1,625
(5)
(3)
17
(2,347)
(518)
(737)
733
124
1,714
(844)
(77,578)
25
(260)
(95)
—
(796)
1,711
—
(49,227)
24
45
(9)
—
932
2,558
—
(50,473)
(2,238)
—
—
—
(2,238)
(1,889)
—
—
—
(1,889)
(8,252)
5
(3,000)
38,200
26,953
—
37,275
78
451
37,537
—
—
75,341
(4,475)
60,676
3,700
—
685
276
29,238
(591)
(1,300)
32,008
8,488
34,664
$ 56,201 $ 60,676 $ 43,152
12,032
—
397
297
61,571
—
(5,657)
68,640
17,524
43,152
$
2,298 $
1,515 $
1,461
$
2,044 $
— $
—
$
214 $
$ 16,434 $
155 $
— $
538
—
$
— $
42 $
108
The accompanying notes are an integral part of these consolidated financial statements.
F-7
Table of Contents
OCULAR THERAPEUTIX, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(Amounts in thousands, except share and per share data)
1. Nature of the Business and Basis of Presentation
Ocular Therapeutix, Inc. (the “Company”) was incorporated on September 12, 2006 under the laws of the State of
Delaware. The Company is a biopharmaceutical company focused on the formulation, development and commercialization
of innovative therapies for diseases and conditions of the eye using its proprietary, bioresorbable hydrogel platform
technology. The Company’s product pipeline candidates provide differentiated drug delivery solutions that reduce the
complexity and burden of the current standard of care (eye drops) by creating local programmed-release alternatives. Since
inception, the Company’s operations have been primarily focused on organizing and staffing the Company, acquiring rights
to intellectual property, business planning, raising capital, developing its technology, identifying potential product
candidates, undertaking preclinical studies and clinical trials, manufacturing initial quantities of its products and product
candidates and building the initial sales and marketing infrastructure for the commercialization of the Company’s approved
products and product candidates and launching its initial product.
The Company is subject to risks common to companies in the biotechnology industry including, but not limited to,
new technological innovations, protection of proprietary technology, dependence on key personnel, compliance with
government regulations, regulatory approval and compliance, reimbursement, uncertainty of market acceptance of products
and the need to obtain additional financing. Recently approved products will require significant sales, marketing and
distribution support up to and including upon their launch. Product candidates currently under development will require
significant additional research and development efforts, including extensive preclinical and clinical testing and regulatory
approval, prior to commercialization.
As of December 31, 2019, the Company’s lead product candidate DEXTENZA (dexamethasone insert) 0.4mg, has
®
been approved by the FDA and the Company’s other product candidates are in clinical stage development. There can be no
assurance that the Company’s research and development will be successfully completed, that adequate protection for the
Company’s intellectual property will be obtained, that any products developed will obtain necessary government regulatory
approval and adequate reimbursement or that any approved products will be commercially viable. Even if the Company’s
product development efforts are successful, it is uncertain when, if ever, the Company will generate significant revenue
from product sales. The Company operates in an environment of rapidly changing technology and substantial competition
from pharmaceutical and biotechnology companies. In addition, the Company is dependent upon the services of its
employees and consultants. The Company may not be able to generate significant revenue from sales of any product for
several years, if at all. Accordingly, the Company will need to obtain additional capital to finance its operations.
Based on the Company’s current forecasted operating plan, which includes estimates related to anticipated cash
inflows from DEXTENZA and ReSure Sealant product sales, and cash outflows for operating expenses, the Company
believes that its existing cash and cash equivalents of $54,437, as of December 31, 2019 along with the net proceeds
received from sales of common stock in 2020 under sales agreement (Note 22), will enable it to fund its planned operating
expenses, debt service obligations and capital expenditure requirements into the first quarter of 2021. The Company has a
limited history of commercialization of DEXTENZA, and management does not yet have sufficient historical evidence to
assert that it is probable that the Company will receive sufficient revenues from its sales of DEXTENZA to fund
operations. Therefore, management has determined that the Company’s accumulated deficit, history of losses, negative
cash flows from operations and future expected losses raise substantial doubt about the Company’s ability to continue as a
going concern within one year of the issuance date of these financial statements. The Company has incurred losses and
negative cash flows from operations since its inception, and the Company expects to continue to generate operating losses
and negative cash flows from operations in the foreseeable future. As of December 31, 2019, the Company had an
accumulated deficit of $383,615.
While the Company has raised capital in the past, the ability to raise capital in future periods is not considered
probable, as defined under the accounting standards and therefore, was not considered in management’s assessment of the
Company’s ability to continue as a going concern. The Company expects to seek additional funds through equity offerings,
debt financings, government or other third-party funding, collaborations, strategic alliances, licensing
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arrangements, royalty agreements, and marketing and distribution arrangements. If the Company is unable to obtain other
financing, the Company would be forced to delay, reduce or eliminate its research and development programs or any future
commercialization efforts or to relinquish valuable rights to its technologies, future revenue streams, research programs or
product candidates or grant licenses on terms that may not be favorable to the Company. The actions necessary to reduce
spending to a level that mitigates the factors described above are not considered probable, as defined in the accounting
standards and therefore were not considered in management’s assessment of the Company’s ability to continue as a going
concern.
The accompanying consolidated financial statements have been prepared in conformity with accounting principles
generally accepted in the United States of America (“GAAP”).
2. Summary of Significant Accounting Policies
Basis of Presentation and Principles of Consolidation
The accompanying consolidated financial statements reflect the operations of the Company and its wholly-owned
subsidiary. All intercompany accounts and transactions have been eliminated.
Use of Estimates
The preparation of consolidated financial statements in conformity with GAAP requires management to make
estimates and assumptions that affect the reported amounts of assets and liabilities, the disclosure of contingent assets and
liabilities at the date of the consolidated financial statements, and the reported amounts of revenues and expenses during the
reporting periods. Significant estimates and assumptions reflected in these consolidated financial statements include, but
are not limited to, revenue recognition, and the fair value of derivatives. Estimates are periodically reviewed in light of
changes in circumstances, facts and experience. Actual results could differ from the Company’s estimates.
Cash Equivalents
The Company considers all short-term, highly liquid investments with original maturities of ninety days or less at
date of purchase to be cash equivalents. Cash equivalents, which primarily consist of money market accounts, are stated at
fair value.
Revenue Recognition
The Company recognizes product revenue from DEXTENZA for the treatment of post-surgical ocular inflammation
and pain, which it began selling to customers in June 2019, and ReSure Sealant. The Company has generated limited
revenues from ReSure Sealant to date and does not expect significant future sales.
In November 2018, the FDA approved DEXTENZA for the treatment of ocular pain following ophthalmic surgery.
The Company entered into a limited number of arrangements with specialty distributors in the United States to distribute
DEXTENZA. The Company recognizes revenue in accordance with Accounting Standards Codification 606 – Revenue
from Contracts with Customers (“Topic 606”). Topic 606 applies to all contracts with customers, except for contracts that
are within the scope of other standards, such as leases, insurance arrangements and financial instruments. Under Topic 606,
an entity recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the
consideration which the entity expects to be entitled to in exchange for those goods or services.
To determine revenue recognition for arrangements that an entity determines are within the scope of Topic 606, the
entity performs the following five steps: (i) identify the contract(s) with a customer, (ii) identify the performance
obligations in the contract, (iii) determine the transaction price, (iv) allocate the transaction price to the performance
obligations in the contract, and (v) recognize revenue when (or as) the entity satisfies a performance obligation. The
Company only applies the five-step model to arrangements that meet the definition of a contract with a customer under
Topic 606, including when it is probable that the Company will collect the consideration it is entitled to in exchange for the
goods or services it transfers to the customer. At contract inception, once the contract is determined to be within the scope
of Topic 606, the Company assesses the goods or services promised within each contract, determines those that are
performance obligations, and assesses whether each promised good or service is distinct. The Company then recognizes as
revenue the amount of the transaction price that is allocated to the respective performance obligation when
F-9
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(or as) the performance obligation is satisfied. For a complete discussion of accounting for product revenue, see Product
Revenue, Net (below).
Product Revenue, Net— The Company derives its product revenues from the sale of DEXTENZA in the United
States to customers, which includes a limited number of specialty distributors, who then subsequently resell DEXTENZA
to physicians, clinics and certain medical centers or hospitals. In addition to distribution agreements with customers, the
Company enters into arrangements with government payers that provide for government mandated rebates and chargebacks
with respect to the purchase of DEXTENZA.
The Company recognizes revenue on product sales when the customer obtains control of the Company's product,
which occurs at a point in time (upon delivery to the customer). The Company has determined that the delivery of
DEXTENZA to its customers constitutes a single performance obligation. There are no other promises to deliver goods or
services beyond what is specified in each accepted customer order. The Company has assessed the existence of a
significant financing component in the agreements with its customers. The trade payment terms with the Company’s
customers do not exceed one year and therefore the Company has elected to apply the practical expedient and no amount of
consideration has been allocated as a financing component. Product revenues are recorded net of applicable reserves for
variable consideration, including discounts and allowances.
Transaction Price, including Variable Consideration— Revenues from product sales are recorded at the net sales
price (transaction price), which includes estimates of variable consideration for which reserves are established.
Components of variable consideration include trade discounts and allowances, product returns, government chargebacks,
discounts and rebates, and other incentives, such as voluntary patient assistance, and other fee-for-service amounts that are
detailed within contracts between the Company and its customers relating to the Company’s sale of DEXTENZA. These
reserves, as detailed below, are based on the amounts earned, or to be claimed on the related sales, and are classified as
reductions of accounts receivable (if the amount is payable to the customer) or a current liability (if the amount is payable
to a party other than a customer). These estimates take into consideration a range of possible outcomes which are
probability-weighted in accordance with the expected value method in Topic 606 for relevant factors such as current
contractual and statutory requirements, specific known market events and trends, industry data, and forecasted customer
buying and payment patterns. Overall, these reserves reflect the Company’s best estimates of the amount of consideration
to which it is entitled based on the terms of the respective underlying contracts.
The amount of variable consideration which is included in the transaction price may be constrained, and is included
in the net sales price, only to the extent that it is probable that a significant reversal in the amount of the cumulative
revenue recognized under the contract will not occur in a future period. Actual amounts of consideration ultimately
received may differ from the Company’s estimates. If actual results in the future vary from the Company’s original
estimates, the Company will adjust these estimates, which would affect net product revenue and earnings in the period such
variances become known.
Trade Discounts and Allowances—The Company compensates (through trade discounts and allowances) its
customers for sales order management, data, and distribution services. However, the Company has determined such
services received to date are not distinct from the Company’s sale of products to the customer and, therefore, these
payments have been recorded as a reduction of revenue within the statement of operations and comprehensive loss
through December 31, 2019, as well as a reduction to accounts receivables, net on the consolidated balance sheets.
Product Returns— Consistent with industry practice, the Company generally offers customers a limited right of
return for product that has been purchased from the Company in certain circumstances as further discussed below. The
Company estimates the amount of its product sales that may be returned by its customers and records this estimate as a
reduction of revenue in the period the related product revenue is recognized, as well as within accrued expenses and other
current liabilities, in the accompanying consolidated balance sheets. The Company currently estimates product return
reserves using available industry data and its own sales information, including its visibility into the inventory remaining in
the distribution channel. The Company has received no returns to date and believes the returns of DEXTENZA will be
minimal.
The Company’s limited right of return allows for eligible returns of DEXTENZA in the following circumstances:
·
Shipment errors that were the result of an error by the Company;
F-10
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·
·
·
·
·
·
Quantity delivered that is greater or less than the quantity ordered;
Product distributed by the Company that is damaged in transit prior to receipt by the customer;
Product from physicians, clinics, medical centers and hospitals that was not administered to the patient that is
rendered non-usable due to spoilage or mishandling;
Expired product, previously purchased directly from the Company, that is returned during the period beginning
six months prior to the product’s expiration date and ending twelve months after the product’s expiration date;
Product subject to a recall; and
Product that the Company, at its sole discretion, has specified to be returned.
Government Chargebacks— Chargebacks for fees and discounts to qualified government healthcare providers
represent the estimated obligations resulting from contractual commitments to sell products to qualified U.S. Department of
Veterans Affairs hospitals and 340B entities at prices lower than the list prices charged to customers who directly purchase
the product from the Company. The 340B Drug Discount Program is a U.S. federal government program created in 1992
that requires drug manufacturers to provide outpatient drugs to eligible health care organizations and covered entities at
significantly reduced prices. Customers charge the Company for the difference between what they pay for the product and
the statutory selling price to the qualified government entity. These reserves are established in the same period that the
related revenue is recognized, resulting in a reduction of product revenue and accounts receivables, net. Chargeback
amounts are generally determined at the time of resale to the qualified government healthcare provider by customers, and
the Company generally issues credits for such amounts within a few weeks of the Customer’s notification to the Company
of the resale. Reserves for chargebacks consist of credits that the Company expects to issue for units that remain in the
distribution channel inventories at each reporting period-end that the Company expects will be sold to qualified healthcare
providers, and chargebacks that customers have claimed, but for which the Company has not yet issued a credit.
Government Rebates— The Company is subject to discount obligations under state Medicaid programs and
Medicare. These reserves are recorded in the same period the related revenue is recognized, resulting in a reduction of
product revenue and the establishment of a current liability which is included in accrued expenses and other current
liabilities on the consolidated balance sheets. For Medicare, the Company also estimates the number of patients in the
prescription drug coverage gap for whom the Company will owe an additional liability under the Medicare Part D program.
For Medicaid programs, the Company estimates the portion of sales attributed to Medicaid patients and records a liability
for the rebates to be paid to the respective state Medicaid programs. The Company’s liability for these rebates consists of
invoices received for claims from prior quarters that have not been paid or for which an invoice has not yet been received,
estimates of claims for the current quarter, and estimated future claims that will be made for product that has been
recognized as revenue, but which remains in the distribution channel inventories at the end of each reporting period.
Other Incentives— Other incentives which the Company offers include voluntary patient assistance programs, such
as the co-pay assistance program, which are intended to provide financial assistance to qualified commercially-insured
patients with prescription drug co-payments required by payers. The calculation of the accrual for co-pay assistance is
based on an estimate of claims and the cost per claim that the Company expects to receive associated with product that has
been recognized as revenue, but remains in the distribution channel inventories at the end of each reporting period. The
adjustments are recorded in the same period the related revenue is recognized, resulting in a reduction of product revenue
and the establishment of a current liability which is included as an accrued expenses and other current liabilities on the
consolidated balance sheets.
Inventory
The Company values its inventories at the lower of cost or estimated net realizable value. The Company determines
the cost of its inventories, which includes amounts related to materials and manufacturing overhead, on a first-in, first-out
basis. The Company performs an assessment of the recoverability of capitalized inventory during each reporting period,
and it writes down any excess and obsolete inventories to their estimated realizable value in the period
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in which the impairment is first identified. Such impairment charges, should they occur, are recorded within cost of
product revenue. The determination of whether inventory costs will be realizable requires estimates by management. If
actual market conditions are less favorable than projected by management, additional write-downs of inventory may be
required, which would be recorded as a cost of product revenue in the consolidated statements of operations and
comprehensive loss.
The Company capitalizes inventory costs associated with the Company’s products after regulatory approval when,
based on management’s judgment, future commercialization is considered probable and the future economic benefit is
expected to be realized. Inventory acquired prior to receipt of marketing approval of a product candidate is expensed as
research and development expense as incurred. Inventory that can be used in either the production of clinical or commercial
product is expensed as research and development expense when selected for use in a clinical manufacturing
campaign. Inventory produced that will be used in promotional marketing campaigns is expensed to selling and marketing
expense when it is selected for use in a marketing program.
Inventory consisted of the following:
Raw materials
Work-in-process
Finished goods
Restricted Cash
December 31,
2019
2018
$
$
217 $
148
589
954 $
112
33
72
217
As of December 31, 2019 and 2018, the Company held restricted cash of $1,764 and $6,614, respectively, on its
consolidated balance sheet. The Company held restricted cash as security deposits for the lease of its manufacturing space
and corporate headquarters.
As of December 31, 2018, the Company held restricted cash as security deposits for the lease of its manufacturing
space and its former corporate headquarters and a financial covenant associated with the terms of its existing debt with
lenders for total indebtedness of $25,000, which restricted the Company's withdrawal or usage of $5,000. On August 2,
2019, the Company entered into a second amendment to the Credit Agreement (Note 9) in which the lenders agreed to
remove the financial covenant requiring the Company to maintain a minimum of $5,000 of cash on hand.
The Company’s statements of cash flows include restricted cash with cash and cash equivalents when reconciling the
beginning-of-period and end-of-period total amounts shown on such statements. A reconciliation of the cash, cash
equivalents, and restricted cash reported within the balance sheet that sum to the total of the same amounts shown in the
statement of cash flows is as follows:
Cash and cash equivalents
Restricted cash
Total cash, cash equivalents and restricted cash
as shown on the statements of cash flows
December 31, December 31, December 31,
$
2019
54,437 $
1,764
2018
54,062 $
6,614
2017
41,538
1,614
$
56,201 $
60,676 $
43,152
Concentration of Credit Risk and of Significant Suppliers and Customers
Financial instruments that potentially expose the Company to concentrations of credit risk consist primarily of cash
and cash equivalents. The Company has all cash and cash equivalents balances at one accredited financial institution, in
amounts that exceed federally insured limits. The Company does not believe that it is subject to unusual credit risk beyond
the normal credit risk associated with commercial banking relationships.
The Company is dependent on a small number of third-party manufacturers to supply products for research and
development activities in its preclinical and clinical programs and for sales of its products. The Company’s development
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programs as well as revenue from future sales of its product sales could be adversely affected by a significant interruption
in the supply of any of the components of these products.
For the year ended December 31, 2019, two individual customers accounted for 27% and 11% of the Company’s total
revenue and three customers accounted for 39%, 18% and 11% of the Company’s total accounts receivable. No other
customer accounted for more than 10% of total revenue or accounts receivable for the year ended December 31, 2019.
Fair Value Measurements
Certain assets and liabilities are carried at fair value under GAAP. Fair value is defined as the exchange price that
would be received for an asset or paid to transfer a liability (an exit price) in the principal or most advantageous market for
the asset or liability in an orderly transaction between market participants on the measurement date. Valuation techniques
used to measure fair value must maximize the use of observable inputs and minimize the use of unobservable inputs.
Financial assets and liabilities carried at fair value are to be classified and disclosed in one of the following three levels of
the fair value hierarchy, of which the first two are considered observable and the last is considered unobservable:
·
·
·
Level 1—Quoted prices in active markets for identical assets or liabilities.
Level 2—Observable inputs (other than Level 1 quoted prices) such as quoted prices in active markets for
similar assets or liabilities, quoted prices in markets that are not active for identical or similar assets or liabilities,
or other inputs that are observable or can be corroborated by observable market data.
Level 3—Unobservable inputs that are supported by little or no market activity and that are significant to
determining the fair value of the assets or liabilities, including pricing models, discounted cash flow
methodologies and similar techniques.
The Company’s cash equivalents at December 31, 2019 and 2018, were carried at fair value determined according to
the fair value hierarchy described above (Note 3). The Company’s derivative liability at December 31, 2019 was carried at
fair value determined according to the fair value hierarchy described above and classified as a Level 3 measurement. The
carrying value of accounts receivable, prepaid expenses and other current assets, accounts payable and accrued expenses
approximate their fair value due to the short-term nature of these assets and liabilities.
The carrying value of the Company’s variable interest rate notes payable (Note 9) are recorded at amortized costs,
which approximates fair value due to their short-term nature.
On March 1, 2019, the Company issued $37,500 aggregate principal amount of unsecured senior subordinated
convertible notes (the “2026 Convertible Notes”) (Note 5) and is carried, net of derivative liability, at its amortized cost of
$24,305 at December 31, 2019. The estimated fair value of the 2026 Convertible Notes was $36,849 at December 31, 2019.
The fair value of the 2026 Convertible Notes was estimated utilizing a binomial lattice model which requires the use of
Level 3 unobservable inputs. The main input when determining the fair value for disclosure purposes is the bond yield
which is updated each period to reflect the yield of a comparable instrument issued as of the valuation date. The estimated
fair value presented is not necessarily indicative of an amount that could be realized in a current market exchange. The use
of alternative inputs and estimation methodologies could have a material effect on these estimates of fair value.
Derivative Liability
The 2026 Convertible Notes allow the holders to convert all or part of the outstanding principal of their 2026
Convertible Notes into shares of the Company’s common stock provided that no conversion results in a holder beneficially
owning more than 19.99% of the issued and outstanding common stock of the Company. The entire embedded conversion
option is required to be separated from the 2026 Convertible Notes and accounted for as a freestanding derivative
instrument subject to derivative accounting. Therefore, the entire conversion option is bifurcated from the underlying debt
instrument and accounted for and valued separately from the host instrument. The Company measures the value of the
embedded conversion option at its estimated fair value and recognizes changes in the estimated fair value in other income
(expense), net in the consolidated statements of operations and comprehensive loss
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during the period of change. The embedded conversion is recognized as a derivative liability in the Company’s
consolidated balance sheet.
Property and Equipment
Property and equipment are stated at cost less accumulated depreciation. Depreciation expense is recognized using
the straight-line method over a three- to five-year estimated useful life. Leasehold improvements are amortized over the
shorter of the lease term or the estimated useful life of the related asset. Expenditures for repairs and maintenance of assets
are charged to expense as incurred. Upon retirement or sale, the cost and related accumulated depreciation of assets
disposed of are removed from the accounts and any resulting gain or loss is included in loss from operations.
Impairment of Long-Lived Assets
Long-lived assets consist of property and equipment. Long-lived assets to be held and used are tested for
recoverability whenever events or changes in business circumstances indicate that the carrying amount of the assets may
not be fully recoverable. Factors that the Company considers in deciding when to perform an impairment review include
significant underperformance of the business in relation to expectations, significant negative industry or economic trends,
and significant changes or planned changes in the use of the assets. If an impairment review is performed to evaluate a
long-lived asset for recoverability, the Company compares forecasts of undiscounted cash flows expected to result from the
use and eventual disposition of the long-lived asset to its carrying value. An impairment loss would be recognized when
estimated undiscounted future cash flows expected to result from the use of an asset are less than its carrying amount. The
impairment loss would be based on the excess of the carrying value of the impaired asset over its fair value, determined
based on discounted cash flows. The Company has had no impairment triggers of long-lived assets.
Research and Development Costs
Research and development costs are expensed as incurred. Included in research and development expenses are
salaries, stock-based compensation and benefits of employees and other operational costs related to the Company’s
research and development activities, including external costs of outside vendors engaged to conduct preclinical studies and
clinical trials, manufacturing costs of the Company’s products prior to regulatory approval, costs related to collaboration
agreements and facility-related expenses.
Research Contract Costs and Accruals
The Company has entered into various research and development contracts with research institutions and other
companies both inside and outside of the United States. Certain of these agreements have cancellation clauses, and related
payments are recorded as research and development expenses as incurred. The Company records accruals for estimated
ongoing research costs. When evaluating the adequacy of the accrued liabilities, the Company analyzes progress of the
studies, including the phase or completion of events, invoices received and contracted costs. Judgments and estimates are
made in determining the accrued balances at the end of any reporting period. Actual results could differ from the
Company’s estimates. The Company’s historical accrual estimates have not been materially different from the actual costs.
Patent Costs
All patent-related costs incurred in connection with filing and prosecuting patent applications are recorded as general
and administrative expenses as incurred, as recoverability of such expenditures is uncertain.
Accounting for Stock-Based Compensation
The Company measures all stock options and other stock-based awards granted to employees and directors at the fair
value on the date of the grant using the Black-Scholes option-pricing model. The fair value of the awards is recognized as
expense, net of estimated forfeitures, over the requisite service period, which is generally the vesting period of the
respective award. The straight-line method of expense recognition is applied to all awards with service-only conditions.
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Following the Company’s adoption of ASU 2018-07, Compensation—Stock Compensation (Topic 718),
Improvements to Nonemployee Share-Based Payment Accounting (“ASU 2018-07”), on January 1, 2019, for stock-based
awards issued to non-employees, the Company no longer revalues non-employee awards at each reporting date and instead
calculates the fair value of the awards as of the grant date using the Black-Scholes option-pricing model. Compensation
expense for these awards is recognized over the related service period.
The Company classifies stock-based compensation expense in its consolidated statement of operations and
comprehensive loss in the same manner in which the award recipient’s payroll costs are classified or in which the award
recipient’s service payments are classified.
The Company recognizes compensation expense for only the portion of awards that are expected to vest. In
developing a forfeiture rate estimate, the Company has considered its historical experience to estimate pre-vesting
forfeitures for service-based awards. The impact of a forfeiture rate adjustment will be recognized in full in the period of
adjustment, and if the actual forfeiture rate is materially different from the Company’s estimate, the Company may be
required to record adjustments to stock-based compensation expense in future periods.
Income Taxes
The Company accounts for income taxes using the asset and liability method, which requires the recognition of
deferred tax assets and liabilities for the expected future tax consequences of events that have been recognized in the
consolidated financial statements or in the Company’s tax returns. Deferred taxes are determined based on the difference
between the financial statement and tax basis of assets and liabilities using enacted tax rates in effect in the years in which
the differences are expected to reverse. Changes in deferred tax assets and liabilities are recorded in the provision for
income taxes. The Company assesses the likelihood that its deferred tax assets will be recovered from future taxable
income and, to the extent it believes, based upon the weight of available evidence, that it is more likely than not that all or a
portion of deferred tax assets will not be realized, a valuation allowance is established through a charge to income tax
expense.
The Company accounts for uncertainty in income taxes recognized in the consolidated financial statements by
applying a two-step process to determine the amount of tax benefit to be recognized. First, the tax position must be
evaluated to determine the likelihood that it will be sustained upon external examination by the taxing authorities. If the tax
position is deemed more-likely-than-not to be sustained, the tax position is then assessed to determine the amount of benefit
to recognize in the consolidated financial statements. The amount of the benefit that may be recognized is the largest
amount that has a greater than 50% likelihood of being realized upon ultimate settlement. The provision for income taxes
includes the effects of any resulting tax reserves, or unrecognized tax benefits, that are considered appropriate as well as the
related net interest and penalties.
Segment Data
The Company manages its operations as a single segment for the purposes of assessing performance and making
operating decisions. The Company’s singular focus is on advancing its bioresorbable hydrogel product candidates for the
programed-release delivery of therapeutic agents, specifically for ophthalmology. All tangible assets are held in the United
States. Revenue to date has been generated through product sales, all of which has been earned in the United States.
Comprehensive Loss
Comprehensive loss includes net loss as well as other changes in stockholders’ equity (deficit) that result from
transactions and economic events other than those with stockholders. For the years ended December 31, 2019 and 2018,
there were no items that gave rise to other comprehensive loss and therefore, there was no difference between net loss and
comprehensive loss. For the year ended December 31, 2017, other comprehensive loss consisted of unrealized gains from
marketable securities.
Net Loss Per Share
The Company follows the two-class method when computing net loss per share as the Company has issued shares
that meet the definition of participating securities. The two-class method determines net loss per share for each class of
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common and participating securities according to dividends declared or accumulated and participation rights in
undistributed earnings. The two-class method requires income available to common stockholders for the period to be
allocated between common and participating securities based on their respective rights to receive dividends as if all income
for the period had been distributed.
Basic net loss per share attributable to common stockholders is computed by dividing the net loss attributable to
common stockholders by the weighted average number of shares of common stock outstanding for the period. Diluted net
loss attributable to common stockholders is computed by adjusting net loss attributable to common stockholders to
reallocate undistributed earnings based on the potential impact of dilutive securities, including the assumed conversion of
the Company’s 2026 Convertible Notes, outstanding stock options and common stock warrants, except where the result
would be anti-dilutive. Diluted net loss per share attributable to common stockholders is computed by dividing the diluted
net loss attributable to common stockholders by the weighted average number of common shares outstanding for the
period, including potential dilutive common shares assuming the dilutive effect of the conversion of the 2026 Convertible
Notes, the exercise of outstanding stock options and common stock warrants. In the diluted net loss per share calculation,
net loss would also be adjusted for the elimination of interest expense on the 2026 Convertible Notes (which includes
amortization of the discount created upon bifurcation of the conversion option from the debt) and, the mark-to-market gain
or loss each period to the bifurcated conversion option, if the impact was not anti-dilutive.
Recently Adopted Accounting Pronouncements
In February 2016, the FASB issued Accounting Standards Update (“ASU”) No. 2016-02, Leases (Topic 842) (“ASU
2016-02”), a new standard issued to increase transparency and comparability among organizations related to their leasing
activities. This standard established a right-of-use model that requires all lessees to recognize right-of-use assets and lease
liabilities on their balance sheet that arise from leases as well as provide disclosures with respect to certain qualitative and
quantitative information related to a company's leasing arrangements to meet the objective of allowing users of financial
statements to assess the amount, timing and uncertainty of cash flows arising from leases.
The FASB subsequently issued the following amendments to ASU 2016-02 that have the same effective date and
transition date: ASU No. 2018-01, Leases (Topic 842): Land Easement Practical Expedient for Transition to Topic 842,
ASU No. 2018-10, Codification Improvements to Topic 842, Leases, ASU No. 2018-11, Leases (Topic 842): Targeted
Improvements, ASU No. 2018-20, Narrow-Scope Improvement for Lessors, and ASU No. 2019-01, Leases (Topic 842):
Codification Improvements. The Company adopted these amendments with ASU 2016-02 (collectively, the “New Leasing
Standards”) effective January 1, 2019.
The Company adopted the New Leasing Standards using the modified retrospective transition approach, as of
January 1, 2019, with no restatement of prior periods or cumulative adjustment to accumulated deficit. Upon adoption, the
Company elected the package of transition practical expedients, which allowed the Company to carry forward prior
conclusions related to whether any expired or existing contracts are or contain leases, the lease classification for any
expired or existing leases and initial direct costs for existing leases. The Company made an accounting policy election to
not recognize leases with an initial term of 12 months or less within its consolidated balance sheets and to recognize those
lease payments on a straight-line basis in its consolidated statements of operations and comprehensive loss over the lease
term.
Upon adoption of the New Leasing Standards the Company recognized operating lease assets of approximately
$5,300 and corresponding operating lease liabilities of approximately $8,800, which are included in the Company’s
consolidated balance sheet. The adoption of the New Leasing Standards did not have an impact on the Company’s
consolidated statements of operations and comprehensive loss.
The Company determines if an arrangement is a lease at contract inception. Operating lease assets represent the
Company’s right to use an underlying asset for the lease term and operating lease liabilities represent the Company’s
obligation to make lease payments arising from the lease. Operating lease assets and liabilities are recognized at the
commencement date of the lease based upon the present value of lease payments over the lease term. When determining the
lease term, the Company includes options to extend or terminate the lease when it is reasonably certain that the Company
will exercise that option. Given the Company’s current business structure, uncertainty of future growth, and the associated
impact to real estate, the Company concluded that it is not reasonably certain that any renewal options would be exercised.
Therefore, the operating lease assets and operating lease liabilities only contemplate the initial lease
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terms. The Company uses its incremental borrowing rate when the implicit rate is not readily determinable based upon the
information available at the commencement date in determining the present value of the lease payments.
The Company’s operating leases are reflected in operating lease assets, current portion of operating lease liabilities
and operating lease liabilities, net of current portion and in the Company’s consolidated balance sheets. The right of use
asset was determined using the present value of the future minimum lease payments over the term of the lease, any lease
payments made to the lessor at or before the commencement date, reduced by lease incentives, and initial direct costs
incurred by the Company. The liabilities are determined using the present value of the future minimum lease payments.
For additional information on the adoption of the New Leasing Standards, see Note 16 - Leases, to these consolidated
financial statements.
On March 31, 2019, the FASB issued ASU No. 2018-07, Improvements to Nonemployee Share-Based Payment
Accounting (“ASU 2018-07”). The new standard simplifies the accounting for share-based payments to nonemployees by
aligning it with the accounting for share-based payments to employees, with certain exceptions. The Company adopted
ASU 2018-07 as required on January 1, 2019, and its adoption did not have any material impact on the Company’s
consolidated financial statements.
Recently Issued Accounting Pronouncements
In August 2018, the FASB issued ASU No. 2018-13, Fair Value Measurement (Topic 820): Disclosure Framework—
Changes to the Disclosure Requirements for Fair Value Measurement (“ASU 2018-13”), which modifies the existing
disclosure requirements for fair value measurements. The new disclosure requirements include disclosure related to
changes in unrealized gains or losses included in other comprehensive income (loss) for recurring Level 3 fair value
measurements held at the end of each reporting period and the explicit requirement to disclose the range and weighted
average of significant unobservable inputs used for Level 3 fair value measurements. The other provisions of ASU 2018-13
include eliminated and modified disclosure requirements. An entity is permitted to early adopt any removed or modified
disclosures upon issuance of ASU No. 2018-13 and delay adoption of the additional disclosures until their effective date.
For all entities, this guidance is required to be adopted for annual periods beginning after December 15, 2019, including
interim periods within those fiscal years. The Company is currently evaluating the impact that the adoption of ASU 2018-
13 will have on its disclosures.
In June 2016, the FASB issued ASU No. 2016-13, Financial Instruments—Credit Losses (Topic 326): Measurement
of Credit Losses on Financial Instruments (“ASU 2016-13”), which requires the measurement and recognition of expected
credit losses for financial assets held at amortized cost. ASU 2016-13 replaces the existing incurred loss impairment model
with an expected loss model. It also eliminates the concept of other-than-temporary impairment and requires credit losses
related to available-for-sale debt securities to be recorded through an allowance for credit losses rather than as a reduction
in the amortized cost basis of the securities. These changes will result in the earlier recognition of credit losses, if any. In
May 2019, the FASB issued ASU No. 2019-05, Financial Instruments—Credit Losses (Topic 326): Targeted Transition
Relief (“ASU 2019-05”), which provides additional implementation guidance on the previously issued ASU 2016-13. For
public entities, this guidance is effective for fiscal years beginning after December 15, 2019, including interim periods
within those fiscal years. The Company is currently evaluating the impact that the adoption of ASU 2016-13 and ASU
2019-05 will have on its consolidated financial statements
In November 2018, the FASB issued ASU No. 2018-18, Collaborative Arrangements (Topic 808): Clarifying the
Interaction between Topic 808 and Topic 606 (“ASU 2018-18”). ASU 2018-18 makes targeted improvements to GAAP for
collaborative arrangements, including (i) clarification that certain transactions between collaborative arrangement
participants should be accounted for as revenue under ASC 606 when the collaborative arrangement participant is a
customer in the context of a unit of account, (ii) adding unit-of-account guidance in ASC 808, Collaborative Arrangements,
to align with the guidance in ASC 606 and (iii) a requirement that in a transaction with a collaborative arrangement
participant that is not directly related to sales to third parties, presenting the transaction together with revenue recognized
under ASC 606 is precluded if the collaborative arrangement participant is not a customer. For public entities, this guidance
is effective for fiscal years beginning after December 15, 2019, including interim periods within those fiscal years. The
Company is currently evaluating the impact that the adoption of ASU 2018-18 will have on its consolidated financial
statements.
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In December 2019, the FASB issued ASU No. 2019-12, Income Taxes Topic 740, Simplifying the Accounting for
Income Taxes (“ASU 2019-12”). ASU 2019-12 removes certain exceptions for investments, intra-period allocations and
interim calculations, and adds guidance to reduce complexity in accounting for income taxes. The guidance is effective for
fiscal years beginning after December 15, 2020, including interim periods within those fiscal years. The Company is
currently evaluating the impact that the adoption of ASU 2019-12 will have on its consolidated financial statements.
3. Fair Value of Financial Assets and Liabilities
The following tables present information about the Company’s financial assets and liabilities that are measured at fair
value on a recurring basis as of December 31, 2019 and 2018 and indicate the level of the fair value hierarchy utilized to
determine such fair value:
Assets:
Cash equivalents:
Money market funds
Liability:
Derivative liability (Note 4)
Total
Assets:
Cash equivalents:
Money market funds
Total
Fair Value Measurements as of
December 31, 2019 Using:
Level 1 Level 2 Level 3
Total
$
$ 45,156 $
— $ 45,156
—
12,124
— $ 45,156 $ 12,124 $ 57,280
12,124
—
$
Fair Value Measurements as of
December 31, 2018 Using:
Level 1 Level 2 Level 3
Total
$
$
— $ 50,906 $
— $ 50,906 $
— $ 50,906
— $ 50,906
During the year ended December 31, 2019 and 2018, there were no transfers between Level 1, Level 2 and Level 3.
4. Derivative Liability
The 2026 Convertible Notes (Note 5) contained an embedded conversion option that met the criteria to be bifurcated
and accounted for separately from the 2026 Convertible Notes (the "Derivative Liability"). The Derivative Liability was
recorded at fair value upon the issuance of the 2026 Convertible Notes and is subsequently remeasured to fair value at each
reporting period. The Derivative Liability was initially valued and remeasured using a "with-and-without" method. The
"with-and-without" methodology involves valuing the whole instrument on an as-is basis and then valuing the instrument
without the embedded conversion option. The difference between the entire instrument with the embedded conversion
option compared to the instrument without the embedded conversion option is the fair value of the derivative, recorded as
the Derivative Liability.
The fair value of the 2026 Convertible Notes with and without the conversion option is estimated using a binomial
lattice approach. The main inputs to valuing the 2026 Convertible Notes with the conversion option as of December 31,
2019 include the Company’s stock price on the valuation date ($3.95 on December 31, 2019), the expected annual volatility
of the Company’s stock (86%) and the bond yield (13.0%), which was derived by making the fair value of the 2026
Convertible Notes equal to the face value on the issuance date. Fair value measurements are highly sensitive to changes in
these inputs and significant changes in these inputs would result in a significantly higher or lower fair value.
A roll forward of the derivative liability is as follows:
Balance at December 31, 2018
Initial value
F-18
As of
December 31, 2019
—
$
16,434
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Change in fair value
Balance at December 31, 2019
$
(4,310)
12,124
5. Convertible Notes
On March 1, 2019, the Company issued $37,500 of 2026 Convertible Notes. Each 2026 Convertible Note accrues
interest at an annual rate of 6% of its outstanding principal amount, which is payable, along with the principal amount at
maturity, on March 1, 2026, unless earlier converted, repurchased or redeemed. The Company includes the deferred
interest in the balance of the 2026 Convertible Notes on its consolidated balance sheet. The effective annual interest rate for
the 2026 Convertible Notes was 14.8% through December 31, 2019.
The holders of the 2026 Convertible Notes may convert all or part of the outstanding principal amount of their 2026
Convertible Notes into shares of the Company’s common stock, par value $0.0001 per share, prior to maturity and provided
that no conversion results in a holder beneficially owning more than 19.99% of the issued and outstanding common stock
of the Company. The conversion rate is initially 153.8462 shares of the Company’s common stock per $1,000 principal
amount of the 2026 Convertible Notes, which is equivalent to an initial conversion price of $6.50 per share. The
conversion rate is subject to adjustment in customary circumstances such as stock splits or similar changes to the
Company’s capitalization.
At its election, the Company may choose to make such conversion payment in cash, in shares of common stock, or a
combination thereof. Upon any conversion of any 2026 Convertible Note, the Company is obligated to make a cash
payment to the holder of such 2026 Convertible Note for any interest accrued but unpaid on the principal amount
converted. Upon the occurrence of a Corporate Transaction (as defined below), each holder has the option to require the
Company to repurchase all or part of the outstanding principal amount of such note at a repurchase price equal to 100% of
the outstanding principal amount of the 2026 Convertible Note to be repurchased, plus accrued and unpaid interest to, but
excluding the repurchase date. In addition, each holder is entitled to receive an additional make-whole cash payment in
accordance with a table set forth in each 2026 Convertible Note.
Upon conversion by the holder, the Company has the right to select the settlement of the conversion in either shares
of common stock, cash, or in a combination thereof. In addition, the Company is obligated to make a cash payment to the
holder of such 2026 Convertible Note for any interest accrued but unpaid on the principal amount converted.
·
·
·
If the Company elects to satisfy such conversion by shares of common stock, the Company shall deliver to the
converting holder in respect of each $1,000 principal amount of 2026 Convertible Notes being converted a
number of common shares equal to the conversion rate in effect on the conversion date;
If the Company elects to satisfy such conversion by cash settlement, the Company shall pay to the converting
holder in respect of each $1,000 principal amount of 2026 Convertible Notes being converted cash in an amount
equal to the sum of the Daily Conversion Values (as defined below) for each of the twenty (20) consecutive
trading days during a specified period. The “Daily Conversion Values” is defined as each of the 20 consecutive
trading days during the specified period, 5.0% of the product of (a) the conversion rate on such trading day and
(b) the Daily VWAP on such trading day. The Daily VWAP is defined as each of the 20 consecutive trading days
during the applicable Observation Period, the per share volume-weighted average price as displayed under the
heading “Bloomberg VWAP” on the Bloomberg page for the Company.
If the Company elects to satisfy such conversion by combination, the Company shall pay or deliver, as the case
may be, in respect of each $1,000 principal amount of 2026 Convertible Notes being converted, a settlement
amount equal to the sum of the Daily Settlement Amounts (as defined below) for each of the twenty (20)
consecutive trading days during the specified period. The “Daily Settlement Amount” is defined as, for each of
the 20 consecutive trading days during the specified period: (a) cash in an amount equal to the lesser of (i) the
Daily Measurement Value (as defined below) and (ii) the Daily Conversion Value on such Trading Day; and (b)
if the Daily Conversion Value on such trading day exceeds the Daily Measurement Value, a number of Shares
equal to (i) the difference between the Daily Conversion Value and the Daily Measurement Value, divided by (ii)
the Daily VWAP for such Trading Day. The “Daily Measurement Value” is defined as the Specified Dollar
Amount (as defined below), if any, divided by 20. The “Specified Dollar
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Amount” is defined as the maximum cash amount per $1,000 principal amount of Notes to be received upon
conversion as specified in the notice specifying the Company’s chosen settlement method.
In the event of a Corporate Transaction, the noteholder shall have the right to either (a) convert all of the unpaid
principal at the conversion rate and receive a cash payment equal to (i) the outstanding accrued but unpaid interest under
the 2026 Convertible Note to, but excluding, the corporate transaction conversion date (to the extent such date occurs prior
to March 1, 2026, the maturity date of the 2026 Convertible Notes) plus (ii) and an additional amount of consideration
based on a sliding scale depending on the date of such as Corporate transaction or (b) require the Company to repurchase
all or part of the outstanding principal amount of such 2026 Convertible Note at a repurchase price equal to 100% of the
outstanding principal amount of the 2026 Convertible Note to be repurchased, plus accrued and unpaid interest to, but
excluding, the repurchase date.
A corporate transaction includes (i) a merger or consolidation executed through a tender offer or change of control
(other than one in which stockholders of the Company own a majority by voting power of the outstanding shares of the
surviving or acquiring corporation); (ii) a sale, lease, transfer, of all or substantially all of the assets of the Company; or (iii)
if the Company’s common stock ceases to be listed or quoted on any of the New York Stock Exchange, the Nasdaq Global
Select Market, the Nasdaq Global Market or the Nasdaq Capital Market (the “Corporate Transaction”).
On or after March 1, 2022, if the last reported sale price of the common stock has been at least 130% of the
conversion rate then in effect for 20 of the preceding 30 trading days (including the last trading day of such period), the
Company is entitled, at its option, to redeem all or part of the outstanding principal amount of the 2026 Convertible Notes,
on a pro rata basis, at an optional redemption price equal to 100% of the outstanding principal amount of the 2026
Convertible Notes to be redeemed, plus accrued and unpaid interest to, but excluding, the optional redemption date.
The 2026 Convertible Notes are subject to acceleration upon the occurrence of specified events of default, including
a default or breach of certain contracts material to the Company and the delisting and deregistration of the Company’s
common stock.
As discussed in Note 4, the Company determined that the embedded conversion option is required to be separated
from the 2026 Convertible Notes and accounted for as a freestanding derivative instrument subject to derivative
accounting. The allocation of proceeds to the conversion option results in a discount on the 2026 Convertible Notes. The
Company is amortizing the discount to interest expense over the term of the 2026 Convertible Notes using the effective
interest method.
A summary of the 2026 Convertible Notes at December 31, 2019 is as follows:
2026 Convertible Notes
Less: unamortized discount
Accrued interest
Total
F-20
December 31,
2019
37,500
(15,101)
22,399
1,906
24,305
$
$
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6. Property and Equipment, net
Property and equipment, net consisted of the following:
Equipment
Leasehold improvements
Furniture and fixtures
Software
Construction in progress
Less: Accumulated depreciation and amortization
December 31,
2018
$
2019
9,511 $ 7,917
8,675
9,074
760
1,132
180
214
331
239
17,863
20,170
(7,627)
(10,019)
$ 10,151 $ 10,236
Depreciation and amortization expense was $2,530, $2,286 and $1,625 for the years ended December 31, 2019, 2018
and 2017, respectively.
7. Accrued Expenses
Accrued expenses consisted of the following:
Accrued payroll and related expenses
Accrued rent
Accrued professional fees
Accrued research and development expenses
Accrued other
December 31, December 31,
2019
2018
$
$
5,042 $
—
1,011
849
733
7,635 $
3,558
267
1,393
380
596
6,194
8. Collaboration Agreement
On October 10, 2016, the Company entered into a Collaboration, Option and License Agreement (the “Collaboration
Agreement”) with Regeneron Pharmaceuticals, Inc. (“Regeneron”) for the development and potential commercialization of
products using the Company’s hydrogel in combination with Regeneron’s large molecule VEGF-targeting compounds for
the treatment of retinal diseases. The Collaboration Agreement does not cover the development of any product candidates
that deliver small molecule drugs, including TKIs for any target including VEGF, or any product candidate that delivers
large molecule drugs other than those that target VEGF proteins.
Under the terms of the Collaboration Agreement, the Company and Regeneron have agreed to conduct a joint
research program with the aim of developing a sustained-release formulation of aflibercept, currently marketed under the
tradename Eylea, that is suitable for advancement into clinical development. The Company has granted Regeneron an
option (the “Option”) to enter into an exclusive, worldwide license to develop and commercialize products using the
Company’s hydrogel in combination with Regeneron’s large molecule VEGF-targeting compounds (“Licensed
Products”). Under the term of the Collaboration Agreement, Regeneron is responsible for funding an initial preclinical
tolerability study.
If Regeneron decided to exercise the Option, Regeneron will conduct further preclinical development and an initial
clinical trial under a collaboration plan. The Company is obligated to reimburse Regeneron for certain development costs
incurred by Regeneron under the collaboration plan during the period through the completion of the initial clinical trial,
subject to a cap of $25,000, which cap may be increased by up to $5,000 under certain circumstances. If Regeneron elects
to proceed with further development following the completion of the collaboration plan, it will be solely responsible for
conducting and funding further development and commercialization of product candidates. If the Option is exercised,
Regeneron is required to use commercially reasonable efforts to research, develop and commercialize at least one Licensed
Product. Such efforts shall include initiating the dosing phase of a subsequent clinical trial within
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specified time periods following the completion of the first-in-human clinical trial or the initiation of preclinical toxicology
studies, subject to certain extensions.
Under the terms of the Collaboration Agreement, Regeneron has agreed to pay the Company $10,000 upon the
exercise of the Option. The Company is also eligible to receive up to $145,000 per Licensed Product upon the achievement
of specified development and regulatory milestones, $100,000 per Licensed Product upon first commercial sale of such
Licensed Product and up to $50,000 based on the achievement of specified sales milestones for all Licensed Products. In
addition, the Company is entitled to tiered, escalating royalties, in a range from a high-single digit to a low-to-mid teen
percentage of net sales of Licensed Products.
In December 2017, the Company delivered to Regeneron a proposed final formulation for the initial preclinical
tolerability study. Regeneron initiated the preclinical study in early 2018. The Company and Regeneron have subsequently
reached an understanding that the proposed formulation was not final and have ceased development of it. The Company is
currently in discussions with Regeneron, in accordance with the terms of the Collaboration Agreement, regarding the
development of an alternative formulation.
9. Notes Payable
The Company entered into a credit and security agreement in 2014 (as amended to date, the “Credit Agreement”)
establishing the Company’s credit facility (the “Credit Facility”). The Company has a total borrowing capacity of $25,000
under the Credit Facility, which has been fully drawn down as of December 31, 2019.
In December 2018, the Company amended the terms of the Credit Agreement to increase total indebtedness under the
Credit Facility to $25,000 which was used primarily to pay-off outstanding balances as of the closing date. The Company
is required to make interest-only payments under the Credit Facility until December 2020. Commencing in January 2021,
the Company is required to make 36 equal monthly installments of principal in the amount of $694, plus interest, through
December 2023. In the event the Company achieves certain milestones under the Credit Agreement, the Company has the
right to extend the interest-only payments through December 21, 2021 and make 24 equal monthly installments of principal
in the amount of $1,042, plus interest. The Company has not assumed the achievement of these milestones for purposes of
disclosures herein.
Amounts borrowed under the Credit Agreement are at LIBOR base rate, subject to 2.00% floor, plus 7.25%. The
interest rate on the date of the amendment was 9.76%. In addition, a final payment (exit fee) equal to 3.5% of amounts
drawn under the Credit Facility, or $875 based on borrowings of $25,000, is due upon the maturity date of December 21,
2023. The Company is accruing the exit fee through December 21, 2023.
On August 2, 2019, the Company entered into a second amendment to the Credit Agreement in which the lenders
agreed to remove the financial covenant requiring the Company to maintain a minimum of $5,000 of cash on hand. Prior to
this amendment, the Company was required to maintain a minimum of $5,000 of cash on hand as a financial covenant to
the borrowing arrangement, which the Company had included in long-term restricted cash.
There are no other financial covenants associated with the Credit Agreement. However, there are negative covenants
restricting the Company’s activities, including limitations on dispositions, mergers or acquisitions; encumbering its
intellectual property; incurring indebtedness or liens; paying dividends; making certain investments; and engaging in
certain other business transactions. The Company is not in violation of any of the covenants. The obligations under the
Credit Agreement are subject to acceleration upon the occurrence of specified events of default, including a material
adverse change in the Company’s business, operations or financial or other condition. The debt is collateralized by
substantially all of the Company’s assets, including its intellectual property.
In accordance with the Credit Agreement, in connection with the Company’s desire to issue and sell the 2026
Convertible Notes, the Company amended the terms of its debt with existing lenders in February 2019. The amendment
added to the Credit Agreement, among other provisions, a negative covenant restricting the Company from paying the
holders of the 2026 Convertible Notes ahead in priority to the existing lenders, for so long as indebtedness remains
outstanding under the Credit Facility, and a cross-default provision to establish that an event of default under the purchase
agreement for the 2026 Convertible Notes also constitutes an event of default under the Credit Agreement.
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Borrowings outstanding are as follows:
Borrowings outstanding
Accrued exit fee
Unamortized discount
December 31, December 31,
2019
25,000 $
180
(173)
25,007 $
2018
25,000
5
(217)
24,788
$
$
As of December 31, 2019, the annual repayment requirements for the Credit Facility, inclusive of interest and the
final payment of $875 due at expiration, were as follows:
Year Ending December 31,
2020
2021
2022
2023
10. Warrants
Principal Final Payment Total
Interest and
—
8,333
8,333
8,334
$ 25,000 $
2,481
2,481
10,427
2,094
9,602
1,269
1,320
9,654
7,164 $ 32,164
The Company has warrants for the purchase of 18,939 shares of common stock outstanding at December 31, 2019 at
a weighted average exercise price of $7.92 per share and an expiration date of April 17, 2021.
11. Preferred Stock
The Amended and Restated Certificate of Incorporation authorized 5,000,000 shares of preferred stock, $0.0001 par
value, all of which is undesignated and none of which are issued or outstanding at December 31, 2019.
12. Common Stock
The Amended and Restated Certificate of Incorporation authorized 100,000,000 shares of the Company’s common
stock. Each share of common stock entitles the holder to one vote on all matters submitted to a vote of the Company’s
stockholders.
On April 5, 2019, the Company entered into an Open Market Sales Agreement
(the “2019 Sales Agreement”) with
Jefferies, LLC (“Jefferies”), under which the Company may offer and sell its common stock having aggregate proceeds of
up to $50,000 from time-to-time through Jefferies, acting as agent. In the twelve months ended December 31, 2019, the
Company sold 7,337,459 shares of common stock under the 2019 Sales Agreement, resulting in net proceeds of
approximately $32,626, respectively, after commissions and expenses.
SM
In January 2018, the Company completed a follow-on offering of its common stock at a public offering price of
$5.00 per share. The offering consisted of 7,475,000 shares of common stock sold by the Company, including those shares
sold in connection with the exercise by the underwriter of its option to purchase additional shares. The Company received
net proceeds from the follow-on offering of $34,704 after commissions and expenses.
In November 2016, the Company entered into a controlled equity offering sales agreement, (the “2016 Sales
Agreement”) with Cantor Fitzgerald & Co., (“Cantor”), under which the Company may offer and sell its common stock
having aggregate proceeds of up to $40,000 may be sold from time to time. During the year ended December 31, 2018, the
Company sold 4,121,173 shares of common stock under the 2016 Sales Agreement, resulting in net proceeds of
approximately $26,824 after underwriting discounts, commissions and expenses. Through December 31, 2018, the
Company had sold 5,011,741 shares of common stock under the 2016 Sales Agreement, resulting in net proceeds of
approximately $33,427 after underwriting discounts, commissions and expenses. In the three months ended March 31,
2019, the Company sold 1,318,481 shares of common stock under the 2016 Sales Agreement, resulting in net proceeds
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of approximately $4,954 after underwriting discounts and commissions and expenses. Through March 31, 2019, the
Company sold 6,330,222 shares of common stock under the 2016 Sales Agreement, resulting in net proceeds of
approximately $38,381 after underwriting discounts and commissions and expenses. As of February 25, 2019, the
Company had no amounts remaining available for future sale under the 2016 Sales Agreement. On February 28, 2019,
pursuant to the 2016 Sales Agreement, the Company delivered a termination notice to Cantor, terminating the 2016 Sales
Agreement.
As of December 31, 2019, the Company had reserved 9,499,615 shares of common stock for the exercise of
outstanding stock options and the number of shares remaining available for grant under the Company’s 2014 Stock
Incentive Plan (the “2014 Plan”) and the 2019 Inducement Stock Incentive Plan (the “2019 Inducement Plan”), the number
of shares available for issuance under the 2014 Employee Stock Purchase Plan (Note 13), and the outstanding warrants to
purchase common stock (Note 10).
13. Stock-Based Awards
2014 Stock Incentive Plan
The 2014 Plan provides for the grant of incentive stock options, non-statutory stock options, restricted stock awards,
restricted stock units, stock appreciation rights and other stock-based awards. The number of shares initially reserved for
issuance under the 2014 Plan was 1,336,907 shares of common stock, which was increased to 2,126,907 on January 1,
2015. The number of shares reserved for issuance may be increased by the number of shares under the 2006 Stock Option
Plan (the “2006 Plan”) that expire, terminate or are otherwise surrendered, cancelled, forfeited or repurchased by the
Company. The number of shares of common stock that may be issued under the 2014 Plan is subject to increase on the first
day of each fiscal year, beginning on January 1, 2015 and ending on December 31, 2024, equal to the least of 1,659,218
shares of the Company’s common stock, 4% of the number of shares of the Company’s common stock outstanding on the
first day of the applicable fiscal year, and an amount determined by the Company’s board of directors. On January 1, 2019,
the number of shares available for issuance under the 2014 Plan increased by 1,659,218. As of December 31, 2019,
636,292 shares remained available for issuance under the 2014 Plan.
As required by the 2006 Plan and 2014 Plan, the exercise price for stock options granted is not to be less than the fair
value of common shares as of the date of grant.
Inducement Stock Option Awards
On June 20, 2017, the Company issued to Antony Mattessich, who became a director of the Company on June 20,
2017 and the Company’s President and Chief Executive Officer on July 26, 2017, a non-statutory stock option to purchase
an aggregate of 590,000 shares of the Company’s common stock at an exercise price of $10.94 per share. Subject to Mr.
Mattessich’s continued service to the Company, the stock option will vest over a four-year period, with 25% of the shares
underlying the option award vesting on the one year anniversary of the grant date and the remaining 75% of the shares
underlying the award vesting monthly thereafter. The stock option was issued outside of the Company’s 2014 Plan as an
inducement material to Mr. Mattessich’s acceptance of entering into employment with the Company in accordance with
Nasdaq Listing Rule 5635(c)(4).
On July 9, 2019, the Company issued to the Senior Vice President, Head of Business Development, a non-statutory
stock option to purchase an aggregate of 60,000 shares of our common stock at an exercise price of $5.13 per share.
Subject to Senior Vice President, Head of Business Development continued service to the Company, the stock option will
vest over a four-year period, with 25% of the shares underlying the option award vesting on the one-year anniversary of the
grant date and the remaining 75% of the shares underlying the award vesting monthly thereafter. The stock option was
issued outside of the Company’s 2014 Plan as an inducement material to Senior Vice President, Head of Business
Development’s acceptance of entering into employment with us in accordance with Nasdaq Listing Rule 5635(c)(4).
On October 29, 2019, the 2019 Inducement Plan was approved by the Board of Directors of the Company. Awards
under the Plan may only be granted to persons who (a) were not previously an employee or director of the Company or (b)
are commencing employment with the Company following a bona fide period of non-employment, in either case as an
inducement material to the individual’s entering into employment with the Company and in accordance with the
requirements of Nasdaq Stock Market Rule 5635(c)(4). For the avoidance of doubt, neither consultants nor
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advisors shall be eligible to participate in the Plan. Each person who is granted an Award under the 2019 Inducement Plan
is deemed a “Participant.” The Plan provides for the following types of awards, each of which is referred to as an “Award”:
non-statutory stock options, stock appreciation rights, restricted stock, restricted stock units and other stock-based
awards. The number of shares of common stock that may be issued under the 2019 Plan is 500,000. As of December 31,
2019, 446,000 shares remained available for issuance under the 2019 Inducement Plan.
2014 Employee Stock Purchase Plan
The Company’s has a 2014 Employee Stock Purchase Plan (the “ESPP”) with a total of 207,402 shares of common
stock reserved for issuance under this plan which increased to 232,402 shares of common stock on January 1, 2015. The
number of shares of common stock that may be issued under the ESPP will automatically increase on the first day of each
fiscal year, commencing on January 1, 2015 and ending on December 31, 2024, in an amount equal to the least of 207,402
shares of the Company’s common stock, 0.5% of the number of shares of the Company’s common stock outstanding on the
first day of the applicable fiscal year, and an amount determined by the Company’s board of directors. On January 1, 2019,
the number of shares available for issuance under the 2014 Plan increased by 207,402. As of December 31, 2019, 477,967
shares of common stock remained available for issuance.
Stock Option Valuation
The fair value of each stock option grant is estimated on the date of grant using the Black-Scholes option-pricing
model. The Company estimates its expected volatility using a weighted average of the historical volatility of its publicly
traded peer companies and the volatility of its common stock, and expect to continue to do so until such time as the
Company has adequate historical data regarding the volatility of its traded stock price. The expected term of the Company’s
stock options to employees has been determined utilizing the “simplified” method for awards that qualify as “plain-vanilla”
options. The expected term of stock options granted to nonemployees is equal to the contractual term of the option award.
The risk-free interest rate is determined by reference to the U.S. Treasury yield curve in effect at the time of grant of the
award for time periods approximately equal to the expected term of the award. Expected dividend yield is based on the fact
that the Company has never paid cash dividends and does not expect to pay any cash dividends in the foreseeable future.
As of December 31, 2019, there were no outstanding unvested service-based stock options held by nonemployees.
The assumptions that the Company used to determine the fair value of the stock options granted to employees and
directors are as follows, presented on a weighted average basis:
Risk-free interest rate
Expected term (in years)
Expected volatility
Expected dividend yield
F-25
Year Ended
December 31,
2019
2017
2.25 % 2.65 % 2.00 %
2018
6
6
87 % 102 % 102 %
— %
— %
— %
6
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The following table summarizes the Company’s stock option activity:
Weighted
Weighted Average
Average
Shares Issuable Exercise
Under Options
Price
Remaining Aggregate
Intrinsic
Contractual
Term Value
Outstanding as of December 31, 2018
Granted
Exercised
Forfeited
Outstanding as of December 31, 2019
Options vested and expected to vest as of December 31, 2019
Options exercisable as of December 31, 2019
5,230,831 $
3,985,025
(28,583)
(1,266,856)
7,920,417 $
7,065,332 $
3,790,742 $
8.67
4.06
2.72
6.84
6.67
6.96
8.67
(In years)
7.5 $
654
7.6 $
7.3 $
6.0 $
704
—
651
The aggregate intrinsic value of stock options is calculated as the difference between the exercise price of the stock
options and the fair value of the Company’s common stock for those stock options that had exercise prices lower than the
fair value of the Company’s common stock. The aggregate intrinsic value of stock options exercised was $54, $551 and
$408 during the years ended December 31, 2019, 2018 and 2017 respectively.
The weighted average grant date fair value of stock options granted to employees and directors during the years
ended December 31, 2019, 2018, 2017 was $2.99, $4.48 and $6.44 per share, respectively.
Stock-based Compensation
The Company recorded stock-based compensation expense related to stock options in the following expense
categories of its statements of operations:
Research and development
Selling and marketing
General and administrative
Year Ended December 31,
2019 2018 2017
$2,312 $2,557 $2,584
633
449
4,104
4,477
$8,759 $7,483 $7,321
1,013
5,434
As of December 31, 2019, the Company had an aggregate of $10,566 of unrecognized stock-based compensation
cost, which is expected to be recognized over a weighted average period of 2.5 years.
14. Net Loss Per Share
Basic and diluted net loss per share attributable to common stockholders was calculated as follows for the years
ended December 31, 2019, 2018 and 2017:
Numerator:
Net loss attributable to common stockholders
$
(86,372) $
(59,978) $
(63,386)
Denominator:
Weighted average common shares outstanding, basic and diluted
45,273,231 38,115,142
28,818,196
Net loss per share attributable to common stockholders, basic
and diluted
$
(1.91) $
(1.57)
(2.20)
2019
Year Ended December 31,
2018
2017
The Company excluded the following common stock equivalents, outstanding as of December 31, 2019, 2018, and
2017, from the computation of diluted net loss per share attributable to common stockholders for the years ended
December 31, 2019, 2018 and 2017 because they had an anti-dilutive impact due to the net loss incurred for the periods.
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The Company also excluded the shares issuable upon conversion of the 2026 Convertible notes from the computation of
diluted net loss per share for the year ended December 31, 2019 because they had an anti-dilutive impact.
Options to purchase common stock
Shares issuable upon conversion of 2026 Convertible Notes, if converted
Warrants for the purchase of common stock
15. Commitments and Contingencies
Intellectual Property Licenses
2019
December 31,
2018
7,920,417 5,230,831 4,002,374
—
5,769,232
18,939
18,939
13,708,588 5,249,770 4,021,313
—
18,939
2017
The Company has a license agreement with Incept, LLC (“Incept”) (Note 19) to use and develop certain patent rights
(the “Incept License”). Under the Incept License, as amended and restated, the Company was granted a worldwide,
perpetual, exclusive license to develop and commercialize products that are delivered to or around the human eye for
diagnostic, therapeutic or prophylactic purposes relating to ophthalmic diseases or conditions. The Company is obligated to
pay low single-digit royalties on net sales of commercial products developed using the licensed technology, commencing
with the date of the first commercial sale of such products and until the expiration of the last to expire of the patents
covered by the license. Any of the Company’s sublicensees also will be obligated to pay Incept a royalty equal to a low
single-digit percentage of net sales made by it and will be bound by the terms of the agreement to the same extent as the
Company. The Company is obligated to reimburse Incept for its share of the reasonable fees and costs incurred by Incept in
connection with the prosecution of the patent applications licensed to the Company under the Incept License. Through
December 31, 2019, royalties paid under this agreement related to product sales were $306 and have been charged to cost
of product revenue.
On September 13, 2018, (the “Effective Date) the Company entered into a second amended and restated license
agreement (the “Second Amended Agreement”) with Incept. The Second Amended Agreement amends and restates in full
the Company’s prior amended and restated Incept License (the “Prior Agreement” or “Original License”) to expand the
scope of the Company’s intellectual property license and modify future intellectual property ownership and other rights
thereunder.
Indemnification Agreements
In the ordinary course of business, the Company may provide indemnification of varying scope and terms to vendors,
lessors, business partners, and other parties with respect to certain matters including, but not limited to, losses arising out of
breach of such agreements or from intellectual property infringement claims made by third parties. In addition, the
Company has entered into indemnification agreements with members of its board of directors and senior management team
that will require the Company, among other things, to indemnify them against certain liabilities that may arise by reason of
their status or service as directors or officers. The maximum potential amount of future payments the Company could be
required to make under these indemnification agreements is, in many cases, unlimited. To date, the Company has not
incurred any material costs as a result of such indemnifications. The Company does not believe that the outcome of any
claims under indemnification arrangements will have a material effect on its financial position, results of operations or cash
flows, and it has not accrued any liabilities related to such obligations in its consolidated financial statements as of
December 31, 2019.
Purchase Commitments
Purchase commitments represent non-cancelable contractual commitments associated with certain clinical trial
activities within the Company’s clinical research organization.
Manufacturing Commitments
Manufacturing contracts generally provide for termination on notice, and therefore are cancelable contracts but are
contracts that the Company is likely to continue, regardless of the fact that they are cancelable.
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Collaboration Agreement
On October 10, 2016, the Company entered into a Collaboration Agreement with Regeneron (Note 8). If the Option
to enter into an exclusive worldwide license is exercised, Regeneron will conduct further preclinical development and an
initial clinical trial under a collaboration plan. The Company is obligated to reimburse Regeneron for certain development
costs incurred by Regeneron under the collaboration plan during the period through the completion of the initial clinical
trial, subject to a cap of $25,000, which cap may be increased by up to $5,000 under certain circumstances; the timing of
such payments are not known. If Regeneron elects to proceed with further development following the completion of the
collaboration plan, it will be solely responsible for conducting and funding further development and commercialization of
product candidates. If the Option is exercised, Regeneron is required to use commercially reasonable efforts to research,
develop and commercialize at least one Licensed Product. Such efforts shall include initiating the dosing phase of a
subsequent clinical trial within specified time periods following the completion of the first-in-human clinical trial or the
initiation of preclinical toxicology studies, subject to certain extensions. Through December 31, 2019, the Option has not
been exercised and no payments have been made to Regeneron.
Legal Proceedings
Securities Class Actions
On July 7, 2017, a putative class action lawsuit was filed against the Company and certain of the Company’s current
and former executive officers in the United States District Court for the District of New Jersey, captioned Thomas
Gallagher v. Ocular Therapeutix, Inc, et al., Case No. 2:17-cv-05011. The complaint purports to be brought on behalf of
shareholders who purchased the Company’s common stock between May 5, 2017 and July 6, 2017. The complaint
generally alleges that the Company and certain of the Company’s current and former officers violated Sections 10(b) and/or
20(a) of the Securities Exchange Act of 1934 (“Exchange Act”) and Rule 10b-5 promulgated thereunder by making
allegedly false and/or misleading statements concerning the Form 483 issued by the FDA related to DEXTENZA and the
Company’s manufacturing operations for DEXTENZA. The complaint seeks unspecified damages, attorneys’ fees, and
other costs. On July 14, 2017, an amended complaint was filed; the amended complaint purports to be brought on behalf of
shareholders who purchased the Company’s common stock between May 5, 2017 and July 11, 2017, and otherwise
includes allegations similar to those made in the original complaint.
On July 12, 2017, a second putative class action lawsuit was filed against the Company and certain of the Company’s
current and former executive officers in the United States District Court for the District of New Jersey, captioned Dylan
Caraker v. Ocular Therapeutix, Inc., et al., Case No. 2:17-cv-05095. The complaint purports to be brought on behalf of
shareholders who purchased the Company’s common stock between May 5, 2017 and July 6, 2017. The complaint includes
allegations similar to those made in the Gallagher complaint, and seeks similar relief.
On August 3, 2017, a third putative class action lawsuit was filed against the Company and certain of the Company’s
current and former executive officers in the United States District Court for the District of New Jersey, captioned Shawna
Kim v. Ocular Therapeutix, Inc., et al., Case No. 2:17-cv-05704. The complaint purports to be brought on behalf of
shareholders who purchased the Company’s common stock between March 10, 2016 and July 11, 2017. The complaint
includes allegations similar to those made in the Gallagher complaint, and seeks similar relief.
On October 27, 2017, a magistrate judge for the United States District Court for the District of New Jersey granted
the defendants’ motion to transfer the above-referenced Gallagher, Caraker, and Kim litigations to the United States
District Court for the District of Massachusetts. These matters were assigned the following docket numbers in the District
of Massachusetts: 1:17-cv-12288 (Gallagher), 1:17-cv-12146 (Caraker), and 1:17-cv-12286 (Kim).
On March 9, 2018, the court consolidated the three actions and appointed co-lead plaintiffs and co-lead counsel for
the consolidated action. On May 7, 2018, co-lead plaintiffs filed a consolidated amended class action complaint. The
amended complaint makes allegations similar to those in the original complaints, against the same defendants, and seeks
similar relief on behalf of shareholders who purchased the Company’s common stock between March 10, 2016 and July 11,
2017. The amended complaint generally alleges that defendants violated Sections 10(b) and/or 20(a) of the Exchange Act
and Rule 10b-5 promulgated thereunder. On July 6, 2018, defendants filed a motion to dismiss the consolidated amended
complaint. Plaintiffs filed an opposition to the motion to dismiss on September 4, 2018, and defendants filed a reply on
October 4, 2018. The court held oral argument on the motion to dismiss on February 6, 2019.
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By order dated April 30, 2019, the court granted defendants’ motion to dismiss. On May 31, 2019, the plaintiffs filed a
notice of appeal to the United States Court of Appeals for the First Circuit regarding the District Court’s opinion and order
of dismissal of the Complaint. The plaintiffs/appellants filed their opening brief on the appeal on October 23,
2019. Defendants/appellees filed their response brief on November 22, 2019. Plaintiffs/appellants filed their reply brief on
December 13, 2019. The First Circuit held an oral argument on the appeal on February 4, 2020, and took the matter
under advisement.
The Company denies any allegations of wrongdoing and intends to vigorously defend against these lawsuits.
Shareholder Derivative Litigation
On July 11, 2017, a purported shareholder derivative lawsuit was filed against certain of the Company’s current and
former executive officers, certain current and former board members, and the Company as a nominal defendant, in the
United States District Court for the District of Massachusetts, captioned Robert Corwin v. Sawhney et al., Case No. 1:17-
cv-11270. The complaint generally alleged that the individual defendants breached fiduciary duties owed to the Company
by making allegedly false and/or misleading statements concerning the Form 483 related to DEXTENZA and our
manufacturing operations for DEXTENZA. The complaint purported to assert claims against the individual defendants for
breach of fiduciary duty, and sought to recover on behalf of the Company for any liability the Company incurs as a result of
the individual defendants’ alleged misconduct. The complaint also sought contribution on behalf of the Company from all
individual defendants for their alleged violations of Sections 10(b) and/or 20(a) of the Exchange Act and Rule 10b-5
promulgated thereunder. The complaint sought declaratory, equitable, and monetary relief, an unspecified amount of
damages, with interest, and attorneys’ fees and costs. On September 20, 2017, counsel for the plaintiff filed a notice of
voluntary dismissal, stating that the plaintiff wished to coordinate his efforts and proceed in a consolidated fashion with the
plaintiff in a similar derivative suit that was pending in the Superior Court of Suffolk County of the Commonwealth of
Massachusetts captioned Angel Madera v. Sawhney et al., Case. No. 17-2273 (which is discussed in the paragraph
immediately below) by filing an action in that court subsequent to the dismissal of this lawsuit. The Corwin lawsuit was
dismissed without prejudice on September 21, 2017. On October 24, 2017, the plaintiff filed a new derivative complaint in
Massachusetts Superior Court (Suffolk County), captioned Robert Corwin v. Sawhney et al., Case No. 17-3425
(BLS2). The new Corwin complaint includes allegations similar to those made in the federal court complaint and asserts a
derivative claim for breach of fiduciary duty against certain of our current and former officers and directors. The complaint
also asserts an unjust enrichment claim against two additional defendants, SV Life Sciences Fund IV, LP and SV Life
Sciences Fund IV Strategic Partners, LP. The complaint also names the Company as a nominal defendant.
On July 19, 2017, a second purported shareholder derivative lawsuit was filed against certain of the Company’s
current and former executive officers, all current board members, one former board member, and the Company as a
nominal defendant, in the Superior Court of Suffolk County of the Commonwealth of Massachusetts, captioned Angel
Madera v. Sawhney et al., Case. No. 17-2273. The complaint included allegations similar to those made in the Corwin
complaint. The complaint purported to assert derivative claims against the individual defendants for breach of fiduciary
duty, unjust enrichment, abuse of control, gross mismanagement, and waste of corporate assets, and sought to recover on
behalf of the Company for any liability the Company incurs as a result of the individual defendants’ alleged misconduct.
The complaint sought declaratory, equitable, and monetary relief, an unspecified amount of damages, with interest, and
attorneys’ fees and costs. On November 6, 2017, the court dismissed this action without prejudice due to plaintiff’s failure
to complete service of process within the time permitted under applicable court rules. On December 21, 2017, the same
plaintiff filed a new derivative complaint in the same court, captioned Angel Madera v. Sawhney et al., Case. No. 17-4126
(BLS2). The new Madera complaint is premised on substantially similar allegations as the previous complaint and
purports to assert derivative claims against certain current and former executive officers and board members for breach of
fiduciary duty, unjust enrichment, and waste of corporate assets, and names the Company as a nominal defendant. Like the
new Corwin complaint, the new Madera complaint also asserts an unjust enrichment claim against two additional
defendants, SV Life Sciences Fund IV, LP and SV Life Sciences Fund IV Strategic Partners, LP.
By order dated January 29, 2018, the court consolidated the state court Corwin and Madera complaints under the
Corwin docket and appointed lead counsel for plaintiffs. On February 28, 2018, plaintiffs filed a consolidated amended
complaint. The consolidated complaint names substantially the same defendants and is premised on substantially similar
allegations as the previous Corwin and Madera complaints, asserting claims for breach of fiduciary duty against the
individual defendants and unjust enrichment against the two SV entity defendants. On April 17, 2018, all defendants
served a motion to dismiss the consolidated amended complaint. On June 22, 2018, plaintiffs served their opposition to
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the motion to dismiss and a cross-motion to stay the proceedings pending a decision on the motion to dismiss in the above-
referenced securities class action in the District of Massachusetts. On July 30, 2018, the parties filed a joint motion to stay
the proceedings pending a decision on the motion to dismiss in the above-referenced securities class action in the District of
Massachusetts. On August 3, 2018, the court granted the motion to stay.
On January 31, 2018, a third purported shareholder derivative suit was filed against certain of the Company’s current
and former executive officers, certain current and former board members, and the Company as a nominal defendant, in the
United States District Court for the District of Massachusetts, captioned Brian Robinson v. Sawhney et al., Case. No. 1:18-
cv-10199. The complaint includes allegations similar to those made in the Corwin and Madera complaints. The complaint
does not name either SV Life Sciences Fund, IV, LP or SV Life Sciences Fund IV Strategic Partners, LP as defendants, and
adds two former officers as defendants. The complaint purports to assert derivative claims against the individual
defendants for breach of fiduciary duty, waste of corporate assets, and unjust enrichment, and seeks to recover on behalf of
the Company for any liability the Company incurs as a result of the individual defendants’ alleged misconduct. The
complaint seeks declaratory, equitable, and monetary relief, an unspecified amount of damages, with interest, and
attorneys’ fees and costs. On April 30, 2018, all defendants filed a motion to dismiss or stay the complaint. Plaintiff filed
his opposition on June 22, 2018. On July 26, 2018, the parties filed a joint motion to extend the deadline for defendants to
file their reply brief pending the potential substitution of the named shareholder plaintiff. On August 20, 2018, the parties
filed a joint stipulation and proposed order regarding plaintiff’s unopposed request to substitute a new shareholder plaintiff
and the parties’ joint request that the court stay the proceedings pending a decision on the motion to dismiss in the above-
referenced securities class action in the District of Massachusetts. On September 4, 2018, the court entered the requested
order substituting the named plaintiff and staying the matter.
On February 16, 2018, a fourth purported shareholder derivative suit was filed against certain of the Company’s
current and former executive officers, certain current and former board members, and the Company as a nominal defendant,
in the United States District Court for the District of Delaware, captioned Terry Kelly v. Sawhney et al., Case. No. 1:18-cv-
00277. The complaint includes allegations similar to those made in the Corwin and Madera complaints. The complaint
purports to assert derivative claims against the individual defendants for breach of fiduciary duty, unjust enrichment and
waste of corporate assets, and seeks to recover on behalf of the Company for any liability the Company incurs as a result of
the individual defendants’ alleged misconduct. The complaint also asserts an unjust enrichment claim against SV Life
Sciences Fund IV, LP and SV Life Sciences Fund IV Strategic Partners, LP. The complaint seeks declaratory, equitable,
and monetary relief, an unspecified amount of damages, with interest, and attorneys’ fees and costs. On June 11, 2018, the
parties filed a stipulation staying the lawsuit pending final judgment in the consolidated derivative action pending in
Massachusetts state court under the Corwin docket, described above. The court entered an order staying the case on June
12, 2018.
The Company denies any allegations of wrongdoing and intend to vigorously defend against these lawsuits.
In addition, the Company received a subpoena from the SEC, dated December 15, 2017, requesting documents and
information concerning DEXTENZA (dexamethasone insert) 0.4mg, including related communications with the FDA,
investors and others. The Company received a second subpoena from the SEC on August 21, 2018, requesting documents
and information concerning its participation in two investor conferences in June 2017. By letter dated May 2, 2019, the
SEC notified the Company that the SEC had concluded its investigation and did not intend to recommend an enforcement
action against the Company or any individuals.
The Company is unable to predict the outcome of these lawsuits or proceedings at this time. Moreover, any
conclusion of these matters in a manner adverse to the Company and for which it incurs substantial costs or damages not
covered by our directors’ and officers’ liability insurance would have a material adverse effect on the Company’s financial
condition and business. In addition, the proceedings could adversely impact the Company’s reputation and divert
management’s attention and resources from other priorities, including the execution of business plans and strategies that are
important to the Company’s ability to grow the Company’s business, any of which could have a material adverse effect on
the Company’s business.
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Table of Contents
16. Leases
The Company leases real estate, including laboratory, manufacturing and office space. The Company’s leases have
remaining lease terms ranging from less than 1 year to 8 years. Certain leases include one or more options to renew,
exercised at the Company’s sole discretion, with renewal terms that can extend the lease term from one year to six
years. All of the Company’s leases qualify as operating leases.
In October 2017, the Company entered into an amendment to a lease agreement for the Company’s laboratory and
manufacturing space located at 34 Crosby Drive and 36 Crosby Drive, each in Bedford, Massachusetts. The lease term
commenced on June 30, 2018 and will expire on July 31, 2023. The Company has a one-time option to terminate the lease
on July 31, 2021.
In June 2016, the Company entered into a lease agreement for approximately 70,712 square feet of general office,
research and development and manufacturing space located at 15 Crosby Drive in Bedford, Massachusetts. The lease term
commenced on February 1, 2017 and will expire on July 31, 2027. The Company has the option to extend the for two
additional periods of five years by delivering written notice of the exercise not earlier than fifteen months nor later than 12
months before expiration of the original term.
On April 4, 2019, the Company entered into a non-cancelable lease for 30,036 square feet of space located at 24
Crosby Drive in Bedford, Massachusetts to be used for office space. The five-year lease commenced on April 18, 2019
and terminates on March 24, 2024 and does not include any lease renewal options.
The following table summarizes the presentation in the Company’s consolidated balance sheet of its operating leases:
Assets:
Operating lease assets
Liability:
Current operating lease liabilities
Non-current operating lease liabilities
Total Operating lease liabilities:
Balance sheet location
December 31,
2019
Operating lease assets
$
6,655
Operating lease liabilities
Operating lease liabilities, net of current
portion
$
1,126
$
8,905
10,031
The following table summarizes the effect of lease costs in the Company’s consolidated statements of operations and
comprehensive loss:
Operating lease costs
Statement of operations and comprehensive loss
location
Research and development
Selling and marketing
General and administrative
The minimum lease payments for the next five years and thereafter are expected to be as follows:
Year Ending December 31,
2020
2021
2022
2023
2024
F-31
For the
Year Ended
December 31,
2019
$
$
1,638
262
315
2,215
December 31,
2019
2,432
2,483
2,548
2,357
1,569
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Thereafter
Total lease payments
Less: interest
Present value of operating lease liabilities
$
$
3,813
15,202
5,171
10,031
The minimum lease payments for the next five years and thereafter is expected to be as follows:
As of December 31, 2019, the weighted average remaining lease term was 6.47 years and the weighted average
incremental borrowing rate used to determine the operating lease liability was 13.55%.
Supplemental disclosure of cash flow information related to our operating leases included in cash flows provided by
operating activities in our consolidated statements of cash flows is as follows:
Cash paid for amounts included in the measurement of lease liabilities
For the
Year Ended
December 31,
2019
$
2,215
During the years ended December 31, 2019, 2018 and 2017, the Company recognized $2,226, $1,788 and $1,733 of
rental expense, respectively, related to office, laboratory, and manufacturing space.
ASC 840 Disclosures
The future minimum lease payments under the Company’s operating leases as of December 31, 2018, were as
follows:
Minimum lease payments
17. Income Taxes
2019
$ 1,809
2020
1,850
2021 2022 2023 Thereafter Total
1,886
1,936 1,730
5,224 $14,435
During the years ended December 31, 2019, 2018 and 2017, the Company recorded no income tax benefits for the
net operating losses incurred or the research and development tax credits generated in each year, due to its uncertainty of
realizing a benefit from those items.
A reconciliation of the U.S. federal statutory income tax rate to the Company’s effective income tax rate is as
follows:
Federal statutory income tax rate
Tax reform change
Research and development tax credits
State taxes, net of federal benefit
Stock-based compensation
Other
Change in deferred tax asset valuation allowance
Effective income tax rate
F-32
Year Ended December 31,
2017
2019
2018
21.0 % 21.0 % 34.0 %
—
—
3.6
2.1
4.5
2.7
(1.3)
(1.3)
(0.1)
(0.5)
(27.7)
(24.0)
(43.0)
3.3
3.8
(2.2)
0.2
3.9
— %
— %
— %
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Net deferred tax assets consisted of the following:
Deferred tax assets:
Net operating loss carryforwards
Tax credit carryforwards
Capitalized start-up costs
Capitalized research and development expenses, net
Operating lease liabilities
Derivative liability
Accrued expenses and other temporary differences
Total deferred tax assets
Valuation allowance
Net deferred tax assets
Deferred tax liabilities:
Operating lease right of use assets
2026 Convertible Notes
Total deferred tax liabilities
Net deferred tax assets
December 31,
2019
2018
$
70,317 $ 49,699
10,160
11,966
695
870
18,418
14,521
—
2,505
—
3,028
5,196
6,987
84,343
110,019
(84,343)
(105,062)
—
4,957
(1,662)
(3,295)
(4,957)
$
— $
—
—
—
—
Changes in the valuation allowance for deferred tax assets during the years ended December 31, 2019, 2018 and
2017 related primarily to the increase in net operating loss carryforwards, capitalized research and development expenses
and research and development tax credit carryforwards offset in 2017 by a decrease in a deferred tax asset resulting from
the decreased federal corporate tax rate and were as follows:
Year Ended December 31,
2018
2019
2017
Valuation allowance as of beginning of year
Increases recorded to income tax provision
Decreases recorded to income tax provision
Valuation allowance as of end of year
$ 84,343 $67,726 $ 70,236
24,773
(27,283)
$105,062 $84,343 $ 67,726
20,719
—
16,617
—
As of December 31, 2019, the Company had net operating loss carryforwards for federal and state income tax
purposes of $274,331 and $219,375, respectively. The federal and state net operating losses generated for annual periods
prior to January 1, 2018 begin to expire in 2024. The Company’s federal net operating losses generated for the years ended
December 31, 2019 and 2018, which amounted to a total of $148,250, can be carried forward indefinitely. As of
December 31, 2019, the Company also had available research and development tax credit carryforwards for federal and
state income tax purposes of $8,211 and $4,342, respectively, which begin to expire in 2026 and 2025, respectively.
Utilization of the net operating loss carryforwards and research and development tax credit carryforwards may be subject to
a substantial annual limitation under Section 382 of the Internal Revenue Code of 1986 due to ownership changes that have
occurred previously or that could occur in the future. These ownership changes may limit the amount of carryforwards that
can be utilized annually to offset future taxable income. In general, an ownership change, as defined by Section 382, results
from transactions increasing the ownership of certain shareholders or public groups in the stock of a corporation by more
than 50% over a three-year period. The Company has not conducted a study to assess whether a change of control has
occurred or whether there have been multiple changes of control since inception due to the significant complexity and cost
associated with such a study. If the Company has experienced a change of control, as defined by Section 382, at any time
since inception, utilization of the net operating loss carryforwards or research and development tax credit carryforwards
would be subject to an annual limitation under Section 382, which is determined by first multiplying the value of the
Company’s stock at the time of the ownership change by the applicable long-term tax-exempt rate, and then could be
subject to additional adjustments, as required. Any limitation may result in expiration of a portion of the net operating loss
carryforwards or research and development tax credit carryforwards before utilization. Further, until a study is completed
and any limitation is known, no amounts are being presented as an uncertain tax position.
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Table of Contents
The Company has evaluated the positive and negative evidence bearing upon its ability to realize the deferred tax
assets. Management considered the Company’s cumulative net losses and concluded that it is more likely than not that the
Company would not realize the benefits of the deferred tax assets. Accordingly, a full valuation allowance was established
against the net deferred tax assets as of December 31, 2019 and 2018.
The Company has not recorded any amounts for unrecognized tax benefits as of December 31, 2019 or 2018.
The Company files tax returns as prescribed by the tax laws of the jurisdictions in which it operates. In the normal
course of business, the Company is subject to examination by federal and state jurisdictions, where applicable. There are
currently no pending income tax examinations. The Company’s tax years are still open under statute from December 31,
2015 to the present. Earlier years may be examined to the extent that tax credit or net operating loss carryforwards are used
in future periods. The Company’s policy is to record interest and penalties related to income taxes as part of its income tax
provision. As of December 31, 2019 and 2018, the Company had no accrued interest or penalties related to uncertain tax
positions and no amounts have been recognized in the Company’s statements of operations and comprehensive loss.
18. 401(k) Savings Plan
The Company established a defined contribution savings plan under Section 401(k) of the Internal Revenue Code.
This plan covers substantially all employees who meet minimum age and service requirements and allows participants to
defer a portion of their annual compensation on a pre-tax basis. Company contributions to the plan may be made at the
discretion of the board of directors. Through December 31, 2019, no contributions have been made to the plan by the
Company.
19. Related Party Transactions
Since October 2017, the Company has engaged McCarter English LLP (“McCarter”) to provide legal services to the
Company, including with respect to intellectual property matters. Mr. Jonathan M. Sparks, Ph.D., a partner at McCarter &
English, has also served in the capacity as the Company’s in-house counsel since October 2017. The Company incurred
fees for legal services rendered by McCarter of $1,119, $1,019 and $42 for the years ended December 31, 2019, 2018 and
2017, respectively. As of December 31, 2019 and 2018, there was $107 and $526 recorded in accounts payable for
McCarter. As of December 31, 2019, there was $242 recorded in accrued expenses for McCarter
20. Restructuring and Other Costs
2019 Restructuring
On November 6, 2019, the Board of Directors approved an operational restructuring to eliminate a portion of the
Company’s workforce to reduce expenses. As part of this operational restructuring, the Company reduced headcount by
approximately 22%. The Company completed the restructuring in the fourth quarter of 2019 and recorded total
restructuring costs of approximately $554 in total costs and operating expenses in the consolidated statements of operations
and comprehensive loss, all of which was paid.
2017 Transition Agreements and Other Costs
On July 31, 2017, the Board of Directors approved a strategic restructuring to eliminate a portion of the Company’s
workforce as part of an initiative to enhance operations and reduce expenses. As part of this strategic restructuring, the
Company eliminated 30 positions across the organization. During the twelve months ended December 31, 2017, the
Company recorded $1,703 of restructuring-related costs in operating expenses in research and development and selling and
marking, including employee severance, benefits and related costs.
On July 31, 2017, the Company entered into a transition, separation and release of claims agreement (the “Ankerud
Transition Agreement”), pursuant to which Eric Ankerud resigned from his role as Executive Vice President, Regulatory,
Quality and Compliance of the Company, effective immediately. Mr. Ankerud continued to serve as an at-will employee of
the Company in the capacity of Senior Advisor until October 31, 2017. Under the Ankerud Transition Agreement, Mr.
Ankerud is entitled to separation benefits until October 31, 2018, in the form of continuation of his base salary in the same
amount in effect as of October 31, 2018; the payment of monthly premiums for healthcare and/or
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Table of Contents
dental coverage; and provided he continues to provide services to the Company as a consultant, the continued vesting of his
outstanding stock options awards in accordance with the applicable equity plans and stock option agreements. During the
twelve months ended December 31, 2017, the Company recorded $386 of severance expense which are included in
operating expenses in research and development.
On October 13, 2017, the Company entered into a transition, separation and release of claims agreement (the
“Fortune Transition Agreement”) with James Fortune, pursuant to which Mr. Fortune resigned from his role as Chief
Operating Officer and any and all other positions he holds as an officer or employee of the Company, effective December
31, 2017 (the “Separation Date”). Pursuant to the Fortune Transition Agreement, effective as of October 13, 2017, the
Employment Agreement, by and between the Company and Mr. Fortune, dated June 19, 2014, was terminated. Under the
Fortune Transition Agreement, Mr. Fortune will be entitled to separation benefits in the form of (i) the continuation of his
base salary for twelve months after the Separation Date in the same amount in effect as of the October 13, 2017 and (ii) the
payment of monthly premiums for healthcare and/or dental coverage at the same rate that is in effect on the Separation Date
until the earlier of twelve months from the Separation Date or the date Mr. Fortune becomes eligible to receive such
benefits under another employer’s benefit plan. Should any annual bonus payments be made to active Company executives
for the calendar year 2017, Mr. Fortune will also be eligible to receive a bonus payment in such amount, if any, he would
have received had he remained employed with the Company through the date of such bonus payments. During the twelve
months ended December 31, 2017, the Company recorded $417 of severance expense which are included in operating
expenses in general and administration.
The following table summarizes the restructuring and other costs by category during the twelve months ended
December 31, 2017:
wwe
Research and development
Selling and marketing
General and administration
Twelve Months Ended
December 31, 2017
Total
690
1,399
417
2,506
$
$
21. Selected Quarterly Financial Data (Unaudited)
Dec. 31,
2019
Sept. 30,
2019
June 30,
2019
Three Months Ended
Mar 31,
Dec. 31,
2019
2018
Sept. 30,
2018
June 30,
2018
Mar 31,
2018
Statements of
Operations Data:
Revenue
Loss from
operations
Net loss
Basic net loss per
common share
Diluted net loss per
common share
2,256
829
650
492
504
498
648
340
(21,401)
(26,017)
(23,144)
(18,778)
(21,599)
(24,453)
(19,658)
(17,124)
(17,283)
(17,399)
(14,816)
(15,010)
(13,564)
(13,804)
(13,455)
(13,765)
$
(0.53) $
(0.40) $
(0.57) $
(0.41) $
(0.42) $
(0.38) $
(0.37) $
(0.40)
$
(0.53) $
(0.45) $
(0.57) $
(0.45) $
(0.42) $
(0.38) $
(0.37) $
(0.40)
22. Subsequent Events
The number of shares of common stock that may be issued under the 2014 Plan is subject to increase on the first day
of each fiscal year, beginning on January 1, 2015 and ending on December 31, 2024, equal to the least of 1,659,218 shares
of the Company’s common stock, 4% of the number of shares of the Company’s common stock outstanding on the first day
of the applicable fiscal year, and an amount determined by the Company’s board of directors. On January 1, 2020, the
number of shares available for issuance under the 2014 Plan increased by 1,659,218.
The number of shares of common stock that may be issued under the ESPP will automatically increase on the first
day of each fiscal year, commencing on January 1, 2015 and ending on December 31, 2024, in an amount equal to the least
of 207,402 shares of the Company’s common stock, 0.5% of the number of shares of the Company’s common stock
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Table of Contents
outstanding on the first day of the applicable fiscal year, and an amount determined by the Company’s board of directors.
On January 1, 2020, the number of shares available for issuance under the ESPP increased by 207,402.
The Company sold an additional 2,229,514 shares of common stock between January 1, 2020 and February 21, 2020,
under the 2019 Sales Agreement discussed in Note 12, resulting in net proceeds of approximately $10,686 after
commissions and expenses.
F-36
DESCRIPTION OF SECURITIES REGISTERED
UNDER SECTION 12 OF THE EXCHANGE ACT
Exhibit 4.3
The following description of registered securities of Ocular Therapeutix, Inc. is intended as a summary
only and therefore is not a complete description. The following description is qualified by reference to our
certificate of incorporation, which we refer to as our Certificate of Incorporation; our by-laws, which we refer to
as our “By-laws”; and applicable provisions of the Delaware General Corporation Law, or the “DGCL”. The
Certificate of Incorporation and the By-laws are incorporated by reference as Exhibit 3.1 and Exhibit 3.2,
respectively, to the Annual Report on Form 10-K of which this Exhibit 4.3 is a part. As used in this “Description
of Securities Registered Under Section 12 of the Exchange Act,” the terms “Company,” “we,” “our” and “us”
refer to Ocular Therapeutix, Inc.
Authorized Capital Stock
Our authorized capital stock consists of 100,000,000 shares of our common stock, par value $0.0001 per
share, and 5,000,000 shares of our preferred stock, par value $0.0001 per share, all of which preferred stock is
undesignated. Our common stock is registered under Section 12(b) of the Securities Exchange Act of 1934, as
amended, or the Exchange Act.
Common Stock
Voting Rights. Holders of our common stock are entitled to one vote for each share held on all matters
submitted to a vote of stockholders and do not have cumulative voting rights. Each election of directors by our
stockholders will be determined by a plurality of the votes cast by the stockholders entitled to vote on the election.
In general, except (1) for the election of directors, (2) as described below under “—Provisions of Our Certificate
of Incorporation and By-laws and Delaware Law That May Have Anti-Takeover Effects—Super-Majority
Voting,” (3) in the future to the extent that we have two or more classes or series of stock outstanding with
separate voting rights and (4) as otherwise required by law, any matter to be voted on by our stockholders at any
meeting is decided by the vote of the holders of a majority in voting power of the votes cast by the holders of
shares of our stock present or represented at the meeting and voting affirmatively or negatively on such matter.
Dividends. Holders of common stock are entitled to receive proportionately any dividends as may be
declared by our board of directors, subject to any preferential dividend rights of outstanding preferred stock.
Liquidation and Dissolution. In the event of our liquidation or dissolution, the holders of our common
stock are entitled to receive proportionately all assets available for distribution to stockholders after the payment
of all debts and other liabilities and subject to the prior rights of any of our outstanding preferred stock.
Other Rights. Holders of our common stock have no preemptive, subscription, redemption or conversion
rights. The rights, preferences and privileges of holders of our common stock are subject to and may be adversely
affected by the rights of the holders of shares of any series of our preferred stock that we may designate and issue
in the future.
Preferred Stock
Under the terms of our Certificate of Incorporation, our board of directors is authorized to issue shares of
our preferred stock in one or more series without stockholder approval, subject to any limitations imposed by
applicable exchange rules. Our board of directors has the discretion to determine the rights, preferences, privileges
and restrictions, including voting rights, dividend rights, conversion rights, redemption privileges and liquidation
preferences, of each series of preferred stock.
The purpose of authorizing our board of directors to issue preferred stock and determine its rights and
preferences is to eliminate delays associated with a stockholder vote on specific issuances. The issuance of
preferred stock, while providing flexibility in connection with possible acquisitions, future financings and other
corporate purposes, could have the effect of making it more difficult for a third party to acquire, or could
discourage a third party from seeking to acquire, a majority of our outstanding voting stock.
Provisions of Our Certificate of Incorporation and By-laws and Delaware Law That May Have Anti-
Takeover Effects
Delaware Law
We are subject to Section 203 of the DGCL. Subject to certain exceptions, Section 203 prevents a publicly
held Delaware corporation from engaging in a “business combination” with any “interested stockholder” for three
years following the date that such person became an interested stockholder, unless either the interested
stockholder attained such status with the approval of our board of directors, the business combination is approved
by our board of directors and stockholders in a prescribed manner or the interested stockholder acquired at least
85% of our outstanding voting stock in the transaction in which it became an interested stockholder. A “business
combination” includes, among other things, (i) a merger or consolidation involving us and the “interested
stockholder” and (ii) the sale of more than 10% of our assets. In general, an “interested stockholder” is any entity
or person beneficially owning 15% or more of our outstanding voting stock and any entity or person affiliated
with or controlling or controlled by such entity or person. The restrictions contained in Section 203 are not
applicable to any of our existing stockholders that owned 15% or more of our outstanding voting stock upon the
closing of our initial public offering.
Staggered Board; Removal of Directors
Our Certificate of Incorporation and our By-laws divide our board of directors into three classes with
staggered three-year terms. In addition, our Certificate of Incorporation and our By-laws provide that directors
may be removed only for cause and only by the affirmative vote of the holders of 75% of the votes that all our
stockholders would be entitled to cast in any annual election of directors . Under our Certificate of Incorporation
and By-laws, any vacancy on our board of directors, including a vacancy resulting from an enlargement of our
board of directors, may be filled only by vote of a majority of our directors then in office. Furthermore, our
Certificate of Incorporation provides that the authorized number of directors may be changed only by the
resolution of our board of directors. The classification of our board of directors and
the limitations on the ability of our stockholders to remove directors, change the authorized number of directors
and fill vacancies could make it more difficult for a third party to acquire, or discourage a third party from seeking
to acquire, control of our company.
Stockholder Action; Special Meeting of Stockholders; Advance Notice Requirements for Stockholder Proposals
and Director Nominations
Our Certificate of Incorporation and our By-laws provide that any action required or permitted to be taken
by our stockholders at an annual meeting or special meeting of stockholders may only be taken if it is properly
brought before such meeting and may not be taken by written action in lieu of a meeting. Our Certificate of
Incorporation and our By-laws also provide that, except as otherwise required by law, special meetings of the
stockholders can only be called by the chairman of our board of directors, our chief executive officer, our
president or our board of directors. In addition, our Bylaws establish an advance notice procedure for stockholder
proposals to be brought before an annual meeting of stockholders, including proposed nominations of candidates
for election to our board of directors. Stockholders at an annual meeting may only consider proposals or
nominations specified in the notice of meeting or brought before the meeting by or at the direction of our board of
directors, or by a stockholder of record on the record date for the meeting who is entitled to vote at the meeting
and who has delivered timely written notice in proper form to our secretary of the stockholder’s intention to bring
such business before the meeting. These provisions could have the effect of delaying until the next stockholder
meeting stockholder actions that are favored by the holders of a majority of our outstanding voting securities.
These provisions also could discourage a third party from making a tender offer for our common stock because
even if the third party acquired a majority of our outstanding voting stock, it would be able to take action as a
stockholder, such as electing new directors or approving a merger, only at a duly called stockholders meeting and
not by written consent.
Super-Majority Voting
The DGCL provides generally that the affirmative vote of a majority of the shares entitled to vote on any
matter is required to amend a corporation’s certificate of incorporation or by-laws unless a corporation’s
certificate of incorporation or by-laws, as the case may be, requires a greater percentage. Our By-laws may be
amended or repealed by a majority vote of our board of directors or the affirmative vote of the holders of at least
75% of the votes that all our stockholders would be entitled to cast in any annual election of directors. In addition,
the affirmative vote of the holders of at least 75% of the votes that all our stockholders would be entitled to cast in
any election of directors is required to amend or repeal or to adopt any provisions inconsistent with any of the
provisions of our Certificate of Incorporation described above.
Exhibit 10.27
EXECUTION VERSION
SEPARATION AND RELEASE OF CLAIMS AGREEMENT
This Separation and Release of Claims Agreement (the “Agreement”) is made as of the Agreement Effective Date
(as defined below) by and between Ocular Therapeutix, Inc. (the “Company”) and Daniel Bollag (“Executive”) (together, the
“Parties”).
WHEREAS, the Company and Executive are parties to the Employment Agreement dated as of July 31, 2017 (the
“Employment Agreement”), under which Executive currently serves as Chief Strategy Officer of the Company;
WHEREAS, Executive is resigning his employment with the Company; and
WHEREAS, the Parties agree that the payments, benefits and rights set forth in this Agreement shall be the
exclusive payments, benefits and rights due Executive, and the Parties acknowledge and agree that Executive is not eligible
to receive any of the payments or benefits for which Executive would have been eligible in connection with a termination of
employment by the Company without Cause or by Executive for Good Reason pursuant to the Employment Agreement;
NOW, THEREFORE, in consideration of the mutual covenants and agreements contained herein, and for other
good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties hereby agree as
follows:
1. Separation Date; Resignation from Position(s) –
(a) Executive’s effective date of separation from employment with the Company will be December 2, 2019, or such
earlier date as may be mutually agreed upon by the Company and Executive (the “Separation Date”). Executive
hereby resigns, as of the Separation Date, from his position as Chief Strategy Officer, and from any and all other
positions he holds as an officer or employee of the Company, and further agrees to execute and deliver any
documents reasonably necessary to effectuate such resignations, as requested by the Company. As of the Agreement
Effective Date, the Employment Agreement will terminate and be of no further force or effect; provided, however,
that Sections 5, 6, 7, 8 and 12 thereof, as amended by this Agreement, shall remain in full force and effect (the
“Surviving Sections”); provided further that Executive acknowledges and agrees that Section 12(a) of the
Employment Agreement is amended hereby to direct notices, requests, consents, or other communications to the
Company hereunder and thereunder to the Company at the following address, as may be updated from time to time
in accordance with the Employment Agreement: Ocular Therapeutix, Inc, 24 Crosby Drive, Bedford, MA 01730,
Attn: General Counsel.
(b) Upon the Separation Date, Executive shall be paid, in accordance with the Company’s regular payroll practices,
all unpaid base salary earned through the Separation Date, including any amounts for accrued unused vacation time
to which Executive is entitled through such date in accordance with Company policy, and reimbursement of any
properly incurred unreimbursed business expenses incurred through the Separation Date (together, the “Accrued
Obligations”). As of the Separation Date, all salary payments from the Company will cease and any benefits
Executive had as of the Separation Date under Company-provided benefit plans, programs, or practices will
terminate, except as required by federal or state law or as otherwise specifically set forth in this Agreement.
2. Separation Benefits – Provided Executive signs and returns this Agreement on or before the final day of the
Consideration Period (as defined below) but not earlier than the Separation Date and
1
does not revoke the Agreement during the Revocation Period (as defined below) as described in Section 14 below,
the Company will provide Executive with the following separation benefits in consideration of Executive’s
commitments and obligations set forth in this Agreement (the “Separation Benefits”):
a. Severance Pay – Commencing on the Company’s first regularly scheduled payroll date that follows the
Agreement Effective Date and continuing for six (6) months, Executive will receive salary continuation
payments, in accordance with the Company’s regular payroll practices, in an aggregate amount equal to the
base salary that Executive would have received had he remained employed with the Company between the
Separation Date and the date that is six (6) months following the Separation Date and continued to receive
his current base salary as in effect as of the Agreement Effective Date, less all applicable taxes and
withholdings.
b. Group Health Insurance – Should Executive be eligible for and timely elect to continue receiving group
health and/or dental insurance coverage under the law known as COBRA, the Company shall, commencing
on the Separation Date, and continuing until the earlier of (x) the date that is twelve (12) months following
the Separation Date and (y) the end of the calendar month in which Executive becomes eligible to receive
group health insurance coverage under another employer’s benefit plan (the “COBRA Contribution
Period”), pay on Executive’s behalf the amount of the premiums for such coverage at the same rate that is in
effect on the Separation Date. The balance of such premiums during the COBRA Contribution Period (if
any), and all premium costs after the COBRA Contribution Period, shall be paid by Executive on a monthly
basis during the elected period of insurance coverage under COBRA for as long as, and to the extent that, he
remains eligible for and elects to remain enrolled in COBRA continuation coverage. Executive agrees that,
should he (i) become eligible to receive group health insurance coverage under another employer’s benefit
plan or (ii) otherwise obtain alternative health and/or dental insurance coverage, in each case prior to the
date that is twelve (12) months following the Separation Date, he will so inform the Company in writing
within five (5) business days of obtaining such coverage.
c. Option Acceleration/Extension of Exercise Period. Effective as of the Agreement Effective Date, the option
to acquire Company common stock granted by the Company to Executive on January 2, 2019 (the “2019
Option”) shall be vested and exercisable with respect to an aggregate of 100,000 shares of Company
common stock (the “Vested Portion of the 2019 Option”), with such Vested Portion of the 2019 Option
being exercisable for a period of 18 months following the Separation Date and otherwise remaining subject
to the terms of the applicable stock option agreement and the plan under which such 2019 Option was
granted. For the avoidance of doubt, as of the date hereof, the Vested Portion of the 2019 Option shall be
treated as a nonqualified stock option for tax purposes even if that option was intended to be an incentive
stock option. The portion of the 2019 Option other than the Vested Portion of the 2019 Option, as well as
the options granted by the Company to Executive on each of August 7, 2017 and the January 31, 2018 shall
be cancelled and terminated as of the Separation Date and shall be of no further force or effect following the
Separation Date.
Other than the Separation Benefits and Accrued Obligations, Executive will not be eligible for, nor shall he have a
right to receive, any payments or benefits from the Company following the Separation Date. For the avoidance of
doubt, Executive is not eligible to receive any Severance Compensation set forth in Section 4(b) of the Employment
Agreement. Executive acknowledges that he will not be eligible to receive the Separation Benefits (or any payments
or benefits from the
2
Company other than the Accrued Obligations) if he fails to timely enter into this Agreement or if he timely revokes
this Agreement as described in Section 14.
It is intended that each installment of the separation payments and benefits provided under this Agreement shall be
treated as a separate “payment” for purposes of Section 409A of the Internal Revenue Code of 1986, as amended,
and the guidance issued thereunder (“Section 409A”). Neither the Company nor Executive shall have the right to
accelerate or defer the delivery of any such payments or benefits except to the extent specifically permitted or
required by Section 409A.
3. Release of Claims – In exchange for the consideration set forth in this Agreement, which Executive acknowledges
he would not otherwise be entitled to receive, Executive hereby fully, forever, irrevocably and unconditionally
releases, remises and discharges the Company, its affiliates, subsidiaries, parent companies, predecessors, and
successors, and all of their respective past and present officers, directors, stockholders, partners, members,
employees, agents, representatives, plan administrators, attorneys, insurers and fiduciaries (each in their individual
and corporate capacities) (collectively, the “Released Parties”) from any and all claims, charges, complaints,
demands, actions, causes of action, suits, rights, debts, sums of money, costs, accounts, reckonings, covenants,
contracts, agreements, promises, doings, omissions, damages, executions, obligations, liabilities, and expenses
(including attorneys’ fees and costs), of every kind and nature that Executive ever had or now has against any or all
of the Released Parties up to the Agreement Effective Date, whether known or unknown, including, but not limited
to, any and all claims arising out of or relating to Executive’s employment with, separation or termination from,
and/or ownership of securities of the Company, including, but not limited to, all claims under Title VII of the Civil
Rights Act, the Americans With Disabilities Act, the Age Discrimination in Employment Act, the Genetic
Information Nondiscrimination Act, the Family and Medical Leave Act, the Worker Adjustment and Retraining
Notification Act, the Rehabilitation Act, Executive Order 11246, Executive Order 11141, the Fair Credit Reporting
Act, and the Employee Retirement Income Security Act, all as amended; all claims arising out of the Massachusetts
Fair Employment Practices Act, Mass. Gen. Laws ch. 151B, § 1 et seq., the Massachusetts Wage Act, Mass. Gen.
Laws ch. 149, § 148 et seq. (Massachusetts law regarding payment of wages and overtime), the Massachusetts Civil
Rights Act, Mass. Gen. Laws ch. 12, §§ 11H and 11I, the Massachusetts Equal Rights Act, Mass. Gen. Laws. ch. 93,
§ 102, Mass. Gen. Laws ch. 214, § 1C (Massachusetts right to be free from sexual harassment law), the
Massachusetts Labor and Industries Act, Mass. Gen. Laws ch. 149, § 1 et seq., Mass. Gen. Laws ch. 214, § 1B
(Massachusetts right of privacy law), the Massachusetts Parental Leave Act, Mass. Gen. Laws ch. 149, § 105D, and
the Massachusetts Small Necessities Leave Act, Mass. Gen. Laws ch. 149, § 52D, all as amended; all common law
claims including, but not limited to, actions in defamation, intentional infliction of emotional distress,
misrepresentation, fraud, wrongful discharge, and breach of contract (including, without limitation, all claims arising
out of or related to the Employment Agreement); all claims to any non-vested ownership interest in the Company,
contractual or otherwise (except as and to the extent explicitly set forth in Section 2(c)); all state and federal
whistleblower claims to the maximum extent permitted by law; and any claim or damage arising out of Executive’s
employment with and/or separation from the Company (including a claim for retaliation) under any common law
theory or any federal, state or local statute or ordinance not expressly referenced above; provided, however, that this
release of claims shall not (i) prevent Executive from filing a charge with, cooperating with, or participating in any
investigation or proceeding before, the Equal Employment Opportunity Commission or a state fair employment
practices agency (except that Executive acknowledges that he may not recover any monetary benefits in connection
with any such charge, investigation, or proceeding, and Executive further waives any rights or claims to any
payment, benefit, attorneys’ fees or other remedial relief in connection with any such charge, investigation or
proceeding), (ii) deprive Executive of any rights under the stock options described in Section 2(c) above and any
3
other accrued benefits to which Executive has acquired a vested right under any employee benefit plan or policy,
stock plan or deferred compensation arrangement, or any health care continuation to the extent required by
applicable law; or (iii) deprive Executive of any rights Executive may have to be indemnified by the Company as
provided in any agreement between the Company and Executive or pursuant to the Company’s Certificate of
Incorporation or by-laws. This release of claims shall not extend to any claims Executive may have against any
persons that are Released Parties to the extent such claims are (x) related solely to Executive’s ownership of the
Company’s stock (including the Vested Portion of the 2019 Option) and (y) unrelated to Executive’s employment
with the Company.
4. Non-Solicitation and Non-Competition Obligations – Executive acknowledges and reaffirms his non-competition
and non-solicitation obligations as set forth in Section 5(b) of the Employment Agreement (the “Restrictive
Covenant Obligations”), which Restrictive Covenant Obligations survive his termination of employment and remain
in full force and effect. Notwithstanding the foregoing, the Company agrees that it will not seek to enforce such
obligations to the extent they would prevent Executive from, following the Separation Date, providing professional
services that (i) are outside the field of ophthalmology, (ii) do not involve or relate to hydrogel technologies, and (iii)
do not otherwise violate Executive’s continuing obligations to the Company as set forth in this Agreement.
5. Non-Disclosure and Assignment Obligations – Executive acknowledges and reaffirms his obligation, except as
otherwise permitted by Section 9 below, to keep confidential and not to use or disclose any and all non-public
information concerning the Company that he acquired during the course of his employment with the Company,
including, but not limited to, any non-public information concerning the Company’s business, operations, products,
programs, affairs, performance, personnel, technology, science, intellectual property, plans, strategies, approaches,
prospects, financial condition or development related matters. Executive also acknowledges his continuing
obligations with respect to: (i) Confidential Information (as defined in the Employment Agreement) and the non-
disclosure and assignment thereof, as set forth in Section 5(a) of the Employment Agreement, and (ii) Inventions
(as defined by the Employment Agreement) and the assignment thereof and cooperation with respect thereto, as set
forth in Section 6 of the Employment Agreement, which survive his separation from employment with the Company
and remain in full force and effect.
6. Non-Disparagement – Executive understands and agrees that, except as otherwise permitted by Section 9 below, he
will not, in public or private, make any false, disparaging, negative, critical, adverse, derogatory or defamatory
statements, whether orally or in writing, including online (including, without limitation, on any social media,
networking, or employer review site) or otherwise, to any person or entity, including, but not limited to, any media
outlet, industry group, key opinion leader, financial institution, research analyst or current or former employee,
board member, consultant, shareholder, client or customer of the Company, regarding the Company, or any of the
other Released Parties, or regarding the Company’s business, operations, products, programs, affairs, performance,
personnel, technology, science, intellectual property, plans, strategies, approaches, prospects, financial condition or
development related matters. For the avoidance of doubt, the foregoing shall not prevent Executive from stating or
repeating factual information with respect to the Company or its assets which is otherwise publicly available. The
Company agrees that its Board members and its named executive officers (as determined pursuant to Item 402(a)(3)
of Regulation S-K) will not, in public or private, make any false, disparaging, negative, critical, adverse, derogatory
or defamatory statements, whether orally or in writing, including online (including, without limitation, on any social
media, networking, or employer review site) or otherwise, to any person or entity, including, but not limited to, any
media outlet,
4
industry group, key opinion leader, financial institution, research analyst or current or former employee, board
member, consultant, shareholder, client or customer of the Company, regarding Executive; provided, however, that
nothing in this Section 6 shall restrict or otherwise limit such Board members or named executive officers from
disclosing events or circumstances in such manner as they or the Company deem necessary to comply with or satisfy
their or the Company’s disclosure, reporting or other obligations under applicable law.
7. Return of Company Property – Executive confirms that he has returned to the Company all property of the
Company, tangible or intangible, including but not limited to keys, files, passwords, records (and copies thereof),
equipment (including, but not limited to, computer hardware, software and printers, wireless handheld devices,
cellular phones, tablets, etc.), Company identification and any other Company-owned property in his possession or
control and that he has left intact all electronic Company documents, including but not limited to those that he
developed or helped to develop during his employment. Executive further confirms that he has canceled all
accounts for his benefit, if any, in the Company’s name, including but not limited to, credit cards, telephone charge
cards, cellular phone and/or wireless data accounts and computer accounts.
8. Confidentiality – Executive understands and agrees that, except as otherwise permitted by Section 9 below, the
contents of the negotiations and discussions resulting in this Agreement shall be maintained as confidential by
Executive and his agents and representatives and shall not be disclosed by Executive and his agents and
representatives except as otherwise agreed to in writing by the Company and except to his immediate family, legal,
financial and tax advisors, on the condition that any individuals so informed must hold the above information in
strict confidence.
9. Scope of Disclosure Restrictions – Nothing in this Agreement or elsewhere prohibits Executive from
communicating with government agencies about possible violations of federal, state, or local laws or otherwise
providing information to government agencies, filing a complaint with government agencies, or participating in
government agency investigations or proceedings. Executive is not required to notify the Company of any such
communications; provided, however, that nothing herein authorizes the disclosure of information Executive obtained
through a communication that was subject to the attorney-client privilege. Further, notwithstanding Executive’s
confidentiality and nondisclosure obligations, Executive is hereby advised as follows pursuant to the Defend Trade
Secrets Act: “An individual shall not be held criminally or civilly liable under any Federal or State trade secret law
for the disclosure of a trade secret that (A) is made (i) in confidence to a Federal, State, or local government official,
either directly or indirectly, or to an attorney; and (ii) solely for the purpose of reporting or investigating a suspected
violation of law; or (B) is made in a complaint or other document filed in a lawsuit or other proceeding, if such filing
is made under seal. An individual who files a lawsuit for retaliation by an employer for reporting a suspected
violation of law may disclose the trade secret to the attorney of the individual and use the trade secret information in
the court proceeding, if the individual (A) files any document containing the trade secret under seal; and (B) does
not disclose the trade secret, except pursuant to court order.”
10. Cooperation – Executive agrees that, to the extent permitted by law, he shall cooperate fully with the Company in
the investigation, defense or prosecution of any claims or actions which already have been brought, are currently
pending, or which may be brought in the future against the Company by a third party or by or on behalf of the
Company against any third party, whether before a state or federal court, any state or federal government agency, or
a mediator or arbitrator. Executive’s full cooperation in connection with such claims or actions shall include, but not
be limited to, being available to meet with the Company’s counsel, at reasonable times and locations designated by
the Company and reasonably agreeable to Executive, to investigate or prepare the
5
Company’s claims or defenses, to prepare for trial or discovery or an administrative hearing, mediation, arbitration
or other proceeding, to provide any relevant information in his possession, and to act as a witness when requested by
the Company. The Company will reimburse Executive for all reasonable and documented out of pocket costs that he
incurs to comply with this paragraph. Executive further agrees that, to the extent permitted by law, he will notify the
Company promptly in the event that he is served with a subpoena (other than a subpoena issued by a government
agency), or in the event that he is asked to provide a third party (other than a government agency) with information
concerning any actual or potential complaint or claim against the Company.
11. Amendment and Waiver – This Agreement, upon the Agreement Effective Date, shall be binding upon the Parties
and may not be modified in any manner, except by an instrument in writing of concurrent or subsequent date signed
by duly authorized representatives of the Parties. This Agreement is binding upon and shall inure to the benefit of
the Parties and their respective agents, assigns, heirs, executors/administrators/personal representatives, and
successors. No delay or omission by the Company in exercising any right under this Agreement shall operate as a
waiver of that or any other right. A waiver or consent given by either Party on any one occasion shall be effective
only in that instance and shall not be construed as a bar to or waiver of any right on any other occasion.
12. Validity – Should any provision of this Agreement be declared or be determined by any court of competent
jurisdiction to be illegal or invalid, the validity of the remaining parts, terms or provisions shall not be affected
thereby and said illegal or invalid part, term or provision shall be deemed not to be a part of this Agreement.
13. Nature of Agreement – Both Parties understand and agree that this Agreement is a transition and separation
agreement and does not constitute an admission of liability or wrongdoing on the part of the Company or Executive.
14. Time for Consideration and Revocation; Acknowledgements – Executive acknowledges that he was initially
presented with this Agreement on November 19, 2019 (the “Receipt Date”), that he has been given at least twenty-
one (21) days from the Receipt Date to consider the Agreement (such 21-day period, the “Consideration Period”),
and that the Company is hereby advising him to consult with an attorney of his own choosing prior to signing this
Agreement. Executive understands that he may revoke the Agreement for a period of seven (7) days after he signs it
(the “Revocation Period”) by notifying the Company in writing. Executive further understands that this Agreement
shall be of no force or effect unless he signs and returns this Agreement no earlier than the Separation Date but on or
before the final day of the Consideration Period and does not revoke the Agreement during the Revocation Period by
notifying the Company in writing (the day immediately following the expiration of such Revocation Period, the
“Agreement Effective Date”). In the event Executive executes this Agreement within fewer than twenty-one (21)
days after the Receipt Date, he acknowledges that such decision is entirely voluntary and that he has had the
opportunity to consider such Agreement until the end of the twenty-one (21) day period. Executive further
acknowledges and agrees that any changes made to this Agreement following his initial receipt of this Agreement on
the Receipt Date, whether material or immaterial, shall not re-start or affect in any manner the Consideration
Period. Executive understands and agrees that by entering into this Agreement, he is waiving any and all rights or
claims he might have under the Age Discrimination in Employment Act, as amended by the Older Workers Benefit
Protection Act, and that he has received consideration beyond that to which he was previously entitled.
15. Voluntary Assent – Executive affirms that no other promises or agreements of any kind have been made to or with
Executive by any person or entity whatsoever to cause him to sign this Agreement,
6
and that he fully understands the meaning and intent of this Agreement and that he has been represented by counsel
of his own choosing. Executive further states and represents that he has carefully read this Agreement, understands
the contents herein, freely and voluntarily assents to all of the terms and conditions hereof, and signs his name of his
own free act.
16. Governing Law – This Agreement shall be interpreted and construed by the laws of the Commonwealth of
Massachusetts, without regard to conflict of laws provisions. Each of the Company and Executive hereby
irrevocably submits to and acknowledges and recognizes the exclusive jurisdiction and venue of the courts of the
Commonwealth of Massachusetts, or if appropriate, the United States District Court for the District of
Massachusetts (which courts, for purposes of this Agreement, are the only courts of competent jurisdiction), over
any suit, action or other proceeding arising out of, under or in connection with this Agreement or the subject matter
thereof. Each of the Company and Executive waives any objection to laying venue in any such action or proceeding
in such courts, waives any objection that such courts are an inconvenient forum or do not have jurisdiction over
either party, and agrees that service of process upon such party in any such action or proceeding shall be effective if
such process is given as a notice in accordance with the terms of this Agreement.
17. Entire Agreement – This Agreement contains and constitutes the entire understanding and agreement between the
Parties hereto with respect to Executive’s separation from the Company, separation benefits and the settlement of
claims against the Company, and cancels all previous oral and written negotiations, agreements, commitments and
writings in connection therewith; provided, however, for the avoidance of doubt, that nothing in this Section 17
shall modify, cancel or supersede (a) Executive’s obligations set forth in the Surviving Sections of the Employment
Agreement or Sections 4 and 5 above or (b) those equity-related agreements pertaining to the Vested Portion of the
2019 Option (as described in Section 2(c)).
18. Tax Acknowledgement – In connection with the Separation Benefits provided to Executive pursuant to this
Agreement, the Company shall withhold and remit to the tax authorities the amounts required under applicable law,
and Executive shall be responsible for all applicable taxes owed by him with respect to such Separation Benefits
under applicable law. Executive acknowledges that he is not relying upon the advice or representation of the
Company with respect to the tax treatment of any of the Separation Benefits set forth in this Agreement. Executive
further acknowledges and agrees that the Company is not making any representations or warranties to him and shall
have no liability to him or any other person if any provisions of or payments and benefits provided under this
Agreement are determined to constitute deferred compensation subject to Section 409A but not to satisfy an
exemption from, or the conditions of, that section.
19. Counterparts – This Agreement may be executed in several counterparts, each of which shall be deemed to be an
original, but all of which together will constitute one and the same Agreement. Facsimile and PDF signatures shall
be deemed to be of equal force and effect as originals.
[Remainder of page intentionally left blank]
7
IN WITNESS WHEREOF, the Parties have set their hands and seals to this Agreement as of the date(s) written below.
OCULAR THERAPEUTIX, INC.
/s/ Antony Mattessich
By:
Name: Antony Mattessich
Title:
CEO
Date: December 3, 2019
I hereby agree to the terms and conditions set forth above. I have been given at least twenty-one (21) days to
consider this Agreement, and I have chosen to execute this on the date below. I intend that this Agreement will
become a binding agreement between me and the Company if I do not revoke my acceptance in writing to the
Company within seven (7) days following the date below and I understand that my receipt of the Separation Benefits
described herein is contingent upon my non-revocation of this Agreement.
Daniel Bollag
/s/ Daniel Bollag
Date: December 2, 2019
Ocular Therapeutix Europe B.V.
Jurisdiction of Incorporation or Organization
The Netherlands
Subsidiaries of Ocular Therapeutix, Inc.
Exhibit 21.1
CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM
We hereby consent to the incorporation by reference in the Registration Statements on Form S-3 (Nos. 333-229085
and 333-230659) and Form S-8 (Nos. 333-198240, 333-202886, 333-210059, 333-216622, 333-223513 and 333-
230126) of Ocular Therapeutix, Inc. of our report dated March 12, 2020 relating to the financial statements and the
effectiveness of internal control over financial reporting, which appears in this Form 10‑K.
Exhibit 23.1
/s/PricewaterhouseCoopers LLP
Boston, Massachusetts
March 12, 2020
Exhibit 31.1
CERTIFICATIONS
I, Antony Mattessich, certify that:
1. I have reviewed this Annual Report on Form 10-K of Ocular Therapeutix, Inc.;
2. Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a
material fact necessary to make the statements made, in light of the circumstances under which such statements were made,
not misleading with respect to the period covered by this report;
3. Based on my knowledge, the financial statements, and other financial information included in this report, fairly
present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and for,
the periods presented in this report;
4. The registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls
and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting
(as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:
a) Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be
designed under our supervision, to ensure that material information relating to the registrant, including its
consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which
this report is being prepared;
b) Designed such internal control over financial reporting, or caused such internal control over financial
reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial
reporting and the preparation of financial statements for external purposes in accordance with generally accepted
accounting principles;
c) Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report
our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered
by this report based on such evaluation; and
d) Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred
during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report)
that has materially affected, or is reasonably likely to materially affect, the registrant’s internal control over financial
reporting; and
5. The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal
control over financial reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or
persons performing the equivalent functions):
a) All significant deficiencies and material weaknesses in the design or operation of internal control over
financial reporting which are reasonably likely to adversely affect the registrant’s ability to record, process,
summarize and report financial information; and
b) Any fraud, whether or not material, that involves management or other employees who have a significant
role in the registrant’s internal control over financial reporting.
Date: March 12, 2020
By: /s/ Antony Mattessich
Antony Mattessich
President and Chief Executive Officer
(Principal Executive Officer)
Exhibit 31.2
CERTIFICATIONS
I, Donald Notman, certify that:
1. I have reviewed this Annual Report on Form 10-K of Ocular Therapeutix, Inc.;
2. Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a
material fact necessary to make the statements made, in light of the circumstances under which such statements were made,
not misleading with respect to the period covered by this report;
3. Based on my knowledge, the financial statements, and other financial information included in this report, fairly
present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and for,
the periods presented in this report;
4. The registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls
and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting
(as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:
a) Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be
designed under our supervision, to ensure that material information relating to the registrant, including its
consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which
this report is being prepared;
b) Designed such internal control over financial reporting, or caused such internal control over financial
reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial
reporting and the preparation of financial statements for external purposes in accordance with generally accepted
accounting principles;
c) Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report
our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered
by this report based on such evaluation; and
d) Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred
during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report)
that has materially affected, or is reasonably likely to materially affect, the registrant’s internal control over financial
reporting; and
5. The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal
control over financial reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or
persons performing the equivalent functions):
a) All significant deficiencies and material weaknesses in the design or operation of internal control over
financial reporting which are reasonably likely to adversely affect the registrant’s ability to record, process,
summarize and report financial information; and
b) Any fraud, whether or not material, that involves management or other employees who have a significant
role in the registrant’s internal control over financial reporting.
Date: March 12, 2020
By:
/s/ Donald Notman
Donald Notman
Chief Financial Officer
(Principal Financial and Accounting Officer)
CERTIFICATION PURSUANT TO 18 U.S.C. SECTION 1350,
AS ADOPTED PURSUANT TO
SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002
Exhibit 32.1
In connection with the Annual Report on Form 10-K of Ocular Therapeutix, Inc. (the “Company”) for the period
ended December 31, 2019 as filed with the Securities and Exchange Commission on the date hereof (the “Report”), the
undersigned, Antony Mattessich, President and Chief Executive Officer of the Company, hereby certifies, pursuant to 18
U.S.C. Section 1350, that to his knowledge:
(1) the Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934;
and
(2) the information contained in the Report fairly presents, in all material respects, the financial condition and results
of operations of the Company.
Date: March 12, 2020
By:/s/ Antony Mattessich
Antony Mattessich
President and Chief Executive Officer
(Principal Executive Officer)
CERTIFICATION PURSUANT TO 18 U.S.C. SECTION 1350,
AS ADOPTED PURSUANT TO
SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002
Exhibit 32.2
In connection with the Annual Report on Form 10-K of Ocular Therapeutix, Inc. (the “Company”) for the period
ended December 31, 2019 as filed with the Securities and Exchange Commission on the date hereof (the “Report”), the
undersigned, Donald Notman, Chief Financial Officer of the Company, hereby certifies, pursuant to 18 U.S.C.
Section 1350, that to his knowledge:
(1) the Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934;
and
(2) the information contained in the Report fairly presents, in all material respects, the financial condition and results
of operations of the Company.
Date: March 12, 2020
By:/s/ Donald Notman
Donald Notman
Chief Financial Officer
(Principal Financial and Accounting Officer)