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Transcript of Ocular
OIS @ AAO
November 12, 2015
Amar Sawhney, Ph.D., President and CEO
Transforming ophthalmic care withsustained therapies
Forward Looking Statements
Any statements in this presentation about future expectations, plans and prospects for the Company,including statements about the advancement and development of the Company’s product candidates, thetiming and conduct of the Company’s clinical trials, the Company’s plans for regulatory submissions, thepotential utility of the Company’s product candidates and other statements containing the words"anticipate," "believe," "estimate," "expect," "intend", "goal," "may", "might," "plan," "predict," "project,""target," "potential," "will," "would," "could," "should," "continue," and similar expressions, constituteforward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995.Actual results may differ materially from those indicated by such forward-looking statements as a result ofvarious important factors. Such forward-looking statements involve substantial risks and uncertainties thatcould cause the Company’s clinical development programs, future results, performance or achievements todiffer significantly from those expressed or implied by the forward-looking statements. Such risks anduncertainties include, among others, those related to the timing and costs involved in commercializingReSure® Sealant, the initiation and conduct of clinical trials, availability of data from clinical trials andexpectations for regulatory submissions and approvals, the Company’s scientific approach and generaldevelopment progress, the availability or commercial potential of the Company’s product candidates, thesufficiency of cash resources and need for additional financing or other actions and other factors discussedin the “Risk Factors” section contained in the Company’s quarterly and annual reports on file with theSecurities and Exchange Commission. In addition, the forward-looking statements included in this pressrelease represent the Company’s views as of the date of this release. The Company anticipates thatsubsequent events and developments will cause the Company’s views to change. However, while theCompany may elect to update these forward-looking statements at some point in the future, the Companyspecifically disclaims any obligation to do so. These forward-looking statements should not be relied uponas representing the Company’s views as of any date subsequent to the date of this release.
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Products and Pipeline
Hydrogel Sealant
Anterior Segment Sustained Release
Therapies
Posterior Segment Sustained Release
Injections
Drug-eluting punctum plugs are investigational new drugs and not commercially available in the United States or other geographies.
Transforming ophthalmic care with sustained therapies.
Program and Pipeline Progress
Near-term Milestones Announcedat AAO@OIS 2014
Progress Made in 1 year
Glaucoma • Initiate enrollment for Phase 2b trialfor OTX-TP to treat glaucoma
• Study complete – topline results reported• Plans for Phase 3 underway
Allergy • Phase 2 results for OTX-DP in allergic conjunctivitis
• Results reported in Phase 2• Completed first Phase 3 and reported topline
results
Post-op • Complete Phase 3a and 3b clinical trials for OTX-DP post-surgical inflammation and pain
• Plan for submission of NDA Q2, 2015
• Two Phase 3 studies completed• Third Phase 3 initiated• NDA submitted for pain indication Q3 2015
Anti-VEGF • Demonstrate feasibility for Anti-VEGF hydrogel depot
• Feasibility demonstrated for protein (Stability, release, tolerability shown)
Implications of sustained release therapy
• Vastly improved compliance leads to more assurance of efficacy and reduced disease progression
– >50% of patients discontinue therapy within 12 months for glaucoma
• No reliance on patient administration or frequent dosing
– Control in the hands of the physician
– Entire course of therapy is assured without errors
– Significantly more convenient
• Low-dose, slow-eluting concentrations minimize “peak dose”-related sideeffects
• Preservative-free medications preserve the ocular surface(1)
Maintain efficacy, improve compliance, better safety profile
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1. Rosin L, Bell N, Clin Ophthalmol 2013:72131–2135
OCUL Clinical Development Approach
Since no currently marketed “front of the eye” sustained therapies exist,adjustments from topical drops clinical trial designs needed:
• Use drugs and mechanisms with known efficacy to reduce development risk
• Conduct Phase 2 trials to titrate study:
– Endpoints and timing of endpoints
– Patient population
– Duration of effect
• Apply learning to design and conduct Phase 3
• Gain initial label and pursue label expansion if appropriate
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DEXTENZA™ For Ocular Pain
Post-Surgical Ocular Pain Phase 2/3a/3b Results ACHIEVED
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Phase 2 Phase 3a Phase 3b
DEXTENZA Placebo DEXTENZA Placebo DEXTENZA Placebo
Absence of Pain at Day8
79.3% 31.0% 76.1% 36.1% 77.5% 58.8%
Statistically significant difference vs. placebo
– Statistically significant and consistent efficacy observed with one-time administration at day 8 in both Phase 3 trials and the Phase 2 trial
– Strong safety profile observed in both studies
• Favorable safety data can be used to support additional indications
– NDA submitted September 2015
DEXTENZA For Allergic Conjunctivitis
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Phase 3 Trial: Mean Ocular Itching Scores at 7 days post-insertion
4
3.5
3
2.5
2
1.5
1
0.5
0
Me
an
Ocu
lar
Itch
ing
Sco
re(0
-4sc
ale
)
OTX-DP (N=35)
Vehicle (N=38)
(p<0.0001) at all post-CAC time points
Pre-CAC 3 5 7
Time (min) Post-CAC
Statistically significant differences (P<0.05) continued at all post-CAC time points at 12-14 days post-insertion and 26-27 days post-insertion
Per FDA guidance, Treatment Success target was to demonstrate:• At least 0.5 units for all 3 post-CAC time points AND• At least 1 unit for majority of post-CAC time points
TREATMENT SUCCESS ACHIEVED
DEXTENZA Label Expansion Strategy
Post-Surgical Ocular Pain
- NDA Filed Q3 2015
Post-Surgical Ocular Inflammation
- Phase 3 trial enrolling
- sNDA expected 2H 2016
Allergic Conjunctivitis
- 1st Phase 3 complete October 2015
- 2nd Phase 3 expected to begin Q4 2015
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Ease of Insertion and Visualization
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Sustained Release Travoprost
(OTX-TP) for Glaucoma
Phase 2a and 2b Trials Showed Consistent Effect
Average Change from Baseline 2 (mmHg)
Phase 2a results Phase 2b Results
-5.3 -5.6
Post-hoc Analysis• Results shown with 5-week washout as baseline• Monotherapy patients only• Does NOT account for:
– travoprost washout in treatment group– timolol enhancement in placebo group
8:00 am results
Day ITT population
Post-hoc analysis Baseline 2, no multi-drug
OTX-TP + saline (n=33)
Placebo + Timolol (n=39)
OTX-TP + saline (n=31)
Placebo + Timolol (n=33)
30 -4.5 -6.6 -4.9 -6.2
60 -4.8 -6.4 -5.3 -6.2
90 -5.2 -7.3 -5.7 -7.2
Average -5.1 -7.0 -5.6 -6.7
Difference -1.9 -1.1
ITT Analysis• Results shown with average of week 4 and 5
washout as baseline• Confounding factors identified
– 4-week washout– multi-drug patients– travoprost washout in treatment group– timolol enhancement in placebo group
Sustained Release Travoprost
(OTX-TP) for Glaucoma
Safety
Depot visualization by patient possible
Improved Retention overPhase 2a
Day Phase 2a Phase 2b
60 71% 91%
75 51% 88%
90 37% 48%
• No SAE• No hyperemia change from baseline• Safety consistent with results from phase 2a
• Accurate correlation between physician and patient observations
Phase 2a and 2b Clinical Trials (cont’d)
Dry Eye Clinical Development
and Research
100
1000
10000
100000
0 2 4 8 10 12
Tea
rF
luid
Co
nce
ntr
ati
on
(ng
/m
L)
6
Weeks
Cyclosporine (Restasis1) drops 1 hour
Cyclosporine (Restasis1) drops 12 hours
10T-cell activation inhibition IC 2
50
1
OTX-CP Depot
Beagle Tear Fluid Results
1. Restasis is a trademark of Allergan,Inc.2. Umland, et al. (1999). American Journal of Respiratory Cell and Molecular Biology 20,481–492.
• Clinical Development: Exploratory Phase 2 DEXTENZA Inflammatory Dry Eye study
• Topline data expected 4Q ’15
• Research: Cyclosporine pre-clinical study results
• Single administration intracanalicular depot with 3-month release
Back of the Eye Program – Parallel Path
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• Goals of feasibility collaborations ACHIEVED• Protein stability• Tolerability
• Release profile
• Seek partnership for anti-VEGF drug
Protein Therapeutics
• Pursue internal development
• Initial PK/PD demonstrated
Small Molecule Drugs
Tyrosine Kinase Inhibitors (TKIs)
Posterior Segment Sustained Release
Injections
TKI candidate
• Slow dissolving - targeting 6 month delivery
• Highly potent and selective
– VEGFR-2, PDGFR-β, TIE-2
• In preclinical studies (rabbit)
– PD and PK (in excess of 1000x IC50 levels)
– Good tolerability
Placebo
No Inhibition- Leakage Inhibition-No Leakage
Inhibition of pre-clinical VEGF-induced leakage
OCUL Injection with TKI
Future Potential Milestones
• Report topline efficacy results for the Phase 2 exploratory trial of DEXTENZA for the treatment of inflammatory dry eye in 4Q 2015
• Conduct 2nd Phase 3 trial for allergic conjunctivitis
• Finalize clinical trial design for 1st Phase 3 OTX-TP trial
• Gain NDA approval of DEXTENZA™ for post-surgical pain
• File NDA supplement for allergic conjunctivitis
• File NDA supplement for post-surgical inflammation
• Complete pre-clinical development for TKI program
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