Posterior Segment Company Showcase - Ocular Therapeutix at OIS@AAO 2016.
Presenter:
Amar Sawhney, PhD, President, CEO & Chairman
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2. Forward looking statements
2
Any statements in this presentation about future expectations, plans and prospects for the Company, including
statements about the potential benefits and future operation of the collaboration with Regeneron, including any
potential future payments thereunder, the ongoing development of the Company’s sustained release hydrogel depot
technology, the development and regulatory status of the Company’s other product candidates, such as the Company’s
expectations and plans regarding regulatory submissions for and the timing and conduct of clinical trials of DEXTENZA™
for post-surgical ocular inflammation and pain, including our expectations regarding the NDA filed with the FDA,
DEXTENZA for the treatment of allergic conjunctivitis, DEXTENZA for dry eye disease and OTX-TP for the treatment of
glaucoma and ocular hypertension, the potential utility of any of the Company’s product candidates, potential
commercialization of the Company’s product candidates, the sufficiency of the Company’s cash resources 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,
constitute forward-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 of various important
factors. Such forward-looking statements involve substantial risks and uncertainties that could cause the Company’s
clinical development programs, future results, performance or achievements to differ significantly from those expressed
or implied by the forward-looking statements. Such risks and uncertainties include, among others, those related to the
timing and costs involved in commercializing ReSure® Sealant or any product candidate that receives regulatory approval,
the initiation and conduct of clinical trials, availability of data from clinical trials and expectations for regulatory
submissions and approvals, the Company’s scientific approach and general development progress, the availability or
commercial potential of the Company’s product candidates, the sufficiency of cash resources and need for additional
financing or other actions and other factors discussed in the “Risk Factors” section contained in the Company’s quarterly
and annual reports on file with the Securities and Exchange Commission. In addition, the forward-looking statements
included in this presentation represent the Company’s views as of the date of this presentation. The Company anticipates
that subsequent events and developments will cause the Company’s views to change. However, while the Company may
elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any
obligation to do so. These forward-looking statements should not be relied upon as representing the Company’s views as
of any date subsequent to the date of this presentation.
3. Intracanalicular Insert
• Extended and tapered delivery for 30 days
• Preservative-free
• Absorbable – no need for removal
Delivery Method
• Non-invasive
• Physician-administered with forceps
DEXTENZA™ (dexamethasone insert)
For Intracanalicular Use
Potential Indication
• Treatment of ocular pain occurring after
ophthalmic surgery
Target Market
• Approximately 5.3 million ocular surgeries in the U.S. in 2015; 27 million worldwide1
One-time insert designed to replace complex
steroid eye drop topical dosing regimen
1 Source: Market Scope 3
4. • DEXTENZA™ (dexamethasone insert) For Intracanalicular Use
– Planned NDA re-submission under discussion with FDA
– Data read-out of Phase 3 study for potential indication
expansion to obtain inflammation by end of Q4, 2016
• OTX-TP (extended release travoprost)
– 1st Phase 3 clinical study enrollment initiated for the
treatment of glaucoma and ocular hypertension
– Potential to be first non-invasive treatment of glaucoma and
ocular hypertension for up to 3 months with one dose
Anterior segment program status
4
6. Regeneron collaboration
6
ANNOUNCED EARLIER TODAY:
BEDFORD, Mass, October 13, 2016 -- Ocular Therapeutix, Inc. (NASDAQ: OCUL)
Regeneron and Ocular Therapeutix will aim to develop a sustained
release formulation of aflibercept (EYLEA®) that is suitable for
advancement into clinical development.
Goal: to advance current standard of care by reducing injection
frequency in the treatment of wet AMD
Global market for anti-VEGF drugs >$7.5 billion per year
7. Dual posterior segment
development strategy
TKIs
Protein
Therapeutics
• Partnership with Regeneron
• Demonstrated pre-clinical:
– Protein stability
– Release profile
– Hydrogel tolerability
Small
Molecule
Drugs
Tyrosine Kinase
Inhibitors (TKIs)
• Pursuing internal development
• Demonstrated pre-clinical:
– PK
– PD
– Hydrogel tolerability
7
8. Ocular Therapeutix
intravitreal depot technology
• Biocompatible with known
anti-angiogenesis drugs and absorbable
• Fine needle delivery
• Little to no visual field impact
• Up to 6-month sustained delivery
Depots to scale
Ocular Therapeutix’s depot
technology has been tested with a
range of anti-angiogenesis drugs
in multiple preclinical models
8
9. • Free floating within the vitreous
• Absorbs after 6-7 months
• Allows for high drug capacity
Protein anti-VEGF depot
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Depot presents a smooth, hydrophilic,
biocompatible surface to tissues
In vivo IR images of depot at 2, 4 and 8 weeks
Depot hydrates and coils
as it exits needle
Depot is soft, lubricious biodegradable hydrogel composed of >50% drug
10. 10
Depot Eye
Inhibition
Leakage score = 1
Control Eye
No Inhibition
Leakage score = 4
Fluorescein
leaking from
vessels
0
1
2
3
4
0 2 4 6 8 10 12 14
LeakageScore
Time (Weeks)
Hydrogel
Protein Depot
Avastin
Bevacizumab depot showed continued inhibition up to
12 weeks vs. < 6 weeks from single human dose of
Avastin (1.25mg) in pre-clinical VEGF Challenge Model.
Continued inhibition
Protein anti-VEGF depot suppressed
vascular leakage for 3 months
Representative FA images
11. 0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 1 2 3 4 5 6
ProteinReleased
Months
Monomer
High MW species
Target 100% release 4-6 months
11
Stable sustained protein
anti-VEGF delivery
Three anti-VEGF agents showed active release
out to 5 months (SEC) in a pre-clinical model
DELIVERY:
Meets 4-6 month target
AGGREGATION:
Highly stable in hydrogel
12. • Fine needle delivery
• Biocompatible, hydrophilic
• Little to no visual field impact
• Absorbs after 6-7 months
TKI depot
12
1 mm
18 mm
Depot is soft and forms
compact depot in situ
Pre-filled ready-to-use applicator
Hydrated depot
13. TKI depot
in vivo ocular tolerability
13
Score Scale
No change
Minimal
Mild
Moderate
Marked
Severe
0
1
2
3
4
5
Vitreous
Inflammation
Retinal, Scleral
Inflammation
Fibrosis around
material
HistologyScore(0-5)
4 weeks
12 weeks
26 weeks
Hydrogel residue
No inflammatory cells
No inflammation at
26 weeks
Tolerability demonstrated at 26 weeks
14. Normal retinal morphology preserved over 26 weeks
TKI depot
retinal tolerability
4 weeks
Drug loaded
12 weeks
Partially released
26 weeks
Mostly absorbed
Normal retinal morphology Normal retinal morphology
Normal retinal morphology
in vivo IR/OCT drug-loaded depot imaging
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15. TKI depot efficacy
in DL-AAA model for AMD
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Pre- injection
(Baseline)
2 weeks
8 weeks
Leakage Leakage
Leakage
Leakage
No Leakage No Leakage
No Leakage
No Leakage
Continuous
leakage model
TKI depotAvastin injection
10 weeks
16. TKI depot
in VEGF challenge model for AMD
16
0
1
2
3
4
1
10
100
1,000
10,000
100,000
0 4 8 12 16 20 24 28 32
FALeakageScore(0-4)
RetinalxIC50
Time (weeks)
Retinal xIC50 FA Score
PK
PD
High sustained concentrations
Continued effect
in vivo PK/PD challenge model over 6-month duration
17. Posterior Segment
• Anti-VEGF protein depots demonstrated:
– in vivo tolerability through 26 weeks in rabbits
– in vivo effect (PD) in VEGF-induced leakage model through 12 weeks
– in vitro sustained release of three (3) anti-VEGFs for 4-6 months
• TKI depot demonstrated to 26 weeks:
– in vivo tolerability
– in vivo high sustained retinal concentration (PK)
– in vivo effect (PD) in DL-AAA and VEGF-induced leakage models
Anterior Segment
• DEXTENZA™ (dexamethasone insert)
– Planned NDA re-submission under discussion with FDA
• OTX-TP (extended release travoprost)
– Phase 3 underway
Ocular Therapeutix
program summary
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As seen in this short animation, the Dextenza depot hydrates and swells on contact with fluid, releasing preservative free dexamethasone steroid medication in a slowly tapered fashion tailored to last 1month, mimicking a standard drop tapering regimen requiring 70 separate drop administrations that need occur with varying and decreasing frequency as the weeks go by. Because the depot is placed by the physician, there is no concern that the patient may be getting too much or too little medication. In fact, the amount of steroid needed to achieve therapeutic effect with Dextenza is only about 7% of what the eye would be exposed to if drops were used for this same course of therapy.
Antibody drugs act to intercept VEGF, PDGF to prevent engagement with their receptors: VEGFR2, PDGFRβ
TKIs inhibit the activity of kinases associated with VEGFR2, PDGFRβ
Ocular Therapeutix technology provides a sustained release vehicle designed to work well with common intravitreal injection practice – and with known anti-angiogenesis drugs
Ocular Therapeutix has recently developed a proprietary technology for a coiling fiber depot that forms a compact shape in situ after ejection from a needle. This is a soft, smooth and lubricious hydrogel, containing embedded drug particles.
We have used a modification of a VEGF angiogenesis induction model in dutch belted rabbits to determine if the anti-angiogenic activity can be sustained beyond the normal Avastin formulation. This model uses repeated challenges at various time points following the single injection of the test article - as long as the rabbits remain protected from VEGF. This particular bevacizumab depot was designed to deliver for 3 months.
We have worked with several antibodies, including anti-angiogenic antibody drugs. The hydrogel has been found to work with a wide molecular weight range from Fab fragments to full antibodies. Aggregation is the first form of protein change seen, in which antibody molecules reversibly join to form mostly dimers, and some trimers. These aggregates are referred to collectively as high molecular weight species. They are not formed from the PEG vehicle. The anti-VEGF molecules we have tested have shown good stability, as evidenced by this low aggregation, which has been minimal and does not result in loss of protein activity.
Ocular Therapeutix has recently developed a proprietary technology for a coiling fiber depot that forms a compact shape in situ after ejection from a needle. This is a soft, smooth and lubricious hydrogel, containing embedded drug particles.