Public Device & Biopharma Ophthalmology Company Showcase - Inotek Pharmaceuticals at OIS@AAO 2016.
Presenter:
David Southwell, President & CEO
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2. Forward Looking Statements
This presentation contains forward-looking statements that are based on
our management’s belief and assumptions and on information currently
available to our management. Although we believe that the expectations
reflected in these forward-looking statements are reasonable, these
statements relate to future events or our future financial performance,
and involve known and unknown risks, uncertainties and other factors
that may cause our actual results, levels of activity, performance or
achievements to be materially different from any future results, levels of
activity, performance or achievements expressed or implied by these
forward-looking statements.
In some cases, you can identify forward-looking statements by
terminology such as “may,” “might,” “could,” “would,” “will,” “should,”
“expect,” “intend,” “plan,” “anticipate,” “believe,” “estimate,” “predict,”
“project,” “target,” “potential,” “continue” or the negative of these
terms or other comparable terminology. These statements are only
predictions. You should not place undue reliance on forward-looking
statements because they involve known and unknown risks,
uncertainties and other factors, which are, in some cases, beyond our
control and which could materially affect results. If one or more of these
risks or uncertainties occur, or if our underlying assumptions prove to be
incorrect, actual events or results may vary significantly from those
implied or projected by the forward-looking statements. No forward-
looking statement is a guarantee of future performance.
2
The forward-looking statements in this presentation represent our views
as of the date of this presentation. We anticipate that subsequent events
and developments will cause our views to change. However, while we
may elect to update these forward-looking statements at some point in
the future, we have no current intention of doing so except to the extent
required by applicable law. You should therefore not rely on these
forward-looking statements as representing our views as of any date
subsequent to the date of this presentation.
All trademarks and registered trademarks are the property of their
respective owners.
Trabodenoson is an investigational compound and is not yet approved
by the FDA for any indication.
3. Inotek: Transforming Glaucoma Treatment
3
*Source: IMS Health in 2013
First fixed-dose combination trial initiated July 2016
1Schwartz GF & Quigley HA, Survey of Ophthalmology 2008;53: S57-S58.
Phase 1 Monotherapy showed
no dose related side effects
(ocular or systemic) at greater
than Phase 3 doses
Phase 2 Monotherapy showed
clear dose response, good ocular
and systemic safety, ability to dose
QD or BID, additive efficacy to
prostaglandins
First Phase 3 Monotherapy,
MATrX-1, tests QD and BID
doses against placebo.
Results 4Q’16
4. * Per Latanoprost Package Insert
Source: Share data represents total prescriptions for IMS Health in 2013
$2 Billion U.S. Glaucoma Market
4
Unmet Need: Effective QD treatment with minimal side effects
5. Trabodenoson’s Novel Mechanism*
5
• Binds to A1 receptors on
Trabecular Meshwork
• Upregulates MMP-2,
digesting extracellular
matrix proteins that clog
the TM
• Research supporting
trabodenoson’s MOA
presented at the 2016
American Glaucoma
Society
*Increased secretion of MMPs contributes to trabodenoson-induced changes in conventional outflow facility;
DS Albers, CE Crosson, JS Myers, CC Rich, R Baumgartner, and WK McVicar; American Glaucoma Society Annual Meeting, March 2016, Poster #: PO047
6. Phase 1: Good Safety Profile and Tolerable
6
Laties A, et al. J Ocul Pharmacol Therap 2016;00:108. doi:10.1089/jop.2015.0147
No Dose Limiting Toxicity; no dose-related
ocular or systemic side effects; limited
systemic exposure at high doses
7. Phase 2: IOP Statistically Lowered at All
Timepoints on Day 28
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Myers JS, et al. J Ocul Pharmacol Therap 2016;00:1-8. doi:10.1089/jop.2015.0148
Pre-randomization
Post-randomization
FIG. 2.
Mean IOP for the trabodenoson 500 mcg and placebo groups pre-randomization
(Day −1) and post-randomization (Days 14, 28, and 29).
8. Placebo
50mcg
100mcg
200mcg
500mcg
0
1
2
3
Day -4 Day -1 Day 1 Day 14 Day 28
Placebo 50mcg 100mcg 200mcg 500mcg
Placebo Run-In Drug Treatment
Randomization
0 = none/trace
1 = mild
2 = moderate
3 = severe
Phase 2 Dose Ranging Trial:
Hyperemia Score Graded (0-3)
8
Hyperemia
scores were
low and
unchanged by
all doses of
trabodenoson
Myers et al., 2016, JOPT, e-pub ahead of print doi:10.1089/jop.2015.0148
9. MATrX-1 Phase 3 Trial Design
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ClinicalTrials.gov Identifier: NCT02565173
Identical population to Phase 2
• IOP ≥24 mmHg
• ~ 300 patients treated for 12 weeks
Three trabodenoson doses
• 1000 mcg QD
• 2000 mcg QD
• 1500 mcg BID
Placebo controlled
• Statistical comparator
Timolol 0.5% BID
• Internal control
• Not part of statistical
comparison
Screening
Period
1 to 14
Days
Washout
Period
1 to 39
Days
Run-in
Period
5 to 9
Days
Observation
Period
7
Days
3 Month Treatment Period
Day 1 to Day 84 AM
Timolol BID OU
Trabodenoson 1500 mcg (4.5%) BID OU
Trabodenoson 2000 mcg (6.0%) QD OU
Placebo BID OU
Day 28* Day 42* Day 84*
Trabodenoson 1000 mcg (3.0%) QD OU
Placebo
BID
No Ocular
Treatment
*Primary endpoint.
10. Phase 2 Fixed-dose Combination Trial of
Trabodenoson and Latanoprost
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GOAL: Identify optimal benefit/
risk profile for confirmatory trials
ClinicalTrials.gov Identifier: NCT 02829996
LP 0.005% LP 0.005%
LP 0.0025% LP 0.0025%
Trabo 3.0% Trabo 3.0%
LP 0.005% LP 0.005%
Trabo 6.0% Trabo 6.0%
LP 0.0025% LP 0.0025%
Screening
Period
1 to 14
Days
Washout
Period
1 to 39
Days
Run-in
Period
5 to 9
Days
Observation
Period
7 Days
2 Month Active Treatment (QD)
Masked 4 Week AM and PM periods
Day 1 to Day 56
4 Weeks 4 Weeks
Trabo 6.0% Trabo 6.0%
LP 0.005% LP 0.005%
Placebo
Run-In
No Ocular
Treatment
• N ~165 subjects
• Diagnosis of ocular hypertension
(OHT) or Primary Open-Angle
Glaucoma (POAG)
• Baseline IOP ≥25 and ≤34 mmHg
• Trabodenoson doses: 3% and 6%
• Latanoprost doses: 0.005%
(commercial dose) and 0.0025%
• Subjects assigned 4 wks of AM
and 4 wks of PM dosing in a
masked manner
Data Readout: 2H 2017
11. Inotek Value Drivers
End-of Phase 2
Meeting
Phase 3 MATrX-1
Initiation
Presented at
Glaucoma 360
Presented Preclinical
Research at AGS
Presented at GTC BIO
ARVO Poster
Presentations
Publication of Phase
1/2 Clinical Data
Initiated FDC Dose
Ranging Trial
Presenting at OIS
• Top-Line Phase 3
MATrX-1 Results
• Initiation of Phase
3 MATrX-2
• Initiation of
Monotherapy
Long-Term Safety
Trial
• FDC Phase 2 Dose
Ranging Results
• Initiation of FDC
Phase 3 Trial
• Phase 3 MATrX-2
Results
• Monotherapy NDA
Submission
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Hi, my name is David Southwell . .
I’m President and CEO of Inotek Pharmaceuticals
I’m here today to talk about glaucoma, an unmet need in the market
And how our company, Inotek, is taking a new approach to treating glaucoma
We are investigating both elevated IOP and the optic neuropathy that occurs in patients with glaucoma
The glaucoma market is an attractive market-$5.6 billion worldwide.
We haven’t seen innovation in medical therapies for glaucoma since the late 90s.
And, this is a market with very low compliance.
Our compound, Trabodenoson, is an adenosine mimetic that stimulates a natural pathway in the body.
We also demonstrated additive efficacy to the prostaglandin, latanoprost
We’re able to do this based on the safety profile of Trabodenoson.
We’re expecting results in 4Q of this year.
Glaucoma is an attractive market… $2 Billion in the U.S.
We’ve already discussed the two main classes of available glaucoma drugs.
These drugs have insufficient efficacy – in 50% of patients more than 1 is required in the effort to achieve target IOP reductions.
They all come with side effects, including ocular tolerability and in the case of the 2nd line agents, systemic effects that can be serious safety issues in rare cases
Poor tolerability and dosing frequencies of 2 or 3 times daily have a negative impact on patient compliance and thus put patients at risk of progressive vision loss
We need new drugs with efficacy from MOAs complementary to existing drugs. There is an unmet need for a once daily treatment with effective IOP lowering and minimal side effects
Trabo works at the TM, by increasing the metabolism of proteins that can clog the outflow path (the “drain”) and it allows the normal pressure control by the TM to be “reset” to a lower, healthier level.
We have shown in animals the mechanism by which trabodenoson exerts its biological effect.
Trabo binds to A1 receptors on Trabecular Meshwork.
Upregulates MMP-2, digesting extracellular matrix proteins that clog the TM.
This research was just presented at the American Glaucoma Society.
Our Phase 1 results demonstrated Trabodenoson is safe and tolerable
The chart on the left shows the design of the phase 1 trial.
We dosed subjects up to 3200ug in a single eye dose administered BID for 14 days
And up to 6400ug in both eyes (3200ug per eye)
The chart on the right hand side of the slide shows how the systemic exposure to the drug is limited as the ocular dose increases.
We believe this limited exposure helps to explain the complete lack of systemic effect detected in this trial.
The solid green and blue curves seen here are the IOP measurements done at day 28 with the highest dose tested – in blue – and the matching Placebo group – in green.
The hashed grey placebo curve shows the natural circadian changes in IOP over the day, in the placebo group before the study started.
The difference between this curve and the green curve - measured 28 days later at the end of the study – is the placebo response. Our results showed the placebo response to be about 2mm, which is the same as the placebo response well–documented in the literature
To see the IOP improvement over placebo, you need to look at the differences in the matched timepoints between the green and blue curves, statistically. What you see is that our drug, at every single timepoint, consistently lowered IOP relative to placebo.
The endpoint and statistical testing in our ongoing Phase 3 trial is identical to this analysis from our phase 2 study, but will be done at several timepoints – 4, 6 and 12 weeks.
The same subjects (POAG and OHT with IOPs >24 mmHg) in Phase 3, and all elements of the Phase 3 design were agreed to with FDA.
Our Phase 3 program consists of three main trials
The MATrX-1 trial has the same patient population and same statistical comparison as our phase 2 that was highly statistically significant and gives us confidence in the Phase 3 study outcome.
This trial is right on target . .slightly ahead of our initial screening projections
As you know, we had a successful End-of Phase 2 Meeting last year and we started our Phase 3 MATrX-1 trial
This year, we have a busy year.
We’re presenting at many medical congresses and are expecting data from our Phase 3 MATrX-1 trial by the end of the year.