July 2016 Corporate Presentation. DAVID P. SOUTHWELL, President and CEO Cantor Fitzgerald 2 nd Annual Health Care Conference

Transcription

1 July 2016 Corporate Presentation DAVID P. SOUTHWELL, President and CEO Cantor Fitzgerald 2 nd Annual Health Care Conference

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 forwardlooking statement is a guarantee of future performance. 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. 2

3 Inotek: Transforming Glaucoma Treatment Trabodenoson: Novel adenosine mimetic that stimulates a natural pathway Glaucoma: *$5.6 billion worldwide market with low compliance 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 First fixed-dose combination trial to initiate in 2016 Adenosine A 1 activation is neuroprotective in the retina and brain neuroprotective in the back of the eye *Source: IMS Health in Schwartz, Quigley, Survey of Ophthalmology, 2008, in press 2 Gomes et al. 2011, 3 Zhong et al. 2013, 4 Cunha

4 Leadership with History Together David P. Southwell, MBA President & CEO Rudolf Baumgartner, M.D. Chief Medical Officer William McVicar, Ph.D. Chief Scientific Officer Claudine Prowse, Ph.D. VP Strategy Cadmus Rich, M.D., MBA VP Clinical and Medical Affairs 4

5 $2 Billion U.S. Glaucoma Market Unmet Need: Effective QD treatment with minimal side effects GLAUCOMA PRESCRIPTION MARKET SHARE First Line: Prostaglandin Analogs Monotherapy QD Dosing IOP Drop from Baseline: 6 8 mmhg* Ocular Side Effects Red eye (hyperemia) Iris discoloration Blurred vision Darkening of the eyelids Adipose tissue shrinkage Eye pain Latanoprost 31% 51% Travatan Travoprost 10% Lumigan Bimatoprost 10% beta blockers (combo) 14% 49% beta blockers (alone) 14% alpha agonist 10% carbonic anhydrase inhibitor Other 6% 5% Second Line: Adjunctive Agents Monotherapy BID or TID Dosing Ocular and Systemic Side Effects Severe respiratory and cardiac reactions Blurred vision Allergic conjunctivitis Itching (pruritus), burning, stinging * Per Latanoprost Package Insert Source: Share data represents total prescriptions for IMS Health in

6 Probability of Being Treated IOP Elevation Drives Treatment Objective: Normalized Intraocular Pressure (IOP) High Usually Treated >25 mmhg Medium Low Normal IOP mmhg Usually not treated without serious risk factors Suspected Glaucoma >22-25 mmhg Medical treatment based on associated risk factors First Line Monotherapy First Line Second Line Co-Administration or Fixed-Dose Combination Increasing IOP Market Opportunity as First or Second Line First Line: IOP Lowering; Safety/Tolerability = Compliance Second Line: Additive efficacy to latanoprost; Minimal added side effects, QD dosing 6

7 Trabecular Meshwork: The Natural Mechanism for Regulating IOP Natural pressure regulating outflow 70% via trabecular meshwork Trabecular Meshwork 30% Secondary outflow via uveoscleral pathway Aqueous humor production 7

8 Trabodenoson s Novel Mechanism* Mechanism: 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 8

9 From Adenosine to Trabodenoson Trabodenoson Rational Design Trabodenoson is an adenosine mimetic optimized to selectively target the A 1 receptor Developed by medicinal chemists at Inotek 9

10 From Adenosine to Trabodenoson Trabodenoson Rational Design Trabodenoson is an adenosine mimetic optimized to selectively target the A 1 receptor Potency High affinity for A 1 receptor Corneal Penetration Lipid solubility = ocular penetration Selectivity Non-target receptor interactions systematically removed Trabodenoson bound to A 1 receptor Eye Tissue Compatibility High compatibility with sensitive tissues in front of eye Compound A 1 (Ki, nm) A 2a (Ki, nm) A 3 (Ki, nm) Trabodenoson ,

11 Trabodenoson mcg Phase 1: Good Safety Profile and Tolerable Design Subjects Cohort Cohort Cohort Cohort Cohort Cohort Cohort Results No Dose Limiting Toxicity; no doserelated ocular or systemic side effects; limited systemic exposure at high doses , ,600 2,400 3,200 Treatment 14-day BID 14-day BID 14-day BID 14-day BID 14-day BID 14-day BID Escalating SD BID: Twice Daily SD: Single Dose Journal of Ocular Pharmacology and Therapeutics. April 2016, ahead of print. doi: /jop Trial authors; Alan Laties 1, Cadmus C. Rich 2, Randall Stoltz 3, Vernon Humbert 4, Chaim Brickman 2, William McVicar 2, and Rudolf A. Baumgartner 2 Journal of Ocular Pharmacology and Therapeutics. April 2016, ahead of print. doi: /jop Trial authors; Alan Laties 1, Cadmus C. Rich 2, Randall Stoltz 3, Vernon Humbert 4, Chaim Brickman 2, William McVicar 2, and Rudolf A. Baumgartner 2 11

12 No Clinically Significant Safety Signals in Trials to Date Phase 1 Comprehensive Safety Assessments included: Continuous cardiac monitor 12-lead ECG Orthostatic BP and heart rate Vital signs Blood cardiac troponin I Spirometry FEV 1 Blood pharmacokinetic sampling Urine pharmacokinetic sampling Renal biomarkers Karolinska sleepiness scale Adverse events Physical examinations Clinical laboratory assessments Toxicology screen Ophthalmology assessments Slit lamp exam/hyperemia Fundus exam Best-corrected visual acuity Intraocular pressure 12

13 IOP Drop SEM (mmhg) Monotherapy Phase 2 Results Dose-Dependent IOP Reduction, Increases with Treatment Duration Day 14 Day mcg 100 mcg 200 mcg 500 mcg 500 mcg * * * ** p=0.016 IOP Drop from Diurnal Baseline on Day -1 IOP Drop from Study Baseline on Day 1 * * *Indicates comparison to placebo group; p-value <0.05 ** p-value refers to Signed Rank test Day 28 versus Day 14 Journal of Ocular Pharmacology and Therapeutics. March 2016, ahead of print. doi: /jop Trial authors; Jonathan S. Myers 1, Kenneth N. Sall 2, Harvey DuBiner 3, Natanya Slomowitz 4, William McVicar 4, Cadmus C. Rich 4 and Rudolf A. Baumgartner 4 13

14 Phase 2: IOP Statistically Lowered at All Timepoints on Day 28 FIG. 2. Mean IOP for the trabodenoson 500 mcg and placebo groups before randomization (Day 1) and after randomization (Days 14, 28, and 29). Published in Journal of Ocular Pharmacology and Therapeutics. Ahead of Print DOI: /jop

15 MATrX-1 Phase 3 Trial Design Trabodenoson 1000 mcg (3.0%) QD OU Identical population to Phase 2 IOP >24 mmhg Trabodenoson 2000 mcg (6.0%) QD OU ~ 360 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 Placebo BID Run-in Period 5 to 9 Days Trabodenoson 1500 mcg (4.5%) BID OU Timolol BID OU Placebo BID OU Day 28* Day 42* Day 84* 3 Month Treatment Period Day 1 to Day 84 AM No Ocular Treatment Observation Period 7 Days ClinicalTrials.gov Identifier: NCT *Endpoint. 15

16 Additional Phase 3 Trials MATrX-2 Similar design as MATrX-1 Optimized dose to be selected from MATrX-1 Large sample size Long-Term Safety Trial Primary endpoint = safety Greater IOP range At least 300 patients treated for at least 6 months, and 100 patients for at least 12 months Phase 3 Program Optimized for Success: Similar patient population to Phase 2 Primary endpoint versus placebo Higher doses than in Phase 2 Below the maximum dose tested in Phase 1 16

17 Hyperemia Rate (%) IOP Drop from BL (mmhg) Path to Approval for Fixed-Dose Combination (FDC) U.S. Regulatory Requirements: Each individual active component adds to efficacy FDA determination of FDC benefit/risk profile Objectives: Phase 2 optimizes dose for Phase 3 Differentiated on efficacy and safety Latanoprost efficacy and hyperemia are dose-related Latanoprost IOP Reduction Latanoprost Hyperemia Raber, Mandema, Li, Nickens, 2015, J. Ocul. Pharmacol. Ther. 17

18 FDC Trial Progress Phase 2 trial of trabodenoson co-administered with latanoprost completed Additive efficacy to latanoprost in PGA poor-responders Phase 2 dose-ranging trial to begin in 2016 top line data in 2017 Determine optimal combination of trabodenoson and latanoprost Phase 3 program to commence following Phase 2 18

19 Back of Eye: Potential for Orphan Indications Optic Neuropathies and Degenerative Retinal Diseases Trabodenoson shows potential in treating the back of the eye: Preclinical data support effect: High Pressure Optic Neuropathy Model Eye drops shown to deliver drug to retina in rabbits and monkeys Orphan indications being evaluated: Retinitis Pigmentosa Non-Arteritic Ischemic Optic Neuropathy (NAION) Adenosine receptors in the back of the eye/retina Retinal Layers Nerve fiber layer Ganglion cell layer Inner plexiform layer Inner nuclear layer Outer plexiform layer Outer nuclear layer Photoreceptor layer Pigment epthelium Section through retina Cells Inner limiting membrane Axons at surface of retina passing via optic nerve, chiasm, and tract to lateral geniculate body Ganglion cell Müller cell (supporting glial cell) Bipolar cell Amarcine cell Horizontal cell Rod Cone Pigment cells of choroid A1 A1 Receptors 19

20 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 Initiation of 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 Dose Ranging Results Results of Neuroprotection Clinical PoP Trial Initiation of FDC Phase 3 Trial Phase 3 MATrX-2 Results Monotherapy NDA Submission 20

21 Thank you