P011643

OIS@ASCRSMay 2016James D. Brandt, M.D.University of California, DavisPrincipal Investigator

The Bimatoprost Ring, ForSight VISION5Brandt disclosures: research funding and travel expenses, ForSight VISION5

Proprietary & Confidential ForSight VISION5 2016

Proprietary & Confidential ForSight VISION5 2016 # 1Good morning. My disclosures are that I have received research funding and travel expenses from ForSight VISION5. I have been the Principal Investigator of this product during Phase 2 and I am not employed by the company.

Case: Patient is Not Adherent to Necessary Medications, Disease Progresses

Source: Real-time Pharmacy Data FeedUC Davis Electronic Medical Record67 year old female with POAG, here for an IOP check, claims religious compliance with her latanoprost & dorzolamide,

Proprietary & Confidential ForSight VISION5 2016 # Let me start by telling you about a recent glaucoma patient whom I knew was high risk. When I looked in our EMR, I see that she has only refilled her latanoprost twice in four months and she has not refilled her dorzolamide eye drops. Although Ive repeatedly emphasized the importance of taking her medications, she has trouble adhering.[ANIMATE] On OCT, I could see damage occurring to the retinal nerve fiber layer, and unfortunately,[ANIMATE] when I saw her last month, she had had a disc hemorrhage. I cant help but think that if she had been using her medications reliably, she might have had a better outcome.2

Patients Dont, Cant & Wont Take Their Eye Drops,Leading to Preventable Vision LossOnly 37% of patients had refilled their initially prescribed medicationat 3 years.Approximately one third of [patients] could not get a drop onto the eye.Patients who were less than 80% adherentwere significantly more likely to have worse [visual] defect severity.In the 4-year data, 85% of patients were not persistently adherent.*Medication Possession Ratio (MPR) Adherence Rate

Proprietary & Confidential ForSight VISION5 2016 # This patient is not alone. If we look at the literature, over a 3 to 4 year period, 60 to 85% of patients are not persistent in taking medication.Of those who refill their prescriptions, about a third of them have physical challenges getting the drop into their eye.

Of course, if a patient is not taking his or her medication, that patient is significantly more likely to lose vision.3

Therapies that Solve Nonadherence Must Balance Risk-Benefit Based on the Patients NeedsAdvanced Disease: Will trade off some safety for efficacyEarly Disease: Safety Must Be Highest PriorityThe Risk:Benefit balance must be appropriate for the treated populationEfficacy & DurationTolerability(patient acceptance)Ease of UsePersistence(patient replaceable)ReversibilityConsistency of EffectSafety

Proprietary & Confidential ForSight VISION5 2016 # Efficacy and duration are critical parameters for a sustained release product. These must be balanced with the patients experience, and most importantly with safety.

Glaucoma is a slowly-progressive disease. For a patient who already has substantial visual field loss, it makes sense to accept a modest safety penalty to achieve higher efficacy and duration of action. For a patient with early disease or ocular hypertension, safety must be the highest priority.

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A Range of Products to Treat Every Patient:Complementary Choices for 4 Million USA Patients1Percentage of Patients calculated based on Leerink Data (Jan. 2015)HighSeverity (13%)OHT/Low Severity (64%)ModerateSeverity (23%)Low Severity GlaucomaHigh Severity GlaucomaNon-AdherentAdherent% Patients

Proprietary & Confidential ForSight VISION5 2016 # We already select treatment types based on a patients disease severity.[ANIMATE] Adherence rates should also influence which product has the Safety, Efficacy, and Human Factors for each Patient.5

A Range of Products to Treat Every Patient:Complementary Choices for 4 Million USA Patients

Low Severity GlaucomaHigh Severity GlaucomaNon-AdherentAdherent

Proprietary & Confidential ForSight VISION5 2016 # For example, monotherapy eye drops work well in early stage patients who take them reliably. The Bimatoprost Ring has the safety and efficacy to treat the one million American patients who are nonadherent and Lower Risk and have No Solution Today.6

A Range of Products to Treat Every Patient:Complementary Choices for 4 Million USA Patients

Low Severity GlaucomaHigh Severity GlaucomaNon-AdherentAdherent

Proprietary & Confidential ForSight VISION5 2016 # Lets focus on solutions for the Non-Adherent patients with Early Stage Glaucoma.7

The Bimatoprost Ring Addresses NonadherenceFilmed at the Sall Research Medical Center; Artesia, CA

Proprietary & Confidential ForSight VISION5 2016 # The Bimatoprost Ring is designed to address these patients who dont get their medications, and it has been has been studied in Phase 2 clinical trials. After the Ring is placed under the upper lid into the fornix, then the ophthalmologist or optometrist places the Ring under the lower lid. The ring elutes bimatoprost continuously and is replaced every six months at the regular office visit. Before I get into the clinical results of the Ring, let me explain how a product would need to perform to meet the clinical need.8

Getting Medication to Nonadherent Ocular Hypertensives & Lower-Risk Patients Would Save SightReducing IOP by target of 20% led to 60% decrease in relative risk of developing Open Angle Glaucoma in OHT Patients

Proprietary & Confidential ForSight VISION5 2016 # How much IOP-lowering is needed to limit disease progression in these Lower Risk patients? In the OHTS Study, we found that lowering the intraocular pressure by 20% decreased the relative risk of developing open angle glaucoma by 60% among carefully defined Ocular Hypertension patients, which is the largest group of patients on the glaucoma spectrum. At this efficacy level, we could prevent many patients from developing substantial vision loss.9

Consistent Performance : >300 Patients Treated,9 Clinical Trials, Longest Duration of Clinical DataTopical, Comfortable (90%), Well-retained (90% at 6 months)Durable EfficacyOne ring provides 4 to 6 mmHg IOP reduction for 6 months1Safety & BenefitsExcellent safety profileRegulatory pathway: NDA in 2019Patient AcceptanceCustomer Preference85% of patients recommend Ring280% of doctors prefer Ring to drops3FutureValidated Platform for Fixed Combination Glaucoma, Allergy, Dry Eye, Other Pipeline

1At T0, FSV5-002 & -004; 2Study 20150706; 3GLG Survey

Proprietary & Confidential ForSight VISION5 2016 # Now that Ive explained what is needed, let me show you what weve measured in clinical studies of the Bimatoprost Ring. More than 300 patients have participated in Phase 1 and 2 studies.Patients like that the Ring is non-invasive, comfortable, and easy to retain.Lower-risk patients typically see their ophthalmologist only twice a year, and one ring provides clinically relevant IOP-lowering for six months, so that patients do not need to alter their visit schedule.Product safety has been excellent, and both patients and physicians like the Ring.I am also excited about the opportunity to use the Ring platform for other indications. Notably, the company is running a Phase 1 study for a Fixed Combination Bimatoprost-Timolol ring.10

Phase 2 Clinical ResultsDiurnal IOP:Bimatoprost Ring IOP through 13 monthsTwo Cycles of Rings for 6 or 7 Months per Cycle:IOP Reduction (T0): 4-6 mmHg over 13 month treatment cycle89% of Subjects retained Rings without Assistance for the First 6 months, and 97% in the Second Cycle of 7 months

91% 88% 83%

Rescue therapy IOPs censoredNotRescued, % : 100% 100% 100% 100% 100% 100% 100%Randomized, Controlled Efficacy & Safety StudyOpen-Label Safety Extension Study

Proprietary & Confidential ForSight VISION5 2016 # These data from two consecutive Phase 2 studies show the reduction in IOP in patients who wore rings for up to 13 continuous months. To our knowledge, no other company has presented sustained release data for a glaucoma product of more than 6 months of continual use.

On the left-hand side of the graphic, patients started in a randomized controlled study, and the bimatoprost cohort data are shown here. During that study, these patients had a 4-6 mmHg reduction in IOP at peak (T0). The full data from this trial were recently published in Ophthalmology.

At the end of six months, patients who elected to enter the Open-Label Extension Study received new Rings in each eye. This study was primarily conducted as a safety study for regulatory purposes and efficacy endpoints were secondary. This study demonstrated continued safety of the Ring and we observed sustained IOP reduction for up to 13 months in these patients. We recently presented more detailed data from this study at American Glaucoma Societys annual meeting. 11

Safety:Treatment Emergent Adverse Events (TEAEs)Day 0 through Month 6* for Bimatoprost RingBimatoprost Ring was safe and well-toleratedMost Ocular AEs were transitory and resolved without sequelaeBimatoprostN=64Subjects with any Ocular TEAE29 (45.3%)Ocular TEAEs 5%Eye discharge10 (15.6%)Conjunctival hyperemia9 (14.1%)Punctate keratitis8 (12.5%)Eye pruritus7 (10.9%)Ocular discomfort4 (6.3%)Serious Adverse Events (SAEs)Ocular SAE0

*FSV5-002 final results of full cohort. Corresponds to period before patients entered optional extension study.

Proprietary & Confidential ForSight VISION5 2016 # Adverse events noted during the clinical trial for the first six month period were consistent with bimatoprost exposure. We encountered no unanticipated or unexpected safety issues during the initial six-month trial. The safety data from the extension study through 13 months were consistent with this first study period.

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The Ring: SummaryBimatoprost Ring:Clinically Relevant IOP ReductionSafe & Well-toleratedExcellent Retention & ComfortPhase 3 Trials Soon

Pipeline OpportunitiesA Solution Where there is Currently None

Proprietary & Confidential ForSight VISION5 2016 # In summary, we showed that Bimatoprost Rings can achieve clinically-relevant sustained reduction in IOP when used for over a year. The Ring is safe and was tolerated easily by patients. The drug safety profile is consistent with bimatoprost exposure. The Bimatoprost Ring aligns well with the needs of the one million Americans who are nonadherent, early stage patients. Data show they would be likely to achieve consistent, safe IOPs with this product.FDA has provided clear Phase 3 guidance and the company is poised to start clinical trials soon.I am excited not only by the Bimatoprost Ring, but also by the opportunity to use the Ring as a platform for delivering other drugs. Because the Ring has sufficient volume to fit two drugs on board, ForSight VISION5 is conducting an early-stage study of a Fixed Combination ring containing both Bimatoprost and Timolol to expand the therapeutic category. The company has also formulated Rings for Dry Eye and Allergy.

Thank you.

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