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Uveitis
(Macular Edema associated with non-infectious uveitis)

  • Uveitis is a collection of inflammatory conditions affecting the eye.
  • In the U.S. there are approximately 120 cases /100,000 adults. Most patients are aged 20-50 years.1 Overall the prognosis is good with appropriate treatment.
  • Uveitis does not cause mortality but morbidity results from chronic swelling in the retina (macular edema) that leads to damage to the structures of the eye, including the retina and the lens (cataracts) and complications from medications.
  • Macular edema may be found associated with any geographic location of uveitis and is the dominant cause of vision deterioration and potential vision loss in patients with uveitis2.

1Jennifer E. Thorne,  Eric Suhler,  Martha Skup  et  al,  JAMA  Ophthalmol. 2016;134(11):1237-1245. 2 Karim R, Sykakis E, Lightman S, Fraser-Bell S. Interventions for the treatment of uveitic macular edema: a systematic review and meta-analysis. Clin Ophthalmol 2013;7:1109-1144.

Treatment Goal

The goal of treatment is to reduce pain and inflammation and prevent damage to the eye due to inflammation.

Current Treatments

Treatments for uveitis are either systemic or local to the eye, if not both. Most common treatments include corticosteroids and other immunomodulators.

  • Ophthalmic anticholinergics that block nerve impulses to the pupillary sphincter and ciliary muscles, easing pain and photophobia
  • Topical and systemic corticosteroids that decrease inflammation
  • Tumor Necrosis Factor Blockers
  • Sustained-release corticosteroid vitreous implants
  • Immunomodulators (off label use)

Treating Ocular Inflammation

Uveitis Phase 2: DOGWOOD Trial

  • Single suprachoroidal injection of CLS-TA 4.0 mg or 0.8 mg
  • Randomized, controlled, masked, multi-center trial
  • 22 subjects with macular edema associated with non-infectious uveitis
  • Primary endpoint: reduction in retinal thickness at 2 months

Primary Endpoint of Reducing Retinal
Thickness was Successfully Achieved

Reduction in CST1 From Baseline – ITT Population N=17

Primary Endpoint

1CST is the central retinal thickness measured using optical coherence tomography (OCT) 

* One patient was not included in this measurement

Secondary Endpoint of Improving Best Corrected Visual Acuity (BCVA) was Achieved

Best corrected Visual Acuity - ITT Population1

Visual Acuity

1N = 17

2Eylea®, Lucentis®, Ozurdex® Prescribing Information

BCVA and ME Improvements at Month 2

Percent of Patients with BCVA Improvement

BCVA and ME

Macular Edema Outcomes  Percentage
20% reduction in retinal thickness 69%
Retinal thickness ≤ 310 microns 56%

Anterior Chamber (AC) Cells, AC Flare and Vitreous Haze – Reduced From Baseline to Month 2 (4.0 mg group; ITT)

AC cells, AC flare and vitreous haze are signs of inflammation of the eye

  • Each of these signs shows favorable changes from baseline
  • The average in each case shows trend toward improvement; a majority of individual patients either improve or maintain low levels

Phase 1/2 study in non-infectious uvetis (NIU)

Study design

Non-Infectious Uvetis

Open label, multi-center study

  • Subjects with noninfectious uveitis
  • Single suprachoroidal injection of TA
  • 8 subjects received a single unilateral suprachoroidal injection of TA
  • Followed for 26 weeks

Phase 1/2 Study - Change in retinal thickness from baseline

change in retinal thickness

The data shown are descriptive; no imputations have been performed on the data. Information for subjects at a time point is shown for subjects who remain on study medication at time of evaluation

Phase 1/2 Study - Change in retinal thickness from baseline

change in visual acuity

The data shown are descriptive; no imputations have been performed on the data. Information for subjects at a time point is shown for subjects who remain on study medication at time of evaluation

Uveitis Phase 2 & Phase 1/2 Summary

Efficacy Summary

  • Improvements in BCVA observed in patients treated in both trials
  • Statistically significant reduction in retinal thickness in patients treated in the Phase 2 trial
  • Duration of improvement in visual acuity of up to 6 months in Phase 1/2 trial

Safety Summary

  • No serious adverse events related to treatment
  • No adverse events leading to discontinuation
  • No steroid-related increase in IOP
  • Only adverse events related to treatment in more than 5% of dosed patients were cystoid macular edema, blurred or decreased vision, and eye pain

Focused Pipeline of SCS Treatments for Multiple Blinding Eye Disease

Clearside’s Current Programs

Indication Study drug U.S. Est. prevalence Current Status
RVO (Retinal Vein Occlusion) Suprachoroidal CLS-TA with anti- VEGF (Intravitreal Eylea) 2.2 million graphic Phase 3 Initiated H1 2017
Macular Edema associated with non-infectious uveitis (Uveitis) Suprachoroidal CLS-TA (Corticosteroid triamcinolone acetonide) 2.2 m graphic Phase 3 data early 2018
DME (Diabetic Macular Edema) Suprachoroidal CLS-TA alone or with anti-VEGF (Intravitreal Eylea aflibercept) 1.1 m graphic Phase 1/2 data H2 2017

Clearside Collaborations

Indication Study drug U.S. Est. prevalence Current Status
Retinal Vascular Disease Proprietary Compound(s) 1.2m graphic Preclinical
Orphan Diseases Gene Therapy Preclinical

Retinal Vein Occlusion (RVO)

  • Retinal vein occlusion is blockage of the veins that drain the retina.
  • RVO is a common cause of vision loss, affecting 16 million people (5.20 per 1000) world wide.
  • It is the leading cause of blindness from retinal vascular disease after diabetic retinopathy.
  • RVO is most often caused by atherosclerosis and the formation of a blood clot. It can lead to further eye problems including glaucoma and macular edema.

Treatment Goal

The goal of treatment is to reduce morbidity and prevent complications

Current Treatments

Anti-VEGF drugs (first line therapy) or intravitreal corticosteroid implants target macular edema which is responsible for vision loss; anti-VEGF drugs also target abnormal blood vessels which can lead to retinal hemorrhage and neovascular glaucoma.

Treating Ocular Inflammation

Retinal Vein Occlusion Phase 2: Tanzanite Trial

  • Single suprachoroidal injection of CLS-TA plus intravitreal Eylea® versus intravitreal Eylea only in treatment naïve RVO patients
  • 1:1 controlled, randomized, masked, multi-center trial
  • 46 subjects with macular edema associated with Retinal Vein Occlusion
  • Treatment naïve patients randomized to treatment first day and evaluated monthly
  • Objective: reduce number of intravitreal Eylea treatments while maintaining visual acuity improvements
  • Primary endpoint: the number of times patients met the criteria for additional intravitreal Eylea treatments over the three-month trial duration

Eylea is a registered trademark of Regeneron®

60% Fewer Additional Intravitreal Eylea Injections in the Suprachoroidal CLS-TA + Intravitreal Eylea Arm Versus Control Over 3 Months

Number of Additional Intravitreal Eylea Injections

60% Fewer Additional Eylea Injections

69% Fewer Patients Required Additional Eylea® Treatments

69 % fewer patients required additional eylea


1 Based on post-hoc analysis

Suprachoroidal CLS-TA + Intravitreal Eylea resulted in Improved Visual Acuity at Months 1, 2, 3 vs. Intravitreal Eylea Alone

suprachoroidal cls-ta

Suprachoroidal CLS-TA + Intravitreal Eylea Resulted in Sustained Retinal Thickness Reductions at Months 1, 2, 3 vs. Intravitreal Eylea Alone


Sustained Retinal Thickness Reductions

Post-TANZANITE Evaluation: 74% of Patients who Received Combination Therapy Did Not Receive Additional Treatment Through a Minimum Nine Months

Post Tanzanite Evaluation

RVO Phase 2 & Post-TANZANITE Evaluation Summary

Suprachoroidal CLS-TA + Intravitreal Eylea vs. Intravitreal Eylea alone

  • Greater improvement of vision compared with Intravitreal Eylea alone in phase 2 trial
  • Sustained clinical benefit over the 3-month trial period
  • Significantly fewer additional Intravitreal Eylea treatments

Safety Summary

  • No serious adverse events
  • No adverse events leading to discontinuation
  • Only adverse events observed in more than 5% of patients in the suprachoroidal CLS-TA + intravitreal Eylea arm were conjunctival hyperemia, eye pain, ocular hypertension and increased IOP

Extension Study

  • Conducted an extended evaluation to better assess the duration of effect of the combination treatment and the potential to reduce the burden of therapy
  • Patients who completed TANZANITE and did not receive first re-treatment during TANZANITE
  • Patients managed according to treating physician’s discretion without a prospective protocol
  • Records were obtained retrospectively
  • Main efficacy outcome: time to first RVO re-treatment

Focused Pipeline of SCS Treatments for Multiple Blinding Eye Disease

Clearside’s Current Programs

Indication Study drug U.S. Est. prevalence Current Status
RVO (Retinal Vein Occlusion) Suprachoroidal CLS-TA with anti- VEGF (Intravitreal Eylea) 2.2 million graphic Phase 3 Initiated H1 2017
Macular Edema associated with non-infectious uveitis (Uveitis) Suprachoroidal CLS-TA (Corticosteroid triamcinolone acetonide) 2.2 m graphic Phase 3 data early 2018
DME (Diabetic Macular Edema) Suprachoroidal CLS-TA alone or with anti-VEGF (Intravitreal Eylea aflibercept) 1.1 m graphic Phase 1/2 data H2 2017

Clearside Collaborations

Indication Study drug U.S. Est. prevalence Current Status
Retinal Vascular Disease Proprietary Compound(s) 1.2m graphic Preclinical
Orphan Diseases Gene Therapy Preclinical

Diabetic Macular Edema (DME)

Diabetic Macular Edema (DME) is an accumulation of fluid in the macula caused by leaky blood vessels as a consequence of diabetes mellitus. It is defined as retinal thickening within 2 disc diameters of the macula center. DME is the most common complication of Diabetes in patient with Diabetes Retinopathy, affecting more than 150 million people worldwide. It may cause images to appear blurry or wavy and colors that seem “washed out”.

Treatment Goal

Prevention of vision loss is important, visual improvement would be preferable.

Current Treatments

  • Corticosteroid Implants
  • Intravitreal injections corticosteroid Implants
  • Anti-VEGF Therapy used off label
  • Laser treatments or pars plana vitrectomy

Clinical Trial Design

Phase 1/2 Study

  • Single suprachoroidal injection of CLS-TA alone and in combination with intravitreal Eylea
  • 10 treatment naïve subjects and 10 subjects treatment non-naïve
  • Safety and efficacy information will be collected through the entire time period

enrolling patients


Focused Pipeline of SCS Treatments for Multiple Blinding Eye Disease

Clearside’s Current Programs

Indication Study drug U.S. Est. prevalence Current Status
RVO (Retinal Vein Occlusion) Suprachoroidal CLS-TA with anti- VEGF (Intravitreal Eylea) 2.2 million graphic Phase 3 Initiated H1 2017
Macular Edema associated with non-infectious uveitis (Uveitis) Suprachoroidal CLS-TA (Corticosteroid triamcinolone acetonide) 2.2 m graphic Phase 3 data early 2018
DME (Diabetic Macular Edema) Suprachoroidal CLS-TA alone or with anti-VEGF (Intravitreal Eylea aflibercept) 1.1 m graphic Phase 1/2 data H2 2017

Clearside Collaborations

Indication Study drug U.S. Est. prevalence Current Status
Retinal Vascular Disease Proprietary Compound(s) 1.2m graphic Preclinical
Orphan Diseases Gene Therapy Preclinical

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