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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
  • Other 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

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

M1 = Month 1 ; M2 = Month 2

In this evaluation data from one patient is not included

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

1N = 17

2 Eylea®, Lucentis®, Ozurdex® prescribing information

BCVA and ME Improvements at Month 2

Percent of Patients with BCVA Improvement

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

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
Macular Edema associated with non-infectious uveitis (uveitis) Suprachoroidal CLS-TA 350 graphic Phase 3 data early 2018
RVO (retinal vein occlusion) Suprachoroidal CLS-TA with anti- VEGF (Intravitreal Eylea) 2.2 m graphic Phase 3
DME (diabetic macular edema) Suprachoroidal CLS-TA alone or with anti- VEGF (Intravitreal Eylea) 1.1 m graphic Phase 1/2 data H2 2017

Focused Pipeline of SCS Treatments for Multiple Blinding Eye Disease

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

69% Fewer Patients Required Additional Eylea® Treatments

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

M1 = Month 1; M2 = Month 2; M3 = Month 3

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

RVO Phase 2 Summary

Patients treated with Suprachoroidal CLS-TA + Intravitreal Eylea vs. Intravitreal Eylea alone

  • Greater improvement of vision in comparison with intravitreal Eylea alone in this 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

Focused Pipeline of SCS Treatments for Multiple Blinding Eye Disease

Clearside’s Current Programs

Indication Study drug U.S. Est. prevalence Current Status
Macular Edema associated with non-infectious uveitis (uveitis) Suprachoroidal CLS-TA 350 graphic Phase 3 data early 2018
RVO (retinal vein occlusion) Suprachoroidal CLS-TA with anti- VEGF (Intravitreal Eylea) 2.2 m graphic Phase 3
DME (diabetic macular edema) Suprachoroidal CLS-TA alone or with anti- VEGF (Intravitreal Eylea) 1.1 m graphic Phase 1/2 data H2 2017

Focused Pipeline of SCS Treatments for Multiple Blinding Eye Disease

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 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.
  • Diabetic retinopathy is a leading cause of new cases of legal blindness among working-age Americans and represents a leading cause of blindness in this age group worldwide.1
  • It may cause images to appear blurry or wavy and colors that seem “washed out”.

1 Klein BE. Overview of epidemiologic studies of diabetic retinopathy. Ophthalmic Epidemiol 2007;14:179-83.

Treatment Goal

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

CURRENT TREATMENTS

  • Intravitreal injections of corticosteroids
  • Anti-VEGF drugs
  • Laser treatments or pars plana vitrectomy
  • Sustained-release corticosteroid vitreous implants

Treating Macular Edema

Phase 1 / 2: Hulk Initiated July 2017

  • 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

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