Advancing Innovative Therapeutics To Improve Ocular Health

OIS San Diego May 2019

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Advancing Innovative Therapeutics To

Improve Ocular Health

Lead asset TOP1630 demonstrated compelling efficacy, safety/tolerability

profile in clinical POC study for dry eye disease (DED)

THEIA-1, Phase 2b/3 study in DED underway with read out in 2H 2019

Library of compounds with robust IP position

Private, clinical-stage, London based biotechnology company

Expertise in inflammation to identify, develop and deliver novel

therapeutics for ocular diseases

Small molecule, topically administered, proprietary kinase inhibitors

deliver a broad and potent anti-inflammatory effect

Unique MOA simultaneously inhibits key inflammatory kinases p38α, Src family kinases (Src & Lck) and Syk

Synergistic anti-inflammatory activity impacting both innate and adaptive pathways*Profound local anti-inflammatory effect with a rapid onset of actionSteroid-like efficacy without steroid side effects

Validated targets Src kinase inhibitor FDA approved dasatinib for leukaemia Syk inhibition FDA approved fostamatinib for cITPp38α validated with clinical effects in Crohn’s Disease

Excellent safety profile in preclinical and clinical studies with >160 patients/volunteers treated to date

Potential use in multiple ocular inflammatory based conditions 3

TopiVert’s Proprietary, Locally Administered Small Molecule Kinase Inhibitors For Multiple Ocular Indications

* Biancheri et al. Inflamm Bowel Disease, 2016; 22; 1306-1315

TOP1630

TOP1630 Has A Unique Mechanism of Action Targeting Key Immune Pathways in DED

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DED PathophysiologyIL-8 Release from Primary Corneal Cells

TNF-α Release from Primary Macrophages

IFNγ Release from α-CD3/CD28 stim PBMCs

Mucosal/epithelial functionp38α / Src

Adaptive immune response

Lck / p38α / Syk

Innate immune responsep38α / Syk

61 patients with moderate to severe dry eye disease

4 weeks treatment duration with TOP1630 0.1% topical eye drops /vehicle

Primary Objective: Safety and Tolerability Excellent safety and tolerability with TOP1630 profile similar to vehicle

Secondary Objectives: Efficacy Multiple positive effects on signs and symptoms vs vehicle in ITT population Consistency of effect across endpoint assessments by different scalesConsistency of effect with endpoint inside and outside CAE including daily diary assessments Fast onset of action as early as Day 15 (first assessment time point)

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A Phase 2 Randomized, Double-Masked, Vehicle-Controlled Study of TOP1630 in Dry Eye Disease

Published: Clinical Ophthalmology 2019:13: 261–275

Broad Efficacy On Both Signs and Symptoms vs Vehicle By Week 4

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Discomfort(p=0.02)

Worst (most severe) Dry Eye Symptom(p=0.06)

Dryness(Discomfort & 4 symptom questionnaire p=0.07)

Eye Pain(p=0.03 VAS)

Grittiness/Foreign Body Sensation(Daily Diary p=0.006, OSDI p=0.015, VAS p=0.02, 4 symptom scale p=0.0001)

Total Ocular Surface Lissamine Staining (p=0.02)

Total Corneal Score(p=0.03)

SYMPTOMS

SIGNSTotal Conjunctival Score

(p=0.03)

Clinical Ophthalmology. 2019:13:261-275.

Sign: Total Ocular Staining

Large Treatment Effects vs Vehicle Starting At Day 15 Increasing At Day 29

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Baseline: mean (SEM): TOP1630: 6.32 (0.40), Placebo: 5.68 (0.40)

Δ = Difference %TOP1630-%Placebo: (%=mean change as % of baseline mean)

Baseline: mean (SEM) :TOP1630: 2.4 (0.25), Placebo: 2.4 (0.25)

Symptom: Grittiness

Clinical stage biotech with pioneering anti inflammatory approach

Compelling PoC for TOP1630 in dry eye disease

Key data read out from Phase 2b/3 Study THEIA-1 in 2H 2019 to support possible NDA 2022

Novel, clinically validated platform with opportunity for multiple ocular indications

Solid IP protection and longevity

TopiVert Pharma: Advancing Innovative Therapeutics To Improve Ocular Health

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