advancing innovative therapeutics to improve ocular health2 advancing innovative therapeutics to...
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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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