Slide 1: Randomized, Comparator-Controlled Phase 2 Trial of ADX-102 in Noninfectious Anterior Uveitis
A Randomized, Comparator-Controlled Phase 2 Clinical Trial of ADX-102 Ophthalmic Solution in Noninfectious Anterior Uveitis May 8, 2017
Slide 2: John D Sheppard, MD, MMSc
John D Sheppard, MD, MMSc President & Managing Partner, Virginia Eye Consultants Professor of Ophthalmology, Microbiology & Immunology Clinical Director, Thomas R Lee Ocular Pharmacology Lab Ophthalmology Residency Research Director Medical Director, Lions Eye Bank of Eastern Virginia Norfolk, Virgi
Slide 3: Disclosures
Disclosures • Alcon: Research Grants, Speaker, Advisor • NovaBay: Advisory Board, Researcher • Aldeyra Pharmaceuticals: Advisory Board, Clinical • Novartis/Ciba Vision: Speaker, Advisor Research • NiCox: Advisory Board • Allergan: Research Grants, Speaker, Advisory Board, • Omeros: Advisory Board Me
Slide 4: Aldehydes Are Mediators of Disease
Aldehydes Are Mediators of Disease • Directly toxic, modify cellular constituents, and pro-inflammatory Aldehydes • Metabolized by enzymes called aldehyde dehydrogenases Protein Signaling Cytokine Release via Thiol and • High levels are implicated Amine Binding in inflammatory diseases and in inborn
Slide 5: Aldehyde Traps: A Novel Therapeutic Approach
Aldehyde Traps: A Novel Therapeutic Approach Aldehyde • Aldeyra’s compounds rapidly Binding trap free aldehydes Adduct • Trapped aldehydes are Transport transported inside the cell Cellular • Drug and aldehydes are Degradation metabolized within hours Aldeyra is not aware of any similar technology,
Slide 6: The Aldehyde Trap Ocular Anti-Inflammatory Platform
The Aldehyde Trap Ocular Anti-Inflammatory Platform Allergy Autoimmune (TH2 (TH1 Cytokines) Cytokines) ✓ ✓ Allergic Uveitis Conjunctivitis Atopic Kerato- Cyclitis, Iritis, Conjunctivitis, Scleritis, DES, etc. etc. ADX-102 (previously NS2) has demonstrated activity in the two major types of inflammat
Slide 7: Noninfectious Anterior Uveitis Phase 2 Clinical Design
Noninfectious Anterior Uveitis Phase 2 Clinical Design ADX-102 0.5% Topical Ocular Dosing Pred Forte® 1% Topical Ocular Active-Controlled 1:1:1 • ADX-102 QID, Randomized • Pred Forte® QID Taper, • ADX-102 QID + Pred Forte® BID Taper Enrollment 45 Patients with Active Disease Treatment 6 Weeks Time E
Slide 8: ADX-102 Comparable to Corticosteroid in NAU Phase 2
ADX-102 Comparable to Corticosteroid in NAU Phase 2 ADX-102 Pred Forte ADX-102 + (n=15) (n=13) Pred Forte (n=16) Week 2 Cell Grade 5 (33%) 4 (31%) 5 (31%) 0 Week 8 Cell Grade 7 (47%) 6 (46%) 7 (44%) 0 ≥ 1 Cell Grade 8 (53%) 6 (46%) 8 (50%) Reduction Rescue Medication 3 (20%) 5 (38%) 4 (25%) Required
Slide 9: Reduced Inflammation in NAU Phase 2
ADX-102 Reduced Inflammation in NAU Phase 2 Change from Baseline in Anterior Chamber Cell Grade over Time (ITT Population, Last Observation Carried Forward) 0.4 Day 4 Week 1 Week 2 Week 4 Mean (±SEM) Change from Baseline 0.2 0 -0.2 ADX-102 Corticosteroid -0.4 -0.6 -0.8 -1 -1.2 Week 4 Grade 0 Percent
Slide 10: ADX-102 Comparable to Corticosteroid in NAU Phase 2
ADX-102 Comparable to Corticosteroid in NAU Phase 2 Baseline-Adjusted 95% Confidence Interval of Difference in Means at Week 2 (mITT Population, Last Observation Carried Forward)* Favors ADX-102 Favors Steroid 0.6 point upper bound (15% ADX-102-Steroid non-inferiority margin) 0.4 point upper bound (
Slide 11: ADX-102 Sustained Grade 0 Responses
ADX-102 Sustained Grade 0 Responses Time to ACC Treatment Success Time to treatment success--defined as the number of days from the initiation of study drug to the date that the anterior chamber cell grade reached and sustained a grade of 0--is estimated using the method of Kaplan-Meier. Subjects wh
Slide 12: Time to ACC Grade Reduction
ADX-102 Time to ACC Grade Reduction Time to cell grade reduction--defined as the number of days from the initiation of study drug to the date that the anterior chamber cell grade reached a grade of at least one less than baseline and did not increase thereafter-- is estimated using the method of Kap
Slide 13: Did Not Increase Intraocular Pressure in this Phase 2 Clinical Trial
ADX-102 Did Not Increase Intraocular Pressure in this Noninfectious Anterior Uveitis Phase 2 Clinical Trial Change from Baseline in Intraocular Pressure (mmHg) over Time (Safety Population) Mean (±SEM) Change from Baseline 4 Day 4 Week 1 Week 2 Week 4 Week 8 3 2 1 0 -1 ADX-102 Corticosteroid -2 Incr
Slide 14: Study Efficacy Summary
Study Efficacy Summary • No statistically significant differences* for anterior chamber cell count or flare were observed between groups in: • Time to sustained grade of 0 • Proportion of subjects with sustained grade 0 • Time to sustained reduction of ≥1-point grade • Subject proportion with sustai
Slide 15: Study Safety Summary
Study Safety Summary • Overall, safety findings indicate ADX-102 0.5% ophthalmic solution was well tolerated over a 6-week treatment duration • No safety issues anticipated for future studies of topical ADX- 102 in subjects with anterior uveitis: • No SAEs during study • Most TEAEs were mild or mode
Slide 16: Conclusions
Conclusions • These results suggest that ADX-102 treatment alone, or in combination with 1% Pred Forte®, was effective in the treatment of Noninfectious Anterior Uveitis • ADX-102 efficacy profile is similar to that of 1% Pred Forte® monotherapy in this clinical trial • ADX-102 Ophthalmic Solution i
Slide 17: Conclusions
Conclusions • Aldehyde Trap Strategies May Prove Clinically Useful in Treating Inflammatory Ocular Disease