Akari Therapeutics Plc · NASDAQ:AKTX
Akari Therapeutics — Investor Presentation (May 2019)
25 slides from Akari Therapeutics's investor presentation, May 29, 2019
Slide 1: May 2019 Investor Presentation
May 2019 Investor Presentation Copyright Akari Therapeutics, Plc - 2019
Slide 2: Disclaimers
2 Disclaimers Certain statements in this presentation constitute contains “forward - looking” statements within the meaning of Section 27A of th e Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. These forward - looking statements reflect our current views about our pla
Slide 3: Treating Orphan Diseases Caused by Complement & Leukotriene Dysregulation
3 Treating Orphan Diseases Caused by Complement & Leukotriene Dysregulation ● Nomacopan (Coversin): Platform molecule with a unique MOA: Bifunctional inhibitor of two synergistic inflammatory pathways (C5 and LTB4) ● Four conditions in the clinic - all with positive initial clinical readouts – TMA ,
Slide 4: Nomacopan Differentiation: Simultaneous Inhibition of C5 and LTB4 Pathways
4 Nomacopan Differentiation: Simultaneous Inhibition of C5 and LTB4 Pathways Unique Bispecific MOA Activity Across Organ Groups Synergistic C5 & LTB4 Pathways Additive Efficacy Unmet Need • Unique bispecific molecule binding C5 and LTB4 independently with high affinity • Dysregulation of Complement
Slide 5: Clinical Programs
5 Clinical Programs
Slide 6: Clinical Programs Diversified by MOA and Routes of Administration
6 Phase I / II Phase II Planned pivotal trial Phase III Clinical Programs Diversified by MOA and Routes of Administration BP AKC PNH TMAs C5 Only C5 & LTB4 Subcutaneous Delivery Topical AKC: Atopic Keratoconjunctivitis; BP: Bullous Pemphigoid; TMA: Thrombotic Microangiopathy; PNH: Paroxysmal Nocturn
Slide 7: Thrombotic Microangiopathy (TMA) After Transplant
7 Thrombotic Microangiopathy (TMA) After Transplant Significant Unmet Need • Orphan condition in which there is evidence that both terminal complement activation and possibly LTB4 have a role in driving disease • Complications following bone marrow transplantation (BMT) in ≤30% patients. In target p
Slide 8: Nomacopan Activity Demonstrated in HSCT – TMA Across Multiple Responder End Points
8 Nomacopan Activity Demonstrated in HSCT – TMA Across Multiple Responder End Points (2 Patients) TMA Marker Patient Baseline Day 7 Day 14 Day 28 Day 60 Hemolytic anemia 1 Yes Resolved 2 Mild Red blood cell fragments 1 Yes Resolved 2 Yes Resolved Thrombocytopenia 1 Yes Resolved 2 Yes Resolved Increa
Slide 9: Bullous Pemphigoid (BP)
9 • Orphan condition in which there is evidence that both terminal complement activation (C5) and LTB4 have a role in driving disease • Preclinical studies showed a dose response and combined C5 & LTB4 more effective than LTB4 alone • Elevated C5/LTB4 in ex - vivo study of BP patients • Existing tre
Slide 10: Bullous Pemphigoid Ongoing Phase II Trial in Mild-to-Moderate Disease
10 Bullous Pemphigoid ongoing Phase II Trial in Patients with Mild - to - Moderate Disease Current Study design • Phase II Single arm (n = 9); 42 days treatment • Test role of C5 & LTB4 dual inhibition in improving BP outcomes • Active bullous pemphigoid; newly diagnosed or recurrent Treatment • Nom
Slide 11: Mean BPDAI and Blister Score, First Three Patients Phase 2 BP Trial
11 Prior to treatment, two of three patients were on topical corticosteroids (mometasone), while the third patient was naïve to steroid treatment & received no steroid while on nomacopan. There was no planned tapering of topical steroid dose, but patients did use less than th e 30g permitted to day
Slide 12: Potential Application in Both Surface and Back of Eye Indications
12 Potential Application in Both Surface and Back of Eye Indications • AKC • Severe dry eye disease • Other keratopathies • MMP Surface of the Eye Back of the Eye Key Indications Development Stage • Uveitis • AMD • Proliferative retinopathies • Clinical – AKC Phase I/II • Preclinical Administration
Slide 13: Indications of C5 & LTB4 Activity in Front and Back of the Eye
13 Indications of C5 & LTB4 Activity in Front and Back of the Eye Indications 18.61 9.97 24.37 464.04 0 100 200 300 400 500 pg/mL Tear fluid LTB4 Normal Tolerant Intolerant Allergic * Eskandarpour M et al. Poster 797 (B0275) ARVO 2019 • Wide range of surface of the eye inflammatory conditions with o
Slide 14: Atopic Keratoconjunctivitis (AKC)
14 Atopic Keratoconjunctivitis (AKC) AKC VKC PKC SAC SJS MMP • AKC: severe eye surface inflammation causing infiltration of immune cells (neutrophils & T cells) – a major cause of blindness • Topical drugs, such as steroids or cyclosporine treatments complicated by issues with comfort and side effec
Slide 15: AKC Phase I/II Proof-of-Principle Trial Design
15 AKC Phase I/II Proof - of - Principle Trial Design Study design • Phase I/II randomized, double masked , placebo - controlled, safety and dose finding study • Part A : 3 patients open label - safety • Part B : 16 randomized patients • All patients on maximum cyclosporine Treatment • Nomacopan top
Slide 16: Initial AKC Clinical Data: First Two Patients
16 • No serious drug - related adverse effects • Post - instillation comfort reported as comfortable at all time points – By Day 14, >35% decrease in composite disease scores in both patients – Patient 1 had a disease flare at Day 42 • Marked improvement in symptoms of discomfort from a mean of 2.5
Slide 17: Paroxysmal Nocturnal Hemoglobinuria (PNH)
17 Paroxysmal Nocturnal Hemoglobinuria (PNH) • PNH: ultra - rare, life threatening, clonal disorder of red blood cells • Phase III clinical trial: (CAPSTONE) ongoing ‒ Naïve patients randomized to nomacopan plus SOC* vs. SOC ‒ Six month treatment / ~30 patients ‒ End points: transfusion independence
Slide 18: C5 Inhibition and Transfusion Reduction in PNH Patients Treated with Nomacopan
18 C5 Inhibition and Transfusion Reduction in PNH Patients When Treated with N omacopan 0 1 2 3 4 5 0 10 20 30 40 50 60 70 80 90 Days PNH COBALT Phase II Median and range LDH x ULN Original maintenance dosing: 30 mg daily (N=5, N=4 after day 43*) Revised maintenance dosing: 45 mg daily (N=3) 1.8 x U
Slide 19: Patients Being Treated With Nomacopan Across Four Primary/Lead Indications
19 Patients Being Treated With N omacopan Across Four Primary/Lead Indications Preclinical Phase I Phase II Phase III * Phase I/II study APS: Antiphospholipid Syndrome; MG: Myasthenia Gravis Ophthalmology AKC* Subcutaneous PNH TMA - HSCT Bullous Pemphigoid Pulmonary Lung (Nebulized form) Engineered
Slide 20: Financial and Clinical Wrapup: Meaningful Upcoming Clinical Milestones
20 ● $20 million financing facility* with Aspire Capital ● ~1.6 billion ordinary shares outstanding / equivalent to 16 million ADSs ● Multiple expected short - to mid - term clinical readouts: – BP : complete mild to moderate patients Q4 2019 – BP : expansion to severe 2H 2019 – TMA : Q4 2019 - pivo
Slide 21: Appendix
APPENDIX
Slide 22: Nomacopan Competitive Advantage: Synergistic C5 and LTB4 Inhibition
22 ALOX5 Engagement GPCRs BLT1/BLT2 Nomacopan Competitive Advantage: Synergistic C5 and LTB4 inhibition PLA2 Arachidonic acid C3 C3b C3 convertase Opsonisation Amplification loop C5 convertase C3a C5b C6 C7 C9 C8 C5 Engagement GPCRs C5aR/C5aL2 C3b Anaphylatoxins C5a LTB4 Membrane Attack Complex noma
Slide 23: LTB4 Ligand Capture Advantageous and Unique MOA
23 LTB4 Ligand Capture Advantageous and Unique MOA Arachidonic acid LTA 4 Lipoxins LTB 4 LTC 4 LTD 4 LTE 4 5 - LOX FLAP LTA 4 H LTC 4 S Lipoxygenases Pro - inflammatory Anti - inflammatory Spasmogenic Zileuton GSK2190915 DG - 031 MK - 0633 TA - 270 5 - LOX / FLAP inhibitors • Reduces anti - inflamma
Slide 24: Expanding Pipeline Focused on Indications Where C5 and LTB4 Both Involved
24 N = 5 mice in each treatment group Start drug treatment Expanding Pipeline Focused on Indications Where C5 and LTB4 Both Involved Zileuton PAS - nomacopan PAS - LTB4 - nomacopan Cell recruitment to Lung Induced by LPS Dual action nomacopan more effective than C5 - only nomacopan (or Zileuton®) al
Slide 25: May 2019
May 2019 Investor Presentation
Akari Therapeutics — Investor Presentation (May 2019) on 6ix