Akari Therapeutics Plc · NASDAQ:AKTX
Akari Therapeutics — Investor Presentation (September 2019)
37 slides from Akari Therapeutics's investor presentation, Sep 10, 2019
Slide 1: September 2019 Investor Presentation
September 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): Bifunctional inhibitor of C5 & LTB4 Focused on orphan inflammatory & autoimmune diseases where treatment options limited and C5 and LTB4 implicated TMA: Thrombotic Microangiopathy; BP: Bullous Pemphig
Slide 4: Dual C5 & LTB4 MOA Provides Unique Option for Multiple Poorly Treated Inflammatory Diseases
4 Dual C5 & LTB4 MOA Provides Unique Option for Multiple Poorly Treated Inflammatory Diseases ● Additive effect demonstrated in preclinical RA, lung and BP models with Nomacopan: significantly more effective than LTB4 or C5 alone ● Elevated levels of C5a and LTB4 seen in human and animal tissue - bl
Slide 5: Nomacopan: Well-Designed by Nature Tightly Binding Both C5 & LTB4
5 Nomacopan: Well - Designed by Nature Tightly Binding Both C5 & LTB4 Independent, Highly Specific C5 & LTB4 Inhibitory Activity • Nomacopan: biological with high specificity for C5 & LTB4 • Avoids off - target effects by binding ligands not receptors • No immunogenicity to date in human studies • M
Slide 6: Nomacopan: Extensive and Growing Positive Efficacy Data Across Four Indications
6 Nomacopan: Extensive and Growing Positive Efficacy Data Across Four Indications PNH Phase II Achieved primary Phase II end point Six Phase II patients transfusion dependant; two - thirds now transfusion independent 9 patients sub Q ~20 cumulative patient - years* of treatment data TMA BP AKC 2 pat
Slide 7: Subcutaneous Nomacopan: Clinically Testing C5 & LTB4 Binding in HSCT-TMA
7 Subcutaneous Nomacopan: Clinically Testing C5 & LTB4 Binding in HSCT – Thrombotic Microangiopathy
Slide 8: HSCT-TMA High Mortality Rate and No Approved Treatments
8 HSCT - TMA High Mortality Rate – and No Approved Treatments • Arteriolar thrombi associated with intimal swelling, fibrinoid necrosis, thickening of arterioles and capillaries, and subendothelial accumulation of proteins & cell debris • Cause of TMA after bone marrow transplant not well understood
Slide 9: Upcoming Pediatric HSCT-TMA Pivotal Trial
9 Upcoming Pediatric HSCT - TMA Pivotal Trial Potential Expansion to Related Indications • Complement’s role highlighted by elevated terminal complement components (sC5b9) in many patients. • LTB4 believed to have a role in TMA - HSCT in terms of graft vs. host disease (GVHD) progression • Nomacopan
Slide 10: Activity Demonstrated in HSCT-TMA Across Multiple Responder End Points
10 Activity Demonstrated in HSCT – TMA Across Multiple Responder End Points (First 2 Named 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 Inc
Slide 11: Nomacopan in HSCT-TMA Differentiation Against Competitors
11 Nomacopan in HSCT - TMA Differentiation Against Competitors • Patient group to be treated identified via histologic TMA diagnosis in tissue biopsy or laboratory & clinical markers • Daily dosing facilitates more complete complement suppression • LTB4 inhibition may further reduce epithelial activ
Slide 12: Subcutaneous Nomacopan: Clinically Testing C5 & LTB4 Binding in Bullous Pemphigoid
Subcutaneous Nomacopan: Clinically Testing C5 & LTB4 Binding in Bullous Pemphigoid
Slide 13: Bullous Pemphigoid Significant Unmet Need
13 Bullous Pemphigoid Significant Unmet Need • Severe autoimmune blistering skin disorder primarily of the elderly • Caused by immune complex mediated inflammation via autoantibodies • No approved therapy. Current treatment with chronic corticosteroids poses substantial health concerns • KOLs: essen
Slide 14: Bullous Pemphigoid Evidence of Combined C5 & LTB4 Involvement
14 • Orphan condition in which there is evidence that both terminal complement activation (C5) and LTB4 have a role in driving disease ‒ Preclinical studies with nomacopan showed a dose response and combined C5 & LTB4 more effective than LTB4 alone (1) ‒ Elevated C5/LTB4 in ex - vivo study of BP pat
Slide 15: Mean BPDAI and Blister Score, First Three Patients Phase 2 BP Trial
15 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 16: Nomacopan in Bullous Pemphigoid Differentiation Against Competitors
16 Nomacopan in Bullous Pemphigoid Differentiation Against Competitors • Positioned as 2nd line treatment for patients with moderate to severe symptoms, previously treated with corticosteroids • Better safety and side effect profile than steroids and non - specific immunosuppressants • Used to reduc
Slide 17: Topical Nomacopan: Clinically Testing C5 & LTB4 Binding in Ophthalmology / AKC
17 Topical Nomacopan: Clinically Testing C5 & LTB4 Binding in Ophthalmology / AKC
Slide 18: Atopic Keratoconjunctivitis: Chronic Ocular Disease Which Can Lead to Vision Loss
18 Atopic Keratoconjunctivitis (AKC): Chronic Ocular Disease Which Can Lead to Vision Loss • Chronic disease can result in severe dry eye, corneal neovascularisation, & formation of sterile corneal ulcers • If left untreated, can lead to vision loss; other complications include cataracts, keratoconu
Slide 19: Atopic Keratoconjunctivitis (AKC)
19 Atopic Keratoconjunctivitis (AKC) AKC VKC PKC SAC SJS MMP • Infiltration of neutrophils & T cells into conjunctival epithelium • LTB4 levels – 20X in allergic conjunctivitis patients • Complement system in tears is functionally active, and concentration of all components is greatly increased in c
Slide 20: Initial AKC Clinical Data: First 2 Patients to Day 56
20 • Patients had deteriorating moderate – severe AKC despite ≥3 months treatment with cyclosporin t.i.d. ± steroids • Part A of study – first in man – successfully completed – drug well tolerated • Overall improvement across both signs and symptoms ‒ Patient 1 had a disease flare at Day 42 but then
Slide 21: Nomacopan in AKC Clear Differentiation Vs. Competitors
21 Nomacopan in AKC Clear Differentiation Vs. Competitors • Positioned as 1st line treatment for patients with moderate to severe symptoms, given clear unmet need • Comfortable on application (pH neutral) • Rapid improvement in signs & symptoms in human studies • Upstream effects on T cells and gran
Slide 22: C5 & LTB4 Activity in Back of the Eye Indications: Uveitis
22 C5 & LTB4 Activity in Back of the Eye Indications Potential New Target Indication: Uveitis * Eskandarpour M et al. Poster 797 (B0275) ARVO 2019 LTB4 receptor C5a receptor Autoimmune Uveitis (EAU) Model • Intravitreal nomacopan reported significant improvement in uveitis model versus control • Sig
Slide 23: Subcutaneous Nomacopan: Paroxysmal Nocturnal Hemoglobinuria
23 Subcutaneous Nomacopan: Paroxysmal Nocturnal Hemoglobinuria
Slide 24: PNH Phase II: Transfusion Reduction Validated Efficacy
24 PNH Phase II: Transfusion Reduction Validated Efficacy - Option Value For Continuing to MAA • Six patients transfused in six months prior to entering Phase II • Three became transfusion independent during Phase II • Four transfusion independent during follow - up long - term safety study Percenta
Slide 25: Wrap up
Wrap up
Slide 26: Four Primary/Lead Indications in Phase II/III Plus Earlier-Stage Targets
26 Four Primary/Lead Indications in Phase II/III Plus Pipeline of Earlier - Stage Targets 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)
Slide 27: Financial and Clinical Wrap up: Meaningful Upcoming Clinical Milestones
27 ● Growing efficacy data set across four severe orphan conditions ● 20 cumulative patient - years of treatment shows positive safety data and well tolerated ● Multiple expected short - to mid - term clinical readouts: – BP : Complete mild to moderate patients Q4 2019 – TMA : Q4 2019 - pivotal tria
Slide 28: Appendix
APPENDIX
Slide 29: Competitive Advantage: Synergistic C5 and LTB4 Inhibition
29 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 30: LTB4 Ligand Capture Advantageous and Unique MOA
30 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 31: Expanding Pipeline Focused on Indications Where C5 and LTB4 Both Involved
31 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 32: Preclinical Efficacy & Elevated C5a/LTB4 in Bullous Pemphigoid Patients
32 LTB4 levels - human blister fluid C5a levels - human blister fluid Elevated levels of LTB4 and C5a indicate activation of complement and synthesis of LTB4 in blisters Epidermolysis Bullosa Acquisita Preclinical Efficacy & Elevated C5a/LTB4 in Bullous Pemphigoid patients Preclinical passive mouse
Slide 33: Dual Acting Nomacopan Significantly More Effective Than LTB4-Only Nomacopan
33 Dual Acting Nomacopan Significantly More Effective Than Long - Acting Nomacopan Only Inhibiting LTB4 ● Long acting LTB4 only nomacopan (10mg/kg) ameliorates blister formation but is less effective than the molar equivalent dose of nomacopan (2.5mg/kg) ● 1mg/kg long acting LTB4 only nomacopan inef
Slide 34: Significant Benefit Demonstrated in Late-Phase Eye Surface Inflammation
34 Collaboration with Institute of Ophthalmology, London, UK EIC pre - clinical model of severe eye surface inflammation (Dr Virginia Calder) Significant Benefit Demonstrated in Late - Phase Eye Surface Inflammation • C57/Bl6 mice sensitized to OVA for 14 days • E ye surface challenge d with OVA for
Slide 35: Bullous Pemphigoid Ongoing Phase II Study
35 Bullous Pemphigoid Ongoing Phase II Study 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 • Nomaco
Slide 36: AKC Phase I/II Proof-of-Principle Trial Design
36 AKC Phase I/II Proof - of - Principle Trial Design Study design • Phase I/II randomized, double masked , placebo - controlled, safety and efficacy study • Part A : 3 patients open label - safety • Part B : 16 randomized patients • All patients on maximum cyclosporine Treatment • Nomacopan topical
Slide 37: September 2019 Copyright Akari Therapeutics, Plc - 2019
September 2019 Investor Presentation Copyright Akari Therapeutics, Plc - 2019
Akari Therapeutics — Investor Presentation (September 2019) on 6ix