Akari Therapeutics Plc · NASDAQ:AKTX
Akari Therapeutics — Investor Presentation (September 2021)
35 slides from Akari Therapeutics's investor presentation, September 2021
Slide 1: Combined Inhibition Of Complement & Leukotriene Pathways To Treat Inflammatory Diseases
Combined Inhibition Of Complement & Leukotriene Pathways To Treat Inflammatory Diseases September 2021
Slide 2: Forward-Looking Statements
Forward-Looking Statements Certain statements in this presentation constitute contains “forward-looking” statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. These forward-looking statements reflect our current views about
Slide 3: Akari Overview: Targeting Inflammatory Diseases With Unmet Need
Akari Overview Targeting Inflammatory Diseases With Unmet Need • First in class, differentiated, dual MOA within the complement mediated disease space: – Nomacopan inhibits complement C5 and leukotriene B4 (LTB4) – Ability to target multiple inflammatory indications where inhibiting both proinflamma
Slide 4: First-In-Class Bifunctional Anti-Inflammatory Biological
First-In-Class Bifunctional Anti-Inflammatory Biological Two Modes of Action • Nomacopan, by binding C5 and LTB4, inhibits both complement and leukotriene immune pathways, which are both active in a wide range Top view of nomacopan (Cyan) bound to C5 Jore of inflammatory disorders et al., Nat Struct
Slide 5: Nomacopan's Competitive Advantage: Synergistic Inhibition of Two Key Effectors
Nomacopan’s Competitive Advantage: Synergistic Inhibition of Two Key Effectors Driving Autoinflammation Complement (C5) inhibition Leukotriene (LTB4) inhibition C3 convertase Mediators of pathology drive C3b C3 disease maintenance PLA2 Opsonization and Granulocyte activation clearance of immune Anap
Slide 6: Nomacopan's Effectiveness Inhibiting C5 & LTB4 Demonstrated In PNH
Nomacopan’s Effectiveness Inhibiting C5 & LTB4 Demonstrated In PNH And Other Models TCA PNH patients treated with nomacopan 170 Terminal complement inhibition demonstrated in PNH patients Treatment Nomacopan • Drug effect: Terminal complement activity (TCA) fully inhibited during 160 rVA576 plus SoC
Slide 7: Clinical Pipeline Progressing Into Phase 3 Studies
Clinical Pipeline Progressing Into Phase 3 Studies Formulation Therapy Area Disease Preclin. Phase 1 Phase 2 Phase 3 Phase 3 expected to initiate Q4 2021 Bullous Pemphigoid Dermatology Hidradenitis Suppuritiva Potential future expansion + additional opportunities Systemic nomacopan Phase 3 initiated
Slide 8: Bullous Pemphigoid: Chronic Disease, No Specific Approved Therapies
Bullous Pemphigoid: Chronic Disease, No Specific Approved Therapies Bullous pemphigoid Hidradenitis suppuritiva (HS) Epidermolysis bullosa acquisita (EBA) Mucous membrane pemphigoid (MMP) Psoriasis 8
Slide 9: Bullous Pemphigoid: Auto-Immune Blistering Disease With No Specific Approved Therapy
Bullous Pemphigoid: Auto-Immune Blistering Disease With No Specific Approved Therapy High dose oral corticosteroid (OCS) use associated with Unmet Need approximately 3-fold increase in mortality in this patient group • Need for rapidly efficacious steroid-sparing therapy Most common auto-immune blis
Slide 10: Central Role For C5 & LTB4 in Bullous Pemphigoid
Central Role For C5 & LTB4 in Bullous Pemphigoid • Preclinical: BP-like model of epidermolysis bullosa acquisita showed c.50% reduction in surface area affected by blisters by inhibiting LTB4 alone but c.80% reduction by inhibiting both LTB4 and C5 • Clinical biomarkers: C5 and LTB4 levels elevated
Slide 11: Phase 2 Outcome: Rapid Reduction in BPDAI Activity Scores
Phase 2 Outcome: Rapid Reduction in BPDAI Activity Scores of 7 Responders On Nomacopan Single arm (n = 9); 42 days treatment; mild - moderate active BP; endpoints safety (primary) and BPDAI/QoL at Day 42 Mean BPDAI Activity + 90% CI Individual Patients BPDAI Activity Phase 2 Observations 50 60 • Rap
Slide 12: BP Phase 3 Design – Visual Summary
BP Phase 3 Design – Visual Summary Disease Control • Recruiting moderate and severe patients • 24-week treatment vs 6-week for phase 2 • Systemic oral steroid - starting 0.5mg/kg/day Oral Steroid Dose Patients who do not complete tapering by week 16 cannot achieve • Steroid tapering and disease remi
Slide 13: BP Phase 3 Design Provides Interim Readout After Part A
BP Phase 3 Design Provides Interim Readout After Part A Part A Part B (not powered) (powered) 10 days 24 weeks 4 weeks 10 days 24 weeks 4 weeks OCS Stabilization, Tapering & Remission OCS Stabilization, Tapering & Remission n = 16 Follow-up Type A FDA Meeting Screening & Randomisation Screening & Ra
Slide 14: Broad Applications Across Dermatology
Broad Applications Across Dermatology Multiple market opportunities with $bn+ aggregate peak sales where both C5 and LTB4 implicated Potential follow on InflaRx: IFX-1 - C5a inhibition - Phase 3 C5a Chemocentryx: Avacopan - C5aR inhibition Phase 2 dermatology targets Nomacopan Hidradenitis uniquely
Slide 15: HSCT-TMA: High Clinical Impact, No Approved Therapies
HSCT-TMA: High Clinical Impact, No Approved Therapies Pediatric & adult HSCT-TMA Anti-phospholipid syndrome TMA in SLE Vasculitis Paroxysmal nocturnal hemoglobinuria Atypical hemolytic uremic syndrome 15
Slide 16: HSCT-TMA (Pediatric & Adult): Potential To Reduce Mortality In Aggressive Disease
HSCT-TMA (Pediatric & Adult): Potential To Reduce Mortality In Aggressive Disease High mortality rate of up to 80% associated with severe pediatric HSCT-TMA Unmet Need • Need for rapid, complete & sustained C5 & potentially LTB4 inhibition ~10K pediatric HSCT and ~60K adult HSCT performed in US + EU
Slide 17: Pediatric HSCT-TMA Phase 3 Program Goals
Pediatric HSCT-TMA Phase 3 Program Goals: Transfusions, Renal Function, Survival Conceptual Treatment Profile Moderate HSCT-TMA Severe HSCT-TMA Extreme • Targeting severe HSCT-TMA with sC5b9 only Elevation Proteinuria Only Elevated sC5b9 & Proteinuria of Markers elevated sC5b9 and proteinuria 100% T
Slide 18: Pediatric HSCT-TMA Open-Label Phase 3 Study
Pediatric HSCT-TMA Open-Label Phase 3 Study: Part A Part B 90-180 days treatment Up to 180 days treatment PK/PD Dose confirmation, Safety and efficacy safety and efficacy (may include Part A patient data) N=7 (three age cohorts) 0.5 to <2 years Severe patients >2 to <9 years Interim readout Responde
Slide 19: Broad Applications Across Hematology: Revenue Potential > $1 Billion
Broad Applications Across Hematology Revenue Potential > $1 Billion Success in HSCT-TMA leads to multiple follow-up market opportunities where role for nomacopan being investigated >$1bn total $100M* market $500M* market markets** • In aHUS ex-vivo model C5b9 elevated on endothelial Atypical Hemolyt
Slide 20: Ophthalmology Program In Dry AMD/GA & Dry Eye
Ophthalmology Program In Dry AMD/GA & Dry Eye Large Markets, Partnering Opportunities Dry AMD / GA Wet AMD Uveitis Dry eye 20
Slide 21: Ophthalmology Programs: Partnering Potential
Ophthalmology Programs: Partnering Potential Surface of the eye - Topical Back of Eye (intra vitreal) Clinical : Preclinical : • Several positive pre-clinical studies demonstrated rapid • C5 & LTB4 receptors both identified in retina onset and effect equivalent to cyclosporin • In EAU* model, PAS-no
Slide 22: PASylated-Nomacopan Provides Unique Treatment Approach In Back Of Eye Indications
PASylated-Nomacopan (Long-Acting) Provides Unique Treatment Approach In Back Of Eye Inflammatory Indications PAS-nomacopan Properties • Geographic Atrophy (GA): no approved therapy treatment • Manufacturing established Current Unmet • Acute IV toxicity complete Need • Dry AMD is estimated as a $5+ b
Slide 23: IVT Nomacopan: Role Of C5 & LTB4 Established In Ocular Inflammatory Conditions
IVT Nomacopan: Role Of C5 & LTB4 Established In Ocular Inflammatory Conditions Nomacopan and PAS-nomacopan • In mouse eye inflammation model (1, 2) Effect on VEGF levels in mouse eye inflammation − Significant VEGF reduction by PAS-nomacopan, equiv. to anti-VEGF − Additionally retinal inflammation r
Slide 24: Potential Across Multiple Pulmonary Indications
Potential Across Multiple Pulmonary Indications Large Markets, Partnering Opportunities Severe asthma COVID-19 COPD PAH 24
Slide 25: Additive Role Of C5 & LTB4 Across Multiple Pulmonary Indications
Additive Role Of C5 & LTB4 Established Across Multiple Pulmonary Indications Lung model of immune-complex alveolitis Dual inhibition superior to C5 or LTB4 inhibition alone • Leukotriene pathway validated in the lung. Zileuton® approved in severe asthma • Preclinical lung models show additive effect
Slide 26: Complex Pathology & Progression Of Severe Lung Inflammatory Diseases
Complex Pathology & Progression Of Severe Lung Inflammatory Diseases Reflects Potential For Inhibiting Multiple Pathways COVID-19 Pneumonia Severe Asthma • Potential in a range of lung disorders, characterised by excessive neutrophil activity and exacerbations • Leukotriene inhibition is an establis
Slide 27: Akari Summary
Akari Summary • Therapeutic targets in C5 and LTB4 validated by recent $1 billion+ acquisitions* of companies targeting complement-mediated diseases • Multiple inflection points in the near term – BP: Phase 3 recruitment expected Q4 2021 – TMA-HSCT: Phase 3 pediatric study ongoing – Ophthalmology: R
Slide 28: Appendix
AKARI Appendix
Slide 29: LTB4 Ligand Capture: Advantageous & Unique MOA
LTB4 Ligand Capture: Advantageous & Unique MOA Arachidonic acid Zileuton* Off-Target Effects of Other Inhibitors MK-0633 5-LOX TA-270 FLAP GSK2190915 5-LOX / FLAP inhibitors LTA4 DG-031 • Reduces anti-inflammatory lipoxins MK886** Lipoxygenases BLT1/BLT2 antagonists LTA4H • Realization that anti-inf
Slide 30: Interaction Of C5 & LTB4 in Bullous Pemphigoid Pathology
Interaction Of C5 & LTB4 in Bullous Pemphigoid Pathology Sadik et al., Semin Immunol 37:21-29 (2018) 30
Slide 31: Rational for Nomacopan in Bullous Pemphigoid
Rational for Nomacopan in Bullous Pemphigoid Preclinical Efficacy & Elevated C5a/LTB4 (In BP Patients) Elevated levels of LTB4 and C5a indicate activation of Nomacopan inhibiting C5+LTB4 more effective ABSA than inhibiting LTB4 alone complement and synthesis of LTB4 in blisters LTB4 levels C5a level
Slide 32: Role Of LTB4 In Neovascularization Of AMD
Role Of LTB4 In Neovascularization Of AMD • LTB4 are released by damaged RPE in AMD • LTB4 recruits immune cells including macrophages • Recruited macrophages produce VEGF • VEGF leads to CNV to form wet AMD • Anti-VEGF is the standard of care for wetAMD. It works mainly by reducing choroidal neovas
Slide 33: Cooperative Research & Development Agreement (CRADA) With US Army In Trauma
Cooperative Research & Development Agreement (CRADA) With US Army In Trauma USAISR study of complement level in trauma patients 4x increase in sC5b-9 levels in trauma patients • Ongoing collaboration with U.S. Army Institute of Surgical Serum sC5b-9 (ng/ml) Research (USAISR) to evaluate nomacopan ac
Slide 34: Active Pipeline Program Expansion
Active Pipeline Program Expansion Engineered Nomacopan Inhibition of complement alternative • Long-acting PASylated nomacopan with potential for weekly SQ / pathway rabbit red blood cell lysis IVT dosing 120 Nomacopan • Tissue targeted : nomacopan linked to peptides which bind to Eculizumab specific
Slide 35: Combined Inhibition Of Complement & Leukotriene Pathways To Treat Inflammatory Diseases
Combined Inhibition Of Complement & Leukotriene Pathways To Treat Inflammatory Diseases September 2021
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