Akari Therapeutics Plc · NASDAQ:AKTX
Akari Therapeutics — Investor Presentation (December 2021)
35 slides from Akari Therapeutics's investor presentation, Dec 21, 2021
Slide 1: Combined Inhibition Of Complement & Leukotriene Pathways To Treat Inflammatory Diseases
December 2021 Combined Inhibition Of Complement & Leukotriene Pathways To Treat Inflammatory Diseases
Slide 2: Forward-Looking Statements
2 Forward - Looking Statements Certain statements in this presentation constitute contains “forward - looking” statements within the meaning of Section 27 A of the Securities Act of 1933 and Section 21 E of the Securities Exchange Act of 1934 . These forward - looking statements reflect our current
Slide 3: Akari Overview: Targeting Inflammatory Diseases With Unmet Need
3 • Lead drug, first in class, differentiated bifunctional mechanism of action – Nomacopan directly inhibits complement C5 and leukotriene B4 (LTB4) – Targeting inflammatory indications where blocking both proinflammatory mediators may be more effective than inhibiting either pathway alone • Positiv
Slide 4: Nomacopan's Competitive Advantage: Synergistic Inhibition of Two Key Effectors
4 Nomacopan achieves synergistic effect by inhibiting two independent but related activation pathways active in multiple inflammatory diseases Nomacopan’s Competitive Advantage: Synergistic Inhibition of Two Key Effectors Driving Autoinflammation Complement (C5) inhibition Leukotriene (LTB4) inhibit
Slide 5: Nomacopan's Mechanism of Action Highly Specific and Supported by Clinical Efficacy Data
5 • Tight binding – nomacopan inhibits activation of complement C5 in a similar way to eculizumab (K D 0.1 - 1nM ) • Terminal complement fully inhibited during long - term self - administration of nomacopan by paroxysmal nocturnal hemoglobinuria (PNH) patients • Nomacopan reduced transfusion depende
Slide 6: Clinical Pipeline Progressing Into Phase 3 Studies
6 Formulation Therapy Area Disease Preclin. Phase 1 Phase 2 Phase 3 Systemic Sub - cutaneous nomacopan Dermatology Bullous Pemphigoid Hidradenitis Suppuritiva + additional opportunities Hematology Pediatric HSCT - TMA Adult HSCT - TMA + additional opportunities Clinical Pipeline Progressing Into Pha
Slide 7: Bullous Pemphigoid: Chronic Disease, No Specific Approved Therapies
7 Bullous Pemphigoid: Chronic Disease, No Specific Approved Therapies Bullous pemphigoid - Hidradenitis suppuritiva (HS) - Epidermolysis bullosa acquisita (EBA) - Mucous membrane pemphigoid (MMP) Psoriasis
Slide 8: Bullous Pemphigoid is an Auto-Immune Blistering Skin Disease with Few Treatment Options
8 Bullous Pemphigoid is an Auto - Immune Blistering Skin Disease with Few Treatment Options and no Biological Therapies High dose oral corticosteroid (OCS) use associated with approximately 3 - fold increase in mortality • Need for rapidly efficacious steroid - sparing therapy Most common auto - imm
Slide 9: Nomacopan's Dual C5 & LTB4 MOA Acts Upstream Of Most Competitors
9 Nomacopan’s Dual C5 & LTB4 MOA Together Act Upstream Of Most Competitors in Development in Bullous Pemphigoid • Nomacopan’s upstream mode of action differentiated in BP • Other drugs in development for BP primarily operate downstream of nomacopan, inhibiting specific cytokines/chemokines or immuno
Slide 10: Phase 2: Rapid Reduction in BPDAI Activity Scores On Nomacopan
10 0 10 20 30 40 50 60 (14) (7) 0 7 14 21 28 35 42 Days Phase 2: Rapid Reduction in BPDAI Activity Scores On Nomacopan • All prior treatment, including steroids, withdrawn circa one week prior to initiation of treatment with nomacopan • Addition of <30g/week low dose 0.1% llesional mometasone, a mod
Slide 11: BP Phase 3 Trial Design Summary
11 BP Phase 3 Trial Design Summary – and example response of two putative patients in the trial Disease Control weeks Tapering Remission Oral Steroid Dose Patients who do not complete tapering by week 16 cannot achieve disease remission for 8 weeks between week 16 - 24 of trial which is primary endp
Slide 12: BP Phase 3 Design Provides Interim Readout After Part A
12 BP Phase 3 Design Provides Interim Readout After Part A 10 days 24 weeks n = 16 45 mg/day nomacopan + starting 0.5 mg/kg/day OCS Primary endpoint: Achievement of Complete Disease Remission (Cr on ) on minimal OCS therapy (0.1mg/kg/day) for 8 weeks or more by Week 24 [CRon = Absence of new or esta
Slide 13: Additional Dermatology Indications for Nomacopan
13 Additional Dermatology Indications for Nomacopan HS : Other mediators being directly targeted include IL17, IL23, IL1alpha and CXCR1/2 which are downstream to and likely to be inh ibi ted by nomacopan (in addition to its direct effect on C5 and LTB4 REFERENCES: Kanni et al., 2018 : Complement act
Slide 14: HSCT-TMA: Hematopoietic Stem Cell Transplant-Related Thrombotic Microangiopathy
14 HSCT - TMA: Hematopoietic Stem Cell Transplant - Related Thrombotic Microangiopathy HSCT - TMA: Potential of high Clinical Impact No Approved Therapies Pediatric & Adult HSCT - TMA Paroxysmal nocturnal hemoglobinuria Atypical hemolytic uremic syndrome Anti - phospholipid syndrome Vasculitis TMA i
Slide 15: HSCT-TMA: Potential To Reduce Mortality In Aggressive Disease
15 HSCT - TMA (Pediatric & Adult): Potential To Reduce Mortality In Aggressive Disease High mortality rate of up to 80% associated with severe pediatric HSCT - TMA • Need for rapid, complete & sustained C5 & potentially LTB4 inhibition ~10K pediatric HSCT and ~60K adult HSCT performed in US + EU ann
Slide 16: Pediatric HSCT-TMA Phase 3 Program Goals
16 Pediatric HSCT - TMA Phase 3 Program Goals: Transfusions, Renal Function, Survival • Targeting severe HSCT - TMA with elevated sC5b9 and proteinuria • Early diagnosis and intervention critical to optimize responder outcomes • Target population c. 50% of patients with HSCT - TMA • Treatment goals
Slide 17: Primary Endpoints Pediatric HSCT-TMA Open-Label Phase 3 Study
17 Primary Endpoints Pediatric HSCT - TMA Open - Label Phase 3 Study: • Response - based end point • Reduced transfusion dependence and renal improvement PK/PD Dose confirmation, safety and efficacy N=7 (three age cohorts) Part B Up to 180 days treatment Safety and efficacy (may include Part A patie
Slide 18: Additional Hematology Indications for Nomacopan
18 Additional Hematology Indications for Nomacopan Atypical Hemolytic Uremic Syndrome Anti - phospholipid syndrome TMA+SLE, Vasculitis, etc. Pediatric HSCT - TMA $100M* market >$1bn total markets** * US and EU5 markets only ** Initial and follow - on indications; company sources Note : market size p
Slide 19: Ophthalmology Program In Dry AMD/GA & Dry Eye
19 Dry eye Dry AMD / GA Uveitis Wet AMD Ophthalmology Program In Dry AMD/GA & Dry Eye Large Markets, Partnering Opportunities
Slide 20: Topical Nomacopan: Surface of the Eye Inflammatory Diseases
20 Topical Nomacopan: Surface of the Eye Inflammatory Diseases • Nomacopan superior to dexamethasone and cyclosporin in experimental immune conjunctivitis; suppresses pro inflammatory Th2 and Th9 cells • LTB4 significantly elevated in tear fluid of allergic conjunctivitis patients and C5 and LTB4 re
Slide 21: Potential for Long-Acting PASylated-Nomacopan in Back of the Eye Diseases
21 Potential for Long - Acting PASylated - Nomacopan in Back of the Eye Diseases, Including Geographic Atrophy/Dry AMD (GA) • C5 & LTB4 receptors both identified in retina and a target for treatment across multiple back of the eye diseases including GA, uveitis and DME • In experimental autoimmune u
Slide 22: Potential Advantages of Treating Geographic Atrophy
• Complement C5 and C3 inhibition for treatment of GA looks promising • APL - 2 (anti - C3) from Apellis in submission to FDA, and Zimura (anti - C5) from Iveric in pivotal Phase 3 However, both drugs : − Have mixed clinical response in reduction in lesion growth − Cause higher incidence of new case
Slide 23: PASylated-nomacopan: Reducing CNV Risk in GA Patients
23 PASylated - nomacopan: Potentially Improved Clinical Response and Safety by Reducing CNV Risk in GA Patients Nomacopan and PAS - nomacopan reduce VEGF levels in mouse model of severe uveitis: PAS - nomacopan has comparable effect to anti - VEGF antibody • PAS - nomacopan inhibits C5 and LTB4, whi
Slide 24: Potential for PAS-nomacopan to Extend Dosing Interval for Intravitreal Injections
24 Potential for PAS - nomacopan to Extend Dosing Interval for Intravitreal Eye Injections, Increasing Safety & Convenience • PASylation of nomacopan provides major half - life extension with same potent binding to C5 and LTB4 as compared to parent drug nomacopan • Addition of PAS (a proline, alanin
Slide 25: Potential Across Multiple Pulmonary Indications
25 Potential Across Multiple Pulmonary Indications Large Markets, Partnering Opportunities COVID - 19 Severe asthma COPD PAH
Slide 26: Inhibition of C5 & LTB4 Established Across Pulmonary Preclinical Models
26 Inhibition of C5 & LTB4 by Nomacopan Established Across Multiple Pulmonary Indications in Preclinical Models Source : Roversi et al (2013) JBC 288: 18789 - 18802 • Leukotriene pathway validated in the lung. Zileuton® (general leukotriene inhibitor) approved in severe asthma • Preclinical lung mod
Slide 27: Targeting Improved Treatment of Severe Lung Exacerbations
27 Targeting Improved Treatment of Severe Lung Exacerbations • High prevalence of respiratory inflammatory disease – 2 nd most common global cause of death – Carries high personal & health care costs • Exacerbations drive clinical visits and hospital admissions, particularly in winter Patients live
Slide 28: Akari Summary
28 Akari Summary • Dysregulation of complement and leukotriene pathways implicated across a wide range of poorly treated inflammatory diseases • Multiple formulations (Sub - Q, topical, inhaled, long - acting PAS - nomacopan) provides risk diversification and flexibility in terms of partnering / col
Slide 29: Appendix
29 Appendix
Slide 30: LTB4 Ligand Capture: Nomacopan's Unique Mode of Action
30 LTB4 Ligand Capture: Nomacopan’s Advantageous & Unique Mode of Action (MOA) Arachidonic acid LTA 4 5 - LOX FLAP LTB 4 LTA 4 H Pro - inflammatory Lipoxins Lipoxygenases Anti - inflammatory LTC 4 LTD 4 LTE 4 LTC 4 S Spasmogenic GSK2190915 DG - 031 MK886** Zileuton* MK - 0633 TA - 270 LY - 293111 ON
Slide 31: Interaction Of C5 & LTB4 in Bullous Pemphigoid Pathology
31 Interaction Of C5 & LTB4 in Bullous Pemphigoid Pathology Sadik et al., Semin Immunol 37:21 - 29 (2018)
Slide 32: Rationale for Nomacopan in Bullous Pemphigoid: Preclinical Efficacy
32 ABSA Rational for Nomacopan in Bullous Pemphigoid Preclinical Efficacy & Elevated C5a/LTB4 (In BP Patients) pg/ml pg/ml LTB4 levels Human blister fluid C5a levels in blister fluid diluted 1:25 Elevated levels of LTB4 and C5a indicate activation of complement and synthesis of LTB4 in blisters • Mo
Slide 33: CRADA With US Army In Trauma
33 Early complementopathy predicts the outcomes of patients with trauma; Li Y, et al. Trauma Surg Acute Care Open 2019;4:e000217 Cooperative Research & Development Agreement (CRADA) With US Army In Trauma Inhibition of the Membrane Attack Complex of the Complement System Reduces Secondary Neuroaxona
Slide 34: Active Pipeline Program Expansion
34 Active Pipeline Program Expansion • New chemical entity with extended patent protection • Long - acting PASylated nomacopan with p otential for weekly Sub - Q and in frequent IVT dosing • Tissue targeted : nomacopan linked to peptides which bind to specific disease related tissue such as neuromus
Slide 35: Combined Inhibition Of Complement & Leukotriene Pathways To Treat Inflammatory Diseases
December 2021 Combined Inhibition Of Complement & Leukotriene Pathways To Treat Inflammatory Diseases
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