Corporate Overview. July 2018

Transcription

1 Corporate Overview July 2018 Copyright Akari Therapeutics, Plc

2 Disclaimers Certain statements in this presentation constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act and Section 21E of the Securities Exchange Act and are usually identified by the use of words such as "anticipates," "believes," "estimates," "expects," "intends," "may," "plans," "projects," "seeks," "should," "will," and variations of such words or similar expressions. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Securities Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a variety of risks and factors that are beyond our control. Risks and uncertainties for our company include, but are not limited to: needs for additional capital to fund our operations; an inability or delay in obtaining required regulatory approvals for Coversin and any other product candidates, which may result in unexpected cost expenditures; risks inherent in drug development in general; uncertainties in obtaining successful clinical results for Coversin and any other product candidates and unexpected costs that may result therefrom; failure to realize any value of Coversin and any other product candidates developed and being developed in light of inherent risks and difficulties involved in successfully bringing product candidates to market; inability to develop new product candidates and support existing products; the approval by the FDA and EMA and any other similar foreign regulatory authorities of other competing or superior products brought to market; risks resulting from unforeseen side effects; risk that the market for Coversin or other product candidates may not be as large as expected; unanticipated delays in clinical trials; inability to obtain, maintain and enforce patents and other intellectual property rights or the unexpected costs associated with such enforcement or litigation; outcome of the putative shareholder litigation; outcome of SEC requests for information; inability to obtain and maintain commercial manufacturing arrangements with third party manufacturers or establish commercial scale manufacturing capabilities; unexpected cost increases and pricing pressures; and uncertainty of our ability to raise capital and our inability to meet working capital needs. Many of these factors that will determine actual results are beyond our ability to control or predict. For a discussion of the factors that may cause our actual results, performance or achievements to differ materially from any future results, performance or achievements expressed or implied in such forward-looking statements, see the Risk Factors section of our most recently filed 20-F and in the Form 6-K filed with the SEC on October 17, Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. The statements made in this presentation speak only as of the date stated herein, and subsequent events and developments may cause our expectations and beliefs to change. Unless otherwise required by applicable securities laws, we do not intend, nor do we undertake any obligation, to update or revise any forward-looking statements contained in this presentation to reflect subsequent information, events, results or circumstances or otherwise. While we may elect to update these forward-looking statements publicly at some point in the future, we specifically disclaim any obligation to do so, whether as a result of new information, future events or otherwise, except as required by law. The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products. 2

3 Akari Overview Creating drugs for acute and chronic orphan inflammatory diseases by modulating the C5 and LTB4 pathways Lead drug candidate, Coversin, has potential in a wide range of diseases Key differentiation: dual complement & leukotriene inhibition Multiple routes of administration possible Phase III trial opened Q in paroxysmal nocturnal hemoglobinuria (PNH) Phase II trial open in atypical hemolytic-uremic syndrome (ahus) Clinical trials focused on Coversin s dual activity. Phase II trial in bullous pemphigoid (BP) opened Q Phase II trial in atopic keratoconjunctivitis (AKC) initiation expected Q Listed on NASDAQ (AKTX); headquartered in London; office in New York 3

4 Phase III Lead Compound Coversin: Differentiated Complement C5 Inhibition Proven C5 binding Met Phase II primary efficacy reduction in LDH 1.8X ULN at day 28 CH50 below limit of quantification (from day 1) Positive safety profile Nine patients on ongoing treatment for between 2 and 28 months; cumulative total of over 100 patient months of treatment No SAEs related to Coversin and no neutralizing antibodies Proven LTB4 binding Inhibits LTB4 induced human neutrophil migration Successfully self administered by subcutaneous injection Engineered versions extend half life or provide disease targeting 4

5 Akari Portfolio Builds on Complement Experience Coversin Systemic SQ PNH 1 (Fast Track & Orphan Drug Designation) ahus 2 (Orphan) BP 3 * (Orphan) Engineered SQ Coversin LA (Long Acting) Tissue Targeted (NMJ 4 ) Coversin Topical Eye AKC 5 * (Orphan) Preclinical Phase I Phase II Phase III 1. PNH: Paroxysmal nocturnal hemoglobinuria; 2. ahus: Atypical hemolytic-uremic syndrome; 3. BP: Bullous Pemphigoid; 4. NMJ: neuromuscular junction; 5. AKC: Atopic keratoconjunctivitis; * Dual action MOA: C5 & LTB4 5

6 Akari s Therapeutic Positioning Two Areas of Focus Complement Inhibition Sub Q delivery differentiated against current IV standard of care Phase III trial : PNH (SQ) (Paroxysmal nocturnal hemoglobinuria) Phase II trial : ahus (SQ) (Atypical hemolytic-uremic syndrome) Engineered Coversin for additional targets Leukotriene Complement Inhibition Differentiated and unique mechanism of action Phase II trial : AKC (topical) (Atopic keratoconjunctivitis) Phase II trial : BP (SQ) (Bullous Pemphigoid) Other earlier stage compounds Potential for significant second-entrant market share Potential to achieve dominant market share as sole provider 6

7 COMPLEMENT PROGRAM 7

8 Coversin Differentiated Complement Inhibitor Coversin TM Soliris (Alexion) Chemistry Recombinant small protein Antibody Target C5 & LBT4 C5 Administration Subcutaneous injections IV infusion Frequency Daily Bi-monthly Advantages Self-administration Treating patient with eculizumab resistant C5 polymorphism Marketed product Proven efficacy Subcutaneous Administration Provides Relevant Patient Benefits Primary market research indicates that >20% of patients likely to prefer subcutaneous delivery vs. every other month IV 8

9 Treatment Duration, Safety, and Tolerability of Patients Treated To Date Eculizumab-resistant PNH patients (CONSENT) 1 M 17 months Continuing Phase II PNH patients* Patient who did not complete Phase II (COBALT) study 43 Days 15 Months 14 Months 13 Months 12 Months 8 Months 7 Months 6 Months 28 Months Drug well tolerated by patients No SAEs related to Coversin *Aggregate time patients included in Phase II COBALT and long term safety CONSERVE trials 9

10 PNH Phase II Clinical Trial Results 8 patients entered Phase II PNH COBALT trial, the last 3 on a revised higher dosing regime 7 patients have completed trial and opted to continue into long-term safety study - CONSERVE 1 patient withdrawn at Day 43 due to suspected co-morbidity unrelated to Coversin treatment Primary efficacy endpoint met (LDH 1.8 x ULN by Day 28) All patients self-injecting Five injecting once-daily; two injecting 12-hourly Coversin well tolerated with good safety profile No treatment related serious adverse events (SAE) Two eculizumab-resistant patients treated under separate clinical protocol 10

11 Median and range LDH x ULN COBALT Phase II LDH x Upper Limit of Normal LDH X Upper Limit of Normal All patients Median Primary efficacy end point day 28 Original dosing regimen Revised dosing regimen Original maintenance dosing: 30 mg daily (N=5, N=4 after day 43*) Revised maintenance dosing: 45 mg daily (N=3) Days since first dose of Coversin LDHx ULN at Day 28 : 1.4, 2.2, 2.3, 1.3, 1.4, 2.7, 1.6, 1.3 : at Day 60 : 1.5, 2.1, 1.8, 2.2, 1.5, 1.4, 1.3 at Day 90 : 1.6, 2.4, 2.0, 2.5, 1.9, 1.5, 1.2 *Patient withdrawn at day 43 with suspected co-morbidity unrelated to treatment 1.8 x ULN 1.5 x ULN 11

12 LDH (IU/ml) LDH (IU/ml) Two PNH Patient Case Studies One Resistant to Eculizumab; One Difficult To Treat Eculizumab-Resistant PNH Patient Phase II Aplastic Anemia Patient x ULN x ULN Weeks Weeks Patient with C5 polymorphism resistant to eculizumab Initial dose ranging exercise over first 3 weeks Stable for over two years of treatment Excluded from other competing trials Treated on 45mg dosing regime Transfusion levels significantly reduced 12

13 LDH x ULN A second Eculizumab-Resistant PNH Patient treated with Coversin LDH X Upper Limit of Normal x ULN Days since first dose of Coversin Patient treated under IND in New York with revised dosing regime 13

14 Units of PRBC transfused COBALT Transfusion Data (Patient B) (Patient C) (Patient D) (Patient E) (Patient G) (Patient H) to 3 months before COBALT 3 to 0 months before COBALT COBALT 3 months after COBALT Six patients transfused in 6 months prior to entering COBALT; 3 became transfusion independent in COBALT and have remained so during the long term safety study 14

15 Ongoing and Upcoming Phase III Program in PNH FDA post-phase II COBALT review meeting completed Phase III PNH program initiated with CAPSTONE First site opened March 2018 Minimum of 30 patients to be enrolled CAPSTONE: Naïve patients Randomized to Coversin + standard of care vs. standard of care Six month duration followed by an observation period of up to three months Primary endpoint based on transfusion avoidance and hemoglobin stabilization ASSET: Eculizumab-treated patients switched to Coversin To be preceded by small proof of principle study 15

16 Coversin Targeting Atypical Hemolytic Uremic Syndrome (ahus) Ongoing open-label Phase II trial Up to 10 naïve ahus patients to be enrolled Primary endpoint: proportion of subjects with normal platelet count at Day 180 (defined as platelet count 150x 10 9 /L) C5 inhibition approved as a treatment for ahus ahus physicians have expressed support for once-daily Coversin More therapeutic flexibility for episodic patients Patient convenience 16

17 Planned Commercial Administration Pen Injector One Week of Dosing Wide range of administration options SubQ Topical Drops Inhaled IV Via PBS eye drops; formulation work ongoing Currently investigating Current Presentation for PNH Coversin lyophilised powder in 6ml vials reconstituted to 30mg/ml in PBS Once daily maintenance dose is 45mg for PNH (1.5ml from three vials) Annual dose is 16.5g of Coversin Higher concentration for pen injector Daily 0.3ml from a 3ml cartridge that provides one week supply Liquid stable room temperature > 2 weeks Proposed Pen Injector 3ml cartridge / one week of dosing Reusable auto injector pen, already commercially approved Planned for 2019: Comparability study in patients Phase I trial and human factor 17

18 DUAL C5 AND LEUKOTRIENE B4 (LTB4) PROGRAMS 18

19 Coversin: Dual Acting Anti-Inflammatory Protein Independent C5 & LTB4 inhibitory activity Complement C5 binding K D 1nM Top view of Coversin (Cyan) bound to C5 Jore et al., Nat Struct Mol Biol Features Compact globular 17kDa protein Highly soluble and low viscosity (like water at 150mg/mL) No post-translational modifications Equally active on C5 and LTB4 from mice to men Binding affinity tuned by natural selection Eicosanoid LTB4 binding K D 300pM Detail Coversin binding to LTB4 Roversi et al., J Immunol

20 Dual Leukotriene & Complement Inhibition by Coversin Potential in Wide Range of Diseases with Unmet Need Complement Only PNH MG ahus NMO Leukotriene & Complement Sjögren s Mucous Membrane Pemphigoid Bullous Pemphigoid AKC Bronchiolitis obliterans Goodpasture s AATD PAH Rheumatoid Arthritis Dry Eye Asthma COPD Trauma 20

21 Combining LTB4 and C5 Inhibition in Single Product Unique Potential Clinical Benefits Mouse Model Neutrophil recruitment to lung induced by LPS Dual action (Coversin) more effective than C5-only Coversin or Zileuton alone LTB4 is a powerful inflammatory mediator, driving recruitment and activation of neutrophils and eosinophils Existing drugs, like Zileuton, block different parts of Leukotriene pathway Coversin direct capture of LTB4 So no off-target effects by targeting higher points in pathway Combined inhibition by direct binding of both LTB4 & C5 has key advantages Both implicated in most autoimmune conditions Both cross-prime pro-inflammatory effects and act independently Pneumolabs, Study No. 679, December

22 Bullous Pemphigoid (BP) Significant Unmet Need Phase I/II open label trial Opened Q : centers in Holland and Germany Autoantibody mediated immune complex deposition initiates complement cascade and inflammatory process LTB4 and C5a recruit neutrophils to dermalepidermal junction and amplifies inflammation Proof of efficacy in BP could allow expansion into other inflammatory skin conditions 22

23 Coversin Demonstrated Benefit in Bullous Pemphigoid Model ~60% reduction in affected area on Coversin (Sub Q) compared to vehicle or steroid in mouse model Clear dose response P= between vehicle and 250 µg/kg Vehicle 250µg/kg Coversin Preclinical passive mouse model from Dr. Sadik in Lubeck, Germany Leading Bullous Pemphigoid center 23

24 Atopic Keratoconjunctivitis (AKC) Phase I/II randomized, double masked, placebo-controlled trial Planned start Q Severe eye surface inflammation causing infiltration of immune cells (neutrophils & T cells) A cause of blindness worldwide Topical drugs, such as steroids or cyclosporin, often not effective or cannot be given chronically Both complement and LTB4 known to be involved Progresses to affect cornea; may lead to vision loss Proof of efficacy in AKC could allow expansion into other topical eye indications 24

25 Inflammation score Significant Benefit in Late-Phase Ocular Inflammation Collaboration with Moorfields Hospital (Institute of Ophthalmology, London) EIC pre-clinical model of severe eye surface inflammation Effect of Coversin on OVA induced inflammation (n=16 per group) Placebo Coversin p<0.01 Day 3 Day 4 Day 5 Day 6 p< C57/Bl6 mice sensitized to OVA for 14 days OVA eye surface challenge for 5 days post sensitization (days 0 6) Coversin applied once daily on days 3 6 after inflammatory response well established Maximum effect seen after 3 days of Coversin treatment (late phase of inflammation) Coversin - 64% reduction in inflammatory score compared to placebo Timing indicative of T cell response Historical comparison*: Cyclosporine A (0.1%) c. 45% reduction Betamethasone (0.1%) - no significant reduction * Shii D, Nakagawa S, Yoshimi M et al. 2010; Biol Pharm Bull 33(8):

26 % Total Lysis Coversin LA: Once Weekly Formulation Human PK simulation of free C5 following single dose injection Coversin Inhibition of complement alternative pathway rabbit red blood cell lysis Coversin Eculizumab PAS Coversin Coversin &Eculizumab 40 5% PAS Coversin Drug concentration (µm) Terminal half life in humans estimated at four days based on pharmacokinetic (PK) data in mice and rats Clean initial toxicology profile comparable to unmodified Coversin Phase I clinical study planned for Q Sources: Scaling PAS-Coversin PK from mouse and rat to man, BAST Inc. Limited. Analysis UCL Laboratories, December

27 Tissue Targeting With Coversin NMJ To Myasthenia Gravis Coversin linked to peptide which binds agrin which differentially concentrates the drug at basal lamina of neuromuscular junction (NMJ) 100% complement inhibitory activity retained Unmodified Coversin excellent therapeutic effect in rat models of MG (1, 2) Rat model of passive MG Both NMJ targeting variants dosed at 1mg/kg Proceeding with NMJ Possible advantages of NMJ-targeted Coversin include : potentially significantly lower dose for same efficacy allowing a lower price point and availability to a larger proportion of patients Increased concentration in target tissue may improve efficacy 1. Hepburn NJ et al. J Biol Chem 282: (2007); 2. Soltys J et al. Ann Neurol 65: (2009) 27

28 Corporate Overview June 2018