Akari Therapeutics
BioFuture Company Presentation Rachelle Jacques, President & CEO
Forward-Looking Statements
Certain statements in this presentation constitute "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 the current views of Akari Therapeutics, Plc (the "Company", "we",. "our" and "us") and its plans, intentions, expectations, strategies and prospects, which are based on the information currently available to it and on assumptions it has 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. Such risks and uncertainties for our company include, but are not limited to: needs for additional capital to fund our operations; our ability to continue as a going concern; uncertainties of cash flows and inability to meet working capital needs; an inability or delay in obtaining required regulatory approvals for nomacopan (Coversin) and any other product candidates that may result in unexpected cost expenditures; our ability to successfully develop nomacopan as a treatment for COVID-19 related pneumonia and to successfully commercialize any product in that indication; our ability to obtain orphan drug designation in additional indications; risks inherent in drug development in general, and risks specific to the development of potential treatments for COVID-19-related illnesses; uncertainties in obtaining successful clinical results for nomacopan and any other product candidates and unexpected costs that may result from difficulties enrolling patients in our clinical trials; failure to realize any value of nomacopan and any other product candidates developed or 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 product candidates; the approval by the FDA and EMA an 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 opportunity for nomacopan may not be as large as expected; risks associated with a resurgence of the COVID-19 pandemic; inability to obtain, maintain and enforce patents another intellectual property rights or the unexpected costs associated with such enforcement or litigation; inability to obtain and maintain commercial manufacturing arrangements with third party manufacturers or establish commercial scale manufacturing capabilities; the inability to timely source adequate supply of our active pharmaceutical ingredients from third-party manufacturers on whom the company depends; unexpected cost increases and pricing pressures and risks and other risk factors detailed in our public filings with the U.S. Securities and Exchange Commission; including our most recently filed Annual Report on Form 20-F filed with the SEC.
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 law, 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.
Unless otherwise indicated, information contained in this presentation concerning our industry, competitive position and the markets in which we operate is based on information from independent industry and research organizations, other third-party sources and management estimates. Management estimates are derived from publicly available information released by third-party sources, as well as data from our internal research, and are based on assumptions made by us upon reviewing such data, and our experience in, and knowledge of, such industry and markets, which we believe to be reasonable, but we have not independently verified the accuracy of this information. Any industry forecasts are based on data (including third-party data), models and experience of various professionals and are based on various assumptions, all of which are subject to change without notice. In addition, projections, assumptions and estimates of the future performance of the industry in which we operate and our future performance are necessarily subject to uncertainty and risk due to a variety of factors, including those described in "Cautionary Note Regarding Forward-Looking Statements." These and other factors could cause results to differ materially from those expressed in the estimates made by the independent parties and by us.
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.
This presentation shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or other jurisdiction
2
Akari Overview
2IN | 1. Novel Complement + LTB4 |
inhibitor | |
Nomacopan is a unique asset inhibiting 2 | |
1 | co-dependent, proinflammatory targets: |
complement C5 and leukotriene B4 (LTB4) |
2. Broad potential
Potential for use in several diseases; commercial flexibility due to multiple routes of administration (subcutaneous, topical, intravitreal, IV)
3. Robust clinical dataset
Extensive clinical and safety data from multiple clinical trials
4. HSCT-TMA Phase 3
Phase 3 clinical trial in pediatric hematopoietic stem cell transplant-related thrombotic microangiopathy (HSCT- TMA); no approved therapies and ~80% mortality; FDA Orphan, Fast Track designations; Rare Pediatric Disease designation with potential for Priority Review Voucher upon approval; granted European Commission orphan drug designation; potential for adult indication
5. GA Pre-Clinical
Pre-clinical program investigating PAS- nomacopan in geographic atrophy (GA) with target dose interval of 3 months or longer without increased risk of choroidal neovascularization (CNV) which is associated with complement-only inhibitors approved for GA treatment
3
Complement Technologies Continue to Garner
Significant Investment
8 acquisitions 2017-2022 | 14 collaborations 2017-2022 |
Company* | Company Value |
Product(s) Status/Phase Type
Indications
Astra Zeneca / Alexion
Apellis
Astellas / Iveric
$39 billion completed acquisition
$3.85 billion market cap**
$5.9 billion completed acquisition
Soliris®/Ultomiris®
Empaveli®/Syfovre®
IZERVAY™
On market | C5 |
On market | C3 |
NDA approved | C5 |
PNH, aHUS, gMG, NMOSD,/PHN, aHUS
PNH/GA
GA
Amgen / ChemoCentryx
$3.7 billion completed acquisition
Tavneos®
On market | C5 |
ANCA-Vasculitis
UCB / Ra Pharma
$2.3 billion completed acquisition
zilucoplan
Phase 3 | C5 |
gMG
* A selection of companies with complement therapeutics on market or in development ** As of July 24, 2023 | |
4 | Sources: Needham January 2023 Complement report, company public disclosures. Accessed June 7, 2023. |
Nomacopan Is a Novel Dual Action Recombinant Protein Discovered In Ticks
Ticks secrete immunomodulatory proteins that help them control host responses (inflammation, pain, itch and blood flow)
• These are the same responses
that may be out of control in certain human autoimmune and inflammatory conditions
Nomacopan inhibits two pathways that can cause damaging inflammation, while preserving important immune functions (such as opsonization)
ComplementLeukotriene
Anaphylatoxins
- C5a, LTB4 and MAC act jointly on neutrophils, macrophages and other cell types that can cause inflammation and damage
- Signaling interplay between C5 and LTB4 may lead to damaging inflammation
1
nomacopan
2 Cell activation, lysis and autoimmunity
Nomacopan does not impair the anti- inflammatory action of the leukotriene pathway
Nunn MA, Sharma A, Paesen GC et al. Complement inhibitor of C5 activation | ||
5 | from the soft tick Ornithodoros moubata. J Immunol. 2005; 174:2084-2091 | CONFIDENTIAL |
The Akari Pipeline Includes Near-Term Potential, Promising Pre-Clinical Program
6
Previous Areas of Clinical Development, Including PNH
and BP, Support Current Development Pathways
- In addition to current areas of focus, Akari has conducted clinical research in several other areas, including Phase 2/3 clinical trials of subcutaneous nomacopan for treatment of bullous pemphigoid (BP) and paroxysmal nocturnal hemoglobinuria (PNH)
- This research set a solid foundation for the current Phase 3 clinical trial in pediatric HSCT-TMA
-
In a Phase 3 study in PNH, 100% of untreated patients were transfusion dependent while 0% of nomacopan patients were transfusion dependent
o >32 patient years of nomacopan exposure in PNH in 19 patients
Proportion of PNH patients who were transfusion independent following entry to trial
N=4
- In clinical studies of nomacopan in BP, 7 of 9 patients
responded to nomacopan1
- 3 showed >80% reduction in BPDAI by day 42 (BP disease activity)
N=5
All prior treatment, including steroids, withdrawn ~one week prior to initiation of treatment
with nomacopan. Lesional mometasone was administered to Day 21.
7 | 1. Sadik CD, et al. Evaluation of nomacopan for treatment of bullous pemphigoid a phase 2a non0randomized controlled trial. JAMA Dermatol. 2022; 158: 641-649 |
THROMBOTIC
MICROANGIOPATHIES
(TMAs)
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Nomacopan May Be the First Treatment for HSCT-TMA, a Condition with Mortality Up to 80%
- HSCT-TMAis a rare but serious complication of HSCT involving complement activation, inflammation, tissue hypoxia and blood clots, leading to progressive organ damage and death
- Graft versus host disease is commonly present in patients with severe HSCT-TMA1
- Mortality is 80% across adults and children (severe)2
- No approved treatment options
Nomacopan in HSCT-TMA
1. Complement C5 inhibition efficacy
Nomacopan C5 inhibition supported by clinical PNH research3
2. Simple, fixed dosing
Nomacopan clinical trials are establishing a simple, fixed dose in children; ease of dosing at home or in hospital for adults
3. Rapid onset & offset of action
Rapid onset/offset of action allows complement re-activation when needed
4. LTB4 inhibition may slow GVHD progression
LTB4 is often elevated in patients with GVHD and nomacopan inhibition of LTB4 may slow GVHD progression4
1. | Jodele S, et al. Complement blockade for TA-TMA: lessons learned from a large pediatric cohort treated with eculizumab. Blood. 2020;135(13):1049-1057. | |
9 | 2. | Rosenthal J. Hematopoietic cell transplantation-associated thrombotic microangiopathy: a review of pathophysiology, diagnosis, and treatment. J Blood Med. 2016;7:181-186. |
3. | Schols S, Nunn MA, Mackie I et al. Succesful treatment of a PNH patient non-responsive to eculizumab with novel complement C5 inhibitor covers (nomacopan). Br J Hematol. 2020; 188: 332-340. | |
4. | Takatsuka H, et al. Predicting the severity of intestinal graft-versus-host disease from leukotriene B4 levels after bone marrow transplantation. Bone Marrow Transplant. 2000;26(12):1313-1316. |
Clinical Trial Patient Case Study Presented at Two
Transplantation and Cellular Therapy Meetings
A patient with severe pediatric HSCT-TMA, which typically involves multi-organ failure and other acute consequences, was discharged home from the hospital following treatment with nomacopan
- 6-year-oldmale received a cord blood HSCT for relapsed refractory acute myelogenous leukemia (AML)
- Post-transplantacute gut graft-versus-host disease (GVHD)
- TMA at day +66 post-transplant
- Treatment with a single-age,weight-based ablating dose of nomacopan day +74 followed by maintenance dosing for 21 days
- After a 3-day break in treatment for encephalopathy unrelated to nomacopan, treatment continued for a further 46 days until the end of the study with correction of the patient's urine protein creatinine ratio for ≥28 days
- Gut pathology and thrombocytopenia resolved
- No adverse events related to nomacopan
Break in nomacopan treatment for 3 days due to SAE (determined unrelated to nomacopan)
Clinical Response to Nomacopan in the Pediatric HSCT-TMASetting presented Feb. 16, 2023, at the Transplantation & Cellular Therapy Tandem Meetings. Poster available http://investor.akaritx.com/news-and-
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Akari Therapeutics plc published this content on 06 November 2023 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 06 November 2023 13:41:47 UTC.