Full Press Release Details
Akari Therapeutics Announces International Clinical Development
Program of Nomacopan for the Potential Treatment of COVID-19 Pneumonia
NEW YORK and LONDON, August 31, 2020 - Akari Therapeutics,
Plc (Nasdaq: AKTX), a Phase III biopharmaceutical company focused on innovative therapeutics to treat orphan autoimmune and inflammatory
diseases where the complement and/or leukotriene systems are implicated, announces its intention to develop nomacopan as a potential
treatment for COVID-19 pneumonia through integrated clinical trial programs in U.S., U.K. and Brazil.
Clive Richardson, Chief Executive Officer of Akari Therapeutics,
said, "There remains an overwhelming need for more effective treatment of hospitalized COVID-19 pneumonia patients. I am
pleased nomacopan has been selected by the U.K.'s AGILE clinical program. I can also report that we are now treating patients
in Brazil and the U.S. in initial proof of principle studies, with the objective of progressing into randomized clinical studies
in the fourth quarter of 2020. We believe nomacopan has the potential to inhibit the key proinflammatory and prothrombotic pathways
driving this disease, and hence meaningfully reduce morbidity and mortality in this COVID-19 patient group."
Scientific rationale for potential use of nomacopan in COVID-19
Nomacopan's dual complement (C5) and leukotriene (LTB4)
inhibition blocks several key inflammatory pathways that drive COVID-19 pneumonia.
Terminal complement activation by formation of C5a and the membrane
attack complex (C5b9) is associated with direct vascular damage, microthrombi and long-term damage to the lung and other organs
in COVID-19 patients1. A causative role for complement activation has been shown in other inflammatory diseases with
shared pathophysiological components, such as hematopoietic stem cell transplant-related thrombotic microangiopathy (TMA-HSCT)2
in which Akari has an open Phase III Investigational New Drug (IND) application.
Neutrophil accumulation in the lungs is another key feature
of COVID-19 pneumonia, resulting in cytokine storm syndrome' and associated epithelial damage in lung and other organs.
Leukotriene (LTB4) is one of the most potent known chemo attractants of neutrophils and other neutrophil chemo-attractants appear
to rely on LTB4 synthesis for recruitment of neutrophils from distal sites. Leukotriene inhibitors are approved for treatment of
asthma and are being tested in COVID-19 pneumonia3 due to their ability to block multiple cytokines. Cytokines and chemokines
inhibited by nomacopan4 include GM-CSF, IL1 alpha, IL1beta, IL2, IL-6, IL17, TNF, RANTES, MCP1, MIP1alpha andMIP1beta
all of which have been reported to be elevated in COVID-19 pneumonia patients5.
The potential additive benefits of both C5 and LTB4 inhibition
by nomacopan have previously been demonstrated in preclinical models of viral induced acute respiratory distress syndrome (ARDS)
with reduced inflammation and mortality6. Moreover, the combined inhibition of both C5 and LTB4 demonstrated by nomacopan
was superior to inhibition by either C5 or LTB4 alone in a mouse model of acute lung inflammation, highlighting the additive effect
of inhibiting both these innate immune pathways7.
Akari believes that this inhibition of multiple inflammatory
pathways distinguishes nomacopan from other potential therapies focused on a single mechanism of action. In addition to nomacopan's
fast onset of action, the rapid normalization of complement and LTB4 levels at the end of treatment has the potential to avoid
the risks of longer-term immunosuppression typical of monoclonal antibodies.
Staged clinical development plan with nomacopan for the treatment
of COVID-19 pneumonia
Akari's strategy for advancing clinical development of
nomacopan as a potential COVID-19 pneumonia treatment includes: (1) identifying biomarkers to optimize patient selection; (2) completing
initial proof of principle studies in hospitalised COVID-19 patients; (3) conducting integrated randomized clinical trials in the
U.S., Brazil and the U.K, and (4) seeking regulatory approval if the results of the randomized clinical trials satisfactorily demonstrate
the safety and efficacy of nomacopan as a treatment of COVID-19 pneumonia.
An observational study relating to biomarkers that may identify
COVID-19 patients who are particularly suitable for nomacopan treatment is ongoing in the U.K. Data has been collected on approximately
50 patients with COVID-19 pneumonia and analysis of the samples is in process with data expected early in the fourth quarter of
2020. The second part of the program, a longitudinal study taking repeat samples from COVID-19 patients with worsening disease
Initial POP treatment in patients with COVID-19 pneumonia via
expanded access programs (EAPs) are ongoing in the US. In Brazil, recruitment to a similar POP treatment study has been completed
and the data will be reviewed for safety by the Data and Safety Monitoring Board (DSMB). If the DSMB concludes that the drug is
safe, the program in Brazil will progress to a randomized study in the fourth quarter of 2020.
These COVID-19 programs build on the existing Akari clinical
experience in the use of nomacopan, underpinned by 35 cumulative patient-years of nomacopan safety data with no reported drug related
SAEs, and clinical response across a range of inflammatory conditions in Phase II and Phase III development.
Planned randomized clinical studies
Akari intends to conduct multiple randomized controlled studies
in the U.S., U.K. and Brazil based on the same clinical study design.
In the U.S., Akari is collaborating on a proposed investigator-led
multi-center randomized study the commencement of which is subject to U.S. Food and Drug Administration (FDA) approval of a related
IND. In Brazil, the POP study is expected to progress into a similar randomized trial, pending successful outcome of the DSMB review.
In the U.K., nomacopan has been selected by the AGILE platform
as a new potential treatment for patients with COVID-19 pneumonia. AGILE is a dedicated therapeutic development platform supported
by the Wellcome Trust and UNITAID to identify, support and develop promising treatments for COVID-19. The AGILE program is sponsored
by the Royal Liverpool Hospital, U.K. With AGILE's support, Akari is also exploring extending the nomacopan COVID-19 clinical
program into multiple countries in Africa, with potential patient recruitment starting in the fourth quarter of 2020.
Subject to additional comments from regulators, the trial protocols
for the planned randomized clinical trials would provide for patients to be randomized 2:1 nomacopan plus standard of care (SoC)
or SoC alone, with an initial target of around 60 patients in each of the individual study settings. Patients would be on supportive
oxygen (not intubated) and be recruited following admission to hospital. The primary endpoint is time to normalization of oxygen,
while the secondary endpoint will include need for intubation and mortality. Patients will receive a daily subcutaneous dose of
nomacopan for up to 14 days, with study monitoring and completion after two months. The SoC arm for the trials incorporates the
latest treatments where available, including dexamethasone and remdesivir, both of which have a different mode of action to nomacopan
and as such, nomacopan has the potential to add additional efficacy to either or both of these treatments. In examining the efficacy
of nomacopan Akari expects to consider the totality of the data across these studies using the same endpoints.
Professor Tim Higenbottam, President Faculty of the Pharmaceutical
Medicine of the Royal Colleges of Physicians U.K., said, "It is increasingly clear that the complexity in treating COVID-19
pneumonia relates to its impact on multiple pro-inflammatory pathways. For an effective treatment, we need a broad acting anti-inflammatory
and the fact that nomacopan has been shown in clinical trials to inhibit the pathways that underpin this severe devastating disease
creates a promising platform for its current clinical investigation."
Conference call and webcast
Akari will host a conference call and webcast today, August
31, 2020, at 8:30 a.m. EDT (1:30 p.m. BST). The conference call may be accessed by dialing (844) 461-9933 (Toll-Free) or (636)
812-6633 (international) using the conference ID 2469894. The webcast can be accessed live via the Investor Relations section
of the Akari website at http://investor.akaritx.com/news-and-events/events.
About Akari Therapeutics
Akari is a biopharmaceutical
company focused on developing inhibitors of acute and chronic inflammation, specifically for the treatment of rare and orphan
diseases, in particular those where the complement (C5) or leukotriene (LTB4) systems, or both complement and leukotrienes together,
play a primary role in disease progression. Akari's lead drug candidate, nomacopan (formerly known as Coversin), is a C5 complement
inhibitor that also independently and specifically inhibits leukotriene B4 (LTB4) activity.
Cautionary Note Regarding Forward-Looking Statements
Certain statements in this press release constitute "forward-looking statements" within the meaning of the Private
Securities Litigation Reform Act of 1995. You should not place undue reliance upon the Company's forward looking statements.
Except as required by law, the Company undertakes no obligation to revise or update any forward-looking statements in order to
reflect any event or circumstance that may arise after the date of this press release. 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 U.S. 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.