Full Press Release Details
Except as otherwise indicated herein
or as the context otherwise requires, references to "Akari," "we," "us," "our,"
the "Company" and similar designations refer to Akari Therapeutics, PLC and its subsidiaries. When we refer to "you,"
we mean prospective investors in the Company.
We are a clinical-stage
biopharmaceutical company focused on developing inhibitors of acute and chronic inflammation, specifically the complement system,
the eicosanoid system and the bioamine system for the treatment of rare and orphan diseases. Each of these systems has scientifically
well-supported causative roles in the diseases being targeted by us. We believe that blocking early mediators of inflammation will
prevent initiation and continual amplification of the processes that cause certain diseases.
Ticks have undergone
300 million years of natural selection to produce inhibitors that bind tightly to key highly-conserved inflammatory mediators,
are generally well tolerated in humans, and remain fully functional when a host is repeatedly exposed to the molecule. Our molecules
are derived from these inhibitors.
Our lead product candidate,
Coversin , which is a second-generation complement inhibitor, acts on complement component-C5, preventing release of C5a
and formation of C5b-9 (also known as the membrane attack complex, or MAC), and independently also inhibits leukotriene B4,
or LTB4, activity, both elements that are co-located as part of the immune/inflammatory response. Coversin is a recombinant small
protein (16,740 Da) derived from a protein originally discovered in the saliva of the Ornithodoros moubata tick, where it modulates
the host immune system to allow the parasite to feed without alerting the host to its presence or provoking an immune response.
Coversin has received
orphan drug status from the U.S. Food and Drug Administration, or the FDA, and the European Medicines Agency, or the EMA, for paroxysmal
nocturnal haemoglobinuria, or PNH, and Guillain Barr Syndrome, or GBS. Orphan drug designation provides us with certain
benefits and incentives, including a period of marketing exclusivity if regulatory approval of the drug is ultimately received
for the designated indication. The receipt of orphan drug designation status does not change the regulatory requirements or process
for obtaining marketing approval and the designation does not mean that marketing approval will be received. We intend to apply
in the future for orphan drug designation in additional indications we deem appropriate. We have also received fast track designation
for the investigation of Coversin for treatment of PNH in patients who have polymorphisms conferring eculizumab resistance.
Our initial clinical
targets for Coversin are PNH and atypical Hemolytic Uremic Syndrome, or aHUS. We are also targeting patients with polymorphisms
of the C5 molecule which interfere with correct binding of Soliris (eculizumab), a first-generation C5 inhibitor currently
approved for PNH and aHUS treatment, making these patients resistant to treatment with that drug. In addition to disease targets
where complement dysregulation is the key driver, we are also targeting a range of inflammatory diseases where the inhibition of
both C5 and LTB4 are implicated, including bullous pemphigoid (a blistering disease of the skin), or BP, and atopic keratoconjunctivitis,
our pipeline include engineered versions of Coversin that potentially decrease the frequency of administration, improve potency,
or allow for specific tissue targeting, as well as new proteins targeting LBT4 alone, as well as bioamine inhibitors (for example,
anti-histamines). In general, these inhibitors act as ligand binding compounds, which may provide additional benefit versus other
modes of inhibition. For example, off target effects are less likely with ligand capture. One example of this benefit is seen with
LTB4 inhibition through ligand capture. LTB4 acts to amplify the inflammatory signal by bringing and activating white blood cells
to the area of inflammation. Compounds that have targeted the production of leukotrienes will inhibit both the production of pro-inflammatory
as well as anti-inflammatory leukotrienes-often diminishing the potential benefit of the drug on the inflammatory system.
Coversin has demonstrated that, by capturing LTB4, it is limited to disrupting the white blood cell activation and attraction aspects,
without interfering with the anti-inflammatory benefits of other leukotrienes.
Coversin is much smaller
than typical antibodies currently used in therapeutic treatment. Coversin can be self-administered by subcutaneous injection, much
like an insulin injection, which we believe will provide considerable benefits in terms of patient convenience. We believe that
the subcutaneous formulation of Coversin may accelerate recruitment for our clinical trials, and, as an alternative to intravenous
infusion, may accelerate patient uptake if Coversin is approved by regulatory authorities for commercial sale. Patient surveys
contracted by us suggest that a majority of patients would prefer to self-inject daily than undergo intravenous infusions.
Designation of Coversin for PNH
we received notice from the FDA of fast track designation for the investigation of Coversin for the treatment of PNH in patients
who have polymorphisms conferring eculizumab resistance. The fast track program was created by the FDA to facilitate the development
and expedite the review of new drugs which show promise in treating a serious or life-threatening disease and address an unmet
medical need. Drugs that receive this designation benefit from more frequent communications and meetings with the FDA to review
the drug's development plan including the design of the proposed clinical trials, use of biomarkers and the extent of data needed
for approval. Drugs with fast track designation may also qualify for priority review to expedite the FDA review process, if relevant
In the fourth quarter
of 2016, we commenced enrollment for a 90 day open-label Phase II, single-arm clinical trial in patients with PNH in five centers
in the European Union. We initially enrolled and treated five patients with Coversin self-administered subcutaneous injections
twice a day for approximately the first month and then switched to once daily injections. Of those five patients, four completed
the 90 day trial while one patient with a suspected co-morbidity unrelated to treatment was withdrawn on day 43 of the trial. Recently,
we enrolled three additional patients, pursuant to an amended protocol based on a revised dosing regime, one of whom has completed
approximately eight weeks of treatment while the other two patients are still within their first month of treatment.
The primary endpoint
in this trial is reduction in serum lactic dehydrogenase, or LDH, to 1.8 X the upper limit of normal, or ULN or 500 I U/L,
whichever is the lower from day 1 (pre-dose) to day 28. Secondary endpoints are LDH at days 60 and 90, hemoglobin, CH50, quality
of life, and transfusion independence. The objectives of our Phase II clinical trial are to validate the safety and efficacy of
Coversin, confirm convenience of our dosing regimen, and study dose ranging to identify the correct treatment dose in advance of
anticipated Phase III clinical trials.
Interim results from
the trial with respect to the first five patients showed that Coversin was well tolerated and patients reported no difficulty with
self administration. Those results showed that there were no serious adverse events, SAEs, related to Coversin. The most commonly
reported adverse events were mild to moderate injection site reactions which declined towards the end of the 90-day trial. Those
results further showed that patients developed low titre antibodies between 2 to 13 weeks after starting daily exposure to Coversin
but the antibodies were non-neutralizing as determined by lytic assay. All four patients that completed the trial saw declines
in lactate dehydrogenase, LDH, levels with two of the four patients meeting the primary endpoint which was assessed at day 28.
A fifth patient withdrawn from the study did not meet the primary endpoint. For the four patients that completed the study, LDH
as a multiple of ULN (xULN) was 1.4, 2.2, 2.5 and 1.4 at day 28; 1.5, 2.1, 1.8 and 1.5 at day 60; and 1.6, 2.4, 2.0 and 1.9 at
day 90. Aspartate aminotransferase, or AST, levels provide another measure of cellular haemolysis; AST decreased following initiation
of dosing. Three of the four patients that completed the study were updosed. Two of the patients were updosed from 30mg to 45mg
once daily at days 40 and 54, respectively and a third patient was updosed to 22.5mg twice daily at day 24 and moved to 45mg once
daily at day 67. One of the patients updosed did not see a decline in LDH with updosing although his haemoglobin level rose after
day 67. All four patients that completed the study had a CH50 level below the limit of quantification (<8 CH50 U Eq/mL) after
the two-day ablating dose phase indicating total blockade of the terminal complement pathway. None of the four patients required
transfusion during the trial, while three of the four patients required transfusions during the three months preceding the trial.
three recently enrolled patients, the first patient who completed more than 28 days of treatment had an LDH value of 1.5 times
the ULN at day 28. The other two patients have not yet reached the primary endpoint measurement date. To date, there have been
no drug-related serious adverse events. The data reported is taken from the current electronic case report forms.
In addition, an eculizumab-resistant
PNH patient has been under treatment with subcutaneous Coversin for over 18 months under an open-label long term safety and efficacy
trial. The patient continues to self-administer Coversin and continues to demonstrate complete complement inhibition without any
change in dose. The four patients that completed the 90 day trial have since moved into our long term safety and efficacy
trial and have been under treatment with subcutaneous Coversin for between six and nine months.
Following advice from
a recent FDA Type B End-of-Phase II Meeting, we plan to advance Coversin, towards Phase III clinical trials in PNH commencing
with CAPSTONE in the first quarter of 2018, a Phase III clinical trial of Coversin in na ve PNH patients in Europe, where
Soliris is not the standard of care, with co-primary clinical endpoints based on hemoglobin and transfusion data. Subsequent to
the commencement of CAPSTONE, at a date to be determined, we plan to commence ASSET, a Phase III clinical trial in PNH patients
in the United States, where Soliris, is the current standard of care. Based on the FDA's advice, we may decide to engage
in additional discussions with the FDA with respect to the protocol design of both CAPSTONE and ASSET.
studies with Coversin have demonstrated positive results in an animal model of aHUS conducted by Prof. Giuseppe Remuzzi and colleagues