Our lead product candidate, Coversin™, a second-generation and potentially best-in-class 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). Coversin also independently inhibits LTB4 activity, an amplifier of inflammation. Coversin is a recombinant small protein (16,740 Da) derived from a protein 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.
Our initial clinical targets for Coversin are paroxysmal nocturnal haemoglobinuria (PNH), and atypical Hemolytic Uremic Syndrome (aHUS). Coversin has the potential to treat patients with polymorphisms of the C5 molecule which interfere with correct binding of Soliris® (eculizumab) and prevents its therapeutic efficacy. Soliris is a first-generation C5 inhibitor currently approved for PNH and aHUS treatment.
To date, Akari has demonstrated: (i) full complement inhibition and marked lactate dehydrogenase reduction in a PNH patient with eculizumab resistance who is self-administering Coversin daily pursuant to an approved clinical protocol in the Netherlands, and who has now been administered Coversin since February 2016; (ii) 100% inhibition of complement C5 activity by Coversin with once daily subcutaneous injections during our ongoing Phase Ib clinical trial in healthy volunteers; (iii) that Coversin inhibits PNH red blood cell lysis in vitro; and (iv) that complement inhibition is complete whether measured by ELISA CH50 U Eq/ml assay or sheep red blood cell lytic CH50 assay, as demonstrated in both a Phase Ib healthy volunteer study and a 28-day safety study in non-human primates.
Akari initiated a Phase II trial in February 2016 for patients with eculizumab resistance. In the first and only patient to date, we have obtained both complete complement inhibition (ELISA CH50 < 8 Eq/ml, lower limit of quantification) and marked LDH reduction to below 1.5 ULN (upper limit of normal), and the drug has proven safe and well tolerated through more than one year of therapy to date with no neutralizing antibodies
The primary objective of Akari’s Phase II eculizumab-resistance program is to provide early access to Coversin as a potentially lifesaving alternative to patients with clinically demonstrated resistance to eculizumab. Resistant patients are entered into an open label protocol where safety and efficacy parameters are evaluated on an ongoing basis. We expect to periodically present topline results from this ongoing trial as they become available.
We believe that availability of convenient self-injected daily subcutaneous Coversin may accelerate recruitment for our upcoming Phase III clinical trials, and, as an alternative to intravenous infusion of eculizumab standard of care, may accelerate patient uptake if Coversin is approved by regulatory authorities for commercial sale.