Benzinga | Dec 1, 2021 08:35AM EST

Akari Therapeutics Highlights Presentation Of New Data Revealing Potential Mechanism Of Action Driving Serious Exacerbations Across Lung Disorders

Data suggest potential therapeutic role for nomacopan in exacerbations in severe lung conditions such as COPD and COVID pneumonia

NEW YORK and LONDON, Dec. 01, 2021 (GLOBE NEWSWIRE) -- Akari Therapeutics, Plc (NASDAQ:AKTX), a late-stage biopharmaceutical company focused on innovative therapeutics to treat orphan autoimmune and inflammatory diseases where complement (C5) and/or leukotriene (LTB4) systems are implicated, today announces data from observational studies in COVID pneumonia and chronic obstructive pulmonary disease (COPD) that highlight the potential role of complement and leukotriene hyperactivity in driving life threatening disease exacerbations and therefore a potential therapeutic role for nomacopan.

An observational study sponsored by Akari on COVID pneumonia undertaken at Portsmouth Hospitals University NHS Trust was reported at the recent British Thoracic Society Annual Meeting November 24-26, 2021 (1). Plasma levels of C5a, C5b9 and LTB4 in COVID pneumonia patients were elevated compared with control patients and increased with disease severity. In addition, the levels of C5a (p = 0.001) and C5b9 (p = 0.019). which are potential biomarkers for disease progression, rose significantly in patients that worsened (i.e., those requiring invasive mechanical ventilation or who died).

These findings align with a prior, separate Akari-sponsored observation study in COPD patients (2) that demonstrated that exacerbating patients have elevated C5a in sputum but not in serum and that the level of C5a was correlated with the duration/severity of the exacerbations (p=0.01). In exacerbations of COPD, Leukotriene B4 (LTB4) is also found in the sputum (3). All three of these inflammatory mediators, LTB4, C5a and C5b9 are inhibited by nomacopan.

Akari is targeting lung diseases such as asthma, COPD and COVID pneumonia where in certain patients, a hyperreactive response to external agents triggers a severe exacerbation. For example, it is estimated that 14% of COPD patients have severe annual exacerbations associated with hospitalization and increased mortality (4).

Complement (C5 and its by products C5a and C5b9) and leukotriene (LTB4) are key inflammatory mediators which through their inhibition by nomacopan may prevent disease progression. Their combined inhibition has been shown in several lung disease models to be more effective than inhibiting either LTB4 or C5 alone. Leukotriene inhibition is an established treatment for severe asthma and complement hyperactivity is increasingly associated with severe lung inflammation. Importantly, the observational data indicate that the inflammatory response may be driven by rising complement and leukotriene levels directly in the lung, indicating that an inhaled form of nomacopan may potentially be the most effective route of administration. Akari has demonstrated full activity and potential for deep delivery to the lung with a nebulized inhaled form of nomacopan.

Akari is investigating the pharmacokinetics of inhaled nomacopan in the lung and a proof of principle study in exacerbating COPD patients to further evaluate the impact of inhibiting C5 and LTB4 with nomacopan.

In addition, the COVID pneumonia observational findings are being further evaluated to explore the potential role of biomarkers in identifying the most appropriate COVID pneumonia patients to be treated with nomacopan.

Professor Tim Higenbottam DSc, MA, MD, FRCP, FPPM commented, "Lung exacerbations are a major problem yet to be adequately treated. There is growing evidence that these exacerbations are driven by both C5 and LTB4 which is important in their potential role as biomarkers of an excessive innate immune response and as a pointer of possible treatment. Nomacopan represents a potential new therapeutic option which could have applicability across COPD, severe Asthma, and COVID pneumonia where an over-reactive innate immune response puts patients at risk of a life-threatening hyperinflammatory response."

References:

2 Wiffen L, Brown T, Chauhan, M et al., Measures of inflammation, complement activation and coagulation in patients with COVID-19. A38 Thorax 2021; 76 (Suppl 2) : A1 -- A205.

4 Westwood J-P, Mackay AJ, Donaldson G....Wedzicha JA. The role of complement activation in COPD exacerbation recovery. ERJ Open Res 2016; 2: 00027-2016 | DOI: 10.1183/23120541.00027-2016.

6 Drozdovszky O, Barta I, Antus B. Sputum Eicosanoid Profiling in Exacerbations of Chronic Obstructive Pulmonary Disease. Respiration 2014;87:408--415. DOI: 10.1159/000358099.

8 Wise RA, Calverley PMA, Carter K,. et al., Seasonal variations in exacerbations and deaths in patients with COPD during the TIO SPIR(c) trial. Int J COPD. 2018: 13; 605-616.