Akari Therapeutcis (AKTX) Presents New Preclinical Data Highlighting Potential of Long-Acting PASylated Nomacopan to Treat Retinal Diseases, Including Age-Related AMD and Uveitis

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, announced today the publication of new data in the journal CELLS. The paper, entitled "Immune-Mediated Retinal Vasculitis in Posterior Uveitis and Experimental Models: The Leukotriene (LT)B4-VEGF Axis," highlights the importance of the LTB4-VEGF axis in the development of sight-threatening retinal inflammation. In a non-infectious allergic uveitis animal model, PAS-nomacopan reduced VEGF by more than 50% compared to saline control, equivalent to the inhibition caused by an anti-VEGF antibody. In addition, PAS-nomacopan was significantly more effective in reducing retinal inflammation than the anti-VEGF antibody.

Separately, Akari recently completed a preclinical study in an industry standard model of laser-induced CNV in which intravitreally injected PAS-nomacopan was compared to Eyelea®, an FDA-approved treatment for wet AMD. In this model, PAS-nomacopan injected once during the 16-day treatment period was equivalent to Eyelea® in reducing neo-vascularisation.

Further pharmacokinetic and pharmacodynamic work is underway with PAS-nomacopan to define the optimal dose interval that could be used in clinical trials. PAS-nomacopan is an engineered version of nomacopan with an extended half-life [Kuhn et al, 2016] to increase residency time, thereby reducing injection intervals into the eye. Virginia Calder, Ph.D., Professor of Ocular Immunology at the University College London Institute of Ophthalmology said, “Nomacopan has shown a promising reduction in disease severity in a pre-clinical uveitis model and therefore has the potential to provide a new therapeutic approach in difficult to treat retinal eye diseases such as uveitis where LTB4, VEGF and complement activation are believed to drive disease pathology.”

The work by Professor Calder and colleagues taken together with the CNV results suggest that long-acting PAS-nomacopan could have important applications in a wide range of sight threatening back of the eye diseases for which there are currently limited treatment alternatives. Akari is currently exploring multiple partnering options for both its surface of the eye program treated with topical nomacopan and with PAS-nomacopan for the back of the eye program.

Overview of Potential Target Diseases

Non-infectious posterior uveitis (NIU) is a major cause of vision loss in young and middle-aged people in the U.S. and Europe accounting for 10-15% of blindness in this population. The only approved products for treatment of NIU are corticosteroids, tumour necrosis factor (TNF) blockers and immunosuppressants, but these all have serious treatment limiting side effects including glaucoma, cataracts and liver failure.

In wet AMD, growth of new blood vessels in the retina, known as choroidal neovascularisation (CNV), together with leakage of proteins and blood components has been associated with vision loss. While VEGF antagonists such as aflibercept (Eyelea®) and ranibizumab (Lucentis®), have become the mainstay of treatment of wet AMD, they do little to combat other types of retinal inflammation such as uveitis and dry AMD1.

Dry AMD also named geographic atrophy (GA) is a more common condition for which there is currently no approved treatment. Because of its association with complement degradation products there has been interest in complement inhibition as a treatment option. However, in clinical trials involving complement inhibitors, a reduction in the progression of GA was associated with the development of CNV in between 9% and 21% of patients2, 3. Nomacopan which simultaneously reduces the complement drive of GA and reduces VEGF through its LTB4 inhibitory activity may potentially be an effective treatment option.

1Nishi Gulati, et al. “Vascular endothelial growth factor inhibition in uveitis: a systematic review.” British Journal of Ophthalmology. 2011.

2Glenn J. Jaffe, MD, et al. “C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration: A Randomized Pivotal Phase 2/3 Trial.” American Academy of Ophthalmology. August, 2020.

3David S. Liao, MD, et al. “Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Randomized Phase 2 Trial.” American Academy of Ophthalmology. July 16, 2019.

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