Votucalis originates from the same research program as nomacopan and shares a similar unique mode of action – specifically, capturing and tightly binding to small highly potent ligands. Votucalis binds to histamine, while nomacopan binds to C5 and LTB4. The inhibition of the histamine pathway may allow Akari to target a range of new diseases, separate from those of nomacopan.
By capturing histamine, votucalis prevents activation of all four histamine G-protein coupled receptors (GPCRs), which can induce diverse pathophysiological processes, including chronic pain, itch and inflammation.
New pre-clinical data showed votucalis blocks symptoms of neuropathic pain that result from damage to the somatosensory nervous system. In addition, data from an itch model demonstrated a potential for votucalis to treat atopic dermatitis and attendant chronic pruritis.
Local administration of votucalis was shown to be more effective than systemic administration. A recently completed human skin penetration study showed votucalis may penetrate the skin’s epidermis, highlighting the potential for topical delivery.
Current treatments for neuropathic pain, including opioids, act through the central nervous system. Votucalis offers a new approach without entering the central nervous system, thereby potentially avoiding attendant side effects and drug dependency.
Akari is working with Dr. Paul Chazot, FBPhS (University of Durham, UK; Chair of NC-IUPHAR subcommittee for histamine pharmacology, past-President of European Histamine Research Society (EHRS)) and Dr. Ilona Obara (Newcastle University, UK; Senior Lecturer of pain pharmacology, council member of EHRS) to further develop the pain and dermatology programs as well as topical delivery in advance of a potential Investigational New Drug Application (“IND”).