Eli Lilly has struck a deal to buy the near-global rights to a P2X7 receptor antagonist from Asahi Kasei Pharma. The agreement will give Lilly control of a treatment for neuroinflammatory pain conditions that recently completed phase 1 studies.
P2X7R is a ATP-gated non-selective cation channel implicated in autoimmune diseases, chronic pain and neurodegenerative conditions. AstraZeneca took a P2X7R antagonist, AZD9056, as far as a phase 2b in rheumatoid arthritis only to terminate the program after it failed to better placebo. Multiple other groups including GlaxoSmithKline, Johnson & Johnson and Pfizer followed AstraZeneca into the clinic.
Lilly is entering the field by paying Asahi Kasei $20 million upfront for rights to AK1780. The deal gives Lilly the exclusive right to promote the orally bioavailable P2X7R antagonist outside of Japan and China. As AK1780 advances, Asahi Kasei could receive up to $210 million in development and regulatory milestones followed by a further $180 million in paydays tied to sales.
While the first clinical trials of P2X7R antagonists targeted rheumatoid arthritis, Lilly sees AK1780 as a potential treatment for neuroinflammatory pain. The focus on those patients builds on evidence from animal models and other sources that suggests targeting P2X7R alleviates inflammatory pain.
Clinical evidence for the efficacy of P2X7R antagonists in neuroinflammatory pain is limited. Asahi Kasei has put AK1780 through single and multiple ascending-dose and clinical pharmacology studies but is yet to share the data. Other groups have tested P2X7R antagonists in conditions including autoimmune diseases and major depressive disorder.
At Lilly, AK1780 will slot into a pain pipeline featuring multiple assets. Lilly has three pain drugs in phase 1—namely a PACAP38 antibody, SSTR4 agonist and TRPA1 antagonist—and a TGFα antibody in phase 2. The pain pipeline is led by the anti-NGF antibody, tanezumab, that Lilly is developing with Pfizer.