AK-1780

iStock, JHVEPhoto Before being discontinued, the P2X7 receptor blocker had cleared a master protocol study in chronic pain, though Eli Lilly said that results were not sufficient for advancement of the Asahi Kasei–partnered asset. Lilly has halted work on another mid-stage pain asset as the pharma continues to find its footing in the analgesic arena. The drug, named LY3857210, is an orally available inhibitor of the P2X7 receptor that is found on a variety of immune cells and considered a key player in chronic pain pathology. Before being discontinued, the drug had completed a Phase II master protocol study covering chronic low back pain , osteoarthritis pain and diabetic peripheral neuropathic pain . In a statement to Fierce Biotech , a spokesperson for Lilly said that data from LY3857210’s development “did not meet our high internal bar for success.” Still, the pharma is “assessing next steps for the program, including possible additional indications.” LY3857210 came to Lilly in early 2021, when it paid $20 million upfront —and promised up to $210 million in milestones—to partner with Japan’s Asahi Kasei and license the drug, then called AK1780. Despite ending LY3857210’s pain run, this partnership is still ongoing, a spokesperson for the Asahi Kasei told Fierce . This is the second mid-stage pain asset that Lilly has dumped in recent months, with the pharma discarding the Phase II oral SSTR4 agonist mazisotine in August. Prior to its discontinuation, mazisotine had also completed a chronic pain master protocol study, testing its safety and efficacy in osteoarthritis , low back pain and diabetic peripheral neuropathic pain . Despite culling two investigational analgesics, Lilly continues to invest in its pain pipeline. In May this year, for instance, the pharma swallowed SiteOne Therapeutics in a deal that could hit $1 billion in value, gaining access to its non-opioid pain drugs. The star of that agreement is STC-004, a Nav1.8 blocker that according to Lilly’s Q3 presentation on Thursday is still in Phase I development. In a May 27 note, analysts at BMO Capital markets said that the deal will help Lilly position itself for “diversification and growth beyond GLP-1s.” Lilly is also working on other pain meds, including one Phase I AT2R blocker and an anti-epiregulin antibody in mid-stage development. In addition, the pharma is positioning its closely watched oral obesity asset orforglipron for knee osteoarthritis pain. The drug is currently in late-stage studies for this indication, with study completion expected in 2027. These pipeline changes on Thursday were vastly overshadowed by Lilly’s financial results , with the pharma claiming that its blockbuster weight-loss franchise tirzepatide finally unseated Merck’s cancer behemoth Keytruda as the top-selling drug in the world. In the third quarter, sister brands Mounjaro and Zepbound together raked in $10.1 billion worldwide, while Keytruda trailed with $8.1 billion in Q3 earnings. All told, Lilly reported an eye-watering $17.6 billion in the third quarter.

LY3857210 joins mazisotine, a non-opioid candidate licensed from Centrexion Therapeutics in 2019, in Lilly’s pain scrapheap.\n Eli Lilly has halted development of a phase 2 P2X7 inhibitor for pain, the company confirmed to Fierce Biotech, in the latest shakeup to a pipeline that has already seen significant pivots this year.The asset, coded LY3857210, was originally licensed from Asahi Kasei Pharma in 2021. The Japanese pharma received $20 million upfront for the candidate, then known as AK1780, and had already put the molecule through phase 1 testing.“P2X7 data did not meet our high internal bar for success and is being removed from the pipeline for pain,” a Lilly spokesperson told Fierce. “Lilly is assessing next steps for the program, including possible additional indications.”Though Lilly is no longer pursuing LY3857210 in pain, the licensing pact remains intact, an Asahi Kasei spokesperson confirmed to Fierce.Lilly had been putting the asset through its paces in osteoarthritis, diabetic neuropathic pain and chronic back pain as part of the Big Pharma’s phase 2 chronic pain master protocol. LY3857210 joins mazisotine in Lilly’s pain scrapheap. The Indianapolis drugmaker dropped the non-opioid pain candidate last quarter after licensing it from Centrexion Therapeutics in 2019 for $47.5 million upfront.In parallel with mazisotine’s shelving, Lilly added a phase 1 NaV1.8 inhibitor from its SiteOne Therapeutics acquisition to its pipeline. That asset, STC-004, hits the same target as Vertex’s pain treatment Journavx.In addition to the NaV1.8 inhibitor, Lilly’s pain pipeline also includes a phase 1 AT2R antagonist licensed from Confo Therapeutics in 2023, a phase 2 epiregulin-targeting antibody called fepixnebart, and star oral GLP-1 candidate, orforglipron, which Lilly is testing in two phase 3 osteoarthritis pain trials.P2X7 receptors have been implicated in a wide swath of diseases, including neurodegenerative conditions and cancer. However, no drugs targeting P2X7 have been approved, though not for lack of trying. GSK once tested its own P2X7 prospect in chronic pain more than a decade ago, but cut the candidate after an unimpressive phase 1 showing. AstraZeneca, meanwhile, pushed a P2X7 candidate through phase 2 for rheumatoid arthritis, but the company then dropped the asset after it failed to top placebo.