Eli Lilly promises $1B to get a drug that rivals the new non-opia painkiller at the Apex

Eli Lilly is expanding its pain medication pipeline by getting access to SiteOne Therapeutics, and the company's lead program is the same as the Vertex Pharmaceuticals product, which approved the new non-opia pain medication earlier this year.

Eli Lilly has agreed to pay up to $1 billion to buy Siteone, based in South San Francisco, according to the terms of the deal announced Tuesday. The pharmaceutical giant did not provide further breakdown of the financial details of the deal, except saying the payment includes advance payments as well as regulatory and commercial milestones. SiteOne's drug candidate STC-004 is on track to begin Phase 2 testing.

SiteOne has developed drugs targeting sodium channels, which are found primarily in the peripheral nervous system. This approach is designed to avoid the risk of addiction to opioid pain medications that hit the receptor in the central nervous system. The role of sodium channels NAV1.7 and NAV1.8 in pain signaling has been played for decades. The challenge of drug research is to identify small molecules that can block these channels without hitting other sodium channels and causing adverse reactions.

SiteOne's technology can identify small molecules that can selectively hit pain-transmitting sodium channels and regulate them. A name on NAV1.7 in a December 2024 interview John Mulcahy refers to a binding site on NAV1.7, enabling startups’ drugs to choose this target. SiteOne's STC-004 is an oral small molecule designed to target NAV1.8.

In February, SiteOne reported results for Phase 1, showing that STC-004 is rapidly absorbed by a half-life that supports a daily dosage. The company said the drug was well tolerated in all doses, and the increased pain threshold in participants indicated that the molecule was involved in its target. Based on these results, the startup plans to advance the drug into phase two testing in acute and chronic peripheral pain in the second half of this year. After the acquisition is over, the research will become Eli Lilly’s responsibility.

“The burden of chronic pain worldwide is still increasing, and effective non-opia treatments remain elusive,” Mark Mintun, vice president of R&D research and development at Lily Group, said in a prepared statement. “Eli Lilly is eager to continue to develop STC-004 with the outstanding Siteone team, part of our efforts to advance the novel, addiction-free pain therapy.”

Lily's Pipeline lists three procedures in the Phase 2 test to address various types of pain. The most advanced of these is Mazisotine, a small molecule agonist of SSTR4, designed to regulate somatostatin signaling and regulate inflammation and pain. According to Lilly's report on the first quarter of 2025 financial results, it is expected that more than 400 participants in diabetes can complete a Phase 2 test in July this year.

Other interim procedure is LY3848575, a monoclonal antibody designed to bind to environmentally friendly proteins that prevent the protein from binding to its receptors as a potential treatment for chronic pain, while Ly3857210, a small P2X7 molecule inhibitor, is an ion channel, an ion channel that enables neurons and non-brain-containing cells and non-meningemen-containing promoters. In Phase 1, Lilly is testing a small molecule AT2R antagonist and six additional drug candidates to ensure undisclosed targets.

Originally founded in 2010, Siteone is based on Mulcahy's Ph.D. Stanford University studies research toxins targeting sodium channels; the startup has university-licensed technology. Amgen is an early collaborator and investor in the startup, although the NAV1.7 drug alliance ended when Pharma Giant exited neuroscience development. In the second half of last year, Novo Holdings led a $100 million Series C funding round, with Siteone planning to fund clinical development of its leading program.

With its collaboration with Vertex in 2022, SiteOne is developing NAV1.7 inhibitors to relieve pain. Other details have not been disclosed. Vertex's Journavx is the product of NAV1.8 research in pharmaceutical companies. The two daily medications were approved in January as a treatment for moderate to severe acute pain in adults, making it the first treatment among new pain medications. JORNAVX has also reached Phase 3 tests in diabetic peripheral neuropathy and Phase 2 tests.

Photo: Craig F. Walker/Boston Globe, by Getty Images