Eli Lilly is expanding its pain drug pipeline with the acquisition of SiteOne Therapeutics, a startup whose lead program addresses the same target as a Vertex Pharmaceuticals product whose approval earlier this year ushered in a new class of non-opioid pain medications.
Under deal terms announced Tuesday, Lilly has agreed to pay up to $1 billion to buy South San Francisco-based SiteOne. The pharma giant did not provide a further breakdown of the financial details of the deal, other than to say the sum is inclusive of an upfront payment as well as regulatory and commercial milestones. SiteOne’s drug candidate, STC-004, is on track to begin Phase 2 testing.
SiteOne develops drugs that target sodium channels, which are found primarily in the peripheral nervous system. This approach is intended to avoid the addiction risks posed by opioid pain drugs that hit receptors in the central nervous sytem. The role that the sodium channels NaV1.7 and Nav1.8 play in the transmission of pain signals has been known for decades. The challenge for drug research has been identifying small molecules capable of blocking these channels without also hitting other sodium channels and causing adverse effects.
SiteOne has technology that identifies small molecules capable of selectively hitting the pain-transmitting sodium channels and modulating them. The name SiteOne refers to a binding site on NaV1.7 that enables the startup’s drugs to be selective to that target, SiteOne scientific co-founder and CEO John Mulcahy told MedCity News in a December 2024 interview. SiteOne’s STC-004 is an oral small molecule designed to target NaV1.8.
In February, SiteOne reported Phase 1 results showing STC-004 was rapidly absorbed with a half-life that supports once-daily dosing. The drug was well tolerated across all doses while increases in the pain threshold of participants indicate the molecule engaged its target, the company said. Based on these results, the startup had planned to advance the drug to Phase 2 testing in acute and chronic peripheral pain in the second half of this year. When the acquisition closes, that study will become the responsibility of Lilly.
“The global burden of chronic pain continues to increase, and an effective non-opioid treatment remains elusive,” Mark Mintun, Lilly group vice president neuroscience research and development, said in a prepared statement. “Lilly is eager to continue the development of STC-004 with the outstanding SiteOne team as part of our efforts to advance novel, addiction-free pain therapies.”
Lilly’s pipeline lists three programs in Phase 2 testing for various types of pain. The most advanced of them is mazisotine, a small molecule agonist of SSTR4 designed to modulate somatostatin signaling, regulating inflammation and pain. A Phase 2 test that enrolled more than 400 participants with diabetic peripheral neuropathy is expected to be complete this July, according to an investor presentation that accompanied Lilly’s report of first quarter 2025 financial results.
The other mid-stage programs are LY3848575, a monoclonal antibody designed to bind to epiregulin, preventing that protein from binding to its receptors as a potential treatment for chronic pain, and LY3857210, a small molecule inhibitor of P2X7, an ion channel that activates neuronal and non-neuronal cells in peripheral and central nervous system pain pathways. In Phase 1 , Lilly is testing a small molecule AT2R antagonist and six additional drug candidates for targets that remain undisclosed.
SiteOne, initially formed in 2010, was based on Mulcahy’s Ph.D. research at Stanford studying toxins that target sodium channels; the startup has technology licensed from the university. Amgen was an early collaborator and investor in the startup, though an alliance on NaV1.7 drugs ended when the pharma giant exited neuroscience R&D. Late last year, Novo Holdings led a $100 million Series C round of financing, which SiteOne was planning to use to finance clinical development of its lead program.
Under a collaboration with Vertex started in 2022, SiteOne is developing NaV1.7 inhibitors for pain; additional details have not been disclosed. Vertex’s Journavx is the product of the pharma company’s internal NaV1.8 research. This twice-daily pill was awarded FDA approval in January as a treatment for moderate-to-severe acute pain in adults, making it the first in a new class of pain drugs. Journavx has also reached Phase 3 testing in diabetic peripheral neuropathy and Phase 2 testing in painful lumbosacral radiculopathy.
Photo: Craig F. Walker/The Boston Globe, via Getty Images
