Eli Lilly to Acquire SiteOne Therapeutics in $1 Billion Deal to Advance Non-Opioid Pain Therapy
In a strategic move aimed at strengthening its neuroscience and pain management portfolio, Eli Lilly and Company (NYSE: LLY) announced on May 28, 2025, that it has entered into a definitive agreement to acquire SiteOne Therapeutics, Inc., a privately held biotechnology company focused on the development of innovative, non-opioid treatments for chronic pain and other neuronal hyperexcitability disorders. The acquisition, which could be worth up to $1 billion including milestone payments, underscores Lilly’s growing ambition to become a leader in pain management therapies that address the opioid crisis and the unmet needs of millions of patients globally.
At the center of the transaction is STC-004, SiteOne’s lead investigational asset. The Phase 2-ready candidate is a selective small molecule inhibitor of the Nav1.8 sodium channel, a validated target implicated in the transmission of pain signals through peripheral sensory neurons. STC-004 holds potential as a next-generation, non-opioid analgesic for individuals living with chronic pain—a population often left with limited and risky options.
Chronic Pain: A Global Public Health Challenge
Chronic pain affects over 1.5 billion people worldwide, and in the United States alone, it impacts nearly 50 million adults, according to the CDC. Despite its prevalence, treatment options remain inadequate. Opioid-based medications, while effective for acute pain, come with serious risks, including addiction, overdose, and long-term dependence. Non-opioid alternatives such as NSAIDs or antidepressants often provide insufficient relief or bring undesirable side effects, leaving a vast unmet need in the medical community.
Dr. Mark Mintun, Lilly’s Group Vice President of Neuroscience Research and Development, emphasized the significance of the acquisition in addressing this issue. “The global burden of chronic pain continues to increase, and an effective non-opioid treatment remains elusive,” Mintun said in a company 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. Innovation in pain management is critical to address the unmet needs of millions of patients around the world.”
The Science Behind STC-004 and Nav1.8 Inhibition
SiteOne Therapeutics has spent over a decade refining its understanding of voltage-gated sodium channels, particularly Nav1.8, which plays a critical role in the excitability of nociceptive (pain-sensing) neurons. Unlike other sodium channels that are more broadly distributed across tissues, Nav1.8 is predominantly expressed in the peripheral nervous system, making it a promising target for selective modulation without affecting cardiac or central nervous system function.
STC-004 is designed to block Nav1.8 channels with high specificity, reducing pain signal transmission while minimizing off-target effects. By preserving other neural pathways, this precision approach could yield significant improvements over existing therapies in both efficacy and safety. SiteOne’s preclinical and early clinical work has demonstrated encouraging signs that STC-004 could provide pain relief without the risks of sedation, cognitive impairment, or dependency that are often associated with opioids.
Deal Terms and Strategic Fit
Under the terms of the agreement, Lilly will acquire SiteOne Therapeutics in a structured transaction valued at up to $1 billion. This includes an upfront payment as well as contingent payments tied to regulatory achievements and commercial milestones related to STC-004 and potentially other assets from SiteOne’s pipeline.
The transaction is expected to close following the satisfaction of customary regulatory and closing conditions. Upon completion, Lilly will integrate SiteOne’s team and pipeline into its existing neuroscience R&D operations, expanding its capabilities in non-opioid pain research and clinical development.
Lilly’s acquisition strategy continues a broader trend among large pharmaceutical companies seeking to in-license or acquire innovative biotech platforms to supplement their internal research. By acquiring a company like SiteOne, which has a strong scientific foundation and a promising late-preclinical or early-clinical stage asset, Lilly can reduce development risk while accelerating its timeline to market.
A Shared Vision for Patient-Centered Innovation
Founded in 2011, SiteOne Therapeutics was launched by a group of Stanford University scientists aiming to translate cutting-edge ion channel research into breakthrough therapies for pain and sensory disorders. Over the years, the company built a proprietary platform centered on sodium channel biology and raised several rounds of private funding to advance its pipeline.
Dr. John Mulcahy, CEO and cofounder of SiteOne Therapeutics, expressed confidence in Lilly’s ability to carry the company’s mission forward. “At SiteOne, we’ve spent more than a decade advancing a vision to deliver safer, more effective, non-opioid therapies for patients suffering from pain and other sensory hyperexcitability disorders,” said Mulcahy. “Lilly shares our deep commitment to scientific rigor, innovation, and patient-centered drug development. We believe their global capabilities and neuroscience leadership will accelerate our efforts to realize the full potential of STC-004 and our broader platform.”
Mulcahy also praised the dedication of the SiteOne team and framed the acquisition as both a validation of their scientific progress and a new chapter in their mission to transform pain treatment paradigms.
Industry Context and Competitive Landscape
Lilly’s move to deepen its investment in pain therapeutics is strategically timed. The opioid epidemic continues to take a heavy toll, with policymakers, clinicians, and patients all urgently seeking alternatives. This has reinvigorated industry and academic interest in non-opioid analgesics, including ion channel modulators, biologics, and gene therapies.
Lilly is not alone in targeting the Nav1.8 pathway. Competitors such as Vertex Pharmaceuticals, Pfizer, and Regeneron are also pursuing similar targets, each at various stages of development. Vertex, for example, has two candidates targeting sodium channels in Phase 3 trials. However, SiteOne’s selective Nav1.8 profile and early clinical differentiation may offer competitive advantages in terms of tolerability and targeted efficacy.
This acquisition also aligns with Lilly’s broader neuroscience strategy, which includes investments in migraine (Emgality), Alzheimer’s disease (donanemab), and neuropathic conditions, indicating the company’s long-term commitment to central and peripheral nervous system disorders.
Financial and Legal Advisors
To facilitate the acquisition, Lilly was advised by J.P. Morgan Securities LLC, acting as exclusive financial advisor, and legal counsel was provided by Jones Day. SiteOne was represented by Centerview Partners LLC as financial advisor, with legal counsel from Skadden, Arps, Slate, Meagher & Flom LLP and Cooley LLP.
The financial impact of the transaction will be assessed by Lilly upon closing, in accordance with Generally Accepted Accounting Principles (GAAP). The company noted that the deal will be reflected in future financial reporting and guidance.
With this acquisition, Lilly is poised to make significant strides in the treatment of chronic pain, positioning STC-004 as a potential blockbuster therapy should clinical trials confirm its efficacy and safety. As regulatory timelines progress and further clinical data becomes available, Lilly could emerge as a frontrunner in a new class of non-addictive pain therapeutics.
The deal not only enhances Lilly’s pain portfolio but also underscores a growing industry emphasis on precision neuroscience, where targeted approaches may finally offer relief for conditions that have long eluded safe, effective treatment. For patients, clinicians, and advocates seeking alternatives to opioids, the Lilly-SiteOne partnership marks a promising advance in the quest to relieve pain without compromise.
