Eyeing an expansion of its pain portfolio, Eli Lilly entered the sodium channel inhibitor space on Tuesday through the acquisition of SiteOne Therapeutics. While the upfront amount was not disclosed, the total deal is valued at up to $1 billion, including regulatory and commercial milestones. The takeout comes on the heels of a megaround for SiteOne — and the first FDA approval for a non-opioid pain medication in more than two decades.In December, the biotech raised a $100-million series C, and then in January, Vertex Pharmaceuticals' NaV1.8 inhibitor Journavx (suzetrigine) was greenlit by the US regulator. SiteOne's lead programme, STC-004, also blocks the NaV1.8 sodium channel. The company reported Phase I data in February showing that the compound was well-tolerated with rapid absorption suitable for once-daily oral dosing. Given the pharmacokinetic results, a Phase II trial had been planned to start next half. SiteOne CEO John Mulcahy previously told FirstWord that STC-004 was designed to achieve "the maximum level of efficacy that is possible" by blocking the ion channel. The company is also developing several NaV1.7-targeting programmes, including one partnered with Vertex under a 2022 agreement, as well as STC-002, a topical candidate for ocular surface pain. Given the unmet need, and the potential value, of the non-opioid pain space, SiteOne is one of several startups pursuing sodium channel inhibitors. Latigo Biotherapeutics, which raised a $150-million series B in March, is developing NaV1.8 inhibitors LTG-001 and LTG-305, which are in Phase II testing for acute pain and Phase I for chronic pain, respectively (see – Spotlight On: The pain of success – Vertex’s non-opioid win entices investors to back would-be usurpers).Vertex has pegged Journavx as a multi–billion-dollar product, and during a call with investors earlier this month, management lauded the drug's early rollout (see – Spotlight On: Vertex plots $1B+ sales trajectories for Casgevy, Journavx).Adding to the pipelineWhile Eli Lilly's current pain pipeline doesn't include a NaV channel blocker, it boasts three mid-stage programmes and a bevvy of undisclosed early assets. According to the company's website, three candidates are in Phase II testing for pain: LY3848575, a monoclonal antibody that targets human epiregulin; mazisotine (LY3556050), a small molecule SSTR4 agonist designed to modulate somatostatin signaling, calming nerve excitability and reducing inflammation and pain; and LY3857210, an oral, brain penetrant, small molecule antagonist of the ATP ligand-gated ion channel P2X7."An effective non-opioid treatment remains elusive," said Mark Mintun, Lilly group vice president of neuroscience R&D. "Lilly is eager to continue the development of STC-004."