AK-1780

iStock, Cinefootage Visuals The acquisition of SiteOne provides a bit of diversification for Lilly, which has burrowed into the obesity and diabetes space with mega-blockbuster tirzepatide and several follow-on molecules. Eli Lilly has executed a bolt-on acquisition of SiteOne Therapeutics for up to $1 billion, adding a clutch of non-opioid pain medicines to its pipeline, which has lately been largely focused on obesity and diabetes medications. “Today’s deal adds another arrow to Lilly’s growing quiver of pipeline opportunities, positioning Lilly with advanced planning for diversification and growth beyond GLP-1s,” BMO Capital Markets analysts wrote to investors Tuesday following the announcement. Key to the deal is the Nav1.8 inhibitor STC-004, which is nearing Phase II development for the treatment of pain, according to Lilly’s morning release . The deal could total $1 billion, including an undisclosed upfront payment for additional payments down the line based on certain regulatory and sales milestones. The addition of SiteOne would represent an expansion into new targets for Lilly, but into a field that Vertex Pharma has also captured with the approval of Journavx earlier this year, BMO said. SiteOne has been chasing Vertex in the pursuit of non-addictive pain medications . The pharma earned an FDA approval for suzetrigine , now known as Journavx, in January, marking a significant moment in the treatment of pain. But suzetrigine, which targets the NaV1.8 voltage-gated sodium channel, had a bumpy road through the clinic , with one Phase II trial showing little differentiation between the treatment and placebo arms. Biotechs like SiteOne, Tris Pharma and Latigo Biotherapeutics are hoping to do even better. Lilly, meanwhile, has been taking its own approach to pain with four assets in development. Mazisotine is a SSTR4 agonist in mid-stage testing for adults with diabetic peripheral neuropathic pain. Other Phase II assets include LY3857210, which targets the ATP ligand-gated ion channel P2X7, and LY3848575, a monoclonal antibody, both in chronic pain. The next readout for mazisotine could be coming soon, as the study’s completion date is listed as July. “A long-time player in the pain space, today’s deal reads as a strategic positive for Lilly, fast following a validated mechanism with an attractively priced deal,” BMO wrote. However, the rollout of Vertex’s asset has been challenging, which gave the analysts some pause. The acquisition of SiteOne provides a bit of diversification for Lilly, which has burrowed into the obesity and diabetes space with the mega-blockbuster dual incretin receptor agonist tirzepatide and several follow-on molecules. The deal “appears prudent as Lilly continues its string of pearls approach to deal making following its incretin success,” BMO wrote.

Eli Lilly is fronting some new cash in a space they’re quite familiar with. The company is partnering with Japan’s Asahi Kasei Pharma on an experimental drug for chronic pain, acquiring the rights for the P2X7 receptor antagonist program dubbed AK1780. Lilly will shell out a pretty penny for the program, promising up to $410 million total should each milestone payment come to pass. Asahi Kasei will receive an upfront sum of $20 million for the candidate. In addition, Lilly is on the hook for up to $210 million in development and regulatory milestones and another potential $180 million in sales milestones. Asahi Kasei can also obtain royalties ranging from the mid-single to low-double digits should an approved product come out of the deal. AK1780 recently completed Phase I single and multiple ascending doses and clinical pharmacology studies, Asahi Kasei said Thursday. Lilly’s immediate plans for the program are unclear, and we’ve sent out a request for comment. The P2X7 receptor that’s the target of this deal comes from a family of purinoceptors that are activated by ATP. P2X7 specifically is activated only by high concentrations of ATP and is thought to play a role in cell death and inflammation, as well as inflammatory bowel disease, neurodegenerative diseases, mood disorders and cancers. Some other receptors in the group, such as P2X3, are activated at lower concentrations and can pop up in diseases caused by abnormal neural transmissions. P2X-related programs saw significant investment in the early 2000s, according to Nature , but poor efficacy results in clinical trials, particularly in rheumatoid arthritis. One major player backed off around this time, with Roche axed a P2X3 candidate. Pain programs are nothing new for Lilly, which currently has tanezumab before the FDA for osteoarthritic pain. Lilly collaborated with Pfizer on the candidate and its expected PDUFA date had been last December, but no decision has been reached just yet. The tanezumab ruling could have implications on the anti-NGF class of pain drugs. Nearly a decade ago, the field was crushed by safety issues and began a long, slow return to late-stage testing. Lilly and Pfizer are hoping to turn the fortunes around, but poor Phase III safety data revealed in early 2019 had analysts running for the hills. Despite the grim outlook, the pair decided to push forward anyway to see if they can squeeze past the FDA with the low-dose version of tanezumab. A rival therapy from Regeneron and Teva was also given long odds after posting Phase III data last August, and Regeneron chief Len Schleifer told Endpoints News at the time that the company will be paying close attention to the FDA’s ruling on tanezumab.