未上市 Biotech Beeline Medicines 的口服 TLR7/8 抑制剂 afimetoran 二期 SLE 达主要终点（SRI-4，p<0.001），拟推进 SLE/CLE 关键性试验；直接主体不可交易，上市可比方（BMS、默克集团、GSK/AZ/罗氏、A股狼疮标的）均无重大近期敞口

A phase 2 trial of Beeline Medicines’ afimetoran has hit its primary endpoint, positioning the biotech to swarm into pivotal development in two forms of lupus.
Beeline exited stealth in April with $300 million, five assets from Bristol Myers Squibb and leaders and investors fresh from the success of SpringWorks Therapeutics. The company sweetened its situation in June by raising a $126 million series A extension. Beeline raised the money to advance a pipeline led by afimetoran, an oral small-molecule inhibitor of Toll-like receptors 7 and 8 (TLR7/8).
Wednesday, the Connecticut-based biotech published phase 2 results on afimetoran in the autoimmune disease systemic lupus erythematosus (SLE). After 48 weeks of daily oral treatment, Beeline saw higher SLE Responder Index-4 (SRI-4) response rates in the afimetoran arms than the placebo cohort.
All three afimetoran doses had a significantly bigger effect than placebo on the SRI-4 response rate, the trial’s primary endpoint. Improvements on secondary endpoints were consistent with SRI-4 results, the biotech said. Beeline has yet to share data beyond a p-value of less than 0.001 for the primary endpoint.
Safety and tolerability were generally consistent with earlier phase 1 trials, Beeline added. BMS tested afimetoran in a first-in-human safety study and a phase 1b trial in cutaneous lupus erythematosus (CLE) before offloading the asset. The trials revealed a favorable safety profile.
Beeline plans to move afimetoran into pivotal development in SLE and CLE, reflecting a belief that the drug candidate could be a best-in-class oral treatment for the two forms of lupus. Germany's Merck KGaA has laid claim to first-in-class status with enpatoran, an oral small-molecule TLR7/8 inhibitor that entered phase 3 development in SLE and CLE this year.
Interest in targeting TLR7 and TLR8 to treat lupus is built on years of research. Scientists implicated TLR7 in SLE in 2018. Four years later, researchers showed TLR7 gain-of-function genetic variation causes lupus. Other groups have analyzed the role TLR8 plays in the autoimmune disease.
The studies suggested a new angle to attack an autoimmune disease that has proven hard to treat. The field waited decades for a new drug, and the pace of approvals has remained slow since GSK broke the logjam with Benlysta in 2011. AstraZeneca won approval for Saphnelo in 2021, adding a subcutaneous nod this year, and Roche’s Gazyva is under FDA review in SLE. Roche used SRI-4 as its primary endpoint.
With lupus representing a blockbuster opportunity, a phase 3-ready asset such as afimetoran could be of interest to a host of drugmakers with autoimmune disease portfolios. Yet Beeline executives have voiced a preference for advancing assets solo, with CEO Saqib Islam recently telling Fierce that the team has experience of “getting drugs through the regulators to an approval with pricing” and aims to do it again.