Septerna sinks as it discontinues lead asset SEP-786

US clinical-stage biotech Septerna (Nasdaq: SEPN) yesterday announced its decision to discontinue the Phase I single- and multiple-ascending dose (SAD/MAD) clinical trial of SEP-786 in healthy volunteers. SEP-786 is an oral small molecule agonist of the parathyroid hormone 1 receptor (PTH1R) being developed for the treatment of hypoparathyroidism.

The news sent the company's shares down 47% to $6.87 on Tuesday. It has now lost more than 61% of its value since its October 2024 initial public offering (IPO), when it raised $288 million.

Septerna said its decision follows the observation of two unanticipated severe (Grade 3) events of elevated unconjugated bilirubin in the MAD portion of the Phase 1 trial, both of which were without elevations in ALT, AST, and GGT liver enzyme levels. Dosing was discontinued for both study participants, and the bilirubin elevations were reversible. Importantly, there were no events of liver injury, cholestasis, or hemolysis across all participants, and there were no serious adverse events (SAEs) in the Phase I trial.