Septerna Halts Phase 1 Trial of SEP-786 Due to Unexpected Bilirubin Elevations

Septerna discontinued the Phase 1 trial of SEP-786, its lead asset for hypoparathyroidism, due to two severe events of elevated unconjugated bilirubin in healthy volunteers14.

The decision came just four months after Septerna's initial public offering, causing the company's stock to plummet by over 60%49.

The bilirubin elevations occurred without accompanying liver enzyme level increases and were reversible. No serious adverse events, liver injury, cholestasis, or hemolysis were observed14.

Despite the setback, SEP-786 showed early signs of on-target pharmacological activity, with increases in serum calcium and decreases in endogenous PTH6.

Septerna plans to select a next-generation PTH1R agonist candidate from its portfolio to advance to clinical trials later this year46.

The company remains financially stable with approximately $440 million in cash reserves, expected to fund operations into at least the second half of 20279.

Septerna is also progressing with SEP-631, a drug candidate for mast cell diseases, which is on track for clinical trials later this year46.

The unexpected bilirubin elevations were not predicted by preclinical research and toxicology studies, highlighting the challenges in drug development46.

Sources:

1. https://www.bioworld.com/articles/717352-septerna-pulls-lead-hypoparathyroidism-drug-on-bilirubin-levels

4. https://www.investing.com/news/stock-market-news/septerna-shares-plummet-following-clinical-trial-halt-93CH-3874511

6. https://www.stocktitan.net/news/SEPN/septerna-announces-discontinuation-of-sep-786-phase-1-clinical-trial-h1nbg11i0yvs.html

9. https://www.investing.com/news/company-news/septerna-halts-trial-for-hypoparathyroidism-drug-93CH-3874317