Septerna simply entered the clinic, and its lack of human knowledge makes it an outlier among the many firms in a position to efficiently go public this 12 months in what remains to be a cautious biotech IPO market. What the younger firm does have is expertise based mostly on analysis from a Nobel laureate and a lead drug candidate that would provide a key benefit over different therapies for a uncommon, inherited illness. Now it has $288 million in IPO money to help its pipeline.
Late Thursday, Septerna priced its providing of 16 million shares at $18 apiece, going past the preliminary monetary phrases it beforehand set. These shares will commerce on the Nasdaq beneath the inventory image “SEPN.”
South San Francisco-based Septerna will use a lot of the IPO proceeds to proceed scientific testing of SEP-786 for hypoparathyroidism, an inherited deficiency of parathyroid hormone (PTH). This hormone regulates calcium and phosphate ranges within the blood. Missing this hormone results in fatigue, mind fog, and muscle weak point. In additional extreme instances, sufferers can develop cardiovascular issues and renal failure.
Customary hypoparathyroidism therapy contains calcium and vitamin D dietary supplements, which don’t handle the entire illness’s signs. Takeda Pharmaceutical’s Natpara, an engineered model of parathyroid hormone, will stop manufacturing by the top of the 12 months as a result of manufacturing points. In August, the FDA accepted Ascendis Pharma’s Yorvipath, the primary in what may very well be wave of recent injectable peptide hypoparathyroidism medication. Septerna takes a distinct strategy to the illness with SEP-786, a small molecule that targets and prompts the parathyroid hormone 1 receptor (PTH1R), sparking it to provide extra of the important thing hormone. As an oral drug, SEP-786 would provide sufferers much less burdensome dosing.
“Hormone alternative with injectable PTH peptides, both marketed or in scientific improvement, might enhance blood chemistry profiles of sufferers through PTH1R activation however would require lifelong day by day injections,” Septerna mentioned within the IPO submitting. “We consider there’s a substantial alternative for an oral small molecule remedy that provides comfort, improved compliance, and probably superior efficacy.”
PTH1R is a G protein coupled-receptor (GPCR), a part of a household of receptors that regulate a variety of physiological processes. The position of those receptors in each well being and illness is understood, and plenty of of them are focused by FDA-approved medication. Nonetheless, an estimated 75% of GPCR targets stay undrugged, Septerna mentioned within the submitting. Septerna’s platform expertise allows scientists to isolate a GPCR and research it outdoors of a cell, however in a method that replicates what occurs to that receptor inside a cell. With this larger understanding of GPCRs, the corporate designs, screens for, and optimizes small molecules that focus on the receptors. This expertise platform, referred to as Native Advanced, relies on the analysis of Robert Lefkowitz, a Duke College professor of biochemistry and chemistry who was awarded the 2012 Nobel Prize in Chemistry for his work within the GPCR area.
In animal exams, Septerna reported its small molecule agonists activated PTH1R and controlled key genes vital for calcium homeostasis in method much like native parathyroid hormone. A placebo-controlled Part 1 research will consider the protection and tolerability of once-daily and twice-daily dosing of the SEP-786 in wholesome volunteers. The first affected person was dosed final month. Preliminary knowledge are anticipated in mid-2025.
The Septerna pipeline contains two preclinical unfavourable allosteric modulators. SEP-631 is in improvement for immunology and irritation indications, such because the pores and skin illness power spontaneous urticaria. TSHR has potential purposes in endocrinology.
Native Advanced has additionally yielded small molecule agonists of the GLP-1, GIP, and glucagon receptors for the potential therapy of metabolic problems. An oral Septerna drug that hits a number of of those receptors might put the biotech in competitors with commercialized injectable peptide medication, comparable to Eli Lilly’s Zepbound and Novo Nordisk’s Wegovy. However Septerna will possible purpose to face out from the subsequent wave of metabolic drugs in improvement as capsules. This competitors contains Construction Therapeutics, whose small molecules come from its personal GPCR platform expertise (when Construction went public final 12 months, it snagged the becoming inventory image “GPCR”). Lead Construction drug candidate GSBR-1290 is at the moment in mid-stage scientific improvement for kind 2 diabetes and weight problems.
Since Septerna’s inception in 2019, the corporate had raised $224.2 million previous to the IPO, most lately a $150 million Collection B spherical final 12 months led by RA Capital Administration. That agency holds a 7.7% post-IPO stake in Septerna, in accordance with the prospectus. Third Rock Ventures is Septerna’s largest shareholder with a 23.6% post-IPO stake. Septerna is led by CEO Jeff Finer, who can also be a enterprise associate at Third Rock.
Septerna’s plans resonated with traders, whose curiosity within the biotech’s inventory enabled the corporate to spice up the IPO dimension. In preliminary monetary phrases set in the beginning of the week, Septerna deliberate to supply greater than 10.9 million shares within the vary of $15 to $17 every, which might have raised $175 million on the pricing midpoint. On Thursday, the biotech boosted the deal dimension to greater than 15.2 million shares priced at $18 apiece, which might have raised $275 million on the pricing midpoint. Late Thursday, the biotech once more revised the phrases upward, boosting the deal to $288 million.
As of the top of the second quarter of this 12 months, Septerna reported its money place was $155.7 million. Following the IPO, the corporate plans to spend $54 million to advance lead drug candidate SEP-786 by means of Part 2 testing in hypoparathyroidism, in accordance with the submitting. The corporate additionally plans to make use of the capital to develop further molecules that focus on the parathyroid hormone receptor. One other $24 million will help the completion of Part 1 testing of SEP-631 and extra molecule inhibitors that may very well be potential therapies for power spontaneous urticaria. And $41 million is put aside for different R&D, together with Septerna’s TSHR and incretin receptor packages.
Photograph: Getty Photos
