Septerna just entered the clinic, and its lack of human data makes it an outlier among the companies able to successfully go public this year in what is still a cautious biotech IPO market. What the young company does have is technology based on research from a Nobel laureate and a lead drug candidate that could offer a key advantage over other treatments for a rare, inherited disease.

Septerna刚刚进入诊所，由于缺乏人类数据，它在今年能够在仍然谨慎的生物技术IPO市场成功上市的公司中是一个例外。这家年轻的公司所拥有的技术是基于一位诺贝尔奖获得者和一位主要候选药物的研究，这可能为一种罕见的遗传性疾病提供优于其他治疗方法的关键优势。

Now it has $288 million in IPO cash to support its pipeline..

现在，它有2.88亿美元的IPO现金来支持其管道。。

Late Thursday, Septerna priced its offering of 16 million shares at $18 apiece, going beyond the preliminary financial terms it previously set. Those shares will trade on the Nasdaq under the stock symbol “SEPN.”

周四晚些时候，Septerna将其发行的1600万股股票定价为每股18美元，超出了之前设定的初步财务条款。这些股票将在纳斯达克交易，股票代码为“SEPN”

South San Francisco-based Septerna will use most of the IPO proceeds to continue clinical testing of SEP-786 for hypoparathyroidism, an inherited deficiency of parathyroid hormone (PTH). This hormone regulates calcium and phosphate levels in the blood. Lacking this hormone leads to fatigue, brain fog, and muscle weakness.

总部位于旧金山南部的Septerna将利用IPO的大部分收益继续对SEP-786进行甲状旁腺功能减退症（一种甲状旁腺激素（PTH）的遗传缺陷）的临床测试。这种激素调节血液中的钙和磷酸盐水平。缺乏这种激素会导致疲劳、脑雾和肌肉无力。

In more severe cases, patients can develop cardiovascular problems and renal failure..

。。

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Health systems have spent billions on portals while investments in modernizing the voice channel — the dominant preference of healthcare consumers — have taken a backseat.

卫生系统在门户网站上花费了数十亿美元，而对语音频道现代化的投资（这是医疗保健消费者的主要偏好）却处于次要地位。

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作者：StephanieBaum

Standard hypoparathyroidism treatment includes calcium and vitamin D supplements, which do not address all of the disease’s symptoms. Takeda Pharmaceutical’s Natpara, an engineered version of parathyroid hormone, will cease production by the end of the year due to manufacturing issues. In August, the FDA approved Ascendis Pharma’s Yorvipath, the first in what could be wave of new injectable peptide hypoparathyroidism drugs.

。武田制药（Takeda Pharmaceutical）的Natpara是甲状旁腺激素的工程版本，由于生产问题，将于年底停止生产。8月，FDA批准了Ascendis Pharma的Yorvipath，这可能是一波新的注射肽甲状旁腺功能减退症药物中的第一种。

Septerna takes a different approach to the disease with SEP-786, a small molecule that targets and activates the parathyroid hormone 1 receptor (PTH1R), sparking it to produce more of the key hormone. As an oral drug, SEP-786 would offer patients less burdensome dosing..

。作为一种口服药物，SEP-786将为患者提供较少的负担剂量。。

“Hormone replacement with injectable PTH peptides, either marketed or in clinical development, may improve blood chemistry profiles of patients via PTH1R activation but will require lifelong daily injections,” Septerna said in the IPO filing. “We believe there is a substantial opportunity for an oral small molecule therapy that offers convenience, improved compliance, and potentially superior efficacy.”.

Septerna在首次公开募股文件中表示：“无论是在市场上还是在临床开发中，用可注射PTH肽替代激素，都可能通过PTH1R激活改善患者的血液化学状况，但需要终身每日注射。”。“我们相信口服小分子疗法有很大的机会，可以提供便利，改善依从性，并可能获得更好的疗效。”。

PTH1R is a G protein coupled-receptor (GPCR), part of a family of receptors that regulate a wide range of physiological processes. The role of these receptors in both health and disease is known, and many of them are targeted by FDA-approved drugs. However, an estimated 75% of GPCR targets remain undrugged, Septerna said in the filing.

PTH1R是一种G蛋白偶联受体（GPCR），是调节多种生理过程的受体家族的一部分。这些受体在健康和疾病中的作用是众所周知的，其中许多是FDA批准的药物靶向的。然而，Septerna在文件中表示，估计有75%的GPCR目标仍未实现。

Septerna’s platform technology enables scientists to isolate a GPCR and study it outside of a cell, but in a way that replicates what happens to that receptor inside a cell. With this greater understanding of GPCRs, the company designs, screens for, and optimizes small molecules that target the receptors.

Septerna的平台技术使科学家能够分离GPCR并在细胞外对其进行研究，但其方式可以复制细胞内该受体发生的情况。随着对GPCR的深入了解，该公司设计，筛选和优化了靶向受体的小分子。

This technology platform, called Native Complex, is based on the research of Robert Lefkowitz, a Duke University professor of biochemistry and chemistry who was awarded the 2012 Nobel Prize in Chemistry for his work in the GPCR field..

这个名为Native Complex的技术平台基于杜克大学生物化学教授罗伯特·莱夫科维茨（RobertLefkowitz）的研究，他因在GPCR领域的工作而获得2012年诺贝尔化学奖。。

In animal tests, Septerna reported its small molecule agonists activated PTH1R and regulated key genes important for calcium homeostasis in manner similar to native parathyroid hormone. A placebo-controlled Phase 1 study will evaluate the safety and tolerability of once-daily and twice-daily dosing of the SEP-786 in healthy volunteers.

在动物试验中，Septerna报道了其小分子激动剂激活PTH1R并以类似于天然甲状旁腺激素的方式调节对钙稳态重要的关键基因。一项安慰剂对照的1期研究将评估健康志愿者每日一次和每日两次服用SEP-786的安全性和耐受性。

The first patient was dosed last month. Preliminary data are expected in mid-2025..

第一名患者上个月服用了药物。初步数据预计将于2025年年中发布。。

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好市多可以向医疗保健公司学习什么

The path forward is clear: employers must evaluate their health plan the same way they do their Saturday shopping excursion.

前进的道路是明确的：雇主必须像周六购物一样评估他们的健康计划。

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The Septerna pipeline includes two preclinical negative allosteric modulators. SEP-631 is in development for immunology and inflammation indications, such as the skin disease chronic spontaneous urticaria. TSHR has potential applications in endocrinology.

Septerna管道包括两个临床前负变构调节剂。SEP-631正在开发用于免疫学和炎症适应症，例如皮肤病慢性自发性荨麻疹。TSHR在内分泌学中具有潜在的应用。

Native Complex has also yielded small molecule agonists of the GLP-1, GIP, and glucagon receptors for the potential treatment of metabolic disorders. An oral Septerna drug that hits one or more of these receptors could put the biotech in competition with commercialized injectable peptide drugs, such as Eli Lilly’s Zepbound and Novo Nordisk’s Wegovy.

天然复合物还产生了GLP-1，GIP和胰高血糖素受体的小分子激动剂，用于潜在的代谢紊乱治疗。一种能够击中一种或多种受体的口服隔膜药物可能会使生物技术与商业化的注射肽药物竞争，例如礼来公司的Zepbound和诺和诺德公司的Wegovy。

But Septerna will likely aim to stand out from the next wave of metabolic medications in development as pills. This competition includes Structure Therapeutics, whose small molecules come from its own GPCR platform technology (when Structure went public last year, it snagged the fitting stock symbol “GPCR”).

但Septerna的目标可能是在下一波正在开发的代谢药物中脱颖而出，成为药丸。。

Lead Structure drug candidate GSBR-1290 is currently in mid-stage clinical development for type 2 diabetes and obesity..

铅结构候选药物GSBR-1290目前正处于2型糖尿病和肥胖症的中期临床开发阶段。。

Since Septerna’s inception in 2019, the company had raised $224.2 million prior to the IPO, most recently a $150 million Series B round last year led by RA Capital Management. That firm holds a 7.7% post-IPO stake in Septerna, according to the prospectus. Third Rock Ventures is Septerna’s largest shareholder with a 23.6% post-IPO stake.

自2019年Septerna成立以来，该公司在首次公开募股前筹集了2.242亿美元，最近一次是去年由RA Capital Management牵头的1.5亿美元B轮融资。根据招股说明书，该公司在Septerna上市后持有7.7%的股份。Third Rock Ventures是Septerna的最大股东，在IPO后持有23.6%的股份。

Septerna is led by CEO Jeff Finer, who is also a venture partner at Third Rock..

Septerna由首席执行官Jeff Finer领导，他也是Third Rock的风险合伙人。。

Septerna’s plans resonated with investors, whose interest in the biotech’s stock enabled the company to boost the IPO size twice. In preliminary financial terms set at the beginning of the week, Septerna planned to offer more than 10.9 million shares in the range of $15 to $17 each, which would have raised $175 million at the pricing midpoint.

Septerna的计划引起了投资者的共鸣，他们对生物技术股票的兴趣使该公司的IPO规模增加了两倍。根据本周初制定的初步财务条款，Septerna计划发行1090多万股股票，每股价格在15美元至17美元之间，这将在定价中点筹集1.75亿美元。

On Thursday, the biotech boosted the deal size to more than 15.2 million shares priced at $18 apiece, which would have raised $275 million at the pricing midpoint. Late Thursday, the biotech again revised the terms upward, boosting the deal to $288 million..

周四，这家生物技术公司将交易规模扩大至1520多万股，每股价格为18美元，在定价中点将筹集2.75亿美元。周四晚些时候，这家生物技术公司再次上调了条款，将交易金额提高到2.88亿美元。。

As of the end of the second quarter of this year, Septerna reported its cash position was $155.7 million. Following the IPO, the company plans to spend $54 million to advance lead drug candidate SEP-786 through Phase 2 testing in hypoparathyroidism, according to the filing. The company also plans to use the capital to develop additional molecules that target the parathyroid hormone receptor.

截至今年第二季度末，Septerna报告称其现金状况为1.557亿美元。根据申请，IPO后，该公司计划斥资5400万美元，通过甲状旁腺功能减退症的第二阶段测试，推进主要候选药物SEP-786。该公司还计划利用这笔资金开发针对甲状旁腺激素受体的其他分子。

Another $24 million will support the completion of Phase 1 testing of SEP-631 and additional molecule inhibitors that could be potential treatments for chronic spontaneous urticaria. And $41 million is set aside for other R&D, including Septerna’s TSHR and incretin receptor programs..

另外2400万美元将用于完成SEP-631和其他可能成为慢性自发性荨麻疹潜在治疗方法的分子抑制剂的第一阶段测试。4100万美元将用于其他研发，包括Septerna的TSHR和肠促胰岛素受体计划。。

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