SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Septerna, a biotechnology company discovering and advancing novel, oral small molecule medicines targeting G protein-coupled receptors (GPCRs), today presented preclinical data from the company’s parathyroid hormone 1 receptor (PTH1R) program and its thyroid stimulating hormone receptor (TSHR) program which validate the application of the Native Complex Platform™ for drug discovery in endocrine disorders.

加利福尼亚州南旧金山（商业新闻短讯）--Septerna是一家发现和开发针对G蛋白偶联受体（GPCR）的新型口服小分子药物的生物技术公司，今天提供了该公司甲状旁腺激素1受体（PTH1R）计划及其促甲状腺激素受体（TSHR）计划的临床前数据，该计划验证了Native Complex Platform™在内分泌疾病药物发现中的应用。

The data were presented in two poster presentations and a rapid-fire oral presentation during the Endocrine Society’s Annual Meeting (ENDO 2024) held June 1-4, 2024, in Boston, MA..

在2024年6月1日至4日于马萨诸塞州波士顿举行的内分泌学会年会（ENDO 2024）上，这些数据以两张海报和一场速射口头报告的形式呈现。。

Data from the PTH1R program showed small molecule agonists of PTH1R engaged endogenous pathways in the kidney and bone similar to native PTH peptide and demonstrated sustained control of serum calcium and phosphate levels over 28 days with daily oral administration. These results suggest that oral small molecule PTH1R agonists may be suitable alternatives to injectable PTH peptides for the treatment of hypoparathyroidism.

来自PTH1R计划的数据显示，PTH1R的小分子激动剂参与了肾脏和骨骼中的内源性途径，类似于天然PTH肽，并证明每天口服给药可在28天内持续控制血清钙和磷酸盐水平。这些结果表明，口服小分子PTH1R激动剂可能是可注射PTH肽治疗甲状旁腺功能减退症的合适替代品。

The company plans to initiate a Phase 1 trial with its lead PTH1R agonist candidate in healthy volunteers in late 2024..

该公司计划于2024年底在健康志愿者中启动一项第一阶段试验，其主要PTH1R激动剂候选物。。

“Our PTH1R agonist is the only small molecule in development to behave similarly to native PTH, and we are excited about its potential to reshape the treatment paradigm for hypoparathyroidism as we advance into the clinic later this year,” said Jeffrey Finer, M.D., Ph.D., Chief Executive Officer and Co-founder of Septerna.

Septerna首席执行官兼联合创始人杰弗里·芬尔（JeffreyFiner）医学博士说：“我们的PTH1R激动剂是唯一一种在开发中表现与天然PTH相似的小分子，随着我们今年晚些时候进入临床，我们对其重塑甲状旁腺功能减退症治疗模式的潜力感到兴奋。”。

“We are also pleased to showcase data from our TSHR antagonist program demonstrating its ability to target the known drivers of Graves’ disease, an indication for which there are currently no disease-modifying oral small molecules. Together, these data validate the ability of our Native Complex Platform™ to unlock difficult-to-drug GPCRs and to discover novel small molecules to address numerous endocrine disorders.”.

“我们也很高兴展示TSHR拮抗剂计划的数据，证明其能够针对格雷夫斯病的已知驱动因素，目前尚无改变疾病的口服小分子。这些数据共同验证了我们的原生复杂平台™解锁难治性GPCR并发现新的小分子以解决多种内分泌疾病的能力。”。

Summary of PTH1R Data

PTH1R数据摘要

The rapid-fire oral presentation and poster, entitled “Characterization of a Novel Oral Small Molecule PTH1R Agonist: Proof of Concept for an Alternative to Injectable Peptide-based Therapy for Hypoparathyroidism,” were presented by Jun Zhang, Ph.D., Senior Director of Disease Biology for Septerna.

Septerna疾病生物学高级主任Jun Zhang博士介绍了rapid fire口腔演示和海报，题为“新型口服小分子PTH1R激动剂的表征：甲状旁腺功能减退症注射肽替代疗法的概念验证”。

To assess PTH1R engagement in key target tissues, primary tissue from the renal cortex and tibial bone was assessed following in vivo treatment with PTH peptide and Septerna’s small molecule PTH1R agonist. The results suggest that PTH1R-regulated genes were similarly impacted by both PTH peptide and small molecule agonists..

为了评估PTH1R在关键靶组织中的参与，在用PTH肽和Septerna的小分子PTH1R激动剂进行体内治疗后，评估了来自肾皮质和胫骨的原代组织。结果表明，PTH1R调节的基因同样受到PTH肽和小分子激动剂的影响。。

Oral administration of a single dose of Septerna’s PTH1R agonist in a surgical rat model that mimics hypoparathyroidism in patients resulted in significant upregulation of serum calcium levels for a period of 24 hours in a dose dependent manner. The data also demonstrated sustained control of serum calcium and phosphate levels over 28 days with daily oral administration.

在模拟患者甲状旁腺功能减退的手术大鼠模型中口服单剂量Septerna的PTH1R激动剂导致血清钙水平以剂量依赖性方式显着上调24小时。数据还表明，每日口服给药可在28天内持续控制血清钙和磷酸盐水平。

The window of calcium upregulation is comparable to injectable PTH peptides currently in development to treat hypoparathyroidism..

钙上调的窗口与目前正在开发的用于治疗甲状旁腺功能减退症的可注射PTH肽相当。。

Summary of TSHR Data

TSHR数据汇总

Additionally, a poster entitled “A Novel, Oral Small Molecule Antagonist Targeting TSHR Improves Hyperthyroidism in an in vivo Model of Graves’ Disease” was presented.

此外，还展示了一张题为“靶向TSHR的新型口服小分子拮抗剂改善格雷夫斯病体内模型中的甲状腺功能亢进”的海报。

Data from the TSHR program demonstrated that Septerna’s small molecule TSHR antagonist blocks the stimulating effects of autoantibodies known to drive Graves’ disease (GD). Sustained treatment with the TSHR antagonist reduced the overall size of the thyroid gland and improved histological parameters associated with GD, providing proof-of-concept that potent small molecules directly targeting TSHR function have the potential to ameliorate the effects of hyperthyroidism in GD.

TSHR计划的数据表明，Septerna的小分子TSHR拮抗剂可阻断已知驱动格雷夫斯病（GD）的自身抗体的刺激作用。TSHR拮抗剂的持续治疗减少了甲状腺的整体大小，并改善了与GD相关的组织学参数，提供了概念证明，直接靶向TSHR功能的有效小分子有可能改善GD中甲状腺功能亢进的影响。

The company is advancing several lead molecules toward the selection of a development candidate for GD and Graves’ ophthalmopathy (also known as thyroid eye disease or TED)..

该公司正在推进几个先导分子，以选择GD和格雷夫斯眼病（也称为甲状腺眼病或TED）的发展候选者。。

About Septerna

关于Septerna

Septerna, Inc. is a biotechnology company focused on advancing novel, oral small molecule medicines targeting the entire class of G protein-coupled receptors (GPCRs). The company’s Native Complex Platform™ recapitulates GPCRs with their native structure, function, and dynamics outside of the cellular environment to rapidly apply new technologies for industrial-scale drug discovery to address both validated GPCRs and many GPCRs that have been undruggable and unexploited to date.

Septerna，Inc.是一家生物技术公司，专注于开发针对整类G蛋白偶联受体（GPCR）的新型口服小分子药物。该公司的Native Complex Platform™概括了GPCR在细胞环境之外的天然结构，功能和动态，以快速应用新技术进行工业规模的药物发现，以解决经过验证的GPCR和许多迄今为止无法药用和未开发的GPCR。

Septerna is building a pipeline of GPCR-targeted, oral small molecule drug candidates, led by its program targeting the parathyroid hormone 1 receptor (PTH1R) for the treatment of hypoparathyroidism. Septerna was launched in 2022 by scientific founders who have made groundbreaking GPCR discoveries. For more information, please visit www.septerna.com..

Septerna正在建立一个针对GPCR的口服小分子候选药物管道，该项目以甲状旁腺激素1受体（PTH1R）为靶点，用于治疗甲状旁腺功能减退症。Septerna于2022年由取得突破性GPCR发现的科学创始人发起。欲了解更多信息，请访问www.septerna.com。。

About the PTH1R Program and Hypoparathyroidism

关于PTH1R程序和甲状旁腺功能减退

Septerna is developing a novel, first-in-class, oral small molecule parathyroid hormone 1 receptor (PTH1R) agonist designed to treat patients with hypoparathyroidism, a harmful condition characterized by a deficiency of the parathyroid hormone (PTH). Hypoparathyroidism results in a wide range of debilitating symptoms, including fatigue, brain fog, muscle weakness, tissue calcification, and in severe cases can lead to seizures, heart arrhythmias, and kidney failure.

Septerna正在开发一种新型的一流口服小分子甲状旁腺激素1受体（PTH1R）激动剂，用于治疗甲状旁腺功能减退症患者，甲状旁腺功能减退症是一种以甲状旁腺激素（PTH）缺乏为特征的有害疾病。甲状旁腺功能减退会导致多种衰弱症状，包括疲劳，脑雾，肌肉无力，组织钙化，严重时会导致癫痫发作，心律失常和肾衰竭。

Current available treatments include supplements that only partially address PTH deficiency, or PTH peptide replacements, which require daily injections. Septerna’s investigational PTH1R agonist has been shown to normalize serum calcium levels in preclinical studies and has the potential to be the first oral alternative to injectable treatments for hypoparathyroidism..

目前可用的治疗方法包括仅部分解决PTH缺乏症的补充剂，或需要每日注射的PTH肽替代品。Septerna的研究性PTH1R激动剂已在临床前研究中显示可使血钙水平正常化，并有可能成为甲状旁腺功能减退症注射治疗的第一种口服替代药物。。

About the TSHR Program and Graves’ disease

关于TSHR计划和格雷夫斯病

Septerna is developing a novel, investigational, oral small molecule thyroid stimulating hormone receptor (TSHR) antagonist for the treatment of Graves’ disease and thyroid eye disease (TED). Graves’ disease is an autoimmune condition in which the body produces antibodies that bind to and activate the TSH receptor on thyroid cells.

Septerna正在开发一种新型的研究性口服小分子促甲状腺激素受体（TSHR）拮抗剂，用于治疗格雷夫斯病和甲状腺眼病（TED）。格雷夫斯病是一种自身免疫性疾病，体内产生抗体，结合并激活甲状腺细胞上的TSH受体。

These antibodies stimulate the thyroid gland to produce too much thyroid hormone, resulting in hyperthyroidism. Additionally, in TED, the antibodies stimulate TSH receptors on cells behind the eyes, causing swelling of the eye muscles, which can result in eye bulging, pain and impaired vision. Current standard-of-care treatments for Graves’ disease are inadequate and focus on the thyroid (surgery, radioactive iodine, and antithyroid medicines) while failing to prevent progression to TED.

这些抗体刺激甲状腺产生过多的甲状腺激素，导致甲状腺功能亢进。此外，在TED中，抗体刺激眼睛后面细胞上的TSH受体，导致眼部肌肉肿胀，从而导致眼睛肿胀，疼痛和视力受损。目前针对格雷夫斯病的标准治疗方法不充分，主要集中在甲状腺（手术，放射性碘和抗甲状腺药物）上，同时未能防止进展为TED。

Septerna’s TSHR program is designed to block the activity of all Graves’ autoactivating antibodies as a single oral therapeutic..

Septerna的TSHR计划旨在阻断所有格雷夫斯自身激活抗体作为单一口服治疗剂的活性。。