CHICAGO--(BUSINESS WIRE)--Xeris Biopharma Holdings, Inc. (Nasdaq: XERS), a growth-oriented biopharmaceutical company committed to improving patients’ lives by developing and commercializing innovative products across a range of therapies, today announced topline results from its recently completed Phase 2 multi-center, open label, study of XP-8121 for the treatment of adults with hypothyroidism.

芝加哥--（商业新闻短讯）--Xeris Biopharma Holdings，Inc.（纳斯达克：XERS），一家以增长为导向的生物制药公司，致力于通过开发和商业化各种疗法的创新产品来改善患者的生活，今天宣布了其最近完成的XP-8121治疗成人甲状腺功能减退症的第二阶段多中心开放标签研究的结果。

XP-8121 employs the Company’s XeriSol™ formulation technology to enable a novel once-weekly SC injection of levothyroxine. This novel formulation significantly increases the bioavailability of levothyroxine reducing overall drug exposure and enabling a dosing regimen with the potential to mitigate the many challenges associated with achieving and maintaining a normal level of thyroid stimulating hormone (TSH) with daily oral formulations of levothyroxine..

XP-8121采用该公司的Xerosol™配方技术，使每周一次的新型SC注射左旋甲状腺素成为可能。这种新型制剂显着提高了左旋甲状腺素的生物利用度，减少了总体药物暴露，并使给药方案有可能减轻与每日口服左旋甲状腺素制剂达到和维持正常促甲状腺激素（TSH）水平相关的许多挑战。。

The Phase 2 study (NCT05823012) was a non-randomized, open-label, single arm, self-controlled study of XP-8121 (levothyroxine sodium) to determine a target dose conversion factor from stably dosed oral levothyroxine to XP-8121 (levothyroxine sodium) in 46 patients with hypothyroidism and to assess the safety and tolerability of XP-8121 (levothyroxine sodium) after once-weekly SC injections.

第二阶段研究（NCT05823012）是XP-8121（左旋甲状腺素钠）的非随机，开放标签，单臂，自身对照研究，以确定46例甲状腺功能减退症患者从稳定剂量口服左旋甲状腺素到XP-8121（左旋甲状腺素钠）的目标剂量转换因子，并评估每周一次SC注射后XP-8121（左旋甲状腺素钠）的安全性和耐受性。

The Phase 2 study leveraged the bioavailability observations of a previous Phase 1 study in which PK analysis showed that participants could achieve comparable systemic exposure with XP-8121 at only 57% of a weekly oral dose. The Phase 2 study included the following periods: Screening, Titration Period (2 to 8 weeks), and Maintenance Period (4 weeks).

第二阶段研究利用了先前第一阶段研究的生物利用度观察结果，其中PK分析显示参与者可以在每周口服剂量的57%下实现与XP-8121相当的全身暴露。第二阶段研究包括以下阶段：筛选，滴定期（2至8周）和维持期（4周）。

Participants entered the study on a stable oral dose (≥ 3 months) with normal TSH and free T4 laboratory values..

参与者以TSH正常和游离T4实验室值的稳定口服剂量（≥3个月）进入研究。。

Participants were receiving a daily oral levothyroxine dose of 83.7 ± 31.14 mcg (mean ± SD) at study entry. To ensure the safety of study participants, once-weekly SC injection of XP-8121 was initiated at 2X their daily dose and titrated every 2 weeks to a target of 4X their daily dose. Participants completing the Maintenance Period were receiving a weekly XP-8121 dose of 324.4 ± 125.59 mcg.

参与者在研究开始时每天口服左旋甲状腺素剂量为83.7±31.14 mcg（平均值±SD）。为了确保研究参与者的安全，每周一次SC注射XP-8121，剂量为每日剂量的2倍，每2周滴定一次，目标剂量为每日剂量的4倍。完成维持期的参与者每周接受324.4±125.59 mcg的XP-8121剂量。

The geometric mean ratio of the once-weekly dose of XP-8121 to the daily dose levothyroxine (aka dose conversion factor) was 4.02 [90% CI 3.79, 4.27]. A total of 30 participants (65.2%) experienced at least 1 TEAE (Treatment Emergent Adverse Event) with most rated mild (87%) and moderate (13%) in severity.

XP-8121每周一次剂量与每日剂量左旋甲状腺素（又名剂量转换因子）的几何平均比为4.02[90%CI 3.79，4.27]。共有30名参与者（65.2%）经历了至少1次TEAE（治疗紧急不良事件），其中轻度（87%）和中度（13%）的严重程度最高。

The most frequent (> 2 participants) TEAE included fatigue (21.7%), injection site pain (10.9%), headache (8.7%) and urinary tract infection (6.5%). No deaths or other serious adverse events (SAEs) were reported. Injection site tolerability was assessed with every SC administration of XP-8121 (> 450 injections).

最常见的（>2名参与者）TEAE包括疲劳（21.7%），注射部位疼痛（10.9%），头痛（8.7%）和尿路感染（6.5%）。没有死亡或其他严重不良事件（SAE）的报告。每次SC施用XP-8121（>450次注射）评估注射部位耐受性。

There were very few reports of discomfort (18%; mostly mild intensity), erythema (7%; Draize scale) or edema (1%; Draize scale). No participant discontinued from the study due to an injection site reaction. The Treatment Satisfaction Questionnaire for Medication (TSQM-9) was administered to assess patient satisfaction.

很少有不适（18%；大多为轻度），红斑（7%；Draize量表）或水肿（1%；Draize量表）的报道。没有参与者因注射部位反应而停止研究。使用药物治疗满意度问卷（TSQM-9）评估患者满意度。

XP-8121 scored consistently higher in all three domains (effectiveness, convenience, and global satisfaction) compared to oral levothyroxine. At the conclusion of the study, participants were asked to rate preference for once-weekly XP-8121. A majority (72%) indicated a strong preference for the SC route of administration based on categorical attributes of convenience (60.6%), ease of administration (45.5%), frequency of administration (54.5%), level of comp.

与口服左旋甲状腺素相比，XP-8121在所有三个领域（有效性，便利性和全球满意度）的得分始终较高。在研究结束时，参与者被要求对每周一次的XP-8121进行评分。基于便利性（60.6%），易用性（45.5%），给药频率（54.5%），comp水平的分类属性，大多数（72%）表示强烈偏好SC给药途径。

“A 2022 study published in the Journal of the Endocrine Society estimated the prevalence of hypothyroidism in the U.S. grew to 11.7% or approximately 30 million adults in 2019*. Innumerable reports have been published documenting the various compliance and absorption challenges that can interfere with the bioavailability of oral levothyroxine.

“2022年发表在《内分泌学会杂志》上的一项研究估计，2019年美国甲状腺功能减退症的患病率增长至11.7%，即约3000万成年人*。已经发表了无数报告，记录了可能干扰口服左旋甲状腺素生物利用度的各种依从性和吸收挑战。

Interestingly, in our own Phase 2 study, 40% of patients considered stable at the time of screening were found to have their TSH or T4 outside of normal range. We believe our once-weekly SC injection can enable control in patients who struggle with oral preparations for a variety of reasons,” said Paul R.

有趣的是，在我们自己的2期研究中，发现筛查时被认为稳定的患者中有40%的TSH或T4超出正常范围。我们相信，我们每周一次的SC注射可以控制因各种原因难以口服制剂的患者，”PaulR。

Edick, Xeris’ Chairman and CEO..

Edick，Xeris的董事长兼首席执行官。

“We are excited by the initial top line results of our Phase 2 dose-finding study of XP-8121. These results are further evidence of our target dose conversion and consistent with the estimates generated from the prior Phase 1 study in healthy volunteers,” said Kenneth E. Johnson, PharmD, Xeris’ Senior Vice President, Global Development and Medical Affairs.

“我们对XP-8121第二阶段剂量发现研究的初步结果感到兴奋。这些结果进一步证明了我们的目标剂量转换，并与之前对健康志愿者进行的第一阶段研究得出的估计值一致，”Xeris全球发展和医疗事务高级副总裁KennethE.Johnson说。

“Given the known challenges of oral bioavailability of levothyroxine and further by the high rate of screen failures observed in our phase 2 study, we believe that XP-8121 could fill a substantial unmet medical need. We look forward to meeting with the FDA later this year and expect to present complete study results at upcoming medical meetings as well as submission to peer-reviewed medical journals.”.

“鉴于左旋甲状腺素口服生物利用度的已知挑战，以及我们在第二阶段研究中观察到的高筛查失败率，我们认为XP-8121可以满足大量未满足的医疗需求。我们期待今年晚些时候与FDA会面，并期望在即将举行的医学会议上提交完整的研究结果，并提交给同行评审的医学期刊。”。

About Hypothyroidism

关于甲状腺功能减退症

Hypothyroidism, or underactive thyroid, happens when your thyroid gland doesn't make enough thyroid hormones to meet your body's needs. Your thyroid is a small, butterfly-shaped gland in the front of your neck. It makes hormones that control the way the body uses energy. These hormones affect nearly every organ in your body and control many of your body's most important functions.

甲状腺功能减退症，或甲状腺功能不全，发生在你的甲状腺没有产生足够的甲状腺激素来满足你的身体需求的时候。你的甲状腺是一个小的蝶形腺体，位于你的脖子前面。它产生的激素控制身体使用能量的方式。这些激素几乎影响你身体的每个器官，并控制你身体的许多最重要的功能。

For example, they affect your breathing, heart rate, weight, digestion, and moods. Without enough thyroid hormones, many of your body's functions slow down..

例如，它们会影响你的呼吸、心率、体重、消化和情绪。如果没有足够的甲状腺激素，你身体的许多功能就会减慢。。

About Levothyroxine

关于左旋甲状腺素

Therapeutically, levothyroxine is administered when the body is deficient in the endogenous hormone. Administration of levothyroxine is thus indicated for acquired thyroid disease (primary hypothyroidism), in cases of decreased secretion of TSH from the anterior pituitary gland (secondary hypothyroidism), and in cases of decreased secretion of TRH from the hypothalamus (tertiary hypothyroidism) and for congenital hypothyroidism.

在治疗上，当身体缺乏内源性激素时，给予左旋甲状腺素。因此，左旋甲状腺素的给药适用于获得性甲状腺疾病（原发性甲状腺功能减退症），垂体前叶TSH分泌减少（继发性甲状腺功能减退症），下丘脑TRH分泌减少（三级甲状腺功能减退症）和先天性甲状腺功能减退症。

In most patients, hypothyroidism is a permanent condition requiring lifelong treatment. The goal of therapy is restoration of the euthyroid state, which can reverse the clinical manifestations of hypothyroidism and significantly improve quality of life..

在大多数患者中，甲状腺功能减退症是一种需要终身治疗的永久性疾病。治疗的目标是恢复甲状腺功能正常状态，这可以逆转甲状腺功能减退症的临床表现，并显着改善生活质量。。

About XeriSol™

XeriSol™

The proprietary XeriSol™ non-aqueous formulation technology platform is designed to address the limitations of aqueous formulations for peptide and small molecule drugs. The solutions are formulated using biocompatible, non-aqueous solutions that impart high stability and solubility to drugs allowing for development of room temperature stable, ready-to-use formulations.

专有的Xerosol™非水性制剂技术平台旨在解决肽和小分子药物水性制剂的局限性。这些溶液是使用生物相容的非水溶液配制的，这些溶液赋予药物高稳定性和溶解度，从而可以开发出室温稳定的即用制剂。

XeriSol™ formulations have been used extensively in global commercial products (Gvoke®/Ogluo®) and clinical trials. The technology is protected by an extensive patent estate, trade secrets and know-how, and it is available for licensing..

Xerosol™制剂已广泛用于全球商业产品（Gvoke®/Oglou®）和临床试验。该技术受到广泛的专利权、商业秘密和专有技术的保护，并且可以获得许可。。

About Xeris

任务

Xeris (Nasdaq: XERS) is a growth-oriented biopharmaceutical company committed to improving patient lives by developing and commercializing innovative products across a range of therapies. Xeris has three commercially available products; Gvoke®, a ready-to-use liquid glucagon for the treatment of severe hypoglycemia, Keveyis®, a proven therapy for primary periodic paralysis, and Recorlev® for the treatment of endogenous Cushing’s syndrome.

Xeris（纳斯达克股票代码：XERS）是一家以增长为导向的生物制药公司，致力于通过开发和商业化各种疗法的创新产品来改善患者的生活。Xeris有三种市售产品；Gvoke®，一种用于治疗严重低血糖的即用型液体胰高血糖素，Keveyis®，一种经证实的原发性周期性麻痹疗法，以及Recorlev®用于治疗内源性库欣综合征。

Xeris also has a robust pipeline of development programs to extend the current marketed products into important new indications and uses and bring new products forward using its proprietary formulation technology platforms, XeriSol™ and XeriJect®, supporting long-term product development and commercial success..

Xeris还拥有强大的开发计划渠道，将当前上市的产品扩展到重要的新适应症和用途，并使用其专有配方技术平台XeriSol™和XeriJect®推出新产品，支持长期产品开发和商业成功。。

Xeris Biopharma Holdings is headquartered in Chicago, IL. For more information, visit www.xerispharma.com, or follow us on X, LinkedIn, or Instagram.

施乐生物制药控股公司总部位于伊利诺伊州芝加哥。有关更多信息，请访问www.xerispharma.com，或通过X、LinkedIn或Instagram关注我们。

Forward-looking Statement

前瞻性声明

Any statements in this press release other than statements of historical fact are forward-looking statements. Forward-looking statements include, but are not limited to, statements about future expectations, plans and prospects for Xeris Biopharma Holdings, Inc. including statements regarding expectations for the release of clinical data or results from clinical trials, the timing of meetings with regulatory authorities, the market and therapeutic potential of its products and product candidates, including the therapeutic potential of XP-8121, the potential utility of its formulation platforms, including XeriSol™-formulated subcutaneous levothyroxine’s potential benefits compared to daily oral formulations, the intellectual property rights associated with XeriSol™ and its availability for licensing and other statements containing the words “will,” “would,” “continue,” “expect,” “should,” “anticipate” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995.

本新闻稿中除历史事实声明外的任何声明均为前瞻性声明。前瞻性声明包括但不限于关于Xeris Biopharma Holdings，Inc.未来预期、计划和前景的声明，包括关于临床数据或临床试验结果发布的预期、与监管机构会面的时间、其产品和候选产品的市场和治疗潜力的声明，包括XP-8121的治疗潜力、其配方平台的潜在效用，包括XeriSol™配制的皮下左旋甲状腺素与每日口服配方相比的潜在益处、与XeriSol™相关的知识产权及其许可可用性以及其他包含“将”、“将”、“继续”、“期望”、“应该”、“预期”和类似表述的声明，构成了前瞻性声明。寻找1995年《私人证券诉讼改革法案》所指的声明。

These forward-looking statements are based on numerous assumptions and assessments made in light of Xeris’ experience and perception of historical trends, current conditions, business strategies, operating environment, future developments, geopolitical factors and other factors it believes appropriate.

这些前瞻性陈述基于众多假设和评估，这些假设和评估是根据Xeris的经验和对历史趋势、当前状况、业务战略、运营环境、未来发展、地缘政治因素和其他其认为合适的因素的看法做出的。

By their nature, forward-looking statements involve known and unknown risks and uncertainties because they relate to events and depend on circumstances that will occur in the future. The various factors that could cause Xeris’ actual results, performance or achievements, industry results and developments to differ materially from those expressed in or implied by such forward-looking statements, include, but are not limited to, its financia.

就其性质而言，前瞻性陈述涉及已知和未知的风险和不确定性，因为它们与事件有关，并取决于未来将发生的情况。可能导致Xeris的实际业绩、业绩或成就、行业业绩和发展与此类前瞻性声明中表达或暗示的有重大差异的各种因素包括但不限于其财务状况。

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