WALTHAM, Mass.--(BUSINESS WIRE)--Upstream Bio, a clinical-stage biotech company advancing new therapies to treat inflammation, today announced the dosing of the first patients in a Phase 2 clinical trial of verekitug in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Verekitug is a recombinant fully human immunoglobulin G1 monoclonal antibody designed to block the thymic stromal lymphopoietin receptor (TLSPR) and thus inhibit TSLP-driven inflammation.

马萨诸塞州沃尔瑟姆（商业新闻短讯）--Upstream Bio是一家临床阶段生物技术公司，致力于开发治疗炎症的新疗法，今天宣布，在verekitug的2期临床试验中，首批患者的剂量将用于慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）患者。Verekitug是一种重组全人免疫球蛋白G1单克隆抗体，旨在阻断胸腺基质淋巴细胞生成素受体（TLSPR），从而抑制TSLP驱动的炎症。

TSLP is a cytokine and a key driver of inflammatory response in CRSwNP, asthma, and other allergic and inflammatory diseases..

TSLP是一种细胞因子，是CRSwNP，哮喘和其他过敏性和炎性疾病炎症反应的关键驱动因素。。

“Enabled by the large and durable effects of verekitug on exhaled nitric oxide and blood eosinophils demonstrated in our recently completed Phase 1b study in asthma patients, we are thrilled to now move verekitug into Phase 2 in CRSwNP. The high potency data documented in our previous studies support a dosing interval of at least every 12 weeks,” said Aaron Deykin, MD, Chief Medical Officer and Head of Research and Development.

“在我们最近完成的哮喘患者1b期研究中，verekitug对呼出的一氧化氮和血液嗜酸性粒细胞产生了巨大而持久的影响，我们很高兴现在将verekitug转移到CRSwNP的第二阶段。我们之前的研究中记录的高效力数据支持至少每12周一次的给药间隔，”医学博士Aaron Deykin说，首席医疗官兼研发主管。

“We also plan to initiate a Phase 2 study in asthma this quarter that will include dosing intervals of 12 weeks and 24 weeks.”.

“我们还计划在本季度启动哮喘的2期研究，其中包括12周和24周的给药间隔。”。

The CRSwNP Phase 2 study is a randomized, double-blind, placebo-controlled study evaluating a dose of 100 mg administered subcutaneously in a single injection every 12 weeks. The study will evaluate verekitug’s efficacy in the treatment of CRSwNP with a primary endpoint of reduction in nasal polyp score.

CRSwNP 2期研究是一项随机，双盲，安慰剂对照研究，评估每12周一次皮下注射100 mg的剂量。该研究将评估verekitug治疗CRSwNP的疗效，其主要终点是降低鼻息肉评分。

Data from the combination of Upstream Bio’s Phase 2 studies in CRSwNP and asthma will inform the dose regimen for Phase 3 in both indications..

来自上游生物在CRSwNP和哮喘方面的2期研究的数据将为两种适应症的3期剂量方案提供信息。。

“This Phase 2 trial presents the opportunity for Upstream Bio to demonstrate verekitug’s potential as a best-in-class biologic for the treatment of a broad range of allergic and inflammatory conditions,” said Sam Truex, Chief Executive Officer. “We expect that the swift, substantial and sustained reduction in disease-related biomarkers seen in the Phase 1b will translate to meaningful results for patients with CRSwNP in our Phase 2 study with the benefit of one injection and a 12-week dosing interval.”.

首席执行官萨姆·特鲁克斯（SamTruex）表示：“这项第二阶段试验为上游生物提供了机会，证明了维列基图作为治疗各种过敏性和炎症性疾病的同类最佳生物制剂的潜力。”。“我们预计，在1b期所见的疾病相关生物标志物的快速，实质性和持续减少将在我们的2期研究中转化为CRSwNP患者的有意义的结果，受益于一次注射和12周的给药间隔。”。

About TSLP and TSLPR Blockade

关于TSLP和TSLPR封锁

Thymic Stromal Lymphopoietin (TSLP) is a cytokine that is a key driver of the inflammatory response in major allergic and inflammatory diseases, such as asthma, where disruption of TSLP signaling has been clinically validated as an effective therapeutic strategy. TSLP signaling is one of the first events in the inflammatory cascade stimulated by allergens, viruses, and other triggers.

胸腺基质淋巴细胞生成素（TSLP）是一种细胞因子，是主要过敏性和炎性疾病（如哮喘）炎症反应的关键驱动因素，其中TSLP信号的破坏已被临床验证为有效的治疗策略。TSLP信号传导是由过敏原，病毒和其他触发因素刺激的炎症级联反应中的首批事件之一。

TSLP signaling activates downstream targets such as IL-4, IL-5, IL-13, IL-17 and IgE. Because TSLP is a target upstream in the inflammatory cascade, there is opportunity to address disease at its root, prior to the influence of other disease-related cytokines. Blocking the TSLP receptor presents an opportunity for a single treatment to impact the drivers of multiple pathological inflammatory processes across a broad set of diseases..

TSLP信号传导激活下游靶标，例如IL-4，IL-5，IL-13，IL-17和IgE。由于TSLP是炎症级联反应上游的靶标，因此在其他疾病相关细胞因子的影响之前，有机会从根本上解决疾病。阻断TSLP受体为单一治疗提供了机会，可以影响多种疾病中多种病理性炎症过程的驱动因素。。

About Verekitug (UPB-101)

关于Verekitug（UPB-101）

Verekitug is a novel recombinant fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to the human thymic stromal lymphopoietin (TSLP) receptor (TSLPR) to inhibit signaling. In pre-clinical studies, verekitug demonstrated inhibition of cytokine production from both CD4+ T cells and ILC2, suggesting that it may be effective against multiple types of inflammation.

Verekitug是一种新型重组全人免疫球蛋白G1（IgG1）单克隆抗体（mAb），可与人胸腺基质淋巴细胞生成素（TSLP）受体（TSLPR）结合以抑制信号传导。在临床前研究中，verekitug证明抑制CD4+T细胞和ILC2产生细胞因子，表明它可能对多种类型的炎症有效。

Data in three Phase 1 studies conducted to date demonstrate that verekitug is safe and well-tolerated..

迄今为止进行的三项第一阶段研究的数据表明，verekitug是安全且耐受性良好的。。

In a Phase 1b study, verekitug became the first TSLP inhibitor to demonstrate sustained target engagement and maintain maximal inhibition of disease-related biomarkers in patients with asthma 24- weeks after the last study dose. Results of the Phase 1b study demonstrated that verekitug is a potent inhibitor of TSLP-driven biology.

在一项1b期研究中，verekitug成为第一个在最后一次研究剂量后24周证明持续靶向参与并维持哮喘患者疾病相关生物标志物最大抑制的TSLP抑制剂。1b期研究的结果表明，verekitug是TSLP驱动生物学的有效抑制剂。

It is the most advanced TSLP inhibitor in development and is the only agent with clinical data out to 32-weeks in asthmatic patients. The Phase 1b study in asthma demonstrated a swift, substantial and sustained effect on FeNO and blood eosinophils which potentially represents best in class potency and inhibition of disease-related biomarkers..

它是开发中最先进的TSLP抑制剂，是哮喘患者中唯一具有32周临床数据的药物。哮喘的1b期研究表明，对FeNO和血液嗜酸性粒细胞具有快速，实质性和持续的作用，这可能代表了最佳的效力和对疾病相关生物标志物的抑制作用。。

The company’s lead indication is asthma, a chronic disease of the lungs that affects approximately 350 million people worldwide and is often under-diagnosed and under-treated.1 Of the more than 25 million people in the U.S. living with asthma2 , about 5-10% suffer from severe asthma. CRSwNP is a chronic disease of the upper airway that obstructs the sinuses and nasal passages.

该公司的主要适应症是哮喘，这是一种慢性肺部疾病，影响全球约3.5亿人，通常诊断不足和治疗不足。1在美国2500多万哮喘患者中，约有5-10%患有严重哮喘。CRSwNP是一种上呼吸道慢性疾病，会阻塞鼻窦和鼻腔。

CRSwNP is highly comorbid with asthma, in fact up to 65% of patients with CRSwNP suffer from asthma.3.

CRSwNP与哮喘高度共病，事实上高达65%的CRSwNP患者患有哮喘。

About Upstream Bio

关于上游生物

At Upstream Bio we strive to reach the source of inflammation and conquer it. Our lead program, verekitug (UPB101), is a clinical-stage monoclonal antibody that inhibits the TSLP receptor. TSLP is a validated target positioned upstream of multiple signaling cascades that affect a variety of immune cells pivotal to common and rare diseases.

在Upstream Bio，我们努力找到炎症的来源并征服它。我们的主要项目verekitug（UPB101）是一种抑制TSLP受体的临床阶段单克隆抗体。TSLP是位于多个信号级联上游的经过验证的靶标，这些级联会影响对常见和罕见疾病至关重要的多种免疫细胞。

We have completed Phase 1b in asthma and are opening Phase 2 studies in both CRSwNP (Chronic rhinosinusitis with nasal polyps) and asthma in Q1 2024. We are leveraging our diverse roots and the team’s substantial industry experience to develop verekitug to ease the burden of inflammatory and allergic diseases on patients and their loved ones..

我们已经完成了哮喘的1b期研究，并在2024年第1季度开始了CRSwNP（慢性鼻-鼻窦炎伴鼻息肉）和哮喘的2期研究。我们正在利用我们多样化的根源和团队丰富的行业经验来开发verekitug，以减轻患者及其亲人的炎症和过敏性疾病负担。。

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1 EEACI Global Atlas of Asthma, April 2021

1 EEACI全球哮喘图谱，2021年4月

2 American Lung Association, website, 2023

2美国肺协会，网站，2023年

3 Bachert C, Bhattacharyya N, Desrosiers M, Khan AH. Burden of Disease in Chronic Rhinosinusitis with Nasal Polyps. J Asthma Allergy. 2021 Feb 11;14:127-134. doi: 10.2147/JAA.S290424. PMID: 33603409; PMCID: PMC7886239

3 Bachert C，Bhattacharyya N，Desrosiers M，Khan AH。慢性鼻-鼻窦炎伴鼻息肉的疾病负担。J哮喘过敏。2021年2月11日；14： 127-134。doi:10.2147/JAA.S290424。PMID:33603409；PMCID:PMC7886239