WALTHAM, Mass.--(BUSINESS WIRE)--Upstream Bio, a clinical-stage biotech company advancing new therapies to treat inflammation, today announced positive interim results in its Phase 1b clinical study of UPB-101, a thymic stromal lymphopoietin receptor (TSLPR) inhibitor. The Phase 1b study is a randomized, double-blinded, placebo-controlled multiple ascending dose (MAD) study with subcutaneous (SC) administration​ conducted in asthma patients.

马萨诸塞州沃尔瑟姆-（BUSINESS WIRE）-上游生物公司，一家临床阶段生物技术公司，推进治疗炎症的新疗法，今天宣布UPB-101（一种胸腺基质淋巴细胞生成素受体）的1b期临床研究取得积极的中期结果（TSLPR）抑制剂。1b期研究是一项随机、双盲、安慰剂对照的多次递增剂量（MAD）皮下注射（SC）的研究​ 在哮喘患者中进行。

The interim data results demonstrated favorable safety, tolerability, immunogenicity, pharmacokinetic (PK) and pharmacodynamic (PD) markers that strongly support moving to Phase 2..

中期数据结果表明有利的安全性，耐受性，免疫原性，药代动力学（PK）和药效学（PD）标记，强烈支持进入第2阶段。。

The Phase 1b trial enrolled 32 asthmatic subjects at 4 sites in the UK into four cohorts of doses: 100 mg every 4 weeks, 200 mg every 4 weeks, 300 mg every 12 weeks and a single dose of 25 mg. Within each cohort, subjects were randomized 6:2 to UPB-101 or placebo. At the week 24 interim evaluation, UPB-101 was safe and well tolerated and demonstrated full receptor saturation in all doses studied.

1b期临床试验将英国4个地点的32名哮喘患者分为4组：每4周100 mg，每4周200 mg，每12周300 mg，单剂量25 mg。在每个队列中，受试者被随机分配到UPB-101或安慰剂6:2。在第24周的中期评估中，UPB-101安全且耐受性良好，并且在所研究的所有剂量中均显示完全受体饱和。

Furthermore, UPB-101 was demonstrated to be a potent suppressor of the disease-related biomarker, fractional exhaled nitric oxide (FeNO). PK/PD modelling indicated a maximal FeNO reduction from baseline (Emax) of 43%. PK observations support exploration of extended interval dose regimens in Phase 2..

此外，UPB-101被证明是疾病相关生物标志物，分数呼出一氧化氮（FeNO）的有效抑制剂。PK/PD模型显示FeNO从基线（Emax）的最大降低为43%。PK观察支持在阶段2中探索延长的间隔剂量方案。。

Detailed topline results are expected to be presented at an upcoming congress.

详细的顶线结果预计将在即将召开的大会上公布。

“These results confirm the high potency of UPB-101 and thus indicate that 12- and 24-week extended interval dosing is appropriate. In this regard, we are excited to pursue both 12- and 24-week regimens in our Phase 2 trial in severe asthma,” said Aaron Deykin, MD, Chief Medical Officer and Head of Research and Development..

“这些结果证实了UPB-101的高效性，因此表明12周和24周的延长间隔给药是合适的。在这方面，我们很高兴在我们的2期临床试验中同时采用12周和24周的治疗方案。严重哮喘，”首席医疗官兼研发主管艾伦·德金博士说。。

Additionally, the company has completed a randomized, double-blinded, placebo-controlled Phase 1 single dose study of UPB-101 in 32 participants representing Japanese and non-east Asian healthy volunteers. The study demonstrated PK/PD and safety data entirely consistent with existing data previously generated in Western populations studied in other trials.

此外，该公司还在代表日本和非东亚健康志愿者的32名参与者中完成了UPB-101的随机，双盲，安慰剂对照的1期单剂量研究。该研究表明PK/PD和安全性数据与先前在其他试验中研究的西方人群中产生的现有数据完全一致。

This study included doses of 100 mg, 200 mg and 300 mg..

该研究包括100mg，200mg和300mg的剂量。。

In June of this year, the company raised a Series B private capital round to pursue registrational Phase 2 clinical trials in asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The company has also grown to 30 people who are highly experienced biotech professionals managing multiple mid-stage clinical trials in partnership with an established global CRO partner..

今年6月，该公司开设了B系列私人资本轮，对鼻息肉（CRSwNP）哮喘和慢性鼻-鼻窦炎进行注册2期临床试验。该公司还拥有30名经验丰富的生物技术专业人员，与已建立的全球CRO合作伙伴合作管理多项中期临床试验。。

“As expected, the Phase 1b study supports continued exploration of the safety and efficacy of UPB-101 at dose intervals that may provide patients and their caregivers with options to extend their dose to every 12 weeks or even every 24 weeks,” added Samantha Truex, CEO. “The Upstream team is taking swift steps to move into our global Phase 2 studies in severe asthma and CRSwNP by Q1 2024.

“正如预期的那样，1b期研究支持继续探索UPB-101的安全性和有效性，剂量间隔可为患者及其护理人员提供将剂量延长至每12周甚至每24周一次的选择，”Samantha Truex，首席执行官。“上游团队正在迅速采取措施，在2024季度之前进入我们关于严重哮喘和CRSwNP的全球2期研究。

These data indicate that UPB-101 and TSLPR inhibition have the potential to offer best-in-class advantages that have yet to be realized across current treatment options.”.

这些数据表明，UPB-101和TSLPR抑制有可能提供目前治疗方案尚未实现的最佳优势。

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.

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信号传导的破坏已被临床验证为有效的治疗策略。

TSLP signaling is one of the first events in the inflammatory cascade stimulated by allergens, viruses, and other triggers. 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.

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信号传导激活下游靶标，例如IL-4，IL-5，IL-13，IL-17和IgE。因为TSLP是炎症级联上游的靶标，所以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。

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..

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 Phase 1b Trial in Asthma (NCT 05448651) and Phase 1 Japanese healthy volunteer Trial (NCT 05653479)

关于哮喘的1b期试验（NCT 05448651）和1期日本健康志愿者试验（NCT 05653479）

The Safety and Biologic Impact (Pharmacodynamics) of Repeated Injections and Increasing Amounts of UPB-101 in Asthmatics (Phase 1b study in Asthma) is a randomized, double-blinded, placebo-controlled multiple ascending dose (MAD) study with subcutaneous (SC) admin​istration conducted in asthma patients.

重复注射和增加哮喘患者UPB-101量的安全性和生物学影响（药效学）（哮喘1b期研究）是一项随机，双盲，安慰剂对照的多次递增剂量（MAD）研究，皮下（SC）给药​在哮喘患者中进行的治疗。

It was designed to demonstrate clinical evidence of safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and immunogenicity. The Phase 1 single dose study in Japanese and non-east Asian healthy volunteers is a randomized, double-blinded, placebo-controlled Phase 1 single dose study of UPB-101.

它旨在证明安全性，耐受性，药代动力学（PK），药效学（PD）和免疫原性的临床证据。日本和非东亚健康志愿者的1期单剂量研究是UPB-101的随机，双盲，安慰剂对照1期单剂量研究。

It was designed to demonstrate clinical evidence of safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and immunogenicity..

它旨在证明安全性，耐受性，药代动力学（PK），药效学（PD）和免疫原性的临床证据。。

About UPB-101

关于UPB-101

UPB-101 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. UPB-101 is designed to address allergic and inflammatory diseases including asthma. In pre-clinical studies, UPB-101 demonstrated inhibition of cytokine production from both CD4+ T cells and ILC2, and completely suppressed skin allergic reactions in a monkey model, suggesting that it may be effective against multiple types of inflammation.

UPB-101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，抑制信号传导。UPB-101旨在解决过敏性和炎症性疾病，包括哮喘。在临床前研究中，UPB-101证明抑制CD4+T细胞和ILC2的细胞因子产生，并完全抑制猴模型中的皮肤过敏反应，表明它可能对多种类型的炎症有效。

Data in all three Phase 1 studies conducted to date demonstrate that UPB-101 is safe and well-tolerated..

迄今为止进行的所有三项1期研究的数据表明，UPB-101安全且耐受性良好。。

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 asthma 2, 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，这是一种肺部慢性疾病，影响全球约3.5亿人，并且经常被诊断和治疗不足.1美国2500多万人患有哮喘2，约5-10%患有严重哮喘。CRSwNP是阻塞鼻窦和鼻腔的上呼吸道慢性疾病。

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

CRSwNP与哮喘高度共存，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, UPB-101, 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.

在上游Bio，我们努力达到炎症源并征服它。我们的领导计划UPB-101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，其影响对常见和罕见疾病至关重要的各种免疫细胞。

We are leveraging our diverse roots and the team’s substantial industry experience to develop therapies that ease the burden of inflammatory and allergic diseases on patients..

我们正在利用我们不同的根源和团队丰富的行业经验来开发减轻患者炎症和过敏性疾病负担的疗法。。

EEACI Global Atlas of Asthma, April 2021

EEACI全球哮喘图谱，2021年4月

American Lung Association, website, 2023

美国肺协会，网站，2023

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.

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