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Upstream Bio’s lead program, verekitug (UPB-101)

Verekitug is the only known clinical-stage antibody targeting the TSLP receptor.

We are developing verekitug, the only known antagonist currently in clinical development that targets the receptor for Thymic Stromal Lymphopoietin (TSLP), a cytokine which is a clinically validated driver of inflammatory response positioned upstream of multiple signaling cascades that affect a variety of immune mediated diseases.

Preclinical and clinical data to date demonstrate verekitug’s highly potent inhibition of the TSLP receptor, which we believe may translate to differentiated efficacy and less frequent dosing as compared to currently approved biologic therapies.

Our experienced team is committed to maximizing verekitug’s unique attributes to address the substantial unmet needs for patients with severe respiratory disease who are underserved by today’s standard of care.

Demonstrating a differentiated profile to date

In clinical trials, verekitug has demonstrated rapid, substantial, and sustained target engagement for up to 24 weeks after the last dose.

Verekitug has been evaluated in three clinical trials: a Phase 1 single-ascending dose trial, a Phase 1b multiple-ascending dose trial in patients with asthma and a Japanese ethnobridging study in healthy volunteers. Across the three clinical trials, we have data from 120 total participants, including 32 patients with asthma. In these trials, verekitug was well tolerated, had no clinically meaningful immunogenicity, and showed a predictable and consistent pharmacokinetic profile with high subcutaneous bioavailability. In patients with asthma, verekitug led to >50% reductions in fractional exhaled nitric oxide (FeNO) and blood eosinophils that were rapid and sustained for up to 24 weeks after the last dose in the Phase 1b MAD trial.

Advancing our ongoing Phase 2 clinical trials for verekitug in severe asthma, CRSwNP and COPD

We are currently conducting three separate global, placebo-controlled, randomized Phase 2 clinical trials for chronic rhinosinusitis with nasal polyps (CRSwNP), severe asthma, and chronic obstructive pulmonary disease (COPD).

These trials have been designed using endpoints that, pending interactions with regulatory authorities, could allow data from these trials to support submissions for product approval.

View Pipeline

Maximizing the potential of verekitug in additional TSLP-driven diseases with high unmet needs

The TSLP signaling pathway is well understood to be either a risk factor or a key driver of inflammatory diseases across multiple therapeutic areas. Beyond our initial focus on respiratory indications, we believe verekitug has broad potential, and we intend to leverage its unique attributes to develop it as a potential therapy for other TSLP-driven diseases.

TSLP

Leveraging TSLP biology to address unmet needs of severe asthma, CRSwNP and COPD.

Click for detailed graphic

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 activation is one of the first events in the inflammatory cascade stimulated by allergens, viruses and other triggers, initiating the activation of downstream targets such as IL-4, IL-5, IL-13, IL-17 and IgE.

Because TSLP is a target upstream in the inflammatory cascade, blocking the TSLP receptor (TSLPR) presents an opportunity for a single treatment to impact the drivers of multiple pathological inflammatory processes across a broad set of diseases, including asthma, CRSwNP and COPD. We believe verekitug has the potential, if approved, to address unmet needs in multiple diseases characterized by TSLP-driven pathobiology due to the high potency and potential for extended dosing intervals that we have observed in our preclinical and clinical development to date.

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Clinical Trials

Upstream Bio has advanced verekitug into Phase 2 clinical development, with ongoing clinical trials in severe asthma, CRSwNP and COPD.

Ongoing clinical trials
Publications



Severe Asthma

A chronic disease of the lungs affecting 350 million patients globally.

Asthma is a common respiratory disease characterized by chronic airway inflammation that is often underdiagnosed and under-treated. For some people, asthma can simply be a nuisance, for others it can interfere with daily life and potentially even be life-threatening. Severe asthma is defined as asthma that remains uncontrolled despite optimized treatment with high-dose inhaled corticosteroids or that requires high-dosed inhaled corticosteroids to prevent symptoms from becoming uncontrolled. It is estimated that approximately 90% of people with severe asthma are eligible for treatment with a biologic, but only 440,000 patients are currently treated with biologics, suggesting more than 80% of eligible patients are not being optimally treated. Key areas of unmet need for people living with severe asthma include improved control of exacerbations and symptoms, and reduced treatment burden (e.g., need for frequent injections).

Learn more about our ongoing Phase 2 clinical trial evaluating verekitug for the treatment of severe asthma.

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Chronic Rhinosinusitis with
Nasal Polyps (CRSwNP)

A chronic disease of the upper airway that is highly comorbid with asthma.

CRSwNP is an inflammatory disease of the upper airway, marked by chronic sinonasal inflammation and the presence of inflammatory polyps in the nasal passages and paranasal sinuses. It is estimated that approximately 900,000 patients in the United States and Europe suffer from CRSwNP. Nasal polyps are associated with significant morbidity and debilitating symptoms; it is estimated that 40% to 45% of people with severe asthma also have CRSwNP and that up to 65% of people with CRSwNP also have asthma, demonstrating a strong association between the two conditions. Despite available treatments such as corticosteroids, surgery and, more recently, biologics, the quality of life studies and post-surgical recurrence rates clearly show that many people with CRSwNP have uncontrolled symptoms that are impacting their daily life and current treatments are not meeting their needs.

Learn more about our ongoing Phase 2 clinical trial evaluating verekitug for the treatment of CRSwNP.

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Chronic Obstructive
Pulmonary Disease (COPD)

A chronic inflammatory disease that obstructs airflow from the lungs.

COPD is a chronic inflammatory disease associated with airflow worsening and episodic exacerbations that drive morbidity and mortality. Chronic inflammation causes structural changes within the lungs, narrowing already small airways and damaging lung tissue which causes air sacs to lose functionality. It is typically caused by long-term exposure to irritants, most often cigarette smoke. People with a history of asthma are also more likely to have COPD.

COPD is the fourth leading cause of death worldwide, causing approximately 3.5 million deaths in 2021. With COPD, everyday activities may result in shortness of breath and frequent exacerbations, which can result in hospitalization and drive health care utilization. People with COPD are also more likely to acquire lung infections like bronchitis and pneumonia.

Elevated levels of TSLP have been found in the airways of people with COPD, and TSLP receptor expression was highest in patients with severe COPD compared to healthy controls. Environmental triggers can also increase TSLP expression in epithelial cells, suggesting a potential role of TSLP in COPD exacerbations.

Currently available treatments for COPD include inhaled steroids to reduce airway inflammation and bronchodilator inhalers to improve airflow. Oxygen and surgery may also be used for some patients with severe COPD. Similar to asthma and CRSwNP, biologics are emerging as new and potentially transformative treatments.

Learn more about our ongoing Phase 2 clinical trial evaluating verekitug for the treatment of COPD.

 

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Relevant Publications

In silico system pharmacology modeling provides insights into a mechanism for greater potency of TSLP/TSLPR pathway inhibition with verekitug, a novel antibody antagonist of the TSLP receptor, as compared with tezepelumab
Ashish Kalra, PhD; Emily Pace, PhD; Bjorn Millard, PhD; Sumathi Sivapalasingam, MD; Aaron Deykin, MD
View Poster

32-Week data from a multiple ascending-dose trial with verekitug, a novel investigational a novel antibody to the human thymic stromal lymphopoietin receptor (TSLPR), in adults with asthma
Aaron Deykin, MD; Chaim M. Brickman, MD; Peter Lloyd, PhD; Ivan Nestorov, PhD; Ashish Kalra, PhD1; Subhabrata Biswas, PhD; Arkadeep Sinha, PhD; Sumathi Sivapalasingam, MD; Oren M. Becker, PhD; Dave Singh, MD
View Poster

A multiple ascending dose study with verekitug, a novel antibody to the human thymic stromal lymphopoietin receptor, in adults with asthma
Dave Singh, MD; Aaron Deykin, MD; Peter Lloyd, Ph; Ivan Nestorov, PhD; Ashish Kalra, PhD; Subhabrata Biswas, PhD; Arkadeep Sinha, PhD; Chaim M. Brickman, MD; Oren M. Becker, PhD
View Poster

A phase 1, first-in-human, single ascending-dose study with a novel antibody to the human thymic stromal lymphopoietin receptor
Aaron Deykin, Chaim M. Brickman, Peter Lloyd, Oren M. Becker
View Poster

ASP7266, a Novel Antibody against Human Thymic Stromal Lymphopoietin Receptor for the Treatment of Allergic Diseases
Numazaki, et al. Journal of Pharmacology and Experimental Therapeutics. January 2022; 380 (1) 26-33
https://doi.org/10.1124/jpet.121.000686