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

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 will translate to a differentiated product profile, including improved clinical outcomes, substantially extended dosing intervals and the potential to treat a broad spectrum of patients.

We have advanced this highly potent monoclonal antibody into separate Phase 2 trials for the treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) and plan to initiate development in chronic obstructive pulmonary disease (COPD). Our experienced team is committed to maximizing verekitug’s unique attributes to address the substantial unmet needs for patients underserved by today’s standard of care.

 

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

Demonstrating a differentiated profile to date

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.

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

We are currently conducting two separate multi-national, placebo-controlled, randomized Phase 2 clinical trials to investigate the efficacy of two extended dosing intervals of 12 and 24 weeks for patients with severe asthma and 12 weeks for patients with CRSwNP. 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.

Expanding the impact of verekitug through an additional development program in COPD

Based on available data from Phase 1 trials with verekitug, we plan to initiate our first clinical trial in COPD. We have commenced planning activities for a Phase 2 clinical trial and expect to dose the first COPD patient in the second half of 2025.

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 member of a class of epithelial cytokines, also including IL-25 and IL-33, commonly referred to as alarmins. TSLP is primarily produced by epithelial cells, especially in the lung, gastrointestinal tract and skin. In response to various environmental triggers, including viruses, bacteria, allergens, chemical irritants and physical injury, TSLP can initiate and amplify a wide range of innate and adaptive immune responses.

TSLP signaling is a central instigator of multiple downstream biologic pathways relevant to human diseases that are characterized by epithelial inflammation, 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 and CRSwNP and a planned clinical trial in 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.

Similar to asthma, COPD is a chronic inflammatory disease that obstructs airflow from the lungs. Chronic inflammation causes structural changes within the lungs, narrowing already small airways and damaging lung parenchyma which causes air sacs to lose functionality and decreases lung elasticity. 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 third leading cause of death worldwide, causing approximately 3.2 million deaths in 2019. Treatments for COPD are similar to those for asthma and CRSwNP. Despite available treatments, 60% of all COPD patients report some limitations in their daily activity, with 45% being unable to work and 75% complaining of difficulty climbing stairs. Given the high levels of morbidity and mortality associated with COPD, the currently available medicines are not sufficient to control symptoms or disease progression.

We have commenced planning activities for a Phase 2 clinical trial and expect to dose the first COPD patient in the second half of 2025.

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Relevant Publications

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
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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
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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