Upstream Bio’s lead program, verekitug (UPB-101)
Our lead program, verekitug, is a monoclonal antibody that inhibits the TSLP receptor (TSLPR). TSLP is a validated target positioned upstream of multiple immune signaling cascades. Based on the consistency of the preclinical and clinical data, verekitug has the potential to be a best-in-class therapeutic based on its high potency and long dosing interval.
Verekitug Phase 1b data demonstrate a swift, substantial, and sustained effect.
Because it is designed to intervene before the release of numerous inflammatory cytokines, verekitug has the potential to address inflammation at its root across a broad spectrum of phenotypic, immune-mediated conditions. Verekitug is the only inhibitor of TSLP signaling to demonstrate sustained target engagement and maintain maximal inhibition of disease-related biomarkers in asthma patients 24 weeks after their last dose.
In the Phase 1b study of 32 asthmatic patients, verekitug resulted in a swift, substantial, and sustained reduction in disease-related biomarkers, including fractional exhaled nitric oxide (FeNO), and eosinophils through 32 weeks.
Completed Single Ascending Dose Data
Upstream Bio acquired verekitug with a completed single ascending dose study in healthy volunteers demonstrating the asset to be safe and have pharmacokinetic effect.
Initiated Multiple Ascending Dose Study
Upstream has established its verekitug program with a focus on serving populations of patients with TSLP-driven inflammatory conditions not sufficiently addressed by available therapies.
Finalized Multiple Ascending Dose Data
Evidence from the Phase 1b study supports verekitug’s best-in-class potential. For example, the 100 mg dose showed a 54% reduction from baseline in FeNo and EOS at week 12 that was sustained through week 32, which was 24 weeks after the last dose. These observations demonstrate the high potency of UPB-101 and enable Upstream to study extended dosing regimens in Phase 2 including every 24 weeks.
Initiated Phase 2 for CRSwNP and Asthma
Upstream Bio is pursuing Phase 2 studies for verekitug in severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), two inflammatory conditions for which there is significant unmet patient need.
The Phase 2 program in asthma will study doses of every 12 weeks and every 24 weeks with a single subcutaneous injection.
TSLP
TSLP is a key driver of the inflammatory response in major allergic and inflammatory diseases.
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 TSLP expression is elevated across lung tissues and blood compared with healthy individuals and correlates with airway obstruction and disease severity. In addition, Genome-Wide Association Studies have identified associations between asthma risk and polymorphisms in the TSLP gene.
TSLP activation is one of the first events in the inflammatory cascade stimulated by allergens, viruses, and other triggers, initiating the upregulation 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, there is opportunity to address disease at its root, prior to the influence of other disease-related cytokines. Targeting TSLP presents an opportunity for a single treatment to impact the drivers of multiple pathological inflammatory processes across a broad set of diseases.
Clinical Trials
Upstream Bio has advanced verekitug into Phase 2 of clinical development, with plans for studies in severe asthma and CRSwNP.
Asthma is a chronic disease of the lungs in which breathing is impaired due to factors like inflammation. Asthma affects approximately 350 million people worldwide and is often under-diagnosed and under-treated. The condition can be triggered by infections or environmental irritants, leading to symptoms including coughing, wheezing and shortness of breath. Cases of asthma can range from mild to severe, and in some situations may be life-threatening. Of the more than 25 million people in the U.S. living with asthma, about 5-10% suffer from severe asthma. It is estimated that only about 20% of people living with severe asthma receive biologic treatments.
Learn more about our Phase 2 clinical trial evaluating verekitug for the treatment of asthma.
ASTHMA
A chronic disease of the lungs affecting 350 million patients.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic disease of the upper airway that obstructs the sinuses and nasal passages. CRSwNP develops when the sinuses become irritated due to infection, pollutants, or allergens, leading to growths inside the nose and sinuses. The sinus irritation and polyps associated with CRSwNP can lead to excess mucus, loss of smell, headaches and facial pain, which affect quality of life such as sleep, and even can lead to trouble breathing. It is estimated that as many as 280 million people worldwide may live with CRSwNP, and the condition is highly comorbid with asthma – as many as 65% of patients with CRSwNP also suffer from asthma.
Learn more about our ongoing Phase 2 clinical trial evaluating verekitug for the treatment of CRSwNP.
CRSwNP
A chronic disease of the upper airway that is highly comorbid with asthma.
Relevant Publications
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
TSLP: from allergy to cancer
Corren J, Ziegler SF. Nat Immunol. 2019 Dec;20(12):1603-1609.
https://doi.org/10.1038/s41590-019-0524-9