Upstream Bio plans dual Phase 3 trials for verekitug in 2027
Upstream Bio has announced its pivotal Phase 3 development strategy for verekitug, its anti-TSLP receptor monoclonal antibody, following productive End-of-Phase 2 meetings with the US FDA. The Nasdaq-listed company (UPB) plans to initiate one placebo-controlled Phase 3 trial in severe asthma and one in chronic rhinosinusitis with nasal polyps (CRSwNP) during the first quarter of 2027, with each study contributing to a combined enrolment target of approximately 1,500 patients across both trials.
The trials will evaluate a single subcutaneous dose of 400 mg administered every 12 weeks, a quarterly regimen the company is positioning as a potential convenience advantage over some existing approved biologics in the space. Crucially, the studies will not restrict enrolment based on baseline biomarkers, a design choice that widens the addressable patient pool and distinguishes the programme from therapies that depend on elevated type-2 inflammatory markers such as blood eosinophils or FeNO for patient selection.
Trial design and endpoints
The primary endpoint for the asthma trial is annualised asthma exacerbation rate over 48 weeks, a standard and well-accepted measure in severe asthma pivotal programmes. The CRSwNP trial will use co-primary endpoints: change from baseline in nasal polyp score and nasal congestion score, each measured at 48 weeks. Both designs align with established regulatory expectations for their respective indications and should support a Biologics Licence Application (BLA) submission to the FDA if results are positive, with the company projecting potential launch as early as 2030.
Aaron Deykin, Chief Medical Officer and Head of Research and Development at Upstream Bio, said the goal is to "deliver best-in-class efficacy with quarterly at-home administration for patients with severe asthma and CRSwNP, irrespective of biomarker status."
Verekitug is a fully human IgG1 monoclonal antibody targeting the TSLP receptor rather than the cytokine itself. TSLP sits upstream of multiple inflammatory pathways, including those driven by IL-4, IL-5, IL-13 and IgE, which are the targets of several already-approved biologics. More than 500 patients have been treated with verekitug across its clinical programmes, and positive Phase 2 data in both indications underpin the company's confidence heading into pivotal studies. Verekitug is also being evaluated in an ongoing Phase 2 trial in chronic obstructive pulmonary disease (COPD).
Competitive landscape
The severe asthma biologics market is densely contested. AstraZeneca's tezepelumab, which also targets TSLP (the ligand rather than the receptor), is already approved in the US and Europe and has demonstrated efficacy regardless of biomarker status. Dupilumab, mepolizumab and benralizumab cover overlapping type-2 inflammatory pathways and command significant market share. Upstream Bio's receptor-antagonist approach is mechanistically distinct from tezepelumab, though whether that distinction translates into a meaningful clinical differentiation will depend heavily on the head-to-head implied by the Phase 3 datasets and any future comparative studies.
The CRSwNP space is similarly competitive, with dupilumab and omalizumab both approved. A quarterly dosing interval would be an improvement over current standard of care if efficacy and safety data support it, but the field will demand robust trial execution and clean safety signals before rewarding the differentiation claim commercially.
Investors will be watching the Q1 2027 trial initiation dates closely, and any delays could affect sentiment given the company is still pre-revenue at clinical stage.