Advancing a differentiated mechanism to treat severe respiratory diseases
Upstream is developing verekitug, the only known clinical-stage monoclonal antibody targeting the receptor of thymic stromal lymphopoietin (TSLP), across multiple respiratory diseases driven by chronic inflammation, where TSLP inhibition may deliver a significant impact for patients.
Verekitug
Verekitug’s unique mechanism of action
We are developing verekitug, a novel recombinant fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to the TSLP receptor and inhibits pro-inflammatory signaling initiated by TSLP. TSLP is a cytokine that 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. In clinical trials, verekitug has demonstrated rapid, substantial, and sustained TSLP receptor inhibition for up to 24 weeks after the last dose. We believe this unique mechanism of action may translate to differentiated efficacy and less frequent dosing as compared to currently approved biologic therapies.
Demonstrating a differentiated profile in early clinical development
Verekitug has been evaluated in three Phase 1 clinical trials including a Phase 1 single-ascending dose trial and a Phase 1b multiple-ascending dose trial in 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 verekitug in severe respiratory diseases
Verekitug has advanced into three separate global, placebo-controlled, randomized Phase 2 clinical trials, one recently completed in chronic rhinosinusitis with nasal polyps (CRSwNP) and two ongoing in severe asthma and chronic obstructive pulmonary disease (COPD). These trials have been designed with endpoints that regulatory authorities use to evaluate potential new medicines.
Recently reported positive top-line data from the Phase 2 trial in CRSwNP demonstrated that verekitug, dosed at 100 mg once every 12 weeks, met both the primary and secondary endpoints at Week 24, and was well tolerated. Learn more about the top-line data here.
Maximizing the broad potential of verekitug
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 with unique attributes as a potential therapy for other TSLP-driven inflammatory diseases.