Upstream Bio Shares Dose Study Findings of Verekitug in Adults with Asthma at ATS Conference

In a recent presentation at the American Thoracic Society International Conference in San Diego, Upstream Bio, Inc. revealed promising clinical data concerning their drug candidate, verekitug (UPB-101), which is aimed at treating severe asthma and related conditions. This novel therapeutic agent has demonstrated significant efficacy and a favorable safety profile in various clinical studies.

Verekitug, a potential first-in-class antagonist of the Thymic Stromal Lymphopoietin (TSLP) receptor, has shown remarkable outcomes in a multiple-ascending dose (MAD) study involving asthma patients. Key findings include a reduction of up to 54% in fractional exhaled nitric oxide concentration (FENO), a biomarker for Type 2 lung inflammation, with effects lasting up to 24 weeks post the final dose. Patients receiving doses higher than 100 mg of verekitug maintained complete TSLP receptor occupancy for a comparable period. This is particularly significant as elevated FENO levels are associated with an increased risk of asthma exacerbations.

The drug was also effective in reducing blood eosinophils, white blood cells often found in large numbers in asthma patients, which further illustrates its potential in mitigating asthma symptoms and improving clinical outcomes. Verekitug's safety and tolerability profile were also positive, with headaches being the most common side effect reported.

Dr. Aaron Deykin, Chief Medical Officer and Head of R&D at Upstream Bio, commented on the findings, emphasizing that the data support the potential of TSLP receptor blockade as an effective and long-lasting approach to managing severe asthma. He noted that the sustained reduction in FENO and blood eosinophils underscores the drug’s potential to deliver significant benefits with dosing intervals of 12 or 24 weeks.

Dr. Rand Sutherland, CEO of Upstream Bio, added that the clinical results bolster their preclinical data and suggest that verekitug could offer a differentiated treatment profile in terms of both efficacy and dosing intervals. The company is advancing two Phase 2 trials: one for severe asthma and another for chronic rhinosinusitis with nasal polyps (CRSwNP), aiming to confirm the extended durability of the drug’s effects.

The MAD study was a multicenter, randomized, double-blind, placebo-controlled trial that included adults with mild to moderate asthma and elevated blood eosinophils. Participants were divided into four dosing cohorts: 100 mg every four weeks, 200 mg every four weeks, 300 mg every 12 weeks, and a single 25 mg dose. They were monitored for 32 weeks post-randomization.

Verekitug’s mechanism involves blocking the TSLP receptor, thereby inhibiting the proinflammatory signaling initiated by TSLP. This cytokine plays a crucial role in the inflammatory response seen in allergic and inflammatory diseases like asthma. By targeting the TSLP receptor, verekitug has the potential to impact various downstream inflammatory processes, making it a versatile candidate for treating multiple conditions.

In preclinical studies, verekitug exhibited high TSLP receptor occupancy and potent inhibition of TSLP signaling. It also demonstrated the ability to suppress cytokine production from CD4+ T cells and ILC2 cells and completely eliminate skin allergic reactions in non-human primate models. These findings suggest its broad applicability in treating different types of inflammation.

To date, three clinical trials have been completed for verekitug, including a Phase 1 single-ascending dose (SAD) trial and a Phase 1b MAD trial. These studies confirmed the drug’s tolerability, lack of clinically meaningful immunogenicity, consistent pharmacokinetic profile, and high subcutaneous bioavailability.

Upstream Bio is focused on maximizing the potential of verekitug, not only for severe asthma and CRSwNP but also for other inflammatory diseases where TSLP signaling plays a pivotal role. The company aims to leverage the drug’s unique attributes to develop it as a therapy for a broader range of conditions.

The ongoing research and clinical trials hold promise for a new, effective treatment paradigm that could significantly improve the quality of life for patients suffering from severe asthma and other related inflammatory diseases.