Upstream Bio announced positive top-line results from its Phase II VALIANT clinical trial evaluating verekitug asthma treatment, demonstrating statistically significant reductions in asthma exacerbations. The novel monoclonal antibody targeting the thymic stromal lymphopoietin (TSLP) receptor showed meaningful clinical improvements in lung function and inflammatory markers, positioning it as a potential breakthrough in severe asthma treatment.
Trial specifics
The global, randomized, placebo-controlled Phase II trial enrolled 478 adults with severe asthma, comparing three different dosing regimens of verekitug against placebo. Participants received subcutaneous injections of either 100 mg every 12 weeks, 400 mg every 24 weeks, or 100 mg every 24 weeks, with the primary endpoint measuring annualized asthma exacerbation rate (AAER).
Key efficacy results revealed statistically significant improvements across multiple parameters. The 100 mg every 12-week dosing demonstrated a 56% reduction in AAER (p<0.0003), while the 400 mg every 24-week regimen showed a 39% reduction (p<0.02). Placebo-adjusted lung function improvements reached 122 mL at week 60 for the 100 mg q12w group and 139 mL for the 400 mg q24w group.
Upstream Bio plans to advance verekitug into Phase III clinical trials for severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), pending regulatory interactions. Over 90% of eligible participants from the VALIANT trial have already enrolled in VALOUR, a long-term extension study designed to evaluate sustained safety and efficacy.
Research context
Thymic Stromal Lymphopoietin (TSLP) acts as an “upstream” master switch in the immune system, sitting at the top of the inflammatory cascade. While traditional biologics target specific downstream cells, TSLP initiates the broad response to triggers like allergens and pollutants. By blocking this pathway, therapies can treat a wide range of severe asthma patients regardless of their specific biomarkers. Currently, the market is led by AstraZeneca’s Tezspire, which targets the TSLP ligand and requires monthly injections. Other competitors are also exploring “alarmins” like IL-33 to achieve similar broad-spectrum control, while established players like Dupixent continue to lead in the IL-4/IL-13 space.
Upstream Bio’s verekitug differentiates itself by targeting the TSLP receptor rather than the ligand, a mechanism that may offer more comprehensive pathway blockade. The most significant disruption, however, lies in its delivery; while current biologics require frequent dosing, verekitug’s Phase II data supports dosing every 12 to 24 weeks. This move toward a “twice-a-year” injection significantly reduces the treatment burden for patients, positioning verekitug not just as a clinical alternative to Tezspire, but as a more convenient, next-generation leader in the multi-billion dollar severe asthma market.
Other long-acting TSLP programs include:
- GSK (GSK5784283): Originally discovered by Jiangsu Hengrui and acquired by GSK via the purchase of Aiolos Bio, GSK5784283 is an anti-TSLP antibody currently in Phase II trials (NCT06748053) and designed to allow twice-yearly dosing.
- Uniquity Bio (solrikitug): Uniquity is advancing the TSLP-targeted solrikitug, also in Phase II studies, with early clinical data suggesting it may support a dosing schedule similar to Upstream’s.
- Sanofi (lunsekimig): lunsekimig, a bispecific Nanobody that targets both TSLP and IL-13. Phase II data is expected in 2026.
- Generate Biomedicines (GB-0895): Optimized for “best-in-class” half-life and binding affinity, this Phase III stage anti-TSLP molecule may also support twice-yearly dosing.