Solrikitug Shows Promise as Next-Generation Anti-TSLP Therapy in Asthma, COPD

A novel monoclonal antibody, solrikitug (Uniquity Bio), may offer a more potent alternative to tezepelumab for patients with severe asthma, chronic obstructive pulmonary disease (COPD), and other thymic stromal lymphopoietin (TSLP)–driven diseases, according to in vitro findings presented at the American Thoracic Society 2025 International Conference.1

TSLP is an upstream cytokine released by epithelial cells during inflammation and tissue damage; it plays a central role in initiating type 2 inflammation by activating dendritic and mast cells. TSLP levels are tied to disease severity, airway obstruction, and glucocorticoid resistance, and blocking this pathway has become a therapeutic strategy for several respiratory and allergic diseases. Tezepelumab, currently approved for severe asthma, was the first monoclonal antibody to target TSLP.2 Solrikitug now appears poised to advance this therapeutic class.

Unique Binding and Enhanced Functional Inhibition

Researchers from Uniquity Bio and Mosaic Biosciences conducted head-to-head in vitro comparisons between solrikitug and another anti-TSLP monoclonal antibody, tezepelumab.1 Both antibodies showed similar binding affinity to TSLP—11.9 pM for solrikitug and 16.7 pM for tezepelumab—however, their binding profiles differed substantially. Competitive assays revealed the 2 therapies bind to distinct epitopes on TSLP, suggesting nonoverlapping mechanisms of action.

Solrikitug is currently being evaluated for patients with moderate to severe asthma. | Image credit: Pixel-Shot – stock.adobe.com

Functionally, solrikitug demonstrated superior potency across multiple assays. It was 15 times more potent than tezepelumab in inhibiting receptor dimerization between TSLPR and interleukin (IL)-7R, a required step for downstream signaling. Solrikitug was also 6 times more effective at reducing STAT5 phosphorylation, a key marker in the JAK/STAT signaling pathway triggered by TSLP, and 10 times more effective at suppressing the expression of TARC (CCL17), a chemokine induced by TSLP in human dendritic cells.

“Moreover, solrikitug demonstrates potentially best-in-class functional inhibition,” the authors wrote. “The differentiated profile of solrikitug compared to tezepelumab supports the potential of solrikitug for the treatment of patients with severe respiratory conditions such as asthma and COPD.”

Ongoing Research for Severe Asthma

Tezepelumab has been shown to reduce severe asthma exacerbations by 56% overall and 41% in those with eosinophils less than 300 cells/µL.3 The drug opened the door for anti-TSLP strategies, but its use is currently limited to severe asthma while solrikitug is being evaluated for a broader set of indications.

Solrikitug is currently being evaluated in the phase 1/2 RAINIER clinical trial (NCT06496607) for patients with moderate to severe asthma.4 The ongoing study aims to assess the safety, tolerability, pharmacokinetics, and early signs of efficacy of solrikitug administered subcutaneously over 16 weeks. Primary results from the trial, along with the current findings, will inform future studies exploring whether solrikitug’s in vitro advantages lead to superior real-world outcomes, and the drug’s potential in other TSLP-driven diseases like COPD and eosinophilic esophagitis. The authors noted that differences in epitope binding and downstream inhibition could affect both the magnitude and durability of therapeutic response.

References

1. Komori K, Lore M, Postlethwaite H, Manga V, Wittmer LL, Ortega H. In-vitro characterization of solrikitug, a differentiated anti-TSLP antibody, provides distinct epitope binding profile and superior potency compared to tezepelumab. Presented at: ATS 2025 International Conference; May 18, 2025; San Francisco, CA. https://www.atsjournals.org/doi/abs/10.1164/ajrccm.2025.211.Abstracts.A1393
2. Inserro A. FDA approves tezepelumab for severe asthma. AJMC®. December 17, 2021. Accessed June 25, 2025. https://www.ajmc.com/view/fda-approves-tezepelumab-for-severe-asthma
3. Inserro A. Tezepelumab cuts severe asthma exacerbations by more than half, study says. AJMC. May 12, 2021. Accessed June 25, 2025. https://www.ajmc.com/view/tezepelumab-cuts-severe-asthma-exacerbations-by-more-than-half-study-says
4. A study to evaluate solriktug in adult participants with asthma (RAINIER). Clinicaltrials.gov. Updated April 30, 2025. Accessed June 25, 2025. https://clinicaltrials.gov/study/NCT06496607