Anti-TSLP Monoclonal Antibody CM326 Shows Efficacy and Safety in CRSwNP

A study showed the effectiveness and safety of CM326, a monoclonal antibody against thymic stromal lymphopoietin, in the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP).1 The findings also indicated that patients with baseline plasma thymic stromal lymphopoietin (TSLP) levels of 330 fg/mL or higher responded particularly well to treatment.

“To our best knowledge, this study pioneers the establishment of plasma TSLP as a predictor in anti-TSLP treatment, which needs to be further validated in an independent cohort,” wrote investigators from the department of otolaryngology at Beijing TongRen Hospital, Capital Medical University, in China.1

The team, co-led by Mu Xian, MD, Feng Lan, PhD, Bing Yan, MD, PhD, and Shen Shen, sought to explore the therapeutic potential of blocking thymic stromal lymphopoietin (TSLP) in patients with CRSwNP. While current biologics target downstream cytokines such as IgE, IL-4, IL-5, and IL-13, inhibiting TSLP offers an upstream strategy that may broadly suppress type 2 inflammation.2,3,4 This approach is supported by findings in asthma, where the TSLP inhibitor tezepelumab effectively reduced exacerbations across different inflammatory profiles, suggesting potential benefits for other type 2–driven diseases like CRSwNP.

To assess the safety and efficacy of CM326, investigators conducted a phase 1b/2a randomized, double-blind, placebo-controlled trial involving 84 patients with CRSwNP.1 Primary endpoints included safety over the 64-week study and change from baseline in endoscopic bilateral endoscopic nasal polyp score in week 16 in patients with eosinophilic CRSwNP (ECRSwNP). Secondary endpoints included the change from baseline in nasal polyp score at week 16 in non-eosinophilic CRSwNP (nonECRwNP) and pharmacodynamic markers.

The sample had a median age of 43.5 years (range, 34.0 – 55), and 71.4% males. More than half of the participants had a history of nasal polyp surgery (56%) and a history of SCS use (61.9%).1

The team randomized participants to receive CM326 220 mg (n = 40) or placebo (n = 20) every 2 weeks and CM326 220 mg (n = 20) or placebo (n = 4) every 4 weeks for 16 weeks.1 Afterward, all participants continued to receive CM326 220 mg for 36 weeks, followed by a 12-week follow-up. The analysis stratified patients based on baseline tissue eosinophil count.

CM326 displayed a favorable safety profile, with most treatment-emergent adverse events (TEAEs) mild or moderate. The most common TEAEs were COVID-19 and upper respiratory tract infection.

Serious TEAEs occurred in 3 patients during the open-label period: unilateral renal calculus and knee ligament injury (CM326 every 2 weeks), community-acquired pneumonia (CM326 every 4 weeks), and ureterolithiasis (CM326 every 4 weeks); 2 patients discontinued due to TEAEs—one for treatment-related allergic dermatitis and one for treatment-unrelated primary biliary cirrhosis. None of the patients developed detectable anti-drug antibodies during the study, suggesting that CM326 has low immunogenicity.

Participants on CM326 every 2 weeks had significantly improved nasal polyp score at week 16 compared to placebo (mean difference, -1.2; 95% confidence interval [CI], -2.3 to -0.1; P =.04), with sustained benefits during the open-label and follow-up periods.1 Participants also had reduced peripheral blood and tissue eosinophil counts and concentrations of plasma IL-13 and IL-5 by week 16 compared to placebo.

A post hoc analysis showed that all patients treated with CM326 who had baseline thymic stromal lymphopoietin levels above 330 fg/mL experienced a significant reduction in nasal polyp score by week 16 (mean difference, −1.75; 95% CI, −3.06 to −0.44; P =.01). These findings suggest that a baseline plasma thymic stromal lymphopoietin level of 330 fg/mL may be a potential predictive marker of CM326 treatment efficacy.1

Investigators noted several limitations, including a small sample size (84 patients) and no multiplicity adjustments, making all P values nominal.1 They also added that long-term use of mometasone furoate nasal spray during the open-label phase may have contributed to improvements in both groups. Investigators also noted that they recruited most participants from the Han population.

“Further studies with larger sample sizes are in preparation to investigate the safety and efficacy of CM326,” investigators wrote.1

References

1. Xian M, Lan F, Yan B, et al. An anti-TSLP monoclonal antibody for uncontrolled CRSwNP: the DUBHE randomized clinical trial. Nat Commun. 2025;16(1):8607. Published 2025 Sep 29. doi:10.1038/s41467-025-63682-x

2. Ebina-Shibuya R, Leonard WJ. Role of thymic stromal lymphopoietin in allergy and beyond. Nat Rev Immunol. 2023;23(1):24-37. doi:10.1038/s41577-022-00735-y

3. Corren J, Parnes JR, Wang L, et al. Tezepelumab in Adults with Uncontrolled Asthma. N Engl J Med. 2017;377(10):936-946. doi:10.1056/NEJMoa1704064

4. Hoy SM. Tezepelumab: First Approval. Drugs. 2022;82(4):461-468. doi:10.1007/s40265-022-01679-2