Belenos' Bispecific Antibody BEL512 Hits All Endpoints in Phase 2 CRSwNP Trial, Secures Breakthrough Therapy Designation in China
核心洞察
BEL512 (搜索) met its primary and all secondary endpoints at Week 24 in a 120-patient Phase 2 trial for inadequately controlled chronic rhinosinusitis with nasal polyps (搜索) (CRSwNP).
Statistically significant improvements were observed as early as Week 4, with durable effects supporting a 6-month dosing interval following a single subcutaneous injection.
The bispecific antibody targeting TSLP (搜索) and IL-13 (搜索) was well tolerated, with TEAE rates similar to placebo and no severe adverse events or discontinuations.
Belenos Biosciences (搜索) announced that its investigational long-acting bispecific antibody, BEL512 (搜索), met its primary and all secondary endpoints in a double-blind, placebo-controlled Phase 2 clinical trial in adults with inadequately controlled chronic rhinosinusitis with nasal polyps (搜索) (CRSwNP). The study, conducted in China by Belenos' partner Keymed Biosciences (搜索), enrolled 120 patients and demonstrated statistically significant improvements across objective and symptomatic measures of disease.
The trial (NCT06930612) randomized patients with a Nasal Polyp Score (NPS) of ≥5, at least two polyps per nostril, and a Nasal Congestion Score (NCS) of 2–3 at baseline. Participants received either 300 mg BEL512 (搜索) every 12 weeks, 300 mg every 24 weeks, 600 mg every 24 weeks, or placebo, all via subcutaneous injection on top of daily intranasal mometasone furoate nasal spray (MFNS 200 µg QD). The treatment period lasted 24 weeks, followed by a 12-week safety follow-up.
Rapid and Durable Efficacy Across All Measures
The primary endpoint — change from baseline in NPS at Week 24 — was met with statistical significance across BEL512 (搜索) treatment groups versus placebo. Improvements were evident as early as Week 4 and were sustained throughout both the treatment and follow-up periods, indicating durable clinical activity following single-dose administration.
Secondary endpoints included Nasal Congestion Score, Loss of Smell (LoS) Score, Total Symptom Score (TSS), Sinus CT Lund-Mackay (LMK) score, and the Sinonasal Outcome Test-22 (SNOT-22). All secondary endpoints were met with statistically significant improvements in the BEL512 (搜索) arms compared with placebo at Week 24.
"The magnitude, speed of onset and durability of improvement across objective measures of nasal polyp disease and the symptoms that matter most to patients, in conjunction with infrequent dosing indicate that BEL512 (搜索) may offer patients an attractive treatment option," said Donnie McGrath, M.D., CEO of Belenos Biosciences (搜索). "These findings further strengthen our conviction in BEL512 as a potentially best-in-class therapy across multiple respiratory and inflammatory diseases."
Favorable Safety Profile
BEL512 (搜索) was well tolerated across all dosing groups. Overall rates of treatment-emergent adverse events (TEAEs) were similar to placebo, with no severe TEAEs reported, no discontinuations in the treatment groups, no serious adverse events (SAEs), and minimal anti-drug antibodies (ADA).
Regulatory Progress and Next Steps
Based on the Phase 2 results, BEL512 (搜索) was recently included by the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) in its Breakthrough Therapy program for the treatment of CRSwNP. Keymed Biosciences (搜索) is rapidly moving to initiate a Phase 3 study in CRSwNP in China, while Belenos plans to launch a Phase 3 study outside Greater China in the first half of 2027. Detailed results are expected to be presented at a scientific meeting and submitted for publication in a peer-reviewed medical journal.
Dual Targeting of Type 2 Inflammation
BEL512 (搜索), known as CM512 in Greater China, is designed to simultaneously inhibit thymic stromal lymphopoietin (TSLP (搜索)) and interleukin-13 (IL-13 (搜索)). TSLP is an upstream epithelial cytokine involved in initiating and amplifying inflammatory responses, while IL-13 is a downstream effector associated with mucus production, tissue inflammation, barrier dysfunction, and remodeling. By targeting both pathways in a single molecule, BEL512 aims to provide broad and durable control of type 2 inflammation.
"These results provide important clinical validation for simultaneously targeting TSLP (搜索) and IL-13 (搜索) in treating CRSwNP," McGrath added.
Unmet Need in CRSwNP
Chronic rhinosinusitis affects between 10.9% and 13.4% of the Western population, with the more severe CRSwNP subtype accounting for approximately 18–20% of all CRS cases, according to Laidlaw TM et al., J Allergy Clin Immunology Pract, 2021. The condition is characterized by nasal obstruction, congestion, facial pressure, impaired or lost sense of smell, sleep disturbance, and often comorbid asthma. Many patients remain symptomatic despite treatment with intranasal corticosteroids, systemic corticosteroids, biologic therapy, or endoscopic sinus surgery.
Dr. Stella Lee, M.D., Associate Professor of Otolaryngology–Head and Neck Surgery at Harvard Medical School and Director of the Sinus Center at Brigham and Women's Hospital, who was not involved in the study, commented: "A treatment that works quickly and provides lasting benefits for many months after a single injection would substantially improve both the quality of life and treatment experience for my patients. The marked improvements observed across nasal polyp burden, congestion, and sense of smell may translate into meaningful improvements in health-related quality of life, strongly supporting continued development of BEL512 (搜索) for CRSwNP."
BEL512 (搜索) is also being developed for other chronic inflammatory diseases characterized by epithelial-immune dysregulation, including asthma, chronic obstructive pulmonary disease, and atopic dermatitis. Belenos holds development and commercialization rights to BEL512 outside Greater China, having licensed ex-China rights from Keymed Biosciences (搜索) Ltd.