BEL512 met primary and secondary endpoints in a Phase 2 CRSwNP trial, with improvements by Week 4 and durable activity supporting potential six-month dosing.
Written by: Kirti Kumbhar M. Pharm (QA)
Reviewed by: Pharmacally Editorial Team
Belenos Biosciences has announced positive topline results from a Phase 2 clinical trial (NCT06930612) evaluating BEL512 in adults with inadequately controlledchronic rhinosinusitis with nasal polyps (CRSwNP). The study met itsprimary and all secondary endpoints at Week 24, with improvements observed as early as Week 4 and durable clinical activity maintained through the treatment and follow-up periods, including with the extended 24-week dosing regimens. BEL512 was also well tolerated across all dosing groups. Based on these results, Belenos plans to begin a Phase 3 study in CRSwNP outside Greater China in thefirst half of 2027, while its partner Keymed Biosciences plans to initiate a Phase 3 study in China.
Disease Background
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the nasal passages and sinuses characterized by nasal polyps, nasal obstruction, congestion, facial pressure, impaired or lost sense of smell, and sleep disturbance. Asthma is also commonly associated with the condition.
Chronic rhinosinusitis affects approximately 10.9%–13.4% of the Western population, with CRSwNP accounting for about 18%–20% of CRS cases. Many patients remain symptomatic despite intranasal or systemic corticosteroids, biologic therapies, or endoscopic sinus surgery, highlighting the need for effective and durable treatment options.
Type 2 inflammation plays an important role in CRSwNP. TSLP is an upstream epithelial cytokine involved in initiating and amplifying inflammatory responses, while IL-13 is a downstream cytokine associated with mucus production, tissue inflammation, barrier dysfunction, and remodelling.
About BEL512
BEL512, known as CM512 in Greater China and 512 in the study announcement, is an investigational, long-acting bispecific antibody designed to simultaneously target TSLP and IL-13.
By targeting an upstream epithelial alarmin and a downstream effector cytokine, BEL512 is intended to provide broad and durable control of type 2 inflammation.
Belenos holds development and commercialization rights to BEL512 outside Greater China.
BEL512 is being developed for several chronic inflammatory diseases associated with epithelial-immune dysregulation, including CRSwNP, asthma, chronic obstructive pulmonary disease, and atopic dermatitis.
Study Design
The Phase 2 (NCT06930612) study was a double-blind, placebo-controlled clinical trial conducted in China by Belenos’ partner, Keymed Biosciences.
The study enrolled120 adults with CRSwNP who had a Nasal Polyp Score (NPS) of≥5, at leasttwo polyps per nostril, and a baseline Nasal Congestion Score (NCS) of2–3.
Participants were randomly assigned to four groups and received subcutaneous injections in addition to daily intranasal corticosteroid treatment with mometasone furoate nasal spray (MFNS 200 µg once daily):
Treatment group | Dosing schedule |
BEL512 | 300 mg every 12 weeks |
BEL512 | 300 mg every 24 weeks |
BEL512 | 600 mg every 24 weeks |
Placebo | Placebo |
Treatment continued for24 weeks, followed by a12-week safety follow-up.
The primary endpoint was the change from baseline in Nasal Polyp Score (NPS) at Week 24. Additional assessments included Nasal Congestion Score, Loss of Smell Score, Total Symptom Score, sinus CT Lund-Mackay score, and Sinonasal Outcome Test-22 (SNOT-22).
Key Findings
The study met its primary endpoint and all secondary endpoints at Week 24, with statistically significant improvements in the BEL512 treatment groups compared with placebo.
Clinical activity appeared early. Improvements were observed as early as Week 4, indicating a rapid onset of treatment effect. The benefits were also maintained throughout the treatment period and subsequent follow-up, supporting the potential for durable disease control with extended dosing intervals.
The findings across nasal polyp burden, nasal congestion, loss of smell, symptoms, sinus imaging, and health-related quality of life provided evidence of activity across both objective measures of disease and symptoms experienced by patients.
The durability of the response is particularly notable because the study included dosing schedules extending to every 24 weeks, supporting the potential for approximately six-month dosing if these findings are confirmed in later-stage studies.
Safety
BEL512 was well tolerated across all dosing groups.
Overall treatment-emergent adverse event (TEAE) rates were similar to placebo. The study reported no severe TEAEs, no treatment discontinuations in the BEL512 groups, no serious adverse events (SAEs), and minimal anti-drug antibodies (ADA).
These findings support the continued clinical development of BEL512, although its safety profile will need to be further evaluated in larger and longer Phase 3 studies.
Expert Perspective
Donnie McGrath, M.D., CEO of Belenos Biosciences, said the results provide clinical validation for simultaneously targeting TSLP and IL-13 in CRSwNP. He highlighted the magnitude, rapid onset, and durability of improvements in nasal polyp disease and symptoms, along with the potential benefit of infrequent dosing.
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, said CRSwNP can significantly affect nasal breathing, smell, and sleep. She noted that a treatment providing rapid and lasting benefits after a single injection could improve patients’ quality of life and treatment experience.
The observed improvements in nasal polyp burden, congestion, and sense of smell support continued development of BEL512 in CRSwNP.
What This Means for Patients
For people with inadequately controlled CRSwNP, BEL512 may offer a long-acting treatment option targeting multiple pathways involved in type 2 inflammation. Improvements observed as early as Week 4, together with durable clinical activity, could provide earlier and sustained relief from symptoms affecting nasal breathing, smell, sleep, and daily life.
BEL512 remains investigational, and the potential for six-month dosing will require confirmation in Phase 3 studies.
Future Direction
The Phase 2 results support continued development of BEL512 in CRSwNP. Keymed Biosciences plans to initiate a Phase 3 study in China, while Belenos plans to begin a Phase 3 study outside Greater China in the first half of 2027. BEL512 has also been included in China’s NMPA CDE Breakthrough Therapy program for CRSwNP.
Detailed Phase 2 results are expected to be presented at a scientific meeting and submitted for publication in a peer-reviewed journal. BEL512 is also being developed for asthma, chronic obstructive pulmonary disease, and atopic dermatitis.
Reference
About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.