BEL512 (CM512 in Greater China), an investigational bispecific antibody targeting thymic stromal lymphopoietin (TSLP) and interleukin-13 (IL-13), met its primary endpoint and all secondary endpoints in a phase 2 trial in adults with inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP), according to Belenos Biosciences.1
The double-blind, placebo-controlled trial (NCT06930612) was conducted in China by Belenos' partner, Keymed Biosciences, and enrolled 120 patients with a Nasal Polyp Score (NPS) of 5 or higher, at least 2 polyps per nostril, and a Nasal Congestion Score of 2 to 3 at baseline.1 Patients were randomized to subcutaneous BEL512 300 mg every 12 weeks, 300 mg every 24 weeks, 600 mg every 24 weeks, or placebo, each added to daily intranasal mometasone furoate 200 μg, over 24 weeks of treatment followed by a 12-week safety follow-up.1
“These results provide important clinical validation for simultaneously targeting TSLP and IL-13 in treating CRSwNP,” said Donnie McGrath, MD, chief executive officer of Belenos Biosciences. “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 may offer patients an attractive treatment option.”1
What were the trial’s end points?
The primary endpoint, change from baseline in NPS at week 24, was met with statistically significant improvement across all BEL512 dosing groups versus placebo.1 All secondary endpoints were also met, including Nasal Congestion Score, Loss of Smell Score, Total Symptom Score, sinus CT Lund-Mackay score, and the 22-item Sino-Nasal Outcome Test (SNOT-22).1 Improvements were observed as early as week 4 and remained durable through the treatment and follow-up periods, including in the every-24-week dosing groups.1
Type 2 inflammation is a key driver of CRSwNP, with TSLP acting as an upstream epithelial alarmin that initiates and amplifies inflammatory responses and IL-13 acting as a downstream effector cytokine linked to mucus production, tissue inflammation, and remodeling.1 BEL512 is designed to inhibit both pathways within a single molecule.1 CRS affects an estimated 10.9% to 13.4% of the Western population, with the more severe CRSwNP subtype accounting for approximately 18% to 20% of CRS cases.2
What was BEL512’s safety profile and what are next steps?
BEL512 was well tolerated across all dosing groups, with overall treatment-emergent adverse event (TEAE) rates similar to placebo.1 There were no severe TEAEs, no discontinuations in the treatment groups, no serious AEs, and minimal anti-drug antibody formation.1 Based on these results, China's National Medical Products Administration Center for Drug Evaluation recently included BEL512 in its Breakthrough Therapy program for CRSwNP.1
Keymed Biosciences plans to initiate a phase 3 trial of BEL512 in CRSwNP in China in the near future, while Belenos plans to initiate a phase 3 trial outside China in the first half of 2027.1 Detailed results are expected to be presented at a scientific meeting and submitted for publication in a peer-reviewed journal.1
“Patients with CRSwNP experience a significant and profound impact on their quality of life, struggling to breathe through their nose, smell, and sleep normally,” said Stella Lee, MD, 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. “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 for CRSwNP.”1
BEL512 is also in development for asthma, chronic obstructive pulmonary disease, and atopic dermatitis, conditions the company characterizes as sharing epithelial-immune dysregulation with CRSwNP.1
References
Laidlaw TM, Mullol J, Woessner KM, Amin N, Mannent LP. Chronic Rhinosinusitis With Nasal Polyps and Asthma. J Allergy Clin Immunol Pract. 2021;9(3):1133-1141. doi:10.1016/j.jaip.2020.09.063
