Advanced bispecific antibody design and inhaled biologics; emerging strategies for asthma

Abstract

Asthma is a chronic inflammatory respiratory disease affecting over 300 million individuals worldwide. While current therapies, including inhaled corticosteroids and monoclonal antibodies, have significantly improved management of Type 2 (T2)-high asthma, treatment options for T2-low, steroid-resistant, and severe asthma remain limited. Recent advances in biologic therapeutics have introduced bispecific antibodies (bsAbs) as a promising next-generation strategy. BsAbs are engineered to simultaneously target two distinct inflammatory pathways, offering broader immunomodulatory effects and the potential to improve disease control in heterogeneous asthma phenotypes. Concurrently, pulmonary delivery systems such as nebulisers, dry powder inhalers (DPIs) and soft mist inhalers (SMIs) have emerged as attractive non-invasive alternatives to injections for biologic administration, providing localised treatment directly to the lungs, reduced systemic side effects, and enhanced patient adherence. This review examines the immunological basis of asthma endotypes, evaluates current monoclonal antibody therapies and their limitations, and explores the design, mechanisms, and clinical progress of bispecific antibodies in the treatment of asthma. Additionally, we analyse the feasibility and challenges of inhaled biologic delivery, including formulation strategies and device optimisation. We conclude by highlighting future research priorities, including the development of inhalable bsAbs for T2-low asthma and the need for scalable, stable, and patient-friendly formulations. This dual-focused approach, combining novel antibody engineering with targeted delivery, represents a critical step towards personalised, effective asthma care.