About LQ059

LQ059 is an inhaled Notch2-targeting VHH therapeutic independently developed by Novamab to alleviate the abnormal airway mucus secretion and epithelial remodeling in cystic fibrosis lung disease. Guided by principles of innovative mechanism, good safety, efficient manufacturing, and achievable commercialization, the development of this program aims to establish a next-generation inhaled VHH platform accelerating clinical translation and commercialization.

Advantages of LQ059

• Highly differentiated target and mechanism: Leveraging the unique structural properties and high-affinity binding of VHHs, LQ059 achieves superior Notch2 engagement and signal modulation, enabling precise intervention in goblet cell metaplasia and mucus hypersecretion.

• Scalable manufacturing system: Our mature Pichia pastoris expression and purification platform provides significant advantages in production cost, scalability, and batch consistency, ensuring reliable supply for clinical development and commercialization.

• Favorable safety and tolerability profile: Local pulmonary delivery minimizes risks associated with systemic Notch2 inhibition, while the low immunogenicity of VHHs offers an improved therapeutic window for chronic or repeat-dose regimens.

• Strategic pipeline expansion potential: With Notch2 implicated in multiple respiratory diseases, LQ059 has opportunities for indication expansion beyond cystic fibrosis lung disease, supporting long-term portfolio expansion.

Mechanism of action

LQ059 specifically binds to Notch2 with high affinity, blocking ligand interactions (e.g., Jag1, Jag2) and inhibiting downstream signaling. This intervention reduces goblet cell metaplasia, suppresses aberrant mucin expression (e.g., Muc5ac/Muc5b), and promotes restoration of ciliated epithelial genes, thereby enhancing mucociliary clearance in cystic fibrosis lung disease.

Key mechanisms include:

• Blockade of Notch2/jag binding and suppression of pathogenic signaling

• Attenuation of pathological cell activation and reversal of epithelial remodeling

• Reduction of inflammatory mediator release and local hyperinflammation

• Restoration of tissue homeostasis and improvement of the pulmonary microenvironment

Indication

• Cystic fibrosis lung disease

Route of administration

• Oral inhalation/local delivery