Innovent Biologics and Spero Therapeutics have entered into an exclusive global licensing agreement for IBI355, a third-generation Fc-silent anti-CD40L monoclonal antibody being developed for immune-mediated diseases. The agreement grants Spero exclusive rights to develop, manufacture and commercialise the therapy worldwide, excluding Greater China, where Innovent will retain all rights.

The transaction has a potential value of approximately USD 1.1 billion, comprising an upfront payment, development, regulatory and commercial milestone payments. Innovent will also be eligible to receive tiered royalties on net sales generated in Spero's licensed territories.

As part of the collaboration, Spero plans to advance IBI355 into a Phase 2 clinical trial for Immunoglobulin G4-related disease (IgG4-RD) during the second quarter of 2027. Meanwhile, Innovent expects to initiate a Phase 2 study in China for Sjögren's disease (SjD) by early 2027.

IBI355 is a humanised, Fc-silent IgG1 monoclonal antibody targeting CD40L, a key immune signalling protein involved in T-cell and B-cell activation. By inhibiting CD40L, the therapy aims to modulate immune responses without depleting B cells, offering a targeted treatment approach for chronic autoimmune and inflammatory disorders. The antibody has also been engineered to overcome platelet activation concerns associated with earlier generations of anti-CD40L therapies while maintaining a favourable pharmacokinetic profile.

The drug candidate has completed two Phase 1 studies in healthy volunteers, including Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) trials. Innovent has also evaluated IBI355 in a Phase 1b MAD study involving patients with Sjögren's disease, with data presented at the EULAR 2026 Congress.

Commenting on the collaboration, Dr. Lei Qian, Chief R&D Officer (General Biomedicine) at Innovent Biologics, said the partnership combines the strengths of both companies in immunology research and development to accelerate the advancement of CD40L-targeted therapies. He noted that the collaboration aims to deliver differentiated treatment options for patients living with chronic autoimmune diseases, including IgG4-related disease and Sjögren's disease.

Esther Rajavelu, President and Chief Executive Officer of Spero Therapeutics, said the licensing agreement establishes the foundation of the company's new immunology pipeline. She added that CD40L represents a clinically validated therapeutic target with the potential to address several immune-mediated diseases, beginning with IgG4-related disease, where patients continue to face limited treatment options and a significant long-term disease burden.

Medical experts also highlighted the potential of targeting CD40L. Dr. Arezou Khosroshahi, Professor of Medicine at Emory University School of Medicine, noted that interrupting CD40L signalling through a non-B-cell-depleting approach could provide an important new treatment strategy for patients with IgG4-related disease, particularly those requiring alternatives to existing therapies.

IgG4-related disease is a chronic fibroinflammatory condition that can affect multiple organs, including the pancreas, kidneys, lungs, salivary glands and lacrimal glands, often leading to inflammation, fibrosis and progressive organ damage. Sjögren's disease is a systemic autoimmune disorder characterised by chronic inflammation, dry eyes, dry mouth and fatigue, with more severe cases involving major organs and an increased risk of lymphoma. Both conditions currently have limited treatment options, highlighting the need for novel targeted therapies.