Antibody therapy headed for Phase 2 trial in IgG4-related disease

A Phase 2 clinical trial Spero Therapeutics plans to start next year will test an investigational antibody-based therapy in people with immunoglobulin G4-related disease (IgG4-RD).

Spero recently signed an exclusive license agreement with Innovent Biologics, the treatment’s original developer, that grants the company worldwide exclusive rights to develop, produce, and commercialize the therapy, known as SP001, except in Greater China, where Innovent retains the rights.

“We are delighted to partner with Innovent Biologics, whose scientific leadership, development expertise, and commitment to innovation have been instrumental in advancing this program to its current stage,” Esther Rajavelu, Spero’s president and CEO, said in a joint company press release.

SP001, also known as IBI355, targets CD40L, a protein involved in activating several types of immune cells that are known to contribute to IgG4-RD and other immune-mediated diseases.

“We view CD40L as a clinically validated pathway with broad applicability across several immune-mediated diseases,” Rajavelu said. “In IgG4-RD, we believe this approach has the potential to meaningfully address the burden patients face from a chronic, relapsing condition with limited treatment options.”

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IgG4-RD occurs when immune cells, including T-cells and B-cells, particularly those producing IgG4, infiltrate tissues. This results in inflammation and tissue scarring, leading to organ damage and causing IgG4-RD symptoms.

SP001, administered directly into the bloodstream, is an antibody-based therapy designed to target CD40L, a protein involved in immune cell activation and communication between T- and B-cells.

By blocking this protein, SP001 aims to interrupt the abnormal immune responses that drive IgG4-RD without killing these immune cells, which are also important for defending the body against infections.

“CD40L is an important upstream mediator of immune activation and T-cell/B-cell collaboration, both of which are relevant to IgG4-RD progression,” said Arezou Khosroshahi, MD, a professor at Emory University School of Medicine. “A non-B cell depleting approach that interrupts CD40L signaling could represent an important area for clinical evaluation in IgG4-RD, where patients need additional options that address chronic inflammation, relapse, and treatment burden.”

A third-generation anti-CD40L antibody, SP001 was engineered to avoid activating platelets (cell fragments involved in blood clotting), a safety concern that limited the development of previous drugs in its class. The new therapy is also designed to remain in the body for a long period.

SP001’s safety, tolerability, and pharmacological properties were evaluated in a total of 85 healthy volunteers in two Phase 1 clinical trials, at single (NCT06110338) or multiple ascending doses (NCT06416787).

An Innovent-sponsored Phase 1b trial (NCT06484855) tested the therapy in people with Sjögren’s disease, an autoimmune disease. Results demonstrated that SP001 was generally safe and well tolerated, and it appeared to reduce disease activity and symptom burden. Innovent expects to start a China-based Phase 2 trial in Sjögren’s patients by early 2027.

The IgG4-RD Phase 2 trial, expected to start between in the second quarter of 2027, will evaluate the safety and efficacy of two SP001 doses in up to 30 people with active IgG4-RD for 24 weeks (about six months). Those completing this period may enter the study’s long-term extension portion, during which they will be evaluated for an additional six months.

Spero is also evaluating SP001 as a potential treatment for other conditions.

Under the agreement, Innovent will receive an upfront payment and is eligible to receive development, regulatory, and commercial milestone payments, for a total of approximately $1.1 billion. It will also receive payments based on product sales.

“IgG4-related disease, Sjögren’s disease, and other autoimmune conditions impose significant burdens on patients worldwide, with many facing limited treatment options,” said Lei Qian, MD, PhD, chief research and development officer for general biomedicine at Innovent. “By combining Innovent and Spero’s immunology expertise and development commitment, we aim to accelerate the delivery of differentiated therapies to patients living with these chronic conditions.”