Spero Therapeutics, a company whose history in antibiotics research culminated in the recent FDA nod for its first product, is pivoting to immunology and inflammation with a Phase 2-ready drug it plans to develop for a rare condition that so far has only one approved treatment.
The drug comes from Innovent Biologics, a company that has become one of China’s most active dealmakers. According to deal terms announced Tuesday, Spero gains global rights to the asset, excluding Greater China where Innovent retains rights. Concurrent with the licensing agreement, Spero secured royalty financing that brings $105 million in non-dilutive capital to support clinical development of its new immunology drug, now known as SP001.
SP001 is a monoclonal antibody designed to target CD40 ligand, a validated protein target that’s been studied in several autoimmune indications for about 20 years, said Spero President and CEO Esther Rajavelu. Early research led to molecules that sparked cardiovascular risks, specifically platelet activation and thrombosis. These drugs never made it to the market. A second generation of CD40L-targeting drugs have reached late-stage clinical development in the hands of a few companies.
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Spero believes SP001 could offer advantages over other CD40L-targeting drugs. Rajavelu said the safety problems associated with the early drugs in the class were due to the Fc region, the “tail” of the antibody. This region’s interaction with CD40L on platelets led to the cardiovascular problems that doomed earlier research. Rajavelu describes SP001 as a third-generation CD40L-targeting antibody engineered with a “silent” Fc region to avoid unwanted interactions.
“There are other features like the half-life of the antibody, and we believe it has potential to be more potent than other competing CD40 ligand-targeting agents,” Rajavelu said. “But the core engineering differentiation is the silenced Fc region.”
This antibody, called IBI355 by Innovent, completed two Phase 1 studies in healthy volunteers and a Phase 1b study in Sjögren’s disease, an autoimmune disease that primarily affects the tear ducts and salivary glands. While Innovent will continue China development of the asset in Sjögren’s, Spero plans to test it in immunoglobulin G4-related disease (IgG4-RD), an inflammatory condition that affects multiple organs. This chronic disease is driven by B cells, leading to research efforts addressing those cells.
Amgen drug Uplizna, which works by binding to and depleting B cells, last year became the first FDA-approved treatment for IgG4-RD. Meanwhile, Zenas Biopharma submitted an application in May seeking FDA approval of obexelimab, a bifunctional antibody designed treat IgG4-RD by inhibiting rather than depleting B cells. Rajavelu said SP001 offers a different approach.
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“The approved agent as well as a couple of others that are in development all target B cells,” she said. “We’re moving upstream of the B cell targeting to work on the B cell/T cell collaboration axis that we believe will have a broader impact on aspects of the disease.”
The Innovent deal continues the business strategy Spero had pursued from its origin, Rajavelu said. The Spero antibiotic now known as Utebzi was licensed from Japan-based Meiji Seika Pharma. Following Utebzi’s FDA approval in June, it will be commercialized by GSK, which holds global rights to the asset, excluding certain regions in Asia.
Rajavelu said Spero began looking in earnest for its next asset in mid-2025 after Utebzi’s Phase 3 readout in complicated urinary tract infections. The company’s global search considered several different therapeutic areas, such as rare disease and immune-mediated disorders. Rajavelu said the company was looking for a drug addressing a validated target that could apply to multiple indications.
According to terms of the licensing agreement, Spero is paying Innovent $35 million up front for rights to SP001. Innovent could receive up to $1.05 billion in milestone payments depending on Spero’s progress. Spero is financing its strategy shift by monetizing royalties for its recently approved antibiotic. Affiliates of Healthcare Royalty will receive a portion of future milestone and royalty payments tied to GSK’s sales of Utebzi.
In its first quarter 2026 financial report, Spero said its cash position was $56.1 million, which would support operations into 2028. With the new financing, the company now expects its capital will last into the second half of 2029. SP001’s Phase 2 trial in IgG4-RD is expected to start in the second quarter of next year. Rajavelu declined to specify a timeline for a data readout, but she said the company is funded to deliver data for SP001 in IgG4-RD and work through some other development aspects related to targeting CD40L.
Amgen’s scope for Uplizna extends beyond IgG4-RD. This drug is also approved for other two rare inflammatory diseases, neuromyelitis optica spectrum disorder and generalized myasthenia gravis. For 2025, Amgen reported $655 million in global sales for this product. The next indication for the drug could be lupus; a Phase 2 study is ongoing.
Companies with CD40L-targeting drugs in clinical development include Sanofi, whose antibody frexalimab has reached late-stage testing for multiple sclerosis and kidney transplant rejection; mid-stage trials are underway for two rare kidney disorders and type 1 diabetes. Other companies with anti-CD40L antibodies in the clinic include Eledon Pharmaceuticals and Tonix Pharmaceuticals.
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