Spero Therapeutics, a company renowned for its antibiotic research, is shifting its focus to immunology and inflammation following the recent FDA approval of its first product, as it plans to develop SP001, a Phase 2-ready drug for a rare disease with only one previously approved treatment.
The drug emerges from a collaboration with Innovent Biologics, a prominent player in the Chinese biopharmaceutical landscape. Under the terms announced on Tuesday, Spero has secured global rights to the asset, excluding Greater China where Innovent retains rights. Along with the licensing agreement, Spero has received non-dilutive financing amounting to $105 million to aid the clinical development of what is now referred to as SP001.
SP001 is a monoclonal antibody intended to target CD40 ligand (CD40L), a validated protein target studied in various autoimmune conditions for approximately 20 years, according to Esther Rajavelu, President and CEO of Spero. Early research efforts led to molecules that triggered cardiovascular risks, particularly platelet activation and thrombosis, resulting in those drugs never reaching commercialization. A second-generation of CD40L-targeting drugs has progressed to advanced clinical development at several companies.
Spero anticipates that SP001 may offer advantages over existing CD40L-targeting therapeutics. Rajavelu stated that safety issues associated with earlier drugs in this class stemmed from the Fc region, the “tail” of the antibody, which interacted with CD40L on platelets and resulted in cardiovascular problems that halted prior research. Rajavelu describes SP001 as a third-generation CD40L-targeting antibody designed with a “silent” Fc region to mitigate unwanted interactions.
“There are other features such as the antibody’s half-life, and we believe it has the potential to be more potent than other competitive CD40L-targeting agents,” Rajavelu noted. “However, the primary technical differentiation lies in the silenced Fc region.”
The antibody, referred to as IBI355 by Innovent, has completed two Phase 1 studies in healthy volunteers and a Phase 1b study in Sjögren’s disease, an autoimmune condition primarily affecting tear and salivary glands. While Innovent will continue the development of the Sjögren’s asset in China, Spero plans to investigate its use in immunoglobulin G4-related disease (IgG4-RD), an inflammatory condition affecting multiple organs.
Last year, Amgen’s Uplizna, which depletes B cells, became the first FDA-approved treatment for IgG4-RD. Concurrently, Zenas Biopharma submitted an application in May seeking FDA approval for obexelimab, a bispecific antibody designed for IgG4-RD treatment by inhibiting rather than depleting B cells. Rajavelu emphasized that SP001 offers a distinct approach.
“The approved agent and several others in development primarily target B cells,” she stated. “We are advancing upstream of B-cell targeting to focus on the B-cell/T-cell collaboration axis, which we believe will have a broader impact on certain aspects of the disease.”
The partnership with Innovent aligns with Spero’s ongoing business strategy, as articulated by Rajavelu. The company’s antibiotic, now named Utebzi, was approved by Meiji Seika Pharma in Japan. Following the FDA’s approval of Utebzi in June, GSK will market the drug, holding global rights excluding certain Asian regions.
Rajavelu mentioned that Spero began earnestly pursuing its next asset in mid-2025 after the Phase 3 reading of Utebzi for complicated urinary tract infections. The company is exploring various therapeutic areas, including rare diseases and immune-mediated disorders, with an emphasis on validated targets applicable to multiple indications.
According to the licensing agreement’s terms, Spero is paying Innovent an upfront fee of $35 million for the rights to SP001. Innovent may receive up to $1.05 billion in milestone payments tied to Spero’s progress. Spero is financing its strategic shift by monetizing royalties from its recently approved antibiotic. Healthcare Royalty-affiliated entities will receive a portion of future milestone payments and royalties associated with Utebzi sales by GSK.
In its first-quarter 2026 financial report, Spero indicated a cash position of $56.1 million, projected to sustain operations into 2028. With the new financing, the company expects its capital to last until the second half of 2029. The Phase 2 trial for SP001 targeting IgG4-RD is set to commence in the second quarter of next year. Although Rajavelu declined to specify a timeline for data reading, she confirmed the company is funded to deliver data for SP001 in IgG4-RD and to advance other development aspects related to CD40L targeting.
Amgen’s reach with Uplizna extends beyond IgG4-RD, as the drug has also been approved for two other rare inflammatory conditions: neuromyelitis optica spectrum disorder and generalized myasthenia gravis. For 2025, Amgen reported projected global sales of $655 million for this product, with potential upcoming indications including lupus, supported by a Phase 2 study currently underway.
Companies developing CD40L-targeting drugs in clinical trials include Sanofi, whose antibody frexalimab is advanced in testing for multiple sclerosis and kidney transplant rejection, as well as mid-stage trials for two rare kidney disorders and type 1 diabetes. Other firms with clinical anti-CD40L antibodies include Eledon Pharmaceuticals and Tonix Pharmaceuticals.
