Spero Therapeutics is pivoting from antibiotics to immune and inflammation indications by licensing a CD40L antibody from Innovent Biologics in a deal worth up to $1.1 billion.
Under the agreement, Spero will receive the rights to research, develop and commercialize the asset, dubbed SP001, outside of China. In return, Innovent will be in line for a mixture of an upfront fee, milestone payments and tiered royalties on potential sales—although the release didn't offer a breakdown of the financials.
CD40L is a protein found on activated T cells that helps regulate cellular survival, vascular inflammation and anti-tumor immunity. Innovent has previously evaluated SP001, formerly known as IBI355, in a pair of phase 1 trials involving healthy volunteers as well as a phase 1b study of patients with Sjögren’s disease, an autoimmune disease in which the patient’s immune system attacks the tear and salivary glands, leading to dry eyes and mouth.
Cambridge, Massachusetts-based Spero expects to advance the therapy into a phase 2 trial for patients with IgG4-related disease, a rare, chronic autoimmune condition characterized by inflammatory lesions and tissue fibrosis. Meanwhile, Innovent is on track to launch a mid-stage trial of the drug in China for Sjögren’s disease by early next year, according to a July 14 release.
Spero CEO Esther Rajavelu said the licensing deal “establishes the foundation of our new pipeline” and noted that the CD40L pathway has the potential to address multiple I&I indications.
“Having successfully advanced and delivered a therapy for patients with serious infectious diseases, we are now applying the same disciplined development approach to immune-mediated diseases,” Rajavelu added. “Beyond IgG4-RD, we see opportunities to explore
the role of CD40L inhibition across multiple autoimmune and inflammatory conditions.”
Spero's news strategy will be bankrolled by $105 million in financing that the company has negotiated from Healthcare Royalty (HCRx) in return for a slice of the royalties for Utebzi. The oral treatment for complicated urinary tract infections was approved by the FDA last month and is being commercialized by GSK. It is the first approved oral carbapenem antibiotic in the U.S., targeting drug-resistant bacteria and patients with complicated infections.
In return for the $105 million, HCRx will receive quarterly principal and interest payments from the royalties that GSK pays Spero from sales of Utebzi until the loan balance is repaid. After that, HCRx will receive 65% of the Utebzi profits.
“By unlocking immediate value from a portion of future Utebzi milestone and royalty streams, we are well positioned to execute on the clinical development for SP001 and continue building a differentiated pipeline for patients with immune-mediated diseases,” Rajavelu said in a separate release.
Spero’s move into I&I was made possible by the bumpy but ultimately successful journey of Utebzi, which was rejected by the FDA in 2022 when it was known as tebipenem pivoxil hydrobromide. The FDA said the phase 3 trial was insufficient to support approval, but GSK stepped in with a $66 million deal to develop the drug and conduct a new study.
Spero laid off 75% of its workforce in the wake of the initial FDA rejection, before saying goodbye to another 39% of its employees in 2024 after its oral treatment for nontuberculous mycobacterial pulmonary disease failed to outperform placebo and showed signs of toxicity.
The company continued to shrink its antibiotic pipeline last year when it discontinued development of SPR206, a next-generation polymyxin that had shown activity against multidrug-resistant Gram-negative pathogens in preclinical studies and had originally been lined up for a phase 2 trial.
GSK and Spero achieved a phase 3 win for Utebzi in 2025 for the treatment of patients with complicated urinary tract infections, but the company's challenges were not over. At the start of this year, two former Spero executives agreed to settle with the Securities and Exchange Commission over allegations they misled investors about the therapy's efficacy—although this didn't stop the FDA granting approval last month.