Spero Pivots to Autoimmune with $1.1B Innovent Deal

Massachusetts-based Spero Therapeutics (Nasdaq: SPRO) has licensed exclusive global rights — excluding Greater China — to SP001 (IBI355), a third-generation Fc-silent anti-CD40L monoclonal antibody developed by China-based Innovent Biologics (HKEX: 01801). The deal carries a total potential value of approximately USD 1.1 billion, comprising an undisclosed upfront payment, development, regulatory, and commercial milestones, and tiered royalties on net sales.

Spero plans to initiate a Phase II trial in IgG4-related disease (IgG4-RD) in Q2 2027. Innovent retains Greater China rights and plans to begin a separate Phase II study in Sjögren's disease (SjD) in China by early 2027. The two companies will run parallel but independent development programs in different indications across their respective territories.

SP001 is a humanized Fc-silent IgG1 antibody targeting CD40L (CD154), blocking an upstream co-stimulatory signal involved in T-cell/B-cell crosstalk. The Fc-silencing is the molecule's defining engineering feature: first-generation anti-CD40L antibodies failed in clinical development due to thromboembolic events caused by Fc-mediated platelet activation. SP001 is designed to retain antibody-like pharmacokinetics via preserved FcRn interaction while eliminating that safety liability. Innovent has completed two healthy-volunteer Phase I studies and a Phase Ib multiple ascending dose study in SjD patients, with data presented at EULAR 2026.

The deal sees Spero expanding beyond its existing pipeline focus on antibiotics, anchored by Utebzi (tebipenem pivoxil), an oral carbapenem antibiotic approved by the US FDA in June 2026 for complicated urinary tract infections under a GSK partnership. Spero is funding the SP001 in-license partly through a USD 105 million non-dilutive royalty financing backed by future Utebzi milestone and royalty streams from Healthcare Royalty (HCRx), announced the same day as Spero's deal with Innovent.

The agreement is Innovent's first publicly disclosed autoimmune out-license and follows a series of oncology partnerships, including a USD 10.5 billion collaboration with Pfizer in May 2026 and a USD 11.4 billion deal with Takeda in October 2025, both of which retained Greater China rights

The CD40L pathway is crowded at the clinical stage. UCB and Biogen's dapirolizumab pegol, a PEGylated anti-CD40L Fab fragment, reported positive Phase III topline data in systemic lupus erythematosus (SLE) at EULAR 2026. Sanofi's frexalimab (SAR441344), a second-generation anti-CD40L antibody licensed from ImmuNext, is in Phase III for relapsing multiple sclerosis. SP001's third-generation Fc-silent design is expected to mitigate the thromboembolic safety concerns associated with earlier anti-CD40L antibodies, although no head-to-head data are available against other next-generation programs. Spero's choice of IgG4-RD as the lead indication — a rare fibroinflammatory condition with no approved therapies — sidesteps direct competition with both programs while offering a potentially faster regulatory path in an orphan-adjacent space.

Innovent's own pipeline update from May 2026 confirmed IBI355 alongside other autoimmune candidates including IBI356 (OX40L) and IBI3002 (IL-4Rα/TSLP), with the potential for further diversification of its out-licensing program beyond oncology. The transaction moves Spero into autoimmune drug development for the first time, broadening its pipeline beyond anti-infectives.

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