Spero Therapeutics Launches Immunology Initiative with SP001, Targeting CD40L to Redefine Treatment of Autoimmune Disease

Spero Therapeutics, renowned for its recent FDA approval of its inaugural antibiotic, is now shifting focus to immunology and inflammation, advancing a Phase‑2 ready therapy aimed at a rare disease that currently lacks effective treatment options.

The therapeutic candidate originates from Innovent Biologics, a prolific Chinese dealmaker. Under the terms disclosed Tuesday, Spero obtains worldwide licensing rights to the asset, while Innovent retains rights in Greater China. Simultaneously, Spero secured $105 million of non‑dilutive royalty financing to fund clinical development of its lead immunology candidate, designated SP001.

SP001 is a monoclonal antibody that targets CD40 ligand, a protein long validated across multiple autoimmune conditions and investigated for roughly two decades, noted Spero President and CEO Esther Rajavelu. Early research revealed that CD40L‑targeting agents can provoke cardiovascular complications, including platelet activation and thrombosis, preventing their market entry. Nevertheless, a second generation of CD40L‑targeting therapies has progressed to late‑stage clinical trials by several firms.

Spero contends that SP001 may surpass existing CD40L‑targeting agents. Rajavelu explained that safety concerns with prior drugs stemmed from the antibody’s Fc region, which interacts with CD40L on platelets and precipitated cardiovascular adverse events. SP001 is engineered as a third‑generation CD40L antibody featuring a “silent” Fc region designed to eliminate such off‑target interactions.

“In addition to an extended half‑life, we anticipate SP001 will demonstrate greater potency compared with other CD40L‑targeting antibodies,” Rajavelu remarked. “However, the defining engineering advance is the silenced Fc region.”

The antibody, known as IBI355 in Innovent’s portfolio, has completed two Phase 1 trials in healthy volunteers and a Phase 1b study in patients with Sjögren’s disease, an autoimmune disorder primarily affecting the lacrimal and salivary glands. Although Innovent will advance the asset for Sjögren’s within China, Spero intends to evaluate SP001 in immunoglobulin G4‑related disease (IgG4‑RD), a multi‑organ inflammatory condition driven by B‑cell activity. Research efforts are consequently targeting these B‑cell pathways.

Amgen’s Uplizna, which functions by binding to and depleting B cells, was approved last year as the first therapy for IgG4‑RD. In May, Zenas Biopharma filed for FDA approval of obexelimab, a bifunctional antibody that treats IgG4‑RD by inhibiting rather than depleting B cells. Rajavelu emphasized that SP001 adopts a distinct mechanistic approach.

“All approved and pipeline agents in this space primarily target B cells,” she observed. “Our strategy moves upstream to modulate the collaborative B‑cell/T‑cell axis, which we believe will yield broader therapeutic impact across disease manifestations.”

The acquisition of SP001 aligns with the business strategy Spero has pursued since its inception, Rajavelu said. The company’s first antibiotic, now marketed as Utebzi, was licensed from Japan’s Meiji Seika Pharma. After receiving FDA approval in June, Utebzi will be commercialized by GSK, which holds global rights to the product, excluding select Asian markets.

Rajavelu noted that Spero intensified its search for a new asset in mid‑2025 following the Phase 3 results of Utebzi in complicated urinary tract infections. A global review encompassed diverse therapeutic areas, including rare diseases and immune‑mediated disorders. The objective was to identify a candidate targeting a validated pathway with applicability across multiple indications.

Under the licensing terms, Spero will pay Innovent $35 million upfront for SP001 rights, with the possibility of up to $1.05 billion in milestone payments contingent on development milestones. The company is financing this strategic transition through royalty streams from its recently approved antibiotic. Affiliates of Healthcare Royalty will receive a share of future milestone and royalty payments derived from GSK’s sales of Utebzi.

According to its Q1 2026 financial disclosure, Spero reported a cash balance of $56.1 million, sufficient to fund operations through 2028. With the additional financing, the company projects its capital runway extending into the second half of 2029. The Phase 2 trial of SP001 in IgG4‑RD is slated to commence in the second quarter of next year. Rajavelu declined to set a specific timeline for data readouts but affirmed that the company is positioned to generate interim results for SP001 in IgG4‑RD and advance other CD40L‑targeting development activities.

Beyond IgG4‑RD, Amgen’s Uplizna is also approved for two additional rare inflammatory conditions — neuromyelitis optica spectrum disorder and generalized myasthenia gravis. In 2025, the product generated $655 million in global sales. The next potential indication is systemic lupus erythematosus, for which a Phase 2 study is currently underway.

Several companies are advancing CD40L‑targeting antibodies in clinical development. Sanofi’s frexalimab has entered late‑stage trials for multiple sclerosis and kidney transplant rejection, with mid‑stage studies ongoing for rare kidney disorders and type 1 diabetes. Additional anti‑CD40L antibodies are being evaluated by Eledon Pharmaceuticals and Tonix Pharmaceuticals.

Image by Juan Gartner, Getty Images

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