Spero Taps Immunology Veteran to Lead Clinical Push for SP001 Asset

CAMBRIDGE, Mass. – July 27, 2026

Spero Therapeutics has appointed Dr. Debra Jeske Zack, a seasoned leader in autoimmune drug development, as its new Chief Medical Officer. The move signals a major strategic acceleration for the company as it pivots to advance its promising immunology asset, SP001, into mid-stage clinical trials for rare and debilitating immune-mediated diseases.

A Strategic Pivot Backed by New Leadership

The appointment comes at a pivotal moment for Spero Therapeutics (Nasdaq: SPRO), a company historically known for its work in anti-infectives. With its oral antibiotic Utebzi (Tebipenem HBr) approved in the U.S. and in the hands of partner GSK for commercialization, Spero is leveraging its success to fund a significant expansion into the highly competitive immunology space. Dr. Zack is central to this new chapter.

“We are delighted to welcome Deb to Spero at an important time as we initiate clinical development of SP001,” said Esther Rajavelu, President and Chief Executive Officer of Spero. “She brings deep expertise in rheumatology and immunology along with firsthand experience advancing innovative therapies for autoimmune diseases. Deb's leadership will be invaluable as we advance our clinical strategy with the goal of delivering meaningful therapies for patients with significant unmet medical needs."

Dr. Zack's resume reads like a tour of immunology's greatest hits. A board-certified rheumatologist with a Ph.D. in immunology, she previously served as Global Development Lead for Enbrel at Amgen, one of the foundational blockbuster drugs for autoimmune disorders. Her experience extends across the industry, with clinical leadership roles at Novartis's Biotherapeutics Development Unit, Xencor Inc., and most recently as Chief Medical Officer of Exagen Inc. This deep industry experience is built on a decade in academia as an associate professor at UCLA, where she treated patients and conducted research in molecular immunology.

Her decision to join Spero underscores the perceived potential of the company's lead immunology program. “I am thrilled to join Spero at such a pivotal time in the Company's evolution," said Dr. Zack. "Spero has set a strong foundation with SP001, targeting CD40 ligand, as its lead asset in immunology. The inhibition of this target, which modulates both B-cell and T-cell activation, has the potential to address multiple drivers of immune-mediated diseases, such as IgG4-RD and the opportunity to evaluate and potentially advance this mechanism is particularly compelling. I look forward to working alongside the talented Spero team to advance SP001 and help shape a disciplined clinical development strategy for this program and future pipeline opportunities in immune-mediated diseases.”

The Science and Promise of SP001

At the heart of Spero's new strategy is SP001, a Phase 2-ready monoclonal antibody that targets a critical immune pathway regulator known as CD40 ligand (CD40L). By blocking this target, the drug aims to interrupt the faulty communication between immune cells—specifically T-cells and B-cells—that drives chronic inflammation, fibrosis, and tissue damage in a host of autoimmune conditions.

What sets SP001 apart, according to the company, is its "third-generation, Fc-silent" design. This is not just technical jargon; it's a direct answer to a historical challenge that has plagued this class of drugs. Early attempts to target the CD40/CD40L pathway in the 1990s and 2000s were halted after some drug candidates were linked to dangerous thromboembolic events, or blood clots, caused by unwanted platelet activation through the antibody's Fc region. SP001 has been engineered to be "silent" in this regard, aiming to deliver the therapeutic benefit of CD40L blockade without the associated risks, while maintaining a long half-life in the body.

The first test for this next-generation approach will be in IgG4-related disease (IgG4-RD), a rare and often misdiagnosed fibroinflammatory condition. Known as "the great mimicker," it can affect nearly any organ, leading to a long and frustrating diagnostic journey for patients. While considered rare, with a U.S. prevalence estimated at around 5.3 per 100,000 people, the disease is severe, associated with a 2.5-fold higher risk of death. Currently, there is a significant unmet need for effective, targeted therapies.

Spero plans to initiate a Phase 2 trial for SP001 in IgG4-RD in the second quarter of 2027. This follows the successful completion of two Phase 1 studies in healthy volunteers and a multiple-ascending-dose trial in patients with Sjögren's disease, another autoimmune condition, which reportedly showed a benign safety profile and early signs of efficacy. Spero's partner in China, Innovent Biologics, is also planning a Phase 2 trial in Sjögren's disease to begin in early 2027.

Navigating a Competitive and High-Stakes Landscape

Spero and Dr. Zack are entering a re-energized but crowded field. After the initial safety setbacks, a new wave of companies is advancing redesigned CD40/CD40L inhibitors, making it one of the most-watched areas in immunology. The race is on to be the first to secure approval for this promising mechanism.

Key competitors include Sanofi, whose drug Frexalimab is already in Phase 3 trials for multiple sclerosis, and UCB, whose Dapirolizumab Pegol is in Phase 3 for systemic lupus erythematosus. Other players like Eledon Pharmaceuticals (Tegoprubart for transplant rejection) and Kiniksa Pharmaceuticals (Abiprubart for rheumatoid arthritis) are also in mid-stage development.

While no drug targeting this pathway has yet reached the market, analysts predict the first approval could come by 2029. In this high-stakes environment, experienced leadership is paramount. Securing a CMO with Dr. Zack's track record in both developing and launching major immunology drugs is a significant strategic coup for Spero, signaling to investors and competitors its serious intent to become a major player in the space.

Fortifying the Financial Backbone for a Long Race

Clinical development, especially in competitive fields like immunology, requires a long-term financial commitment. Spero appears to have shored up its resources for the marathon ahead. Just this month, the company announced a $105 million non-recourse royalty financing transaction with Healthcare Royalty, an affiliate of KKR.

The deal is structured against future milestone and royalty payments from GSK for the company's antibiotic, Utebzi. This clever financing provides Spero with a significant, non-dilutive cash infusion specifically intended to fund the development of SP001. The company has stated that this capital, combined with its existing cash reserves, is expected to extend its operational runway into the second half of 2029. This timeline provides a crucial window to advance SP001 through multiple phases of clinical trials.

The financing comes on the back of the company's exclusive licensing agreement with Innovent Biologics for SP001, for which Spero paid a $35 million upfront fee and holds worldwide rights outside of Greater China. While Spero's stock (SPRO) has recently traded below its 200-day moving average, the new funding and strong leadership appointment could reshape investor sentiment as the company executes its clear, well-funded strategy to tackle some of immunology's most challenging diseases.