CHARDAN HEALTHCARE CONFERENCE – 10 YEARS OF DISRUPTIVE INNOVATION - SPERO THERAPEUTICS INC

Financial Performance:

• Secured $105 million via non-dilutive, non-recourse partial monetization of commercial milestones from GSK (partner for approved asset Dutepsi).
• Company remains a development-stage entity with no reported revenue; funding provides runway into the second half of 2029.
• No specific details provided regarding debt levels, profit margins, or cash flow statements beyond the new financing.

Guidance and Future Outlook:

• Planning to initiate a Phase II clinical trial for SP-001 in IgG4-related disease (IgG4RD) in the second quarter of 2027.
• Partner InnoVent is guided to initiate a Phase II trial in Sjögren's syndrome by early 2027.
• Next major catalyst is the launch of the IgG4RD Phase II trial; current focus is establishing proof of concept and determining optimal dosing.

Business Segments and Product Lines:

• Lead asset SP-001 is a third-generation anti-CD40 ligand antibody licensed from InnoVent, repositioned to target immunology indications.
• Primary clinical focus shifted to IgG4-related disease, a relatively early-lifecycle indication, though Sjögren's remains a secondary priority.
• SP-001 is currently formulated as a once-monthly intravenous (IV) infusion; subcutaneous or oral modalities are under potential future exploration.
• Two doses are planned for the upcoming IgG4RD Phase II trial to determine appropriate dosing for future registrational studies.

Market and Competitive Landscape:

• SP-001 differentiates by targeting CD40 ligand upstream of both T and B cells, aiming to address fibrosis and organ damage rather than just flare control.
• Competitors include Plisna, Obilexamab, and Rilzabrutinib, which primarily focus on B-cell targeting or flares.
• Management posits that while current B-cell agents are effective for flare management, there is an unmet need for therapies addressing long-term tissue preservation and fibrosis.

Risks and Challenges:

• Historical challenge of first-generation CD40 antibodies involved thrombotic events due to Fc binding; SP-001 features a fully silent Fc region to mitigate this.
• No thrombotic events observed in over 100 human subjects across Phase I and Phase 1b trials, but safety monitoring for infections and tolerability remains a priority.
• The IgG4RD market is in early development; definitive positioning within the treatment paradigm (e.g., after B-cell therapy failure) is not yet determined.
• IV-only administration may present patient convenience hurdles compared to future self-injectable or oral options.

Management Commentary and Tone:

• Tone is confident and focused on strategic pivot, emphasizing the company's strong cash position and clear path to data generation.
• Management expressed conviction that the CD40 ligand mechanism offers a differentiated approach to address aspects of disease (fibrosis, organ damage) not covered by existing B-cell therapies.
• Viewed the company as well-positioned following the GSK partnership and financing to execute the 12-month development roadmap.

Analyst Questions and Answers:

• Q: Rationale for IgG4RD over larger Sjögren's market?
  • A: IgG4RD offers a compelling early-life-cycle opportunity with high unmet need; Sjögren's data will evolve in parallel, and the mechanism may address broader disease aspects.
• Q: How does SP-001 address the thrombosis risks of first-gen CD40 inhibitors?
  • A: The silent Fc region eliminates FC-gamma R2A binding on platelets, with no thrombotic events observed in >100 human subjects to date.
• Q: What is the strategy for dose selection?
  • A: Dose selection relies on the totality of PK/PD and safety data from Phase I, I, and Phase 1b trials, with Phase II results in IgG4RD further informing the strategy.
• Q: How does SP-001 compare to competitors regarding efficacy on flares?
  • A: While competitors show strong flare control (e.g., 56-87% reduction), SP-001 aims to demonstrate benefits on fibrosis and tissue damage, requiring new evidence from Phase II.

Other Key Points:

• The Phase 1b Sjögren's trial data (8 active, 2 placebo patients) showed activity across all doses despite small sample size and short duration, supporting continued investment.
• The Phase II IgG4RD trial design mirrors other trials conducted in the indication to satisfy FDA expectations.
• Management believes the current data package from InnoVent positions them well to initiate FDA conversations prior to trial launch.