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

Explicit Guidance:

• Clinical Trial Initiation: Initiation of the Phase II trial for SP-001 in IgG4-related disease (IgG4RD) is guided for the second quarter of 2027.
• Cash Runway: The company projects a cash runway extending into the second half of 2029, supported by a $105 million non-dilutive financing arrangement.
• Partner Milestone: InnoVent is guided to initiate a Phase II trial for SP-001 in Sjögren's syndrome by early 2027.

Business-Segment Outlook:

• Product Portfolio: The company is repositioned entirely around SP-001 (anti-CD40 ligand antibody) as its lead asset in immunology; it remains a development-stage company with no current commercial revenue from SP-001.
• Indication Strategy: Focus is on IgG4RD due to early lifecycle status and unmet need for non-B-cell mechanisms; Sjögren's remains a secondary pipeline opportunity to be informed by IgG4RD data.
• Differentiation: The strategy targets T cells, B cells, and antigen-presenting cells (upstream of current B-cell therapies) to address tissue fibrosis and organ damage preservation, rather than solely controlling flares.

Market and Competitive Outlook:

• Competitive Landscape: Current market players (e.g., Obexelimab, Opleznab) focus on B-cell targeting with efficacy primarily in flare control. SP-001 aims to differentiate by addressing fibrosis and preventing organ damage, potentially filling a gap in long-term disease management.
• Treatment Paradigm: The precise positioning (e.g., post-B-cell therapy failure vs. maintenance) is not yet defined; the objective is to establish the mechanism's ability to manage broader disease features.
• Formulation: The initial Phase II formulation is IV dosing (once-monthly) to establish proof of concept; future subcutaneous or oral modalities are not ruled out for potential patient convenience but are not currently scheduled.

Macro / Industry Outlook:

• Regulatory Environment: The company believes the existing data package (non-clinical, Phase 1, Phase 1B) positions it well to engage with the FDA regarding the Phase II trial design, which mirrors designs used in other Phase II trials within the IgG4RD indication.
• Safety Monitoring: As an immunomodulatory agent, the company anticipates heightened focus on infection risks and safety tolerability (specifically thrombosis) throughout the Phase II development.

Strategic Initiatives:

• Pipeline Advancement: Launching the Phase II IgG4RD trial to generate data on the impact of CD40 ligand targeting on fibrosis and T-cell mediated pathophysiology.
• Commercialization Partnership: Leveraging a license with GSK for the commercialization of the first approved drug (Dutepsi) to generate non-dilutive cash flow ($105 million raised via partial monetization of commercial milestones).
• Target Validation: Capitalizing on fully silent Fc region technology (SP-001) which has demonstrated safety in ~100 human subjects (no thrombotic events observed) compared to first-generation antibodies.

Risks and Headwinds to Outlook:

• Clinical Uncertainty: The Phase II trial's success is contingent on generating evidence for T-cell involvement in IgG4RD; outcomes could deviate if fibrosis benefits are not demonstrated.
• Safety Risks: Potential for thrombotic events (though not observed in prior small trials) or upper respiratory infections could impact trial progression or FDA approval.
• Data Interpretation: Cross-trial comparisons with competitors (e.g., Xylomab, Obexelimab) are deemed contextual rather than definitive due to differences in patient demographics and trial designs.
• Timing Risk: Reliance on specific catalysts (Q2 2027 readout) with no explicit financial milestones tied to the Phase II completion.

Management Tone on the Future:

• Confidence Level: High confidence in the safety profile of the silent Fc technology (based on 100+ human subjects) and the differentiation potential of the mechanism.
• Strategic Clarity: Management expresses certainty in the capital efficiency of the current runway and the strategic validity of prioritizing IgG4RD to inform the broader pipeline, including Sjögren's.
• Hedges: Explicitly notes that dosing selection and specific treatment paradigm positioning remain to be determined by Phase II data, avoiding premature assertions on market share or specific efficacy benchmarks (e.g., flare reduction rates).

Miscellaneous:

• Dosing Strategy: Phase II IgG4RD trial will utilize two doses to determine appropriate dosing for future registrational trials.
• Diligence Focus: The in-licensing of SP-001 from InnoVent was driven by target validation, partial clinical proof, and IP/regulatory interactions.