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

Explicit Guidance:

• No explicit financial guidance provided (e.g., revenue, earnings, or cash flow forecasts).
• Cash Runway: Financing positions the company with a runway extending into the second half of 2029.
• Trial Initiation: Phase II trial in IgG4-related disease (IgG4RD) guided to initiate in the second quarter of 2027.
• Partner Trial: Partner InnoVent is guided to initiate a Phase II trial in Sjögren's by early 2027.

Business-Segment Outlook:

• Lead Asset (SP-001): Strategy repositioned around the anti-CD40 ligand antibody SP-001; Phase II trial design will utilize two doses to determine appropriate dosing for future registrational trials.
• Target Indications: Primary focus on IgG4RD (early lifecycle indication with high unmet need) and Sjögren's (no approved therapy in the West).
• Differentiation: Aiming to address disease aspects beyond flare control (e.g., fibrosis, organ damage preservation) rather than solely targeting B-cells like competitors.
• Commercialization: Existing commercial partner GSK holds rights to license the previously approved drug (Dutepsi) for commercialization.

Market and Competitive Outlook:

• Competitive Landscape: Anticipates entry of Plisna (Obiliximab), Rilzabrutinib, and others.
• Market Positioning: SP-001 targets upstream mechanisms (CD40 ligand affecting T cells, B cells, and antigen-presenting cells) to address fibrosis and organ preservation, distinguishing from current B-cell therapies focused on flare control.
• Treatment Paradigm: No definitive positioning established yet (e.g., monotherapy vs. subsequent therapy); objective is to contribute to understanding the disease landscape and define the appropriate role post-Phase II data.

Macro / Industry Outlook:

• Regulatory Path: Believes current data package from InnoVent positions the company well to initiate FDA conversations prior to Phase II dosing.
• Safety Standards: Monitoring for infections and safety is prioritized as a critical metric for all immunomodulatory trials; Phase II design mirrors other two Phase II trials in the indication.

Strategic Initiatives:

• Licensing: In-licensed SP-001 from InnoVent based on validated targets and differentiation potential.
• Financing: Secured $105 million in non-dilutive, non-recourse financing via partial monetization of royalties from GSK (Dutepsi) to fund development.
• Delivery Modality: Currently formulated for once-monthly IV dosing to establish proof of concept in Phase II; subcutaneous or oral options may be explored later to improve patient convenience.

Risks and Headwinds to Outlook:

• Safety Risks: History of first-generation CD40 antibodies showed thrombotic events; while SP-001 has a silent Fc region and no thrombotic events observed in ~100 human subjects (Phase 1/1B), safety and tolerability remain a primary monitoring focus.
• Development Uncertainty: Phase II results are required to characterize the role of T cells in IgG4RD and confirm the ability to target fibrosis; failure to demonstrate efficacy or safety could impact future development.
• Pricing/Access: Patient convenience (IV vs. subcutaneous) is identified as a potential hurdle for long-term adoption in a chronic condition.
• Data Interpretation: Cross-trial comparisons with other agents (e.g., Xylomab) are viewed as contextual only due to differing demographics/geographies, limiting definitive dose-response conclusions without new data.

Management Tone on the Future:

• Confidence: Expressed "very good position" regarding capitalization and asset portfolio; high confidence in the safety profile of SP-001 given the silent Fc region and human trial data.
• Caution: Maintains a "development stage" mindset; emphasizes gathering new evidence rather than making head-to-head claims against current standards of care.
• Strategic Focus: Emphasis on "contribute to the understanding of this disease" and "information gathering" prior to defining the treatment paradigm.

Miscellaneous:

• Preclinical vs. Clinical: In vivo mouse model data demonstrates biological activity but will not be used for direct translation to human dosing; human Phase 1/1B data and PK/PD profiles will drive dosing selection.
• Trial Design: Phase II for IgG4RD will generate evidence on T cell roles and fibrosis impact; Phase II for Sjögren's is handled by InnoVent.