GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - SCYNEXIS INC

Explicit Guidance:

• Cash Runway: Current cash position of $63.2 million (as of September 2024) provides a runway extending into 2029, sufficient to complete Phase II studies for SY770 and the SY247 program (with SY247 largely subsidized).
• BARDA Funding Milestones: Potential for up to $240 million in non-dilutive funding for SY247 development if all options are exercised; initial tranche committed at $18.5 million.

Business-Segment Outlook:

• SY770 (ADPKD):
  • Development Timeline: Phase II study initiation planned for the end of the current year (2024); Phase II interim analysis expected by Q4 2027; Phase II completion anticipated in 2028.
  • Study Design: One-year treatment duration with three arms (two dose groups of SY770, one placebo) focusing on rapid progressor patients.
  • Efficacy Targets: Aiming to demonstrate a 50% relative reduction in Total Kidney Volume (TKV) compared to placebo (baseline 5% progression) by interim readout.
  • Regulatory Path: Plan for one Phase II and one single Phase III study; target accelerated approval based on TKV surrogate endpoint initially, with long-term GFR endpoint data required subsequently.
• SY247 (Invasive Candidiasis):
  • Development Timeline: Phase II study initiation planned for mid-2027.
  • Study Scope: Initial focus on treatment of invasive candidiasis, with potential for Phase III studies in both treatment and prophylaxis (prevention) to support a broad label.
  • Formulation Strategy: Full oral and intravenous (IV) formulations available to enable IV-to-oral step-down therapy.
• Brexafemme (BFXA): Currently out-licensed to GSK; awaiting their relaunch for vulvovaginal candidiasis (VVC) and recurrent VVC indications; no specific timing disclosed for market availability.
• Revenue Streams: Potential future revenue from sales milestones on the BFXA license and BARDA milestones; no specific revenue guidance provided.

Market and Competitive Outlook:

• ADPKD Landscape: Significant unmet medical need with only one approved therapy (Tolvaptan, $1.5B sales in 2024) noted for safety/tolerability issues.
• Competitive Position: Synexis claims to be the only clinical-stage company exploring an AMPK activator for ADPKD. Competitors include Novartis (inhibiting microRNA, entering Phase III) and others targeting genetic mechanisms (mostly Phase I/1b).
• Combination Potential: SY770 is agnostic to genetic mutation type (PKD1/PKD2), positioning it as a potential combination partner with future therapies, though initial development focuses on monotherapy.
• Invasive Fungal Disease: Market characterized by high mortality, limited treatment options, and increasing multidrug resistance; unmet need is high for oral step-down options alongside current IV-only therapies.

Macro / Industry Outlook:

• Regulatory Environment: Management actively engaging with the FDA regarding Phase II study design for SY770 to align on endpoints (TKV vs. GFR).
• Funding Environment: Utilization of BARDA programs as a strategy to de-risk development through non-dilutive public funding.

Strategic Initiatives:

• Asset Acquisition: Strategic shift from antifungals to include ADPKD via acquisition of SY770, expanding the portfolio into an underserved rare disease with attractive market dynamics.
• Platform Evolution: Transitioning from a single-focus antifungal platform to a dual-program biopharma company addressing rare diseases and invasive fungal infections.
• Product Launch Preparation: Monitoring GSK's relaunch progress for Brexafemme to anticipate potential milestone payments or new partnership dynamics.

Risks and Headwinds to Outlook:

• Regulatory Uncertainty: Phase II design and endpoints must be agreed upon with the FDA; failure to align could delay initiation or impact approval pathway.
• Clinical Failure: Risk that SY770 fails to achieve the 50% TKV reduction target in the interim readout or that GFR data in Phase III is insufficient.
• Competitive Pressure: Rapid advancement of competitors (e.g., Novartis entering Phase III) could alter the commercial landscape or pricing power.
• Relaunch Dependency: Revenue from BFXA milestones is contingent on GSK's ability and timeline to relaunch the product.
• Funding Dilution: While current runway is secure, the outlook assumes BARDA milestones are realized; failure to meet BARDA milestones could impact long-term funding.

Management Tone on the Future:

• Confidence: Management expresses strong confidence in the "clear path" for regulatory approval for SY770 and the "fantastic opportunity" of the SY247 program.
• Strategic Clarity: Tone reflects a decisive transformation completed over the past year, with a focus on execution of specific, timed milestones (Phase II starts, interim data).
• Financial Discipline: Emphasis on non-dilutive funding and extended cash runway (into 2029) to support the pipeline without immediate equity pressure.

Miscellaneous:

• Key Catalysts: End-of-year Phase II start (SY770), Q4 2027 interim data readout (SY770), mid-2027 Phase II start (SY247), and GSK relaunch announcement (BFXA).