GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - SCYNEXIS INC

Financial Performance:

• Reported cash position of $63.2 million as of September end.
• Cash runway extends to 2029, sufficient to complete Phase II studies for the ADPKD program (770).
• Secured up to $240 million in non-dilutive potential funding from BARDA for the antifungal program (SY247), with an initial committed tranche of $18.5 million.
• Generates potential future revenue via sales milestones from the fully out-licensed Brexfem product to GSK.

Guidance and Future Outlook:

• Plans to initiate Phase II clinical trials for the ADPKD candidate (770) by the end of the current year.
• Aims for an interim readout of the 770 Phase II data by Q4 2027, with study completion targeted for 2028.
• Plans to initiate Phase II trials for the antifungal candidate (SY247) in mid-2027.
• Long-term commercial outlook targets a broad label for SY247 covering both treatment and prophylaxis of invasive fungal diseases.
• Expects the Phase II 770 design to mirror the standard one-year treatment period with placebo and two dose groups.

Business Segments and Product Lines:

• ADPKD Segment (Candidate 770): Novel direct AMPK activator targeting a market with no effective alternatives besides the poorly tolerated Tolvaptan; currently in pre-Phase II preparation following successful Phase I dose-ranging.
• Antifungal Segment (Candidate SY247): Select analog within a proprietary platform designed for invasive candidiasis, featuring enhanced oral viability and tissue penetration; Phase I completed for both IV and oral formulations.
• Out-Licensed Asset (Brexafem): Previously partnered with GSK for Vulvovaginal Candidiasis (VVC) indications; GSK is currently progressing a relaunch, though no specific date is disclosed.
• Strategic Pivot: Company has transitioned from a sole focus on antifungals to a dual-platform strategy addressing rare diseases (ADPKD) and infectious diseases (invasive candidiasis).

Market and Competitive Landscape:

• ADPKD Market: Currently dominated by Tolvaptan ($1.5B sales in 2024) with significant safety and tolerability issues; 770 is the only clinical-stage AMPK activator in development.
• Competitive Activity: High interest in the space with Novartis (Farabusten/microRNA inhibitor) nearing Phase 3; other candidates in genetic modification stages are largely Phase 1.
• Antifungal Market: Critical unmet need due to high mortality in immunocompromised patients and rising multidrug resistance; SY240 offers a unique IV-to-oral step-down capability not available in current echinocandin or polyene classes.
• Commercial Strategy: 770 is agnostic to genetic mutations (PKD1/PKD2) and may eventually serve as a combination therapy with other modalities.

Risks and Challenges:

• Regulatory Uncertainty: Phase II study designs for both programs are still in discussion with the FDA, specifically regarding the definition of the surrogate endpoint (Total Kidney Volume vs. GFR decline) for accelerated approval.
• Market Execution: Dependence on GSK's timeline for the Brexfem relaunch, with no guaranteed date for market availability.
• Clinical Validation: Success relies on demonstrating a 50% relative reduction in Total Kidney Volume (TKV) to match Tolvaptan's efficacy signal, alongside GFR data.

Management Commentary and Tone:

• Management tone is confident and optimistic regarding the transformative nature of the past year and the clear regulatory pathways for both assets.
• Emphasized the strategic advantage of the BARDA partnership in de-risking development through non-dilutive funding.
• Highlighted the "clear path to approval" for 770 due to validated mechanisms and strong safety profiles established in Phase I.

Analyst Questions and Answers:

• Q: What is the mechanism of action for 770 and why is it suitable for ADPKD?
• A: 770 is a selective AMPK activator that modulates mTOR and cAMP pathways to reduce cyst proliferation and fluid secretion, addressing three key disease hallmarks with high renal selectivity.
• Q: How does 770 compare to current market standards?
• A: It offers a novel mechanism compared to the single approved competitor (Tolvaptan), which suffers from poor tolerability, and targets a 50% TKV reduction benchmark.
• Q: What is the status of the SY247 Phase I data?
• A: Phase I is complete for both IV and oral formulations, confirming good tolerability and supporting the transition to Phase II for invasive candidiasis.
• Q: Will 770 be used in combination therapies?
• A: Primary development is as a monotherapy, but its downstream mechanism makes it theoretically compatible with other modalities for combination use.

Other Key Points:

• The company operates as a biopharma focused on rare diseases, specifically expanding into ADPKD while maintaining a robust antifungal pipeline.
• SY247 is positioned to address multidrug-resistant fungal infections in immunocompromised populations (cancer, transplant patients).
• The Phase II 770 study will focus on "rapid progressors" to accelerate the observation of Total Kidney Volume (TKV) changes.
• Financial stability is reinforced by the 2029 cash runway, which covers the critical Phase II milestones for the primary growth driver.