Guggenheim 3rd Annual Healthcare Innovation Conference - SPRUCE BIOSCIENCES INC

Explicit Guidance:

• Regulatory Timelines: BLA submission planned for December (current year); FDA acceptance expected in February (following year); product approval anticipated in late August/early September of the following year.
• Pipeline Status: Second Process Performance Qualification (PPQ) run for Drug Product (DP) to be completed by end of current year; second PPQ data to be included in regulatory review package.
• Data Release: Additional biomarker data (NFL, GM2, GM3) scheduled for presentation at the World Meeting in San Diego in February.
• Commercial Monetization: Proceeds from the Pediatric Review Voucher (PRV) monetization expected to fund US commercialization; anticipated upon approval (Aug/Sept) and likely to occur shortly thereafter.

Business-Segment Outlook:

• US Market Potential: Claims database analysis currently identifies ~1,400 MPS III patients, with an estimated ~450 diagnosed MPS 3B patients in the US; natural history studies suggest prevalence could range between 250 and 2,000 patients depending on incidence assumptions (0.5–4 per 100,000).
• Patient Identification Strategy: Sales force and Medical Science Liaison (MSL) teams targeting the 15 NORD-approved lysosomal storage disease centers of excellence (5 specific to MPS) to access the concentrated patient pool.
• Treatment Scope: Intention to treat patients beyond early childhood, including older children and young adults, aiming to halt disease progression even in advanced cases.
• Dosing Regimen: Finalizing a fixed-dose, every-other-week administration schedule for the BLA proposal to avoid weight-based pricing volatility.

Market and Competitive Outlook:

• Pricing Strategy: Pricing expected to fall between $1 million and $4 million per patient/year, positioning the product competitively against Denali's weight-based therapy (<del>$1–2.8M) and Biomarin's Fayuvi (</del>$4M) while ensuring patient access.
• Competitive Landscape: No other approved products for MPS3B; product viewed as a life-transforming therapy with a "tight story" that the field is "clamoring" for.
• Global Expansion: Revamping European commercialization initiatives starting in Q4 of the current year via local distributors, partners, or name-patient programs due to increasing complexity in the European market.

Macro / Industry Outlook:

• Regulatory Precedent: Leveraging the FDA's acceptance of heparin sulfate as a "reasonably likely to predict clinical benefit" endpoint, similar to the pathway used for the recent approval of Fayuvi (MPS3A) and Avalaya (MPS2).
• Pediatric Designation: Reliance on Rare Pediatric Disease designation to secure a Pediatric Review Voucher (PRV), which Spruce Biosciences will retain and monetize.
• Natural History Data: Utilization of an internally run, proprietary natural history study (initiated by Biomarin) rather than external control arms to strengthen the regulatory narrative against disease heterogeneity.

Strategic Initiatives:

• Confirmatory Trial: A registration/confirmatory trial focused on Bayley's cognitive scoring (subdomains) is underway at the time of BLA submission to facilitate full approval; recruitment is operationalized to ensure feasibility by launch.
• Expanded Access Program: Running parallel to the confirmatory trial to provide patient access between now and commercial launch.
• Manufacturing Qualification: Transfer of Drug Product manufacturing completed from Vetter (Germany) to Samsung Bioepis (South Korea); qualification batches included in the review process.
• European Engagement: Restarting and advancing CHMP and PIP engagement for European approval starting in Q4.

Risks and Headwinds to Outlook:

• Regulatory Uncertainty: While a clear pathway exists, the "acceptance of the biomarker as a surrogate" remains a review issue subject to FDA final determination; FDA may debate functional measures and baseline imbalances in patient age/progression stages.
• Disease Heterogeneity: Patient variability in decline speed and diagnosis timing creates baseline imbalances that require robust modeling and propensity score matching to validate efficacy.
• Manufacturing Risk: Qualification of the new manufacturing site (South Korea) for the Drug Product is a critical dependency for the BLA.
• Commercial/Milestone Obligations: Spruce retains obligations to pay tiered royalties and sales milestones to Biomarin, estimated at $20–$30 million in net sales over the first two years globally, alongside a small fraction of PRV proceeds.
• Market Access: European regulatory and pricing environments are described as "becoming more difficult."

Management Tone on the Future:

• Confidence Level: High confidence in the regulatory pathway, describing the clinical and biomarker data as "incredibly robust," "compelling," and a "tight story."
• Strategic Outlook: Optimistic about the commercialization potential, noting that caregivers are "very willing" to treat patients even in advanced disease stages to prevent progression.
• Adcom Expectations: No expectation of an Advisory Committee (ACOM) meeting, citing strong FDA alignment and positive meeting trends; management feels the data is sufficient for a direct review decision.
• Forward Hedges: Management emphasizes that while the package meets standards, the FDA ultimately decides the final approval status and any remaining regulatory debates.

Miscellaneous:

• Biomarker Updates: Will publicly share new data on NFL, GM2, and GM3 biomarkers in February, following the precedent set by Fayuvi and Avalaya where biomarker improvement correlated with clinical benefit.
• FDA Interactions: Completed two pre-BLA meetings (CMC and Clinical) addressing 20 specific questions to finalize the BLA framework.
• Voucher Value: The PRV is a strategic financial lever specifically intended to fund the initial commercialization ramp-up in the US.