Spruce Biosciences (SPRB) investor relations material

Program overview and development status

• Lead asset is tralesinidase alfa, an enzyme replacement therapy delivered intracerebroventricularly for MPS IIIB, a severe neurodegenerative pediatric disease with no approved therapies.

• The therapy uses a surrogate endpoint approval pathway, aiming for accelerated approval based on normalization of heparan sulfate biomarkers.

• Received FDA Breakthrough and Rare Pediatric Disease designations, enabling potential PRV opportunity if approved.

• Clinical program includes a 48-week treatment trial with 22 patients, five years of follow-up data, and a confirmatory randomized controlled trial with 14 patients underway.

• Submission for approval is planned for Q4, with potential priority review and approval by mid-next year.

Clinical and biomarker results

• Profound reductions in heparan sulfate and non-reducing ends observed, with biomarker levels normalized over five years.

• No other ERT has achieved similar biomarker normalization in neuropathic MPS; strong clinical evidence of cognitive benefit shown.

• Confirmatory trial uses Bayley Cognitive Raw Score as primary endpoint; Vineland questionnaire also shows benefit in motor and communication skills.

• Imaging data indicate stable cortical grey matter volume after six months of treatment, contrasting with decline in untreated patients.

• Systemic benefits include normalization of liver and spleen sizes, suggesting peripheral clearance of heparan sulfate.

Market opportunity and commercialization plans

• Estimated patient pool: 450 in the U.S., 500 in Europe, 1,800 in Asia Pacific, and 350 in Latin America.

• Projected to treat 200–250 U.S. patients five years post-launch, with a peak pool of 500.

• Pricing benchmarked at $1.5–2.5 million per year, anchored around $2 million.

• Commercial team expansion underway, including hiring of Chief Commercial Officer with rare disease launch experience.

• Expanded access program planned for the second half of 2026 to transition trial patients to commercial therapy.