Ultragenyx (RARE) investor relations material

Strategic positioning and financial outlook

• Positioned for a transformative year with key phase III Angelman data expected in the second half, aiming for profitability by 2027 with three new product launches and robust late-stage pipeline development.

• Revenue and cash flow expected to be significantly boosted by two gene therapy launches (Sanfilippo and GSD1a) and potential sale of up to three PRVs, each possibly generating $200 million, supporting a strong balance sheet.

• Base business has grown at 20% annually, with global rights to new products supporting transition to profitability and further growth.

• Cost controls and monetization of PRVs are planned to bridge the gap to profitability, with flexibility in timing to optimize financial outcomes.

• Current valuation seen as an opportunity, with substantial cash reserves and additional revenue expected from new launches.

Angelman syndrome program and clinical development

• Phase II data show long-term, durable benefit and excellent safety, with high patient retention indicating strong perceived value.

• Phase III study design includes rigorous operational controls, third-party endpoint assessment, and is expected to report data after final cleaning and analysis in mid-2024.

• Primary endpoint is Bayley-4 cognition, chosen for its fundamental relevance and regulatory familiarity; multi-domain responder index (mDRI) included for broader assessment and increased statistical power.

• Placebo effect minimized by excluding caregiver input and using blinded third-party assessors; historical data support low placebo risk.

• Safety concerns from earlier studies addressed by improved administration techniques, with no recurrence of lower extremity weakness in long-term treated patients.

Gene therapy launches: Sanfilippo and GSD1a

• Sanfilippo launch expected to see urgent uptake due to severe neurodegeneration and lack of alternatives, with strong patient and international interest.

• GSD1a patients face daily life-threatening challenges, driving high demand for gene therapy; both programs expected to generate meaningful revenue.

• Manufacturing capacity has increased due to launch delays, ensuring sufficient supply for both products in the first year.

• Commercial strategy leverages existing sales force, with added specialized teams for gene therapy logistics, patient support, and real-time supply chain management.

• Flat pricing model across age groups implemented, requiring tailored supply chain solutions.