Risk Factors Update Summary

• European Commission proposed revisions to pharmaceutical legislation, potentially impacting industry, adoption expected by early 2026.
• Entered into a license agreement with Alnylam for the development and commercialization of products containing an siRNA targeting the TMPRSS6 gene. Intend to develop a licensed product for potential treatment of PV. This could result in up to $130.0 million in potential development and regulatory milestones, in addition to sales milestones and tiered royalties on annual net sales.
• FDA continues to apply orphan-drug exclusivity regulations, tying it to approved uses.
• Received marketing authorization for PYRUKYND® in the EU and Great Britain. Currently providing access to PYRUKYND® free of charge for eligible patients in those jurisdictions through a global managed access program.
• Medicare out-of-pocket drug costs capped at $4,000 in 2024, $2,000 annually from 2025.
• Developing a gene therapy targeting PK deficiency, a potential treatment for transfusion-dependent anemia in LR MDS, and other therapies for rare diseases. Facing substantial competition from major pharmaceutical companies and biotechnology firms.
• Consolidated Appropriations Act delays 4% Medicare sequester until end of 2024, lowers payment reduction percentages.
• Potential milestone payment and royalties from Servier if a new drug application for vorasidenib is approved by the FDA for the adjuvant treatment of Grade 2 glioma patients with specific mutations.
• IRA introduces civil penalties for non-compliance, caps Medicare drug costs, and faces legal challenges.
• Accumulated deficit of $822.6 million as of December 31, 2022, with net losses of $352.1 million and $231.8 million for the twelve months ended December 31, 2023 and 2022, respectively.
• States awaiting FDA approval for Section 804 Importation Program proposals for Canadian drug importation.
• Facing challenges related to privacy laws and data transfers internationally, including increased scrutiny on data transfers from the EEA to the U.S. and potential impacts from the EU-U.S. Data Privacy Framework.
• Proposed regulations eliminate Medicare drug rebates' safe harbor, create new safe harbors.
• Ongoing litigation challenging the FDA's approval of another company's drug may threaten the development and approval of new drug products, potentially delaying efforts to develop and market new drugs.