Summary of Jazz Pharmaceuticals (JAZZ) Update / Briefing on Modesto Company and Industry Overview - **Company**: Jazz Pharmaceuticals - **Product**: Modesto (formerly known as dorbapril) - **Industry**: Oncology, specifically focused on rare brain tumors Key Points and Arguments 1. **FDA Approval**: Modesto received accelerated approval from the FDA on August 6, 2025, for treating adult and pediatric patients with diffuse midline glioma harboring an H3K27M mutation with progressive disease following prior therapy [5][41] 2. **Market Need**: This is the first and only FDA-approved treatment for this ultra-rare and aggressive brain tumor, primarily affecting children and young adults, with an estimated annual incidence of approximately 2,000 patients in the U.S. [10][49] 3. **Launch Readiness**: Following the acquisition of Chimerix, Jazz Pharmaceuticals has prepared for a rapid launch, with Modesto available to patients as of August 15, 2025 [5][6] 4. **Mechanism of Action**: Modesto is a first-in-class small molecule that reverses the loss of H3K27 trimethylation, a hallmark of H3K27M mutant diffuse midline glioma, leading to decreased tumor cell proliferation and death [13][14] 5. **Clinical Data**: In clinical studies, the overall response rate for Modesto was 22%, with a median duration of response of 10.3 months. Approximately 73% of responders maintained their response for at least six months [40][28] 6. **Safety Profile**: Modesto has been well tolerated, with only 2.1% of patients discontinuing due to adverse reactions. Serious adverse reactions occurred in 33% of patients, but no treatment-related deaths were reported [44][36] 7. **Commercial Strategy**: The launch strategy includes targeting academic centers of excellence, with a dedicated neuro-oncology sales team and disease education campaigns to raise awareness about the H3K27M mutation and the importance of testing [50][52] 8. **Pricing**: The wholesale acquisition cost for Modesto is set at $32,000 per bottle, reflecting the value and innovation it brings to patients [54] 9. **Future Trials**: The ongoing Phase III ACTION trial aims to confirm the benefits of Modesto in newly diagnosed patients, with expectations for broader international submissions based on supportive trial results [46][47] Additional Important Information - **Patient Support Services**: Jazz Pharmaceuticals has established robust access and patient support services to help patients navigate reimbursement and ensure access to Modesto [53] - **Long-term Outlook**: The patent for Modesto extends to 2037, with potential for patent term extension, indicating a long-term product lifecycle [58] - **Epidemiology Insights**: The disease was codified in the WHO classification in 2016, and the company is working to increase biopsy rates and improve diagnostic accuracy for H3K27M mutations [100][83] - **Potential for Expansion**: There is ongoing research into the broader applicability of Modesto beyond its current indication, exploring similar biological mechanisms in other tumor types [104][106]