Key Takeaways MRK and Daiichi start dosing in a phase III study of HER3-DXd in HR-positive, HER2-negative breast cancer.The study follows early data where HER3-DXd showed promising responses in metastatic breast cancer.Primary endpoints include progression-free and overall survival, with safety as a secondary measure.Merck (MRK) and Japan’s Daiichi Sankyo announced the dosing of the first patient in the phase III HERTHENA-Breast04 study evaluating their investigational HER3-directed DXd antibody-drug conjug ...

Group 1: FDA Breakthrough Therapy Designation - Merck's B7-H3-directed ADC, ifinatamab deruxtecan (I-DXd), received FDA's Breakthrough Therapy designation for treating extensive-stage small cell lung cancer in adults whose disease progressed after platinum-based chemotherapy [1][8] - The Breakthrough Therapy designation accelerates the development and review of drugs for serious conditions when early clinical evidence indicates significant improvement over existing treatments [2] Group 2: Clinical Studies and Data - The FDA's decision was based on data from the phase II IDeate-Lung01 study, which evaluated the safety and efficacy of I-DXd, supported by the phase I/II IDeate-PanTumor01 study [3][8] Group 3: Stock Performance - Year to date, Merck's shares have decreased by 15.3%, while the industry has seen a decline of 2.8% [4] Group 4: Collaboration and Development - Merck acquired global co-development and co-commercialization rights to I-DXd and two other ADCs from Daiichi Sankyo for a potential total consideration of up to $22 billion, although Daiichi retains exclusive rights for development in Japan [6][9] - I-DXd is also being evaluated in phase III studies for esophageal and prostate cancers, and it has an orphan drug designation for small-cell lung cancer in multiple regions [5][8] Group 5: ADC Market Competition - ADCs are viewed as a disruptive innovation in the pharmaceutical industry, enhancing cancer treatment by targeting tumors with cytotoxic drugs [11] - Daiichi Sankyo has multiple ADCs in clinical development and markets Enhertu in partnership with AstraZeneca, which is approved for various cancer indications [12] - Pfizer entered the ADC market by acquiring Seagen for $43 billion, adding several ADCs to its portfolio that have contributed significantly to its revenues [13][14]

Core Insights - Pfizer has strengthened its position in the oncology space with the acquisition of Seagen in 2023, adding four antibody-drug conjugates (ADC) to its portfolio [1] - The oncology segment contributed over 25% to Pfizer's total revenues in Q1 2025, with a year-over-year growth of 7% [1] - The overall oncology sales for Q2 2025 are estimated at $4.0 billion, reflecting a 2% increase year over year [3] Oncology Segment Performance - Sales of Xtandi, Lorbrena, and Braftovi/Mektovi are expected to have increased, while Ibrance's sales are likely to have declined due to competitive pressures and the impact of the Inflation Reduction Act [2] - ADC products show mixed trends, with Padcev benefiting from strong demand, while Adcetris faced competitive pressure in the U.S. [7] Competitive Landscape - AstraZeneca's oncology sales accounted for nearly 41% of its total revenues, with a 13% increase in Q1 2025 driven by products like Tagrisso and Lynparza [4] - Merck's Keytruda accounted for over 46% of its total revenues in Q1 2025, highlighting its significance in the oncology market [5] Valuation and Estimates - Pfizer's shares are currently trading at a price/earnings ratio of 8.25, which is lower than the industry average of 15.12 and its own 5-year mean of 10.86, indicating attractive valuation [8] - The bottom-line estimate for 2025 has slightly decreased from $3.08 to $3.05, while the estimate for 2026 has increased from $3.08 to $3.09 [9]