Immunotherapy-TKI combination therapies

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Will Zanzalintinib Ease Out EXEL's Reliance on Cabometyx for Growth?
ZACKSยท 2025-08-13 13:55
Core Insights - Exelixis is developing zanzalintinib, a next-generation oral investigational tyrosine kinase inhibitor (TKI) targeting receptor tyrosine kinases involved in cancer growth, with recent studies showing positive data [1] Study Results - In June 2025, Exelixis announced positive top-line results from the STELLAR-303 study, a phase III trial involving 901 patients with metastatic colorectal cancer, comparing zanzalintinib plus Tecentriq against regorafenib [2] - The STELLAR-303 study met one of its dual primary endpoints, showing a statistically significant improvement in overall survival (OS) for the intent-to-treat population treated with zanzalintinib plus Tecentriq compared to regorafenib [3] - Enrollment for the STELLAR-304 study was completed in May 2025, evaluating zanzalintinib in combination with Opdivo versus sunitinib in advanced non-clear cell renal cell carcinoma [4] - Exelixis has opted not to proceed with the phase III portion of the STELLAR-305 trial based on emerging data and competition in advanced squamous cell carcinoma [5] - The company initiated the phase III STELLAR-311 study in advanced neuroendocrine tumors, comparing zanzalintinib to everolimus [6] Competitive Landscape - The competitive environment for renal cell carcinoma (RCC) is intensifying, with significant competition for Exelixis's lead drug, Cabometyx, from various immunotherapy-TKI combinations [7] - Keytruda, approved for advanced RCC, accounts for approximately 50% of Merck's pharmaceutical sales, highlighting the competitive pressure in the market [10] Financial Performance - Exelixis shares have increased by 14% year-to-date, contrasting with a 0.9% decline in the biotech industry [11] - The company's shares are currently trading at a price/sales ratio of 4.09x forward sales, above its historical mean of 3.64x and the biotech industry's average of 1.59x [13] - The bottom-line estimate for 2025 has risen from $2.64 to $2.68, while the estimate for 2026 has decreased from $3.13 to $3.09 over the past 30 days [14]