Exelixis' Zanzalintinib: A Breakthrough in Kidney Cancer with Massive Upside Potential

The biotech sector is rarely this excited about a single data readout, but Exelixis (NASDAQ: EXEL) has just delivered what looks like a paradigm-shifting moment in advanced kidney cancer treatment. At the 2025 ASCO Annual Meeting, the company unveiled Phase 1b/2 STELLAR-002 trial results for its novel therapy, zanzalintinib, in combination with nivolumab. The numbers are staggering: a 63% objective response rate (ORR), 90% disease control, and a median 18.5-month progression-free survival (PFS)—all in first-line clear cell renal cell carcinoma (ccRCC). These data aren’t just better than existing standards; they’re redefining what’s possible in this deadly disease. For investors, this is a once-in-a-decade opportunity to capitalize on a therapy that could command a $100M+ near-term revenue upside and a $33B+ kidney cancer market. Here’s why EXEL is a buy now, before pivotal Phase 3 data further accelerates its valuation.

Why Zanzalintinib Stands Out: Data That Beats the Competition

The current gold standard for first-line ccRCC is cabozantinib (CABOMETYX) plus nivolumab. In the CheckMate 9ER trial, that combo delivered a 51% ORR and a median 16.6-month PFS. Zanzalintinib’s 63% ORR and 18.5-month PFS crush those benchmarks, while its third-generation mechanism—a multitargeted tyrosine kinase inhibitor (TKI) inhibiting VEGFR, MET, AXL, and MER kinases—avoids some of the metabolic and cardiovascular side effects that plague earlier TKIs like cabozantinib.

The trial’s 90% disease control rate further underscores its durability. In high-risk patients (75% of the cohort had intermediate/poor-risk disease), these results are transformative. For context, cabozantinib/nivolumab’s PFS in poor-risk patients is just 10.8 months. Zanzalintinib’s longer half-life and selective kinase targeting mean fewer dose reductions and better tolerability—a critical edge in real-world use.

Market Potential: A $33B+ Opportunity Ignited by Clinical Superiority

The kidney cancer treatment market is projected to exceed $33 billion by 2030, driven by rising incidence and better early detection. ccRCC alone accounts for ~75% of renal cell carcinoma cases, and first-line therapy is where the money is. If zanzalintinib secures FDA approval in this setting—a near-certainty given these data—it could quickly carve out a 20–30% market share, generating $1.2–$1.8 billion in annual sales by 2030.

But the near-term upside is even more compelling. The Phase 1b/2 data are so strong that Exelixis could file for accelerated FDA approval by late 2025, leveraging the 18.5-month PFS as a surrogate endpoint. This would allow Zanzalintinib to hit the market in 2026, raking in $100M+ in first-year sales as physicians adopt it ahead of Phase 3 confirmatory trials.

The Catalyst Timeline: Immediate and Long-Term Drivers

• Q4 2025: Phase 3 STELLAR-304 trial design finalized. This trial will compare zanzalintinib/nivolumab head-to-head with sunitinib in first-line ccRCC, with primary endpoints (PFS/OS) likely readout by mid-2027.
• 2026: Potential accelerated approval in ccRCC, followed by $100M+ in revenue as sales ramp up.
• 2027–2028: Phase 3 data readouts could extend Zanzalintinib’s label to non-ccRCC subtypes and other solid tumors (e.g., colorectal cancer), unlocking even more market share.

The risk-reward here is asymmetric. Even a 10% market share in ccRCC would add ~$150 million to Exelixis’ top line—far outweighing its modest current revenue ($1.3B in 2024, mostly from cabozantinib).

Safety: A Critical Differentiator Over Competitors

Zanzalintinib’s tolerability is a game-changer. While cabozantinib’s combination therapy causes grade 3/4 adverse events in ~40% of patients (commonly hypertension and palmar-plantar erythrodysesthesia), Zanzalintinib’s incidence is similar but with fewer metabolic side effects. The trial’s 2% treatment-related discontinuation rate (vs. 20% in the nivolumab/relatlimab arm) signals a smoother path to approval and adoption.

Conclusion: Buy EXEL Now—Before the Phase 3 Catalysts Hit

The ASCO data has already positioned Zanzalintinib as a first-line therapy to beat, but the stock remains undervalued. At current levels (~$50/share), EXEL trades at just 5x its 2026 revenue estimates—a historic discount for a biotech with such a high-growth, high-margin pipeline. With $1.5B in cash and no major near-term liabilities, Exelixis is perfectly positioned to capitalize on its own success.

Investors who act now will own a category-defining therapy at a fraction of its future value. The Phase 3 readouts will only amplify this story—don’t wait. EXEL is a buy.