Lyell Immunopharma Secures Rights to Promising CAR-T Therapy for Colorectal Cancer in $185M Deal

Lyell Immunopharma has entered into a significant licensing agreement with Innovative Cellular Therapeutics (ICT) for a phase 1-stage CAR-T cell therapy targeting colorectal cancer. The deal, announced on November 10, 2025, involves a substantial upfront payment and potential milestone rewards, signaling a major development in the field of solid tumor immunotherapy.

Deal Structure and Financial Terms

Lyell is acquiring the rights to the therapy, now called LYL273, for all territories outside China, Hong Kong, Macau, and Taiwan. The agreement includes:

• An upfront payment of $40 million in cash
• 1.9 million Lyell shares, valued at approximately $33 million
• Potential future payments of up to $820 million, including:
  • A $30 million clinical milestone
  • $115 million in late-stage regulatory milestones
  • 1.85 million additional Lyell shares upon regulatory milestones
  • Up to $675 million in commercial sales milestones
• Tiered royalties on potential future sales

Clinical Promise and Technical Details

LYL273, formerly known as GCC19CART, targets the guanylyl cyclase-C (GCC) protein receptor, which is expressed in over 95% of colorectal cancers and a majority of pancreatic adenocarcinomas. The therapy has shown promising results in an ongoing U.S. phase 1 study involving 12 patients with refractory metastatic colorectal cancer:

• 67% overall response rate
• 83% disease control rate
• Median progression-free survival of 7.8 months at the highest dose tested

Dr. Benjamin L. Schlechter of Dana-Farber Cancer Institute, lead investigator on the phase 1 study, noted, "We rarely see such deep and durable responses in colorectal cancer patients treated with multiple prior lines of chemotherapy."

Safety Considerations and Management

While the therapy has shown efficacy, safety concerns have been noted:

• Five out of six patients receiving the higher dose experienced cytokine release syndrome and diarrhea
• One patient experienced a dose-limiting toxicity, including grade 3 diarrhea and grade 4 intestinal inflammation, resulting in death from fungal sepsis 48 days post-infusion

Lyell emphasized that no grade 3 or higher diarrhea had occurred in the last three patients treated with the higher dose since implementing an optimized management protocol, including prophylaxis for diarrhea.

Strategic Implications and Industry Perspectives

The acquisition of LYL273 represents a significant addition to Lyell's pipeline of next-generation CAR-T therapies. CEO Lynn Seely, M.D., stated, "We believe LYL273 has the potential to be a transformational advance in the treatment of colorectal cancer, an area of tremendous unmet need."

Richard Klausner, M.D., Lyell's co-founder and board chairman, highlighted the broader implications of this development: "The ability to treat solid tumors with an acceptable safety profile has become the holy grail for CAR T-cell therapy for cancer. These impressive early results suggest we may be on the path to finally breaking the barrier for solid cancer."

The news has been positively received by investors, with Lyell's share price increasing by approximately 4% to $18.19 in early trading following the announcement.