A New Hope in Cancer Treatment
Lyell Immunopharma has entered a new licensing agreement that grants it access to a phase 1 CAR-T cell therapy designed to treat colorectal cancer. Under the terms, the company will pay $40 million in cash and issue nearly 2 million shares to secure global rights to the program.
Promising Early Results
The therapy was originally developed by Innovative Cellular Therapeutics, which operates in both the U.S. and China. Lyell said it was encouraged by the early results from an ongoing American study evaluating the treatment in 12 patients with advanced, treatment-resistant metastatic colorectal cancer. According to Lyell’s November 10 update, the highest dose group has recorded an overall response rate of 67%, a disease control rate of 83%, and a median progression-free survival of 7.8 months.
Targeting and Potential
Now renamed LYL273, the candidate targets the guanylyl cyclase-C (GCC) receptor, a protein present in more than 95% of colorectal tumors and in a large portion of pancreatic adenocarcinomas, giving it potential utility across multiple gastrointestinal cancers, Lyell added.
A Potential Breakthrough
In a statement, Lyell CEO Lynn Seely said that LYL273 could represent a major breakthrough for patients with colorectal cancer, a condition where treatment options remain severely limited. She added that the company plans to draw on its deep experience in T-cell biology and CAR T-cell development to quickly advance this program, along with its two late-stage studies of ronde-cel for individuals with relapsed or treatment-resistant large B-cell lymphoma.
Terms of the Agreement
To obtain exclusive rights to the therapy across all territories outside of China, Macau, Taiwan and Hong Kong, Lyell will provide $40 million in cash along with 1.9 million of its own shares to Innovative Cellular Therapeutics. Based on Lyell’s Friday closing share price of just over $17.5, the equity component of the payment is valued at roughly $33 million.
Under the agreement, ICT stands to receive a $30 million payment once an early-stage clinical milestone is achieved, followed by an additional $115 million and 1.85 million Lyell shares linked to later regulatory achievements.
If LYL273 successfully makes entry into the market, ICT could further collect up to $675 million in sales-based milestone payments, along with tiered royalties tied to global product revenues.
Safety and Side Effects
Regarding safety, Lyell reported that five of the six participants given the higher dose developed cytokine release syndrome, which is a typical CAR-T–related reaction, as well as diarrhea.
One individual experienced a dose-limiting toxicity that included grade 3 diarrhea, grade 4 intestinal inflammationand ultimately passed away from fungal sepsis 48 days after treatment. Despite the death, the company noted that no cases of grade 3 or higher diarrhea have been observed in the last three patients treated at the higher dose since implementing a refined diarrhea management plan with preventive measures.
The Future of Solid Tumor Treatment
Richard Klausner, Lyell’s co-founder, said that achieving safe and effective treatment of solid tumors has long been considered the ultimate goal in CAR T-cell cancer therapy, and the results indicate that the company is well on its way to achieving that objective.
Using a CAR-T approach in colorectal cancer is particularly significant, given that standard treatments (such as chemotherapy, targeted therapy, immunotherapy) have had only moderate success in advanced disease. The fact that LYL273 shows a 67% overall response rate in heavily pre-treated patients suggests a meaningful shift. Also, because the GCC receptor is found on the vast majority of colorectal cancer tumours, the therapy has a potentially broad addressable patient population.
However, the path ahead remains challenging. The solid-tumour microenvironment presents obstacles—including T-cell infiltration, immunosuppressive signalling and the risk of on-target/off-tumour toxicity—that CAR-T therapies have historically struggled to overcome. But Lyell’s experience in T-cell biology and solid-tumour CAR-T development give it a stronger basis than many earlier efforts.
