In a licensing deal unveiled Monday, Lyell Immunopharma is handing over $40 million in cash and almost 2 million of its shares to secure rights to a phase 1-stage CAR-T cell therapy for colorectal cancer.
The biotech pointed to the “impressive results” that the therapy’s creator, U.S.- and China-based Innovative Cellular Therapeutics, saw in an ongoing U.S. study in 12 patients with refractory metastatic colorectal cancer. That phase 1 trial has so far shown a 67% overall response rate, an 83% disease control rate and median progression-free survival of 7.8 months in the highest dose tested, Lyell noted in its Nov. 10 release.
The therapy, formerly known as GCC19CART and now called LYL273, targets cancers expressing the guanylyl cyclase-C (GCC) protein receptor. GCC is expressed on more than 95% of colorectal cancers and a majority of pancreatic adenocarcinomas, according to Lyell.
“We believe LYL273 has the potential to be a transformational advance in the treatment of colorectal cancer, an area of tremendous unmet need,” Lyell CEO Lynn Seely, M.D., said in a statement.
“We look forward to leveraging our expertise in T-cell biology and CAR T-cell clinical development to rapidly progress this program, as well as our two pivotal clinical trials evaluating ronde-cel for patients with relapsed or refractory large B-cell lymphoma,” Seely added.
To secure the rights to the asset outside of China, Hong Kong, Macau and Taiwan, Lyell is handing over $40 million upfront along with 1.9 million of its own shares. The company's shares closed Friday trading at $17.51, putting the value of the upfront equity in the transaction at about $33 million.
Further down the line, ICT is eligible for a $30 million clinical milestone payout, followed by $115 million and an additional 1.85 million Lyell shares upon hitting late-stage regulatory milestones.
Should LYL273 make it to market, ICT could also receive up to $675 million in commercial sales milestones as well as tiered royalties.
When it comes to safety, five of the six patients who received the higher dose experienced cytokine release syndrome—a common side effect of CAR-Ts—and diarrhea. One of the patients “experienced a dose-limiting toxicity," including grade 3 diarrhea, grade 4 inflammation of the intestine and then “death from fungal sepsis 48 days post-infusion,” Lyell noted.
Despite the fatality, Lyell emphasized that no grade 3 or higher diarrhea had occurred in the last three patients treated with the higher dose “since establishing an optimized management protocol for diarrhea, including prophylaxis.”
Lyell’s co-founder and board chairman Richard Klausner, M.D., said 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,” added Klausner, a former director of the National Cancer Institute.
Lyell further backed up its purchase with perspectives from the Dana-Farber Cancer Institute’s Benjamin L. Schlechter, M.D., who is lead investigator on the phase 1 study of LYL273.
“We rarely see such deep and durable responses in colorectal cancer patients treated with multiple prior lines of chemotherapy,” Schlechter said in the release. “Patients with metastatic colorectal cancer have a tremendous need for innovations like LYL273.”
LYL273 will be joining Lyell’s pipeline of next-gen CAR-Ts led by rondecabtagene autoleucel, an autologous dual-targeting CD19/CD20 therapy that recently began a phase 3 study for patients with aggressive large B-cell lymphoma.
In early trading Monday, the company's share price increased by about 4% to $18.19.