Lyell Immunopharma is set to advance its next-generation CAR T-cell therapy pipeline, with a focus on IMPT-314 for aggressive large B-cell lymphoma. The company plans to initiate pivotal trials for IMPT-314 in the 3rd line+ setting in 2025 and in the 2nd line setting by early 2026.
IMPT-314: A Dual-Targeting CAR T-Cell Therapy
IMPT-314 is an autologous, dual-targeting CD19/CD20 CAR T-cell product candidate engineered to improve complete response rates and prolong the duration of responses compared to existing CD19-targeted CAR therapies for large B-cell lymphoma. The therapy utilizes a true 'OR' logic gate to target B-cells expressing either CD19, CD20, or both, and is manufactured to enrich for CD62L-expressing cells, generating more naïve central memory CAR T cells with enhanced stem-like features and antitumor activity.
Clinical Data and Development Strategy
Initial clinical data presented at ASH demonstrated an overall response rate of 94% and a complete response rate of 71% in patients treated with IMPT-314 in the 3rd-line+ setting. Lyell is now concentrating its resources on advancing IMPT-314 for patients with large B-cell lymphoma in both the 2nd and 3rd line+ settings.
According to Lynn Seely, M.D., President and Chief Executive Officer of Lyell, the company is accelerating the development of IMPT-314 based on positive initial clinical data and its promising clinical profile, aiming for a differentiated benefit in overall and complete response rates, as well as duration of response, compared to first-generation CD19 CAR therapies.
Pipeline Prioritization and Financial Outlook
To support the pivotal trials of IMPT-314 and focus on next-generation solid tumor CAR T-cell programs in preclinical development, Lyell is discontinuing the development of LYL119, a ROR1-targeting CAR T-cell product candidate for solid tumors. The company expects net cash use of $175 million - $185 million for 2025, extending its cash runway further into 2027 through multiple clinical milestones.
Upcoming Milestones
Lyell anticipates the following milestones for IMPT-314:
- Presenting data from the ongoing Phase 1-2 trial in mid-2025, including mature data from the 3rd line+ cohort and initial data from the 2nd line cohort.
- Presenting more mature clinical data from the 2nd line cohort in late 2025.
- Initiating a pivotal trial in the 3rd line+ setting in mid-2025.
- Initiating a pivotal trial in the 2nd line setting by early 2026.
For its early-stage solid tumor programs, Lyell plans to submit its first IND application for a new solid tumor CAR T-cell product candidate in 2026.
About Large B-Cell Lymphoma
Large B-cell lymphoma is an aggressive form of non-Hodgkin lymphoma that affects B-cells, a type of white blood cell responsible for producing antibodies. It is one of the most common types of lymphoma, accounting for a significant proportion of non-Hodgkin lymphoma cases worldwide. Current treatment options include chemotherapy, radiation therapy, and stem cell transplantation, but there remains a need for more effective and durable therapies, especially for patients who relapse or are refractory to initial treatments.
