Lyell Accelerates IMPT-314 CAR T-Cell Therapy for Large B-Cell Lymphoma
Key Insights
Lyell Immunopharma is prioritizing IMPT-314, a dual-targeting CD19 (search)/CD20 (search) CAR T-cell therapy, for aggressive large B-cell lymphoma (search), based on promising Phase 1-2 data.
Pivotal trials for IMPT-314 in 3rd line+ are expected to commence in 2025, with 2nd line trials anticipated to begin by early 2026, marking significant clinical milestones.
Lyell is streamlining its pipeline, discontinuing LYL119 development, to focus resources on IMPT-314 and next-generation CAR T-cell programs for solid tumors.
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 (search). 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 (search)/CD20 (search) 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 (search). 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 (search) 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 (search) 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 (search) 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.