On January 9, 2025 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical-stage company advancing a pipeline of next-generation CAR T-cell therapies for patients with cancer, reported pipeline updates, including its plans to advance IMPT-314, a potentially best-in-class therapy for aggressive large B-cell lymphoma, into pivotal trials (Press release, Lyell Immunopharma, JAN 9, 2025, View Source [SID1234649542]). IMPT-314 is an autologous dual-targeting CD19/CD20 chimeric antigen receptor (CAR) T-cell product candidate designed to increase complete response rates and prolong the duration of the responses as compared to the approved CD19‑targeted CAR therapies for the treatment of large B-cell lymphoma.

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"Based on the positive initial clinical data reported at ASH (Free ASH Whitepaper) and the promising emerging clinical profile, we are accelerating the development of IMPT-314 as a potentially transformative product with differentiated benefit in overall and complete response rates as well as duration of response over first-generation CD19 CAR therapies in patients with aggressive large B-cell lymphoma," said Lynn Seely, M.D., Lyell’s President and Chief Executive Officer. "Having presented an initial dataset that demonstrated an overall response rate of 94% and a complete response rate of 71% in patients treated in the 3rd-line+ setting, we are focusing our resources on advancing IMPT-314 for patients with large B-cell lymphoma in both the 2nd and 3rd line+ settings. To ensure a sustainable cost structure that delivers multiple clinical readouts with our current balance sheet, we have streamlined and focused our pipeline and organization to prioritize investment in IMPT-314 and early-stage research programs for solid tumors."

Pipeline Focus

Lyell is focused on advancing next-generation CAR T cell therapies with the potential to deliver higher response rates and longer duration of responses for patients with hematologic malignancies and solid tumors. Lyell is developing products enhanced with its novel technologies and manufacturing protocols.

In hematologic malignancies, Lyell is focused on advancing products designed to deliver improved outcomes over first-generation CD19 CAR T cell therapies. Lyell’s lead program, IMPT-314, is a dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of the responses as compared to the currently approved CD19‑targeted CAR therapies for the treatment of large B-cell lymphoma. IMPT-314 is designed with a true ‘OR’ logic gate to target B-cells that express either CD19, CD20 or both and is manufactured through a process that enriches for CD62L-expressing cells to generate more naïve central memory CAR T cells with enhanced stemlike features and antitumor activity.

To realize the potential of cell therapy for solid tumors, Lyell is also developing next-generation CAR T-cell product candidates enhanced with anti-exhaustion and additional arming technologies, and manufactured with proprietary protocols. These approaches are designed to endow CAR T cells with attributes needed to drive durable tumor cytotoxicity and achieve consistent and long-lasting clinical responses – the ability to resist exhaustion, maintain qualities of durable stemness and function in the hostile tumor microenvironment.

Upcoming Milestones and Financial Outlook

For IMPT-314, a next-generation dual-targeting CD19/CD20 CAR T-cell product candidate for the treatment of large B-cell lymphoma:

Present data from the ongoing Phase 1-2 trial in mid-2025, including more mature data from the 3rd line+ cohort and initial data from the 2nd line cohort
Present more mature clinical data from the 2nd line cohort in late 2025
Initiate a pivotal trial in the 3rd line+ setting in mid-2025
Initiate a pivotal trial in the 2nd line setting by early 2026
For early-stage solid tumor programs:

Submit first IND application for a new solid tumor CAR T-cell product candidate in 2026
To accelerate the pivotal trials of IMPT-314 and focus resources on next-generation solid tumor CAR T-cell programs in preclinical development, Lyell has streamlined its operations and is discontinuing development of LYL119, its ROR1-targeting CAR T cell product candidate, and IMPT-514, an autoimmune disease program previously initiated by ImmPACT Bio that was acquired by Lyell in connection with its acquisition of ImmPACT Bio.

Lyell expects net cash use in 2025 to be $175 million – $185 million, which extends its cash runway further into 2027 through multiple clinical milestones.

J.P. Morgan Healthcare Conference

Members of Lyell’s senior management team will present and participate in the 43rd Annual J.P. Morgan Healthcare Conference on Wednesday, January 15th at 9:00 am PT.

A live webcast of the presentation can be accessed through the Investors section of the Company’s website at www.lyell.com. Following the live presentation, a replay of the webcast will be available on the Company’s website.

About IMPT-314

IMPT-314 is a next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of the responses as compared to the approved CD19‑targeted CAR therapies for the treatment of large B-cell lymphoma.

IMPT-314 is designed with a true ‘OR’ logic gate to target, with high potency, B cells that express either CD19, CD20 or both. IMPT-314 is manufactured to produce a CAR T-cell product with higher proportions of naïve and central memory T cells through a process that enriches for CD62L-expressing cells. This manufacturing process is designed to generate more naïve central memory CAR T cells with enhanced stemlike features and antitumor activity.

IMPT-314 has received Fast Track Designation from the U.S. Food and Drug Administration for the treatment of relapsed/refractory aggressive B-cell lymphoma.

Initial data from 23 patients with relapsed or refractory, CAR T-naive large B-cell lymphoma who received IMPT-314 were reported at the 2024 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The efficacy evaluable population consisted of 17 patients. The overall response rate was 94% (16/17 patients), with 71% (12/17 patients) achieving a complete response by three months. The median follow up was 6.3 months (range 1.2 – 12.5 months) and 71% of patients were in response at last follow-up. In the safety evaluable population of 23 patients, no Grade 3+ CRS was reported. Grade 3 ICANS was reported in 13% (3/23) of patients with a median time to complete ICANS resolution of 5 days, and rapid improvement to Grade 2 or lower with standard therapy.