Lyell Immunopharma, a clinical-stage biopharmaceutical company, is at the forefront of the cell therapy revolution, pioneering next-generation chimeric antigen receptor (CAR) T-cell therapies for patients with solid tumors and hematologic malignancies. With a focus on innovative science, strategic acquisitions, and a streamlined pipeline, Lyell is poised to make a significant impact in the oncology landscape.
Business Overview and History Lyell Immunopharma was founded in June 2018 with the mission of developing advanced cell therapies that can drive long-lasting clinical responses in cancer patients. The company's approach centers around leveraging its proprietary technology platforms to enhance the potency and durability of T-cell therapies. Since its inception, Lyell has focused on developing T-cell therapies, conducting research and development, acquiring technology and product candidates, entering into strategic collaborations, and establishing its manufacturing capabilities and intellectual property portfolio.
In 2019, Lyell entered into a collaboration agreement with GlaxoSmithKline (GSK) for potential T-cell therapies that apply the company's platform technologies. However, GSK terminated this agreement in December 2022 after concluding research activities on an undisclosed target. The following year, Lyell entered into a research and collaboration agreement with Stanford University, focused on the research and development of cellular immunotherapy products. As part of this agreement, the company granted Stanford rights to certain success payments based on increases in Lyell's stock price.
Lyell faced some early challenges in its research and development efforts. In 2021, the company filed for arbitration seeking to rescind an agreement with PACT Pharma related to the development of an anti-cancer T-cell therapy for solid tumors. This dispute was settled in 2022 with PACT issuing shares of its Series D convertible preferred stock to Lyell. Additionally, in 2023, the company recorded a $12.9 million impairment charge related to investments in other non-publicly traded companies, as it determined the fair values of these investments to be negligible. These impairments were due to factors such as the underlying companies' inability to raise additional funding and uncertain operating cash flow requirements.
Despite these early setbacks, Lyell continued to advance its pipeline of cell therapy product candidates. The acquisition of ImmPACT Bio in October 2024 was a transformative event for Lyell, as it strengthened the company's clinical pipeline and brought IMPT-314 into the fold. IMPT-314 is a next-generation CAR T-cell therapy designed to overcome the limitations of first-generation CD19-targeted therapies by targeting both CD19 and CD20 antigens on B cells. This dual-targeting approach is aimed at increasing complete response rates and prolonging the duration of response in patients with aggressive large B-cell lymphoma (LBCL).
Concurrent with the ImmPACT Bio acquisition, Lyell made the decision to discontinue the development of LYL797, LYL845, and its earlier-stage TIL programs. This streamlining of the pipeline allowed the company to focus its resources on the accelerated development of IMPT-314 and its next-generation solid tumor CAR T-cell programs, which are in the preclinical stage.
Financial Performance and Liquidity As of December 31, 2024, Lyell reported cash, cash equivalents, and marketable securities of $383.5 million, providing a strong financial foundation to support the company's development activities. This cash position is expected to fund operations into 2027, well beyond the anticipated initiation of pivotal trials for IMPT-314 in the 3rd line and 2nd line settings for the treatment of aggressive LBCL.
For the year ended December 31, 2024, Lyell reported a net loss of $343 million, or $1.31 per diluted share. This loss was primarily driven by the company's continued investment in research and development, as well as the $87.18 million in-process research and development (IPR&D) expense recognized in connection with the ImmPACT Bio acquisition. Lyell's research and development expenses for the year were $171.6 million, reflecting the company's commitment to advancing its pipeline of cell therapy candidates.
The company's financial performance in 2024 showed a significant increase in net loss compared to the previous year's $234.63 million. This increase was primarily due to the $87.18 million IPR&D expense related to the ImmPACT Bio acquisition and a $51.3 million impairment charge on long-lived assets. However, research and development expenses decreased from $182.94 million in 2023 to $171.6 million in 2024, primarily due to a $14.02 million reduction in personnel-related expenses. General and administrative expenses also decreased from $66.98 million in 2023 to $52.04 million in 2024, mainly due to a $13 million reduction in personnel costs.
In the most recent quarter (Q3 2024), Lyell reported revenue of $34,000 and a net loss of $44.58 million. The company's net cash use in 2025 is expected to be between $175 million and $185 million, as it concentrates its resources on the pivotal trials for IMPT-314 and its preclinical solid tumor CAR T-cell programs.
Lyell's liquidity position remains strong, with no debt and a debt-to-equity ratio of 0. The company's current ratio and quick ratio both stand at 13.43, indicating a robust ability to meet short-term obligations. This financial stability provides Lyell with the flexibility to pursue its strategic objectives and advance its pipeline without immediate funding concerns.
Clinical Pipeline and Upcoming Milestones Lyell's lead program, IMPT-314, is a dual-targeting CD19/CD20 CAR T-cell therapy that is currently in a Phase 1-2 clinical trial for the treatment of relapsed/refractory aggressive LBCL. In December 2024, the company presented positive initial data from this trial at the American Society of Hematology (ASH) Annual Meeting, highlighting an impressive objective response rate of 94% and a complete response rate of 71% in CAR T-cell naive patients who had received at least two prior lines of therapy.
The initial data for IMPT-314 demonstrated a manageable safety profile, with no instances of high-grade cytokine release syndrome (CRS) and low rates of Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS). These results are consistent with the clinical experience from the UCLA trial of CART19/20, a product candidate with the same CAR construct as IMPT-314 that has shown durable responses in a Phase 1 trial of patients with non-Hodgkin lymphoma.
Based on the promising initial data, Lyell is on track to initiate a pivotal trial for IMPT-314 in the 3rd line and later setting in mid-2025, with plans to initiate a pivotal trial in the 2nd line setting by early 2026. The company is also expected to present more mature data from the ongoing Phase 1-2 trial of IMPT-314 in the 3rd line setting and initial data in the 2nd line setting in mid-2025.
In addition to the advancement of IMPT-314, Lyell is developing a pipeline of next-generation CAR T-cell product candidates targeting solid tumors. The company plans to submit an Investigational New Drug (IND) application for its first fully-armed solid tumor CAR T-cell product candidate in 2026. These programs leverage Lyell's proprietary technologies, including anti-exhaustion approaches and novel enhancements designed to overcome the challenges of treating solid malignancies.
Industry Trends and Market Position The cell therapy industry, in which Lyell operates, has experienced rapid growth in recent years. Market research reports indicate a compound annual growth rate (CAGR) of approximately 29.5% from 2019 to 2024. This significant expansion reflects the increasing recognition of cell and gene therapies as promising approaches to treat various diseases, particularly cancer.
As a small-cap company primarily operating in the United States, Lyell is well-positioned to capitalize on this growing market. The company's focus on developing next-generation CAR T-cell therapies for both hematologic malignancies and solid tumors aligns with the industry's direction and addresses significant unmet medical needs.
Risks and Challenges As a clinical-stage biopharmaceutical company, Lyell faces a number of risks and challenges inherent to the development of novel cell therapies. These include the inherent uncertainties of the drug development process, the potential for unexpected safety or efficacy issues, and the substantial time and resources required to navigate the regulatory landscape.
Furthermore, the company's reliance on its proprietary technologies and the success of its pipeline candidates, particularly IMPT-314, poses significant risks. Any setbacks or delays in the development or commercialization of IMPT-314 could have a material adverse impact on Lyell's financial performance and future prospects.
The company also faces competition from other cell therapy developers, both in the hematologic malignancy and solid tumor settings. Maintaining a competitive edge through continued innovation and successful clinical execution will be crucial for Lyell's long-term success.
Lastly, Lyell's recent acquisition of ImmPACT Bio and the integration of IMPT-314 into its pipeline introduces additional operational and integration risks that the company will need to effectively manage.
Conclusion Lyell Immunopharma is a clinical-stage biopharmaceutical company that is transforming the landscape of cell therapy through its innovative pipeline of next-generation CAR T-cell therapies. The company's strategic focus on IMPT-314, a dual-targeting CD19/CD20 CAR T-cell product candidate, and its preclinical solid tumor programs, positions Lyell at the forefront of the cell therapy revolution.
With a strong financial foundation, a streamlined pipeline, and a team of renowned experts, Lyell is poised to make significant strides in the treatment of hematologic malignancies and solid tumors. The positive initial data for IMPT-314 and the company's plans to initiate pivotal trials in the coming years underscore Lyell's commitment to delivering transformative therapies to patients in need. As the company navigates the challenges inherent to cell therapy development, investors will closely follow Lyell's progress and its ability to capitalize on the vast potential of its innovative pipeline.