Lyell Immunopharma NASDAQ: LYEL President and CEO Lynn Seely outlined the company’s clinical development priorities, regulatory strategy and manufacturing plans during a Stifel investor session moderated by Stephen Willey, senior biotech analyst at Stifel.
Seely described Lyell as a cell therapy company focused on next-generation treatments for hematologic malignancies and solid tumors. She highlighted two lead clinical programs: ronde-cel, a CD19/CD20 CAR T-cell therapy being developed in large B-cell lymphoma, and LYL273, a GC-C-targeting CAR T-cell therapy for metastatic colorectal cancer.
Ronde-cel Designed to Target CD19 and CD20
Seely said ronde-cel was designed as a tandem CAR construct that can bind either CD19 or CD20 with “full potency.” She said the dual-targeting approach is intended to improve complete response rates and durability by addressing malignant B cells with low CD19 expression and reducing the likelihood of antigen escape.
She also pointed to Lyell’s manufacturing approach, which enriches the product for CD62L-positive cells. Seely characterized those cells as more naive, fit T cells that may persist longer, have more activity and contribute to a “softer safety profile.”
Discussing clinical data presented to date, Seely said Lyell has not seen any Grade 3 or higher cytokine release syndrome in the ronde-cel program. She said the neurotoxicity, or ICANS, rate has been in the single digits and below 5%.
In third-line or later large B-cell lymphoma, Seely said data presented at ASH showed a 93% overall response rate, a 76% complete response rate and median progression-free survival of 18 months. She compared those results with the labels of approved CD19 CAR T therapies Yescarta and Breyanzi, which she said show about a 70% overall response rate, a 50% complete response rate and median progression-free survival of six to seven months.
In second-line disease, Seely said Lyell studied a cohort that was “almost completely primary refractory” and reported an 83% overall response rate and a 61% complete response rate. She said those patients were particularly difficult to treat because they had not responded to frontline chemotherapy.
Pivotal Trial and Regulatory Strategy
Lyell is enrolling the single-arm PiNACLE trial in third-line or later disease. Seely said the company’s goal is to enroll about 120 patients and that it needs 100 treated patients to submit to the U.S. Food and Drug Administration. She said the pivotal data set is expected to include approximately 100 treated patients followed for at least six months after their first response.
Seely said Lyell expects to finish enrollment by the end of this year to remain on track for a mid-2027 pivotal data disclosure, followed by a planned biologics license application submission at the end of 2027. She said a significant data update in the second half of this year will include both more patients and longer follow-up from the ongoing trial.
On the regulatory outlook, Seely said Lyell’s interactions with the FDA to date suggest that full approval could be possible based on the third-line or later single-arm study. She added that accelerated approval would still be acceptable because it would allow the company to get on the market while using an ongoing randomized controlled trial to confirm the benefit.
Seely noted that Lyell is running a head-to-head randomized trial of ronde-cel versus investigator’s choice of Breyanzi or Yescarta. She said the trial is designed as a superiority study and described it as “real-world,” with no upper age limit, no requirement for CD19 or CD20 testing before enrollment, and allowance for bridging therapy.
Competitive Landscape
Seely said Lyell’s goal is to displace currently approved CD19 CAR T-cell therapies. She contrasted Lyell’s head-to-head trial design with earlier randomized trials for Breyanzi and Yescarta, which she said did not include patients over age 75. She also said Yescarta’s trial did not allow bridging therapy.
Asked about competing CD19/CD20 programs, Seely said Kite/Gilead is developing a different CD19/CD20 product that she described as about a year behind Lyell. She said Kite’s trial randomizes only to Yescarta as the comparator and does not allow bridging therapy, while Lyell allows investigators to choose either Yescarta or Breyanzi.
Seely also discussed Johnson & Johnson’s decision to discontinue its CD19/CD20 dual CAR T program. She said she could not know the company’s internal reasoning but viewed the discontinuation as positive for Lyell because it removes a significant competitor from the market.
LYL273 Update Expected in Colorectal Cancer
Seely also discussed LYL273, Lyell’s GC-C-targeting CAR T-cell therapy for metastatic colorectal cancer. She said GC-C is upregulated in more than 95% of metastatic colorectal cancers and described the product as a dual-targeting therapy that includes both a GC-C CAR and a separate CD19 CAR.
According to Seely, the CD19 CAR is engineered to release supportive cytokines after interacting with B cells following one day of lymphodepletion. She said this mechanism is designed to promote cell expansion and make the tumor microenvironment more favorable for CAR T-cell activity. Seely said Lyell has seen response rates across two dose levels in the 50% range.
Seely said Lyell expects an update on the LYL273 program in the first half of the year focused largely on safety. She noted that diarrhea has been a side effect and discussed one patient who developed significant colitis requiring immunosuppressive therapy and later died from an infection. Seely said an autopsy showed no evidence of disease. She said Lyell implemented a prophylactic regimen and safety management plan after that case and will update investors on subsequent patients treated under that plan. A fuller outcomes update is expected at a medical conference in the second half of the year.
Manufacturing and Cash Position
Seely said Lyell operates its own manufacturing facility and can manufacture more than 1,200 ronde-cel doses per year, which she said can support the company “well into launch.” She said Lyell is transferring in the GC-C CAR program and believes it can manufacture both ronde-cel and LYL273 within its facility for the time being.
On the balance sheet, Seely said Lyell reported $261 million in cash as of its first-quarter filing. She said that cash is expected to fund operations through the third quarter of next year and through upcoming catalysts, including pivotal data.
About Lyell Immunopharma NASDAQ: LYEL
Lyell Immunopharma is a clinical-stage biotechnology company focused on developing next-generation T cell therapies for cancer. Leveraging a proprietary platform that combines cell therapy, gene editing and molecular discovery, Lyell seeks to overcome key barriers in the treatment of solid tumors. The company's approach centers on engineering T cells to enhance their persistence, functionality and resistance to the immunosuppressive tumor microenvironment.
The company's pipeline includes multiple autologous T cell programs engineered to target tumor-associated antigens in solid malignancies such as melanoma, ovarian and pancreatic cancers.
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