Lyell takes on J&J and Gilead

Various companies are trying to improve Car-T efficacy by targeting both CD19 and CD20, and on Tuesday Lyell strengthened its bid here with updated results from a phase 1/2 trial of LYL314 in relapsed/refractory aggressive large B-cell lymphoma.

The data look in line with those reported recently by Johnson & Johnson and Gilead with similarly acting projects, with the usual caveats around cross-trial comparisons and small patient numbers. But Lyell reckons it’ll be able to compete with these bigger rivals, and has already sped into a pivotal study, Pinacle, in third-line disease.

Still, investors seemed cool on the data, with Lyell's share price down 2% on Tuesday.

Pinacle is in fact an extension of the phase 1/2 study, and will be uncontrolled, but Lyell believes this will be enough to gain FDA approval. When asked about the hurdle LYL314 will have to clear, the company’s chief executive, Lyn Seely, estimated an overall response rate of “better than 60-70%”.

She added that approved CD19 Car-Ts, like Bristol Myers Squibb’s Breyanzi and Gilead’s Yescarta, have produced ORRs of around 70% in the third line, and complete response rates of around 50%. It’s hoped that hitting CD20 as well as CD19 might avoid relapse by way of CD19 antigen escape.

Source: Company presentation.

Based on the data so far, the dual targeting Car-Ts seem to be doing better than the incumbents on efficacy, as well as showing lower rates of grade 3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS).

Lyell reported data on Tuesday from Car-T-naive patients in its trial, most of whom had received the recommended phase 2 dose of 100 million Car-T cells.

Among 25 third-line or later patients, LYL314 produced an ORR of 88% and a complete response rate of 72%. This looks similar to early data presented recently at EHA by J&J on its contender, JNJ-90014496.

Gilead’s KITE-363, meanwhile, produced an ORR of 100% in its phase 1 trial, presented at ASCO – however, this was only in seven patients. All had Car-T-naive, third-line or later LBCL and received the go-forward dose of two million Car-T cells.

Cross-trial comparison of CD19 x CD20 Car-Ts in Car-T naive r/r B-cell lymphoma

Note: *JNJ4496 data with RP2D of 75m Car-T cells; **KITE-363 data with RP2D of 2m Car-T cells. Source: Company releases, EHA & ASCO 2025.

Data also looked good in the second line. Here, Lyell is planning a pivotal randomised, controlled trial in second-line LBCL, slated to start by early 2026.

As for adverse events, LYL314 had no high-grade CRS, but ICANS rates look a little higher than its competitors.

When asked how Lyell planned to differentiate versus competition from J&J and Gilead, Seely replied: “We believe we’re in strong position with the data we’re putting up now.” One advantage, she said, is that Lyell has already taken LYL314 pivotal.

She added it was “gratifying” that the benefit of dual targeting has been confirmed by others, adding it was “very clear” where the field is now heading.

Lyell acquired LYL314, previously known as IMPT-314, last October via the takeover of ImmPACT Bio. J&J licensed JNJ-90014496 from AbelZeta in 2023; the project is already in a Chinese phase 2, Elevation. 

Meanwhile, KITE-363 came through Gilead’s acquisition of Kite. Gilead has previously said that KITE-363 is one of three projects is could take into pivotal trials, along with two fast manufactured Car-Ts: KITE-753, which also hits CD19 and CD20, and KITE-197, which targets CD19.