Lyell Immunopharma (LYEL) Goldman Sachs’ RxChange Series: Framing Lyell’s next-generation lymphoma CAR-T data in 4Q summary

Ronde-cel clinical profile

• Third-line-plus data: 91% ORR, 77% CR; 75% of patients remained in CR at 12 months. Estimated 24-month PFS was 54%; median PFS was not reached.

• Second-line data: 95% ORR, 76% CR; 92% of patients remained in CR at six months, including a high share of primary-refractory patients.

• A clinician characterized third-line-plus response rates as above typical commercial CD19 CAR-T and bispecific results, while noting cross-trial comparison caveats.

• Third-line-plus data showed no high-grade CRS and a relatively low incidence of ICANS; the clinician viewed the safety profile as favorable and closer to liso-cel.

• CD19/CD20 targeting may address CD19-low or -negative tumors; CD20 is described as rarely dim or low in second- and third-line settings.

Development plans and timelines

• PiNACLE enrollment is completing, with the last patient expected to be treated by year-end 2026; full pivotal data are expected mid-2027 and BLA submission is planned by year-end 2027.

• PiNACLE is a single-arm, third-line-plus registrational trial with ORR as the primary endpoint; duration of response will also be considered.

• Phase III PiNACLE-H2H is a 400-patient randomized superiority trial comparing ronde-cel with investigator-selected axi-cel or liso-cel; primary endpoint is event-free survival.

• PiNACLE-H2H has 90% power, an interim analysis and a final analysis; recruitment is exceeding expectations, with about 60 largely U.S. centers planned for the eventual launch footprint.

• ASH presentations include a pivotal PiNACLE data update and a second-line cohort poster; the second-line abstract also examines primary-refractory patients.

Manufacturing and commercial opportunity

• The in-house center can produce more than 3,000 CAR-T doses annually at full capacity; commercial-process success in delivering product to patients is 98%, with median vein-to-ship time of 16 days.

• The estimated third-line-plus opportunity is 6,000–7,000 patients; claims analysis found 57% of large B-cell lymphoma patients had two prior chemotherapy regimens before cell collection.

• The approved CD19 CAR-T market was described as $3 billion today, with expected growth to $5 billion by 2030; the stated launch priority is switching patients from existing CD19 CAR-Ts.

• Commercial rationale includes efficacy, safety, manufacturing performance and treatment access for older patients; trial experience includes patients aged 85 and older.