Cullinan Therapeutics (CGEM) investor relations material

Strategic milestones and program updates

• 2026 is projected as a defining year with major milestones for two high-priority T-cell engager programs: CLN-978 (CD19xCD3 for autoimmune diseases) and CLN-049 (FLT3xCD3 for AML).

• CLN-978 is positioned as a best-in-class molecule for autoimmune diseases, with high affinity for CD19 and subcutaneous administration; initial clinical data in SLE and RA expected in Q2 2026, multi-dose RA data in Q3, and Sjögren's data in Q4.

• CLN-049 showed compelling monotherapy efficacy in AML, received FDA Fast Track designation, and will move to pivotal studies after phase II dose selection this year; a frontline combination study with Venetoclax is planned.

• NDA submission for zipalertinib has been completed, and top-line data from Taiho’s frontline study are expected by year-end; Velinotamig data in autoimmune diseases is also anticipated in Q4.

• Over $430 million in cash reported at year-end, providing runway into 2029 to support ongoing and future programs.

Scientific rationale and competitive positioning

• Deep B-cell depletion via T-cell engagers can induce durable, treatment-free remission in autoimmune diseases, with CD19 offering broad B-cell targeting and sparing humoral memory.

• CD19 is favored over CD20 and BCMA for its broader expression and lower risk of compromising immune memory, reducing the need for immunoglobulin supplementation or revaccination.

• Early clinical data in B-cell NHL showed a complete response at the starting dose with favorable safety, supporting dose escalation in autoimmune trials.

• The competitive landscape includes CAR T, T-cell engagers, and monoclonal antibodies, with CLN-978 aiming to combine T-cell therapy potency with antibody convenience; Roche, Novartis, Merck, and GSK are also developing similar agents.

• Subcutaneous delivery and small molecular size are highlighted as differentiators, with the goal of outpatient administration, though self-administration remains unlikely due to safety monitoring needs.

Clinical development and trial design

• Current protocols require 48 hours of in-hospital monitoring for initial doses, with outpatient administration possible for subsequent doses; dose selection focuses on balancing efficacy and safety, particularly minimizing high-grade CRS and ICANS.

• Dose escalation in autoimmune studies is informed by prior oncology experience, aiming for rigorous, systematic development to accelerate later phases.

• Enrollment in lupus trials improved significantly after entry criteria changes, reducing screen failure rates by 50% and making up for previous delays.

• For CLN-978, at least nine SLE and seven RA patients will be included in the Q2 data presentation, with potential for more as dose escalation continues.