Cullinan Therapeutics (NASDAQ:CGEM) outlined a milestone-heavy roadmap during a presentation at Leerink Partners’ Annual Healthcare Conference in Miami, with management emphasizing 2026 as a potentially “defining year” driven by multiple clinical readouts across its pipeline. Chief Executive Officer Nadim and Chief Medical Officer Jeff highlighted two “high-priority” T-cell engager (TCE) programs—CLN-978 in autoimmune diseases and CLN-049 in acute myeloid leukemia (AML)—alongside updates on other assets and the company’s cash position.
Management points to 2026 catalysts led by two T-cell engagers
Nadim said Cullinan expects “so many milestones across our programs” in 2026, particularly for:
- CLN-978, a CD19xCD3 T-cell engager being developed for autoimmune diseases.
- CLN-049, a FLT3xCD3 bispecific T-cell engager for AML.
CLN-978: Autoimmune strategy focused on deep B-cell depletion
Discussing CLN-978, management described the molecule as potentially “best in class” and “highly differentiated” among CD19 T-cell engagers, citing high-affinity binding to CD19, small molecular size that could aid tissue penetration, and subcutaneous administration.
Jeff framed the therapeutic hypothesis around “deep B-cell depletion” leading to an “immune reset” and, in some cases, “treatment-free remission” in autoimmune diseases. He said emerging data over the last two years suggest T-cell engagers targeting B-cell antigens—CD20, CD19, and BCMA—can reach similar depths of B-cell depletion as cell therapies. He argued CD19 may offer advantages by broadly depleting B cells while sparing long-lived plasma cells in certain disease settings, which could preserve humoral memory and reduce the need for immunoglobulin supplementation and revaccination.
On timing, Nadim said Cullinan plans to present the first company-sponsored data for a CD19 T-cell engager in autoimmune diseases during 2026, with specific milestones laid out as:
- Q2 2026: initial clinical data from systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA)
- Q3 2026: initial multi-dose data from RA
- Q4 2026: initial data from the Sjögren’s disease study
Early clinical and operational details for CLN-978
Jeff referenced a prior first-in-human study in B-cell non-Hodgkin’s lymphoma in which three patients were treated. At a 30-microgram starting dose, he said one patient with refractory mantle cell lymphoma achieved a complete response, and no patients experienced worse than Grade 1 cytokine release syndrome (CRS). He also noted that in two of three patients with measurable baseline B cells, there was “greater than 95% reduction” in peripheral blood B cells after a single 30-microgram dose.
Those observations are informing the autoimmune dosing strategy. Jeff said the autoimmune program is starting at 10 micrograms, with step-up dosing to mitigate CRS risk, and the company plans to escalate to at least 30 micrograms. On expected Q2 data sets, he said Cullinan anticipated completing safety evaluation at the 30-microgram target dose level in both SLE and RA before the Q2 presentation, implying “a minimum of nine patients” in SLE and “seven patients” in RA, with potential for additional patients through dose escalation and backfilling.
He also described a protocol requirement of 48 hours of in-hospital monitoring after a step-up dose and the first target dose, with subsequent repeat doses administered outpatient. While outpatient administration was described as a goal, both speakers said self-administration at home would require “remarkable safety,” particularly given ongoing expectations of some CRS risk.
On enrollment, Jeff said modifications to lupus trial entry criteria increased the screening pool and reduced screen failure rates by about 50% compared with the second half of the prior year, helping the company “make up for lost time.”
CLN-049: ASH data and a path toward pivotal development in AML
Turning to oncology, Cullinan highlighted CLN-049, which Jeff described as a first-in-class immunotherapeutic approach for a broad AML population. He said the company presented dose-escalation results in 45 patients at ASH, showing “favorable safety” and “compelling efficacy.” At doses of six micrograms and above, he said there was a consistent likelihood of complete responses. At a target dose of 12 micrograms per kilogram, he reported a 31% composite complete response rate (CR plus CRh), which he said compares favorably with therapies approved in relapsed/refractory AML over the last decade.
Jeff emphasized that using FLT3’s extracellular domain as an immunotherapy target could enable treatment of both wild-type and FLT3-mutated AML, describing an “80+% addressable patient population.” He said CRS occurred in 35% overall, all grades, with one Grade 3 CRS case in a patient who received only one step-up dose, and that using two step-up doses improved the safety profile while maintaining efficacy.
Management also highlighted activity in TP53-mutated AML, with Nadim noting responses appeared comparable between TP53-mutated and non-mutated patients. Jeff added that previously untreated TP53-mutated AML could be included in initial expansion plans given the high medical need.
On regulatory progress, Nadim said the FDA granted Fast Track designation shortly before ASH. He said the company plans to select a recommended Phase II dose this year and then move into a pivotal study in relapsed/refractory AML. In parallel, Cullinan plans to initiate a Phase I/II frontline combination study with venetoclax by the end of the year. Jeff said updated dose-escalation data and longer follow-up, including durability in responders, are planned for presentation in the second half of the year.
Other pipeline updates: zipalertinib NDA and additional data timelines
Nadim noted that Cullinan announced it had completed an NDA submission for zipalertinib, describing it as a milestone in getting the company’s “first NDA under our belt.” He also said partner Taiho has guided to completing recruitment in a frontline study and expects top-line data by the end of the year. Additionally, he said the company has guided to data in Q4 for velinotamig, described as a BCMA x CD3 program in autoimmune diseases.
About Cullinan Therapeutics (NASDAQ:CGEM)
Cullinan Therapeutics, Inc, a biopharmaceutical company, focuses on developing oncology therapies for cancer patients in the United States. The company's lead program comprises CLN-619, a monoclonal antibody that is in Phase I clinical trial for the treatment of solid tumors. Its development portfolio also includes CLN-049, a humanized bispecific antibody that is in Phase I clinical trial for the treatment of acute myeloid leukemia or myelodysplastic syndrome; CLN-418, a human bispecific immune activator that is in Phase 1 clinical trial for the treatment of multiple solid tumors; and Zipalertinib, a bioavailable small-molecule for treating patients with non-small cell lung cancer.
