Novel FLT3/CD3 T-Cell Engager Earns Orphan Drug Designation in R/R AML

The FDA has granted orphan drug designation to the investigational T-cell engager CLN-049 as a treatment for patients with relapsed/refractory acute myeloid leukemia (AML), according to a press release from the developer, Cullinan Therapeutics, Inc.¹

Previously, the FDA granted fast track designation to CLN-049 as a therapeutic strategy for this patient population in December 2025.²

Developers designed CLN-049 to simultaneously target FLT3-expressing leukemia cells as well as CD3. The agent is intended to bind to both mutated and nonmutated forms of FLT3, thereby facilitating targeted action regardless of a patient’s mutational status.

Investigators are currently assessing the safety, tolerability, pharmacokinetics, pharmacodynamics, and early activity of CLN-049 among patients with relapsed/refractory AML or myelodysplastic syndrome (MDS) as part of a phase 1 study (NCT05143996). Preliminary data from the study were shared at the 2025 American Society of Hematology Annual Meeting and Exposition.³

With a data cutoff of June 9, 2025, antileukemic activity with CLN-049 was reported at a target dose of at least 6 µg/kg among 23 patients with AML, which included a complete response (CR) rate of 9% (n = 2 of 23). Additionally, the composite CR rate was 30% (n = 7 of 23) and the overall response rate (ORR) was 57% (n = 13 of 23).

Among patients who received the highest target dose of 12 µg/kg (n = 13), the composite CR rate was 31% (n = 4 of 13) and the ORR was 69% (n = 9 of 13). Investigators noted responses among patients with AML regardless of baseline genetic risk. Among 5 patients with TP53-mutated AML who received 12 µg/kg, investigators observed 4 responses.

Across the overall population, 95% of patients experienced any-grade treatment-emergent adverse effects (TEAEs), with the most common including cytokine release syndrome (40%), infusion-related reactions (35%), febrile neutropenia (17.5%), pneumonia (17.5%), stomatitis (17.5%), and white blood cell count decreases (17.5%). Grade 3 or higher TEAEs included febrile neutropenia (17.5%), white blood cell count decreases (17.5%), and pneumonia (12.5%).

“FDA orphan drug designation for CLN-049 emphasizes both the urgent need for new therapies for people living with relapsed or refractory [AML]—including patients with TP53-mutated AML who currently [have] a particularly poor prognosis—and the potential of this FLT3-directed T-cell engager to expand treatment options across the broadest population of [patients with] AML,” Jeffrey Jones, MD, MBA, chief medical officer at Cullinan Therapeutics, stated in the press release.¹ “Coupled with promising results from our ongoing phase 1 program, this designation by the FDA reinforces a shared goal to rapidly advance novel therapies for patients living with AML.”

Investigators of the first-in-human phase 1 trial are evaluating CLN-049 across 3 parts.⁴ Part A will assess intravenous CLN-049 at a single ascending dose. Additionally, investigators will evaluate multiple ascending doses of intravenous and subcutaneous CLN-049 in parts B and C of the trial, respectively.

The trial’s primary end points include the number of TEAEs, maximum drug concentration, and observed plasma concentration of a dosing interval. The immunogenicity of CLN-049 is a secondary end point.

Patients 18 years or older with a confirmed diagnosis of relapsed/refractory AML or MDS, an ECOG performance status of 0 to 2, and adequate laboratory values were eligible for enrollment in the trial. Having experienced previous progression or recurrence on or intolerance to approved therapies was another requirement for enrollment in the trial. Patients were ineligible for enrollment if they had a diagnosis of acute promyelocytic leukemia or active central nervous system leukemia.

References

1. Cullinan Therapeutics receives FDA orphan drug designation for CLN-049, a novel FLT3xCD3 T cell engager, in relapsed/refractory acute myeloid leukemia. News release. Cullinan Therapeutics Inc. May 19, 2026. Accessed May 20, 2026. https://tinyurl.com/3b2x8f3n
2. Cullinan Therapeutics receives FDA fast track designation for CLN-049, a novel FLT3xCD3 T cell engager, in relapsed/refractory acute myeloid leukemia. News release. Cullinan Therapeutics Inc. December 1, 2025. Accessed May 20, 2026. https://tinyurl.com/4t9mtw5a
3. Abdul-Hay M, Vale C, Chan O, et al. Preliminary anti-leukemia activity from a phase 1 study of CLN-049, a novel anti-FLT3 x anti-CD3 bispecific T-cell engager, in relapsed/refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Blood. 2025;146(suppl 1):768. doi:10.1182/blood-2025-768
4. CLN-049 in patients with relapsed/​refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). ClinicalTrials.gov. Updated January 16, 2026. Accessed May 20, 2026. https://tinyurl.com/3ktnd6yc