CLN-049 Gains FDA Orphan Drug Designation in R/R AML

CLN-049, a novel investigational FLT3xCD3 T cell engager, has earned orphan drug designation from the FDA for the treatment of relapsed or refractory acute myeloid leukemia (R/R AML).¹

The FDA’s orphan drug designation program is intended for therapies targeting rare diseases affecting fewer than 200,000 individuals in the United States. The designation provides several potential development incentives, including tax credits for qualified clinical trials, waiver of certain FDA user fees, and the potential for 7 years of market exclusivity following approval.

“FDA [o]rphan [d]rug [d]esignation for CLN-049 emphasizes both the urgent need for new therapies for people living with [R/R AML]—including patients with TP53-mutated AML who currently face 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,” said Jeffrey Jones, MD, MBA, chief medical officer of Cullinan Therapeutics, in a news release.¹ “Coupled with promising results from our ongoing [p]hase 1 program [NCT05143996], this designation by the FDA reinforces a shared goal to rapidly advance novel therapies for patients living with AML.”

In December 2025, the FDA also awarded fast track designation to CLN-049 in the same indication.

About CLN-049 and the Unmet Need in AML

AML remains an area of substantial unmet need, particularly in the R/R setting. Despite advances in targeted therapies and combination regimens, outcomes remain poor for many patients, especially those with adverse-risk molecular features such as TP53 mutations.

Interest in T-cell engager approaches in AML has thus increased as a potential immunotherapeutic strategy to overcome resistance to standard therapies. CLN-049 is designed to target FLT3-expressing leukemia cells by simultaneously binding FLT3 on malignant cells and CD3 on T cells. Unlike therapies directed at a narrow genomic subset, CLN-049’s ability to bind both mutated and nonmutated FLT3 may support broader applicability across AML populations if clinical benefit is confirmed in later-stage development.

Clinical Development Status of CLN-049

CLN-049 is being evaluated in an ongoing phase 1, open-label, multicenter dose-escalation study in patients with relapsed/refractory AML or myelodysplastic syndrome (MDS).² The first-in-human study, which is currently recruiting patients across 11 US sites, is evaluating intravenous CLN-049 across multiple ascending-dose cohorts. Investigators are assessing safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy.

The agent is also under investigation in a parallel phase 1 study in Europe among patients with AML who have measurable residual disease (EUCT 2023-506572-27-00).

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. May 19, 2026. Accessed May 19, 2026. https://tinyurl.com/3z3p79sw

2. CLN-049 in patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). ClinicalTrials.gov. Updated January 16, 2026. Accessed May 19, 2026. https://clinicaltrials.gov/study/NCT05143996