Novel T-Cell Engager CLN-049 Earns FDA Fast Track Status for R/R AML

CLN-049, a novel FLT3/CD3 bispecific T-cell engager, has received fast track designation from the FDA for the treatment of relapsed or refractory (R/R) acute myeloid leukemia (AML).¹

FDA’s fast track program is intended to accelerate the development and regulatory review of novel agents that seek to address serious unmet medical needs.² The designation of CLN-049 paves the way for a new immunotherapy option that can reach a broad population of patients with R/R AML and myelodysplastic syndrome (MDS) regardless of FLT3 mutational status.

“Fast [t]rack designation underscores both the urgent need for new options in [R/R AML] and the promise of CLN-049,” said Jeffrey Jones, MD, MBA, chief medical officer of Cullinan Therapeutics, in a news release.¹ “Initial results from our [p]hase 1 study [NCT05143996] have shown meaningful efficacy, including complete responses, reinforcing the broad potential of this FLT3-directed T-cell engager in a population where effective treatment options are currently limited and fragmented. This regulatory milestone provides important momentum for development, and we look forward to collaborating closely with the FDA to rapidly advance CLN-049 for patients who desperately need more effective therapies.”

Ongoing Development of CLN-049

The safety, pharmacokinetics, and preliminary efficacy of CLN-049 in AML and MDS is currently under clinical investigation in a first-in-human phase 1 study taking place across several US centers.³ The study is recruiting and aims to enroll a total of 60 adult patients.

Here, dose escalation will be conducted in various cohorts, beginning with a cohort receiving CLN-049 via subcutaneous (SC) injection, followed by 2 cohorts receiving CLN-049 via intravenous (IV) administration. For SC injection, patients will receive CLN-049 every 7 days. For IV administration, patients in the single ascending dose cohort will receive a single dose of CLN-049, while patients in the multiple ascending dose cohort will receive CLN-049 every 7 days. All patients will be followed for safety for 28 days and will subsequently enter a long-term follow-up period for up to 2 years.

The primary end points of the study are the number of treatment-emergent adverse events and pharmacokinetic measures, while the secondary end point is immunogenicity of CLN-049. Data from this trial will be presented at the upcoming American Society of Hematology (ASH) Annual Meeting.

Parallel to this trial, another phase 1 dose-escalation and dose-expansion study (EUCT 2023-506572-27-00) is investigating CLN-049 in adult patients with AML with measurable residual disease.⁴ This study has enrolled patients across centers in Germany and Spain.

REFERENCES

1. 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. December 1, 2025. Accessed December 1, 2025. https://tinyurl.com/2wm46bw4

2. Fast track. US Food & Drug Administration. Updated August 13, 2024. Accessed December 1, 2025. https://tinyurl.com/ms2695jn

3. CLN-049 in patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). ClinicalTrials.gov. Updated November 25, 2025. Accessed December 1, 2025. https://clinicaltrials.gov/study/NCT05143996

4. Heitmann JS, Walz JS, Salih HR, et al. A phase 1, open-label, dose escalation and dose expansion study of CLN-049 for the treatment of acute myeloid leukemia patients with measurable residual disease. Blood. 2024;144(Supplement 1):2883.1-2883.1. doi:10.1182/blood-2024-201478