FDA Grants Orphan Drug Status to Novel CD33-Directed Immunotherapy for AML

The FDA has granted orphan drug designation to the acute myeloid leukemia (AML) treatment candidate M2T-CD33 (LTI-214), signaling a potential entrance for a novel, differentiated therapeutic approach to this aggressive disease.¹

FDA orphan drug designation is a recognition of novel treatments for rare conditions affecting fewer than 200,000 people in the US.² With this designation, Leukogene Therapeutics, the sponsor, is now qualified for incentives including tax credits, exemption from FDA user fees, and a potential 7 years of market exclusivity upon approval.

“We are honored that the FDA has recognized the therapeutic promise of [M2T-CD33] by granting [o]rphan [d]rug [d]esignation,” said Sandeep Gupta, PhD, CEO of Leukogene Therapeutics, in a news release.¹ “AML remains one of the most challenging hematologic cancers, and outcomes for relapsed or refractory patients remain poor. The [M2T-CD33] program embodies our commitment to advancing new immunotherapy approaches that are both potent and safer for patients. This designation represents an important step toward our goal of transforming the treatment paradigm for AML.”

A Next-Generation Approach to CD33 Targeting

The glycoprotein CD33 is an emerging target for immunotherapy in AML due to its widespread prevalence in AML cases (90%).³ One such CD33-targeted AML immunotherapy approved by the FDA is gemtuzumab ozogamicin (Mylotarg), an antibody-drug conjugate that links a CD33-targeted monoclonal antibody to the toxin calicheamicin.⁴ Following approval, various associated safety concerns were observed in clinical studies, particularly a higher incidence of grade ≥3 hepatotoxicities. Consequently, the agent was withdrawn from the market in 2010 for 7 years and re-approved in 2017 following dose adjustment, underscoring a need to develop safer and more effective immunotherapies.

M2T-CD33 is a myeloid-targeted treatment being developed in response to this need, with the objective of reducing toxicities while delivering in efficacy. The agent utilizes Leukogene Therapeutics’ proprietary M2T™ platform, consisting of a high affinity MHCII binding protein conjugated to tumor associated antigens.¹ The platform is designed to selectively eliminate CD33-positive leukemic blasts and stem cells by generating a potent T and B cell response against the selected antigen.

Preliminary preclinical data show that M2T-CD33 elicited encouraging responses and prolonged overall survival in vivo while having a favorable safety profile.³ Clinical development is imminent, with sponsors expecting to advance the agent to a first-in-human clinical trial in the coming months. Once initiated, this trial will provide deeper insights on the agent’s human-level performance in AML.

REFERENCES

1. U.S. FDA grants orphan drug designation to Leukogene Therapeutics’ M2T-CD33 (LTI-214) for the treatment of acute myeloid leukemia. News release. Business Wire. November 5, 2025. Accessed November 5, 2025. https://tinyurl.com/32js69yc

2. Designating an orphan product: drugs and biological products. US Food & Drug Administration. Updated August 12, 2024. Accessed November 5, 2025. https://tinyurl.com/5n77pu2w

3. Golick L, Robinson R, Reyes L, et al. An MHC class II targeted immunotherapy for CD33-positive pediatric acute myeloid leukemia [abstract]. J Immunother Cancer. 2023;11(Suppl 1): A1–A1731. doi:10.1136/jitc-2023-SITC2023.1352

4. Swaminathan M, Cortes JE. Update on the role of gemtuzumab-ozogamicin in the treatment of acute myeloid leukemia. Ther Adv Hematol. 2023;14:20406207231154708. Published 2023 Feb 9. doi:10.1177/20406207231154708