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 is now qualified for incentives such as 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 orphan drug designation,” Sandeep Gupta, PhD, CEO of Leukogene Therapeutics, said 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 high prevalence in AML cases (approximately 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 the FDA approval, various associated safety concerns were observed in clinical studies, particularly a higher incidence of grade 3 or higher hepatotoxicities. Consequently, the agent was withdrawn from the market in 2010 and reapproved in 2017 following dose adjustment, underscoring the need to develop safer and more effective immunotherapies.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 efficacy. The agent utilizes Leukogene Therapeutics’ proprietary M2T platform, consisting of a high-affinity MHC II 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 indicate that M2T-CD33 elicited encouraging responses and prolonged overall survival in vivo, with 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 into 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. FDA. 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):1506. 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. doi:10.1177/20406207231154708