FDA Grants Orphan Drug Status to Immunotherapy for Acute Myeloid Leukemia Treatment

The FDA has granted orphan drug designation to M2T-CD33 (LTI-214; Leukogene Therapeutics Inc.), a myeloid-targeted immunotherapy for the treatment of acute myeloid leukemia (AML).

“We are honored that the FDA has recognized the therapeutic promise of LTI-214 by granting orphan drug designation,” Sandeep Gupta, PhD, CEO of Leukogene, said in a news release.¹

What is Acute Myeloid Leukemia?

AML typically develops from immature myeloid cells that would normally become white blood cells; however, it can also occur from other myeloid cell types. The cancer commonly begins in the bone marrow, where new blood cells are made. In most cases, AML quickly moves from the bone marrow into the blood and could spread to other parts of the body, including the lymph nodes, liver, spleen, central nervous system, and testicles. The disease progresses quickly and needs immediate treatment, according to the American Cancer Society.²

AML is one of the most common types of leukemia in adults, with various subtypes classified based on the appearance of the leukemia cells compared to normal cells. The disease affects about 4 in 100,000 adults annually, and around 1160 children receive an AML diagnosis. Early on, AML symptoms could feel like a cold or influenza but later progress to more serious complications. In later stages, individuals could experience dizziness, easy bruising or bleeding, fatigue, feeling cold, fever, night sweats, headache, loss of appetite, shortness of breath, and weakness.³

The exact cause of AML is unknown, but risk factors include older age, being born male, smoking, being exposed to certain chemicals, being treated with certain chemotherapy drugs, being exposed to radiation, having certain blood disorders, having a family history of AML, and uncertain and unproven or controversial risk factors.⁴

Treatment for AML could involve chemotherapy, targeted therapy such as monoclonal antibodies, or allogeneic stem cell transplantation, with similar options for both adults and children.³

“AML remains one of the most challenging hematologic cancers, and outcomes for relapsed or refractory patients remain poor,” Gupta said.¹

Understanding the M2T Platform

The M2T platform is a novel MHCII-binding protein that activates antigen-presenting cells to drive strong immune responses. As a myeloid-targeted immunotherapy, its lead candidate, LTI-214, is designed to selectively eliminate CD33-positive leukemic blasts and leukemic stem cells that lead to disease progression in AML. It has shown potential anti-leukemic activity, reduced disease burden, extended survival, and a favorable safety profile in preclinical studies, with plans for clinical evaluation soon.¹

“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,” Gupta said.¹

The company’s second candidate, LTI-002, targets mesothelin. It is being developed for pancreatic, ovarian, and other solid tumors.¹

“This is an important step forward for Leukogene and the company’s Major Histocompatibility Complex Class II (MHCII) engager technology. The M2T platform is a completely new approach to cancer immunotherapy, and the endorsement from the FDA is a testament to its high impact potential,” Nathan Dolloff, PhD, founder and CSO of Leukogene, said in the news release.¹

REFERENCES

1. U.S. FDA Grants Orphan Drug Designation to Leukogene Therapeutics’ M2T-CD33 (LTI-214) for the Treatment of Acute Myeloid Leukemia. Leukogene Therapeutics Inc. News release. November 6, 2025. https://www.businesswire.com/news/home/20251105454890/en/U.S.-FDA-Grants-Orphan-Drug-Designation-to-Leukogene-Therapeutics-M2T-CD33-LTI-214-for-the-Treatment-of-Acute-Myeloid-Leukemia

2. American Cancer Society. What Is Acute Myeloid Leukemia (AML)? Updated March 4, 2025. Accessed November 6, 2025. https://www.cancer.org/cancer/types/acute-myeloid-leukemia/about/what-is-aml.html

3. Cleveland Clinic. Acute Myeloid Leukemia (AML). News release. Updated March 21, 2023. Accessed November 6, 2025. https://my.clevelandclinic.org/health/diseases/6212-acute-myeloid-leukemia-aml

4. American Cancer Society. Risk Factors for Acute Myeloid Leukemia (AML). Updated March 4, 2025. Accessed November 6, 2025. https://www.cancer.org/cancer/types/acute-myeloid-leukemia/causes-risks-prevention/risk-factors.html