FDA Grants Orphan Drug Designation to LYT-200 in AML


The FDA has granted orphan drug designation to LYT-200 for the treatment of acute myeloid leukemia.



The FDA has granted orphan drug designation to LYT-200 for the treatment of patients with acute myeloid leukemia (AML).1

LYT-200 is a fully human IgG4 monoclonal antibody that targets galectin-9, which is a potent oncogenic driver in leukemia cells and an immunosuppressive protein. The agent is currently under investigation in a phase 1 trial (NCT04666688) in patients with relapsed/refractory, locally advanced or metastatic solid tumors, as well as a phase 1 trial (NCT05829226) in patients with relapsed/refractory AML or high-risk myelodysplastic syndrome (MDS).

Initial data from the phase 1 study investigating the agent alone and in combination with tislelizumab (BGB-A317) in patients with solid tumors were presented at the 2023 ESMO Immuno-Oncology Congress and showed that LYT-200 demonstrated an acceptable safety/tolerability profile, both as monotherapy and in combination with the anti–PD-1 antibody. Preliminary antitumor activity was also observed in patients with relapsed/refractory head and neck cancer.2

"Orphan drug designation from the FDA validates our belief that targeting galectin-9 with LYT-200 is a novel, promising approach that may offer patients a better tolerated, more effective treatment," Aleksandra Filipovic, MD, PhD, head of oncology at PureTech Health, stated in a press release.

The phase 1 study evaluating LYT-200 in patients with relapsed/refractory AML or high-risk MDS is enrolling patients at least 18 years of age who have an ECOG performance status of 2 or less. Patients with AML are required to have primary or secondary disease that is relapsed/refractory to at least 1 prior line of therapy and for whom no standard therapy is available. Prior allogeneic stem cell transplant is permitted but not required.3

Those with high-risk MDS must have relapsed/refractory disease following at least 1 line of treatment per the revised International Prognostic Scoring System and have no available standard treatment.

Key exclusion criteria include acute promyelocytic leukemia; active malignant tumors other than AML/MDS; hematopoietic stem cell transplant (HSCT) within 6 months of first study dose; grade 2 or higher, persistent, non-hematological toxicity related to HSCT donor lymphocytes infusion; active graft vs host disease (GVHD) and patients receiving immunosuppressive treatment for GVHD; and symptomatic central nervous system (CNS) involvement of leukemia or other CNS diseases related to the underlying and secondary effects of the malignancy.

In the dose-escalation study, patients are receiving LYT-200 alone or in combination with venetoclax (Venclexta) and/or azacitidine or decitabine. In both arms, LYT-200 is being administered as an intravenous infusion over 60 minutes once per week. In the combination arm, patients are also receiving venetoclax at 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3 to 28 of each cycle, and/or 75 mg/m2 of subcutaneous azacitidine for 7 days per cycle or 20 mg/m2 of decitabine for 5 days per cycle.

Safety and dose-limiting toxicities are the primary end points of the study. Secondary end points include pharmacokinetics and rates of disease responses, time-to-event end points, and hematological improvements.

"The current long-term survival rates of patients with relapsed/refractory AML are very poor, and there remains a tremendous unmet need for more effective therapies," Amir Fathi, MD, director of the Leukemia Program at Massachusetts General Hospital in Boston and lead investigator of the trial, added in a news release.1


  1. PureTech receives orphan drug designation for LYT-200 in acute myeloid leukemia. News release. PureTech Health. March 13, 2024. Accessed March 13, 2024. https://news.puretechhealth.com/news-releases/news-release-details/puretech-receives-orphan-drug-designation-lyt-200-acute-myeloid
  2. Falchook GS, Papadopoulos K, Parikh A, et al. A phase I dose escalation and expansion trial of LYT-200, a Galectin-9 antibody +/- tislelizumab. Ann Oncol. 2023;20(suppl 1):100589. doi:10.1016/iotech/iotech100589
  3. A phase 1 study with LYT-200 in patients with relapsed/​refractory acute myeloid leukemia (AML), or with relapsed/​refractory, high-risk myelodysplastic syndrome (MDS). ClinicalTrials.gov. Updated January 11, 2024. Accessed March 13, 2024. https://clinicaltrials.gov/study/NCT05829226
Related Videos
Catherine C. Coombs, MD, associate clinical professor, medicine, University of California, Irvine School of Medicine
Alessandra Ferrajoli, MD
Dipti Patel-Donnelly, MD, Johns Hopkins
Jasmin M. Zain, MD
Andrew Ip, MD
Sagar S. Patel, MD