FDA Grants Fast Track Designation to LYT-200 in Recurrent/Metastatic HNSCC


The galectin-9–targeted monoclonal antibody LYT-200 received FDA fast track designation for recurrent/metastatic head and neck squamous cell cancer.



The FDA has granted fast track designation to the IgG4 monoclonal antibody LYT-200 in combination with a PD-1 inhibitor for the treatment of patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC), according to an announcement from PureTech Health.1

“By granting fast track designation to LYT-200 for HNSCC, the FDA continues to highlight areas of critical need within oncology as well as the potential for LYT-200,” Aleksandra Filipovic, MD, PhD, head of Oncology at PureTech, stated in the press release. “As galectin-9’s role in suppressing immune-mediated activity has been well-validated, it represents an important area of clinical research, especially in aggressive cancers with increased mortality.”

LYT-200 is a fully human monoclonal antibody designed to target the potent oncogenic driver and immunosuppressor galectin-9. Galectin-9 has been implicated in disease progression in acute myeloid leukemia (AML) by interacting with cytotoxic CD8 T-cells and natural killer cells. Extensive preclinical research has underscored the significance of galectin-9 as a therapeutic target for biomarker development. Notably, galectin-9 exhibits high expression across various blood cancers and solid tumor types, correlating with poor survival outcomes.

Preclinical models have shown direct cytotoxic and anti-leukemic effects with LYT-200 through multiple mechanisms, as well as synergy with standard-of-care chemotherapy and venetoclax (Venclexta).

In addition to its ongoing development in hematologic malignancies such as AML and high-risk myelodysplastic syndrome (MDS), LYT-200 has potential applications for the management of other locally advanced or metastatic solid tumors characterized by poor survival rates, including head and neck cancers.

“In the United States, there are approximately 66,000 people diagnosed with head and neck cancers each year, and the prognosis for metastatic disease is unfavorable, with a median survival rate of about ten months,” Eric Sherman, MD, head and neck oncologist at Memorial Sloan Kettering Cancer Center in New York, New York, and an investigator in PureTech’s phase 1/2 clinical trial of LYT-200, added in the press release. “There is an important need to explore promising new mechanisms and targets such as galectin-9 to bring therapeutic innovation to this patient population.”

LYT-200 is currently being evaluated in 2 ongoing, early-phase clinical trials.

A phase 1/2 trial (NCT04666688) is investigating the efficacy and safety of LYT-200 as a monotherapy and in combination with tislelizumab-jsgr (Tevimbra) in advanced, metastatic solid tumors. Initial data from this trial were presented at the 2023 ESMO Immuno-Oncology Congress and demonstrated a favorable safety/tolerability profile and disease control for LYT-200 across both the monotherapy and combination cohorts.2 Moreover, preliminary antitumor activity was reported in patients with relapsed/refractory HNSCC.

Additionally, a phase 1 trial (NCT05829226) is evaluating LYT-200 both alone and in combination with venetoclax and hypomethylating agents in patients with hematological malignancies, including AML and high-risk MDS.1 In this study, LYT-200 demonstrated favorable safety and tolerability alongside early signals of clinical activity.

The trial is enrolling adult patients with an ECOG performance status of 2 or less.3 Patients with AML must have primary or secondary relapsed/refractory disease after 1 or more prior lines of therapy and have no available standard therapies. Those who underwent prior allogeneic stem cell transplant are allowed to enroll onto the study, but this is not required. Patients with high-risk MDS also must have relapsed/refractory disease after exposure to 1 or more lines of therapy per the revised International Prognostic Scoring System, and no available standard treatments.

In the dose-escalation portion, patients will receive intravenous LYT-200 alone or in combination with venetoclax and/or azacitidine or decitabine. In the combination arm, patients were also treated with 100 mg of venetoclax 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.

The coprimary end points are safety and dose-limiting toxicities. Secondary end points include pharmacokinetics, disease response rates, time-to-event end points, and hematological improvements.

In March 2024, LYT-200 was granted orphan drug designation (ODD) by the FDA for the treatment of patients with acute myeloid leukemia (AML).4 The agent also received ODD from the FDA for use as a potential therapeutic option for patients with pancreatic cancer in November, 2021.5


  1. PureTech receives FDA fast track designation for LYT-200 in head and neck cancers. News release. PureTech Health. April 11, 2024. Accessed April 11, 2024. https://news.puretechhealth.com/news-releases/news-release-details/puretech-receives-fda-fast-track-designation-lyt-200-head-and
  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 April 11, 2024. https://clinicaltrials.gov/study/NCT05829226
  4. PureTech receives orphan drug designation for LYT-200 in acute myeloid leukemia. News release. PureTech Health. March 13, 2024. Accessed April 11, 2024. https://news.puretechhealth.com/news-releases/news-release-details/puretech-receives-orphan-drug-designation-lyt-200-acute-myeloid
  5. PureTech receives orphan drug designation for wholly owned candidate LYT-200 for the treatment of pancreatic cancer. News release. PureTech Health. November 11, 2021. Accessed November 11, 2021. https://investors.puretechhealth.com/news-releases/news-release-details/puretech-receives-orphan-drug-designation-wholly-owned-candidate
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