Novel Monoclonal Antibody Wins FDA Fast Track Designation in High-Risk MDS

The FDA has granted fast track designation to LYT-200 in combination with a hypomethylating agent (HMA) for the treatment of patients with relapsed/refractory high-risk myelodysplastic syndromes (HR-MDS), according to a news release from the developer, PureTech Health.¹ The designation followed a successful end-of-phase 1 (EOP1) meeting with the FDA that supports advancing the first-in-class, anti–galectin-9 monoclonal antibody into the planned phase 2 STRIDE-MDS trial.

What supported the fast track designation and end-of-phase 1 meeting?

The EOP1 meeting was supported by positive topline data from the completed phase 1b trial (NCT05829226) evaluating LYT-200 in combination with azacitidine (Vidaza) or decitabine (Dacogen) in heavily pretreated patients with HR-MDS, all of whom had relapsed or become refractory to prior HMA treatment.² Among efficacy-evaluable patients treated with LYT-200 at 12 mg/kg plus an HMA (n = 11), the combination produced a complete response rate of 27.3%, a partial response rate of 9.1%, a marrow complete response rate of 9.1%, and an overall response rate of 45.5%, with an 18% conversion-to-transplant rate. No dose-limiting toxicities or myeloid suppression were reported.

The efficacy-evaluable patients had received a median of 3 prior lines of therapy (range, 1-5) and all had high-risk cytogenetics. The median overall survival (OS) of 6.4 months was not considered fully mature, as more than 50% of patients were alive at study completion. Across the overall phase 1b trial (n = 101), which was conducted at 9 US sites, LYT-200 demonstrated a favorable and consistent safety profile with no dose-limiting toxicities, infusion-related reactions, or treatment-related serious adverse events, discontinuations, or deaths.

What is the design of the planned phase 2 STRIDE-MDS trial?

The STRIDE-MDS study will be a randomized, double-blind, placebo-controlled phase 2 trial enrolling approximately 125 patients with relapsed/refractory HR-MDS. Patients will be randomly assigned 2:2:1 to receive LYT-200 at 12 mg/kg plus an HMA, LYT-200 at 7.5 mg/kg plus an HMA, or placebo plus an HMA. The trial will assess the efficacy of LYT-200 as measured by the rate of complete and partial responses to support dose selection, with the inclusion of 2 doses intended to fulfill dose-selection requirements in accordance with the FDA’s Project Optimus.

“Patients with higher-risk MDS who relapse or become refractory to HMA treatment have very limited therapeutic options and poor outcomes...the clinical activity observed with LYT-200 in combination with an HMA in the phase 1b study is particularly encouraging,” Amer Zeidan, MBBS, MHS, professor of medicine at Yale University and chief of the Division of Hematologic Malignancies at Yale Cancer Center, who will serve as global principal investigator, said in the news release.¹ “STRIDE-MDS will allow us to further evaluate this activity in a randomized, placebo-controlled study.”

What is LYT-200, and how does it work?

LYT-200 is a first-in-class, fully human monoclonal antibody that targets galectin-9, an oncogenic driver and potent immunosuppressor whose elevated expression in HR-MDS is associated with shorter survival. Through a mutation-agnostic, dual mechanism of action, the antibody is designed to address both malignant cells and the immunosuppressive environment that sustains disease, which the developer says gives it the potential to benefit a broad range of patients regardless of a specific genetic mutation. LYT-200 has also been granted fast track designation for the treatment of acute myeloid leukemia.

What is the unmet need in relapsed/refractory high-risk MDS?

HMAs such as azacitidine and decitabine are the current standard frontline treatments for HR-MDS, but most patients do not respond or eventually stop benefiting from them. Additionally, outcomes in the relapsed/refractory setting are especially poor, with survival often limited to a few months. According to the press release, the only approved therapy for those with relapsed/refractory HR-MDS targets a genetic mutation found in approximately 3% of patients, leaving a significant unmet need for the majority of patients. HR-MDS is associated with a median OS of typically less than 2 years following diagnosis.

References

1. PureTech announces successful end-of-phase 1 meeting with US Food and Drug Administration (FDA) and receipt of fast track designation for LYT-200 in relapsed/refractory (R/R) high-risk myelodysplastic syndromes (HR-MDS). News release. PureTech Health plc. September 21, 2026. Accessed September 22, 2026. https://tinyurl.com/4hrwyy37
2. PureTech reports positive topline data from phase 1b trial of LYT-200 in relapsed/refractory (R/R) high-risk (HR) myelodysplastic syndrome (MDS) and R/R acute myeloid leukemia (AML). News release. PureTech Health plc. April 22, 2026. Accessed September 22, 2026. https://tinyurl.com/5ff3bysa