FDA Grants Fast Track Status to LYT-200 Combo in High-Risk MDS

The FDA has granted fast track designation to LYT-200, a galectin-9–targeting monoclonal antibody, in combination with a hypomethylating agent (HMA) for relapsed/refractory (R/R) high-risk myelodysplastic syndromes (HR-MDS).¹

Early efficacy signals of the LYT-200 combination in this setting came from the completed phase 1b trial (NCT05829226) of LYT-200 plus azacitidine or decitabine in heavily pretreated patients whose disease had relapsed after or become refractory to an HMA. Among 11 efficacy-evaluable patients with R/R HR-MDS who received LYT-200 at 12 mg/kg with an HMA, the overall response rate was 45.5%. The complete response (CR) rate was 27.3%, the partial response (PR) rate was 9.1%, and the marrow CR rate was 9.1%, for a combined CR plus PR rate of 36.3%. Additionally, 18% of patients converted to transplant. Efficacy evaluable required at least 1 full cycle of LYT-200 (4 doses) and 1 post-baseline assessment; the intent-to-treat population was 12 patients.

“Our productive End-of-Phase 1 meeting with the US FDA provides a clear path to advance LYT-200 into phase 2 development,” said Eric Elenko, PhD, acting chief executive officer of Gallop Oncology and cofounder of PureTech, stated in a news release.¹ “The STRIDE-MDS trial will seek to confirm the unprecedented clinical activity observed in phase 1b, while its randomized, double-blind design will enable a clear assessment of the contribution of effect of LYT-200. Additionally, the inclusion of 2 doses is intended to fulfill the dose-selection requirements in accordance with FDA’s Project Optimus. With its mutation-agnostic approach and potential to benefit a broad range of patients, LYT-200 could represent an important new treatment option for R/R HR-MDS.”

No dose-limiting toxicities or myeloid suppression were observed among the 11 efficacy-evaluable patients. The company characterized the overall safety profile in the phase 1b trial as consistent.

STRIDE-MDS Trial Design

The LYT-200 regimen is now moving forward into STRIDE-MDS (Study of Two Regimens Investigating Dose and Efficacy of LYT-200 in Relapsed/Refractory High-Risk MDS), a randomized, double-blind, placebo-controlled phase 2 trial planned to enroll approximately 125 patients with R/R HR-MDS. Patients will be randomized 2:2:1 to LYT-200 at 12 mg/kg plus an HMA, LYT-200 at 7.5 mg/kg plus an HMA, or placebo plus an HMA. Efficacy will be measured by the CR and PR rate to support dose selection.

“Patients with higher-risk MDS who relapse or become refractory to HMA treatment have very limited therapeutic options and poor outcomes, and the literature and clinical practice suggest that fewer than 5% of these patients typically respond to retreatment with an HMA rechallenge,” 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 of STRIDE-MDS, stated in the news release.¹ “Against this backdrop, the clinical activity observed with LYT-200 in combination with an HMA in the phase 1b study is particularly encouraging. STRIDE-MDS will allow us to further evaluate this activity in a randomized, placebo-controlled study.” Zeidan has received honoraria from PureTech as a clinical advisor.

LYT-200 is a fully human monoclonal antibody and the most advanced candidate targeting galectin-9, an oncogenic driver and potent immunosuppressor. Its mutation-agnostic, dual mechanism is designed to act on both malignant cells and the immunosuppressive environment.¹

“R/R HR-MDS remains an area of profound unmet need, particularly for the vast majority of patients without an actionable mutation,” said Aleksandra Filipovic, MD, PhD, chief medical officer of Gallop Oncology, stated in the news release.¹ “Galectin-9 represents a compelling therapeutic target because of its role as both an oncogenic driver and potent immunosuppressor, and its elevated expression in HR-MDS is associated with shorter survival. By addressing the foundational biology independent of a specific genetic mutation, LYT-200 has the potential to offer a new approach for a broad population of patients, and we welcome the opportunity Fast Track designation provides to work more closely with the US FDA as we advance its development.”

LYT-200 previously received fast track designation from the FDA for the treatment of patients with acute myeloid leukemia.

REFERENCES

1. PureTech announces successful end-of-phase 1 meeting with U.S. 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 21, 2026. https://tinyurl.com/5n9yyk95