FDA Grants Fast Track Designation to LYT-200 in R/R 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 (MDS).¹

LYT-200 is a first-in-class, anti–galectin-9 monoclonal antibody, and the designation was announced alongside the completion of an end-of-phase 1 meeting with the FDA.

That meeting was supported by topline data from a phase 1b trial (NCT05829226) of LYT-200 plus an HMA in heavily pretreated patients with relapsed/refractory high-risk MDS.

Efficacy-evaluable patients treated with LYT-200 (n = 11), achieved an overall response rate (ORR) of 45.5%, including a complete response (CR) rate of 27.3%, and a partial response rate of 9.1%. Additionally, 18% of patients converted to transplant. Median overall survival (OS) was 6.4 months; the company noted that this value is not fully mature because more than 50% of patients were alive at study completion.²

“Patients with higher-risk MDS who relapse or become refractory to HMA treatment have 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,” said Amer Zeidan, MBBS, MHS, in a 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 is a professor of Internal Medicine, chief of the Division of Hematologic Malignancies at the Yale School of Medicine, as well as director of Early Therapeutics Research and Leukemia and Myeloid Malignancies Program, assistant medical director of Clinical Trials Office, and co-leader of the Leukemia and Myeloid Malignancies Clinical Research Team at Yale Cancer Center, in New Haven, Conneticut.

LYT-200 previously received fast track and orphan drug designation for the treatment of acute myeloid leukemia (AML). LYT-200 has also previously received fast track designation in recurrent or metastatic head and neck squamous cell cancer.

How was the phase 1b trial evaluating LYT-200 in R/R AML and high-risk MDS designed?

The open-label, non-randomized, multicenter study enrolled patients who were at least 18 years of age with relapsed/refractory AML after at least one prior line of therapy, with or without allogeneic stem cell transplant, or relapsed/refractory high-risk MDS after at least one line of treatment with no available standard therapy expected to provide clinical benefit.³ Patients also needed to have an ECOG performance status of 2 or less and have a white blood cell count of less than 25,000/uL at the time of their first dose.

If patients had acute promyelocytic leukemia, malignant tumors other than AML or MDS, underwent prior hematopoietic stem cell transplantation in the 6 months prior to their first dose, or active graft versus host disease, they were not included in the trial.

Notably, patients in the trial received 12mg/kg of LYT-200 plus an HMA.² Azacitidine and decitabine were HMAs used for patients with MDS compared with venetoclax (Venclexta) for those with AML.

The primary end point was safety, tolerability, and dose-limiting toxicities (DLTs) of LYT-200.³ Secondary end points included pharmacokinetics and antitumor activity.

Efficacy-evaluable patients had received a median of 3 prior lines of therapy (range, 1-5), all had previously received an HMA, and all had high-risk cytogenetics.

What are the additional data and next steps for LYT-200?

Patients also demonstrated a 9.1% marrow CR rate. Regarding safety, no DLTs or myeloid suppression were reported.¹

The upcoming phase 2 STRIDE-MDS trial will be a double-blind, placebo-controlled, randomized study enrolling approximately 125 patients with relapsed/refractory high-risk MDS and evaluating LYT-200.¹ Patients will be randomly assigned 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.

“Relapsed/refractory high-risk MDS remains an area of profound unmet need, particularly for the vast majority of patients without an actionable mutation,” Aleksandra Filipovic, MD, PhD, chief medical officer of Gallop Oncology said in a news release. “Galectin-9 represents a compelling therapeutic target because of its role as both an oncogenic driver and potent immunosuppressor, and its elevated expression in high-risk MDS is associated with shorter survival. By addressing the foundational biology, LYT-200 has the potential to offer a new approach for a broad population of patients.”

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://www.businesswire.com/news/home/20260920743286/en/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-RelapsedRefractory-RR-High-Risk-Myelodysplastic-Syndromes-HR-MDS
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 21, 2026. https://news.puretechhealth.com/news-releases/news-release-details/puretech-reports-positive-topline-data-phase-1b-trial-lyt-200
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 May 6, 2026. Accessed September 21, 2026. https://clinicaltrials.gov/study/NCT05829226