PureTech’s LYT-200 Advances to Phase 2 in High-Risk MDS With FDA Fast Track Designation

PureTech Health has completed an End-of-Phase 1 meeting with the U.S. Food and Drug Administration (FDA), supporting advancement of LYT-200 into Phase 2 development for relapsed/refractory (R/R) high-risk myelodysplastic syndromes (HR-MDS). The FDA also granted Fast Track designation to LYT-200 in combination with a hypomethylating agent (HMA) for the same setting.

LYT-200 Targets Galectin-9 in HR-MDS

LYT-200 is a fully human monoclonal antibody targeting galectin-9, a protein involved in tumor biology and immune suppression. Its development follows a mutation-agnostic approach, meaning treatment does not depend on the presence of a specific genetic alteration.

Galectin-9 has been associated with malignant cell survival and an immunosuppressive environment in HR-MDS. LYT-200 has a dual mechanism intended to address both malignant cells and the immune-suppressive biology that can support disease progression.

The need for new treatments is substantial. Hypomethylating agents such as azacitidine and decitabine remain standard frontline therapies for HR-MDS, but many patients either fail to respond or eventually relapse. Once disease becomes refractory or relapses after HMA treatment, therapeutic options remain limited and outcomes are poor.

Phase 1b Data Support Phase 2 Development

The FDA meeting was supported by topline results from a Phase 1b study (NCT05829226) evaluating LYT-200 with azacitidine or decitabine in heavily pretreated patients with R/R HR-MDS. All patients had previously relapsed or become refractory to HMA therapy.

Among 11 efficacy-evaluable patients receiving LYT-200 at 12 mg/kg with an HMA, the overall response rate reached 45.5%, comprising a 27.3% complete response (CR) rate, a 9.1% partial response (PR) rate, and a 9.1% marrow complete response rate. The CR plus PR rate was 36.3%.

The study also reported an 18% conversion-to-transplant rate. No dose-limiting toxicities or myeloid suppression were observed in this treatment group.

These findings provide early clinical evidence from a small Phase 1b cohort and will require confirmation in a randomized study.

STRIDE-MDS to Evaluate Two LYT-200 Doses

The planned STRIDE-MDS Phase 2 trial will enroll approximately 125 patients with R/R HR-MDS in a randomized, double-blind, placebo-controlled design.

Patients will be randomized in a 2:2:1 ratio 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 complete and partial response rates to support dose selection.

The two-dose design is also intended to address FDA dose-selection requirements under Project Optimus, which emphasizes dose optimization and selection based on benefit-risk assessment during oncology drug development.

FDA Fast Track Designation Supports Development

Fast Track designation provides opportunities for more frequent interactions with the FDA during development and can facilitate the regulatory review process for therapies addressing serious conditions with unmet medical needs.

Amer Zeidan, MBBS, MHS, Professor of Medicine at Yale University and Global Principal Investigator of STRIDE-MDS, will lead the global Phase 2 study. He noted that patients with HR-MDS who relapse or become refractory to HMA therapy have limited treatment options.

The company cited literature and clinical practice suggesting that fewer than 5% of patients in this setting typically respond to HMA rechallenge, providing context for the response signal observed in the Phase 1b study.

PureTech Plans External Funding for Further Development

PureTech plans to continue developing LYT-200 through Gallop Oncology, its wholly owned Founded Entity. The company expects to secure external capital in the first half of 2027 to support development through completion of the Phase 2 program.

LYT-200 also holds FDA Fast Track designation for acute myeloid leukemia (AML), giving the program a second hematologic malignancy development pathway.

The STRIDE-MDS study will provide the next clinical assessment of whether the response signals observed with LYT-200 plus HMA therapy can be reproduced in a randomized patient population and help establish the dose for further development.

 Reference

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), PureTech health, 21 September 2026

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 ID NCT05829226