FDA Fast Track for PureTech's LYT-200 in Relapsed/Refractory High-Risk MDS; Phase 2 STRIDE-MDS Cleared
Key Insights
PureTech Health and its Founded Entity Gallop Oncology (search) completed an End-of-Phase 1 meeting with the FDA and received Fast Track designation for LYT-200 in relapsed/refractory high-risk myelodysplastic syndromes (search).
The randomized, double-blind, placebo-controlled Phase 2 STRIDE-MDS trial will enroll approximately 125 patients randomized 2:2:1 to LYT-200 at 12 mg/kg, 7.5 mg/kg, or placebo, each with a hypomethylating agent.
In the completed Phase 1b trial, efficacy-evaluable patients receiving LYT-200 12 mg/kg plus an HMA (n=11) achieved a 27.3% complete response rate and a 45.5% overall response rate, with no dose-limiting toxicities.
PureTech Health plc announced that its Founded Entity, Gallop Oncology (search), has completed a successful End-of-Phase 1 (EOP1) meeting with the U.S. Food and Drug Administration (search) and received Fast Track designation for LYT-200 in combination with a hypomethylating agent (HMA) for the treatment of relapsed/refractory (R/R) high-risk myelodysplastic syndromes (search) (HR-MDS). The FDA feedback supports advancement of the candidate into the Phase 2 STRIDE-MDS trial.
LYT-200 is a Phase 2-ready, fully human monoclonal antibody that targets galectin-9 (search), described by the company as an important oncogenic driver and potent immunosuppressor. It is the most advanced therapeutic candidate directed at that target. The antibody has also received Fast Track designation from the FDA for the treatment of acute myeloid leukemia (search).
Phase 1b Data Underpin the Regulatory Path
The EOP1 meeting was supported by positive topline data from a completed Phase 1b trial that evaluated LYT-200 in combination with an HMA (azacitidine or decitabine) in heavily pretreated patients with R/R HR-MDS, all of whom had relapsed or become refractory to prior HMA treatment.
Among efficacy-evaluable patients receiving LYT-200 at 12 mg/kg plus an HMA (n=11), the trial reported a 27.3% complete response rate, a 36.3% complete response plus partial response rate, a 9.1% partial response rate, a 9.1% marrow complete response rate, a 45.5% overall response rate and an 18% conversion to transplant rate. No dose-limiting toxicities and no myeloid suppression were observed.
"Our productive End-of-Phase 1 meeting with the U.S. FDA provides a clear path to advance LYT-200 into Phase 2 development," said Eric Elenko, PhD, Acting Chief Executive Officer of Gallop Oncology (search) and Co-founder of PureTech. "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."
STRIDE-MDS Design and Dose Selection
The Study of Two Regimens Investigating Dose and Efficacy of LYT-200 in Relapsed/Refractory High-Risk MDS (STRIDE-MDS) will be a randomized, double-blind, placebo-controlled Phase 2 trial enrolling 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. The trial will assess efficacy as measured by the rate of complete and partial responses to support dose selection.
Elenko said the inclusion of two doses is intended to fulfill the dose-selection requirements in accordance with FDA's Project Optimus.
Rationale for a Mutation-Agnostic Target
"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 (search). "Galectin-9 (search) 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."
Filipovic added that 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. The company describes the antibody as having a mutation-agnostic, dual mechanism of action designed to address both malignant cells and the immunosuppressive environment that sustains disease.
Disease Burden and Treatment Gap
Myelodysplastic syndromes are a group of serious blood cancers characterized by ineffective blood cell production in the bone marrow, leading to anemia, infections and bleeding complications. MDS affects approximately 60,000 to 170,000 people in the United States, with an estimated 30% to 40% of patients diagnosed with the more aggressive high-risk form. HR-MDS is associated with poor outcomes, with median survival typically less than two years following diagnosis.
The current standard frontline treatments for HR-MDS are HMAs such as azacitidine and decitabine, but most patients do not respond to these therapies or eventually stop benefiting from them. Once the disease becomes relapsed or refractory, survival is often limited to only a few months.
Only one therapy has been approved by the FDA specifically for R/R HR-MDS in the past two decades, and it targets a genetic mutation found in only approximately 3% of patients.
"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," said Amer Zeidan, MBBS, MHS, Professor of Medicine at Yale University and Chief of the Division of Hematologic Malignancies at Yale Cancer Center, who will be the Global Principal Investigator of the Phase 2 STRIDE-MDS trial. "Against this backdrop, the clinical activity observed with LYT-200 in combination with an HMA in the Phase 1b study is particularly encouraging."
Development and Financing Plans
LYT-200 is being advanced through Gallop Oncology (search), a clinical-stage biotechnology company founded by and currently wholly owned by PureTech Health. PureTech intends to leverage external capital to support continued development of LYT-200 through completion of the Phase 2 trial and expects to secure capital in the first half of 2027.
Fast Track designation is a process designed to facilitate the development and expedite the review of drugs that target serious conditions with unmet medical need. Drugs receiving the designation may benefit from more frequent interactions with the FDA throughout development.