PureTech's LYT-200 Shows Promising Results in Phase 1b Trial for Relapsed/Refractory Blood Cancers
核心洞察
PureTech Health reported positive Phase 1b trial results for LYT-200, a first-in-class anti-galectin-9 (搜索) monoclonal antibody, demonstrating complete responses in heavily pretreated patients with relapsed/refractory high-risk myelodysplastic syndrome (搜索) and acute myeloid leukemia (搜索).
The therapy showed a favorable safety profile across 101 patients with no dose-limiting toxicities, infusion-related reactions, or treatment-related serious adverse events, while achieving response rates of 45.5% in MDS and 42.3% in AML patients.
Based on the compelling data, particularly in high-risk MDS where treatment options are extremely limited, Gallop Oncology (搜索) plans to engage with the FDA to discuss a subsequent trial design with potential to support registration.
PureTech Health announced positive topline data from a completed Phase 1b clinical trial of LYT-200, a first-in-class, fully human anti-galectin-9 (搜索) monoclonal antibody, in heavily pretreated patients with relapsed/refractory (R/R) high-risk (HR) myelodysplastic syndrome (搜索) (MDS) and R/R acute myeloid leukemia (搜索) (AML). The results have prompted PureTech's Founded Entity, Gallop Oncology (搜索), to select a recommended Phase 2 dose and engage with the U.S. Food and Drug Administration to discuss a subsequent trial design with potential to support registration in R/R HR-MDS.
Robust Clinical Activity with Favorable Safety Profile
The Phase 1b trial (NCT05829226), conducted across nine U.S. sites, evaluated LYT-200 both as monotherapy and in combination regimens in two heavily pretreated patient populations. LYT-200 demonstrated a favorable and consistent safety profile across all cohorts and dose levels studied (N=101), with no dose-limiting toxicities, infusion-related reactions, LYT-200 dose reductions, or LYT-200-related serious adverse events, discontinuations, or deaths.
"The safety profile, combinatorial potential, and level of clinical activity observed with LYT-200 in this Phase 1b study across both R/R HR-MDS and R/R AML is very encouraging, particularly given the number of prior lines of treatment and the risk profile in the populations studied," said Amir T. Fathi, M.D., Program Director of the Center for Leukemia at the Mass General Brigham Cancer Institute and Professor of Medicine at Harvard Medical School.
Compelling Efficacy Results in High-Risk MDS
In the R/R HR-MDS cohort, across all efficacy-evaluable patients (n=11), the recommended Phase 2 dose (LYT-200 12mg/kg in combination with a hypomethylating agent) demonstrated a 27.3% complete response rate, 9.1% partial response rate, 9.1% marrow complete response rate, and 45.5% overall response rate. Additionally, 18% of patients achieved conversion to transplant.
The efficacy-evaluable patients had a median of 3 prior lines of therapy (range: 1-5), and all (100%) had previously been treated with a hypomethylating agent. All patients had high-risk cytogenetics, which, coupled with prior exposure to treatment, suggests biologically aggressive, treatment-refractory disease with elevated risk of progression and poor clinical outcomes.
Strong Performance in Acute Myeloid Leukemia
In the R/R AML cohort, across all efficacy-evaluable patients (n=26), LYT-200 12mg/kg in combination with venetoclax and a hypomethylating agent demonstrated a 30.8% composite complete response rate, with responders including patients with mutations associated with venetoclax resistance. The overall response rate reached 42.3%, with 19.2% of patients achieving conversion to transplant.
Efficacy-evaluable patients had a median of 2 prior lines of therapy (range: 1-9), and 84.6% had previously been treated with venetoclax and hypomethylating agent combination therapy.
Addressing Critical Unmet Medical Need
"In R/R high-risk MDS, where treatment options are extremely limited and outcomes are poor, the findings are particularly notable," noted Dr. Fathi. "In this context, the potential to achieve clinical responses without added toxicity would represent a meaningful advance in the MDS treatment landscape and warrants continued clinical development."
Treatment options for patients with R/R HR-MDS remain very limited, with only one therapy approved specifically for this setting in the past two decades, targeting only a small subset of patients (approximately 3-5%) with a specific genetic mutation. Once the disease becomes relapsed or refractory, outcomes are especially poor, with survival often limited to only a few months.
Novel Mechanism of Action
LYT-200 is a fully human IgG4 monoclonal antibody that targets galectin-9 (搜索), an important oncogenic driver and potent immunosuppressor in cancer. Pharmacodynamic analyses suggest that LYT-200 engages complementary and potentially synergistic pathways directed at cancer cell killing and anti-cancer immune responses when combined with venetoclax and hypomethylating agent-based therapy.
"The data from the completed Phase 1b trial highlight the potential for LYT-200 to offer a differentiated treatment approach across a range of myeloid hematological malignancies," said Aleksandra Filipovic, M.D., Ph.D., Head of Oncology at PureTech and Chief Medical Officer of Gallop Oncology (搜索).
Strategic Development Focus
Based on the results, Gallop Oncology (搜索) has decided to prioritize relapsed/refractory high-risk MDS for continued development. "Our decision to prioritize relapsed/refractory high-risk MDS reflects a focused and disciplined approach, grounded in both the data generated to date and the potential to address a tremendous patient need," said Eric Elenko, Ph.D., President and Co-founder of PureTech and Acting Chief Executive Officer of Gallop Oncology.
LYT-200 has been granted Fast Track and Orphan Drug designations from the U.S. Food and Drug Administration for the treatment of acute myeloid leukemia (搜索), supporting its continued development in these challenging hematological malignancies.