Positive Topline Results Demonstrated for LYT-200 in MDS, AML

Positive topline results were reported for the phase 1b clinical trial (NCT05829226) of LYT-200, a first-in-class monoclonal antibody targeting galectin-9. The findings show notable clinical activity in patients with heavily pretreated myeloid malignancies. The trial specifically highlighted the potential of LYT-200 in the relapsed and refractory high-risk myelodysplastic syndrome (R/R HR-MDS) population.¹

In the efficacy-evaluable cohort of 11 patients with R/R HR-MDS, the combination of LYT-200 at the recommended phase 2 dose of 12 mg/kg plus a hypomethylating agent (HMA) yielded an overall response rate (ORR) of 45.5%. The data revealed a complete response (CR) rate of 27.3%, a partial response rate of 9.1%, and a marrow complete response rate of 9.1%. Furthermore, 18% of these patients were able to convert to a stem cell transplant. The study participants had a median of 3 prior lines of therapy and 100% had their disease previously fail to respond to HMA treatment. All patients in this cohort also presented with high-risk cytogenetics, suggesting a biologically aggressive and treatment-refractory disease state.

Safety data across all 101 patients in the study indicated that LYT-200 maintains a favorable and consistent profile with no dose-limiting toxicities or dose reductions reported. There were no serious adverse events, treatment discontinuations, or deaths attributed to LYT-200. Although 6 patients at 1 site reported grade 3 or 4 hematologic toxicities such as decreased platelets and neutrophils, these were consistent with baseline deficits common in advanced MDS and acute myeloid leukemia (AML) populations or those receiving venetoclax (Venclexta) and HMA combinations. No other study sites reported grade 3 or higher adverse events related to the investigational antibody.

Abstract at 2024 ASH Annual Meeting

Findings from the phase 1 dose escalation and expansion trial were presented at the 2024 ASH Annual Meeting.² That trial illustrated that single-agent LYT-200 in combination with venetaclax/HMA is safe, well-tolerated, and shows initial clinical activity.

The trial enrolled patients in single-agent (SA) and combination cohorts (CC) using a 4+2 design. Dose escalation in the SA cohorts has been completed across 5 dose levels of LYT-200 (2, 4, 7.5, 12, and 16 mg/kg administered weekly). Enrollment in the CC evaluating LYT-200 plus venetoclax/hypomethylating agents (VEN/HMA) has been completed for 3 cohorts, with VEN/HMA administered as standard of care and LYT-200 at dose levels of 4, 7.5, and 12 mg/kg.

What Is LYT-200?

LYT-200 is a fully human IgG4 monoclonal antibody designed to target galectin-9, a protein identified as a potent immunosuppressor and oncogenic driver in hematological malignancies. By neutralizing galectin-9, the therapy aims to trigger a dual effect: the direct killing of cancer cells and the reactivation of anti-cancer immune responses. Pharmacodynamic analyses suggest that LYT-200 engages these complementary pathways even in patients whose disease failed to respond to prior standard-of-care therapies.

FDA Fast Track Designation

The clinical development of LYT-200 has been supported by multiple regulatory milestones. In January 2025,³ the FDA granted fast track designation (FTD) to LYT-200 for the treatment of AML. This reinforces the potential for the agent to address urgent needs in the AML space and follows a prior FTD for the treatment of recurrent or metastatic head and neck squamous cell carcinoma.

Combination Potential in AML

The trial also evaluated LYT-200 in combination with venetoclax and an HMA specifically for patients with relapsed and refractory acute myeloid leukemia (R/R AML). The HMAs utilized in these combination regimens across both MDS and AML cohorts included azacitidine or decitabine. In the group of 26 efficacy-evaluable patients with R/R AML, the triplet regimen produced an ORR of 42.3% and a composite CR rate of 30.8%.

Notably, these AML responders included patients with mutations typically associated with venetoclax resistance. The conversion to transplant rate for the AML cohort stood at 19.2%. Although median overall survival was recorded at 8.2 months for AML and 6.4 months for MDS, these figures are not yet considered mature because approximately 50% of patients remained alive at the time of study completion. Given the robust response in the MDS cohort, the manufacturer intends to discuss a registrational trial design with the FDA focused on R/R HR-MDS.

REFERENCES

1. 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. April 22, 2026. Accessed April 22, 2026. https://tinyurl.com/yveas2pw

2. Fathi AT, Filiovic A, Maher K, et al. A phase I dose escalation and expansion trial of lyt-200 (a first-in-class anti-galectin-9 antibody) alone and in combination with venetoclax/HMA in relapsed/refractory AML/MDS. Blood. 2025;146(suppl 1):1648. doi:10.1182/blood-2025-1648

3. Sava J. LYT-200 gains FDA fast track status in acute myeloid leukemia. January 14, 2025. Accessed April 22, 2026. https://tinyurl.com/46nffn4x