PureTech Presents LYT-200 Data for Relapsed/Refractory AML/MDS at 2024 ASH Meeting

PureTech Health plc, a clinical-stage biotherapeutics company, recently presented promising results from the dose escalation phase of their ongoing Phase 1b trial of LYT-200 at the 2024 American Society of Hematology Annual Meeting. This trial focuses on patients with relapsed or refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

LYT-200 is an innovative anti-galectin-9 monoclonal antibody currently being tested as both a monotherapy and in conjunction with standard treatments like venetoclax and hypomethylating agents. Galectin-9, which is significantly upregulated in AML and MDS, plays a crucial role in the progression of these diseases and in drug resistance. The initial results have shown LYT-200 to have a favorable safety profile across both treatment arms and all dose levels, with no dose-limiting toxicities. The treatment has also demonstrated evidence of response, hematological improvement, and sustained disease management.

In the monotherapy arm of the trial, patients received LYT-200 at various dose levels ranging from 2.0 mg/kg to 16.0 mg/kg. Out of the 22 evaluable patients, 59% achieved stable disease or better, including two partial responses. The mean duration of treatment was over two months, which is notably better than the standard overall survival of approximately 1.7 months for patients who are refractory to venetoclax and hypomethylating agents.

When LYT-200 was combined with venetoclax and hypomethylating agents, the results were even more promising. Patients received LYT-200 at dose levels from 4.0 mg/kg to 12.0 mg/kg. Among the 15 evaluable patients in this combination arm, 80% achieved stable disease or better, with two complete responses and one patient reaching a morphologic leukemia-free state. This combination therapy has shown clinical benefits even in patients with challenging KRAS/NRAS mutations, with the mean duration on treatment also exceeding two months.

Luba Greenwood, Entrepreneur-in-Residence at PureTech, expressed optimism about the potential of LYT-200, stating that the responses and long-term disease stabilization observed in heavily pre-treated patients are encouraging. Greenwood emphasized the potential of LYT-200 to become a critical therapeutic option for treating a majority of AML patients, given the dire prognosis associated with relapsed or refractory AML.

Dr. Aleksandra Filipovic, Head of Oncology at PureTech, highlighted the novel approach of LYT-200 in treating AML. The drug works by directly inducing cancer cell apoptosis and DNA damage while also re-activating central anti-cancer effectors of the immune system. Filipovic pointed out that the dual mechanism of LYT-200 could transform its treatment potential both as a single agent and in combination with existing standard-of-care treatments.

Pharmacodynamic assessments of treated patients, which included gene and protein analyses of patient cells, have validated the dual mode of action of LYT-200. These assessments have also revealed critical AML cellular pathways and specific immune cell types that are essential for response.

Based on these promising early results, the development of LYT-200 will continue in relapsed/refractory AML/MDS, moving towards a Phase 2 clinical trial. PureTech Health has indicated that they plan to advance LYT-200 through their Founded Entity, Gallop Oncology.

LYT-200 is a fully human IgG4 monoclonal antibody targeting galectin-9, an important oncogenic and immunosuppressive protein. This treatment is being explored for its potential efficacy in hematological malignancies and locally advanced metastatic solid tumors. Preclinical data have supported the clinical potential of LYT-200, showing its effectiveness in various solid tumor types and blood cancers, and its ability to synergize with anti-PD-1 therapies.

PureTech Health is committed to developing transformative therapeutics for devastating diseases, driven by a robust pipeline advanced by an experienced research and development team. The company has developed multiple therapeutic candidates, including three that have been approved by the U.S. Food and Drug Administration.