PureTech Health presents data from dose escalation phase of LYT-200 trial

PureTech Health (PRTC) presented data from the dose escalation phase of its ongoing Phase 1b trial evaluating LYT-200, an anti-galectin-9 monoclonal antibody, in patients with relapsed or refractory acute myeloid leukemia, or AML, and myelodysplastic syndromes, or MDS, at the 2024 American Society of Hematology, or ASH, annual meeting in San Diego, California. LYT-200 is currently being evaluated both as a monotherapy and in combination with the venetoclax and hypomethylating agents, or HMA, for patients whose disease is relapsed/refractory to at least one line of prior treatment. It targets galectin-9, a glycan-binding protein that is significantly upregulated in AML and MDS and plays a role in disease development, progression, immune interference and drug resistance. Initial results show a favorable safety profile across both arms and all dose levels with no dose limiting toxicities, as well as evidence of response, hematological improvement and sustained disease management. In the monotherapy arm, patients received LYT-200 at five dose levels. Across all dose levels, LYT-200 induced clinical benefit and responses in heavily pre-treated, relapsed/refractory AML/MDS patients, even in those with complex cytogenetics and mutations such as KRAS, NRAS, BRAF as well as patients previously fully refractory to standard of care. Out of 22 evaluable patients who received monotherapy, 59% achieved stable disease or better with two partial responses. The mean duration on treatment is greater than two months, which exceeds the standard overall survival of approximately 1.7 months in venetoclax/HMA-refractory patients. When administered in combination with venetoclax/HMA, results demonstrate that LYT-200 may enhance the efficacy of standard-of-care therapies, even in relapsed or refractory patients. In the combination arm, patients received LYT-200 across three dose levels with venetoclax/HMA. Out of 15 evaluable patients who received combination therapy, 80% achieved stable disease or better, with two experiencing complete responses and one patient achieving a morphologic leukemia free state. The combination regimen has also demonstrated clinical benefit in patients with KRAS/NRAS mutations and the mean duration on treatment up until the point of data cut-off is greater than two months. Pharmacodynamic assessments of treated patients, using gene and protein analyses of patient cells, validate the LYT-200 dual mode of action, and reveal AML cellular pathways as well as specific immune cell types which may be most critical for response. Based on these data, LYT-200 will continue development in relapsed/refractory AML/MDS towards a Phase 2 clinical trial. PureTech previously announced that it intends to advance LYT-200 via its Founded Entity, Gallop Oncology.