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PureTech Presents Data for LYT-200 (anti-galectin-9 monoclonal antibody) for Relapsed/Refractory AML/MDS at the 2024 ASH Annual Meeting

December 9, 2024 – Clinical Trials, Drug Discovery, Pharmaceutical – AML/MDS, ASH 2024, PureTech Health, clinical trials, monoclonal antibodies

LYT-200 is generally safe and well-tolerated as a single agent as well as in combination with standard-of-care venetoclax and hypomethylating agents
LYT-200 demonstrates clinical benefit as a single agent, with two partial responses and 59% of evaluable patients achieving stable disease or better
In combination, two complete responses were seen and 80% of evaluable patients achieved stable disease or better
Data support LYT-200 as a potential first-line treatment for AML/MDS patients.

9 December 2024 — Massachusetts, US — PureTech Health plc, a clinical-stage biotherapeutics company dedicated to changing the lives of patients with devastating diseases, presented data from the dose escalation phase of its ongoing Phase 1b trial evaluating LYT-200, a first-in-class anti-galectin-9 monoclonal antibody, in patients with relapsed or refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) at the 2024 American Society of Hematology (ASH) Annual Meeting in San Diego, California.

LYT-200 is currently being evaluated both as a monotherapy and in combination with the standard-of-care venetoclax and hypomethylating agents (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 key 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.

“Relapsed/refractory acute myeloid leukemia is one of the most dire cancer diagnoses, with 50% of patients non-responsive to or relapsing after initial treatment and a median survival time of less than six months,2” said Luba Greenwood, J.D., Entrepreneur-in-Residence at PureTech who is leading the Gallop Oncology work. “We are encouraged to see that LYT-200 achieved responses as well as long-term disease stabilization in heavily pre-treated patients, and we look forward to progressing LYT-200 as a critical therapeutic option with the potential to treat most AML patients.”

In the monotherapy arm, patients received LYT-200 at five dose levels (2.0 mg/kg to 16.0 mg/kg). 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 meanduration 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 (4.0 mg/kg to 12.0 mg/kg) 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 (MLFS). 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.

“Galectin-9 is an essential driver of both disease proliferation and immune suppression in AML that has not yet been addressed therapeutically,” said Aleksandra Filipovic, M.D., Ph.D., Head of Oncology at PureTech. “LYT-200 represents a novel approach for treating AML via a two-gear mode of action that kills cancer cells directly via apoptosis and DNA damage, as well as by re-activating central anti-cancer effectors of the immune system. We are excited by these Phase 1 data that demonstrate the transformative potential of this dual mechanism of LYT-200, both as a single agent and in combination with existing standard-of-care treatments.”

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.

About PureTech Health

PureTech is a clinical-stage biotherapeutics company dedicated to giving life to new classes of medicine to change the lives of patients with devastating diseases. The Company has created a broad and deep pipeline through its experienced research and development team and its extensive network of scientists, clinicians and industry leaders that is being advanced both internally and through its Founded Entities. PureTech’s R&D engine has resulted in the development of 29 therapeutics and therapeutic candidates, including three that have been approved by the U.S. Food and Drug Administration. A number of these programs are being advanced by PureTech or its Founded Entities in various indications and stages of clinical development, including registration-enabling studies. All of the underlying programs and platforms that resulted in this pipeline of therapeutic candidates were initially identified or discovered and then advanced by the PureTech team through key validation points. Visit: puretechhealth.com.