PureTech Presents Data for LYT-200 Targeting Galectin-9 in Preclinical Leukemia Cancer Models at the 64th American Society of Hematology (ASH) Annual Meeting
- Data support the role of galectin-9 in multiple types of leukemia and the ability of anti-galectin-9 antibodies to provide effective anti-tumor activity in these cancers
- Clinical trial has initiated evaluating LYT-200 as a single agent in acute myeloid leukemia (AML) patients
- LYT-200 is also being evaluated in a range of metastatic solid tumors as a monotherapy and in combination with chemotherapy or an anti-PD-1 antibody; the first part of the Phase 1 trial has completed, with the combination part beginning in the first quarter of 2023
PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to changing the treatment paradigm for devastating diseases, today shared new data supporting the clinical potential of LYT-200, a fully human monoclonal antibody (mAb) designed to inhibit the activity of galectin-9, as a therapeutic agent for the treatment of leukemia. The data were shared in a scientific poster presented at the American Society of Hematology (ASH) 64th Annual Meeting. LYT-200 is a therapeutic candidate targeting galectin-9, which is expressed by tumors and immune cells and plays a key role in cancer treatment resistance. It is also in development as a treatment for a range of cancer indications with otherwise poor survival rates.
“The data we are presenting at ASH add further support to the hypothesis that galectin-9 is an important therapeutic target for not just AML but multiple blood cancers, suggesting LYT-200 may be beneficial across a range of hematologic malignancies and underscores the potential of LYT-200 in an area with significant clinical need for novel treatment regimens,” said Aleksandra Filipovic, M.D., Ph.D., Head of Oncology at PureTech. “The National Cancer Institute estimates that about 61,000 new cases of leukemia are diagnosed each year, including about 20,000 in AML. More than 50% of AML patients either don’t respond to initial treatment or experience relapse or death after responding to initial treatment, and have an approximately 12.6% five-year survival rate. The poor overall survival highlights the need for more effective therapies for patients with relapsed and refractory AML.”
The ASH poster evaluates galectin-9 expression and the effects of LYT-200 in multiple types of leukemia. Compared to healthy human peripheral blood mononuclear cells, where galectin-9 surface expression was low or absent, galectin-9 was highly expressed on the surface of all human blood cancer cells tested. Notably, surface expression of galectin-9 often exceeded that of the known inhibitory checkpoint proteins TIM-3 and PD-1.
In all models used, LYT-200 demonstrated significant anti-tumor activity and in addition to its established effects on the immune system in solid tumor models, it also notably induced direct apoptosis or cell death across all leukemia cell types. In a model assessing DNA damage in AML cells, LYT-200 significantly outperformed an anti-TIM3 antibody and had effects that were comparable to Venetoclax, an approved therapeutic for AML. The effects were greatest when both compounds were combined. The in vitro efficacy of LYT-200 against the leukemia subtypes also extended to in vivo survival benefit in both immunocompromised and immunocompetent patient-derived xenograft mouse models. In these models, LYT-200 outperformed chemotherapy and produced the greatest effect in combination.
Collectively, these new data support galectin-9 as a strong potential therapeutic target for a range of cancers. Based on this and other compelling preclinical data generated with LYT-200 in blood cancers, PureTech has initiated a clinical trial to evaluate LYT-200 as a single agent for the treatment of AML with results expected in 2023. PureTech has also completed the bi-monthly and weekly, monotherapy dose escalation portion of the Phase 1 program assessing the safety and tolerability of escalating doses of LYT-200 as a potential treatment of metastatic solid tumors. No dose-limiting toxicities were reported, and the full results will be presented in an upcoming scientific forum. The combination part of the Phase 1 trial in certain metastatic solid tumors with LYT-200 in combination with tislelizumab is expected to begin in the first quarter of 2023.
The scientific poster presented today is available at https://puretechhealth.com/LYT-200-ASH-2022-poster.
LYT-200 is a fully human IgG4 monoclonal antibody targeting a foundational immunosuppressive protein, galectin-9, for the potential treatment of solid tumors, including pancreatic ductal adenocarcinoma, colorectal cancer and cholangiocarcinoma, with otherwise poor survival rates. A wide variety of preclinical data supports the potential clinical efficacy of LYT-200 and the importance of galectin-9 as a target and suggests a potential opportunity for biomarker development. For example, PureTech has presented data demonstrating high expression of galectin-9 across various solid tumor types and blood cancers and has found in several cancers that galectin-9 levels correlate with shorter time to disease relapse and poor survival. LYT-200 is currently being evaluated in a Phase 1/2 adaptive design trial for the potential treatment of metastatic solid tumors and in a clinical trial for the potential treatment of AML.
About PureTech Health
PureTech is a biotherapeutics company dedicated to changing the treatment paradigm for devastating diseases. The Company has created a broad and deep pipeline through the expertise of its experienced research and development team and its extensive network of scientists, clinicians and industry leaders. This pipeline, which is being advanced both internally and through PureTech's Founded Entities, is comprised of 28 therapeutics and therapeutic candidates, including two (Plenity® and EndeavorRx®) that have received both U.S. FDA clearance and European marketing authorization and a third (KarXT) that will soon be filed for FDA approval, as of the most recent update by the Company. 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 based on unique insights in immunology and drug development.
For more information, visit www.puretechhealth.com or connect with us on Twitter @puretechh.
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