Metastatic/locally advanced solid tumors, including urothelial and head and neck cancers, and hematological malignancies, such as acute myeloid leukemia
Metastatic/locally advanced solid tumors, including urothelial and head and neck cancers, and hematological malignancies, such as acute myeloid leukemia
Our programs 1
Discovery
Preclinical
Phase 1
Phase 2
Phase 3
LYT-200
Anti-Galectin-9 mAb
Solid tumors and hematological malignancies

1

Solid tumors

~82K/year U.S. (Bladder cancer)
~66K/year U.S. (Head and neck cancers)
~20K/year U.S. (AML)


Fully human IgG4 monoclonal antibody, or mAb, designed to inhibit the activity of galectin-9, an immunomodulatory molecule expressed by tumors and immune cells and shown to suppress the immune system from recognizing and destroying cancer cells. We are developing LYT-200 for the treatment of metastatic/locally advanced solid tumors that have poor survival rates, including urothelial and head and neck cancers. We are also developing LYT-200 for the treatment of hematological malignancies, such as acute myeloid leukemia (AML).

Phase completedPhase in progress
1 We have an active IND on file with the FDA for LYT-200. The FDA and corresponding regulatory authorities will ultimately review our clinical results and determine whether our wholly-owned therapeutic candidates are safe and effective. No regulatory agency has made any such determination that LYT-200 is safe or effective for use by the general public for any indication.

Metastatic/locally advanced solid tumors, including urothelial and head and neck cancers, and hematological malignancies, such as acute myeloid leukemia and high-risk myelodysplastic syndrome

LYT-200 is being developed for the treatment of metastatic/locally advanced solid tumors, including urothelial and head and neck cancers, as well as for the treatment of hematological malignancies, such as acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS). It is a fully human IgG4 monoclonal antibody designed to inhibit the activity of galectin-9, an immunomodulatory molecule expressed by tumors and immune cells and shown to suppress the immune system from recognizing and destroying cancer cells. A wide variety of preclinical data support the potential clinical efficacy of LYT-200 and the importance of galectin-9 as a target and suggests a potential opportunity for biomarker development.
  • Key Points of Innovation & Differentiation
    • Galectin-9 promotes and facilitates multiple immunosuppressive pathways by expanding regulatory T cells, shifting macrophages from the M1 to M2 phenotype, and inducing apoptosis of activated CD4+ and CD8+ T cells. High expression of galectin-9 is evident in solid tumors and in hematological malignancies, both in patients’ tumors and blood, and correlates with poor survival outcomes and aggressive disease. Our preclinical work demonstrates single agent mechanistic and anti-tumor efficacy of LYT- 200 in multiple animal and patient-derived tumor cell models. For example, LYT-200 outperforms anti-PD-1 in a standard B16F10 melanoma model as a single agent. LYT-200 also synergizes with anti-PD-1 in activating CD4 and CD8 T cells in melanoma and pancreatic in vivo models. We are advancing LYT-200 to inhibit the multiple effects of galectin-9 and thereby potentially removing a key immunosuppressive barrier that would enable the immune system to attack and destroy the tumor.
    • A 2021 study published in Nature Communications proposed that the molecular mechanism by which PD-1 and galectin-9 interact to shield tumors from the immune system demonstrates for the first time that galectin-9 is a ligand for PD-1 and emphasizes its importance as a promising target for immunotherapy3. This provided further evidence that galectin-9 acts as a key regulator of the immune response to tumors and supports its importance as a potential target for cancer treatment.
    • We believe that LYT-200 is the most advanced clinical program against this target. It has the potential to be used as a single agent and safely in combination with checkpoint inhibitors and other anti-cancer therapies, depending on the cancer type, treatment setting and line of treatment. Additionally, targeting galectin-9 gives LYT-200 the potential to address a high unmet need for more effective therapies with improved tolerability for acute myeloid leukemia (AML), a devastating disease in which prognosis is poor.
  • Program Discovery Process by the PureTech Team
  • Patient Need & Market Potential
  • Milestones Achieved & Development Status
  • Expected Milestones
  • Intellectual Property
1 Walter, R. B., Othus, M., Burnett, A. K., Löwenberg, B., Kantarjian, H. M., Ossenkoppele, G. J., Hills, R. K., Ravandi, F., Pabst, T., Evans, A., Pierce, S., Vekemans, M.,
Appelbaum, F. R., & Estey, E. H. (2015). Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOG and MD Anderson Cancer Center.
Leukemia, 29(2), 312–320. https://doi.org/10.1038/leu.2014.242
2 Brandwein, J., Saini, L. M., Geddes, M., Yusuf, D., Liu, F., Schwann, K., Billawala, A., Westcott, C., Kurniawan, J. A., & Cheung, W. Y. (2020). Outcomes of patients with
relapsed or refractory acute myeloid leukemia: a population-based real-world study. American Journal of Blood Research, 10(4), 124–133.
3 Cancer of the Urinary Bladder – Cancer Stat Facts. (n.d.). National Cancer Institute. https://seer.cancer.gov/statfacts/html/urinb.html
4 Saginala, K., Barsouk, A., Aluru, J. S., Rawla, P., Padala, S. A., & Barsouk, A. (2020). Epidemiology of Bladder Cancer. Medical Sciences, 8(1), 15. https://doi.org/10.3390/
medsci8010015
5 Head and Neck Cancer – Statistics. (2022, December 16). Cancer.Net. https://www.cancer.net/cancer-types/head-and-neck-cancer/statistics
6 Pisani, P., Airoldi, M., Allais, A., Valletti, P. A., Battista, M., Benazzo, M., Briatore, R., Cacciola, S., Cocuzza, S., Colombo, A., Conti, B., Costanzo, A., Della Vecchia, L., Russi,
E. G., Fantozzi, C., Galizia, D., Garzaro, M., Genta, I., Iasi, G. A., . . . Zigliani, A. (2020). Metastatic disease in head & neck oncology. Acta Otorhinolaryngologica Italica,
40(SUPPL. 1), S1–S86. https://doi.org/10.14639/0392-100x-suppl.1-40-2020
7 Leukemia – Cancer Stat Facts. (n.d.). National Cancer Institute. https://seer.cancer.gov/statfacts/html/leuks.html
8 Acute Myeloid Leukemia – Cancer Stat Facts. (n.d.). National Cancer Institute. https://seer.cancer.gov/statfacts/html/amyl.html
9 Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. doi: 10.1056/NEJMoa0802656. PMID: 18784101.
Given its design to inhibit the activity of galectin-9, LYT-200 is being advanced to potentially remove a key immunosuppressive barrier that would enable the immune system to attack and destroy the tumor. Our fully human monoclonal antibody candidate has potential both as a single agent and in combination with existing therapies such as checkpoint inhibitors and chemotherapeutics.

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