LYT-200

 

Our programs
Discovery
Preclinical
Phase 1
Phase 2
Phase 3
LYT-200
Anti-Galectin-9 MAb
Solid tumors
IND & initiation of Phase 1 study in 2020

Preclinical

Solid tumors

>50K/year U.S. (Metastatic CRC)
>28K/year U.S. (Metastatic pancreatic cancer)
>4K/year U.S. (Metastatic cholangiocarcinoma)


LYT-200 is a fully human IgG4 mAb that is designed to block galectin-9, which we are developing for the treatment of solid tumors, including PDAC, CRC and CCA, that do not respond to approved checkpoint inhibitors and have poor survival rates.

Phase completedPhase in progress
Monoclonal antibody targeting galectin-9 in development for the treatment of solid tumors 

LYT-200 is a fully human IgG4 mAb that is designed to block galectin-9, which PureTech is developing for the treatment of solid tumors, including pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC) and cholangiocarcinoma (CCA), that do not respond to approved checkpoint inhibitors and have poor survival rates.

  • Program Discovery Process by the PureTech Team
    • PureTech undertook a global, proactive search to discover important new scientific insights and technologies that could address the challenge of multiple mechanisms of immunosuppression in current therapeutics. Through this process, PureTech identified the pioneering work of its collaborator prior to publication in Cell and Nature Medicine. The publications demonstrate the role of newly discovered immunosuppressive mechanisms involving galectin-9, which was the basis of developing LYT-200.
  • Patient Need & Market Potential
    • Each year the United States there are approximately:
      • 57,000 new pancreatic cancer patients, of which 50 percent present with metastatic disease;
      • 146,000 new CRC patients, of which 35 percent present with metastatic disease; and
      • 8,000 new cholangiocarcinoma patients, of which 50 percent present with metastatic disease.
    • These all represent significant patient populations that have yet to receive benefits from any immuno-therapy agents.
  • Innovative Approach to Solving the Problem
    • LYT-200 is a fully human IgG4 mAb that is designed to block galectin-9, which PureTech is developing for the treatment of solid tumors, including PDAC, CRC and CCA, that do not respond to approved checkpoint inhibitors and have poor survival rates.
    • PureTech believes LYT-200 could meet the criteria for a potential immuno-oncology therapeutic because:
      • Galectin-9 promotes and facilitates multiple immunosuppressive pathways by, for example, 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 tumors and in cancer patients’ blood, and correlates with poor survival outcomes and aggressive disease in multiple solid tumor types;
      • In order to assess the effects of LYT-200 in murine models of cancer, a mouse monoclonal antibody, which PureTech refers to as mIgGI-200, that targets the same epitope on galectin-9 was developed. A mouse IgG1 isotype has blocking function similar to the human IgG4 isotype. Preclinical evidence PureTech generated has confirmed that mIgG1-200 is efficacious in inhibiting tumor growth in pancreatic cancer (KPC) and melanoma (B16F10) mouse models of cancer. PureTech has used mIgG1-200 as single agent in both the pancreatic cancer (KPC) and the melanoma (B16F10) mouse models of cancer. In both of these models, compared to control, PureTech saw a significant tumor growth reduction. Equally, in the KPC model the Company observed that administration of LYT-200 both as a single agent, and in combination with chemotherapy (gemcitabine/nab-paclitaxel), significantly prolonged survival of pancreatic tumor bearing mice, compared to control, while chemotherapy alone did not give a significant prolongation of survival compared to control animals;
      • LYT-200 also activated effector T cells in ex vivo models of patient derived tumor organoids (PDOTs) in multiple tumor types (pancreatic cancer, colon cancer, cholangiocarcinoma, etc.);
      • While elevated in the context of cancer, galectin-9 has low expression under normal physiological conditions which indicates a potential safety window which has been further supported by the lack of tolerability concerns to date in our good laboratory practice, or GLP, studies with LYT-200 even at extremely high doses, such as 300 mg/kg in non-human primates (~100 mg/kg human equivalent dose).
  • Intellectual Property
    • PureTech has broad intellectual property coverage for these antibody-based immunotherapy technologies, including exclusive rights to nine families of patent filings that are exclusively licensed from or co-owned with New York University which cover antibodies that target immunosuppressive agents and mechanisms and methods of use for the treatment of solid tumors, such as pancreatic cancer, CRC, melanoma, gastric cancer, breast cancer and various other cancers, and one family of patent filings that cover antibodies directed to pro-inflammatory γδT cells for use in the treatment of inflammatory conditions, such as autoimmune disorders, for example, IBD, ulcerative colitis, Crohn’s disease and celiac disease, among others.
    • PureTech exclusively licensed and co-own a patent portfolio of ten patent families from New York University. As of June 30, 2020, there are five families of intellectual property within this patent portfolio covering compositions of matter and methods of use for antibodies targeting galectin-9, including LYT-200, which in total comprise two issued U.S. patents which are expected to expire in 2038, seven pending U.S. patent applications, which if issued are expected to expire 2037-2040, three international PCT applications, and 12 pending applications in foreign jurisdictions. There are two families covering compositions of matter and methods of use for antibodies targeting γδT cells, including LYT-210, which are directed to the use of these antibodies for the treatment of cancer and pro-inflammatory and autoimmune disorders, which in total comprise one granted U.S. patent, one pending U.S. patent application and two international PCT applications.
    • In addition, there are two additional families of intellectual property covering compositions of matter and methods of use for related IO technologies, which in total comprise six patent applications in U.S. and foreign jurisdictions. PureTech's issued patents and any patents issuing from pending applications with respect to LYT-200 are expected to expire in between 2038 and 2040, any patents issuing from pending applications with respect to LYT-210 are expected to expire in between 2039 and 2040, and PureTech's additional families of pending applications are expected to expire in 2037, all of which expiration dates are exclusive of possible patent term adjustments or extensions or other periods of exclusivity.
  • Milestones Achieved
    • In June 2020, PureTech presented new data at the American Association for Cancer Research (AACR) 2020 Virtual Annual. The data established galectin-9 as a novel target for cancer immunotherapy and provided compelling evidence that therapies targeting galectin-9 may enable the immune system to attack an array of solid tumors. The research also established galectin-9 as an important biomarker for patient stratification.
    • In November 2019, PureTech presented new preclinical data at the Society for Immuno-therapy of Cancer (SITC) 34th Annual Meeting. The presented data indicated that galectin-9 is not only a potent therapeutic target, but also a potentially relevant biomarker. Across multiple cohorts, galectin-9 was significantly increased in blood samples of individuals with primary and metastatic pancreatic cancer, lung tumors and colorectal carcinoma, compared to healthy individuals.
  • Expected Milestones
    • PureTech intends to file an IND for LYT-200 and initiate a Phase 1 clinical trial in solid tumors in the second half of 2020, with results anticipated in 2021.

PureTech's LYT-200 is an investigational, fully human, monoclonal antibody, or mAb, that is designed to target galectin-9, a protein that regulates immunosuppression and is prominently expressed in hard-to-treat cancers such as CRC, CCA and pancreatic cancer. PureTech believes LYT-200 has shown preliminary POC in both preclinical human and mouse cancer models.


Targeting galectin-9, a fundamental immunosuppressor in cancer 

Foundational biology

  • Galectin-9 modulates multiple pathways of cancer immunosuppression disabling immune mediated cancer attack 
  • LYT-200 has potential single agent activity, as well as combination treatment potential with chemo- and immunotherapies

Proof-of-concept in preclinical models

Galectin-9 blockade: 

  • Inhibits tumor growth and increases survival in pancreatic cancer models (KPC)
  • Inhibits tumor growth in standard melanoma model outperforming anti-PD-1 treatment
  • Induces accumulation and activation of intra-tumoral cytotoxic T cells
  • Restores T cell activity in patient derived organoids

Biomarker opportunity

  • Blood and tissue expression increased in multiple tumor types, correlating with worse survival

Image adapted from J Mol Biol; 428 (16): 3266-3281; 2016

Treg = T regulatory cell; MDSC = myeloid derived suppressor cell; M1/M2 = tumor associated macrophage (TAM)1 (immunoactive) and 2 (immunosuppressed) cell; Th1 = T helper1 cell