LYT-200

 

Our programs
Discovery
Preclinical
Phase 1
Phase 2
Phase 3
LYT-200
Anti-Galectin-9 MAb
Solid tumors

1

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 monoclonal antibody targeting a foundational immunosuppressive protein, galectin-9, for the potential treatment of solid tumors, including pancreatic ductal adenocarcinoma, colorectal cancer and cholangiocarcinoma, that are difficult to treat and have poor survival rates.

Phase completedPhase in progressRegistration-enabling studies planned
Monoclonal antibody targeting galectin-9 in development for the treatment of solid tumors 

LYT-200 is a fully human IgG4 monoclonal antibody (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 are difficult to treat 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 are difficult to treat 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 December 2020, PureTech announced the initiation of its Phase 1 clinical trial of LYT-200 for the potential treatment of metastatic solid tumors that are difficult to treat and have poor survival rates. LYT-200 is currently being evaluated in the first stage of an adaptive Phase 1/2 trial. The primary objective of the Phase 1 portion of the trial is to assess the safety and tolerability of escalating doses of LYT-200 in order to identify a dose to carry forward into a subsequent Phase 2 trial. The Phase 1 will also assess LYT-200’s pharmacokinetic and pharmacodynamic profiles. 
    • 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 expects results from its Phase 1 clinical trial of LYT-200 for the potential treatment of metastatic solid tumors in the fourth quarter of 2021. Following the topline results, PureTech intends to initiate the Phase 2 expansion cohort portion of the trial, which will further assess the recommended Phase 2 dose as a single agent or in combination with chemotherapy and anti-PD-1 therapy in multiple solid tumor types, including pancreatic cancer and cholangiocarcinoma.

PureTech's LYT-200 is a clinical stage, fully human mAb that is designed to target galectin-9, an immunosuppressive protein that simultaneously activates multiple immunosuppressive pathways in the tumor microenvironment and is prominently expressed in multiple difficult-to-treat cancers, including breast cancer, pancreatic and cholangiocarcinoma. PureTech has presented preclinical data demonstrating high expression of galectin-9 across breast cancer, pancreatic and cholangiocarcinoma samples and found that the highest levels of galectin-9 correlated with shorter time to disease relapse and poor survival. These data suggest that galectin-9 could be significant both as a therapeutic target for a range of cancers and as a cancer biomarker. Preclinical animal and patient-derived organoid tumor models also showed the potential efficacy of LYT-200 and the importance of galectin-9 as a target. LYT-200 is currently being evaluated in a Phase 1/2 adaptive design trial.


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