LYT-210

Our programs
Discovery
Preclinical
Phase 1
Phase 2
Phase 3
LYT-210
Anti-Delta-1 MAb
Solid tumors

Preclinical

Solid tumors

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


LYT-210 is a fully human IgG1 mAb directed against the δ1 chain of T cells bearing γδT cell receptors (TCRs) we are designing for antibody-dependent cell-mediated cytotoxicity and antibody-dependent cellular phagocytosis (ADCP).

Phase completedPhase in progress
Fully human monoclonal antibody targeting immunosuppressive and pathogenic γδ1 T cells for immuno-oncology

PureTech is developing LYT-210, a fully human IgG1 mAb directed against the δ1 chain of T cells bearing γδT cell receptors (TCRs), which is being designed for antibody-dependent cell-mediated cytotoxicity and antibody-dependent cellular phagocytosis (ADCP).

  • 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. The publication demonstrated the role of newly discovered immunosuppressive mechanisms involving immunosuppressive γδ1 T cells, which was the basis of developing LYT-210.
  • 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-210 is a fully human IgG1 mAb directed against the δ1 chain of T cells bearing γδT cell receptors (TCRs) that PureTech is designing for antibody-dependent cell-mediated cytotoxicity and ADCP.
    • γδ1 T cells execute potent immunosuppressive function via multiple mechanisms, which facilitates cancer progression. PureTech is designing LYT-210 to eliminate γδ1 T cells, and thereby potentially relieve immunosuppression, which PureTech believes could enable immune-mediated cancer attack.
    • PureTech believes that γδ1 T cells represent an important new immuno-oncology target because they:
      • Activate multiple immunosuppressive pathways;
      • Have expression correlated with poor outcomes for multiple solid tumor types;
      • Have preclinical evidence that showed improvement in survival in the KPC pancreatic cancer mouse model where approved checkpoint inhibitors are ineffective. PureTech has since obtained data with anti-δ1 antibodies in PDOT systems;
      • While elevated in the context of cancer, have low expression under normal physiological conditions which indicates a potential safety window;
      • Represent an attractive target; to PureTech's knowledge, there are no other companies developing a therapeutic candidate targeting immunosuppressive and pathogenic γδ1 T cells.
  • 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 November 2019, PureTech presented new preclinical data at the Society for Immunotherapy of Cancer (SITC) 34th Annual Meeting. The data presented on LYT-210 showed that γδ1 T cells were the abundant T cell within the studied tumors, which included pancreatic, colorectal, cholangiocarcinoma and liver cancer. PureTech also presented data showing that LYT-210 depletes immunosuppressive γδ1 T cells through cytotoxicity and phagocytosis in patient blood and tumor samples. Together, these findings further support the ability of LYT-210 to potentially restore the immune system’s ability to fight difficult-to-treat cancers.
  • Expected Milestones
    • PureTech plans to advance additional preclinical and biomarker studies for LYT-210 in 2021.

LYT-210 is PureTech's product candidate targeting immunosuppressive γδ1 T cells in solid tumors and autoimmune disorders for a range of cancer indications and autoimmune disorders. LYT-210 is being designed to eliminate γδ1 T cells, and thereby potentially relieve immunosuppression, which PureTech believes could enable immune mediated cancer attack.


Monoclonal antibody aimed at immunosuppressive γδ1 T cells

Immunosuppressive γδ1 T cells

  • Solid tumors harbor immunosuppressive γδ1 T cells that correlate with tumor aggressiveness / lower rate survival
  • Works through multiple pathways to cause immunosuppression in the tumor micro-environment 
  • LYT-210 is a fully human monoclonal IgG1 antibody (cross reacts with monkey)

Image adapted from CellPress: REVIEW: γδ T cells: Unexpected Regulators of Cancer Development and Progression.

DC = dendritic cell; TAM = tumor associated macrophage; MDSC = myeloid derived suppressor cell; IL17 = interleukin 17

 


Multiple lines of preclinical data supporting therapeutic potential

Single agent activity in KPC (pancreatic cancer) model (Published in Cell)



T cell activation with an anti-δ1 mAb in patient-derived organoid model


Colorectal cancer

Colorectal cancer liver metastases

LYT-210 candidate clone has excellent drug properties


  • High affinity and specificity/selectivity for pathogenic γδ1 T cells
  • Species cross reactivity to enable IND tox
  • Desired function: Inducing ADCC/ADCP and activating suppressed effector T cells in patient-derived tumor models
  • Proof of principle in animal models:
    • Targeting immunosuppressive γδ T cells significantly prolongs survival in a KPC model
    • Targeting immunosuppressive γδ T cells synergizes with checkpoint inhibitors in melanoma and lung cancer models


Cell. 2016 Sep 8;166(6):1485-1499; *Tool antibody that blocks mouse immunosuppressive γδ T cells

Note: For patient-derived organoids: Analyzed n = 22 tumor samples; success defined as: >20% upregulation of at least two out of three T cell activation markers; Success achieved in 63% of tumors with majority showing >2-fold activation