LYT-210

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

Preclinical

Solid tumors

>32K/year U.S. (Metastatic pancreatic cancer)
>33K/year U.S. (Metastatic CRC)
>4K/year U.S. (Metastatic cholangiocarcinoma)


Fully human IgG1 monoclonal antibody directed against the delta-1 chain of T cells bearing gamma delta-1 T cell receptors that we have designed to target and deplete immunosuppressive gamma delta-1 T cells in cancer.

Phase completedPhase in progress

1 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-210 is safe or effective for use by the general public for any indication.

Fully human monoclonal antibody (mAb) targeting immunomodulatory gamma delta-1 (γδ1) T cells for immuno-oncology

LYT-210 is a preclinical therapeutic candidate designed to target immunomodulatory γδ1 T cell receptors (TCRs), and is being developed for a range of cancer indications.

  • Key Points of Innovation & Differentiation
    • Immune checkpoint inhibitors, including therapies that target PD-1, PDL-1 and cytotoxic T-lymphocyte-associated antigen 4, or CTLA-4, have been developed to counteract multiple mechanisms of immune evasion by a number of different tumor types. Recent reports suggest that marketed drugs against these targets had sales exceeding $28 billion in 20202. Unfortunately, a large proportion of patients, especially those with immunologically silent tumors such as PDAC, CCA and some types of CRC, respond sub-optimally to such agents.

      

    • Gamma delta-1 T cells execute potent immunosuppressive function via multiple mechanisms, as illustrated on the left side of the figure above (LYT-210 gamma delta-1 mAb), which facilitates cancer progression. We have designed LYT-210 to eliminate gamma delta-1 T cells, and thereby potentially relieve immunosuppression, which we believe could enable immune mediated cancer attack.
    • We believe that gamma delta-1 T cells represent an important new IO target because they:
      • Activate multiple immunosuppressive pathways in the tumor microenvironment, or TME;
      • Have expression correlated with poor outcomes for multiple solid tumor types; and
      • Target immunosuppressive gamma delta T cells in vivo, which improved survival and reactivated cytotoxic T cells in the TME in the KPC orthotopic pancreatic cancer mouse model where approved checkpoint inhibitors are ineffective.
    • We are targeting immunosuppressive, tumorigenic gamma delta-1 T cells for depletion, rather than administering cytotoxic gamma delta-2 T cells as a cell therapy, which is a complementary gamma delta T cell modality.
  • Program Discovery Process by the PureTech Team
    • In order to identify approaches with the potential to provide significant therapeutic benefit to cancer patients, we 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. As a result of this search, and through our extensive network of advisors and collaborators, we identified a foundational immunosuppressive mechanism involving immunosuppressive gamma delta-1 T cells, which was the basis of LYT-210.
  • Patient Need & Market Potential
    • In the U.S., there are approximately 62,210 new pancreatic cancer patients, of which 52% present with metastatic disease, approximately 151,030 new CRC patients, of which 22% present with metastatic disease, and approximately 8,000 new CCA patients, of which 50% present with metastatic disease, in each case, per year. Unfortunately, a large proportion of patients, especially those with immunologically silent tumors such as PDAC, CCA and some types of CRC respond sub-optimally to immune checkpoint inhibitors, representing a significant patient population that has yet to receive benefit from any immuno-therapy agents.
  • Milestones Achieved & Development Status
    • In April 2021, we presented new research at the American Association for Cancer Research (AACR) Annual Meeting demonstrating that LYT-210 is both highly specific and highly potent, rapidly inducing cell death of immunomodulatory gamma delta-1 T cells, while sparing other T cells, such as cytotoxic gamma delta T cells, that play important roles in a healthy immune response. The research was conducted using both patient blood and cancer tissue.
    • Antibodies against gamma delta-1 T cells reactivated immunosuppressed T cells in the TME in PDOTs: To better assess the potential activity of the anti-delta-1 antibody, we employed PDOTs from primary and metastatic tumors spanning various solid tumor types such as pancreatic, CRC, CCA, hepatocellular cancer and neuroendocrine tumors of the gastrointestinal (GI) tract in order to assess the prevalence of tumor-infiltrating gamma delta-1 T cells and the capacity of the antibodies to restore tumor-infiltrating immune cell effector activity. We observed positive responses in approximately 60% of the PDOTs we analyzed, representing 19 patients, which showed that direct treatment of PDOTs with LYT-210 resulted in robust reactivation of effector T cells.
    • The figure below illustrates representative data from CRC patients, from a collection of 19 human tumor organoid samples where we ran this experiment.

      

    • Absence of gamma delta T cells greatly increased survival in a pancreatic cancer mouse model: In order to assess the relevance of gamma delta T cells in the development and progression of pancreatic cancer, we assessed the survival of immunocompetent mice which have gamma delta T cells (wild type) in a KPC mouse pancreatic model. Mice were treated with an antibody, UC3-10A6, which functionally blocks immunosuppressive mouse gamma delta T cells. As shown in the figure below, when mice harboring pancreatic tumors are treated with an antibody against immunosuppressive gamma delta T cells, survival was
      greatly increased, as represented by the navy curve.  

     

    • Mucosa-infiltrating pathogenic gamma delta-1 T cells may contribute to autoimmune diseases: Intraepithelial lymphocytes expressing gamma delta-1 T cells are tissue-resident T cells that play a key role in homeostasis of the intestinal epithelium. It has been recently observed that chronic inflammation can permanently reconfigure the tissue-resident T cell compartment resulting in the repopulation of the GI mucosa with pathogenic and cytotoxic gamma delta-1 T cells. Establishment of pathogenic gamma delta-1 T cells along the GI tract tilts the gut environment towards a chronic inflammatory state, contributing to the pathophysiology of GI tract and inflammatory diseases, such as refractory celiac disease.
  • Expected Milestones
    • We expect to complete additional biomarker studies for LYT-210 in 2022.
  • Intellectual Property
    • We have broad intellectual property coverage for these antibody-based immunotherapy technologies, including exclusive rights to two patent families 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 use related immuno-oncology technologies and antibodies directed to pro-inflammatory gamma delta T cells for use in the treatment of inflammatory conditions, such as autoimmune disorders.
    • As of December 31, 2021, there are two families covering compositions of matter and methods of use for antibodies targeting gamma delta-1 T cells, including LYT-210, which are directed to the use of these antibodies for the treatment of cancer. This intellectual property in total comprises one granted U.S. patent, two pending U.S. patent applications and eight foreign patent applications. Any patents issuing from pending applications with respect to LYT-210 are expected to expire in between 2037 and 2041, of which expiration dates are exclusive of possible patent term adjustments or extensions or other periods of exclusivity.

2 GlobalData Sales and Forecast Database, 2020 sales data pulled 1/24/2022.

3 Tool antibody that blocks mouse immunosuppressive gamma delta T cells.

Our anti-cancer programs target emerging, foundational immunosuppressive mechanisms pursue a differentiated approach to cancer types that currently do not have adequate effective treatments. 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.