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 an investigational, fully human IgG1 monoclonal antibody (mAb) directed against the delta-1 (γδ1) chain of T cells bearing γδ1 T cell receptors (TCRs) for antibody dependent cell-mediated cytotoxicity and antibody-dependent cellular phagocytosis (ADCP).

Phase completedPhase in progress
Monoclonal antibody aimed at immunosuppressive γδ1 T cells

PureTech is developing LYT-210, an investigational, fully human IgG1 monoclonal antibody (mAb) directed against the delta-1 (γδ1) chain of T cells bearing γδ1 T cell receptors (TCRs) for antibody-dependent cell-mediated cytotoxicity and antibody-dependent cellular phagocytosis (ADCP).

We are advancing a broad pipeline of programs to treat cognitive deficiency and improve symptoms associated with medical conditions across neurology and psychiatry, including attention-deficit hyperactivity disorder (ADHD), major depressive disorder (MDD), autism spectrum disorder (ASD), multiple sclerosis (MS) and various other neuroinflammatory diseases. We are also developing associated clinical monitors and measurement-based care applications. Our lead, patented technology platform is exclusively licensed from the lab of Dr. Adam Gazzaley at the University of California, San Francisco (UCSF), and augmented by proprietary adaptive algorithms developed by our team.

  • 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 George Miller, MD, at New York University. PureTech began collaborating with Dr. Miller prior to his ground-breaking research being published 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 in the US 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 an investigational, fully human, IgG4 mAb targeting immunosuppressive/pathogenic γδ1 T cells for a range of cancer indications and autoimmune disorders.
    • γδ1 T cells execute potent immunosuppressive function via multiple mechanisms, which facilitates cancer progression. PureTech has designed 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;
      • 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 our 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 this immuno-therapy technology, including exclusive rights to four families of patent filings that are exclusively licensed from or co-owned with New York University. Three of these families 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. The fourth family covers antibodies that are directed to pro-inflammatory γδ T 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.
    • As of December 2019, there are three families of intellectual property within this patent portfolio covering compositions of matter and methods of use for antibodies targeting delta-1 chain of T cell Receptor, including LYT-210, which include one issued patent, nine pending U.S. applications and one PCT application. Two of these families, one of which includes the issued patent, are related to compositions and methods of use in oncology applications. The third family is directed to methods of use in the treatment of inflammatory conditions, such as autoimmune disorders. The issued patent and any patents issuing from pending applications with respect to LYT-210 are expected to expire in 2039 through 2040.
    • In addition, there is one family of intellectual property covering compositions of matter and methods of use for related immuno-oncology technologies, which in total comprises three pending patent applications in U.S. and foreign jurisdictions. This family is expected to expire in 2037. All 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 continue to advance preclinical and biomarker studies for LYT-210 in 2020.

PureTech’s LYT-210 targets γδ1 T cells for the potential treatment of a range of solid tumors and autoimmune disorders. LYT-210 is designed to eliminate γδ1 T cells, and thereby potentially relieve immunosuppression, which PureTech believes could enable immune-mediated cancer attack.


This figure illustrates the impact of protumorigenic γδ1 T cells on tumor progression

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 lgG1 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

 


As shown in the below figure on the left, when mice with pancreatic cancer were treated with an antibody against immunosuppressive γδ T cells, which is represented by the dark blue curve, survival was greatly increased. The below figure in the middle illustrates examples of in vitro T cell activation with antibodies against γδ T cells.

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


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


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