Sensei Biotherapeutics is developing a pipeline of investigational medicines that work by “awakening” the immune system to defend and defeat cancer and infectious diseases.

 

APPROACH/TARGET
INDICATION
DISCOVERY
PRECLINICAL
PHASE 1
PHASE 2
PHASE 3
SNS-101
VISTA
Solid Tumors
 
 
 
 
 
 
  • VISTA is an immunoregulatory receptor and is highly expressed on various immune system cells including neutrophils, monocytes, macrophages, basophils, and dendritic cells.
  • VISTA blockade appears to dramatically modulate the tumor microenvironment toward a state that favors an immune system response, resulting in improved T cell effector function and anti-tumor activity.
SNS-102
VSIG4
Solid Tumors
 
 
 
 
 
 
SNS-103
ENTPDase1/CD39
Solid Tumors
 
 
 
 
 
 
SNS-401-NG
Multiple Tumor Antigens
Merkel Cell Carcinoma
 
 
 
 
 
 
  • First custom MCC vaccine consisting of Merkel Cell Polyoma Virus (MCPyV) epitopes together with other patient-specific antigens.
  • MCC is a rare but highly aggressive neuroendocrine carcinoma of the skin in which MCPyV infection and chronic exposure to ultraviolet radiation are key risk factors.
  • Although systemic PD-1/PD-L1 inhibition therapy is associated with a high overall response rate, prolonged durable responses, and good tolerability in advanced-stage MCC, refractory PD-1/PD-L1 inhibitor disease remains a significant unmet medical need with an aggressive clinical course.
Head and Neck Cancer
 
 
 
 
 
 
Lung Cancer
 
 
 
 
 
 
Melanoma
 
 
 
 
 
 
Breast Cancer
 
 
 
 
 
 
ImmunoPhage
Antibody

SNS-101

VISTA is an antibody that is rich in opportunities for clinical development

VISTA is a novel immune checkpoint that is expressed primarily on myeloid cells; it has been shown in multiple experimental mouse tumor models to be highly complementary to the PD-1/PD-L1 pathway. Preclinical studies have shown that VISTA is implicated in PD-1/PD-L1 resistance, and that therapeutic intervention has the potential to be effective as a monotherapy and synergistic with PD-1/PD-L1 inhibition in vivo.

For years, VISTA has been shown to be an important and highly relevant cancer immunotherapy target. However, development of therapeutics targeting VISTA was hampered by the presence of a pharmacological ‘sink’ due to the high expression of VISTA on hematopoietic (blood) cells. In addition, recent findings have shown that VISTA binds its receptor on T-cells (called PSGL-1) at sub-physiologic pH (~6).

Sensei has developed SNS-101, a potent pH-dependent product candidate antibody that blocks the interaction of VISTA with its receptor, PSGL-1, which could result in a favorable pharmacokinetic (PK) profile and selective activity in the acidic tumor microenvironment – a critical feature of this product candidate. SNS-101 targets VISTA only at the pH of the tumor (pH ~6), which is lower than the blood (pH 7.4), enabling the selective inhibition of VISTA within the tumor.  Preclinical studies have shown that SNS-101 binds VISTA with >600-fold specificity at pH 6.0 compared to pH 7.4. In vivo studies conducted to date confirm the promising activity of SNS-101.

VISTA has been shown to play an important role in multiple tumor types, including non-small cell lung cancer (NSCLC).  We believe therapeutic intervention with SNS-101 has the potential to be an effective monotherapy as well as to act synergistically with agents inhibiting the PD-1 checkpoint.

Sensei presented preclinical data for SNS-101 at the Society for Immunotherapy of Cancer’s (SITC) Annual Meeting in November 2021 and has initiated IND-enabling studies.

 

 

VISTA is a Negative Regulator of T Cell Function

SNS-VSIG4

VSIG4 (V-Set And Immunoglobulin Domain Containing 4): VISG4 is a potent inhibitor of T cell activity, often overexpressed on macrophages within the tumor microenvironment. Sensei believes that a tumor-selective blocking monoclonal antibody will have potent anti-tumor immune effects. Sensei is extending its approach to developing antibodies with enhanced tumor selective activity to other candidate immune checkpoint targets, and anticipates selecting a product candidate from this program in 2023.

SNS-401-NG

SNS-401-NG is an ImmunoPhage™ being developed in collaboration with investigators at the University of Washington. The University of Washington is one of the premier cancer centers worldwide for the research and treatment of Merkel Cell Carcinoma. Researchers there have mapped the B- and T-cell epitopes of the Merkel Cell Polyoma Virus. Sensei intends to initiate IND-enabling studies for this product candidate in the second half of 2022. The first clinical application is directed to the treatment Merkel Cell Carcinoma (MCC), an aggressive form of skin cancer commonly driven by the Merkel Cell Polyoma Virus. If clinical proof of concept is achieved, Sensei plans to evaluate a broader basket study in patients with head and neck cancer, lung cancer, melanoma, and triple negative breast cancer.

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