Nodality Develops Disease-Associated PD-1 Assay System for Application in Immuno-oncology

Results of Nodality’s Single Cell Network Profiling (SCNP) Reported at the 26^th EORTC-NCI-AACR Symposium

Nodality, Inc., presented today at the 26^th EORTC-NCI-AACR Symposium (Barcelona, Spain) a newly-developed human cell-based system to quantitate PD-1 activity. Nodality’s Single Cell Network Profiling (SCNP) technology detected significant differences in PD-1+ T cell subset signaling when comparing samples from patients with chronic lymphocytic leukemia (CLL) and healthy donors. Specifically, the SCNP platform demonstrated PD-1+ T cells from CLL patients displayed dysfunctional signaling following modulation with the cytokines IL-2, IL-7 and IL-15 versus healthy donor cells. Further, the ability to quantify the effects of PD-1 modulation on T Cell Receptor (TCR) signaling through phosphorylated Extracellular signal-Regulated Kinase (p-ERK) in PD-1+ T cells was established.

“Drugs inhibiting PD-1 on the surface of T cells infiltrating tumors have provided a new and exciting approach to cancer treatment; however, the role of PD-1 on the surface of CLL cells has yet to be ascertained in depth,” commented Bernard A. Fox, Ph.D., Chief, Laboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center. “As the authors report, the evidence of dysregulated cytokine signaling, in conjunction with other findings in PD-1+ T cells demonstrate the ability to interrogate functional biology in specific immune cells targeted by immunotherapeutics. This valuable research shows the broad applicability of a technology such as SCNP to studying the effects of the tumor microenvironment on immune signaling, to developing uniquely informative markers of disease biology and the potential to inform the development of new therapies to restore T cell function.”

“Complementing our broad platform in immunology and autoimmune disease, as featured in multiple presentations at this week’s American College of Rheumatology conference, Nodality also has a strong commitment to advancing the understanding of both blood cancers and new modalities in cancer therapy,” said Laura Brege, CEO and President of Nodality, Inc. “We are proud of the PD-1 program and data being presented at the EORTC-NCI-AACR Symposium today. This work exemplifies our ability to understand key pathways relevant to discovery and development of next-generation immuno-oncology monotherapies and combinations. Our SCNP approach to the analysis of human disease promises to find answers to some of the most pressing questions in immuno-oncology and beyond.”

Poster Presentation at the EORTC-NCI-AACR Symposium:

• “Functional activity, but not PD-1 expression level, differentiates primary CLL from healthy PD1+ T cells using SCNP”

  In this study, the researchers profiled PD-1 expression and responsiveness to cytokine modulation in the CD4/CD8 T cell subsets of CLL patients (N=12) and healthy donors (N=12). The effect of T cell receptor (TCR) modulation, with or without PD-1 blockade, also was studied. IL-2, IL-7 and IL-15 induced p-STAT5 levels to a lower degree than in comparator healthy donors in PD-1+ CD8 T cells and PD-1+ CD4-/CD8- T cells in CLL patients. Further, CLL T cells showed decreased proliferation in response to TCR modulation, which was partially reversed by PD-1 blockade. The ability to quantify PD-1 modulation effects on TCR signaling through the MAP kinase pathway was also established. Additional findings of the research are available in the abstract found at this link.

  Date: Wednesday, November 19, 2014, from 6:00 PM to 7:30 PM CET
  Session: Immunotherapy (Immune checkpoints, Vaccination, Oncolytic viruses, Cytokines)
  Abstract number: 109
  Poster board: P103
  Location: International Convention Center of Barcelona, Exhibition Hall
  Authors: Erwan Le Scolan, Spencer Liang, Ling Leung, Nguyen Tan, Albert Tai, Santosh Putta, Drew Hotson, David B. Rosen, Rachael E. Hawtin

About Single Cell Network Profiling

Contemporary pharmaceutical research and development remains challenged in producing drugs able to revolutionize the treatment of many of our most intractable diseases. Nodality offers solutions with its Single Cell Network Profiling (SCNP) a multiparametric flow cytometry-based assay that, coupled with Nodality’s proprietary data analysis and visualization tools, uniquely reveals complex functional biology to inform more effective drug development decisions.

Characterizing cell signaling networks in millions of cells at the single cell level, SCNP uses simple blood draw samples and then measures functional pathway signaling in robust, human primary cell-based translational models of disease, drug activity and patient responses. Originally developed at Stanford University, SCNP does not require physical isolation of cell subsets and therefore provides real-time information on cell-cell interactions, identifies the functional signaling capacity of rare cell subsets, such as drug-resistant cells and stem cell populations, reveals the functional consequences of epigenetic mutations and enables the interrogation of immune cell communication and dysfunction in disease.

About Nodality

Nodality is advancing drug discovery, therapeutic development, and precision medicine by delivering critical and clinically actionable information to bridge gaps left by traditional R&D approaches. Nodality’s proprietary functional biology platform, Single Cell Network Profiling (SCNP), provides unprecedented insights into diseases and partners’ product candidates and is applicable through the full discovery and development process, including disease profiling, drug profiling, clinical development, and life cycle management. Nodality’s teams have expertise in achieving solutions across a very broad therapeutic landscape, with a focus on immunology and oncology, including immuno-oncology. SCNP enables smarter spending decisions and is applicable across a very broad therapeutic landscape and throughout the full discovery and development process. Nodality has established multi-year strategic collaborations with UCB Pharma S.A. (Euronext Brussels: UCB), Pfizer (NYSE: PFE) and Johnson & Johnson (NYSE: JNJ), utilizing its SCNP technology to assist the discovery and development of new therapeutic compounds.