On November 7, 2022 Pionyr Immunotherapeutics, Inc., a company developing first-in-class Myeloid TuningTM antibody therapeutics that enhance the body’s anti-tumor immunity by altering, or "tuning," immune cells within the tumor microenvironment, reported that it will present pre-clinical data showing the potential for its PY265 program to treat solid tumors, as a single agent and in combination with checkpoint inhibitor (CPI) therapy (Press release, Pionyr Immunotherapeutics, NOV 7, 2022, View Source [SID1234623299]). The data will be presented in a poster session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th annual meeting November 10th to the 11th in Boston, Massachusetts.
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PY265 is a monoclonal antibody targeting macrophage receptor with a collagenous structure (MARCO), a protein expressed on the surfaces of immuno-suppressive myeloid cells including tumor-associated macrophages (TAMs) and monocytic myeloid-derived suppressor cells (MDSCs). In experiments with human monocyte-derived macrophages, PY265 bound MARCO and stimulated myeloid cell reprogramming through induction of rapid phosphorylation events, transcriptional activation of pro-inflammatory pathways, production of cytokines and chemokines, and upregulation of cell surface activation receptors. By reprogramming myeloid cells, PY265 remodels the TME to unleash anti-tumor immunity and converts CPI-resistant tumors into treatment-responsive tumors.
In mice, a murine version of PY265 demonstrated significant anti-tumor activity—as a single agent in CPI-sensitive tumor models and in combination with anti-PD-1 in CPI-resistant tumor models. In a non-human primate toxicokinetic study, PY265 was generally well tolerated at all dose levels tested.
"MARCO is an attractive target for Myeloid Tuning representing a novel mechanism of action distinct from other myeloid-directed therapies currently in development," said Kevin Baker, Ph.D., Pionyr Senior Vice President and Chief Development Officer. "Inside the tumor microenvironment, MARCO is highly expressed on immunosuppressive myeloid cells, and blocking MARCO has been shown in earlier studies to reprogram those immunosuppressive cells into pro-inflammatory myeloid cells. The data we present at SITC (Free SITC Whitepaper) is consistent with the body of research in myeloid tuning we’ve assembled, adds to our confidence in the powerful therapeutic potential for this approach, and supports clinical development of PY265."
Poster Presentation at SITC (Free SITC Whitepaper) 2022
Abstract 1342
Title: Therapeutic targeting of MARCO with PY265 antibody promotes myeloid cell reprogramming and unleashes anti-tumor immunity
Location: Poster Hall
Date/Time: November 10-11, 9:00 AM to 9:00 PM ET
The poster will be available on the Pionyr company website after the completion of the SITC (Free SITC Whitepaper) poster session.
About Myeloid TuningTM
Pionyr has developed a therapeutic platform called Myeloid TuningTM, a process that rebalances the tumor microenvironment (TME) to promote anti-tumor immunity. Myeloid cells are a type of immune cell and are part of a family of cell types that regulate both the activation and suppression of the immune response to cancer.
One such critical type of myeloid cell, tumor-associated macrophages (TAMs), are a key component of the TME. TAMs are generally categorized into two functionally contrasting subtypes, called M1-like and M2-like macrophages. M1-like macrophages are inflammatory and have anti-tumor functions, including directly mediating antibody-dependent cell-mediated cytotoxicity (ADCC) to kill tumor cells. Alternatively, M2-like macrophages are immune suppressive, and thereby inhibit T-cell-mediated anti-tumor responses, allowing for tumor angiogenesis, growth, and progression.
Myeloid Tuning describes the process of introducing agents that shift the balance of inhibitory myeloid cells—including M2-like TAMs—toward a more inflammatory, M1-like phenotype, to promote anti-tumor immune responses in the TME that destroy solid tumors.