PRESS RELEASE

Pionyr Immunotherapeutics Doses First Patient in Phase 1b Expansion Study of PY159

  • Expansion study will evaluate PY159, an anti-TREM1 antibody, as a monotherapy and in combination with pembrolizumab in patients with selected prespecified tumor histologies

SOUTH SAN FRANCISCO, CA, September 20, 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, announced it has begun dosing patients in its Phase 1b expansion study investigating PY159 in patients with prioritized cancer types: ovarian cancer, pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), HR+HER2- breast cancer, head and neck squamous cell carcinomas (HNSCC), and colorectal cancer (CRC).

We developed PY159 to target TREM1 and reprogram myeloid cells within the tumor microenvironment to promote anti-tumor responses – a novel approach to TREM1 biology for anti-tumor drug development,” said Leonard Reyno, M.D., Pionyr Executive Vice President and Chief Medical Officer. “In the Phase 1a dose escalation study, PY159 was well tolerated in doses up to 10 milligrams per kilogram and showed dose-proportional pharmacokinetics. With these conclusions from Phase 1a, we are excited to begin this Phase 1b expansion study with leading clinical sites and investigators.”

PY159 is an afucosylated humanized monoclonal antibody (mAb) that specifically binds human Triggering Receptor Expressed on Myeloid Cells 1 (TREM1). In preclinical studies, PY159 effectively induces signaling through the TREM1–DAP12 complex, leading to downstream phosphorylation, and an increase in production of cytokines and chemokines and the upregulation of costimulatory and activation markers. Taken together, Pionyr’s research indicates that PY159 converts suppressive tumor-associated myeloid cell populations into inflammatory cells that promote anti-tumor immune responses.

This Phase 1b portion of the study follows Pionyr’s Phase 1a dose-escalation trial. The multi-centered, US-based Phase 1a study evaluated the safety and tolerability of PY159 alone and in combination with pembrolizumab in multiple solid tumors and determined a recommended Phase 1b dose for expansion.

The Phase 1b study will evaluate PY159 administered alone and in combination with pembrolizumab in predefined tumor types. The first patient has been dosed in the single-agent ovarian cancer cohort. In addition to characterizing the anti-tumor activity of PY159, this study will continue to evaluate the safety, tolerability, and pharmacokinetics of PY159. Additional exploratory biomarkers will be evaluated, including analysis of TREM1-expression in the immune infiltrate of tumor biopsy samples. For more information, please visit www.clinicaltrials.gov (Identifier: NCT04682431).

PY159 is an investigational compound and is not approved by any regulatory authority.

About Myeloid TuningTM

Pionyr has developed a therapeutic platform called Myeloid Tuning, 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 play an important role in both the activation and suppression of the immune response to cancer.

One such critical type of myeloid cell, tumor-associated macrophages (TAM), 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 typically exerts anti-tumor functions, including directly mediating antibody-dependent cell-mediated cytotoxicity (ADCC) to kill tumor cells; M2-like macrophages can promote the occurrence and metastasis of tumor cells, inhibit T cell-mediated anti-tumor immune response, promote tumor angiogenesis and lead to tumor progression.

Myeloid Tuning TM effectively describes the mechanism of introducing agents that shift the balance of inhibitory myeloid cells – including M2-like TAMs – towards more inflammatory M1-like TAMs to promote anti-tumor immune responses in the TME and destroy solid tumors.

About Pionyr Immunotherapeutics

Pionyr is exploiting novel target discovery and antibody generation platform technologies to create the next generation of immuno-oncology therapeutics after checkpoint inhibitors. The company’s initial approach, termed “Myeloid TuningTM,” is designed to enhance the immune system’s anti-tumor response by specifically altering the cellular infiltrate of the tumor microenvironment. Pionyr’s two lead programs in Phase 1 development, PY314 and PY159 targeting TREM2 and TREM1 respectively, are designed to selectively deplete and in some cases reprogram certain tumor-associated macrophages responsible for immunosuppression. In July 2020, Pionyr entered into a transformational alliance with Gilead Sciences whereby Gilead acquired a minority interest in the company and has an exclusive option to acquire Pionyr upon completion of certain Phase 1b studies. Pionyr’s additional investors include New Enterprise Associates, OrbiMed, SV Health Investors, Sofinnova Ventures, Vida Ventures, Osage University Partners, Mission Bay Capital, and Trinitas Ventures. For more information, please visit www.pionyrtx.com.

Media Contact:

Evan Feeley

Evoke Canale

Evan.Feeley@evokegroup.com