PY-314

PY314 was well tolerated over a range of doses both as a single agent and in combination with checkpoint inhibitor pembrolizumab at its label approved dose A recommended dose for study expansion both as a single agent and in combination with pembrolizumab was derived, and enrollment of patients with metastatic refractory solid tumors into individual expansion cohorts of five prespecified cancers is ongoing PY314 targets TREM2, a protein receptor highly expressed on the surface of immunosuppressive, pro-tumor myeloid cells SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Pionyr Immunotherapeutics, Inc., a company developing first-in-class Myeloid TuningTM antibody therapeutics that enhance the body’s antitumor immunity by altering, or “tuning,” immune cells within the tumor microenvironment, announced today that PY314, a monoclonal antibody targeting TREM2 (triggering receptor expressed on macrophages 2), was safe and well-tolerated in a Phase 1a dose-escalation study as a single agent and in combination with pembrolizumab at its label-approved dose. A maximum tolerated dose (MTD) was not observed over the range of PY314 doses tested and a dose for study expansion was recommended based on an analysis of clinical data (including PK exposure) in the context of supportive preclinical data models. The study will be featured in a poster presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3-7 virtually and in Chicago. “Pionyr developed PY314 to precisely bind human TREM2 and retune the tumor microenvironment by driving the selective depletion of TREM2 positive tumor-associated macrophages. Removing these macrophages shifts the balance of myeloid cells towards more pro-inflammatory populations and is expected to increase and promote anti-tumor immune responses,” said Leonard Reyno, EVP and Chief Medical Officer of Pionyr Immunotherapeutics. “We have applied what we have learned from the Phase 1a study to identify a recommended dose for Phase 1b expansion studies. We have already begun enrolling patients in these studies and expect to have new data this year and into 2023.” Safety and Tolerability as a Monotherapy and in Combination with Pembrolizumab Support Additional Clinical Studies The Phase 1a dose-escalation study of PY314 was a non-randomized, open-label study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PY314 as a single agent and in combination with checkpoint inhibitor pembrolizumab in 28 subjects with advanced solid tumors. Dosing was intravenous and administered once every three weeks. Four predefined dose levels of PY314 were delivered both as a single agent and in combination with pembrolizumab. No dose-limiting toxicities, drug-related serious adverse reactions, or high-grade treatment-related adverse events (TRAEs) that resulted in treatment discontinuance were seen. Twelve patients experienced at least one TRAE, and these were low-grade in all but one subject who experienced a treatment-related immune system disorder. Eight patients experienced serious adverse events, all unrelated to treatment. Linear Dose-Response Observed and Recommended Dose for Expansion Studies Determined PY314 pharmacokinetics were linear and dose-proportional, with a half-life of five to nine days and no evidence of interference by pembrolizumab. The best radiographic response was stable disease, observed in eleven subjects (39.3%), which ranged in duration from nine to 42 weeks. Ten mg/kg PY314 was determined to be the recommended dose for expansion. Five expansion cohorts in patients with metastatic refractory solid tumors (triple-negative or HR-positive HER2 negative metastatic breast cancer, non-small cell lung cancer, renal cell carcinoma, colorectal cancer, ovarian cancer) are enrolling. Information about the ongoing Phase 1b expansion study is available at . Poster Presentation at ASCO 2022 The poster titled, “A Phase 1a Dose Escalation Study of PY314, a TREM2 (Triggering Receptor Expressed on Myeloid Cells 2)-Targeting Monoclonal Antibody,” will be featured in a poster session at the ASCO 2022 Annual Meeting on Sunday, June 5, 2022, 8:00 AM-11:00 AM CDT. The abstract is currently available on the ASCO 2022 website here, and the poster will be available on the Pionyr company website here after the completion of the ASCO poster session. 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 PY314 PY314 is a humanized IgG1 afucosylated monoclonal antibody, delivered by intravenous infusion, that binds Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) on the surface of immunosuppressive, pro-tumorigenic myeloid cells. It is designed to deplete TREM2-expressing TAMs, leading to productive anti-tumor immunity. Preclinical data generated by Pionyr suggest that when TAMs are depleted from tumors, pro-inflammatory, anti-tumorigenic immune cells such as CD8 T-cells, natural killer (NK), and M1-like macrophages become activated and penetrate tumors leading to tumor destruction. PY314 is currently being evaluated in a Phase 1b dose-expansion study as a single agent and in combination with pembrolizumab (Keytruda) as a treatment for refractory solid tumors and gynecologic cancer, colorectal cancer, lung adenocarcinoma, renal cell carcinoma, triple-negative breast cancer, hormone receptor/growth factor receptor-negative breast cancer, and ovarian cancer. 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 lead programs 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 .

FILE PHOTO: A Gilead Sciences, Inc. logo is seen outside the company headquarters in Foster City, California, U.S. May 1, 2018. REUTERS/Stephen Lam/File Photo (Reuters) - Gilead Sciences Inc said on Tuesday it would buy a 49.9% stake in privately held Pionyr Immunotherapeutics Inc for $275 million, strengthening its cancer portfolio by securing access to two promising drugs. The drugmaker, which is racing to secure enough supplies of its antiviral drug remdesivir for use in COVID-19, said it has also secured the right to acquire the rest of the drug developer for a $315 million option exercise fee. Pionyr’s immuno-oncology experimental drugs, PY314 and PY159, have shown potential against solid tumors in animal studies and it plans to file applications with the U.S. Food and Drug Administration in the third quarter to begin human testing. This is the third deal by Gilead in the span of four months aimed at expanding its oncology portfolio, Jefferies analyst Michael Yee said in a client note. In March, the company announced a $4.9 billion deal for Forty Seven Inc, snapping up an experimental treatment that targets blood cancer. This was followed by a 10-year pact last month with Arcus Biosciences Inc to co-develop and market cancer immunotherapies. “This is the most rational way to create long-term value rather than one big acquisition - and sets up Gilead for lots of interesting data in 2021,” Yee said. Pionyr’s shareholders are also eligible to receive up to an additional $1.47 billion in option exercise fees and future milestone payments. Remdesivir is at the forefront in the fight against the virus after the drug helped shorten hospital recovery times in a clinical trial, but some analysts express skepticism about its potential to bring in profits.