Pionyr Immunotherapeutics’ Phase 1a Study of TREM1-targeting Antibody PY159 for the Treatment of Solid Tumors Featured at ASCO 2023
- Category: Antibodies
- Published on Friday, 26 May 2023 08:45
- Hits: 1203
- PY159 was well tolerated with an acceptable safety profile over a range of doses both as a single agent and in combination with checkpoint inhibitor pembrolizumab
- Radiographic response included two partial responses and stable disease in nine subjects ranging in duration from 12 to more than 96 weeks
- 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 seven prespecified cancers is ongoing
- PY159 targets TREM1, a protein receptor highly expressed on the surface of immunosuppressive myeloid cells
SOUTH SAN FRANCISCO, CA, USA I May 25, 2023 I Pionyr Immunotherapeutics, Inc., a company developing first-in-class Myeloid Tuning™ antibody therapeutics that enhance the body’s antitumor immunity by altering, or “tuning,” immune cells within the tumor microenvironment, announced today that PY159, a monoclonal antibody targeting TREM1 (triggering receptor expressed on macrophages 1), was well-tolerated with signals of durable therapeutic activity in a Phase 1a dose-escalation study as a single agent and in combination with pembrolizumab. In 37 evaluable patients, two demonstrated partial responses and nine showed stable disease. A recommended dose of 3 mg/kg of PY159 has been determined, and seven expansion cohorts in prespecified indications are currently enrolling in the Phase 1b portion of the study. The study will be featured in a poster discussion session at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2-6 in Chicago and virtually.
“PY159 is designed to activate the signaling of TREM1, which reprograms tumor-associated myeloid cells to stimulate anti-tumor immunity,” said Leonard Reyno, President, R&D and Chief Medical Officer of Pionyr Immunotherapeutics. “The radiographic response data provide encouraging signals of efficacy, which is exciting given the novel Myeloid Tuning approach we are pursuing. This response combined with acceptable safety and tolerability both as a monotherapy and in combination with checkpoint inhibitor demonstrate the potential of this approach for treating solid tumors.”
Safety and Tolerability as a Monotherapy and in Combination with Pembrolizumab Support Additional Clinical Studies
The Phase 1a dose-escalation study of PY159 was a non-randomized, open-label study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PY159 as a single agent and in combination with checkpoint inhibitor pembrolizumab in 37 subjects with advanced solid tumors. Dosing was intravenous and administered once every three weeks. Seven predefined dose levels of PY159 were delivered as a single agent, and four dose levels of PY159 were delivered in combination with pembrolizumab. No clinically relevant neutropenia was observed. The most common treatment-related adverse events were infusion-related reactions, arthralgia, fatigue, myalgia, and stomatitis, which were primarily Grade 1 or 2; however, one subject experienced a dose-limiting toxicity of asymptomatic Grade 3 transaminitis.
Early Radiographic Response Data Support Additional Clinical Studies
Out of the 37 evaluable subjects, the best radiographic response for clinical study participants was stable disease in nine subjects (25.7%: duration range 12-96+ weeks) and partial response in two subjects (5.7%, duration range 24-42 weeks). The two partial responses were in pancreatic and ovarian cancer. Dose expansion cohorts are currently enrolling in ovarian, breast (triple negative and HR+HER2-), colorectal, pancreatic, non-small cell lung, and head and neck cancers.
Poster Presentation at ASCO 2023
The poster titled, “A Phase 1a Dose Escalation Study of PY159, a Monoclonal Antibody Targeting TREM1, Triggering Receptor Expressed on Myeloid Cells 1,” will be featured in a poster discussion session at the ASCO 2023 Annual Meeting at 3-4:30 pm CDT on June 3, 2023. The abstract is currently available on the ASCO 2023 website, and the poster will be available on the Pionyr company website here after the completion of the ASCO poster session.
About Myeloid Tuning™
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™ 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.
PY159 is an afucosylated humanized IgG1 monoclonal antibody 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. PY159 repolarizes intratumoral immunosuppressive myeloid cells, including M2-like anti-inflammatory tumor associated macrophages (TAMs), monocytes (monocytic myeloid derived suppressor cells, mMDSCs), and neutrophils (TANs) within the tumor microenvironment to become proinflammatory to promote anti-tumor immunity.
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 Tuning™,” 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. Pionyr’s investors include Gilead, New Enterprise Associates, OrbiMed, SV Health Investors, Sofinnova Investments, Vida Ventures, Osage University Partners, Mission Bay Capital, and Trinitas Ventures. For more information, please visit www.pionyrtx.com.
SOURCE: Pionyr Immunotherapeutics