PY159 / ImageneBio, Foundery Biosciences - LARVOL DELTA

Attenuated levels of surface TREM1 on circulating neutrophils impair NETosis and increase infection risk in DLBCL patients (AACR 2025) - "Neutrophils from low TREM1 patients had significantly impaired NETosis, which was restored by the TREM1 agonist PY159.In conclusion, low surface TREM1 levels on circulating neutrophils predict poorer PFS and OS, higher infection risk, and impaired NETosis in untreated DLBCL patients. These findings warrant further clinical investigation."

Clinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Oncology • PTPRC

Myeloid targeting antibodies PY159 and PY314 for platinum-resistant ovarian cancer. (PubMed, J Immunother Cancer) - "Both PY159 and PY314 were well tolerated, with an acceptable safety profile, as both single agents and in combination with pembrolizumab. Both agents warrant further investigation in heavily pretreated PROC."

Journal • Musculoskeletal Pain • Oncology • Ovarian Cancer • Solid Tumor

Foundery Immune Studio, LLC Acquires Rights to a Suite of Next-Generation Clinical Stage Immunotherapies (PRNewswire) - " Foundery Immune Studio, LLC...announced today its acquisition of worldwide rights for three clinical-stage immune tuning therapies from Ikena Oncology, Inc...Antibodies PY314 and PY159, targeting TREM2 and TREM1, respectively, completed Phase 1 trials and were well tolerated. Both antibodies demonstrated promising pharmacodynamic effects alone and in combination with pembrolizumab. The third program targeting MARCO, PY265, is Investigational New Drug (IND)-ready."

Commercial • Non Small Cell Lung Cancer • Ovarian Cancer

A Phase 1a/1b FIH Study of PY159 and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=127 | Terminated | Sponsor: Ikena Oncology | Phase classification: P1a/1b ➔ P1 | N=343 ➔ 127 | Trial completion date: Dec 2025 ➔ Aug 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2025 ➔ Aug 2023; Sponsor business decision.

Combination therapy • Enrollment change • Metastases • Phase classification • Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Gynecologic Cancers • Head and Neck Cancer • Hepatology • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-1 • PD-L1

Evaluation of Myeloid Targeting Agents, PY159 and PY314, in Two Dose Expansion Phase 1b Trials in Platinum-Resistant Ovarian Cancer (ESMO-IO 2023) - P1a/1b | "Conclusions Both PY159 and PY314 were well tolerated, with an acceptable safety profile, as a single agent and in combination with pembrolizumab. Both agents warrant further investigation in heavily pretreated PROC."

P1 data • Oncology • Ovarian Cancer • Solid Tumor

TREM1 activation of myeloid cells promotes antitumor immunity. (PubMed, Sci Transl Med) - "An antibody against mouse TREM1, PY159m, promoted antitumor efficacy in syngeneic mouse tumor models. These results suggest that PY159-mediated agonism of TREM1 on tumoral myeloid cells can promote a proinflammatory TME and offer a promising strategy for immunotherapy."

Journal • Oncology

A Phase 1a/1b FIH Study of PY159 and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1a/1b | N=343 | Active, not recruiting | Sponsor: Pionyr Immunotherapeutics Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2023 ➔ Dec 2025 | Trial primary completion date: Apr 2023 ➔ Dec 2025

Combination therapy • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Gynecologic Cancers • Head and Neck Cancer • Hepatology • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-1 • PD-L1

A phase 1a dose-escalation study of PY159, a monoclonal antibody targeting TREM1 (triggering receptor expressed on myeloid cells 1). (ASCO 2023) - P1a/1b | "PY159 was well tolerated, with an acceptable safety profile, as a single agent and in combination with pembrolizumab. A dose for expansion was derived and enrollment of subjects with 7 prespecified cancers is ongoing. Clinical trial information: NCT04682431."

IO biomarker • P1 data • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Head and Neck Cancer • Hepatology • HER2 Breast Cancer • Immune Modulation • Lung Cancer • Musculoskeletal Pain • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2

Pionyr Immunotherapeutics’ Phase 1a Study of TREM1-targeting Antibody PY159 for the Treatment of Solid Tumors Featured at ASCO 2023 (Businesswire) - P1a | N=343 | NCT04682431 | Sponsor: Pionyr Immunotherapeutics Inc. | "Pionyr Immunotherapeutics...announced today that PY159...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....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....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."

Enrollment status • P1 data • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • HER2 Negative Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer

Pionyr Immunotherapeutics and Gilead Change Exclusive Option Agreement (Businesswire) - "Pionyr Immunotherapeutics, Inc...announced that Pionyr and Gilead Sciences, Inc...have mutually agreed to change their 2020 exclusive option agreements....As part of this agreement, Gilead waives its exclusive option to acquire Pionyr. Pionyr will be responsible for ongoing development of its pipeline, which includes PY159, PY314 and PY265. The company has the resources to advance its pipeline for the next two years. Within that timeframe, Pionyr will continue enrollment in Phase 1b expansion cohorts for both PY159 and PY314 in the refractory setting and is planning to add new frontline cohorts for both candidates. Pionyr has also completed IND-enabling studies for PY265 and will be ready to file an IND for that program in 2023."

IND • Licensing / partnership • Trial status • Oncology • Solid Tumor

Tuning the tumor microenvironment by reprogramming TREM1+ myeloid cells to unleash anti-tumor immunity in solid tumors (SITC 2021) - P1a/1b | "PY159 safety and efficacy are currently being evaluated in first-in-human clinical trial (NCT04682431) involving select advanced solid tumors patients resistant and refractory to standard of care therapies alone and in combination with a CPI. The TREM1 IHC assay is successfully being used on FFPE archival tumor tissues from enrolled patients to determine TREM1 expression levels."

Biomarker • IO biomarker • Tumor microenvironment • Oncology • Solid Tumor

Pionyr Immunotherapeutics Doses First Patient in Phase 1b Expansion Study of PY159 (Businesswire) - "Pionyr Immunotherapeutics, Inc...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)....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."

Trial status • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Head and Neck Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

Pionyr Immunotherapeutics to Present on Myeloid Tuning Platform and TREM1 Targeting Antibody Program at the Tumor Myeloid-Directed Therapies Summit (Businesswire) - "The presentation will highlight preclinical and early clinical research on Pionyr’s first in class TREM1-targeting monoclonal antibody called PY159...Preclinical evidence showing TREM1 as a promising therapeutic opportunity for patients with checkpoint inhibitor (CPI)-hypo-responsive or resistant tumors as the receptor is expressed on the three myeloid immuno-suppressive cell populations. In vivo model data demonstrating administration of PY159 alone or in combination with CPIs resulted in complete regressions of tumors...Outline clinical plans for further study in patients with advanced refractory solid tumor."

Preclinical • Oncology • Solid Tumor

Pionyr Immunotherapeutics Presents on Third Myeloid-Directed Therapeutic Program at Keystone Symposium (PRNewswire) - '"Our lead programs, PY314 (anti-TREM2) and PY159 (anti-TREM1), are currently in the clinic, and PY265 is on track to complete IND-enabling studies and enter the clinic in 2023.'"

IND • Oncology

A Phase 1a/1b FIH Study of PY159 and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1a/1b; N=298; Recruiting; Sponsor: Pionyr Immunotherapeutics Inc.; N=216 ➔ 298; Trial completion date: Nov 2023 ➔ Apr 2023; Trial primary completion date: Nov 2023 ➔ Apr 2023

Clinical • Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-1 • PD-L1

[VIRTUAL] TREM1 agonist PY159 promotes myeloid cell reprogramming and unleashes anti-tumor immunity (ITOC 2021) - P1a/1b | "Conclusions These results show that PY159 is a TREM1 agonist that reprograms myeloid cells and unleashes anti-tumor immunity. PY159 safety and efficacy are currently being evaluated in first-in-human clinical trial ([NCT04682431][1]) involving patients resistant and refractory to standard of care therapies."

IO biomarker • Oncology

[VIRTUAL] Therapeutic targeting of TREM1 with PY159 promotes myeloid cell reprogramming and unleashes anti-tumor immunity (AACR-NCI-EORTC 2021) - No abstract available

Oncology

Investigation into the Effect of Spinel Pigments on the Photostability and Combustion Properties of Ethylene-Norbornene Copolymer. (PubMed, Materials (Basel)) - "Multicolor ethylene-norbornene (EN) composites filled with three different spinel pigments (Cobalt Green-PG50, Zinc Iron Yellow-PY 119, Praseodym Yellow-PY159) were prepared by melt mixing and characterized in terms of their stability under destructive environmental conditions...Moreover, the spinel pigments had a positive effect on the flame retardancy of the EN composites. Microcombustion tests (MCC) showed that the incorporation of both the spinels and the organic pigment PY139 into the EN matrix reduced the heat release rate (HRR) and total heat release (THR) parameters."

Journal

A Phase 1a/1b First-In-Human (FIH) Study of PY159 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1a/1b; N=216; Recruiting; Sponsor: Pionyr Immunotherapeutics Inc.

Clinical • Combination therapy • New P1 trial • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Adenocarcinoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Gilead Sciences Secures Exclusive Option to Acquire Pionyr Immunotherapeutics (Businesswire) - "Gilead Sciences, Inc…announced today that for $275 million the company will acquire a 49.9 percent equity interest in Pionyr Immunotherapeutics Inc…and an exclusive option to purchase the remainder of Pionyr. Under the agreement, Pionyr’s shareholders may receive up to an additional $1.47 billion in option exercise fees and future milestone payments…Pionyr plans to file investigational new drug (IND) applications with the U.S. Food and Drug Administration for both PY314 and PY159 in the third quarter of this year….Gilead may exercise its exclusive option upon completion of Phase 1b studies for PY314 and PY159, or at an earlier time if Gilead chooses to do so, for a $315 million option exercise fee and up to $1.15 billion in potential future milestone payment."

IND • M&A • Oncology • Solid Tumor