NEW YORK, April 11, 2022 /PRNewswire/ — Phosphlatin Therapeutics Inc.A clinical-stage pharmaceutical company focused on small molecule immunogenic therapies in oncology today presented new non-clinical data on its lead candidate PT-112, “PT-112 induced, at the 2022 American Academy of Cancer Research (AACR) Annual Meeting potent mitochondrial stress and immunogenic cell death in human prostate cancer cell lines” can be viewed in person at the AACR, which runs through the end of September April 13th in New Orleans, Louisiana and online one Procedures of the AACR through the meeting website.
“The study results suggest that PT-112 inhibits prostate cancer cell growth without affecting healthy cells, including affecting organelles such as mitochondria, which are consistent with immunogenic cell death (ICD),” said Alberto Anel, PhD, Research Associate at the University of Zaragoza/Aragón Health Research Institute who led the study. “We found that PT-112 selectively induced mitochondrial reactive oxygen species as well as the release of damage-associated molecular patterns or DAMPs, suggesting that this activity on cell organelles may be an important component of PT-112’s immunogenic cell death mechanism. “
“We are encouraged by the activity of this research conducted in parallel with our ongoing Phase 2 clinical trial of PT-112 in patients with metastatic castration-resistant prostate cancer,” said Phosplatin Executive Vice President and Chief Operating Officer, Matthew price. “The outcome of this study provides a better understanding of the mechanism of action of PT-112 in a way that is related to its demonstrated immunogenic cell death effects. We view this as very supportive of our ongoing clinical efforts to treat patients with metastatic castration-resistant prostate cancer, a disease state that is heterogeneous and requires an immune-priming approach such as ICD.”
The PT-112 non-clinical study (available Monday 11 April 2022 out of 9:00 am – 12:30 PM CST as poster presentation number 5) evaluated differential sensitivity, cell death mechanism, induction of mitochondrial stress and release of DAMPs. Susceptibility to PT-112 was evaluated in human prostate cancer cell lines and the non-cancer prostate cell line RWPE-1. Key findings from the study included the following:
PT-112 caused growth arrest and cancer cell death without affecting healthy RWPE-1 cells.
Caspase inhibition reduced PT-112-induced cell death, while milder effects were observed in necroptosis inhibition, suggesting that cell death is primarily apoptotic.
PT-112-induced cell death was accompanied by a marked increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, as well as DAMP emission.
PT-112 activated markers of autophagy, a process associated with ICD and the cellular stress response
In this panel, there was a positive relationship between HIF-1alpha expression and susceptibility to PT-112.
PT-112 is a novel small molecule with clinical activity reported in Phase 1 studies in advanced solid tumors including lung, thymoma, castration-resistant prostate cancer and multiple myeloma. Previous research has shown that PT-112-induced cancer cell death is independent of nuclear DNA damage. Additionally, in vitro Experiments showed that PT-112 causes the accumulation of mtROS and the release of DAMP, leading to immunogenic cell death (ICD), a unique form of cancer cell death that elicits an anti-cancer immune response associated with the specific pathway , upon which a cancer cell dies, and T cell infiltration.
For more information on Phosphlatin clinical trials, visit the website at www.phosplatin.com.
PT-112 is a novel small molecule with a unique, pleiotropic mechanism of action that promotes immunogenic cell death (ICD) through the release of damage-associated molecular patterns (DAMPs) that bind to dendritic cells and result in downstream recruitment of immune effector cells to the microenvironment of the tumor. PT-112 is possibly the best-in-class inducer of this immunological form of cancer cell death. In addition, PT-112 exhibits a property known as osteotropism, or the drug’s propensity to reach its highest concentrations in certain areas of bone, making it a candidate for treating patients with cancers that originate from have in the bone or metastasize there. The first human study of PT-112 showed an attractive safety profile and evidence of long-lasting responses in heavily pretreated patients and was recognized as “Best Poster” in the Developmental Therapeutics category at the 2018 ESMO Annual Meeting. The combination phase 1b Dose escalation study of PT-112 with the PD-L1 checkpoint inhibitor avelumab in solid tumors was reported in an oral presentation at the ESMO 2020 Virtual Congress. The Phase 1 study presented at ASH in patients with relapsed or refractory multiple myeloma is the third completed Phase 1 study of PT-112. Phase 2 monotherapy development in mCRPC is ongoing and the PD-L1 combination study is ongoing in a dose-confirmation cohort of non-small cell lung cancer (NSCLC) patients and will soon enter the Phase 2 proof-of-concept study Thymic epithelial tumors include, as part of the company’s collaboration with the NCI.
About phosphate therapeutics
Phosplatin Therapeutics Inc. is a privately held, clinical-stage pharmaceutical company focused on the development of small molecule immunomodulating therapeutics. The Company’s lead candidate, PT-112, is a novel investigational chemical in clinical development with a unique combination of properties including immunogenic cell death and osteotropism. Clinical data generated from three Phase 1 studies to date have demonstrated single agent anticancer efficacy and an attractive safety profile, and three Phase 2 studies of PT-112 are ongoing. The company’s research and development work was funded by private investors and family investment offices The United States, Europe and Asiaalong with a sublicense agreement for the development, commercialization and use of PT-112 in Greater China. The company also sponsors the ongoing clinical trial of PT-112 in combination with the PD-L1 inhibitor avelumab under a collaboration agreement with Pfizer and Merck KGaA, Darmstadt, Germany (operates as EMD Serono in the US and Canada) and has an active research and development agreement (CRADA) with NCI to conduct a Phase 2 study using PT-112 in thymic epithelial tumors.
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