Phosplatin Therapeutics Reports on PT-112's Selective Effects and Immunogenic Cell Death in Human Prostate Cancer Cell Models at the AACR Annual Meeting 2022

NEW YORK, April 11, 2022 /PRNewswire/ -- Phosplatin Therapeutics Inc., a clinical stage pharmaceutical company focused on small molecule immunogenic therapies in oncology, reported today new non-clinical data on its lead candidate, PT-112, at the American Academy of Cancer Research (AACR) Annual Meeting 2022. The poster presentation, titled, "PT-112 induces potent mitochondrial stress and immunogenic cell death in human prostate cancer cell lines," is available for viewing in person at AACR, which is taking place through April 13 in New Orleans, Louisiana and online in Proceedings of the AACR through the meeting website.

"The study results indicate that PT-112 causes growth inhibition of prostate cancer cells without affecting healthy cells, including effects seen on organelles such as mitochondria, that are consistent with immunogenic cell death (ICD)," said Alberto Anel, PhD, Scientific Researcher at 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, which suggests this activity on cellular organelles may be an important component of PT-112's immunogenic cell death mechanism."

"We are encouraged by the activity seen in this research, which was 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 result of this study provides a better understanding of PT-112's mechanism of action, in a manner that is linked to its established immunogenic cell death effects. We view this as very supportive of our ongoing clinical efforts in treating metastatic castration resistant prostate cancer patients, a disease state that is heterogenous and that requires an immune priming approach such as ICD."

The non-clinical study of PT-112 (available Monday, April 11, 2022 from 9:00am – 12:30pm CST as poster presentation number 5) assessed differential sensitivity, cell death mechanism, induction of mitochondrial stress and release of DAMPs. Sensitivity to PT-112 was assessed in human prostate cancer cell lines and the non-tumorigenic prostate cell line RWPE-1. Key findings of the study included the following:

• PT-112 caused growth inhibition and cancer cell death without affecting healthy RWPE-1 cells.
• Caspase inhibition reduced PT-112-induced cell death, with more mild effects seen with necroptosis inhibition, suggesting that cell death is primarily apoptotic.
• PT-112-induced cell death was accompanied by a prominent increase of mitochondrial reactive oxygen species (mtROS) and decrease in mitochondrial membrane potential, as well as by DAMP emission.
• PT-112 activated markers of autophagy, a process associated with ICD and the cellular stress response
• There was a positive relationship between HIF-1alpha expression and the sensitivity to PT-112 in this panel.

PT-112 is a novel small molecule with clinical activity reported across Phase 1 studies in advanced solid tumors including lung, thymoma, castration-resistant prostate cancer, and multiple myeloma. In previous research, PT-112-induced cancer cell death has been shown to be independent of nuclear DNA damage. Additionally, in vitro experiments showed that PT-112 causes mtROS accumulation and DAMP release leading to immunogenic cell death (ICD), a unique form of cancer cell death that elicits an anti-cancer immune response related to the specific way in which a cancer cell dies, and T-cell infiltration.

For more information about Phosplatin's clinical trials, visit the website at www.Phosplatin.com.

About PT-112

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 lead to downstream immune effector cell recruitment in the tumor microenvironment. PT-112 may represent the best-in-class inducer of this immunological form of cancer cell death. Further, PT-112 harbors a property known as osteotropism, or the propensity of the drug to reach its highest concentrations in certain areas of the bone, making it a candidate for treatment of patients with cancers that originate in, or metastasize to, the bone. The first in-human study of PT-112 demonstrated an attractive safety profile and evidence of long-lasting responses among heavily pre-treated patients and won "Best Poster" within the Developmental Therapeutics category at the ESMO 2018 Annual Congress. The combination Phase 1b dose escalation study of PT-112 with PD-L1 checkpoint inhibitor avelumab in solid tumors was reported in an oral presentation at the ESMO 2020 Virtual Congress. The Phase 1 study in patients with relapsed or refractory multiple myeloma presented at ASH is the third completed Phase 1 study of PT-112. Monotherapy Phase 2 development is ongoing in mCRPC, and the PD-L1 combination study is ongoing in a dose confirmation cohort of non-small cell lung cancer (NSCLC) patients, and will soon include the Phase 2 proof of concept study in thymic epithelial tumors under the company's collaboration with the NCI.

About Phosplatin Therapeutics

Phosplatin Therapeutics Inc. is a privately held, clinical stage pharmaceutical company that is focused on the development of small molecule immune-modulating therapeutics. The company's lead candidate, PT-112, is a novel chemical entity under clinical development that exhibits a unique combination of properties, including immunogenic cell death and osteotropism. Clinical data generated to date across three Phase 1 studies have demonstrated single-agent anti-cancer activity and an attractive tolerability profile, and three Phase 2 studies of PT-112 are underway. The company's research and development work has been funded by private investors and family investment offices in the United States, Europe and Asia, along with a sub-license agreement for the development, commercialization and use of PT-112 in Greater China. The company also sponsors the ongoing clinical study of PT-112 in combination with the PD-L1 inhibitor avelumab under a collaboration agreement with Pfizer and Merck KGaA, Darmstadt, Germany (operating as EMD Serono in the US and Canada), and has an active collaborative research and development agreement (CRADA) with the NCI to conduct a Phase 2 trial utilizing PT-112 in thymic epithelial tumors.

CONTACTS:

Phosplatin Therapeutics Taylor B. Young
Senior Director of Strategic Development
Tel: +1 646 974 6456
Email: [email protected]

ICR Westwicke Investors:
Stephanie Carrington
Tel: +1 646 277 1282
Email: [email protected]

Media: 
Mark Corbae
Tel: +1 203 682 8288
Email: [email protected]

SOURCE Phosplatin Therapeutics