Promontory Therapeutics Presents on the Immunological Effects of PT-112 in Cancer Cell Mitochondria at SITC 2022

NEW YORK, Nov. 11, 2022 /PRNewswire/ -- Promontory Therapeutics Inc., a clinical stage pharmaceutical company advancing small molecule immunotherapies in oncology, today presented data on lead therapeutic candidate PT-112 and its immunological effects on cancer cell mitochondria at the 34th Annual Meeting of the Society for Immunotherapy of Cancer (SITC). The poster titled, "Immunologically relevant effects of PT-112 on cancer cell mitochondria" demonstrated that PT-112 caused anti-cancer activity, which is related to its ability to induce immunogenic cell death (ICD).

"Under our ongoing collaboration with the lab of Lorenzo Galluzzi, PhD, Weill Cornell Medical College, we are exploring how PT-112 impacts on cancer cell mitochondria in the context of immunogenic cell death," said Matthew Price, Promontory Therapeutics co-founder and Chief Operating Officer. "The data presented at SITC further confirm that PT-112 induces mitochondrial dysfunction in cancer cells, with two key insights: that PT-112 causes the accumulation of mitochondrial (mt)DNA in the cytosol, a phenomenon referred to as 'viral mimicry'; and that PT-112 could drive immunogenic signaling before the induction of cancer cell death – both consistent with the understanding of ICD. These findings are particularly important as PT-112 progresses through clinical development."

PT-112 is under Phase 2 clinical development for metastatic castration-resistant prostate cancer, thymoma and thymic carcinoma, and non-small cell lung cancer. In addition to mediating cytostatic and cytotoxic effects in a variety of human and mouse cancer cell lines, PT-112 elicits multiple damage-associated molecular patterns (DAMPs), linked to immunogenic cancer cell death. Findings from the study include:  

• PT-112 causes pronounced mitochondrial dysfunction in cancer cells, coupled with the accumulation of mtDNA in the cytosol.
• PT-112-driven reactive oxygen species production is mediated in part by a BAX/BAK1-dependent pathway, further indicative of mitochondrial involvement.
• Functional BAX/BAK1 and CASP3, but not CASP2, render mouse cancer cells susceptible to PT-112-induced cell death.
• CASP3 activation appears to limit interferon secretion by mouse cancer cells responding to PT-112, suggesting that interferon release may not be required in PT-112-induced ICD in this model system, as observed previously and reported in OncoImmunology.

SITC abstracts are available for viewing here.

For more information about PT-112 and Promontory Therapeutics' clinical pipeline visit www.PromontoryTx.com.

PT-112 is the first small-molecule conjugate of pyrophosphate in oncology, and possesses 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 represents a highly potent 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 now includes the Phase 2 proof of concept study in thymic epithelial tumors under the company's formal collaboration with the NCI. The PD-L1 combination Phase 2a study is ongoing in a dose confirmation cohort of non-small cell lung cancer (NSCLC) patients.

Promontory Therapeutics Inc. is a privately held, clinical stage pharmaceutical company focused on small molecule immunotherapy. The company's lead candidate, PT-112, is the first small molecule conjugate of pyrophosphate in oncology, and possesses a unique pleiotropic mechanism of action that promotes immunogenic cell death (ICD), through the release of damage associated molecular patterns (DAMPs) that bind to pattern recognition receptors on dendritic cells and promote the adaptive immune response in the tumor microenvironment. Clinical data generated 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 conducted 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 Phase 2 trial underway with the NCI utilizing PT-112 in thymic epithelial tumors where PT-112 has received Orphan Drug designation.

To learn more about Promontory Therapeutics, visit the company's website here.

Promontory Therapeutics
Brooke Raphael
VP, Strategy & Operations
Tel: +1 646 974 6453
Email: [email protected]

ICR Westwicke

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SOURCE Promontory Therapeutics Inc.