The Expansive Potential of Pelareorep
Cancer has evolved myriad mechanisms to evade immune detection, blunting the therapeutic effect of a broad range of drugs developed to treat it. Pelareorep is a first-in-class, nonpathogenic, oncolytic virus that can be delivered intravenously and works by generating, recruiting, and training immune cells to recognize and kill cancer while remodeling the tumor microenvironment to enable immune cell access. In addition to its demonstrated single-agent activity, pelareorep can also work in synergy with chemotherapy, immune checkpoint inhibitors (ICIs), CAR T-cell therapy, proteasome inhibitors, bispecific antibodies, and CDK4/6 and PARP inhibitors to enhance its antitumor potential and meaningfully extend patient remissions.
Pelareorep specifically targets cancer cells and induces a cascade of inflammatory responses that enable the immune system to destroy the tumor while sparing normal tissue. These responses, which include PD-L1 upregulation and enhanced T-cell infiltration, are partially due to pelareorep’s unique ability to introduce double-stranded RNA into cancer cells. Because pelareorep replicates only in tumor cells, it is well-tolerated by patients.
In non-cancer cells, pelareorep enters the cells but is unable to replicate and the virus is actively cleared.
In cancer cells
Pelareorep selectively replicates in permissive cancer cells. Upon virus replication, cancer cells lyse/die releasing additional virus particles to infect nearby cancer cells.
- Defective cell signaling pathways
- A high level of genomic mutations (or mutations in key tumor suppressor genes and oncogenes)
- Cellular stress from chemo and radiation therapy
A Case Study of Combination Therapy
Cancer cells evade immune destruction by signaling to the immune system that they do not need to be destroyed. Since immune evasion is a feature across oncologic disease, ICIs such as anti–PD-(L)1s can be applied to a broad range of cancers to facilitate tumor clearance. However, as few as 12.5% of patients see results with currently available ICIs.4
Pelareorep’s intravenous administration enables it to work systemically to unmask cancer cells, thereby allowing the immune system to identify and target them for destruction. On its own, pelareorep has the potential to treat primary and metastatic cancers. When added to existing treatment regimens, pelareorep can bolster their efficacy, offering patients the hope of longer, healthier lives.
Metastatic breast cancer
Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, with fewer than 10% of those diagnosed surviving beyond 5 years.4 While advances in immunotherapy have revolutionized the treatment of many cancers, pancreatic cancer has continued to present a challenge, with pancreatic tumors being poorly immunogenic and thus showing little to no response to anti–PD‐(L)1 and anticytotoxic T‐lymphocyte–associated antigen 4 (anti–CTLA‐4) therapies.5
Interim clinical data showed a 69% objective response rate, which is nearly triple historical control trial averages, with 1 complete response and 8 partial responses out of 13 patients.
- Best responses for the 13 evaluable patients at cut-off date: CR=1, PR=8, SD=2 and PD=2.
- Of the 9 patients with CR or PR, 7 responses were confirmed by a subsequent scan.
- Objective response rate (ORR) and clinical benefit rate (CBR) are 69% and 85%, respectively.
- Haslam A, Gill J, Prasad V. Estimation of the Percentage of US Patients With Cancer Who Are Eligible for Immune Checkpoint Inhibitor Drugs. JAMA Netw Open. 2020;3(3):e200423. Published 2020 Mar 2. doi:10.1001/jamanetworkopen.2020.0423
- SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. Accessed September 27, 2022. https://seer.cancer.gov/explorer/
- Chun-Yu Liu, Chia-Yun Wu, Karineh Petrossian, Tzu-Ting Huang, Ling-Ming Tseng, Shiuan Chen, Treatment for the endocrine resistant breast cancer: Current options and future perspectives, The Journal of Steroid Biochemistry and Molecular Biology, Volume 172, 2017, Pages 166-175, ISSN 0960-0760, https://doi.org/10.1016/j.jsbmb.2017.07.001.
- Lee DH, Jang JY, Kang JS, et al. Recent treatment patterns and survival outcomes in pancreatic cancer according to clinical stage based on single-center large-cohort data. Ann Hepatobiliary Pancreat Surg. 2018;22(4):386-396. doi:10.14701/ahbps.2018.22.4.386
- Manji GA, Olive KP, Saenger YM, Oberstein P. Current and emerging therapies in metastatic pancreatic cancer. Clin Cancer Res. 2017;23(7):1670-1678. doi:10.1158/1078-0432.CCR-16-2319
Mechanism of action (MOA)
Pelareorep’s MOA has been validated in clinical studies by measuring T-cell infiltration, PD-L1 expression, and other effects of pelareorep treatment on tumors. The ability of pelareorep to turn “cold” tumors “hot” has been established in multiple tumor types including breast cancer and pancreatic cancer. By turning “cold” tumors “hot,” pelareorep makes tumors more easily recognized by the immune system, thus enhancing the effectiveness of oncology treatments like chemotherapy or ICIs.
Ongoing studies are evaluating pelareorep for a variety of indications, including HR+/HER2- breast cancer, advanced pancreatic cancer, metastatic colorectal cancer, unresectable anal cancer, triple-negative breast cancer, and multiple myeloma.
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