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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.

Normal Cells/Cancer Cells
In normal cells
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.
Direct Cell Lysis
Pelareorep is able to selectively replicate in cancer cells, but not in normal cells due to a number of factors that are unique to cancer cells, including:
  • 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
Pelareorep enhances the body's natural anti-cancer immune response by activating both the innate and adaptive immune systems, converting immune unresponsive 'cold tumors' into immune responsive 'hot tumors.'
Innate Immune Response
Cancer cells infected with pelareorep release inflammatory cytokines. This inflammatory milieu activates natural killer (NK) cells and promotes the migration of NK cells, dendritic cells, and T-cells, to the tumor microenvironment which aids in immune cell mediated cancer cell death.
Adaptive Immune Response
Following pelareorep mediated cancer cell death, the release of the tumor and viral associated antigens are taken up by antigen presenting cells (APCs). APCs then process and present antigens to T-cells. This trains the adaptive immune system to recognize and kill cancer cells. An adaptive immune response allows for: existing cancer cells to be eliminated, constant cancer cell surveillance, relapse prevention, and increased overall survival.

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.

cell graphic - case study section

Demonstrated Efficacy

Metastatic breast cancer

Patients with HR+/HER2- breast cancer comprise approximately 70% of all breast cancer cases.2 Unfortunately, these tumors eventually develop resistance to endocrine-blocking therapies and can reoccur in approximately 50% of patients, underscoring the need for more treatment options.3
When pelareorep was added to standard metastatic breast cancer treatment, overall survival rates nearly doubled in a randomized study of patients with HR+/HER2- breast cancer.

Pancreatic 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

Updated clinical data showed a 62% objective response rate, which is more than double historical control trial averages.

Tumor responses Chart
  1. 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
  2. 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/
  3. 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.
  4. 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
  5. 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
Pelareorep promotes an anti-cancer immune response

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.

Broad potential

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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