Our lead Investigational product Pexa-Vec (pexastimogene devacirepvec, JX-594) is an attenuated (weakened) Wyeth strain vaccinia virus engineered to directly lyse tumor cells and stimulate anti-tumor immunity. Preclinical and clinical research indicate that Pexa-Vec acts in three ways:
- by directly killing cancer cells by replicating inside cancer cells and lysing them,
- reducing the blood supply to tumors through infection of tumor associated vasculature; and
- by activating the body’s own immune system to recognize and kill tumor cells.
While vaccinia virus is inherently selective for cancer, 1 Pexa-Vec was engineered for even greater cancer selectivity by exploiting the genetic changes that are hallmarks of cancer. 2 Pexa-Vec replication and spread are dependent on activation of the EGFR/Raf/Ras signaling, a pathway that is frequently activated in cancer 3 and, the viral Thymidine Kinase (TK) gene has been deactivated, resulting in a virus that depends on high levels of cellular TK activity, as is found in proliferating cancer cells. Pexa-Vec was also engineered to express the potent immunostimulatory cytokine granulocyte-macrophage colony stimulating factor (GM-CSF), which may stimulate a tumor specific immune response. 4
Over 300 patients in clinical trials have been treated with Pexa-Vec .5 The trials have demonstrated that Pexa-Vec can be delivered to tumors by Intravenous (IV) transfusion or Intratumoral (IT) injection, 6 that treatment is able to disrupt the tumor-associated vasculature, 7 and that treatment can induce the production of cancer targeting antibodies. 8 The most frequent side effects are transient flu-like symptoms, including fever and chills. Pexa-Vec is currently being evaluated in patients with liver cancer in the global Phase 3 PHOCUS trial.
1 Yu, YA et al., Nat Biotech 2004
2 Hanahan, D and Weinberg, RA, Cell 2011
3 Katsafanas GC and Moss B, J Biol Chem 2004
4 Dranoff G et al., Proc Natl Acad Sci USA 1993
6 Breitbach CJ et al., Nature 2011
7 Breitbach CJ et al., Cancer Res 2013
8 Kim MK et al., Sci Transl Med 2013
JX-963 is an attenuated (weakened) Western Reserve strain of vaccinia virus that has been engineered for systemic delivery and the ability to stimulate a systemic anti-tumor immune response. Deletion of the viral thymidine kinase (TK) and vaccinia growth factor genes (VGF) genes resulted in a virus that is highly selective for cancer with significantly decreased ability to infect and multiply in normal cells. JX-963 was also engineered to produce the potent immunostimulatory cytokine granulocyte-macrophage colony stimulating factor (GM-CSF), which may stimulate a tumor specific immune response. Preclinical testing with JX-963 has demonstrated cancer selectivity, efficacy and systemic delivery. (Thorne SH et al., J Clin Invest 2007)