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Pexa-Vec (JX-594) Targeting, Attacking, and Eradicating Cancers®

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Pexa-Vec (JX-594) Wyeth Strain Backbone Pipeline

pexa-vec

Pexa-Vec (Pexa-Vec, JX-594)

Our lead Investigational product Pexa-Vec is a Wyeth strain vaccinia virus engineered to directly lyse tumor cells and stimulate anti-tumor immunity. We believe that Pexa-Vec acts in three ways:

  1. by infecting and selectively replicating in cancer cells and causing lysis,
  2. reducing the blood supply to tumors through infection of tumor associate vasculature; and
  3. by activating the body’s own immune system to recognize and kill tumor cells.
펙사벡 JX594

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 cancer3 and high cellular levels of thymidine kinase (TK) found in proliferating cancer cells.Viral TK gene has been deactivated in Pexa-Vec so that the virus cannot replicate efficiently in normal cells. Pexa-Vec is also engineered to express the potent immune stimulatory cytokine granulocyte-macrophage colony stimulating factor (GM-CSF), which may stimulate a tumor specific immune response.4

펙사벡 JX594

Monotherapy

Over 400 patients in clinical trials have been treated with Pexa-Vec5. These trials have demonstrated that Pexa-Vec is safe with most frequent side effects being transient flu-like symptoms. It was also shown that (1) Pexa-Vec can be delivered to tumors by Intravenous (IV) transfusion or by direct Intratumoral (IT) injection,6 (2) that treatment is able to disrupt the tumor-associated vasculature,7 and (3) that treatment can induce the production of cancer targeting antibodies.8 Pexa-Vec is currently being evaluated in patients with liver cancer in the global Phase 3 PHOCUS trial.

Combination Therapy

In preclinical studies, Pexa-Vec its unique mechanisms of action, has shown synergy with anti-PD-1 antibodies and anti-CTLA-4 antibodies in preclinical studies. SillaJen and our partners have launched new clinical programs to explore the power of the combination therapy with the various immune checkpoint inhibitors.

Key Reference:

  • 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
  • 5 https://clinicaltrials.gov/ct2/results?term=JX594&Search=Search
  • 6 Breitbach CJ et al., Nature 2011
  • 7 Breitbach CJ et al., Cancer Res 2013
  • 8 Kim MK et al., Sci Transl Med 2013