Date: 2017-04-24
Type of information: Milestone
Compound: JX-594/TG6006 (Pexa-Vec -pexastimogene devacirepvec)
Company: Transgene (France) Sillajen (Republic of Korea)
Therapeutic area: Cancer - Oncology
Type agreement: development
commercialisation
Action mechanism: oncolytic virus/gene therapy. Pexa-Vec is an oncolytic immunotherapy that utilizes the vaccinia poxvirus strain as its backbone. This strain has been used safely in millions of people as part of a worldwide vaccination program. This strain naturally targets cancer cells due to common genetic defects in cancer cells; Pexa-Vec was engineered to enhance this by deleting its thymidine kinase (TK) gene, thus making it dependent on the cellular TK expressed at persistently high levels in cancer cells. Pexa-Vec is also engineered to express the immunogenic GM-CSF protein. GM-CSF complements the cancer cell lysis of the product candidate, leading to a cascade of events resulting in tumor necrosis, tumor vasculature shutdown and sustained anti-tumoral immune attack.
Pexa-Vec is designed to attack cancer through three diverse mechanisms of action: 1) the lysis of cancer cells through viral replication, 2) the shutdown of the blood supply to tumors through vascular targeting and destruction, and 3) the stimulation of the body\\\'s immune response against cancer cells, i.e., active immunotherapy.
Transgene has an exclusive license from SillaJen, Inc. to develop and commercialize Pexa-Vec for the treatment of solid tumors in Europe, the Commonwealth of Independent States and the Middle East.
Disease: hepatocellular carcinoma
Details:
- • On November 12, 2015, Transgene and SillaJen announced that they have signed an amended agreement for the development and commercialization of oncolytic viral therapy Pexa-Vec to streamline the conduct of clinical trials and to reflect important areas of interest for each company.
- SillaJen will assume responsibility for conducting the Phase 3 trial (PHOCUS) in hepatocellular carcinoma (HCC). Transgene remains responsible for submitting for marketing approval and retains commercialization rights in its territories. In return, Transgene will pay a total of $6 million to SillaJen over four years beginning this year. Under the terms of the original contract, Transgene was responsible for the development costs in its licensed territories.
- Transgene has returned rights to SillaJen for all Middle Eastern countries, Russia, Ukraine, Belarus and Turkey. This change enables Transgene to focus on Europe, its core area of interest, while returning to SillaJen markets that provide additional commercialization opportunities.
- Under the amended agreement, Transgene has also committed to initiate independently an exploratory trial evaluating Pexa-Vec in combination with nivolumab for the treatment of HCC. Transgene will be responsible for all costs related to this trial, as well as any other exploratory trials it independently initiates.
- The companies also outlined key parts of the current clinical development plan for Pexa-Vec. Phase 3 trial in HCC expected to initiate soon. The Phase 3 trial of Pexa-Vec, named PHOCUS, followed by sorafenib in the first-line treatment of patients with advanced HCC, the most common form of liver cancer, is on track to initiate in the fourth quarter of this year. Sorafenib is currently the only approved treatment for this disease, and new therapies are urgently needed. The trial is being led by SillaJen and is planned to enroll approximately 600 patients in North America, Europe and Asia. The study is being conducted under a Special Protocol Assessment (SPA) with the FDA.
- Ongoing and planned exploratory trials. Transgene is independently conducting several exploratory studies with Pexa-Vec. Two trials in combination with immune checkpoint inhibitors are being planned and are expected to initiate during 2016: a study with nivolumab in advanced HCC and another with ipilimumab in advanced melanoma. Two other studies are underway and patients have been dosed: 1) a study evaluating Pexa-Vec in combination with metronomic cyclophosphamide, a drug used in combination with other therapies to treat a wide variety of cancers, mainly in patients with advanced breast cancer or soft tissue sarcoma, is being sponsored by the Bergonié Institute (Bordeaux, France); and
2) a study evaluating Pexa-Vec in cancer patients in the pre-surgery (neoadjuvant) setting to further document the mechanism of action of Pexa-Vec is being sponsored by the University of Leeds (Leeds, United Kingdom).
Financial terms:
Latest news:
- • On April 24, 2017, SillaJen and Transgene have enrolled the first European patient in the ongoing multinational randomized Phase 3 open-label study of Pexa-Vec (formerly JX-594), in patients with advanced hepatocellular carcinoma.
The enrollment of the first European patient triggers a $4 million milestone to be paid to SillaJen by Transgene.
Is general: Yes
