Jennerex

Last updated
Jennerex , Inc.
Type Private [1]
Industry Biopharmaceuticals
Founder David H. Kirn [1]
Fateacquired by SillaJen, Inc.
Headquarters
450 Sansome Street, 16th Floor, San Francisco, California
,
U.S. [2]
Number of locations
4 (USA, Canada, South Korea)
Products Pexa-Vec (JX-594), JX-929 [1]
OwnerSillaJen, Inc.
Number of employees
~50
Website www.sillajen.com

Jennerex Biotherapeutics, Inc. (now owned by SillaJen) was an American private biopharmaceutical company [1] [3] that developed the oncolytic viruses JX-594 [1] [4] and JX-929 [1] among others. By creating oncolytic viruses that can (1) kill tumor cells directly through lysis, (2) activate the immune system by delivering genes that encode immunostimulants and by overcoming tumor cell-induced immunological tolerance, and (3) reduce tumor nutrient supply through the destruction of blood vessels, Jennerex aimed to create a novel approach to treating and possibly curing cancer.

Contents

Company

Jennerex received its name in honor of Edward Jenner, [5] the pioneer of the smallpox vaccine [6] and "the father of immunology". [7]

Locations

Headquarters are located in the Financial District, San Francisco. R&D and manufacturing operations are located at the UCSF Mission Bay campus in San Francisco, at the Ottawa Hospital Research Institute (OHRI) in Ottawa, Ontario, Canada, and at SillaJen, Inc. in Busan, South Korea. [2] [8]

Company History

2003. Jennerex, Inc. (San Francisco, USA) was established. [9]

2007. Jennerex completed Pexa-Vec Phase 1 clinical trial (HEP001). [10]

2008. Jennerex initiated Pexa-Vec Phase 2a clinical trial (HEP007). [10]

2009. European Medicines Agency (EMA) designated Pexa-Vec as an orphan drug for Live Cancer. [11]

2011. Jennerex initiated Pexa-Vec Phase 2b clinical trial (HEP018) for Liver Cancer. [10]

2013. US FDA designated Pexa-Vec as an orphan drug. [12]

2014. SillaJen acquires Jennerex, Inc. [13] SillaJen changed its name after the acquisition to SillaJen Biotherapeutics. [14]

Pipeline

Oncolytic viruses developed by Jennerex are based on the vaccinia virus.

Pexa-Vec (Jx-594)

Pexa-Vec is an engineered oncolytic virus that selectively destroys cancer cells and induces tumor immune response. Uncontrolled cell division, inactivation of the interferon pathway that is necessary to defend against viral infections, and constitutively active EGFR-Ras signaling pathway, are common features of cancer cells. These features enable rapid replication of the JX-594 virus and lysis of the host cancer cells. Deletion of thymidine kinase (TK) from the JX-594 genome prevents virus replication in normal cells. The immunostimulatory cytokine GM-CSF is produced from the JX-594 genome following infection, inducing immune response against both the virus and the tumor and enabling lasting tumor immunity. Finally, JX-594 reduces nutrient supply to tumors through blood vessel destruction. Because JX-594 is based on the Wyeth strain vaccinia virus that is commonly used for vaccination, it is well tolerated by rats, rabbits, and humans. [15]

Design

To engineer JX-594, human GMCSF gene (encoding granulocyte macrophage colony-stimulating factor or GM-CSF; driven by a synthetic early/late promoter) and lacZ gene (encoding β-galactosidase or β-gal; driven by the p7.5 early/late promoter) were inserted into the TK gene (encoding thymidine kinase or TK) in the J segment of the Wyeth strain vaccinia virus. [16] [17] Elimination of TK from the JX-594 genome restricts viral replication to tumor cells, whereas GM-CSF production facilitates tumor immune response against, and β-gal is included for virus tracking purposes. [17]

Efficacy

Initially, it was demonstrated that patients with refractory melanomas who received intratumoral injection of JX-594 (104-2x107 PFU/lesion; 104-8x107 PFU/session for 6 weeks) had mixed (3/7), partial (1/7), or complete (1/7) responses. [16]

Upon comparison of intravenous (i.v.) delivery of JX-594 (109 PFU) to intratumoral (i.t.) injection in immunocompetent liver cancer model in rabbits over 7 weeks, it was found that the i.t. treatment reduced the average primary tumor volume from 425 cm3 in control animals to 20 cm3 in i.t.-treated animals, and to 35 cm3 in the i.v. treatment group. [17] Furthermore, the average number of lung metastases was reduced from 17 in control animals to 0.5 in i.t.-treated animals and none in the i.v.-treated animals. [17]

Immune response

Dense infiltration of with CD4+ and CD8+ T lymphocytes into the tumor was observed following intratumoral injection of JX-594. [16] [17] Despite the presence of anti-vaccinia antibodies, virally encoded GM-CSF mRNA was detected at injection sites up to 31 weeks following the intratumoral JX-594 inoculation and was not present in the serum. [16] Systemic GM-CSF was detected up to 7 weeks following both intratumoral and intravenous injection of JX-594. [17]

Safety

Side effects following intratumoral injection are limited to flu-like symptoms and resolve within 24 hours. [16] Toxicology studies in New Zealand White rabbits (3 weekly i.v. doses of 1010 PFU) showed that JX-594 was well tolerated, and no toxicologically significant effects were observed. There were no overt clinical signs, with the exception of ~5% of body weight loss by day 6 that was followed by a recovery by day 33. [17]

JX-929

JX-Next Generation

Novel oncolytic viruses in Jennerex pipeline are engineered through the Selective Oncolytic Vaccinia Engineering (SOLVE) platform. This platform is used to optimize virus targeting to specific cancer types, to select transgenes to include into the viral genome, and to optimize viral infection and/or replication selectivity through targeted mutations. [18]

Partnerships

Jennerex has partnered with Transgene, Green Cross, Lee's Pharmaceuticals, Rex Medical, and SillaJen for JX-594 development and commercialization. As of October 9, 2012, Jennerex has not licensed rights for JX-594 in either the United States or Japan. [19]

Further reading

Related Research Articles

<span class="mw-page-title-main">DNA vaccine</span> Vaccine containing DNA

A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.

A cancer vaccine is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", being prepared from samples taken from the patient, and are specific to that patient.

<i>Poxviridae</i> Family of viruses

Poxviridae is a family of double-stranded DNA viruses. Vertebrates and arthropods serve as natural hosts. There are currently 83 species in this family, divided among 22 genera, which are divided into two subfamilies. Diseases associated with this family include smallpox.

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspecialty of oncology.

An oncolytic virus is a virus that preferentially infects and kills cancer cells. As the infected cancer cells are destroyed by oncolysis, they release new infectious virus particles or virions to help destroy the remaining tumour. Oncolytic viruses are thought not only to cause direct destruction of the tumour cells, but also to stimulate host anti-tumour immune system responses. Oncolytic viruses also have the ability to affect the tumor micro-environment in multiple ways.

Virotherapy is a treatment using biotechnology to convert viruses into therapeutic agents by reprogramming viruses to treat diseases. There are three main branches of virotherapy: anti-cancer oncolytic viruses, viral vectors for gene therapy and viral immunotherapy. These branches use three different types of treatment methods: gene overexpression, gene knockout, and suicide gene delivery. Gene overexpression adds genetic sequences that compensate for low to zero levels of needed gene expression. Gene knockout uses RNA methods to silence or reduce expression of disease-causing genes. Suicide gene delivery introduces genetic sequences that induce an apoptotic response in cells, usually to kill cancerous growths. In a slightly different context, virotherapy can also refer more broadly to the use of viruses to treat certain medical conditions by killing pathogens.

<span class="mw-page-title-main">John Cameron Bell</span>

John Cameron Bell is a senior cancer researcher at the OHRI. He currently resides in Ottawa, Ontario with his wife Sheila.

Pelareorep is a proprietary isolate of the unmodified human reovirus being developed as a systemically administered immuno-oncological viral agent for the treatment of solid tumors and hematological malignancies. Pelareorep is an oncolytic virus, which means that it preferentially lyses cancer cells. Pelareorep also promotes an inflamed tumor phenotype through innate and adaptive immune responses. Preliminary clinical trials indicate that it may have anti-cancer effects across a variety of cancer types when administered alone and in combination with other cancer therapies.

JX-594 is an oncolytic virus is designed to target and destroy cancer cells. It is also known as Pexa-Vec, INN pexastimogene devacirepvec) and was constructed in Dr. Edmund Lattime's lab at Thomas Jefferson University, tested in clinical trials on melanoma patients, and licensed and further developed by SillaJen.

<span class="mw-page-title-main">Talimogene laherparepvec</span> Gene therapy medication

Talimogene laherparepvec, sold under the brand name Imlygic, is a biopharmaceutical medication used to treat melanoma that cannot be operated on; it is injected directly into a subset of lesions which generates a systemic immune response against the recipient's cancer. The final four year analysis from the pivotal phase 3 study upon which TVEC was approved by the FDA showed a 31.5% response rate with a 16.9% complete response (CR) rate. There was also a substantial and statistically significant survival benefit in patients with earlier metastatic disease and in patients who hadn't received prior systemic treatment for melanoma. The earlier stage group had a reduction in the risk of death of approximately 50% with one in four patients appearing to have met, or be close to be reaching, the medical definition of cure. Real world use of talimogene laherparepvec have shown response rates of up to 88.5% with CR rates of up to 61.5%.

<span class="mw-page-title-main">Oncolytic herpes virus</span>

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Adenovirus varieties have been explored extensively as a viral vector for gene therapy and also as an oncolytic virus.

GL-ONC1 is an investigational therapeutic product consisting of the clinical grade formulation of the laboratory strain GLV-1h68, an oncolytic virus developed by Genelux Corporation. GL-ONC1 is currently under evaluation in Phase I/II human clinical trials in the United States and Europe.

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SillaJen, Inc. is a South Korea-based biotechnology company, with offices in Busan, Yangsan and Seoul, South Korea, and San Francisco, California.

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References

  1. 1 2 3 4 5 6 "Jennerex facts sheet: Q3 2012" (PDF). 2012. Archived from the original (PDF) on February 28, 2013. Retrieved September 23, 2012.
  2. 1 2 "Company contact information on Jennerex website". 2012. Archived from the original on August 22, 2012. Retrieved October 8, 2012.
  3. ↑ "Jennerex website". 2012. Retrieved September 9, 2012.
  4. ↑ Breitbach C.J.; Burke J.; Jonker D.; Stephenson J.; Haas A.R.; Chow L.Q.M.; Nieva J.; Hwang T.H.; Moon A.; Patt R.; Pelusio A.; Le Boeuf F.; Burns J.; Evgin L.; De Silva N.; Cvancic S.; Robertson T.; Je J.-E.; Lee Y.-S.; Parato K.; Diallo J.-S.; Fenster A.; Daneshmand M.; Bell J.C.; Kirn D.H. (2011). "Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans". Nature . 477 (7362): 99–102. doi:10.1038/nature10358. PMID   21886163. S2CID   4365604.
  5. ↑ "Jenner-ex story". 2012. Archived from the original on January 15, 2013. Retrieved September 9, 2012.
  6. ↑ Riedel S. (2005). "Edward Jenner and the history of smallpox and vaccination". Baylor University Medical Center Proceedings. 18 (1): 21–25. doi:10.1080/08998280.2005.11928028. PMC   1200696 . PMID   16200144.
  7. ↑ "Edward Jenner (1749 - 1823)". BBC: Historic Figures. 2012. Retrieved September 9, 2012.
  8. ↑ "SillaJen website". 2012. Archived from the original on February 2, 2013. Retrieved October 8, 2012.
  9. ↑ "Jennerex Biotherapeutics Inc". BioCentury – BCIQ. Retrieved 2018-06-17.
  10. 1 2 3 "Search of: JX-594 - List Results - ClinicalTrials.gov" . Retrieved 2018-06-17.
  11. ↑ "Jennerex Granted FDA Orphan Drug Designation for Pexa-Vec in Hepatocellular Carcinoma (HCC)" . Retrieved 2018-06-17.
  12. ↑ France, Kelly (May 8, 2013). "Jennerex Granted FDA Orphan Drug Designation for Pexa-Vec in Hepatocellular Carcinoma (HCC)". marketwired.com/. Retrieved June 16, 2018.
  13. ↑ "SillaJen Announces Agreement to Acquire Jennerex, Inc" . Retrieved 2018-06-17.
  14. ↑ "SillaJen changes its name to mark Jennerex acquisition". www.thepharmaletter.com. Retrieved 2020-06-24.
  15. ↑ "JX-594 description on Jennerex website". 2012. Archived from the original on November 17, 2012. Retrieved October 2, 2012.
  16. 1 2 3 4 5 Mastrangelo M.J.; Maguire M.C.J.; Eisenlohr L.C.; Laughlin C.E.; Monken C.E.; McCue P.A; Kovatich A.J.; Lattime E.C. (1999). "Intratumoral recombinant GM-CSF-encoding virus as gene therapy in patients with cutaneous melanoma". Cancer Gene Therapy . 6 (5): 409–422. doi:10.1038/sj.cgt.7700066. PMID   10505851.
  17. 1 2 3 4 5 6 7 Kim J.H.; Oh J.Y.; Park B.H.; Lee D.E.; Kim J.S.; Park H.E.; Roh M.S.; Je J.E.; Yoon J.H.; Thorne S.H.; Kirn D.; Hwang T.H. (2006). "Systemic Armed Oncolytic and Immunologic Therapy for Cancer with JX-594, a Targeted Poxvirus Expressing GM-CSF". Molecular Therapy . 14 (3): 361–370. doi: 10.1016/j.ymthe.2006.05.008 . PMID   16905462.
  18. ↑ "JX-Next Generation description on Jennerex website". 2012. Archived from the original on September 27, 2012. Retrieved October 8, 2012.
  19. ↑ "Company partnerships on Jennerex website". 2012. Archived from the original on September 26, 2012. Retrieved October 9, 2012.
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