Pipeline

Telomelysin (OBP-301)

Outline

Telomelysin or OBP-301 is oncolytic adenovirus in which gene is modified to be able to selectively replicate in cancer cells by introducing human telomerase reverse transcriptase (hTERT) promotor. Oncolytic adenovirus has much potential for cancer immunotherapy because its viral replication is highly immunogenic, and oncolysis induced by such virus releases tumor epitopes and provides costimulatory danger signals. From the result of phase 1 clinical study in the US, Oncolys obtained promising data showing abscopal effect in melanoma patients after single injection into one single tumor and found that not only increasing infiltration of CD8 and antigen presenting cells but diminishing Treg cells in injected tumor site.
Oncolys has been conducting phase1/2 clinical study of Telomelysin for hepatocellular carcinoma in Korea and Taiwan and phase 2 clinical study for melanoma. We will also soon initiate phase 1/2 study for esophageal cancer in combination with radiation, and another phase 1/2 study for esophageal cancer in combination with a check-point inhibitor in Japan.

Telomelysin

Target indication

Esophageal cancer, melanoma and hepatocellular carcinoma

Current status

In preclinical studies for Telomelysin, Oncolys has demonstrated effective anti-tumor activity on various cancer cells, and there was no finding that may bring safety concerns in toxicological studies as well as bio-distribution study. Oncolys completed the phase 1 clinical trial for solid tumors in the US with 16 subjects for single dosing and 6 subjects for repeated dosing. Most of the adverse events observed in the study was mild to moderate and transient, and there was a sign of efficacy showing tumor shrinkage in 8 out of 12 evaluable patients.
In Japan, investigator initiated clinical research for esophageal cancer in combination with radiotherapy has been conducted in Okayama University. 4 out of 7 patients (1 withdrawn due to the progress of other diseases) showed CR (complete response), and CD8 T cell infiltration was observed in tumor area. Based on positive results in this study, Oncolys is in preparation to initiate company-sponsored clinical trial with same study design in Japan.
In addition, Oncolys has been conducting phase 1/2 clinical trial of Telomelysin targeting hepatocellular carcinoma patients refractory to existing cancer treatments in Korea and Taiwan under the IND approved by the US FDA, which is collaboratively conducted with Taiwanese biotech company, called Medigen Biotechnology Corp. Nine patients in total (single dosing cohorts, 1 to 3; 3 patients in each cohort) have been enrolled to date, and DSMB confirmed the safety of intrahepatically administered Telomelysin. Two patients showed efficacy sign, one showed necrotic region in the injected site and another showed stable disease for long time.
We further have a plan to initiate two clinical studies. One is melanoma study in the US, and Oncolys has already submitted the study protocol to the US FDA. We anticipate the first patient enrollment in 1Q 2017. The other one is esophageal cancer study in combination with check-point inhibitor, which will be initiated in 2Q, 2017.

  • (Countries where patent was issued)
  • Japan, United States, Europe, South Africa, Singapore, New Zealand, Australia, China, Hong Kong,
    South Korea, Canada.

References

Efficacy of a Cell-Cycle Decoying Killer Adenovirus on 3-D Gelfoam Histoculture and Tumor-Sphere Models of Chemo Resistant Stomach Carcinomatosis Visualized by FUCCI Imaging

Shuya Yano, Kiyoto Takehara, Hiroshi Tazawa, Hiroyuki Kishimoto, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara, Robert M.Hoffman
PLOS ONE DOI:10.1371/Journal.pone.0162991 September27, 2016

Targeted Photodynamic Virotherapy Armed with a Genetically Encoded Photosensitizer

Kiyoto Takehara, Hiroshi Tazawa,Naohiro Okada, Yuuri Hashimoto, Satoru Kikuchi, Shinji Kuroda, Hiroyuki Kishimoto, Yasuhiro Shiralawa, Nobuhiro Narii, Hiroyuki Mizuguchi, Yasuo Urata, Shunsuke Kagawa, and Toshiyoshi Fujiwara
Molecular Therpy, January2016 Ther;15(1), 2016

Biological Ablation of Sentinel Lymph Node Metastasis in Submucosally Invaded Early Gastrointestinal Cancer

Satoru Kikuchi, Hiroyuki Kishimoto, Hiroshi Tazawa, Yuuri Hashimoto, Shinji Kuroda, Masahiko Nishizaki, Takeshi Nagasaka, Yasuhiro Shirakawa, Shunsuke Kagawa, Yasuo Urata, Robert M Hoffman and Toshiyoshi Fujiwara
Molecular Therpy,mar2015 vol.23 no.3,501-509, 2015

Asimple detection system for adenovirus receptor expression using a telomerase-specific replication-competent adenovirus

T Sasaki, H Tazawa, Hashimoto, S Yano, R Yoshida, S Kagawa, F Uno, Y Urata, T Ozagi, and T Fujiwara
Gene Therapy(2013)20,112-118, 2013

A Genetically Engineered Oncolytic Adenovirus Decoys and Lethally Traps Quiescent Cancer Stek-like Cells in S/G2/M Phases

Shuya Yano, Hiroshi Tazawa, Yuuri Hashimoto, Yasuhiro Shirakawa, Shinji Kuroda, Masahiko Nishizaki, Hiroyuki Kishimoto, Futoshi Uno, Takeshi Nagasaka, Yasuo Urata, Shunsuke Kagawa, Robert M. Hoffman, and Toshiyoshi Fujiwara
Clinical Cancer Research, 19(23)December 1,2013, Dec. 2013

Enhanced antitumor efficacy of telomerase-selective oncolytic adenovirus with valproic acid against human cancer cell

Y Watanabe, Y Hahimoto, S Kagawa, H Kawamura, K Nagai, Y Urata and T Fujiwara
Cencer Gene Therapy(2012)19,,767-772, Oct. 2012

A novel apototic mechanism of genetically engineered adenovirus-mediated tumour-specific p53 overexpression through E1A-dependent p21 and MDM2 suppression

Yasumoto Yamasaki, Haroshi Tazawa, Yuuri Hashimoto, Taru Kojimaa, Shinji Kuroda, Shuya Yano, Ryosuke Yoshida, Futoshi Uno, Hiroyuki Mizuguchi, Akira Ohtsuru, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara
European Journal of Cancer(2012)48,2282-2291, Aug. 2012

Clicical development directions in oncolytic viral therapy RM Eager1,2 and J Nemunaitis1,3,4

Mary Crowley Cancer Research Centers, Dallas, TX, USA; Department of Internal Medicine, TheUniversity of Hawaii, Honolulu, HI, USA; Texas Oncology PA Dallas, TX USA and Medical City Dallas Hospital, Dallas, TX, USA
Cancer Gene Therapy (2011)18,305-317, May 2011

Telomerase-Dependent Oncolytic Adenovirus Sensitizes Human Cancer Cells to lonzing Radiation via Inhibition of DNA Repair Machinery

Shinji Kuroda, Toshiya Fujiwara, Yasuhiro Shirakawa, Yasumoto Yamasaki, Shuya Yano, Futoshi Uno, Hiroshi Tazawa, Yuuri Hashimoto, Yuichi Watanabe, Kazuhiro Nomo, Yasuo Urata, Shunsuke Kagawa, and Toshiyoshi Fujiwara
CANCER RESEARCH, 70(22): Nov 15,2010, Nov. 2010

Preclinical Evaluation of Differentially Targeting Dual Virotherapy for Human Solid Cancer

Ryo Sakai, Shusuke Kagawa, Yasumoto Yamasaki, Toru Kojima, Futoshi Uno, Yuuri Hashimoto, Yuichi Watanabe, Yasuo Urata, Noriaki Tanaka1, and Toshiyoshi Fujiwara
Mol Cancer Ther, 9;8(4): June 2010, Aug. 2010

In Vivo Biological Purging forLymph Node Metastasis of Human Colorectal Cancer by Telomerase-Specific Oncolytic Virotherapy

Toru Kojima,MD, Yuichi Watanabe,PhD, Yuuri Hashimoto,BS, Shinji Kuroda,MD, Yasumoto Yamasaki,MD, Shuya Yano,MD, Masaaki Ouchi,BS, Hiroshi Tazawa,MD,PhD, Futoshi Uno,MD,PhD, Shunsuke Kagawa,MD,PhD, Satoru Kyo,MD,PhD,
Annals of Surgery Volume251, Number6, June 2010, Jun. 2010

A novel translational approach for human malignant pleural mesothelioma:heparnase-assisted dual virotherapy

Y Watanabe, T Kojima, S Kagawa, F Uno, Y Hashimoto, S Kyo, H Mizuguchi, N Tanaka, H Kawamura, D Ichimaru, Y Urata and T Fujiwara
Oncogene(2010)29.1145-1154, 2010

Antiumor effects of telomelysin in combination with paclitaxel or cisplatin on head and neck squamous cell carcinoma

NORIO KONDO, MAMORU TSUKUDA, MACHIKO KIMURA, KYOKO FUJITA, ATSUKO SAKAKIBARA, HIDEAKI TAKAHASHI, YUKARI ISHIGURO, GABOR TOTH and HIDEKI MATSUDA
.ONCOLOGY REPORTS.23:355-363.2010, Jan. 2010

A Phase I Study of Telomerase-specific Replication Competent Oncolytic Adenovirus(Telomelysin) for Various Solid Tumors

John Nemunaitis, Alex W Tong, Michael Nemunaiitis, Neil Senzer, Anagha P Phadke, Cynthia Bedell, Ned Adams, Yu-An Zhang, Phillip B Maples, Salina Chen, Beena Pappen, James Burke, Daijyu Ichimaru, Yasuo Urata and Toshiyoshi Fujiwara
Molecular Therpy,Nov 2009, Nov. 2009

Preclinical evaluation of synergistic effect of telomerasespesific oncolytic viritherrapy and gemcitabine for human lung cancer

Dong Liu, Toru Kojima, Masaaki Ouchi, Shinji Kuroda, Yuichi Watanabe, Yuuti Hashimoto, Hideki Onimatsu, Yasuo Urata, and Toshiyoshi Fujiwara
Mol Cancer Ther, 2009;8(4): April 2009, Apr. 2009

Telomerase-Specific Virotheranostics for Human Head and Neck Cancer

Yuji Kurihara, Yuichi Watanabe, Hideki Onimatsu, Toru Kojima, Tatsuo Shitota, masashi Hatori, Dong Liu, Satoru Kyo, Hirosyuki Mizoguchi, Yasuo Urata, Satoru Shintani, and Toshiyoshi Fujiwara
Clinical Cancer Research, 2009;15(7): 2335-2343, Apr. 2009

Antiviral activity of cidofovir against telomerase-speciffic replication-selective oncolytic adenovirus, OBP-301(Telomelysin)

Masaaki Ouchi, Hitoshi Kawamura, Yasuo Urata, Toshiyoshi Fujiwara
Invest New Drugs, 2009 27: 241-245, 2009

A Novel Antiangiogenic Effect for Telomerase-Spaecific Virotherapy through Host Immune System

Yoshiko Ikeda, Toru Kojima, Shinji Kurada, Yohikatsu Endo, Ryo Sakai, Masayoshi Hioki, Hiroyuki Kishimoto, Futtoshi Uno, Shunsuke Kagawa, Yuichi Watanabe, Yuuri Hashimoto, Yasuo Urata, Noriaki Tanaka, and Toshiyoshi Fujiwara
The Journal of Immunology, 182: 1763-1769, 2009

Telomerase-specific virotherapy in an animal model of human head and neck cancer

Oumi Nakajima, Atsuko Matsunaga, Daiju Ichimaru, Yasuo Urata, Toshiyoshi Fujiwara, and Koji Kawakami
Mol Cancer Ther, 2009;8(1): 171-177, Jan. 2009

Establishment of biological and pharmacokinetic assayas of telomerase-specific replication-selective adenovirus

Yuuri Hashimoto, Yuichi Watanebe, Yoshiko Shirakiya, Futoshi Uno, Shunsuke Kagawa, Hitoshi Kawamura, Katsuyuki Nagai, Noriaki Tanaka, Horomi Kumon, Yasuo Urata and Toshiyoshi Fujiwara
Cancer Sci, 99(2): 385-390, Feb. 2008

Virus-mediated oncolysis induces danger signal and stimulates cytotoxic T-lymphocyte activity via proteasome activator upregulation

Y Eodo, R Sakai, M Ouchi, H Onimatsu, M Hioki, S Kagawa, F Uno, Y Watanabe, Y Urata, N Tanaka, and T Fujiwara
Onvogene(2008)27, 2375-2381, 2008

Telomerase-Specific Oncolytic Virotherapy for Human Cancer with the hTERT Promoter

Toshiya Fujiwara, Yasuo Urata, Noriaki Tanaka
Current Cancer Drug Targets, 7(2): 191-201, Jul. 2007

Histone deacetylase inhibitor FR901228 enhances the antitumor effect of telomerase-specific replication-selective adenoviral agent OBP-301 in human lung cancer cells

Takanori Watanabe, Masayoshi Hioki, Toshiya Fujiwara, Masahiko Nishizaki, Shunsuke Kagawa, Masaki Taki, Hiroyuki Kishimoto, Yoshikatsu Endo, Yasuo Urata, Noriaki Tanaka, Toshiyoshi Fujiwara
Experimental Cell Research, 312: 256–265, 2006

Visualization of Intrathoracically Disseminated Solid Tumors in Mice with Optical Imaging by Telomerase-Specific Amplification of a Transferred Green Fluorescent Protein Gene

Tatsuo Umeoka, Takeshi Kawashima, Shunsuke Kagawa, Fuminori Teraishi, Masaki Taki, Masahiko Nishizaki, Satoru Kyo, Katsuyuki Nagai, Yasuo Urata, Noriaki Tanaka, and Toshiyoshi Fujiwara
CANCER RESEARCH, 64(17): 6259-65, Sep. 1, 2004

Telomerase-Specific Replication-Selective Virotherapyfor Human Cancer

Takeshi Kawashima, Shunsuke Kagawa, Naoya Kobayashi, Yoshiko Shirakiya, Tatsuo Umeoka, Fuminori Teraishi, Masaki Taki, Satoru Kyo, Noriaki Tanaka, and Toshiyoshi Fujiwara
Clinical Cancer Research, 10: 285-92, Jan. 1, 2004

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