Potent biological activity observed in injected and non-injected lesions
Findings presented at Melanoma Bridge 2013 Conference
Conference Call Scheduled for 8:00 am EST on Monday, December 9
BOSTON, MA, USA I December 7, 2013 I ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP) today announced positive interim results from its ongoing Phase 1/2 study of Ad-RTS-IL-12, a novel DNA-based therapeutic candidate that is being evaluated with the oral activator, veledimex, in patients with advanced melanoma. The results from this multicenter study were presented at Melanoma Bridge 2013 Conference at the session “Best Abstracts on News in Immunotherapy”, an international conference co-sponsored by Istituto Nazionale Tumori Fondazione, Sidra Medical and Research Center, and the Society for ImmunoTherapy of Cancer that is being held in Naples, Italy.
In this study, 21 patients with unresectable, recurrent stage III/IV melanoma have been treated with intratumoral injections of Ad-RTS-IL-12 and the oral activator veledimex. The purpose of the study is to evaluate the safety and tolerability of the Ad-RTS-IL-12 and veledimex therapy, determine tumor and immune response, and select the optimal dose and schedule of veledimex for future study. To date, expression of IL-12 mRNA in study subjects’ tumors was determined to be very high and tightly controlled by veledimex dose with expression ranging from a median increase of approximately 1,000 times with an oral dose of 100 mg to approximately 100,000 times with an oral dose of 160 mg. In addition, upon stopping veledimex dosing, expression of the IL-12 mRNA returned to baseline levels, demonstrating the “on” and “off” control of Intrexon Corporation’s (NYSE:XON) RheoSwitch Therapeutic System® platform. In this dose range, results to date demonstrate that Ad-RTS-IL-12 + veledimex has potent biologic activity, as measured by on-mechanism and on-target toxicity and response in injected and non-injected lesions. In addition, increased tumor infiltrating lymphocytes were observed in the tumor microenvironment at these doses, suggesting multiple favorable biologic effects of IL-12 expression. Following treatment, 11 of 16 evaluable patients have demonstrated a response of stable disease or better on a per lesion basis.
The most common severe adverse events (SAEs) were pyrexia, hypotension, mental status changes, and cytokine release syndrome. Four of seven patients with SAEs had veledimex dosing stopped during cycle 1. Three had SAEs during subsequent cycles, and stopped veledimex dosing at that time. Importantly, all SAEs were reversed after veledimex dosing was stopped, demonstrating the “on” and “off” control of veledimex on gene expression.
“Immunotherapy is a powerful and promising approach to the treatment of many cancers, including advanced melanoma,” said Dr. John Nemunaitis, MD, Executive Medical Director, Mary Crowley Medical Research Center, and lead investigator of the study. “A major limitation to turning on the immune system in cancer is the many checks and balances that mask the tumor from the immune system. Delivery of interleukin-12 using the regulated gene expression system Ad-RTS-IL-12 provides us with the ability to turn on the immune system and finely control this potent anti-cancer immune response to derive clinical effect and manage tolerability. To date, this study has demonstrated immune response and encouraging activity, along with a tolerability profile that is well controlled by dose of the activator ligand veledimex. This should combine well with other emerging treatments to create a new treatment option for advanced melanoma and other cancers.”
“The ability to precisely modulate gene expression at the site of the cancer represents a potential paradigm shift in cancer treatment,” said Francois Lebel, M.D., Senior Vice President, Clinical Development and Medical Operations at ZIOPHARM. “We believe the evidence of safety, efficacy and control of gene expression in this study is encouraging and warrants the completion of this trial and the pursuit of a larger Phase 2 clinical trial in patients with advanced melanoma in 2014. We look forward to reporting the full results of this study at a future medical meeting and to initiating later-stage clinical testing in a larger patient population.”
ZIOPHARM is developing Ad-RTS-IL-12 using Intrexon Corporation’s RheoSwitch Therapeutic System® platform to control the expression of interleukin-12 and enable its safe and effective delivery as an anti-tumor agent. The company is advancing the Ad-RTS-IL-12 platform in melanoma, breast cancer and glioblastoma.
Conference Call Information:
ZIOPHARM management, joined by Larry Norton, M.D., Deputy Physician-in-Chief for Breast Cancer Programs, Memorial Sloan-Kettering Cancer Center, Medical Director, Breast Cancer Programs, will host a conference call and live audio webcast on Monday, December 9, 2013, at 8:00 AM ET. The call can be accessed by dialing (877) 402-8188 (U.S. and Canada) or (330) 871-4581 (international). The passcode for the conference call is ‘ZIOPHARM.’ To access the live audio webcast, or the subsequent archived recording, visit the “Investors – Events & Presentations” section of the ZIOPHARM website at www.ziopharm.com. The webcast will be recorded and available for replay on the Company’s website for two (2) weeks.
About ZIOPHARM Oncology, Inc.:
ZIOPHARM Oncology is a Boston, Massachusetts-based biotechnology company employing novel gene expression and control technology to deliver DNA for the treatment of cancer. ZIOPHARM’s technology employs Intrexon Corporation’s RheoSwitch Therapeutic System® platform to turn on and off, and precisely modulate, gene expression at the cancer site in order to improve the therapeutic index. This technology is currently being evaluated in Phase 2 clinical studies of the immune system cytokine interleukin-12 for the treatment of breast cancer and advanced melanoma. Multiple new Investigational New Drug applications for new targets using synthetic biology technology with monogenic and multigenic approaches are expected in 2014 and 2015. ZIOPHARM is also developing novel small molecules as potential cancer therapeutics.
SOURCE: ZIOPHARM Oncology
Post Views: 107
Potent biological activity observed in injected and non-injected lesions
Findings presented at Melanoma Bridge 2013 Conference
Conference Call Scheduled for 8:00 am EST on Monday, December 9
BOSTON, MA, USA I December 7, 2013 I ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP) today announced positive interim results from its ongoing Phase 1/2 study of Ad-RTS-IL-12, a novel DNA-based therapeutic candidate that is being evaluated with the oral activator, veledimex, in patients with advanced melanoma. The results from this multicenter study were presented at Melanoma Bridge 2013 Conference at the session “Best Abstracts on News in Immunotherapy”, an international conference co-sponsored by Istituto Nazionale Tumori Fondazione, Sidra Medical and Research Center, and the Society for ImmunoTherapy of Cancer that is being held in Naples, Italy.
In this study, 21 patients with unresectable, recurrent stage III/IV melanoma have been treated with intratumoral injections of Ad-RTS-IL-12 and the oral activator veledimex. The purpose of the study is to evaluate the safety and tolerability of the Ad-RTS-IL-12 and veledimex therapy, determine tumor and immune response, and select the optimal dose and schedule of veledimex for future study. To date, expression of IL-12 mRNA in study subjects’ tumors was determined to be very high and tightly controlled by veledimex dose with expression ranging from a median increase of approximately 1,000 times with an oral dose of 100 mg to approximately 100,000 times with an oral dose of 160 mg. In addition, upon stopping veledimex dosing, expression of the IL-12 mRNA returned to baseline levels, demonstrating the “on” and “off” control of Intrexon Corporation’s (NYSE:XON) RheoSwitch Therapeutic System® platform. In this dose range, results to date demonstrate that Ad-RTS-IL-12 + veledimex has potent biologic activity, as measured by on-mechanism and on-target toxicity and response in injected and non-injected lesions. In addition, increased tumor infiltrating lymphocytes were observed in the tumor microenvironment at these doses, suggesting multiple favorable biologic effects of IL-12 expression. Following treatment, 11 of 16 evaluable patients have demonstrated a response of stable disease or better on a per lesion basis.
The most common severe adverse events (SAEs) were pyrexia, hypotension, mental status changes, and cytokine release syndrome. Four of seven patients with SAEs had veledimex dosing stopped during cycle 1. Three had SAEs during subsequent cycles, and stopped veledimex dosing at that time. Importantly, all SAEs were reversed after veledimex dosing was stopped, demonstrating the “on” and “off” control of veledimex on gene expression.
“Immunotherapy is a powerful and promising approach to the treatment of many cancers, including advanced melanoma,” said Dr. John Nemunaitis, MD, Executive Medical Director, Mary Crowley Medical Research Center, and lead investigator of the study. “A major limitation to turning on the immune system in cancer is the many checks and balances that mask the tumor from the immune system. Delivery of interleukin-12 using the regulated gene expression system Ad-RTS-IL-12 provides us with the ability to turn on the immune system and finely control this potent anti-cancer immune response to derive clinical effect and manage tolerability. To date, this study has demonstrated immune response and encouraging activity, along with a tolerability profile that is well controlled by dose of the activator ligand veledimex. This should combine well with other emerging treatments to create a new treatment option for advanced melanoma and other cancers.”
“The ability to precisely modulate gene expression at the site of the cancer represents a potential paradigm shift in cancer treatment,” said Francois Lebel, M.D., Senior Vice President, Clinical Development and Medical Operations at ZIOPHARM. “We believe the evidence of safety, efficacy and control of gene expression in this study is encouraging and warrants the completion of this trial and the pursuit of a larger Phase 2 clinical trial in patients with advanced melanoma in 2014. We look forward to reporting the full results of this study at a future medical meeting and to initiating later-stage clinical testing in a larger patient population.”
ZIOPHARM is developing Ad-RTS-IL-12 using Intrexon Corporation’s RheoSwitch Therapeutic System® platform to control the expression of interleukin-12 and enable its safe and effective delivery as an anti-tumor agent. The company is advancing the Ad-RTS-IL-12 platform in melanoma, breast cancer and glioblastoma.
Conference Call Information:
ZIOPHARM management, joined by Larry Norton, M.D., Deputy Physician-in-Chief for Breast Cancer Programs, Memorial Sloan-Kettering Cancer Center, Medical Director, Breast Cancer Programs, will host a conference call and live audio webcast on Monday, December 9, 2013, at 8:00 AM ET. The call can be accessed by dialing (877) 402-8188 (U.S. and Canada) or (330) 871-4581 (international). The passcode for the conference call is ‘ZIOPHARM.’ To access the live audio webcast, or the subsequent archived recording, visit the “Investors – Events & Presentations” section of the ZIOPHARM website at www.ziopharm.com. The webcast will be recorded and available for replay on the Company’s website for two (2) weeks.
About ZIOPHARM Oncology, Inc.:
ZIOPHARM Oncology is a Boston, Massachusetts-based biotechnology company employing novel gene expression and control technology to deliver DNA for the treatment of cancer. ZIOPHARM’s technology employs Intrexon Corporation’s RheoSwitch Therapeutic System® platform to turn on and off, and precisely modulate, gene expression at the cancer site in order to improve the therapeutic index. This technology is currently being evaluated in Phase 2 clinical studies of the immune system cytokine interleukin-12 for the treatment of breast cancer and advanced melanoma. Multiple new Investigational New Drug applications for new targets using synthetic biology technology with monogenic and multigenic approaches are expected in 2014 and 2015. ZIOPHARM is also developing novel small molecules as potential cancer therapeutics.
SOURCE: ZIOPHARM Oncology
Post Views: 107