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ZIOPHARM Announces Expansion of Ground-Breaking Synthetic Immuno-Oncology Programs With Intrexon and Clinical Program Update

On July 22, 2014 ZIOPHARM Oncology reported the expansion of synthetic immuno-oncology programs in conjunction with Intrexon Corporation (NYSE:XON) to include chimeric antigen receptor T-cell (CAR-T) therapy (Press release Ziopharm, JUL 22, 2014, View Source [SID:1234501132]). Additionally the Company has provided an update on its development efforts with the proprietary RheoSwitch Therapeutic System (RTS) platform, an inducible regulator for expression of therapeutic molecules through administration of an oral activator ligand, as well as its clinical program with Ad-RTS-IL-12, a novel DNA-based therapeutic candidate for the controlled expression of IL-12.

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Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

CAR-T cells represent an emerging, high value immunological therapy that can target and destroy cancer cells displaying "personalized" fingerprints, yet current approaches feature challenges associated with toxicity, off-target effects, and uneconomical manufacturing. Intrexon possesses the integrated technology platforms, molecular engineering, systems biology, and cell engineering capabilities required to overcome these challenges and fully realize the potential of CAR-T cell therapies. Most significantly, utilization of the RTS platform will facilitate exquisite regulation of one or more bioeffectors in CAR-T cells enabling physicians to control systemic effects of cell therapies with an appropriate dosing regimen of the oral activator ligand (veledimex), and eventually bring about improved safety and efficacy of these and related therapeutic strategies. Further preclinical work is underway in this promising area of study, and ZIOPHARM and Intrexon expect to provide a progress update in the second half of 2014.

Samuel Broder, M.D., EVP of Scientific and Public Affairs at Intrexon, said, "As a leader in the second generation of biotechnology, Intrexon is applying industrial engineering principles to synthetic immunology to potentiate important biotechnology platforms enabling end-to-end solutions for complex biologic challenges. In particular, the utilization of our proprietary RheoSwitch platform may be especially advantageous in CAR-T treatments."

To date, the RheoSwitch platform has been shown to function as a regulatable switch in an array of cell types for multiple proteins, and RTS expansion into CAR-T therapy is further demonstration of the breadth of Intrexon’s single and multi-genic expression and control technologies. According to data from ClinicalTrials.gov, more than 1,000 clinical trials utilizing gene therapy are currently underway, with the majority in either Phase I or Phase II. Intrexon’s proprietary switch system is uniquely positioned as the first clinically-evaluated gene switch with in vivo data showing the ability to control gene expression with a broad dynamic range. The RTS platform provides a mechanism for titrating therapeutic effects on a patient-specific and predictable basis, as well as a safety switch to rapidly turn off gene-expression. The ability to administer or withdraw the veledimex pill to sustain continued treatment cycles is a key benefit exclusive to RTS technology.

"We are excited by the prospects of applying our advanced synthetic immuno-oncology toolkit towards targeted immunotherapies like CAR-T," said Jonathan Lewis, M.D., Ph.D., CEO of ZIOPHARM. "We also look forward to expanding RTS applications in novel therapeutic strategies for cancer where the ability to control gene expression is essential."

With respect to the Ad-RTS-IL-12 clinical programs, ZIOPHARM continues to conduct Phase II studies in melanoma and breast cancer using Ad-RTS-IL-12 as a monotherapy. Additionally, the Company is evaluating future trials with IL-12 in potential combination therapies with other immune-targeting agents in various cancers including melanoma and breast. ZIOPHARM also plans to initiate a Phase I trial to evaluate Ad-RTS-IL-12 as a single agent in the treatment of patients with Glioblastoma Multiforme in the second half of 2014.

"The development of potent yet tightly controlled cancer depleting therapies such as CAR-T and other targeted cellular products through the molecular rewiring of immunologic gene programs adds to the foundation of our multifaceted strategy in synthetic immuno-oncology," remarked Gregory Frost, Ph.D., SVP of Intrexon’s Health Sector.

ZIOPHARM Announces Expansion of Ground-Breaking Synthetic Immuno-Oncology Programs With Intrexon and Clinical Program Update

On July 22, 2014 ZIOPHARM Oncology reported the expansion of synthetic immuno-oncology programs in conjunction with Intrexon to include chimeric antigen receptor T-cell (CAR-T) therapy (Press release Intrexon, JUL 22, 2014, View Source;p=RssLanding&cat=news&id=1949640 [SID:1234500637]). Additionally the Company has provided an update on its development efforts with the proprietary RheoSwitch Therapeutic System (RTS) platform, an inducible regulator for expression of therapeutic molecules through administration of an oral activator ligand, as well as its clinical program with Ad-RTS-IL-12, a novel DNA-based therapeutic candidate for the controlled expression of IL-12.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

CAR-T cells represent an emerging, high value immunological therapy that can target and destroy cancer cells displaying "personalized" fingerprints, yet current approaches feature challenges associated with toxicity, off-target effects, and uneconomical manufacturing. Intrexon possesses the integrated technology platforms, molecular engineering, systems biology, and cell engineering capabilities required to overcome these challenges and fully realize the potential of CAR‐T cell therapies. Most significantly, utilization of the RTS platform will facilitate exquisite regulation of one or more bioeffectors in CAR-T cells enabling physicians to control systemic effects of cell therapies with an appropriate dosing regimen of the oral activator ligand (veledimex), and eventually bring about improved safety and efficacy of these and related therapeutic strategies. Further preclinical work is underway in this promising area of study, and ZIOPHARM and Intrexon expect to provide a progress update in the second half of 2014.

Samuel Broder, M.D., EVP of Scientific and Public Affairs at Intrexon, said, "As a leader in the second generation of biotechnology, Intrexon is applying industrial engineering principles to synthetic immunology to potentiate important biotechnology platforms enabling end-to-end solutions for complex biologic challenges. In particular, the utilization of our proprietary RheoSwitch platform may be especially advantageous in CAR-T treatments."

To date, the RheoSwitch platform has been shown to function as a regulatable switch in an array of cell types for multiple proteins, and RTS expansion into CAR-T therapy is further demonstration of the breadth of Intrexon’s single and multi-genic expression and control technologies. According to data from ClinicalTrials.gov, more than 1,000 clinical trials utilizing gene therapy are currently underway, with the majority in either Phase I or Phase II. Intrexon’s proprietary switch system is uniquely positioned as the first clinically-evaluated gene switch with in vivo data showing the ability to control gene expression with a broad dynamic range. The RTS platform provides a mechanism for titrating therapeutic effects on a patient-specific and predictable basis, as well as a safety switch to rapidly turn off gene-expression. The ability to administer or withdraw the veledimex pill to sustain continued treatment cycles is a key benefit exclusive to RTS technology.

"We are excited by the prospects of applying our advanced synthetic immuno-oncology toolkit towards targeted immunotherapies like CAR-T," said Jonathan Lewis, M.D., Ph.D., CEO of ZIOPHARM. "We also look forward to expanding RTS applications in novel therapeutic strategies for cancer where the ability to control gene expression is essential."

With respect to the Ad-RTS-IL-12 clinical programs, ZIOPHARM continues to conduct Phase II studies in melanoma and breast cancer using Ad-RTS-IL-12 as a monotherapy. Additionally, the Company is evaluating future trials with IL-12 in potential combination therapies with other immune-targeting agents in various cancers including melanoma and breast. ZIOPHARM also plans to initiate a Phase I trial to evaluate Ad-RTS-IL-12 as a single agent in the treatment of patients with Glioblastoma Multiforme in the second half of 2014.

"The development of potent yet tightly controlled cancer depleting therapies such as CAR-T and other targeted cellular products through the molecular rewiring of immunologic gene programs adds to the foundation of our multifaceted strategy in synthetic immuno-oncology," remarked Gregory Frost, Ph.D., SVP of Intrexon’s Health Sector.

Halozyme Resumes Patient Enrollment And Dosing In PEGPH20 Clinical Program In Pancreatic Cancer

On July 22, 2014 Halozyme Therapeutics reported that it has resumed enrollment and dosing of patients in its ongoing Phase 2 trial (Study 202) evaluating PEGPH20 in patients with pancreatic cancer under the revised clinical protocol agreed to with the FDA in June (Press release Halozyme, JUL 22, 2014, View Source [SID:1234500636]). PEGPH20 is an investigational PEGylated form of Halozyme’s proprietary recombinant human hyaluronidase under development for the systemic treatment of tumors that accumulate hyaluronan.

“Our diligent effort to rapidly re-initiate patient enrollment and dosing of both previously enrolled and new patients in this trial underscores our commitment to evaluating the potential role of PEGPH20 in patients with stage 4 metastatic pancreatic cancer. Approximately 50% of the anticipated clinical sites have received IRB approvals, and we anticipate continued IRB approvals in the coming weeks,” commented Dr. Helen Torley, President and Chief Executive Officer.

Study 202 Trial Design
Study 202 (Halo 109-202) is a Phase 2 multicenter, randomized clinical trial evaluating PEGPH20 as a first-line therapy for treatment of patients with stage 4 metastatic pancreatic cancer. The primary outcome of the trial is to measure improvement in progression-free survival in patients receiving PEGPH20 in combination with gemcitabine and nab-paclitaxel compared to gemcitabine and nab-paclitaxel alone. A second primary endpoint will assess the thromboembolic event rate in the PEGPH20 treatment arm. Secondary endpoints also include objective response rate and overall survival.

Advaxis and MedImmune Partner on Immuno-Oncology Combination Clinical Trial

On July 22, 2014 Advaxis reported that it has entered into a clinical trial collaboration with MedImmune, the global biologics research and development arm of AstraZeneca (Press release Advaxis, JUL 22, 2014, View Source [SID:1234500635]). The Phase I/II immunotherapy study will evaluate the safety and efficacy of MedImmune’s investigational anti-PD-L1 immune checkpoint inhibitor, MEDI4736, in combination with Advaxis’ lead cancer immunotherapy vaccine, ADXS-HPV, as a treatment for patients with advanced, recurrent or refractory human papillomavirus (HPV)-associated cervical cancer and HPV-associated head and neck cancer.

Both MEDI4736 and ADXS-HPV are cancer immunotherapies, a new class of treatments that use the body’s own immune system to help fight cancer. MEDI4736 is designed to counter the tumour’s immune-evading tactics by blocking a signal that helps tumours avoid detection, while ADXS-HPV enhances the ability of immune cells to combat the tumour. Preclinical evidence suggests that the combination of ADXS-HPV with a checkpoint inhibitor, such as MEDI4736, can enhance overall anti-tumour response.

“Our collaboration with Advaxis is further evidence of MedImmune’s commitment to explore novel combination approaches as we progress our immuno-oncology portfolio,” said Dr. Bahija Jallal, Executive Vice President, MedImmune. “We believe there could be an important clinical benefit from the combination of MEDI4736 with Advaxis’s antigen-specific cancer vaccine.”

Under the terms of the agreement, MedImmune and Advaxis will evaluate the combination as a treatment for HPV-associated cervical cancer and squamous cell carcinoma of the head and neck. The Phase I part of the trial is expected to establish a recommended dose regimen of MEDI4736 with ADXS-HPV, and the Phase II portion will assess the safety and efficacy of the combination. The study will be funded and conducted by Advaxis. Results from the study will be used to determine whether further clinical development of this combination is warranted.

Under the terms of the deal, MedImmune has a non-exclusive relationship with respect to HPV-driven tumour types. MedImmune has first right of negotiation for future development of combinations involving MEDI4736 and ADXS-HPV.

“We are excited to be partnering with MedImmune and evaluating MEDI4736 in combination with our immunotherapy,” said Daniel J. O’Connor, Chief Executive Officer, Advaxis. “This is the first time a PD-L1 checkpoint inhibitor will be used with a new class of immunotherapies. As multiple companies vie for a competitive advantage in the future PD-L1 market, the ability of our immunotherapy platform to attack multiple tumour targets makes it an attractive combination therapy.”

Aduro BioTech Receives Breakthrough Therapy Designation from FDA for Innovative Pancreatic Cancer Combination Immunotherapy

On July 21, 2013 Aduro BioTech reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for its pancreatic cancer combination treatment that consists of its CRS-207 and GVAX Pancreas immunotherapies (Press release Aduro BioTech, JUL 21, 2014, View Source [SID:1234500634]). According to the FDA, a breakthrough therapy designation is for a drug that treats a serious or life-threatening condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on a clinically significant endpoint over available therapies.

The designation was based on findings from a Phase 2 trial in metastatic pancreatic cancer patients, which were presented and featured earlier this year at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium conference. The randomized, controlled, multi-center study, which enrolled 93 patients who failed or refused prior therapy, demonstrated a statistically significant survival benefit in patients receiving the combination of GVAX Pancreas and CRS-207 cancer vaccines (Arm A) compared to GVAX Pancreas vaccine alone (Arm B). The median overall survival of the patients receiving the combination was 6.1 months compared to 3.9 months for those receiving GVAX monotherapy (HR=0.59, one-sided p=0.0172).

“We are extremely pleased to receive Breakthrough Therapy Designation and the high degree of FDA collaboration toward advancement of our program that it confers,” said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro. “This designation underscores the potential of our combination immunotherapy approach to make a difference in the lives of patients with pancreatic cancer, which remains a very difficult cancer to treat. We are encouraged by our Phase 2 results and look forward to completing enrollment in our Phase 2b ECLIPSE trial by end of 2015.”