On July 21, 2014, Advaxis, Inc. ("Advaxis") and MedImmune, LLC ("MedImmune"), the global biologics research and development arm of AstraZeneca, entered into a Clinical Trial Collaboration Agreement (the "Agreement") pursuant to which the parties intend to initiate Phase I and Phase II clinical trials in the United States to evaluate the safety and efficacy of MedImmune’s investigational anti-PD-L1 immune checkpoint inhibitor, MEDI4736, in combination with Advaxis’s investigational Lm-LLO cancer immunotherapy, ADXS-HPV, as a combination treatment for patients with advanced, recurrent or refractory human papillomavirus (HPV) associated cervical cancer and HPV-associated head and neck cancer (Filing 8-K , Advaxis, JUL 24, 2014, View Source [SID:1234500643]). A joint steering committee, to be composed of equal numbers of Advaxis and MedImmune representatives, will be responsible for various matters associated with the clinical trials, including approving protocols for the trials, as well as reviewing and monitoring the progress of the trials.

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MedImmune will be responsible for providing MEDI4736 for the clinical trials at no cost. Advaxis will be the sponsor of the clinical trials and be responsible for the submission of all regulatory filings to support the trials, the negotiation and execution of the clinical trial agreements associated with each study site, and the packaging and labelling of the Advaxis and MedImmune product candidates to be used in the clinical trials and the costs associated therewith.

For a period beginning upon the completion of the clinical trials and the receipt by MedImmune of the last final report for the trials and ending one hundred twenty (120) days thereafter (unless extended), MedImmune will be granted first right to negotiate in good faith in an attempt to enter into an agreement with Advaxis with respect to the development, regulatory approval and commercialization of ADXS-HPV and MEDI4736 to be used in combination with each other for the treatment or prevention of cancer. Neither party is obligated to enter into such an agreement. In the event the parties do not enter an agreement and Advaxis obtains regulatory approval for ADXS-HPV in combination with any PD-1 antibody or PD-L1 antibody, Advaxis shall pay MedImmune a royalty obligation and one-time payment.

All intellectual property rights made, conceived or generated through the clinical trials that relate solely to a MedImmune development product shall be owned solely by MedImmune. All intellectual property rights made, conceived or generated through the clinical trials that relate solely to an Advaxis development product shall be owned solely by Advaxis. All intellectual property rights made, conceived or generated through the clinical trials that relate to the combination of one or more MedImmune development product and one or more Advaxis development product shall be jointly owned by MedImmune and Advaxis; provided, however that in the event the parties do not enter into a clinical development and commercialization agreement, Advaxis will not exploit, commercialize or license the joint inventions, except for the performance of its obligations under the Agreement. MedImmune has the sole right to prosecute and enforce all patents and other intellectual property rights covering all joint inventions and all associated costs will be shared by the parties.

The Agreement shall remain in effect until the earlier of (i) permitted termination, (ii) the parties entering into a clinical development and commercialization agreement or expiration of the negotiation period (unless extended), except with respect to rights that survive termination. Either party may terminate the Agreement upon thirty (30) days written notice upon material breach of the other party, unless the breach is cured in such period or reasonable actions to cure the breach are initiated and pursued (if the breach is not capable of being cured during the 30-day notice period). In addition, either party may terminate the Agreement immediately if the party determines in good faith that the trials may unreasonably affect the safety of trial subjects.

On July 22, 2014 OBI Pharma reported hat it has completed patient enrollment in its Phase 2/3 clinical trial evaluating the safety and efficacy of its lead compound, OBI-822, an active immunotherapy for the treatment of metastatic breast cancer (Press release OBI Pharma, JUL 22, 2014, View Source;fn=news_content&no=11 [SID:1234501492]).

"Completing enrollment in the Phase 2/3 clinical trial is a major milestone in the development of OBI-822", said Michael N. Chang, Ph.D., Chairman of the Board of OBI. "Our next target is a global phase 3 trial – now that there is a current IND with the US FDA and an IND application already submitted in China. We look forward to the results of this trial being confirmed once the course of treatment is completed in all enrolled patients early next year."

"The cancer active immunotherapy, OBI-822 guides the immune system to attack breast cancer cells, with minimal side effects, [as observed in the OBI’s Phase 1 and Phase 2/3 clinical trials]" said Amy Huang, General Manager of OBI. "OBI-822’s anti-cancer potential goes beyond breast cancer. All tumor cells expressing Globo series glycan (Globo H, SSEA-3 and SSEA-4) are possible treatment targets for OBI-822. According to the latest research findings reported by Taiwan’s Academia Sinica, the Globo H vaccine can potentially treat up to 16 different types of cancer. In fact, OBI Pharma and Mackay Memorial Hospital jointly initiated a Phase 2 ovarian cancer trial in November 2013 which is currently on-going."

Earlier clinical results
Phase 1 studies of the OBI-822/OBI-821 combination conducted at MSKCC induced both IgM and IgG responses demonstrating that Globo H-specific antibodies can effectively induce complement-mediated cytotoxicity as well as antibody-dependent cytotoxicity. The most commonly observed side effects in the Phase I clinical studies of metastatic breast and prostate cancers were mild local skin reactions and minor flu-like symptoms.

Clinical Study Design
The Phase 2/3 randomized controlled trial (RCT) was initiated in December, 2010 with an enrollment target of 342 subjects. The study enrolled female subjects with metastatic breast cancer who achieved stable disease (SD), partial response (PR), or complete response (CR) after at least 1 regimen of anticancer therapy. Subjects were randomized to receive either active treatment (OPT‐822/OPT‐821) plus cyclophosphamide or control (PBS) plus cyclophosphamide in a 2:1 allocation.

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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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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.

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.

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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

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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.

On July 22, 2014 MonoSol Rx, the developer of PharmFilm drug delivery technology, reported that it has licensed Zuplenz (ondansetron) to Galena Biopharma, a biopharmaceutical company developing and commercializing innovative, targeted oncology treatments that address major unmet medical needs to advance cancer care (Press release, MonoSol Rx, JUL 22, 2014, View Source [SID:1234508915]). Zuplenz is an oral soluble film (OSF) for the prevention of chemotherapy-induced, radiotherapy-induced, and postoperative nausea and vomiting.

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The licensing agreement includes an undisclosed upfront payment from Galena, as well as double digit royalty payments from sales of Zuplenz. Zuplenz is the first oral soluble lingual film product approved by the U.S. Food and Drug Administration (FDA) as a prescription medication, based on MonoSol Rx’s proprietary PharmFilm technology.

Keith J. Kendall, Co-President and Chief Operating Officer of MonoSol Rx, remarked, "Partnering with Galena Biopharma to provide Zuplenz to patients in need further reinforces MonoSol Rx’s position as a leader in the oral soluble film pharmaceutical market. Through this partnership, we hope to empower supportive care providers with a more comfortable, easier-to-use formulation of ondansetron that addresses a significant unmet medical need, particularly among cancer patients. With the increased availability of Zuplenz, clinicians will be able to improve the level of care they provide by utilizing our innovative drug delivery technology to eliminate swallowing issues and discomfort associated with chemotherapy, radiotherapy, and surgery."

"We are pleased to be working with MonoSol Rx to offer Zuplenz to patients in need," said Mark J. Ahn, Ph.D., President and Chief Executive Officer of Galena Biopharma. "MonoSol Rx’s oral film delivery technology represents a substantive advancement in terms of ease of use and compliance for supportive care patients, where difficulty swallowing can be a major issue. Providing patients with an alternative solution for nausea and vomiting has long been a concept that oncologists and the general surgeon and oncology nurse communities have sought, and that we are eager to deploy."

Zuplenz is a unique formulation of ondansetron using MonoSol Rx’s proprietary PharmFilm technology, co-developed with partner APR Applied Pharma Research s.a. of Switzerland. It is based on a novel and proprietary oral drug delivery technology platform and consists of a polymeric OSF containing ondansetron. Once placed in the mouth, it dissolves in a few seconds, allowing the medication to be absorbed and delivered without water.