On March 27, 2017 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new immunotherapies, reported the receipt of positive guidance from an End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) for its lead gene therapy product candidate, Ad-RTS-hIL-12 plus orally administered veledimex (V), to harness and control IL-12 production for the investigational treatment of recurrent glioblastoma (GBM), an aggressive form of brain cancer with few treatment options (Press release, Ziopharm, MAR 27, 2017, View Source [SID1234518275]).

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"We are pleased with our productive interactions with the FDA and the valuable direction we received at the End-of-Phase 2 meeting. Our controlled approach utilizing the RheoSwitch platform represents the next-generation of gene therapy enabling IL-12 to be regulated through a transcriptional switch. We appreciate the FDA’s feedback surrounding our plans to advance Ad-RTS-hIL-12-based therapy to a pivotal registration study for patients with recurrent GBM in 2017 and look forward to establishing the benefits of this novel therapeutic approach," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM.

"The median overall survival remains very promising and continues to be greater than 12 months for these heavily compromised patients," said Francois Lebel, M.D., Chief Medical Officer of ZIOPHARM. He added, "After positive meetings with both FDA and European regulators, the Company is working towards finalization of the optimal pathway for our pivotal trial for Ad-RTS-hIL-12 + veledimex."

In collaboration with its investigators and regulators, the Company is currently assessing its protocol design options for the pivotal trial, including the potential for a single-arm study comparing Ad-RTS-hIL-12 + V to historical controls in a subpopulation of patients with recurrent GBM. Details of the pivotal Phase 3 trial will be made available following evaluation and completion of discussions with clinical advisors as well as regulators.

About Glioblastoma:
GBM represents approximately 15% of all primary brain tumors and remains a high unmet clinical need that affects roughly 74,000 people worldwide annually. GBM is an aggressive form of brain cancer with recurrence rates near 90%, and prognosis for patients is poor with treatment often combining multiple approaches including surgery, radiation, and chemotherapy. Median overall survival (OS) is only 6 to 7 months in patients who have experienced multiple recurrences, and the prognosis is even poorer for patients who have failed temozolomide and bevacizumab, or equivalent salvage chemotherapy with a median OS of approximately 3 to 5 months.

On March 27, 2017 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported that AGI-134, an immunotherapy for the treatment of multiple cancers, obtained through its recently announced acquisition of Agalimmune Ltd., will be featured at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Washington, DC to be held on April 1-5, 2017 (Filing, 6-K, BioLineRx, MAR 27, 2017, View Source [SID1234518274]).

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An abstract titled "The novel α-Gal-based immunotherapy AGI-134 invokes CD8+ T cell-mediated immunity by driving tumor cell destruction, phagocytosis and tumor-associated antigen cross-presentation via multiple antibody-mediated effector functions" was accepted for a poster presentation at the T-Cell Immunity to Cancer: New Progress session on April 2nd, 2017.

About AGI-134
AGI-134 is a synthetic alpha-Gal immunotherapy in development for solid tumors. AGI-134 harnesses the body’s pre-existing, highly abundant anti-alpha-Gal antibodies to induce a systemic, specific anti-tumor response to the patient’s own tumor neo-antigens. This response not only kills the tumor cells at the site of injection, but also brings about a durable, follow-on, anti-metastatic immune response. AGI-134 has completed numerous pre-clinical studies, demonstrating robust protection against the development of secondary tumors in a model of melanoma with a single dose only. Synergy has also been demonstrated in additional pre-clinical studies when combined with a PD-1 immune checkpoint inhibitor, offering the potential to broaden the utility of such immunotherapies, and improve the rate and duration of responses in multiple cancer types. AGI-134 is in near-clinical development and is expected to commence a first-in-man study in patients with solid tumors in the first half of 2018.

On March 27, 2017 Alkermes plc (NASDAQ: ALKS) reported that preclinical data on the company’s immuno-oncology drug candidate, ALKS 4230, an engineered fusion protein designed for selective activation of the interleukin-2 (IL-2) receptor, will be presented at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting to be held from April 1-5, 2017 in Washington D.C (Press release, Alkermes, MAR 27, 2017, View Source [SID1234518272]). ALKS 4230 is designed to preferentially bind and signal through the intermediate affinity IL-2 receptor complex, thereby selectively activating and increasing the number of tumor-killing immune cells while avoiding the expansion of immunosuppressive cells that interfere with anti-tumor response.

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Details of the preclinical data poster presentations are as follows:

April 2, 2017, 1:00 – 5:00 p.m. ET – Abstract 591 (Poster): Efficacy of ALKS 4230, a novel immunotherapeutic agent, in murine syngeneic tumor models alone and in combination with immune checkpoint inhibitors.

In a murine lung tumor metastasis model, treatment with ALKS 4230 as a single agent resulted in greater anti-tumor efficacy relative to recombinant human IL-2 (rhIL-2) and was associated with selective expansion of memory CD8+ T cells and NK cells (tumor-killing cells), without expansion of regulatory T (Treg) cells. Specifically, ALKS 4230 treatment resulted in dose-dependent reduction of lung tumor colonization, with 100% inhibition at the highest dose tested. In contrast, the maximal level of inhibition achieved by rhIL-2 was 60-70% at multiple dose levels, demonstrating that increasing doses of rhIL-2 did not result in greater inhibition.
Combination regimens with ALKS 4230 and either anti-CTLA4 or anti-PD-1 checkpoint inhibitor therapies in murine tumor models resulted in durable anti-tumor immunotherapeutic effects and increased survival rates.
April 3, 2017, 1:00 – 5:00 p.m. ET – Abstract 2663 (Poster): Characterization of the pharmacodynamic immune response to a novel immunotherapeutic agent, ALKS 4230, in mice and non-human primates.

Data demonstrated that ALKS 4230 drove dose-dependent expansion of memory CD8+ T cells and NK cells in mice, and total CD8+ T cells and NK cells in non-human primates, without activation and minimal expansion of CD4+ Tregs in mice and non-human primates. These pharmacodynamics effects persisted for several days after ALKS 4230 was cleared from circulation.
In addition to these preclinical data presentations, a poster outlining the dose selection rationale for the ongoing phase 1 study of ALKS 4230 will be presented. The poster presentation details are as follows:

April 4, 2017, 1:00 – 5:00 p.m. ET – Abstract 4088 (Poster): First-in-human dose selection for ALKS 4230, an investigational immunotherapeutic agent.

The selection of the 0.1 µg/kg starting dose for the first-in-human study of ALKS 4230 was determined, based on the Minimal Anticipated Biological Effect Level (MABEL) approach.
For more information, including a complete list of abstracts, please visit the AACR (Free AACR Whitepaper) website at View Source

About ALKS 4230
ALKS 4230 is an engineered fusion protein designed to preferentially bind and signal through the intermediate affinity interleukin-2 (IL-2) receptor complex, thereby selectively activating and increasing the number of immunostimulatory tumor-killing immune cells while avoiding the expansion of immunosuppressive cells that interfere with anti-tumor response. The selectivity of ALKS 4230 is designed to leverage the proven anti-tumor effects while overcoming limitations of existing IL-2 therapy, which activates both immunosuppressive and tumor-killing immune cells.

On March 27, 2017 Advaxis, Inc. (NASDAQ:ADXS), a biotechnology company developing cancer immunotherapies, reported that it has published online a poster previously presented at the National Cancer Research Institute (NCRI) Cancer Conference in Liverpool that showed axalimogene filolisbac achieved durable response in a patient with persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC) (Press release, Advaxis, MAR 27, 2017, View Source [SID1234518271]).

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Nine patients who had documented disease progression after they had received curative treatments of chemotherapy and/or radiation with or without bevacizumab were enrolled in this phase 1, open-label, dose-determining study. Axalimogene filolisbac was well-tolerated across two dose levels. The study also established a recommended phase 2 dose of 1×1010 CFU and demonstrated antitumor activity at that dose. Axalimogene filolisbac was safely administered at 5 and 10 times the dose levels previously studied, without any significant toxicity. One patient experienced an ongoing and durable partial response. This patient was recently featured in the Augusta Chronicle, as she is being treated at the Georgia Cancer Center at Augusta University. Read the full Augusta Chronicle article here.

"The best overall tumor response in eight of the nine enrolled patients is encouraging in evaluating the potential of axalimogene filolisbac," said Sharad Ghamande, principal investigator and Professor and Director of Gynecologic Oncology at the Georgia Cancer Center at Augusta University. "We were pleased to see a sustained and durable partial response in one patient, which is very rare for this kind of tumor that is unresponsive to chemotherapy, and survival in these patients is often less than 10 months. In addition, we could safely administer the drug at 5 and 10 times the dose levels previously studied, without any significant toxicity."

There was only one instance of dose-limiting toxicity, with that patient experiencing a grade 3 treatment related adverse event (TRAE) of hypotension at a dose of 5×109 CFU. Across all doses, eight of nine patients experienced a grade 1-2 TRAE, including chills, nausea and hypotension.

The poster on the phase 1 data, "High-dose treatment with ADXS11-001, a Listeria monocytogenes-listeriolysin O (Lm-LLO) immunotherapy, in women with cervical cancer: a phase I, dose-escalation study" (no. 58) is available at www.advaxis.com. The company is preparing to initiate a phase 3 trial in PRmCC later this year.

About Axalimogene Filolisbac

Axalimogene filolisbac is a targeted Listeria monocytogenes (Lm)-based immunotherapy that attacks HPV-associated cancers by altering a live strain of Lm bacteria to generate cancer-fighting T cells against cancer antigens while neutralizing the tumor’s natural protections that guard the tumor microenvironment from immunologic attack. In a phase 2 trial evaluating axalimogene filolisbac for the treatment of persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC), the drug candidate showed a 12-month overall survival rate of 38 percent observed in 50 patients in the trial. This is a 52 percent improvement over the 12-month overall survival rate that was expected in the trial’s patient population based on prognostic factors.

Axalimogene filolisbac has received Fast Track designation for adjuvant therapy for high-risk locally advanced cervical cancer (HRLACC) and a Special Protocol Assessment for the Phase 3 AIM2CERV trial in HRLACC patients. The immunotherapy has also received orphan drug designation in three clinical indications.