On June 19, 2017 VBL Therapeutics (Nasdaq:VBLT) reported an update on the long term status and survival of patients from three completed Phase 2 trials, which investigated the company’s lead candidate, VB-111, respectively in recurrent glioblastoma (rGBM), recurrent platinum-resistant ovarian cancer and radioiodine refractory differentiated thyroid cancer. All three trials had previously shown signals of an overall survival benefit for VB-111 (Press release, VBL Therapeutics, JUN 19, 2017, View Source [SID1234519623]). The company has continued to follow the survival of patients from these trials.

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"We are pleased to report that in all three indications over 50% of patients have achieved long term survival following treatment with VB-111 as detailed below. Each of these Phase 2 trials enrolled difficult to treat patients for whom prior treatments had failed," said Prof. Dror Harats, CEO of VBL Therapeutics. "In addition, we continue to follow patients from our Phase 1 studies, who responded to VB-111 and have now survived for more than 5 years, although they were end-stage patients whose tumors had previously progressed in spite of several lines of therapy. We are now conducting pivotal trials with the goal of investigating these survival benefits and providing data to support regulatory approval and commercialization of VB-111. Our GLOBE pivotal trial in rGBM has completed enrollment and we expect top line data from the full dataset becoming available in early 2018. We expect patient enrollment in our planned Phase 3 OVAL study in ovarian cancer to begin in the second half of 2017. In addition, we plan to launch a combination study of VB-111 with a checkpoint inhibitor in lung cancer by year-end 2017."

Summary of Data

rGBM: In the Phase 2 study in rGBM patients, 12 months survival was 54% in patients who were treated with VB-111 through progression, including an rGBM patient who remains alive with complete response after 38 months, compared to 23% of patients who had limited exposure of a therapeutic dose of VB-111. According to a meta-analysis, the 12 months survival on Avastin (bevacizumab) is only 24%.

Ovarian Cancer: In the Phase 2 study in recurrent platinum-resistant and refractory ovarian cancer, 53% of patients treated with a therapeutic dose of VB-111 in combination with paclitaxel were alive at 15 months, some of whom remain alive and are on active follow up. No patients in the sub-therapeutic dose were alive at the 15-month timepoint.

Thyroid Cancer: In the Phase 2 study in radioiodine refractory differentiated thyroid cancer, 53% of those who received multiple therapeutic doses of VB-111 were alive at 24 months, compared to 33% of those who received a single, sub-therapeutic dose of VB-111. 35% of patients on the therapeutic dose cohort remain alive at 39 to 46 months.
VBL’s presentation at BIO will take place tomorrow at 11.45am PDT in the San Diego Convention Center. A webcast of the live presentation can be viewed here: http://www.veracast.com/webcasts/bio/internationalconvention2017/17205139583.cfm.

About Ofranergene Obadenovec (VB-111)
Ofranergene obadenovec is a unique biologic agent that uses a dual mechanism to target solid tumors. Based on a non-integrating, non-replicating, Adeno 5 vector, ofranergene obadenovec utilizes VBL’s proprietary Vascular Targeting System (VTS) to target the tumor vasculature for cancer therapy. Unlike anti-VEGF or TKIs, ofranergene obadenovec does not aim to block a specific pro-angiogenic pathway; instead, it uses an angiogenesis-specific sensor (VBL’s PPE-1-3x proprietary promoter) to specifically induce cell death in angiogenic endothelial cells in the tumor milieu. This mechanism retains activity regardless of baseline tumor mutations or the identity of the pro-angiogenic factors secreted by the tumor and shows activity even after failure of prior treatment with other anti-angiogenics. Moreover, ofranergene obadenovec induces specific anti-tumor immune response, which is accompanied by recruitment of CD8 T-cells and apoptosis of tumor cells. Clinical data indicate that continuous exposure to VB-111 can lead to attenuation of tumor growth and to tumor shrinkage, which can translate to survival benefit.

Ofranergene obadenovec completed a Phase 2 study in rGBM, which showed a statistically significant improvement in overall survival in patients treated with ofranergene obadenovec through progression, compared to either patients treated with ofranergene obadenovec followed by bevacizumab alone, or to historical bevacizumab data. In a Phase 2 trial for recurrent platinum-resistant ovarian cancer, ofranergene obadenovec demonstrated a statistically significant increase in overall survival and 60% durable response rate (as measured by reduction in CA-125), approximately twice the historical response with bevacizumab plus chemotherapy in ovarian cancer. In a Phase 2 study in recurrent, iodine-resistant differentiated thyroid cancer, ofranergene obadenovec met the primary endpoint demonstrating disease stabilization with a positive safety profile, along with a dose-response and evidence of an overall survival benefit. Ofranergene obadenovec has received Fast Track Designation for recurrent glioblastoma in the U.S. and orphan drug status for glioblastoma in both the U.S. and EU.

On June 19, 2017 MetaStat, Inc. (OTCQB: MTST), a personalized medicine company developing therapeutic and diagnostic treatment solutions for cancer patients, reported it has completed the second milestone under its pilot research project with Celgene Corporation (Press release, MetaStat, JUN 19, 2017, View Source [SID1234519622]). To date, MetaStat has received aggregate milestone payments of approximately $730,000 from Celgene pursuant to the terms of the pilot materials transfer agreement.

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"We are very pleased to have successfully completed the second milestone and are now working on the next phase of the Celgene pilot research project," stated Douglas A. Hamilton, MetaStat’s President, CEO and Director.

On June 19, 2017) Clinical-stage oncology company Prescient Therapeutics Ltd (ASX: PTX; Prescient) reported that a pre-clinical study published in the scientific journal Nature this week indicates that Prescient’s geranylgeranyl transferase inhibitor GGTI-2418, known as PTX-100, plays a key role in mitigating a new cancer pathway discovered by Professor Michele Pagano at New York University’s Langone Medical Center, in New York (Press release, Prescient Therapeutics, JUN 19, 2017, View Source [SID1234519615]). Nature is regarded as one of the world’s most cited and prestigious scientific publications.

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In the study, Professor Pagano’s group in collaboration with Prescient’s Chief Scientific Officer Professor Said Sebti, demonstrated new details about the tumor suppressor gene, PTEN, which is defective in 30-60% of certain breast, brain and uterine cancers.

"When defective, PTEN cannot control a protein known as FBXL2, which is thought to be responsible for cancer growth in many patients." said Professor Pagano.

Professor Pagano’s study also showed in mouse models that when administered with Prescient’s drug candidate PTX-100, plus photodynamic therapy, FBXL2 is "switched-off" allowing abnormal cells to self-destruct. Therefore, patients whose tumors harbor defective PTEN may also be more likely to respond to a combination of PTEN and photodynamic therapy.

Professor Said Sebti said "These findings have important translational implications for Prescient as patients whose tumors harbor defective PTEN may be more likely to respond to a combination of PTX-100 and photodynamic therapy." "Furthermore, given that PTEN is known to also suppress the Akt tumor survival pathway, patients with PTEN defective tumors could respond to a combination of PTX-100 and an Akt inhibitor like PTX-200."

Prescient’s CEO and Managing Director, Steven Yatomi-Clarke said "This discovery of a new cancer-causing pathway targeted by PTX-100 is an exciting development for Prescient. Our precision medicine strategy uses targeted therapies to address specific cancer mutations. Therefore, this discovery opens up a new frontier of clinical possibilities for PTX-100."

PTEN has been the subject of cancer research for many years, but this new study is very exciting in showing a novel way in which defective PTEN adds to cancer risk, and more importantly, demonstrates that it can be inhibited with PTX-100."

PTX-100 was developed by Professor Sebti, Chair of the Department of Drug Discovery at H. Lee Moffitt Cancer Center, and Chief Scientific Officer at Prescient Therapeutics, and NYU President Andrew Hamilton while he was at Yale University. PTX-100 has already been tested as a single agent in patients with advanced solid tumors in a Phase 1 trial and will be the focus of studies in rare hematological malignancies.

The Nature publication can be previewed at www.nature.com.

FBLX2
FBXL2 is a cancer-causing protein in tumors where PTEN is defective prompting the researchers to look for ways to block FBXL2 in these cancers. To this end, they took advantage of the fact that FBXL2 requires a piece of lipid called geranylgeranyl to localize in the ER membrane near IP3R3, and disabled FBXL2 with GGTI-2418, a drug that blocks the attachment of geranylgeranyl to proteins.

GGTI-2418 was developed by Said Sebti, Chair of the Department of Drug Discovery at Moffitt Cancer Center, and Chief Scientific Officer at Prescient Therapeutics, and NYU President Andrew Hamilton while he was at Yale University. Currently being clinically developed by Prescient Therapeutics, GGTI-2418 (PTX-100) has already been tested as a single agent in patients in a Phase 1 trial, and will enter clinical trials in combination with other drugs.

Photodynamic Therapy
Photodynamic therapy (PDT) is a treatment that uses special drugs, called photosensitizing agents, along with light to kill cancer cells. The drugs only work after they have been activated or "turned on" by certain kinds of light.

Experiments showed that PDT significantly reduced tumor weight and cancer growth rate in mice where PTX-100 made sure that IP3R3 was there to trigger cell death. PDT had little effect on cancer cells with depleted supplies of PTEN or IP3R3. Pagano says his team in collaboration with Sebti’ s team is set to study next the effect of combining GGTI-2418 with PDT in patients with low PTEN, as well as the combination of GGTI-2418, PDT and P13K/AKT inhibitors.

Also of note, the research team found that blocking the ability of FBXL2 to target IP3R3 with GGTI-2418 made tumors in mice more vulnerable to photodynamic therapy or PDT. PDT, which is based on the ability of photosensitizer drugs to cause cytotoxicity after irradiation with visible light, has been applied in the clinic with encouraging results to treat non-small cell lung cancer, dermatological cancers, and premalignant lesions of the upper digestive tract, and is currently in clinical trials for treatment of a large variety of other malignancies, including prostate, brain, and breast cancers.

On June 19, 2017 Janssen-Cilag International NV ("Janssen") reported three-year follow-up data from the Phase 3 RAY study in patients with relapsed or refractory mantle cell lymphoma (MCL) (Press release, , JUN 19, 2017, View Source [SID1234519614]). These results demonstrated that the subset of patients treated with IMBRUVICA▼ (ibrutinib) at first relapse after one prior line of therapy achieved a median progression-free survival (PFS) of more than two years (25.4 months).[1] This was four-fold longer than treatment with temsirolimus (6.2 months [HR, 0.40; 95% CI, 0.25–0.64]).1 Data showed median overall survival (OS) with ibrutinib after one prior line of therapy of 3.5 years (42.1 months vs 27.0 months with temsirolimus [HR, 0.74; 95% CI, 0.43–1.30]).1

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Results from the Phase 3, international, randomised, open-label RAY study were presented on June 17, 2017 during an oral session at the 14th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland. Ibrutinib, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, is jointly developed and commercialised by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.

In the overall study patient population, which included patients who had received more than one prior line of therapy (median two prior therapies), median PFS was also significantly increased in patients treated with ibrutinib vs temsirolimus (15.6 months vs 6.2 months [HR, 0.45; 95% CI, 0.35-0.60; p< 0.0001]).1 In addition, ibrutinib tended to increase OS, with a median OS with ibrutinib of 30.3 vs 23.5 months with temsirolimus (HR, 0.74; 95% CI, 0.54-1.02; p=0.0621).1

"The data from this long-term follow-up further highlight the potential of ibrutinib for patients with mantle cell lymphoma, especially if used at first relapse," said Simon Rule, M.D., Professor of Clinical Haematology at Plymouth University, Peninsula Schools of Medicine & Dentistry.*

Complete response (CR) was achieved in nearly a quarter (23.0%) of all patients who received ibrutinib.1 The CR rate in patients who had received one line of therapy prior to ibrutinib (33.3%) was more than double that achieved in patients who had received more than one line of therapy prior to ibrutinib (15.9%).1 The duration of response in all patients who achieved a CR with ibrutinib was almost three years (35.6 months).1

The safety profile was consistent with primary analysis and known safety data on ibrutinib. No new safety signals for ibrutinib were observed in the trial. Overall frequencies of adverse events (AEs) were similar or lower in the ibrutinib arm, even with longer treatment exposure.1 Nearly twice as many patients discontinued temsirolimus due to AEs vs ibrutinib (31.7% vs 17.3%).1 In addition, exposure adjusted rates of atrial fibrillation were similar between the two groups (0.392 vs 0.331 with ibrutinib and temsirolimus, respectively) and exposure adjusted bleeding rates were lower with ibrutinib vs temsirolimus (2.880 vs 6.683).1 In the ibrutinib arm, Grade ≥3 AEs included thrombocytopenia, anaemia and neutropenia in 9.4%, 8.6% and 12.9% of patients respectively.1

MCL is an incurable, aggressive B-cell malignancy with a median OS of three to four years.[2] Most patients relapse after first-line therapy and have a poor prognosis.2,[3] Despite recent advances and with the exception of a small patient population eligible for allogeneic stem cell transplant, there is no globally recognised standard of care in relapsed MCL.[4],[5],[6]

"We are encouraged by these long-term data which demonstrated the efficacy and safety of ibrutinib after one prior line of therapy in patients with previously treated mantle cell lymphoma. These data add to the growing body of evidence which shows that using ibrutinib earlier in the treatment pathway may have significant benefits for patients," said Dr Catherine Taylor, Haematology Therapeutic Area Lead, Janssen Europe, Middle East and Africa. "We are committed to addressing critical unmet need in B-cell malignancies such as mantle cell lymphoma which has traditionally had poor outcomes and are aiming to make this a more manageable disease for patients in the future."

About the RAY study

The Phase 3, randomised, open-label RAY study compared ibrutinib with temsirolimus in patients with relapsed or refractory mantle cell lymphoma and ≥1 prior rituximab-containing therapy.7 Two hundred and eighty patients were randomised 1:1 to oral ibrutinib (560 mg once-daily; n = 139) or intravenous temsirolimus (175 mg: days 1, 8, 15 of cycle 1; 75 mg: days 1, 8, 15 of subsequent cycles; n = 141) until disease progression/unacceptable toxicity. Long-term efficacy was investigator-assessed.[7]

About ibrutinib

Ibrutinib is a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, which works by forming a strong covalent bond with BTK to block the transmission of cell survival signals within the malignant B-cells.[8] By blocking this BTK protein, ibrutinib helps kill and reduce the number of cancer cells, thereby delaying progression of the cancer.[9]

Ibrutinib is currently approved in Europe for the following uses:[10]

As a single agent for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL), adult patients with relapsed or refractory mantle cell lymphoma (MCL), or adult patients with Waldenström’s Macroglobulinaemia (WM) who have received at least one prior therapy or in first-line treatment for patients unsuitable for chemo-immunotherapy.
As a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received at least one prior therapy.
Please see the ibrutinib Summary of Product Characteristics for further information.10

About MCL

Mantle Cell Lymphoma (MCL) is considered a rare disease, characterised by high unmet need and small patient populations impacting fewer than one in 200,000 people in Europe and with a median age at diagnosis of 65.[11],[12] MCL predominantly affects more men than women and accounts for five to 10 percent of all non-Hodgkin’s lymphomas.6,[13] MCL typically involves the lymph nodes, but can spread to other tissues, such as the bone marrow, liver, spleen and gastrointestinal tract.12

On June 19, 2017 Genexine Inc., a clinical stage biotechnology company developing innovative biologics focused on immuno-oncology and orphan diseases, reported that the Ministry of Food and Drug Safety (MFDS) in Korea has granted approval to initiate a Phase Ib/II trial of GX-188E, an HPV therapeutic DNA vaccine, in combination with KEYTRUDA (pembrolizumab), an anti-PD-1 therapy marketed by Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the United States and Canada), for the treatment of patients with HPV-induced advanced non-resectable cervical cancer.

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The goal of this clinical trial is to evaluate the safety and efficacy of this combination, which aims to promote an anti-tumor immune response in multiple ways. In previous clinical trials, GX-188E has demonstrated the ability to induce tumor-specific immune response and curative activity against high-grade cervical intraepithelial neoplasia. KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Genexine and Merck & Co., Inc., Kenilworth, NJ, USA believe the combination of GX-188E with KEYTRUDA may have synergistic qualities that could improve the clinical response rates already observed with KEYTRUDA monotherapy in cervical cancer patients; a hypothesis further supported by data presented at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper).

The Phase Ib/II study will be initiated in Korea with plans to enroll up to 46 patients. Under the terms of the agreement Genexine will undertake and fund the study and Merck & Co., Inc., Kenilworth, NJ, USA will provide KEYTRUDA. The agreement includes the potential for further expansion to a Phase III study.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.


▶ About GX-188E:

GX-188E, currently being developed in Phase 2 clinical trials, is an HPV therapeutic DNA vaccine for cervical intraepithelial neoplasia (CIN) and HPV-induced cancers caused by persistent infection by high-risk HPV types, 16/18. A Phase I study demonstrated that GX-188E, a rationally designed HPV DNA vaccine to target HPV antigens preferentially on dendritic cells, elicited significant E6/E7 specific IFN-γ-producing T-cell responses in all CIN3 patients when administered intramuscularly by electroporation. Seven out of nine patients had complete regression of their CIN3 lesions, viral clearance, and exhibited enhanced antigen-specific polyfunctional CD8 T-cell responses within 36 weeks of follow-up. These results were published in October 2014 in Nature Communications.