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AVEO Oncology Announces Pivotal Phase 3 TIVO-3 Study of Tivozanib in Renal Cell Carcinoma Reaches Enrollment Target

On June 20, 2017 AVEO Oncology (NASDAQ: AVEO) reported that the Company’s pivotal TIVO-3 trial, a randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in subjects with refractory advanced renal cell carcinoma (RCC) has reached its enrollment target of 322 patients, more than two months ahead of the Company’s initial guidance (Press release, AVEO, JUN 20, 2017, View Source [SID1234519616]). Tivozanib, the Company’s lead program, is a potent, selective, long half-life inhibitor of all three vascular endothelial growth factor (VEGF) receptors. A pre-planned futility analysis of the TIVO-3 trial is expected around midyear 2017, with topline data expected in the first quarter of 2018. The trial, together with the previously completed TIVO-1 trial of tivozanib in the first line treatment of RCC, is designed to support regulatory approval of tivozanib in the U.S. as a first and third line treatment for RCC.

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"Reaching our enrollment goal for the TIVO-3 trial is a meaningful milestone for AVEO, which we believe reflects the support of many individuals within the Company, our medical partners in the oncology community and the patients we serve," said Michael Bailey, president and chief executive officer of AVEO. "As previously noted, based on a recommendation by the Safety Monitoring Committee, the study will continue enrolling additional patients for the next few weeks to replace early dropouts. We look forward to several key upcoming potential inflection points in the tivozanib program, including a European regulatory decision and ongoing enrollment in the TiNivo study, culminating in the readout of the TIVO-3 trial, expected in the first quarter of 2018."

The TIVO-3 trial is enrolling patients with recurrent RCC who have failed at least two prior regimens, including VEGFR-TKI therapy (other than sorafenib). Eligible patients may also have received checkpoint inhibitor therapy in earlier lines of treatment. Patients will be randomized 1:1 to receive either tivozanib or sorafenib, with no crossover between arms. The primary endpoint of the study is progression free survival. Secondary endpoints include overall survival, overall response rate, and safety and tolerability.

About Tivozanib

Tivozanib is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI). It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications. Tivozanib has been investigated in several tumors types, including renal cell, colorectal and breast cancers.

OncoSynergy and Infuseon Therapeutics Partner to Combat Glioblastoma

On June 20, 2017 Infuseon Therapeutics and OncoSynergy have entered into a strategic alliance to test an investigational glioblastoma therapeutic, OS2966, in combination with a novel delivery device, the Cleveland Multiport CatheterTM (Press release, OncoSynergy, JUN 20, 2017, View Source [SID1234519626]). Glioblastoma is the most common and malignant primary brain tumor. Despite a median survival of merely 12 months, there have been only four FDA approved therapies and no improvement in overall survival in nearly three decades. This unmet need is driven in part by the inability of most chemotherapies and particularly biologics to penetrate the blood-brain-barrier.

Infuseon Therapeutics’ unique therapy delivery device, the Cleveland Multiport CatheterTM (CMC), a multiport convection-enhanced delivery catheter, was designed by neurosurgeon Michael Vogelbaum, MD, PhD, from Cleveland Clinic’s Brain Tumor and NeuroOncology Center, to more effectively deliver life-saving drugs to patients at the site of their disease. The reliability of the CMC as a loco-regional delivery device has been validated in pilot clinical trials involving delivery of a chemotherapy along with an MRI visible tracer in patients with recurrent high grade gliomas.

OncoSynergy is a UCSF spinout headquartered at Johnson & Johnson Innovation, JLABS (JLABS) in South San Francisco. JLABS @ SSF is a 30,000 square-foot life science innovation incubator, located in South San Francisco. The labs provide a flexible environment for start-up companies pursuing new technologies and research platforms to advance medical care. Through a “no strings attached” model, Johnson & Johnson Innovation does not take an equity stake in the companies occupying JLABS and the companies are free to develop products – either on their own, or by initiating a separate external partnership with Johnson & Johnson Innovation or any other company. OncoSynergy’s first-in-class humanized and de-immunized monoclonal pan-CD29 antibody, OS2966, has demonstrated dramatic efficacy in multiple models of highly aggressive and metastatic solid cancers. Based on these data, the FDA has granted two Orphan Drug Designations for OS2966 including in the treatment of glioblastoma.

“We are pleased to join forces with Infuseon Therapeutics to tackle the complex biology of glioblastoma,” commented Anne-Marie Carbonell, MD, Vice President of Clinical Development at OncoSynergy. “The innovative combination of OS2966 and the CMC device seeks to address a huge unmet need and potentially change the way we treat patients suffering from malignant brain tumors.”

The collaboration aims to establish proof of concept that OS2966 can be successfully delivered directly to the brain with the CMC device as an impetus for a Phase I trial for the treatment of glioblastoma.

“Infuseon’s Cleveland Multiport Catheter was designed specifically to deliver therapeutics directly to the site of disease,” said Michael Vogelbaum, MD, PhD, co-Founder and Chief Medical Officer of Infuseon Therapeutics. “We are excited to pursue a potentially novel therapeutic approach to this difficult disease.”

About Infuseon Therapeutics – Infuseon Therapeutics was founded in 2012 by Cleveland Clinic for the purpose of developing its patented unique therapeutic delivery device, the Cleveland Multiport CatheterTM (CMC). Infuseon has collaborated with Parker-Hannifin Corporation, a global leader in motion and control technologies to enhance the medical design, development, and manufacturing expertise of the company. As an inventor of the multiport catheter, Dr. Vogelbaum is entitled to a portion of any commercialization revenues Cleveland Clinic receives from Infuseon. To learn more visit www.infuseontherapeutics.com

Media contact: Neema Mayhugh, PhD [email protected] (216) 312-9165

About OncoSynergy – Oncosynergy is a UCSF spinout with primary operations in JLABS @ SSF, California. The company was founded in 2011 to address the complexity of cancer for more durable patient outcomes through the development of a new class of oncology therapeutics, called Resistance Mechanism Inhibitors (RMIs). RMIs uniquely inhibit multiple Cancer Hallmarks simultaneously. The lead RMI drug candidate, OS2966, is on track for Phase I clinical trials in 2018. To learn more visit www.oncosynergy.com

Media Contact: Shawn Carbonell, MD, PhD, [email protected] +1 (415) 666-2391

20-F – Annual and transition report of foreign private issuers [Sections 13 or 15(d)]

On December 18, 2017 Pharmaceuticals, Inc. (NASDAQ: REGN) and ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company, reported a clinical collaboration to advance ISA101, an immunotherapy targeting human papillomavirus type 16 (HPV16)-induced cancer, in combination with cemiplimab (REGN2810), a PD-1 (programmed cell death protein 1) antibody (Press release, Regeneron, DEC 18, 2017, View Source [SID1234522678]). Regeneron and ISA will jointly fund and conduct clinical trials of the combination treatment in cervical cancer and head-and-neck cancer.

Expression of HPV oncoproteins contributes to the development of cervical and head-and-neck cancers, and approximately 55 percent of cervical cancers and over 60 percent of head-and-neck cancers are HPV16 positive.1

Regeneron and ISA will share clinical trial costs and exchange product supply. In addition, Regeneron will provide an upfront payment and an equity investment in exchange for an option to an exclusive, global license for ISA101. If Regeneron exercises its option to commercialize ISA101, there is potential for various milestone payments and tiered royalty payments to ISA contingent on regulatory approvals, sales and additional indications. Further financial details were not disclosed.

"Regeneron continues to expand and advance our immuno-oncology program by studying multiple combination therapies in order to fully explore the scientific possibilities in this relatively new field," said Israel Lowy, M.D., Ph.D., Vice President Clinical Sciences, Head of Translational Science and Oncology at Regeneron. "Early clinical results with ISA101 in HPV16-positive indications have been promising, and we’re eager to investigate the impact of adding cemiplimab with the goal of further enabling the body’s immune system to attack the cancer."

"This collaboration with Regeneron is a strong validation of our proprietary SLP (Synthetic Long Peptides) platform and know-how," added Ronald Loggers, Chief Executive Officer of ISA Pharmaceuticals. "We are proud to work with Regeneron, a science- and technology-driven biotechnology company, and aim to further strengthen our pioneering role in the development of innovative treatment options for oncology indications with a high unmet medical need."

Cemiplimab is being jointly developed by Regeneron and Sanofi under a global collaboration agreement for immuno-oncology therapeutics, and was developed using Regeneron’s proprietary VelocImmune technology that yields optimized fully-human antibodies. Cemiplimab is currently being studied as a monotherapy in multiple cancers – including cutaneous squamous cell carcinoma (CSCC), basal cell carcinoma (BCC), non-small cell lung cancer (NSCLC) and cervical cancer – and in various therapeutic combinations. Cemiplimab is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.

ISA101 is an SLP immunotherapy based on the delivery of oncogenic antigens in the form of synthetic long peptides and targets HPV-induced diseases. This innovative concept was discovered by emeritus professor Cornelis J. M. Melief and his team at the Leiden University Medical Center and has been the subject of multiple studies and peer-reviewed publications. It is ISA´s most advanced clinical-stage immunotherapeutic and is in clinical development in advanced and recurrent cervical cancer and incurable HPV16-positive solid tumors (such as squamous cell carcinoma of the head and neck). The first proof-of-concept data on ISA101 as a monotherapy treatment were published in the New England Journal of Medicine2 and initial results from the recently completed ISA101 combination trials in advanced cervical cancer and head-and-neck cancer were presented at ASCO (Free ASCO Whitepaper)-SITC and ESMO (Free ESMO Whitepaper), respectively, in 2017.

WILEX AG: Subsidiary Heidelberg Pharma Signs Exclusive Multi-target Research Agreement with Takeda for the Development of Antibody Targeted Amanitin Conjugates

On June 19, 2017 WILEX AG (ISIN DE000A11QVV0 / WL6 / FSE) reported its subsidiary, Heidelberg Pharma GmbH, Ladenburg, Germany, has signed an exclusive multi-target research agreement with Takeda Pharmaceutical Company Limited (TSE: 4502) for the joint development of antibody drug conjugates (ADCs) that use Amanitin as the payload (Press release, Wilex, JUN 19, 2017, View Source [SID1234526974]).

Under the terms of the exclusive multi-target research agreement, Heidelberg Pharma will produce Antibody Targeted Amanitin Conjugates (ATACs) using antibodies from Takeda’s proprietary portfolio for up to three undisclosed targets. Takeda has an option for an exclusive license for global development and commercialization rights to each of the product candidates resulting from the research collaboration. If it exercises the option, Takeda would be responsible for further preclinical and clinical development, as well as potential commercialization, of any product candidate it licenses.

Professor Andreas Pahl, Chief Scientific Officer of WILEX AG and Heidelberg Pharma GmbH, commented: "We are delighted about the collaboration with Takeda, which has broad expertise in oncology and is a leading ADC company. We believe this partnership provides further validation of our technology. Working with Takeda will allow us to jointly test and expand the application of the ATAC technology to selected antibodies."

Heidelberg Pharma will receive an upfront technology access fee and payments for research services. In the event Takeda exercises its option for an exclusive license, Heidelberg Pharma would receive an option fee. Under the exclusive license agreement, Heidelberg Pharma would be eligible to receive clinical development, regulatory and sales-related milestone payments of up to USD 113 million for each product candidate, as well as royalties.

The expected financial impact of this partnership is already reflected in WILEX’s financial outlook for the current fiscal year provided in March 2017.

"We see significant potential for Heidelberg Pharma’s ATAC technology, combined with our deep oncology expertise, to develop ADC therapies for patients with unmet medical needs," said Christopher Arendt, PhD, Head, Oncology DDU & Immunology Unit, Takeda. "We are excited about this relationship with Heidelberg Pharma, as partnerships such as this one are integral for us to achieve our aspiration of curing cancer."

Takeda signed the agreement with Heidelberg Pharma through its wholly-owned subsidiary, Millennium Pharmaceuticals, Inc.

About Heidelberg Pharma’s proprietary ATAC technology
Antibody-drug conjugates (ADCs) combine the high affinity and specificity of antibodies with the potency of cytotoxic small molecules for the treatment of cancer and inflammatory diseases. Antibody Targeted Amanitin Conjugates (ATACs) are ADCs whose active ingredient is made up of amatoxin molecules. Amatoxins are small bicyclic peptides naturally occurring in the death cap mushroom. They inhibit mRNA transcription by binding to RNA polymerase II, a mechanism that is crucial for the survival of eukaryotic cells. In preclinical testing, ATACs have been shown to be highly efficacious, overcoming frequently encountered resistance mechanisms and combating even quiescent tumor cells.

VBL Therapeutics Provides Update on Long-Term Survival in Phase 2 Trials of Patients with Multiple Tumor Types

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.

"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.