On June 20, 2017 The Cell and Gene Therapy Catapult (CGT Catapult) reported the sale of its subsidiary, Catapult Therapy TCR Ltd, to Cell Medica (Press release, UCLB, JUN 20, 2017, View Source [SID1234519619]). The CGT Catapult, through Catapult Therapy TCR Ltd, has been developing and conducting phase I/II clinical trials of a gene-modified T cell therapy that actively targets several blood cancers and multiple solid tumours. Financial terms were not disclosed.

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Catapult Therapy TCR Ltd is a joint venture company set up by the CGT Catapult, UCL Business (UCLB) and Imperial Innovations which focused on the development of a gene-modified WT1 TCR T cell therapy for acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) that are known to overexpress the antigen WT1. It represents a promising novel treatment approach in a therapeutic area where prognosis is often poor and therapeutic options limited. Early development work on this therapy conducted at UCL and Imperial was funded by the UK charity Bloodwise. The WT1 antigen is also present on a large variety of solid tumours, giving this treatment very broad therapeutic potential.

The acquisition of Catapult Therapy TCR Ltd by Cell Medica will enable and accelerate the further development and commercialisation of this innovative treatment in one of the most promising areas of cancer immunotherapy. The optimisation and development of next-generation T cells will be conducted by Cell Medica and CGT Catapult and manufacturing will take place at CGT Catapult’s large-scale cell and gene therapy manufacturing centre located at the Stevenage BioScience Catalyst in Hertfordshire, following a grant awarded earlier this year by Innovate UK.

"We are pleased that Cell Medica has acquired the WT1 T-cell immunotherapy," said Keith Thompson, Chief Executive Officer, Cell and Gene Therapy Catapult. "With their complementary technologies, they will take over the development of this exciting new therapy. The next generation product developed in our manufacturing centre underlines our ability to support the localisation of cell manufacturing processes in the UK. It reflects the CGT Catapult’s mission to work with academia and industry in bringing forward important new technologies that can be industrialised and turned into the advanced medicines of the future, building new industries."

"Immuno-oncology is an expanding discipline representing the next generation of cancer treatments, and WT1 has shown excellent results so far. We are delighted to have created this opportunity with our academic partners UCLB and Imperial Innovations."

Gregg Sando, Chief Executive Officer, Cell Medica, said: "The acquisition of the WT1-TCR cell therapy leverages the investment we made in 2016 for exclusive rights to the Dominant TCR technology. Our objective is to show how we can enhance any existing TCR cell therapy with the Dominant TCR technology to create a more effective treatment for patients with solid tumours who otherwise have a very poor prognosis. We are also looking forward to an important collaboration with CGT Catapult to initiate manufacturing at the Stevenage GMP facility where we will work together on scale-up strategies for commercial production."

Catapult Therapy TCR Ltd academic partners highlighted the relevance of T-cell immunotherapy to future cancer therapy options.

"Gene-modified T cells targeting WT1 have enormous potential to transform the lives of cancer patients, and the expertise of UCL Professors Hans Stauss and Emma Morris have enabled this innovative treatment to evolve," said Cengiz Tarhan, Managing Director, UCL Business. "Cell Medica is excellently placed to further develop this novel treatment approach."

Tony Hickson, Managing Director, Imperial Innovations Limited, said: "This project provides a case study of two leading UK universities working together alongside a Catapult to translate their high quality research outputs into clinical stage advanced therapeutics."

On June 20, 2017 Seattle Genetics, Inc. (Nasdaq: SGEN) reported that it has submitted a supplemental Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) based on data from the phase 3 ALCANZA trial and two phase 2 investigator-sponsored trials of ADCETRIS (brentuximab vedotin) in patients with cutaneous T-cell lymphoma (CTCL) (Press release, Seattle Genetics, JUN 20, 2017, View Source [SID1234519618]). ADCETRIS is currently not approved for the treatment of CTCL.

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"The submission of the supplemental BLA requesting label expansion for ADCETRIS as a treatment in CTCL patients who require systemic therapy is an important milestone. CTCL is an incurable and disfiguring disease in need of new therapeutic options, particularly those that achieve durable responses," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development of Seattle Genetics. "Results from the phase 3 ALCANZA trial demonstrated that CTCL patients treated with ADCETRIS had superior outcomes across all primary and secondary endpoints compared to patients in the control arm who were treated with either methotrexate or bexarotene standard of care agents. In addition to the ALCANZA results, data from two investigator-sponsored trials also support ADCETRIS use in this disease setting. We believe these data are clinically meaningful and support a label expansion for ADCETRIS in CTCL, which would be the fourth indication for this program."

In November 2016, based on preliminary analysis of ALCANZA, the FDA granted ADCETRIS Breakthrough Therapy Designation (BTD) for the treatment of patients with CD30-expressing mycosis fungoides and primary cutaneous anaplastic large cell lymphoma who require systemic therapy and have received one prior systemic therapy. These represent the most common subtypes of CTCL. Based on discussions with the FDA following the BTD, additional data from investigator-sponsored phase 2 trials have been incorporated into the supplemental BLA to support the potential for a broader label in CTCL.

The supplemental BLA is primarily based on positive results from a phase 3 trial called ALCANZA that were presented at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2016 and published in the Lancet in June 2017. Results from the ALCANZA trial in 128 CTCL patients requiring systemic therapy included:

The trial achieved its primary endpoint with the ADCETRIS treatment arm demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4) versus the control arm as assessed by an independent review facility. ORR4, as assessed by Global Response Score, was 56.3 percent in the ADCETRIS arm compared to 12.5 percent in the control arm (p-value <0.0001).
Key secondary endpoints specified in the protocol, including complete response rate, progression-free survival and reduction in the burden of symptoms during treatment (Skindex-29), were all highly statistically significant in favor of the ADCETRIS arm.
The safety profile associated with ADCETRIS from the ALCANZA trial was generally consistent with the existing prescribing information. The most common adverse events of any grade include: peripheral neuropathy, nausea, diarrhea, fatigue, vomiting, alopecia, pruritis, pyrexia, decreased appetite and hypertriglyceridemia.
About CTCL

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Cutaneous lymphomas are a category of non-Hodgkin lymphoma that primarily involve the skin. According to the Cutaneous Lymphoma Foundation, CTCL is the most common type of cutaneous lymphoma and typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis. Progression from limited skin involvement may be accompanied by skin tumor formation, ulceration and exfoliation, complicated by itching and infections. Advanced stages are defined by involvement of lymph nodes, peripheral blood and internal organs.

The standard treatment for systemically pretreated CTCL includes skin-directed therapies, radiation and systemic therapies. The systemic therapies currently approved for treatment have demonstrated 30 to 45 percent objective response rates, with low complete response rates.

About ADCETRIS

ADCETRIS is being evaluated broadly in more than 70 ongoing clinical trials, including three Phase 3 studies, the ongoing ECHELON-1 trial in frontline classical Hodgkin lymphoma and the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, as well as the completed ALCANZA trial in cutaneous T-cell lymphoma, from which data were submitted in a supplemental BLA.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells.

ADCETRIS for intravenous injection has received approval from the FDA for three indications: (1) regular approval for the treatment of patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (2) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. The European Commission extended the current conditional marketing authorization of ADCETRIS and approved ADCETRIS for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT.

ADCETRIS has received marketing authorization by regulatory authorities in 67 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

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.

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.

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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