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Celsion Announces Collaboration with the Children’s Research Institute to Evaluate the Use of ThermoDox® and High Intensity Focused Ultrasound in the Treatment of Solid Tumors in Children and Young Adults

On October 11, 2016 Celsion Corporation (NASDAQ:CLSN), a leading oncology drug development company, reported a collaboration with the Children’s Research Institute to conduct a clinical study of ThermoDox, Celsion’s heat activated liposomal encapsulation of doxorubicin, in combination with magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) to treat relapsed or refractory solid tumors in children and young adults (Press release, Celsion, OCT 11, 2016, View Source [SID:SID1234515733]). This investigator-sponsored Phase I clinical study is being partially funded by the National Institutes of Health and is expected to commence in the fourth quarter of 2016.

"Even with the use of intensive therapy, the prognosis for children diagnosed with metastatic sarcoma and recurrent solid tumors remains poor and has not improved over the past three decades," stated Dr. Nicolas Borys, Celsion’s chief medical officer. "Recent advances in the use of non-invasive MR-HIFU coupled with novel therapies such as ThermoDox have demonstrated the clear potential to overcome the challenges to treating pediatric malignancies by enabling safer, more tolerable targeted therapies with the potential to change cancer treatment paradigms."

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The trial targeting treatment of childhood sarcomas will be carried out as a multi-disciplinary collaboration among Celsion, the research groups of Dr. AeRang Kim, MD, PhD at the Children’s National Medical Center – Department of Hematology/Oncology, and Dr. Brad Wood and Dr. Rosandra Kaplan at the National Institutes of Health.

"Celsion’s experience in combining ThermoDox with HIFU, a non-invasive next generation heating technology, supports this very important research in childhood cancers. From a safe dose, ThermoDox’s proven ability to deliver high concentrations of an effective chemotherapy directly to a heated tumor makes it an ideal candidate for a trial involving children and young adults," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "This study will further define ThermoDox’s potential in combination with ultrasound-induced hyperthermia, and highlight potential applications of ThermoDox in combination with a broad range of heating technologies that could address an even larger population of patients."

ThermoDox is currently in late stage clinical trials in primary liver cancer and recurrent chest wall breast cancer. It is positioned for use with multiple heating technologies, and has the potential for applications in the treatment of other forms of cancer including metastatic liver and non-muscle invading bladder cancers.

About ThermoDox
Celsion’s most advanced program is a heat-mediated, tumor-targeting drug delivery technology that employs a novel heat-sensitive liposome engineered to address a range of difficult-to-treat cancers. The first application of this platform is ThermoDox, a lyso-thermosensitive liposomal doxorubicin (LTLD), whose novel mechanism of action delivers high concentrations of doxorubicin to a region targeted with the application of localized heat at 40°C, just above body temperature. ThermoDox has the potential to address a broad range of cancers.

Celsion’s LTLD technology leverages two mechanisms of tumor biology to deliver higher concentrations of drug directly to the tumor site. In the first mechanism, rapidly growing tumors have leaky vasculature, which is permeable to liposomes and enables their accumulation within tumors. Leaky vasculature influences a number of factors within the tumor, including the access of therapeutic agents to tumor cells. Administered intravenously, ThermoDox is engineered with a half-life to allow significant accumulation of liposomes at the tumor site as these liposomes recirculate in the blood stream. In the second mechanism, when an external heating device heats tumor tissue to a temperature of 40°C or greater, the heat-sensitive liposome rapidly changes structure and the liposomal membrane selectively dissolves, creating openings that can release a chemotherapeutic agent directly into the tumor and into the surrounding vasculature. Drug concentration increases as a function of the accumulation of liposomes at the tumor site, but only where the heat is present. This method damages only the tumor and the area related to tumor invasion, supporting more precise drug targeting.

Delcath Announces New U.S. Clinical Sites For FOCUS Phase 3 Trial For Ocular Melanoma Liver Metastases

On October 11, 2016 Delcath Systems, Inc. (NASDAQ: DCTH), an interventional oncology Company focused on the treatment of primary and metastatic liver cancers, reported that five new clinical trial sites in the U.S. have been activated in the Company’s global FOCUS Phase 3 clinical trial for patients with hepatic dominant ocular melanoma (the FOCUS Trial) (Press release, Delcath Systems, OCT 11, 2016, View Source;p=RssLanding&cat=news&id=2210776 [SID:SID1234515730]). These accredited centers join several other prestigious centers as active participants in the FOCUS Trial. Currently, Delcath now has a total of 8 cancer centers in the U.S. open for patient enrollment in the FOCUS Trial.

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The new participating centers are:

Ohio State University Comprehensive Cancer Center
MD Anderson Cancer Center
Thomas Jefferson University Sidney Kimmel Cancer Center
University of Chicago Comprehensive Cancer Center
University of Maryland Greenebaum Cancer Center
"We are pleased to add these respected cancer research institutions to our FOCUS Trial, and to expand the regional coverage available to patients in the U.S. with ocular melanoma liver metastases," said Jennifer K. Simpson, Ph.D., MSN, CRNP, President and CEO of Delcath. "Interest in the FOCUS Trial has been strong, and we expect to achieve our goal of activating approximately 30 centers in both the U.S. and Europe in the coming months."

About the FOCUS Trial
The FOCUS Trial is a global Phase 3 clinical study evaluating the safety, efficacy and pharmacokinetic profile of the Company’s Melphalan/HDS system versus best alternative care in 240 patients with ocular melanoma liver metastases. The FOCUS Trial’s primary endpoint is a comparison of overall survival between the two study arms; secondary and exploratory endpoints include progression-free survival, overall response rate and quality-of-life measures. The FOCUS Trial is being conducted under a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA). The SPA provides agreement that the Phase 3 trial design adequately addresses objectives that, if met, would support the submission for regulatory approval of Melphalan/HDS.

Cellerant Therapeutics, Inc. Presents Preclinical Data Showing Promise of a Novel Differentiated Target on Leukemic Stem Cells

On October 11, 2016 Cellerant Therapeutics, Inc., a clinical-stage company developing innovative cell- and antibody-based immunotherapies for hematologic malignancies (blood cancers) and other blood-related disorders, reported preclinical data showing potent killing of leukemic blast and stem cells by CSC030-ADC, the Company’s antibody drug-conjugate (ADC) product candidate being developed as a treatment for acute myeloid leukemia (AML) (Press release, Cellerant Therapeutics, OCT 11, 2016, View Source [SID:SID1234515756]). CSC030-ADC targets CSC030, or the C-type-like lectin 1 (CLL-1), a cell surface antigen widely expressed in nearly all AML cell subtypes, including leukemic stem cells. However, CSC030 is not expressed on normal hematopoietic stem and progenitor cells, making it a highly attractive target for an AML therapeutic. The data was presented today by Jagath Reddy Junutula, Ph.D., Vice President, Antibody Discovery & Development of Cellerant Therapeutics, at the 7th Annual World ADC meeting being held in San Diego, October 10-13, 2016.

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"We have shown that CSC030-ADC can specifically target and kill leukemic blast and stem cells," said Dr. Junutula. "Leukemic stem cells are believed to be responsible for tumor relapse, so an ADC that can target the leukemic stem cells precisely while minimally affecting normal stem cells would potentially have an important safety advantage compared to other targeted therapies for AML."

CSC030-ADC is a humanized monoclonal ADC that utilizes a potent DNA-damaging payload to target CSC030, an antigen expressed specifically on AML blasts and leukemic stem cells. The Company and others have shown that CSC030 is expressed in approximately 90% of all AML patient types, including all French American British (FAB) classifications, all cytogenetic risk categories, and in patients independent of FLT-3 status. When combined with a cytotoxic payload, the CSC030-ADC displayed potent target-dependent activity on several AML cell lines and robust tumor colony inhibition. CSC030-ADC also demonstrated a broad therapeutic index, e.g., greater than 10-fold therapeutic efficacy to toxicity, in AML tumor models. In addition, CSC030-ADC showed killing of both proliferating and quiescent CSC030-expressing cells. Importantly, CSC030 is not expressed on normal hematopoietic stem or progenitor cells and thus should have minimal effect on the formation of normal blood cell types. In contrast, the CD33 antigen is expressed on both normal stem and progenitor cells.

"We are excited with the preclinical results of CSC030-ADC and we look forward to advancing our product candidate to the clinic," said Ram Mandalam, Ph.D., President and Chief Executive Officer of Cellerant Therapeutics. "CSC030 is the first of multiple candidates identified through our stem cell target discovery efforts. In combination with Cellerant’s engineered antibodies and payload technology, we are well positioned to develop next generation of ADCs for the treatment of cancer."

Transgene Announces Collaboration with Merck KGaA, Darmstadt, Germany, and Pfizer to Evaluate the Combination of TG4001 with Avelumab in HPV-Positive Head & Neck Cancer in a Phase 1/2 Study

On October 11, 2016 Transgene (Paris:TNG), a company focused on designing and developing targeted immunotherapies for the treatment of cancer and infectious diseases, reported it has entered a collaboration agreement with the science and technology company Merck KGaA, Darmstadt, Germany, and Pfizer (NYSE: PFE) under which Transgene will sponsor a Phase 1/2 study evaluating the potential of the therapeutic vaccine candidate TG4001 in combination with avelumab, an investigational fully human anti-PD-L1 IgG1 monoclonal antibody, for the treatment of human papilloma virus- (HPV-) positive head and neck squamous cell carcinoma (HNSCC), after failure of standard therapy (Press release, Transgene, OCT 11, 2016, View Source [SID:SID1234515755]).

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Philippe Archinard, Chairman and CEO of Transgene, commented: "We are pleased to enter this collaboration with Merck KGaA, Darmstadt, Germany, and Pfizer to evaluate our therapeutic vaccine TG4001 in association with avelumab. In previous clinical trials, TG4001 has demonstrated promising activity in terms of HPV viral clearance and was well tolerated. TG4001 is one of the few drugs targeting HPV-associated cancers that can be combined with an immune checkpoint blocker such as avelumab. The preclinical and clinical data that have been generated with both TG4001 and avelumab individually suggest this combination could potentially demonstrate a synergistic effect, delivering a step up in therapy for HPV-positive HNSCC patients."

The combination of TG4001 and avelumab aims to target two distinct steps in the immune response to target cancer cells. This is an exclusive agreement between the parties to study the combination of these two classes of investigational agents in HPV-positive HNSCC.

Prof. Christophe Le Tourneau, M.D., Head of the Early Phase Program at Institut Curie, and a world expert in ENT cancers, will be the Principal Investigator of the Phase 1/2 study. This trial is expected to begin in France, with the first patient expected to be recruited in H1 2017. It will seek to recruit patients with recurrent and/or metastatic virus-positive oropharyngeal squamous cell carcinoma that have progressed after definitive local treatment or chemotherapy, and cannot be treated with surgical resection and/or re-irradiation.

Prof. Christophe Le Tourneau said: "HPV-induced head and neck cancers are currently treated with the same regimen as non-HPV-positive HNSCC tumors. However, their different etiology clearly suggests that differentiated treatment approaches are needed for HPV-positive patients. Immunotherapy, and in particular the therapeutic vaccine TG4001 together with the PD-L1 blocker avelumab, by targeting two distinct steps in the immune response, could deliver improved efficacy for patients who have not responded to or have progressed after a first line of treatment."

TG4001 is an active immunotherapeutic designed by Transgene to express the coding sequences of the E6 & E7 tumor-associated antigens of HPV-16 and the cytokine, IL-2. This therapeutic vaccine, which is based on a non-propagative, attenuated vaccinia vector (MVA), has already been administered to more than 300 patients with high grade cervical intra-epithelial neoplasia (CIN 2/3). It has demonstrated good safety, a significant HPV clearance rate and promising efficacy results. Its mechanism of action and good safety profile make TG4001 a particularly appropriate candidate for combinations with other therapies, such as avelumab.

Avelumab is an investigational, fully human antibody specific for a protein found on tumor cells called PD-L1, or programmed death ligand-1. As a checkpoint inhibitor, avelumab is thought to have a dual mechanism of action that may potentially enable the immune system to find and attack cancer cells. By binding to PD-L1, avelumab is thought to prevent tumor cells from using PD-L1 for protection against white blood cells such as T-cells, exposing them to anti-tumor responses. Avelumab is also thought to help white blood cells such as natural killer (NK) cells find and attack tumors in a process known as ADCC, or antibody-dependent cell-mediated cytotoxicity. In 2014, the science and technology company Merck KGaA, Darmstadt, Germany, and Pfizer signed a strategic alliance to co-develop and co-commercialize avelumab.

Alise Reicin, M.D., Head of Global Clinical Development in the biopharma business of Merck KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD Serono, commented: "We believe combination regimens show significant promise in the development of novel and efficacious immuno-oncology treatments. Through this study, we hope to discover the potential of avelumab as a combination therapy with TG4001 for patients fighting this recurring cancer."

Chris Boshoff, M.D., Ph.D., Head of Immuno-Oncology, Early Development, and Translational Oncology at Pfizer, said: "Through this collaboration, we hope to better understand how therapeutic vaccines may help support the clinical development program for avelumab as our end goal is to find the best treatment options for patients."

About HPV-mediated Head and Neck Cancer

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of cancers that can affect the oral cavity, pharynx, and larynx. HPV-16 infection is recognized to participate in the development of a substantial proportion of head and neck cancers and is associated with a subset of HNSCC, especially those arising from the oropharynx (more than 80%), which are the most frequent, and the larynx (~70%).

The incidence of HPV-16-related head and neck cancer has significantly increased in recent years. Although there are more than 100 subtypes of HPV, HPV-16 accounts for 90% of all HPV-related head and neck cancers. Global spending on head and neck cancer indications amounted to $1 billion in 2010.

Current treatments include surgical resection with radiotherapy or chemoradiotherapy. However, better options are needed for advanced and metastatic HPV+ HNSCC. It is thought that immunotherapy combined with immune checkpoint inhibitors could provide a promising potential treatment option that would address this strong medical need.

About TG4001

TG4001 is an investigational therapeutic vaccine based on a non-propagative, highly attenuated vaccinia vector (MVA), which is engineered to express HPV-16 antigens (E6 & E7) and an adjuvant (IL-2). It is one of the few therapies targeting HPV+ sub population. TG4001 is designed to have a two-pronged antiviral approach: to alert the immune system specifically to HPV-16-infected cells that have started to undergo precancerous transformation (cells presenting the HPV-16 E6 and E7 antigens) and to further stimulate the infection-clearing activity of the immune system through interleukin 2 (IL-2). TG4001 has been administered to more than 300 patients, demonstrating good safety, significant HPV clearance rate and promising efficacy results. Its mechanism of action and good safety profile make TG4001 an excellent candidate for combinations with other therapies in solid tumors.

About Avelumab

Avelumab (also known as MSB0010718C) is an investigational, fully human antibody specific for a protein found on tumor cells called PD-L1, or programmed death ligand-1. Avelumab is thought to have a dual mechanism of action which may enable the immune system to find and attack cancer cells. By binding to PD-L1, avelumab is thought to prevent tumor cells from using PD-L1 for protection against white blood cells such as T-cells, exposing them to anti-tumor responses. Avelumab is also thought to help white blood cells such as natural killer (NK) cells find and attack tumors in a process known as ADCC, or antibody-dependent cell-mediated cytotoxicity. In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

Kymab and EpimAb Biotherapeutics Announce Multi-Target, Bispecific Antibody Cross-Licensing Agreement

On October 11, 2016 Kymab, a leading human monoclonal antibody biopharmaceutical company, and EpimAb Biotherapeutics, an emerging biopharmaceutical company specializing in bispecific antibodies, reported a cross-licensing and development agreement to develop bispecific therapeutic antibodies against multiple targets (Press release, EpimAb Biotherapeutics, OCT 11, 2016, View Source [SID:SID1234515754]). The parties will focus their efforts on immuno-oncology and will combine EpimAb’s proprietary Fabs-In-Tandem Immunoglobulin (FIT-Ig) platform to generate multiple bispecific antibodies combined with antibodies sourced from Kymab’s proprietary Kymouse platform. Kymab will have the development and commercialization rights to these bispecifics in all geographical regions outside of China, and, under the terms of the cross license agreement, EpimAb will have the rights for the China market. Each party is eligible to receive milestone payments and royalties for development programs pursued by the other party.

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"Today’s agreement with Kymab represents our first license agreement outside of China and we are looking forward to combining our complementary antibody technologies to create novel treatments for severe human diseases," said Dr. Chengbin Wu, CEO and founder of EpimAb. "Kymab’s expertise in generating world class antibodies specifically in the immuno-oncology area is a perfect strategic fit for EpimAb. The candidates from this collaboration will significantly strengthen EpimAb’s proprietary pipeline with highly innovative molecules."

"Bispecific antibodies have enormous potential to exploit our growing molecular and cellular understanding of the tumor microenvironment as it relates to immuno-oncology," said Dr. David Chiswell, CEO of Kymab. "This provides new opportunities to realize genuinely synergistic therapeutic activities and our collaboration with EpimAb will allow us to generate innovative bispecific molecules based on parental antibodies from our KymouseTM platform quickly and efficiently".
EpimAb’s innovative FIT-Ig technology offers a novel approach for generating bispecific antibodies, with the resulting molecules fully retaining the biological properties of their parental monoclonal antibodies without the need to significantly modify the basic structural elements of the bispecific antibody. FIT-Ig molecules generated to date have demonstrated excellent biological and pharmacological characteristics, as well as excellent physical-chemical properties. The combination of Kymab’s Kymouse human antibody discovery platform with the FIT-Ig technology will assure the highest probability of finding the best-in-class bispecific antibodies with highly attractive drug properties.