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.

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.

On October 11, 2016 Curis, Inc. (Nasdaq:CRIS), a biotechnology company focused on the development and commercialization of innovative and effective drug candidates for the treatment of cancer, reported the expansion of its pipeline with CA-327, an oral, small molecule immune checkpoint antagonist targeting programmed death ligand-1 (PD-L1) and T-cell immunoglobulin and mucin domain containing protein-3 (TIM-3) (Press release, Curis, OCT 11, 2016, View Source [SID:SID1234515734]).

Curis licensed the PD-1/ TIM-3 antagonist program, and designated CA-327 as the development candidate, by exercising its option under the collaboration, license and option agreement established with Aurigene in January 2015. The collaboration is focused on the discovery, development and commercialization of small molecule drug candidates in the fields of immuno-oncology and selected precision oncology targets. The previous licensed programs within the collaboration include CA-170, a first-in-class oral, small molecule antagonist targeting PD-L1 and V-domain Ig suppressor of T cell activation (VISTA) immune checkpoints that is currently being studied in a Phase 1 trial in patients with solid tumors and lymphomas, and CA-4948, an oral small molecule inhibitor of Interleukin-1 receptor-associated kinase 4 (IRAK4) that is completing IND-enabling studies.

In addition to targeting PD-L1, a negative regulator of immune activation, CA-327 also targets TIM-3, an inhibitory checkpoint molecule that plays an important role in immune suppression and is co-expressed with programmed cell death-1 (PD-1) receptors on exhausted cytotoxic T cells in tumor tissues as well as expressed on certain regulatory T cells.

The in-license of CA-327 comes three months after the collaboration’s first oral immuno-oncology program entered the clinic and less than a month after a $24.5M investment in Curis by Aurigene.

“We are pleased with the progress of our collaboration,” said Dr. Ali Fattaey, Curis’s CEO, “and look forward to working with our partner, Aurigene, to complete IND-enabling studies for CA-327 in the coming months and expect to file an IND in 2017.”

“We are delighted that our collaboration is advancing its third small molecule program in less than two years,” said CSN Murthy, Aurigene’s CEO. “We continue to work closely with Curis to focus our collective resources, creating and developing innovative drug candidates in the field of oncology, including multiple first-in-class oral small molecule checkpoint antagonists within immuno-oncology.”

On October 11, 2016 Heat Biologics, Inc. (Nasdaq:HTBX), reported that they have advanced their biomarker discovery collaboration with Adaptive Biotechnologies. Adaptive will use its patented immune profiling assay, immunoSEQ, to enable an in-depth characterization of the immune response to Heat’s ImPACT and ComPACT-based immunotherapies, including HS-410, Heat’s Phase 2 product candidate for non-muscle invasive bladder cancer (Press release, Heat Biologics, OCT 11, 2016, View Source [SID:SID1234515727]). The immunoSEQ Assay, when used to evaluate the mechanism of action of the ImPACT platform, provides a significant biomarker identification opportunity to better select patients and accelerate future enrollment based on immune status.

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"Previously reported data using Adaptive’s immunoSEQ Assay, demonstrated a trend between established anti-tumor immune responses and clinical outcomes with HS-410," stated Taylor Schreiber, M.D., Ph.D., Heat’s Chief Scientific Officer. "The Adaptive Assay allows us to quantify the clonality of a T-cell response generated by our ImPACT platform. Future work should continue to be fruitful as we advance our understanding of the patients that benefit most from treatment."