On March 17, 2016 Allergan plc (NYSE: AGN), a leading global pharmaceutical company, reported that it has filed an Abbreviated New Drug Application (ANDA) with the U.S. Food and Drug Administration (FDA) seeking approval to market Paclitaxel Protein-Bound Particles for Injectable Suspension, 100 mg/vial (Press release, Allergan, MAR 17, 2016, View Source;p=irol-newsArticle&ID=2149174 [SID:1234509619]).

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Allergan’s ANDA product is a generic version of Celgene’s Abraxane, which is indicated for the treatment of metastatic breast cancer, after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy; locally advanced or metastatic non-small cell lung cancer (NSCLC), as first-line treatment in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy; and metastatic adenocarcinoma of the pancreas as first-line treatment, in combination with gemcitabine.

Based on available information, Allergan believes it is a "first applicant" to file an ANDA for the generic version of Abraxane and, should it’s ANDA be approved, may be entitled to 180 days of generic market exclusivity.

For the 12 months ending January 31, 2016, Abraxane had total U.S. sales of approximately $683 million, according to IMS Health data.

Abraxane is a registered trademark of Abraxis BioScience, LLC.

(Filing, Annual, Adaptimmune, 2015, MAR 17, 2016, View Source [SID:1234509607])

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On March 16, 2016 Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to treat cancer, reported the presentation of scientific data at the 2016 American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 16-20, 2016 in New Orleans, LA (Press release, Verastem, MAR 16, 2016, View Source;p=RssLanding&cat=news&id=2149075 [SID:1234509592]).

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"The data that will be presented at the upcoming 2016 AACR (Free AACR Whitepaper) Annual Meeting continue to build on the premise that focal adhesion kinase (FAK), and the related proline-rich tyrosine kinase 2 (PYK2), inhibition enhances the efficacy of standard of care treatments such as platinum, and notably, immune checkpoint inhibitors," said Dr. Jonathan Pachter, Verastem Head of Research. "Key immune-related observations include VS-6063 and VS-4718 dose-dependently stimulating proliferation of CD8+ cytotoxic T cells. This is in distinct contrast to other protein kinase inhibitors which impair the proliferation of CD8+ cytotoxic T cells. These data further extend the rationale for Verastem’s ongoing clinical trials testing FAK inhibitors in combination with the immune checkpoint inhibitors, pembrolizumab or avelumab."

Details for the AACR (Free AACR Whitepaper) presentations are as follows:

Poster Presentations

Title: FAK/PYK2 Inhibition Enhances Immune Checkpoint Inhibitor Efficacy
Session: Immunology: Immune Modulating Agents 1
Abstract No.: 568
Date and time: Sunday Apr 17, 2016 1:00 – 5:00 PM
Location: Convention Center, Halls G-J, Poster Section 26
Summary: Durable responses have been observed with single-agent immune checkpoint inhibitors, but combinations of immunotherapy agents with compounds that modulate the tumor microenvironment have the potential to overcome the mechanisms that tumor cells develop, which assist them in evading the immune attack. In addition to targeting cancer stem cells, Verastem’s dual FAK/PYK2 inhibitors, VS-6063 and VS-4718, have been shown to beneficially modulate the tumor microenvironment in squamous cell carcinoma models. In these study results, researchers at Verastem reported the findings from combinations of VS-6063 and VS-4718 with multiple immunotherapies.

The combination of VS-4718 with an anti-PD-1 monoclonal antibody (mAb) showed improved efficacy over anti-PD-1 mAb alone and extended survival in vivo. Analysis of the tumors at Day 12 of treatment revealed a significant increase in the CD8+ T cells/Treg ratios in tumors in the VS-4718 + anti-PD-1 combination group, providing a mechanistic understanding for the enhanced efficacy of this combination.

The combination of VS-4718 with anti-4-1BB was also tested in the same in vivo model. Consistent with what was observed with the anti-PD-1 combination, VS-4718 also enhanced the efficacy of the anti-4-1BB mAb. In in vitro T cell proliferation assays, VS-6063 and VS-4718 dose-dependently stimulated proliferation of CD8+ cytotoxic T cells isolated from healthy donors. In addition, both VS-4718 and VS-6063 decreased CD8+ T cell exhaustion markers, and increased T cell-mediated tumor cell killing in vitro. These data support the thesis that Verastem’s FAK/PYK2 inhibitors, VS-6063 and VS-4718, beneficially modulate the tumor microenvironment, and in combination with immune checkpoint inhibitors, may increase the breadth of responsive tumor types, increase the number of responders, and confer more durable anti-tumor responses.

Title: FAK Inhibition Re-sensitizes Platinum-resistant Serous Ovarian Cancer
Session: Novel targets: Experimental and Molecular Therapeutics
Abstract No.: 3811
Date and time: Tuesday Apr 19, 2016 1:00 – 5:00 PM
Location: Convention Center, Halls G-J, Poster Section 17
Summary: Ovarian cancer stem cell (CSC) resistance to chemotherapy treatment can give rise to tumor recurrence, which occurs in a high percentage of patients and is directly related to poor overall survival. FAK, an intracellular tyrosine kinase, has been linked to CSC survival in many cancers. In this study, researchers tested Verastem’s FAK inhibitor VS-4718 in certain ovarian cancer models.

In vitro results demonstrated that elevated FAK was present in platinum (CP)-resistant ovarian cancer cells and FAK tyrosine phosphorylation was increased after CP treatment of CP-sensitive ovarian cancer cells. VS-4718 selectively blocked CP-resistant ovarian carcinoma methylcellulose colony growth via cell cycle inhibition, but not apoptosis. In vivo, oral VS-4718 reduced CP-resistant orthotopic tumor burden with a simultaneous decrease in tumor-associated aldehyde dehydrogenase (ALDH) activity, a marker of ovarian CSCs. VS-4718 also reduced the expression of several other CSC-related biomarkers. These results suggest that FAK signaling facilitates ovarian carcinoma CSC phenotypes and support the testing of FAK inhibitors in combination with CP to prevent recurrent and chemo-resistant ovarian cancer.

A copy of the poster presentations will be available at http://bit.ly/R3M6wc following the respective presentation times of each poster.

About Focal Adhesion Kinase
Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase encoded by the PTK-2 gene that is involved in cellular adhesion and, in cancer, metastatic capability. VS-6063 (defactinib) and VS-4718 are orally available compounds that are potent inhibitors of FAK. VS-6063 and VS-4718 utilize a multi-faceted approach to treat cancer by reducing cancer stem cells, enhancing anti-tumor immunity, and modulating the local tumor microenvironment. VS-6063 and VS-4718 are currently being studied in multiple clinical trials for their ability to improve patient outcome.

On March 16, 2016 Cellectis (Paris:ALCLS) (NASDAQ:CLLS) (Alternext: ALCLS – Nasdaq: CLLS), a biopharmaceutical company focused on developing immunotherapies based on gene edited CAR T-cells (UCART), and MabQuest SA, a biotech company focused on the development of antibody-based therapeutic interventions, reported that they have entered into a research collaboration and license agreement pertaining to the development of a new class of monoclonal antibodies targeting PD-1 (Filing, 6-K, Cellectis, MAR 16, 2016, View Source [SID:1234509593]). The action of these PD-1 antibodies is to promote the recovery of T-cells from exhaustion through a new mechanism of action. This new class of antibodies differs from currently approved anti-PD-1 mAbs in that they do not block the PD-1-PD-L1 interaction. These anti-PD-1 mAbs have potential uses for multiple indications in immunotherapy, including notably treatments for a variety of cancers. Cellectis plans to use this new class of anti-PD-1 antibodies either in combination therapy with its gene-edited UCART product candidates or single-agent or in combination with other already approved immunotherapy drugs.

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In vitro studies have shown that the combination of these novel PD-1 mAbs with currently approved anti-PD-1 mAbs enhances the recovery of T-cells from exhaustion. Due to their new mechanism of action, these anti-PD-1 mAbs may be used in combination with other PD-1/PD-L1 inhibitors, such as Nivolumab and Pembrolizumab, or other checkpoints inhibitors and immunotherapy approaches for boosting the therapeutic effects of single therapy. Furthermore, this novel class of anti-PD-1 mAbs may represent an alternative and effective therapeutic intervention in those cancer patients with tumors expressing low levels of PD-L1, with respect to the currently approved anti-PD-1 mAbs. In addition, Cellectis intend to combine these PD-1 mAbs with its gene-edited UCART product candidates to enhance their activity and increase their half-life.

The agreement includes a collaboration phase funded by Cellectis whereby Cellectis and MabQuest will jointly pursue preclinical research on several candidate antibodies; and a clinical development and commercialization phase of the best selected antibodies which will be led by Cellectis.

Under the agreement, MabQuest has granted an exclusive option to Cellectis. Upon exercise of the option, Cellectis would be granted worldwide exclusive rights over the family of PD-1 antagonist antibodies developed under the collaboration for all fields, and further potential derivatives of these antibodies.

"We are very pleased to have signed this agreement with MabQuest, with founders and lead scientists who have great expertise in the field of immunology and monoclonal antibodies," said André Choulika, Chairman and Chief Executive Officer of Cellectis. "This collaboration is an important building block for our gene-edited UCART product candidates and for our immunotherapy franchise. This new partnership fits perfectly into Cellectis’ strategy of expanding our focus in the cancer immunotherapy space with our CAR T-cell based approaches."

"The collaboration agreement with Cellectis is a tremendous opportunity for MabQuest to move into clinical development with this new class of anti-PD-1 mAbs. This collaboration will also boost MabQuest’s discovery program to develop additional antibody-based strategies to modulate the host immune system," said Dr. Giuseppe Pantaleo, President of MabQuest and Professor of Medicine and Chief of the Service of Immunology and Allergy at the Lausanne University Hospital, Lausanne, Switzerland.

On March 16, 2016 Cellectis (Alternext: ALCLS – Nasdaq: CLLS), a biopharmaceutical company focused on developing immunotherapies based on gene edited CAR T-cells (UCART), and MabQuest SA, a biotech company focused on the development of antibody-based therapeutic interventions, reported that they have entered into a research collaboration and license agreement pertaining to the development of a new class of monoclonal antibodies targeting PD-1 (Press release, Cellectis, MAR 16, 2016, View Source [SID1234645116]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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The action of these PD-1 antibodies is to promote the recovery of T-cells from exhaustion through a new mechanism of action. This new class of antibodies differs from currently approved anti-PD-1 mAbs in that they do not block the PD-1-PD-L1 interaction. These anti-PD-1 mAbs have potential uses for multiple indications in immunotherapy, including notably treatments for a variety of cancers. Cellectis plans to use this new class of anti-PD-1 antibodies either in combination therapy with its gene-edited UCART product candidates or single-agent or in combination with other already approved immunotherapy drugs.

In vitro studies have shown that the combination of these novel PD-1 mAbs with currently approved anti-PD-1 mAbs enhances the recovery of T-cells from exhaustion. Due to their new mechanism of action, these anti-PD-1 mAbs may be used in combination with other PD-1/PD-L1 inhibitors, such as Nivolumab and Pembrolizumab, or other checkpoints inhibitors and immunotherapy approaches for boosting the therapeutic effects of single therapy. Furthermore, this novel class of anti-PD-1 mAbs may represent an alternative and effective therapeutic intervention in those cancer patients with tumors expressing low levels of PD-L1, with respect to the currently approved anti-PD-1 mAbs. In addition, Cellectis intend to combine these PD-1 mAbs with its gene-edited UCART product candidates to enhance their activity and increase their half-life.

The agreement includes a collaboration phase funded by Cellectis whereby Cellectis and MabQuest will jointly pursue preclinical research on several candidate antibodies; and a clinical development and commercialization phase of the best selected antibodies which will be led by Cellectis.

Under the agreement, MabQuest has granted an exclusive option to Cellectis. Upon exercise of the option, Cellectis would be granted worldwide exclusive rights over the family of PD-1 antagonist antibodies developed under the collaboration for all fields, and further potential derivatives of these antibodies.

"We are very pleased to have signed this agreement with MabQuest, with founders and lead scientists who have great expertise in the field of immunology and monoclonal antibodies," said André Choulika, Chairman and Chief Executive Officer of Cellectis. "This collaboration is an important building block for our gene-edited UCART product candidates and for our immunotherapy franchise. This new partnership fits perfectly into Cellectis’ strategy of expanding our focus in the cancer immunotherapy space with our CAR T-cell based approaches."

"The collaboration agreement with Cellectis is a tremendous opportunity for MabQuest to move into clinical development with this new class of anti-PD-1 mAbs. This collaboration will also boost MabQuest’s discovery program to develop additional antibody-based strategies to modulate the host immune system," said Dr. Giuseppe Pantaleo, President of MabQuest and Professor of Medicine and Chief of the Service of Immunology and Allergy at the Lausanne University Hospital, Lausanne, Switzerland.