6-K – Report of foreign issuer [Rules 13a-16 and 15d-16]

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.

Verastem to Present Data Supporting FAK/PYK2 Inhibition at the 2016 American Academy of Cancer Research Annual Meeting

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.

OncoMed to Present Data at the American Association of Cancer Research Annual Meeting 2016

On March 16, 2016 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED) reported that it will present new data related to its clinical and preclinical anti-cancer stem cell and immuno-oncology therapeutic candidates in a total of five presentations at the upcoming American Association of Cancer Research (AACR) (Free AACR Whitepaper) Meeting to be held April 16-20, 2016 in New Orleans, LA (Press release, OncoMed, MAR 16, 2016, View Source [SID:1234509590]).

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Among the presentations will be multiple abstracts related to the company’s novel GITRL-Fc immuno-oncology therapeutic candidate, biomarker research associated with its vantictumab (anti-FZD7, OMP-18R5) and anti-RSPO3 (OMP-131R10) clinical programs, and xenograft data for demcizumab (anti-DLL4, OMP-21M18) in non-small cell lung cancer.

The following abstracts have been selected for presentation by OncoMed scientists:

Sunday, April 17, 2016 1:00 PM — 5:00 PM

1. "Development of a RSPO3 CLIA-validated assay as a predictive biomarker for response to anti-RSPO3 antibody treatment in patients with solid tumors"
Abstract Number: 404
Presenting author: Chun Zhang, Ph.D., Associate Director, Translational Medicine
Session: Biomarkers

Monday, April 18, 2016 1:00 PM — 5:00 PM

2. "GITR ligand fusion protein (GITRL-Fc) induces T cell mediated anti-tumor immune response and can combine with anti-PDL1 to enhance anti-tumor immunity and long-term immune memory"
Abstract Number: 2214
Presenting author: Minu Srivastava, Ph.D., Senior Scientist
Session: Adoptive Cell Therapy, Immune Checkpoints and Vaccines

Tuesday, April 19, 2016 8:00 AM — 12:00 PM

3. "GITRL-Fc can significantly reduce tumor growth by stimulating innate and adaptive immunity"
Abstract number: 3215
Presenting author: Hyun-Bae Jie, Ph.D., Scientist
Session: Immune Checkpoints 2

4. "Predictive biomarker identification for response to vantictumab (OMP-18R5; anti-Frizzled) using primary patient-derived human pancreatic tumor xenografts"
Abstract Number: 3129
Presenting author: Chun Zhang, Ph.D., Associate Director, Translational Medicine
Session: Biomarkers for Gastrointestinal, Hematologic, and Uncommon Cancers

Wednesday, April 20, 2016 8:00 AM — 12:00 PM

5. "Effects of anti-DLL4 treatment on non-small cell lung cancer (NSCLC) human xenograft tumors"
Abstract number: 4652
Presenting author: Alayne Brunner, Ph.D., Senior Scientist
Session: Cellular Responses to Anticancer Drugs

Merrimack to Present on Multiple Oncology Programs at the 2016 American Association for Cancer Research Annual Meeting

On March 16, 2016 Merrimack Pharmaceuticals, Inc. (Nasdaq: MACK) reported that it will present preclinical and clinical data on its extensive oncology pipeline at the 2016 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, April 16-20, 2016 at the Ernest N. Morial Convention Center, New Orleans, Louisiana (Press release, Merrimack, MAR 16, 2016, View Source [SID:1234509589]). Of particular focus will be preclinical data on the latest novel therapeutic developed from Merrimack’s nanoliposome platform and systems biology approach – MM-310, an ephrin receptor A2 (EphA2)-targeted nanoliposome delivering docetaxel.

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EphA2 is a key receptor associated with poor prognosis and is shown to be overexpressed in several solid tumors including prostate, ovarian, gastric and lung cancer. In preclinical models, MM-310 has demonstrated that Merrimack’s proprietary delivery platform provides controlled biodistribution and sustained exposure of the drug at the site of the tumor. This design has shown improvement in antitumor activity while avoiding the hematologic toxicities common with docetaxel or the bleeding associated with a traditional antibody drug conjugate (ADC) format in preclinical models.

Merrimack will also present a late-breaking abstract describing in vitro and in vivo targeting effects of MM-302 in HER2 intermediate cancer cells as well as research on ONIVYDE (irinotecan liposome injection) and other targeted therapies currently in development.

Oral presentation
MM-310: a novel EphA2 targeted nanoliposome for delivery of docetaxel

Session Title: Antibody-targeted Therapy
Nanoliposomal targeting of Ephrin receptor A2 (EphA2): Preclinical in vitro and in vivo rationale (Abstract #871)
Sunday, April 17, 2016, 4:15 PM – 6:15 PM ET

Poster Sessions
MM-310: a novel EphA2 targeted nanoliposome for delivery of docetaxel

Session Title: Targeting the Microenvironment
Nanoliposomal targeting of Ephrin receptor A2 (EphA2): Clinical Translation (Abstract #750, Poster Section 33)
Sunday, April 17, 2016, 1:00 PM – 5:00 PM ET

Session Title: Drug Delivery
Activity of an EphA2-targeted docetaxel nanoliposome in pancreatic patient-derived models as monotherapy and in combination with gemcitabine (Abstract #2069, Poster Section 15)
Monday, April 18, 2016, 1:00 PM – 5:00 PM ET

Session Title: Therapeutics
MM-310, a novel EphA2-targeted docetaxel nanoliposome (Abstract #3912, Poster Section 21)
Tuesday, April 19, 2016, 1:00 PM – 5:00 PM ET
MM-398 (ONIVYDE (irinotecan liposome injection) or "Nal-IRI"): a novel encapsulation of irinotecan in a liposomal formulation

Session Title: Drug Delivery
Differential tissue clearance results in improved therapeutic index for irinotecan liposome injection (ONIVYDE) when combined with the PARP inhibitor veliparib in preclinical cervical tumors (Abstract #2075, Poster Section 15)
Monday, April 18, 2016, 1:00 PM – 5:00 PM ET

Session Title: Targeted Therapy
Preclinical anti-tumor activity of nanoliposomal irinotecan (Nal-IRI, MM-398) + 5-FU + oxaliplatin in pancreatic cancer (Abstract #4830, Poster Section 20)
Wednesday, April 20, 2016, 8:00 AM – 12:00 PM ET
MM-302: a novel HER2 targeted liposomal doxorubicin

Session Title: Late-Breaking Research: Cancer Chemistry
HER2-targeted PEGylated liposomal doxorubicin (MM-302) efficiently targets the HER2 intermediate cell population in vitro and in vivo (Abstract #LB-061, Poster Section 12)
Sunday, April 17, 2016, 1:00 PM – 5:00 PM ET
MM-141 (istiratumab): a monoclonal antibody that acts as a tetravalent inhibitor of PI3K/AKT/mTOR

Session Title: Growth Factor Receptors and Surface Antigens as Therapeutic Targets
Istiratumab (MM-141), a bispecific antibody targeting IGF-1R and ErbB3, inhibits pro-survival signaling in vitro and potentiates the activity of standard of care chemotherapy in vivo in ovarian cancer models (Abstract #1209, Poster Section 15)
Monday, April 18, 2016, 8:00 AM – 12:00 PM ET
MM-151: an oligoclonal therapeutic consisting of a mixture of 3 fully human monoclonal antibodies designed to bind and inhibit signaling of the epidermal growth factor receptor (EGFR)

Session Title: New Drugs, Therapeutic Targets, and Treatment Approaches
MM-151 elicits broad and unique inhibition of cells harboring EGFR extracellular domain mutations —results of multiscale experiments with genome-edited cell lines (Abstract #2148, Poster Section 18)
Monday, April 18, 2016, 1:00 PM – 5:00 PM ET
Companion Therapeutics:

Session Title: Growth Factor Receptors and Surface Antigens as Therapeutic Targets
A network biology screen reveals ligand-receptor pathway connections and resistance mechanisms to RTK-directed therapies in cancer cells (Abstract #1199, Poster Section 15)
Monday, April 18, 2016, 8:00 AM – 12:00 PM ET
Preclinical Research:

Session Title: Targeting Protein Kinases, Death Pathways, and the Tumor Microenvironment
Design and engineering of TRAIL fusion proteins for cancer therapy (Abstract #3842, Poster Section 19)
Tuesday, April 19, 2016, 1:00 PM – 5:00 PM ET

Incyte’s Immuno-oncology and Targeted Therapy Portfolio to be Featured at the AACR Annual Meeting 2016

On March 16, 2016 Incyte Corporation (Nasdaq: INCY) reported that ten abstracts featuring data from its emerging development portfolio will be presented at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016 in New Orleans, Louisiana from April 16–20, 2016 (Press release, Incyte, MAR 16, 2016, View Source;p=RssLanding&cat=news&id=2149072 [SID:1234509588]). These abstracts include data from the Company’s monoclonal antibody agonist programs targeting GITR and OX40 as well as its small molecule inhibitor programs targeting LSD1, BRD (BET), PI3Kδ and JAK1.

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"We are pleased to present the latest scientific data that underlie the potential of our emerging development portfolio at the upcoming AACR (Free AACR Whitepaper) annual meeting," stated Reid Huber, PhD, Chief Scientific Officer, Incyte. "This collection of abstracts exemplifies our discovery team’s innovative approach to cancer research, and reinforces Incyte’s commitment to the advancement of novel therapeutics which have the potential to improve and extend the lives of patients living with cancer."

In addition to these presentations, Incyte has been invited to present "IDO1 Inhibition as a Modifier of the Immune Composition of the Tumor Microenvironment and a Component of Combination Immunotherapy for Cancer," as part of an AACR (Free AACR Whitepaper) Major Symposia entitled, "Cancer Immunotherapy: Small Molecule Approaches" scheduled for Wednesday, April 20, 2016 from 10:15 a.m.–12:00 p.m., Ernest N. Morial Convention Center, Theater C, New Orleans, La.

Key abstract presentations, including Incyte-sponsored and independent investigator studies, include:

Effects of INCB052793, a Selective JAK1 Inhibitor, in Combination with Standard of Care Agents in Human Multiple Myeloma (MM) Cell Lines and Xenograft Models (Abstract #1339)
Monday April 18, 8:00 a.m.–12:00 p.m., Halls G-J, Poster Section 19

Preliminary safety, efficacy, and pharmacodynamics of a highly selective PI3Kδ inhibitor, INCB050465, in patients with previously treated B-cell malignancies (Abstract #CT056)
Monday Apr 18, 2016 1:00–5:00 p.m., Halls G-J, Poster Section 13

INCAGN01949: An anti-OX40 agonist antibody with the potential to enhance tumor specific T cell responsiveness, while selectively depleting intratumoral regulatory T cells (Abstract #3204)
Tuesday, April 19, 2016, 8:00 a.m.–12:00 p.m., Halls G-J, Poster Section 25

A novel agonist antibody (INCAGN01876) that targets the co-stimulatory receptor GITR (Abstract #3220)
Tuesday, April 19, 2016, 8:00 a.m. –12:00 p.m., Halls G-J, Poster Section 25

Activity of the BET Inhibitor INCB054329 in models of lymphoma (Abstract #3780)
Tuesday, April 19, 2016, 1:00–5:00 p.m., Halls G-J, Poster Section 16

The LSD1 inhibitor INCB059872 is synergistic with ATRA in models of non-APL acute myelogenous leukemia (Abstract #4696)
Wednesday, April 20, 2016, 8:00 a.m.–12:00 p.m., Halls G-J, Poster Section 16

Combination of BET inhibitor INCB054329 and LSD1 inhibitor INCB059872 is synergistic for the treatment of AML in vitro and in vivo (Abstract #4702)
Wednesday, April 20, 2016, 8:00 a.m.–12:00 p.m., Halls G-J, Poster Section 16

The evaluation of INCB059872, an FAD-directed Inhibitor of LSD1, in preclinical models of human small cell lung cancer (Abstract #4704)
Wednesday, April 20, 2016, 8:00 a.m.–12:00 p.m., Halls G-J, Poster Section 16

Discovery of INCB059872, a novel FAD-directed LSD1 inhibitor that is effective in preclinical models of human and murine AML (Abstract #4712)
Wednesday, April 20, 2016, 8:00 a.m.–12:00 p.m., Halls G-J, Poster Section 16

The BET inhibitor INCB054329 enhances the activity of checkpoint modulation in syngeneic tumor models (Abstract #4904)
Wednesday, April 20, 2016, 8:00 a.m.–12:00 p.m., Halls G-J, Poster Section 23

Full session details for AACR (Free AACR Whitepaper) 2016 can be found here.