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Unum Therapeutics to Present New Data on its Antibody-Coupled T Cell Receptor (ACTR) Platform at the Upcoming American Association for Cancer Research (AACR) 2017 Annual Meeting

On April 3, 2017 Unum Therapeutics, a clinical stage biopharmaceutical company developing a universal cellular immunotherapy to treat multiple cancers, reported that the Company has been selected for two poster presentations on its Antibody-Coupled T cell Receptor (ACTR) platform at the AACR (Free AACR Whitepaper) 2017 Annual Meeting, which is being held in Washington DC, April 1-5, 2017 (Press release, Unum Therapeutics, APR 3, 2017, View Source [SID1234518436]). The first poster presentation will highlight data from non-clinical studies on targeting BCMA-positive multiplemyeloma cells with ACTR in combination with a humanized non-fucosylated anti-BCMA antibody, SEA-BCMA, developed using Seattle Genetics’ novel sugar-engineered antibody (SEA) technology. This is the first named program under Unum’s global collaboration with Seattle Genetics. The second poster will provide data from exploratory work on targeting Glypican-3 (GPC3) with ACTR in combination with an anti-GPC3 antibody, one of the targets that the companies are also investigating under their collaboration.

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The accepted abstracts are listed below and are available online on the AACR (Free AACR Whitepaper) 2017 conference website: www.aacr.org.

Presentation Details:

Abstract Number: 4605
Title: Efficient targeting of BCMA-positive multiple myeloma cells by Antibody-Coupled T cell Receptor (ACTR) engineered autologous T cells in combination with an anti-BCMA antibody
Authors: Tooba Cheema, Taylor Hickman, Katie O’Callaghan, *Lori Westendorf, *Luke Manlove, *Shyra Gardai, Allison Nelson, Ryan Boomer, Kathleen McGinness, Birgit Schultes, Seth Ettenberg, *Django Sussman and Heather Huet.
Authors’ Affiliation: Unum Therapeutics, *Seattle Genetics
Presenter: Tooba Cheema, Senior Scientist, Unum Therapeutics
Session: Immunoconjugates and Antibodies
Session Date and Time: April 4, 2017, 1:00 – 5:00 PM
Location: Convention Center, Halls A-C, Poster Section 26
Poster Board Number: 20

Abstract Number: 3762
Title: Superior T cell activity of a membrane-proximal binding antibody when targeting Glypican-3 with an Antibody-Coupled T cell Receptor (ACTR) armed T cell
Authors: Greg Motz, John Shin, Kathy Whiteman, Birgit Schultes, Tapasya Pai, Lori Westendorf*, Seth Ettenberg, Travis Biechele*, Django Sussman* and Heather Huet
Authors’ Affiliation: Unum Therapeutics, *Seattle Genetics
Presenter: Greg Motz, Senior Scientist, Unum Therapeutics
Session: Innate Effectors in Immunity to Cancer
Session Date and Time: April 4, 2017, 8:00 – 12:00 PM
Location: Convention Center, Halls A-C, Poster Section 30
Poster Board Number: 18

The posters will be posted on Unum’s website following the presentations.

About Antibody-Coupled T cell Receptor (ACTR) Technology

Unum’s proprietary ACTR is a chimeric protein that combines components from receptors normally found on two different human immune cell types – natural killer (NK) cells and T cells – to create a novel approach to cancer cell killing. T cells bearing the ACTR receptor protein can be directed to attack a tumor by combining with a monoclonal antibody that binds antigens on the cancer cell surface.

In contrast to other T cell therapy approaches for cancer that are limited to a single cancer cell surface target and, therefore, treat a narrow set of tumors, Unum’s approach is not restricted by a specific tumor cell antigen and, thus, may have applications for treating many different types of cancers when combined with the right antibody.

Unum is developing ACTR in combination with a range of tumor-targeting antibodies for use in both hematologic and solid tumor indications. ACTR087, Unum’s most advanced product candidate, combines Unum’s proprietary ACTR with rituximab, an anti-CD20 antibody. The ACTR087 study is the first clinical trial using a viral vector to permanently insert the ACTR gene into the genome of patients’ T cells.

SYROS PRESENTS NEW PRECLINICAL DATA AT AACR SHOWING ANTI-TUMOR ACTIVITY OF SY-1365, ITS FIRST-IN-CLASS SELECTIVE CDK7 INHIBITOR, IN MULTIPLE DIFFICULT-TO-TREAT SOLID TUMORS

On April 3, 2017 Syros Pharmaceuticals (NASDAQ:SYRS), a biopharmaceutical company pioneering the discovery and development of medicines to control the expression of disease-driving genes, reported that SY-1365, its first-in-class selective cyclin-dependent kinase 7 (CDK7) inhibitor, shows significant anti-proliferative activity in multiple in vitro and in vivo models of difficult-to-treat solid tumors, including triple negative breast, small cell lung and ovarian cancers (Press release, Syros Pharmaceuticals, APR 3, 2017, View Source [SID1234518435]). Leveraging its expertise in transcriptional biology and chemistry, Syros also showcased its work to further elucidate the biology of cyclin-dependent kinase 12 (CDK12) and cyclin-dependent kinase 13 (CDK13), advancing its aim of designing the first highly selective CDK12 and CDK13 inhibitors suitable for clinical development. These data were presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Washington, D.C.

"SY-1365, our first-in-class selective CDK7 inhibitor, as well as our CDK12 and CDK13 inhibitor program highlight the power of our gene control platform to selectively target transcription and potentially treat diseases that have been underserved by other genomic-based approaches," said Nancy Simonian, M.D., Chief Executive Officer of Syros. "These new data show SY-1365 reduces proliferation and induces apoptosis in cancer cells in several difficult-to-treat tumors. The results build on earlier data demonstrating that SY-1365 preferentially kills cancer cells over non-cancerous cells and lowers the expression of disease-driving transcription factors. Our CDK12 and CDK13 inhibitor program further highlights the potential of our platform to produce drug candidates that target the transcription of unique sets of genes linked to specific tumors."

SY-1365 in Aggressive Transcriptionally Driven Solid Tumors
Data generated and presented by Syros scientists show SY-1365 induces anti-proliferative and pro-apoptotic effects in multiple solid tumor cell lines and preclinical models of aggressive, transcriptionally driven solid tumors. Results from these studies show SY-1365:

Induces potent anti-proliferative activity in a range of solid tumor cell lines, including triple negative breast, small cell lung and ovarian cancer cells, when profiled across a broad panel of more than 130 cancer cell lines.
Demonstrates substantial anti-tumor activity in both cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models of triple negative breast cancer, including regressions at a twice weekly dosing regimen consistent with the initial regimen planned for the Company’s upcoming Phase 1 clinical trial.
Demonstrates synergistic anti-tumor activity with a BCL-2 inhibitor in cancer cells, providing a mechanistic rationale for further investigating SY-1365 in combination with inhibitors targeting apoptotic pathways.
SY-1365 has been previously shown to induce apoptosis and preferentially kill cancer cells over non-cancerous cells in preclinical models of a range of aggressive cancers, including certain solid tumors and acute leukemias. Preclinical studies have also shown that SY-1365 lowers the expression of oncogenic transcription factors, such as MYC, in these transcriptionally driven cancers.

Syros is on track to begin a Phase 1 clinical trial of SY-1365 in the second quarter, initially in patients with advanced solid tumor malignancies including the transcriptionally driven solid tumors, triple negative breast, small cell lung and ovarian cancers. Syros plans to expand future clinical development of SY-1365 into acute leukemias based on data generated in this trial.

CDK12 and CDK13 Inhibition as Promising New Approach for Treating Cancer
Syros scientists presented data on the selective inhibition of CDK12 and CDK13 in ovarian and breast cancers. Using its gene control platform, Syros is optimizing potent and selective CDK12 and CDK13 inhibitors that may be suitable for clinical development. Syros scientists presented data on a suite of proprietary assays capable of assessing selectivity and cellular target engagement of CDK12. Using breast and ovarian cancer cell lines sensitive to CDK12 inhibition, Syros scientists further showed important differences between non-selective and selective inhibition of transcriptional kinases to guide development of these inhibitors.

Selectively inhibiting CDK12 and CDK13 has previously been shown to decrease the expression of DNA damage response genes and super-enhancer associated transcription factors implicated in cancer, including breast and ovarian cancers. These findings suggest that a selective CDK12 and CDK13 inhibitor could be effective as a monotherapy in certain cancers and as a combination therapy in other cancers by increasing their susceptibility to targeted therapies involved in DNA damage repair, such as PARP1 inhibitors.

Ipsen Completes Acquisition of ONIVYDE® (irinotecan liposome injection) and Additional Oncology Assets from Merrimack Pharmaceuticals

On April 3, 2017 Ipsen reported that it has completed its acquisition of global oncology assets from Merrimack Pharmaceuticals, in Cambridge, MA., focusing on ONIVYDE (irinotecan liposome injection) for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy, in combination with fluorouracil and leucovorin (Press release, Ipsen, APR 3, 2017, View Source [SID1234518434]).1,[1] Ipsen has gained exclusive commercialization rights for the current and potential future indications for ONIVYDE in the U.S., as well as the current licensing agreements with Shire for commercialization rights ex-U.S. and PharmaEngine for Taiwan. The acquisition also includes the Merrimack commercial and manufacturing infrastructure for Onivyde, and generic doxorubicin HCl liposome injection.

"The addition of ONIVYDE to Ipsen’s Oncology portfolio is very important, first and foremost for patients with pancreatic cancer across the U.S., as there are limited approved therapies," said Cynthia Schwalm, Executive Vice President and President, North American Commercial Operations, Ipsen. "Together with our experienced commercial and medical teams and the legacy we have gained through the acquisition of ONIVYDE, we are confident in our ability to meet the growing needs of these patients."

Along with this acquisition, Ipsen will continue to advance the clinical development program for ONIVYDE.

Financial terms of the acquisition include an upfront cash payment of $575 million to Merrimack Pharmaceuticals, and up to $450 million upon the approval of potential additional indications for ONIVYDE in the U.S.

About Pancreatic Cancer

Pancreatic cancer is a rare and deadly disease with approximately 338,000[2] new patients diagnosed globally each year, approximately 50,000 of which are in the United States[3]. More than half are diagnosed with metastatic disease, which has an overall 5-year survival rate of less than three percent4, and often rapidly progresses during or shortly after receiving chemotherapy[4]. Pancreatic cancer is the 3rd leading cause of cancer-related death in the United States, surpassing breast cancer.4 It is expected to become the 2nd leading cause of cancer-related death in the U.S. by the year 2030, surpassing colorectal cancer.4,[5]

About ONIVYDE

ONIVYDE is an encapsulated formulation of irinotecan. This long-circulating liposomal form is designed to increase length of tumor exposure to both irinotecan and its active metabolite, SN-38. ONIVYDE was approved by the U.S. FDA in combination with fluorouracil and leucovorin for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy. For full prescribing information, including Boxed WARNING, please visit www.ONIVYDE.com.

Oncodesign presents its latest scientific developments at the AACR annual global meeting on oncology

On April 3, 2017 ONCODESIGN (FR0011766229 – ALONC), a biotechnology company serving the pharmaceutical industry in the discovery of new therapeutic molecules to fight cancer and other serious illnesses with no known effective treatment, reported that it will present its latest scientific developments at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2017 held on April 1-5, in Washington DC, USA (Press release, Oncodesign, APR 3, 2017, View Source [SID1234518433]).

The AACR (Free AACR Whitepaper) is the largest global organisation that brings together public and private actors involved in cancer research. Its annual meetings attract every year over 18,000 researchers from the industry and academia.

On this occasion, Oncodesign will present several of its recent scientific developments:

As part of the IMODI project, Oncodesign will present a poster on one of the more important collections of extensively characterised predictive models for pancreatic cancer in the world. The collection of breast cancer models, particularly documented and representative of the human disease, caught the attention of the organisers of the AACR (Free AACR Whitepaper) meeting and will be presented during a dedicated conference on April 4, 2017. According to the INCA study, breast cancer is the cancer with highest incidence in women, with over 54,000 new cases each year in France.
As part of the IMAkinib project, Oncodesign will present the preclinical, cellular and in vivo imaging results obtained with its first PET-tracer generated by the Nanocyclix technology, currently in phase 1 of its development in patients with non-small cell lung cancer.
Oncodesign will also present the results of its Experimentation’s research activities on a new immunotherapy formulation conducted for the US company Checkmate Pharmaceuticals (Cambridge, MA). Remarkable efficacy results have been obtained, in combination with immune checkpoint modulators, in several cancer indications.
Finally, Oncodesign will describe in a fourth poster Experimentation’s internal research conducted on the resistance to PD-11 blockade. Antibodies targeting PD-1 have been recently approved as second line treatments for several types of cancer (urethra, kidney, head and neck, Hodgkin’s lymphoma), or as first line treatment for metastatic melanoma and metastatic non-small cell lung cancer. In spite of the positive response rates and increased survival in the majority of treated patients, a resistance phenomenon develops in certain patients. The Oncodesign research presented at the AACR (Free AACR Whitepaper) meeting aims to develop combination strategies to overcome such resistance and to identify biomarkers. This research showcases complex data analyses, such as cytokine profiles studied in syngeneic models.
Jan Hoflack, Ph.D., Chief Scientific Officer of Oncodesign, said: "Being represented in this way in one of the largest global medical meetings on oncology is a privilege, which provides unparalleled visibility to Oncodesign. This reinforces further the reputation of Oncodesign in terms of its research quality, upheld by the commitment of all our teams to promote the discovery of more effective new drugs."

Full details on Oncodesign presentations during the AACR (Free AACR Whitepaper) meeting:

Abstract n°5169: "Overcoming pd1 targeting antibody resistance using combination strategies"
Presentation: Dr. Jean-François Mirjolet (Oncodesign, Dijon, France)
Poster session/Section: Poster Section 28
Date: April 3, 2017
Time: 8:00am – 12:00pm EDT
Venue: Convention Center, Halls A-C

Abstract n°52217: "Preclinical proof of concept for the first Nanocyclix TKI-PET radiotracer targeting activated EGFR positive lung tumors"
Presentation: Dr. Francis Bichat (Oncodesign, Dijon, France)
Poster session/Section: Poster Section 39
Date: April 3, 2017
Time: 8:00am – 12:00pm EDT
Venue: Convention Center, Halls A-C

Abstract n°28: "Antitumor activity of the CMP-001 (TLR9 agonist) alone or combined with immune modulators in syngeneic tumor models"
Presentation: Dr. Aaron Morris (Checkmate Pharmaceuticals, Boston, US) and
Dr Sylvie Maubant (Oncodesign, Dijon, France)
Poster session/Section: Poster Section 26
Date: April 3, 2017
Time:
1:00pm – 5:00pm EDT
Venue: Convention Center, Halls A-C

Abstract n°3846: "Imodi initiative: A novel holistic and integrative approach with patient-derived tumor models against pancreatic cancer"
Presentation: Dr. Juan Iovanna (Inserm U1068, Marseille, France)
Poster session/Section: Poster Section 37
Date: April 4, 2017
Time: 8:00am – 12:00pm EDT
Venue: Convention Center, Halls A-C

Abstract n°5015: "Innovative and predictive models against breast cancer"
Presentation: Dr. S. Tabonne (Leon Berard clinical center, Lyon, France)
Section: Tumor biology Minisymposium session
Date: April 4, 2017
Time:
3:00pm – 5:00pm EDT

OncoSec Presents Preclinical Data Demonstrating Improved Systemic Anti-Tumor Response Following Modifications to IL-12 Gene Delivery Therapy at AACR Annual Meeting

On April 3, 2017 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported a poster titled "Intratumoral Delivery of a P2A-linked Bicistronic IL-12 Construct Leads to High Intratumoral Expression and Systemic Anti-tumor Response" (Abstract ID # 1614) at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, in Washington, D.C (Press release, OncoSec Medical, APR 3, 2017, View Source [SID1234518431]). The poster included preclinical data demonstrating the latest developments of OncoSec’s gene delivery platform in a murine melanoma model.

Previous studies have shown the use of immunomodulatory cytokines is effective in the regression of a wide range of tumors. However, systemic delivery of recombinant cytokines has often resulted in life-threatening adverse effects. Intratumoral gene electrotransfer of plasmid encoded interleukin-12 (IL-12) has shown acceptable safety and efficacy profiles in regressing tumors, both preclinically and clinically.

"We sought to optimize the anti-tumor immune response of our IL-12 immunotherapy platform that combines intratumoral injection of plasmid DNA coding for IL-12 and electroporation. Using a mouse model of melanoma, we were able to demonstrate that the changes made to plasmid design and to electroporation parameters can significantly increase production of IL-12, leading to an improved anti-tumor effect," said Punit Dhillon, OncoSec President and CEO. "The new IL-12 construct is the backbone of our next generation combination molecules."

Copies of the abstract are available and can be viewed on the AACR (Free AACR Whitepaper) website at View Source!/4292/presentation/6375. The poster is available in the Publications section of OncoSec’s website.