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Epizyme to Present New Data in Support of Tazemetostat Clinical Development Program

On March 17, 2016 Epizyme, Inc. (NASDAQ:EPZM), a clinical stage biopharmaceutical company creating novel epigenetic therapies for cancer patients, reported that data from five accepted abstracts of tazemetostat (EPZ-6438), its clinical stage inhibitor of EZH2, will be presented during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016 being held April 16-20 in New Orleans (Press release, Epizyme, MAR 17, 2016, View Source [SID:1234509613]).

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Tazemetostat is a first-in-class EZH2 inhibitor currently in phase 2 studies in advanced B-cell non-Hodgkin lymphoma (NHL) and certain genetically defined solid tumors. Among the data to be presented at the meeting are studies on the food effect and drug interaction characteristics of tazemetostat.

"We are pleased to be able to present these important new data, including mechanism of action and biomarker studies that continue to guide us in developing patient selection criteria for tazemetostat," said Peter Ho, M.D., Ph.D., Chief Medical Officer, Epizyme. "Additionally, the clinical pharmacology studies being presented have helped to more fully inform the dosing of patients in our ongoing clinical programs."

Planned Presentations:

Evidence of EZH2 Dependent and Independent Mechanisms of Tazemetostat Treatment Emergent Resistance in Models of Diffuse Large B Cell Lymphoma

Speaker: Carly T. Campbell, Epizyme, Inc.
Session Title: Mechanisms of Drug Resistance 1
Abstract Number: 312
Poster Number: 23
Presentation Time: Sunday, April 17, 2016, 1:00 PM – 5:00 PM

Development and Application of a 62-gene Panel for Assessment of Somatic Sequence and Structural Variants in Tumor DNA Derived from non-Hodgkin Lymphoma Patients Treated in a Phase 1 Clinical Trial with the EZH2 Inhibitor Tazemetostat

Speaker: Scott R. Daigle, Epizyme, Inc.
Session Title: Genomic Profiling of Cancers
Abstract Number: 137
Poster Number: 21
Presentation Time: Sunday, April 17, 2016, 1:00 PM – 5:00 PM

The Effect of Tazemetostat on CYP3A-mediated Metabolism of Midazolam in Patients with Solid Tumors

Speaker: Sherri Smith
Session Title: Phase I Clinical Trials in Progress
Abstract Number: CT029
Poster Number: 10
Presentation Time: Monday April 18, 2016 8:00 AM – 12:00 PM

The Effect of Food on the Pharmacokinetics of Tazemetostat in patients with Cancer

Speaker: Benjamin Suttle
Session Title: Phase I Clinical Trials in Progress
Abstract Number: CT031
Poster Number: 12
Presentation Time: Monday April 18, 2016 8:00 AM – 12:00 PM

The Effect of EPZ011989, an Enhancer of Zeste Homolog 2 Inhibitor, in Acute Myeloid Leukemia

Speaker: Sydney Fobare, Hendrix College, Conway, AR
Session Title: Histone Modifications and Chromatin Dynamics
Abstract Number: 4520
Poster Number: 7
Presentation Time: Wednesday, April 20, 8:00 AM – 12:00 PM

About EZH2 in Cancer

EZH2 is a histone methyltransferase (HMT) that is increasingly understood to play a potentially oncogenic role in a number of cancers. These include non-Hodgkin lymphoma, INI1-negative cancers such as malignant rhabdoid tumors and epithelioid sarcomas, certain SMARCA4-negative solid tumors, synovial sarcoma, and a range of other solid tumors.

About Tazemetostat

Epizyme is developing tazemetostat for the treatment of patients with non-Hodgkin lymphoma and for patients with certain genetically defined solid tumors. Tazemetostat is a first-in-class small molecule inhibitor of EZH2 created by Epizyme using its proprietary product platform. In some human cancers, aberrant EZH2 enzyme activity results in dysregulation of genes that control cell proliferation resulting in the rapid and unconstrained growth of tumor cells. Tazemetostat is the WHO International Non- Proprietary Name (INN) for compound EPZ-6438.

Additional information about tazemetostat, including clinical trial information, can be found here.

OncoMed Initiates Phase 1b Immuno-Oncology Combination Clinical Trial for Demcizumab and Pembrolizumab (anti-PD1)

On March 17, 2016 OncoMed Pharmaceuticals, Inc. (NASDAQ:OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported dosing of the first patient in its Phase 1b clinical trial of OncoMed’s investigational agent demcizumab (anti-DLL4, OMP-21M18), with Merck’s anti-Programmed Cell Death 1 (PD1) therapy pembrolizumab (KEYTRUDA) (Press release, OncoMed, MAR 17, 2016, View Source [SID:1234509608]).

The combination of these agents may act as a double blockade for cancer-induced immune suppression with potential application to a number of solid tumor cancers.

The Phase 1b clinical trial is enrolling patients with advanced or metastatic solid tumors to receive escalating dose cohorts of demcizumab plus an approved dose of pembrolizumab. Once an optimal combination dose is established, three expansion study cohorts will be enrolled in non-small cell lung cancer (NSCLC), anti-PD1 refractory solid tumors and castrate-resistant prostate cancer.

The primary objective of the trial is to determine the safety and tolerability of the demcizumab-pembrolizumab combination. The trial will also look at comparative pharmacokinetic profiles, incidence of antibodies against demcizumab or pembrolizumab, biomarker and immunological response, response rates and survival outcome in patients with advanced solid tumors, NSCLC, castrate-resistant prostate cancer and anti-PD1 antibody refractory cancers.

"We’ve designed the Phase 1b study to investigate the safety profile for the demcizumab and pembrolizumab combination and to look for signals of immunological, biomarker and anti-tumor activity in advanced solid tumors," said Jakob Dupont, M.D., OncoMed’s Chief Medical Officer. "Based on our preclinical studies, we believe demcizumab may have a distinctive immune modulatory effect of decreasing monocytic myeloid-derived suppressor cells, or MDSCs, within patient tumors. MDSCs are important cells that prevent a patient’s immune system from fighting their cancer, even in the setting of the new anti-PD1 treatments. In our preclinical studies, we have observed synergistic anti-tumor activity when combining anti-DLL4 and anti-PD1, which we attribute to their complementary mechanisms. We look forward to testing this novel combination in the clinic with the study investigators."

At the American Association of Cancer Research Annual Meeting in 2015, OncoMed reported on the impact of an anti-DLL4 and anti-PD1 on antitumor immune responses in preclinical studies. The combination of anti-DLL4 and anti-PD1 was found to have more potent antitumor and enhanced immuno-oncology activity than either agent alone. In addition to the synergistic anti-cancer immune responses observed, the combination of anti-DLL4 and anti-PD1 reduced tumor growth in re-implantation experiments, suggesting a more profound memory immune response was induced by the combination than either anti-DLL4 or anti-PD1 alone.

The Phase 1b combination study will be conducted at several sites in the U.S. and U.K., including Memorial Sloan Kettering Cancer Center, Columbia University, START Center for Cancer Care, University of Michigan Medical Center, Sarah Cannon Research Institute, University of California San Francisco, Rocky Mountain Cancer Centers and The Royal Marsden Hospital. Patients interested in participating in one of OncoMed’s clinical trials may learn more by calling 1-866-914-7347 or emailing [email protected].

About Demcizumab (anti-DLL4, OMP-21M18)
Demcizumab is a humanized monoclonal antibody targeting Delta-like Ligand 4 (DLL4), a key member of the Notch signaling pathway. Based on preclinical studies, demcizumab appears to have a multi-pronged mechanism of action: halting cancer stem cell growth and reducing cancer stem cell frequency, disrupting angiogenesis in the tumor and augmenting anti-tumor immune responses by decreasing tumor myeloid-derived suppressor cells (MDSCs).

In addition to the multi-arm demcizumab plus pembrolizumab Phase 1b clinical trial, demcizumab is currently being studied in two randomized Phase 2 clinical trials. The YOSEMITE trial is testing demcizumab with gemcitabine plus Abraxane versus gemcitabine plus Abraxane in first-line advanced pancreatic cancer patients. The DENALI trial is testing demcizumab with pemetrexed and carboplatin versus pemetrexed and carboplatin alone in first-line advanced non-small cell lung cancer patients. Demcizumab is part of OncoMed’s collaboration with Celgene Corporation.

Kite Pharma Announces Clinical Collaboration to Evaluate Two Novel Immunotherapies for Patients with Non-Hodgkin Lymphoma

On March 17, 2016 Kite Pharma, Inc. (Nasdaq:KITE) reported that it has entered into a clinical trial collaboration with Genentech, a member of the Roche Group, to evaluate the safety and efficacy of KTE-C19, in combination with atezolizumab (also known as MPDL3280A), in patients with refractory, aggressive non-Hodgkin lymphoma (NHL) (Press release, Kite Pharma, MAR 17, 2016, View Source [SID:1234509602]).

KTE-C19 is an investigational immunotherapy in which a patient’s T cells are genetically modified to express a CAR designed to target the antigen CD19, a protein expressed on the cell surface of B cell lymphomas and leukemias. Atezolizumab is an investigational monoclonal antibody designed to target and bind to a protein called PD-L1, which is expressed on tumor cells and tumor-infiltrating immune cells. PD-L1 interacts with PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T cells. Use of the two compounds in combination could provide a synergistic effect since inhibiting PD-L1 with atezolizumab may enhance and prolong the activity and proliferation of KTE-C19.

"Kite is a pioneer in engineered T cell therapy, and we are excited to collaborate with Genentech, an industry leader with a history of developing transformative therapies for cancer," said Arie Belldegrun, M.D., FACS, Chairman, President and Chief Executive Officer of Kite. "KTE-C19 is currently in four pivotal studies and early clinical findings have shown a potential for breakthrough efficacy in refractory, aggressive NHL and other B cell malignancies. The scientific rationale for combining KTE-C19 and atezolizumab in refractory, aggressive NHL is compelling, and could potentially lead to opportunities to advance this combination in other indications."

A multi-center Phase 1b/2 study is expected to begin in 2016. The study will use the same KTE-C19 dose and regimen as Kite’s ongoing, potential registration study (ZUMA-1) in patients with refractory, aggressive NHL. Kite will be the sponsor of the study, and the results will be used to evaluate options for further development of the combination.

About KTE-C19

KTE-C19 is an investigational therapy in which a patient’s T cells are genetically modified to express a CAR designed to target the antigen CD19, a protein expressed on the cell surface of B cell lymphomas and leukemias. Kite is currently enrolling four pivotal studies (also known as ZUMA studies) for KTE-C19 in patients with various B cell malignancies. The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation status to KTE-C19, for the treatment of patients with refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B cell lymphoma (PMBCL), and transformed follicular lymphoma (TFL). KTE-C19 has also secured Orphan Drug Designation in the U.S. for DLBCL and in the EU for various hematological indications.

Deciphera Pharmaceuticals to Present Data on its Highly-Selective Small Molecule CSF1R Immunokinase Inhibitor, DCC-3014, at American Association for Cancer Research Annual Meeting 2016

On March 17, Deciphera Pharmaceuticals, a clinical-stage biotechnology company focused on developing advanced kinase inhibitor treatments targeting the tumor cell and the tumor microenvironment, reported that an abstract highlighting the company’s highly-selective small molecule CSF1R inhibitor, DCC-3014, has been selected for presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016, taking place April 16-20, 2016 in New Orleans (Press release, Deciphera Pharmaceuticals, MAR 17, 2016, View Source [SID:1234509598]).

DCC-3014 was designed as a highly-specific macrophage immunomodulatory agent based on the company’s Switch Control Inhibitor platform. In preclinical cancer models, DCC-3014 was shown to significantly enhance anti-tumor activity when used in combination with an anti-PD-1 checkpoint inhibitor. Deciphera expects to initiate a Phase 1 clinical trial of DCC-3014 in the second half of 2016.

"We are pleased to present data at the AACR (Free AACR Whitepaper) Annual Meeting 2016 demonstrating DCC-3014’s robust inhibition of the CSF1R kinase, both as a single agent and in combination with an anti-PD1 inhibitor, across a number of cancer models," said Michael D. Taylor, Ph.D., Deciphera’s President and Chief Executive Officer. "We look forward to initiating the first-in-human Phase 1 trial with DCC-3014 later this year."

Details of the Poster Presentations on DCC-3014:
Poster Title: The highly specific CSF1R inhibitor DCC-3014 exhibits immunomodulatory and anti-invasive activities in cancer models
Author: Smith, Bryan D.
Abstract #: 4889
Session: Immune Modulating Agents 2
Date & Time: Wednesday, April 20, 2016, 8:00 AM – 12:00 PM
Location: Halls G-J, Poster Section 2. Poster Board #30

Cellectis and MabQuest Announce Immunotherapy Partnership on New Class of PD-1 Antagonist Monoclonal Antibodies

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]).

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.