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Epizyme to Present New Preclinical Data on Tazemetostat and Epigenetic Target Identification Efforts at AACR Annual Meeting

On March 29, 2017 Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage biopharmaceutical company creating novel epigenetic therapies, reported that new preclinical data on tazemetostat, Epizyme’s lead product candidate and first-in-class EZH2 inhibitor, along with other epigenetic target identification efforts, will be presented in poster sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2017 taking place in Washington, D.C., April 1-5, 2017 (Press release, Epizyme, MAR 29, 2017, View Source [SID1234518311]).

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"2017 continues to be a transformational year for Epizyme as we work to rewrite cancer treatment through novel epigenetic medicines," said Rob Bazemore, CEO of Epizyme. "We look forward to sharing these new data on tazemetostat and our innovative approach to advancing our preclinical pipeline with the oncology community at AACR (Free AACR Whitepaper)."

"As we evaluate these data, we are particularly encouraged by new research revealing the important role EZH2 plays in the proliferation of multiple myeloma, and preclinical activity of our first-in-class EZH2 inhibitor, tazemetostat, as both monotherapy and combination therapy in in vitro models of multiple myeloma," said Richard Chesworth, DPhil, senior vice president of research at Epizyme. "These findings reinforce the potential for tazemetostat as a treatment option across multiple B-cell malignancies."

Multiple myeloma is a cancer arising from terminally differentiated B-cell lymphocyte plasmablasts. Mounting evidence suggests that EZH2 is an important regulator of B-cell differentiation and may play an important role in clinical B-cell malignancies. Consistent with this role, inhibition of EZH2 alone has shown potent anti-proliferative effects in in vitro and in vivo preclinical models of multiple myeloma.

In a new study being presented at AACR (Free AACR Whitepaper), Epizyme evaluated the efficacy of tazemetostat, an EZH2 inhibitor, as monotherapy and in combination with standard of care agents in preclinical models of multiple myeloma. Tazemetostat selectively inhibited intracellular H3K27 methylation in multiple myeloma cell lines and elicited a robust anti-proliferative effect in 14-day assays. Synergistic activity was observed when tazemetostat was combined with commonly used multiple myeloma therapeutics (glucocorticoid receptor agonists and small molecule immune system modulators) when cells were treated with tazemetostat for seven days prior to the addition of the standard-of-care drugs. Based on these results, studies with selected therapeutic modalities were expanded into in vivo xenograft models to further evaluate monotherapy and combination activity of tazemetostat in multiple myeloma.

Data will also be presented from preclinical studies demonstrating synergistic activity following the addition of tazemetostat to current small molecule treatments for malignant rhabdoid tumors and atypical teratoid rhabdoid tumors, both rare and aggressive forms of cancer with high unmet medical need, typically affecting pediatric patients. In addition, Epizyme will present data demonstrating that tazemetostat induces potent and selective apoptosis in SMARCA2 and SMARCA4-deficient ovarian cell lines, which confirms SCCOHT (small cell carcinoma of the ovary hypercalcemic type) is also sensitive to CRISPR-mediated EZH2 gene ablation. These findings support Epizyme’s ongoing Phase 2 trial of tazemetostat in solid tumors, and may support future clinical evaluation in other tumor types such as lung cancers.

Details of the poster presentations are as follows:

Date & Time: Sunday, April 2, 1:00 – 5:00 p.m. ET
Title: CRISPR pooled screening of hundreds of cancer cell lines identifies differential dependencies on epigenetic pathways and synthetic lethal relationships
Abstract Number: 406/6
Location: Section 17

Date & Time: Monday, April 3, 8:00 a.m. – 12:00 p.m. ET
Title: Tazemetostat displays synergistic antiproliferative activity with backbone therapies in preclinical models of AT/RT and MRT
Abstract Number: 1944/16
Location: Section 42

Date & Time: Tuesday, April 4, 8:00 a.m. – 12:00 p.m. ET
Title: Selective killing of SMARCA2- and SMARCA4-deficient tumors by inhibition of EZH2: In vitro and in vivo preclinical models
Abstract Number: 3345/6
Location: Section 15

Date & Time: Wednesday, April 5, 8:00 a.m. – 12:00 p.m. ET
Title: Activity of the EZH2 inhibitor tazemetostat as a monotherapy and in combination with multiple myeloma therapies in preclinical models
Abstract Number: 5060/5
Location: Section 2

Cellectis to Present at the 2017 Annual Conference of the American Association for Cancer Research

On March 29, 2017 Cellectis (Paris:ALCLS) (NASDAQ:CLLS) (Alternext: ALCLS; Nasdaq: CLLS), a biopharmaceutical company focused on developing immunotherapies based on gene edited CAR T-cells (UCART), reported that data on its gene-edited allogeneic CAR T-cells will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Filing, 6-K, Cellectis, MAR 29, 2017, View Source [SID1234518310]). This includes both wholly-controlled Cellectis programs and Pfizer/Cellectis collaboration programs. The meeting will be held from April 1st to April 5th, 2017 in Washington, D.C., USA.

Cellectis presentation:

UCART22: An Allogeneic Adoptive Immunotherapy for Leukemia Targeting CD22 with CAR T-cells
Agnès Gouble1, Cécile Schiffer-Mannioui1, Séverine Thomas1, Anne-Sophie Gautron1, Laurent Poirot1, Julianne Smith2.
1Cellectis, Paris, France; 2Cellectis, New York, NY

Innate Effectors in Immunity to Cancer session – section 30
April 4, 2017, 8:00 AM – 12:00 PM Eastern Time

Pfizer/Cellectis presentations:

Allogeneic EGFRvIII Chimeric Antigen Receptor T Cells for Treatment of Glioblastoma
Oi Kwan Wong1, Mathilde Dusseaux2, Jing-Tyan Ma1, Melinda Au1, Sophie Leduc2, Joyce Chou1, Jessica M. Yu1, Marjorie Bateman1, Thomas Pertel1, Kevin C. Lindquist1, Julianne Smith3, Barbra Sasu1, Shu-Hui Liu1.
1Pfizer Inc., South San Francisco, CA; 2Cellectis, Paris, France; 3Cellectis, New York, USA

Innate Effectors in Immunity to Cancer session – section 30
April 4, 2017, 8:00 AM – 12:00 PM Eastern Time

Differential modulation of the PD-1 pathway impacts the anti-tumor activity of CAR T cells
Regina J. Lin1, Anne-Sophie Gautron2, Laurent Poirot2, Oi Kwan Wong1, Barbra Sasu1, Bijan Boldajipour1.
1Pfizer, South San Francisco, CA; 2Cellectis, Paris, France; 3Cellectis, New York, USA

Late-Breaking Research: Immunology session – section 35
April 4, 2017, 8:00 AM – 12:00 PM Eastern Time

Collaboration with Pfizer

In June 2014, Cellectis and Pfizer began collaborating on a joint clinical development program for UCAR-T therapies, in the field of oncology, directed at numerous targets selected by Pfizer and several targets selected by Cellectis.

Aeglea BioTherapeutics to Present Preclinical Data for AEB1102 at 2017 AACR Annual Meeting

On March 29, 2017 Aeglea BioTherapeutics, Inc. (NASDAQ:AGLE), a biotechnology company committed to developing enzyme-based therapeutics in the field of amino acid metabolism to treat rare genetic diseases and cancer, reported that it will deliver a poster presentation at the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 1 – 5 in Washington, DC (Press release, Aeglea BioTherapeutics, MAR 29, 2017, View Source [SID1234518308]).

Full abstracts are available online at www.aacr.org. Details of the poster presentation are listed below: Title: Reducing systemic arginine with arginase (AEB1102) therapy does not suppress the immune response induced by anti-PD-1 and anti-PD-L1, and exerts an additive anti-tumor and synergistic survival benefit

Abstract Number: 3964
Session Title: Tumor Microenvironment 5
Date: Tuesday, April 4
Presentation Time: 8 a.m. – 12 p.m. ET
Location: Walter E. Washington Convention Center, Halls A-C, Poster Section 42

Novartis announces first CAR-T cell therapy BLA for pediatric and young adult patients with r/r B-cell ALL granted FDA Priority Review

On March 29, 2017 Novartis reported that the US Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA) filing and granted priority review for CTL019 (tisagenlecleucel-T), an investigational chimeric antigen receptor T cell (CAR-T) therapy, in relapsed and refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL) (Press release, Novartis, MAR 29, 2017, View Source [SID1234518306]). This is the first BLA submission by Novartis for a CAR-T. The priority review designation is expected to shorten the anticipated review time by the FDA.

CAR-T is different from typical small molecule or biologic therapies currently on the market because it is manufactured for each individual patient. During the treatment process, T cells are drawn from a patient’s blood and reprogrammed in the laboratory to create T cells that are genetically coded to hunt the patient’s cancer cells and other B-cells expressing a particular antigen.

"With CTL019, Novartis is at the forefront of the science and development of immunocellular therapy as a potential new innovative approach to treating certain cancers where there are limited options," said Vas Narasimhan, Global Head of Drug Development and Chief Medical Officer, Novartis. "The priority review and file acceptance of CTL019 by the FDA brings us one step closer to delivering this novel treatment option to children and young adults with r/r B-cell ALL in the United States."

CTL019 was first developed by the University of Pennsylvania. In 2012, Novartis and the University of Pennsylvania entered into a global collaboration to further research, develop and then commercialize CAR-T cell therapies for the investigational treatment of cancers, including CTL019. Through the collaboration, Novartis holds the worldwide rights to CARs developed through the collaboration with the University of Pennsylvania for all cancer indications.

"The past five years have seen tremendous progress in the development and application of cellular engineering in an effort to personalize the treatment of cancer," said the Penn team’s leader, Carl June, MD, director of the Center for Cellular Immunotherapies in the Perelman School of Medicine at the University of Pennsylvania. "We now know that it is possible to treat patients in clinical trials across the world using this approach, and the results we have observed mark a potential new paradigm in the treatment of blood cancers that have not responded to standard therapies."

The priority review designation and BLA submission for CTL019 is based on the results from the Novartis-sponsored ELIANA study (NCT02435849), the first global CAR-T cell trial with study enrollment having occurred across 25 centers in the US, EU, Canada, Australia and Japan. In the Phase II study, 82% (41 of 50) of patients infused with CAR-T cells achieved complete remission or complete remission with incomplete blood count recovery at three months post CTL019 infusion. The data were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) meeting in December 2016 (Abstract #221)[1].

Forty-eight percent of patients in the ELIANA trial experienced grade 3 or 4 cytokine release syndrome (CRS), a known complication of an investigational therapy that may occur when the engineered cells become activated in the patient’s body. CRS was managed per protocol on a global scale using prior site education with implementation of the CRS treatment algorithm. There were no deaths due to CRS. Fifteen percent of patients experienced grade 3 neurological and psychiatric events including confusion, delirium, encephalopathy, agitation and seizure. No cerebral edema was reported and no grade 4 neurological and psychiatric events were observed[1].

The submission is also supported by findings from a US multicenter trial and an earlier single site trial led by the Children’s Hospital of Philadelphia (CHOP) examining the safety and efficacy of CTL019 among pediatric and young adult patients with r/r B-cell ALL. Stephan Grupp, MD, PhD, from CHOP was the lead investigator of the trials.

"Even if a patient has difficult-to-treat relapsed/refractory leukemia, we have seen treatment with CTL019 in clinical trials put cancer into remission," said Grupp, Director of the Cancer Immunotherapy Frontier Program and Director of Translational Research for the Center for Childhood Cancer Research at CHOP. "This could be a first-of-its-kind treatment with exciting potential to help pediatric and young adult r/r B-cell ALL patients."

Acute lymphoblastic leukemia makes up approximately 25% of cancer diagnoses among children under 15 years old and is the most common childhood cancer in the US[2]. Patients with r/r ALL have limited treatment options, and the chance of survival for children with the disease who relapse or fail to attain remission is between 16% to 30%[3].

According to the FDA guidelines, Priority Review status may potentially shorten the window for the agency to take action on an application to within six months of the filing acceptance compared to a standard review. The designation aims to prioritize the evaluation of products that have the potential to provide significant improvements in the treatment, diagnosis or prevention of serious conditions when compared to standard applications. CTL019 previously received Breakthrough Therapy designation from the FDA for the treatment of patients with r/r ALL.

Novartis plans additional filings for CTL019 in the US and EU markets later this year, including a BLA with the FDA for treatment of adults with r/r diffuse large B-cell lymphoma (DLBCL) and applications for marketing authorization with the European Medicines Agency in r/r B-cell ALL and r/r DLBCL.

Because CTL019 is an investigational therapy, the safety and efficacy profile has not yet been established. Access to investigational therapies is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the therapy. Because of the uncertainty of clinical trials, there is no guarantee that CTL019 will ever be commercially available anywhere in the world.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by words such as "priority review," "commitment," "investigational," "plans," "expected," "potential," "possible," "may," "could," "potentially," "aims to," "designed to," "will," or similar terms, or by express or implied discussions regarding potential additional filings or potential marketing approvals for CTL019, or regarding potential future revenues from CTL019. You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that CTL019 will be submitted or approved for sale in any market, or at any particular time. Nor can there be any guarantee that CTL019 will be commercially successful in the future. In particular, management’s expectations regarding CTL019 could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; the company’s ability to obtain or maintain proprietary intellectual property protection; general economic and industry conditions; global trends toward health care cost containment, including ongoing pricing pressures; safety, quality or manufacturing issues, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

FDA Advisory Committee Provides Unanimous Recommendation For Subcutaneous Rituximab Coformulated With Halozyme Enhanze Technology

On March 29, 2017 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported that an Oncologic Drug Advisory Committee of the U.S. Food and Drug Administration voted 11 to 0 that the benefit/risk of rituximab/hyaluronidase for subcutaneous (under the skin) injection was favorable for patients in the proposed indications of follicular lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia (Press release, Halozyme, MAR 29, 2017, View Source [SID1234518305]). The FDA action date is June 26, 2017.

"We are pleased with the support from today’s advisory committee," said Dr. Helen Torley, president and chief executive officer. "Upon approval, subcutaneous rituximab would offer a new treatment option for U.S. patients that could reduce the administration time for the rituximab portion of their treatment to 5 to 7 minutes as compared with an hour and a half or more for intravenous administration."

Efficacy, safety, pharmacokinetic and patient-reported outcome data from five clinical studies presented by Genentech, a member of the Roche Group, at today’s advisory committee meeting supported the rituximab SC application.

Rituximab co-formulated with Halozyme’s recombinant human hyaluronidase was approved in Europe in 2014 and is currently marketed as the subcutaneous (SC) formulation of MabThera (rituximab) in approximately 50 countries worldwide.