On May 18, 2017 Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage biopharmaceutical company creating novel epigenetic therapies, reported positive interim data on its first-in-class EZH2 inhibitor, tazemetostat, from the epithelioid sarcoma cohort of its ongoing Phase 2 study in adult patients with molecularly defined solid tumors (Press release, Epizyme, MAY 18, 2017, View Source [SID1234519211]). In addition, the Company announced that it recently conducted a positive meeting with the U.S. Food and Drug Administration (FDA) to discuss the registration strategy for tazemetostat for the treatment of epithelioid sarcoma. Based on discussions with the FDA, the Company has identified a path to submission for accelerated approval of tazemetostat based on the 60-patient cohort from its Phase 2 study, and will target a New Drug Application (NDA) submission in 2018.

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An interim assessment of the epithelioid sarcoma cohort of patients (n=31), as of May 1, 2017, shows that treatment with tazemetostat resulted in a 32 percent disease control rate and a 13 percent overall response rate, with a median duration of response of seven months and ongoing. In addition, tazemetostat continues to demonstrate a favorable safety profile.

"Epithelioid sarcoma is a difficult cancer for sarcoma oncologists like me to treat due to there being few available therapeutic options, which are associated with limited benefit and challenging side effects for patients," said Mrinal M. Gounder, M.D., attending physician at Memorial Sloan Kettering Cancer Center and lead investigator in the Phase 2 clinical trial. "INI1 loss is a defining feature of epithelioid sarcoma and the mechanism of tazemetostat makes this a compelling agent. These data show encouraging activity of tazemetostat as characterized by objective responses, duration of responses and prolonged disease stabilization, and I look forward to its continued development."

"Bringing tazemetostat to patients is our number one priority," said Robert Bazemore, president and chief executive officer of Epizyme. "We stand today with a line of sight to an expedited pathway of bringing tazemetostat to patients with this rare and devastating form of cancer. I am very proud of the hard work and dedication of the entire Epizyme team in advancing tazemetostat this far, so that we may provide a new treatment option to patients who are in desperate need of effective and tolerable medicines."

Phase 2 Study in Molecularly Defined Solid Tumors
Epizyme’s Phase 2 study is evaluating the efficacy and safety of 800mg of tazemetostat orally administered twice-daily in adult patients with certain molecularly defined solid tumors, stratified into five different cohorts based on tumor type, including: epithelioid sarcoma, synovial sarcoma, malignant rhabdoid tumor, renal medullary carcinoma and other INI1-negative tumors.

Epizyme will present interim efficacy data from the epithelioid sarcoma and synovial sarcoma cohorts and safety data from all cohorts at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The remaining three arms of the study have not yet reached futility assessment by the Independent Data Monitoring Committee. Epizyme anticipates providing updates from those cohorts later in 2017.

Epithelioid Sarcoma Efficacy Data
The epithelioid sarcoma cohort in Epizyme’s Phase 2 study represents the largest prospective study of epithelioid sarcoma with any approved or investigational treatment to date. Epithelioid sarcoma is an ultra-rare and aggressive soft tissue sarcoma, characterized by a loss of the INI1 protein. It is most commonly diagnosed in young adults (20-40 years old) and is often fatal. There is no established standard-of-care for treating these patients, who are typically resistant to chemotherapy.

The cohort was initially designed to enroll 30 patients, and was expanded to enroll an additional 30 patients in December 2016 based on encouraging early activity. The cohort has enrolled 49 front-line and relapsed or refractory epithelioid sarcoma patients out of a projected total of 60 patients. Interim data to be presented are from 31 patients in the initial study group, as of the data cutoff on May 1, 2017.

In these patients, tazemetostat treatment resulted in a 32 percent disease control rate (DCR), the primary endpoint. DCR is comprised of confirmed objective responses by RECIST 1.1 for any duration or disease stabilization of 32 weeks or more. Thus far, four patients (13%) have achieved confirmed objective responses (all partial), and the time to response ranged from two months to six months. The median duration of response is seven months and ongoing. Prolonged disease stabilization of 32 weeks or more has been observed in six patients (19%), including two patients having stable disease for more than 15 months. These Phase 2 data complement the Company’s experience from its Phase 1 study, in which two of three patients with epithelioid sarcoma remain on tazemetostat with stable disease out over two years.

A median progression-free survival (PFS) of 5.7 months has been observed, and initial assessment of overall survival for those patients in the DCR group compared to the non-DCR group showed distinct separation in survival curves, favoring the DCR group. The data from this cohort are still maturing, and an initial assessment suggests the potential for prolonged clinical benefit with tazemetostat treatment.

These interim data will be presented at ASCO (Free ASCO Whitepaper) by Dr. Gounder in a poster titled "Phase 2 multicenter study of the EZH2 inhibitor tazemetostat in adults with INI1 negative epithelioid sarcoma (NCT02601950)" on June 4 (Abstract No.: 11058, Poster Board No.: 381).

Tazemetostat Safety Profile
Tazemetostat has demonstrated a favorable safety profile in the Phase 2 study, particularly when considering the adverse effects associated with currently utilized chemotherapeutic regimens and other STS therapies. Safety data from patients in all study cohorts (n=121) are consistent with the overall safety profile observed in a nearly 400 patient-safety database from tazemetostat clinical trials to date, showing favorable tolerability without significant safety events. There were no discontinuations due to adverse events in any of the study cohorts. The majority of treatment-emergent adverse events (TEAEs) were grade 1 or 2, with only 12 percent of patients experiencing grade 3 or higher treatment-related TEAEs. Reported TEAEs regardless of attribution with an incidence of 10 percent or greater were fatigue (34%), dyspnea and nausea (27% each), cough (22%), decreased appetite (20%), vomiting (19%), constipation (18%), anemia (17%), diarrhea (16%), back pain and headache (12% each), pleural effusion (11%) and death and peripheral edema (10% each). All deaths that occurred during the study were attributed to the patients’ underlying disease and not to treatment with tazemetostat.

There were no clinically relevant differences in the safety profile for either the epithelioid sarcoma or the synovial sarcoma cohorts compared to that of the entire study.

Synovial Sarcoma Efficacy Data
The cohort of patients with synovial sarcoma (n=33) in the Phase 2 study completed enrollment in November 2016. Data show tazemetostat treatment resulted in stable disease as the best response in 10 patients (30%) with five patients (15%) meeting the primary endpoint of disease stabilization for 16 weeks or longer. The level of activity was determined to be insufficient to advance tazemetostat as a monotherapy for this tumor type.

These data will be presented in a poster by Patrick Schöffski, M.D., Department of General Medical Oncology and the Laboratory of Experimental Oncology at the University Hospitals Leuven, KU Leuven, Belgium, titled "Phase 2 multicenter study of the EZH2 inhibitor tazemetostat in adults with synovial sarcoma (NCT02601950)" on June 4 (Abstract No.: 11057, Poster Board No.: 380).

Conference Call Information
Epizyme will host a conference call and audio webcast today at 8:30 a.m. Eastern Time. To participate in the conference call, please dial (877) 844-6886 (domestic) or (970) 315-0315 (international) and refer to conference ID 12186629. The webcast, and accompanying slides for the call, can be accessed under "Events and Presentations" in the Investor Relations section of the company’s website at www.epizyme.com.

About Epithelioid Sarcoma
Epithelioid sarcoma is an ultra-rare soft tissue sarcoma characterized by a loss of function of the protein INI1. Patients are most commonly diagnosed as young adults, between 20 and 40 years of age. Median overall survival from initial diagnosis is 30 months. Epithelioid sarcoma becomes more aggressive after recurrence or metastases, with a typical survival of eight to 12 months for patients with metastatic disease. There is no approved treatment indicated specifically for epithelioid sarcoma, and there is no established standard of care.

About the Tazemetostat Clinical Trial Program
Tazemetostat, a first-in-class EZH2 inhibitor, is currently being studied in ongoing Phase 2 programs in both follicular lymphoma and diffuse large B-cell lymphoma (DLBCL) forms of non-Hodgkin lymphoma; certain genetically defined solid tumors, including INI1-negative and SMARCA4-negative tumors and synovial sarcoma; and mesothelioma; as well as in combination studies in DLBCL. Tazemetostat has been granted Fast Track designation by the U.S. Food and Drug Administration for both relapsed/refractory follicular lymphoma with or without an EZH2 activating mutation and DLBCL with EZH2 activating mutations, as well as Orphan Drug designation for malignant rhabdoid tumors.

On May 18, 2017 ArQule, Inc. (Nasdaq: ARQL) reported that preclinical data for ARQ 531 in diffuse large B-cell lymphoma (DLBCL) in vitro and in vivo tumor models will be presented on June 23, 2017 at EHA (Free EHA Whitepaper) Congress in Madrid, Spain (Press release, ArQule, MAY 18, 2017, View Source [SID1234519210]). The data supports clinical trials with ARQ 531 in the ibrutinib resistant patient population. A phase 1 trial with ARQ 531 in patients with B-cell malignancies refractory to other therapeutic options, including ibrutinib, is planned to commence by the third quarter of 2017. ARQ 531 is an investigational, orally bioavailable, potent and reversible inhibitor of both wild type and C481S-mutant Bruton’s tyrosine kinase (BTK).

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Presentation Details

Friday, June 23, 2017: Non-Hodgkin and Hodgkin Lymphoma – Biology

ARQ 531
Abstract E1400
ARQ 531, a reversible BTK inhibitor, demonstrates potent anti-tumor activity in ABC-DLBCL and GCB-DLBCL
E-poster Screens
Time: 9:30 AM CET

About BTK and ARQ 531

ARQ 531 is an investigational, orally bioavailable, potent and reversible Bruton’s tyrosine kinase (BTK) inhibitor. Biochemical and cellular studies have shown that ARQ 531 inhibits both the wild type and C481S-mutant forms of BTK. The C481S mutation is a known emerging resistance mechanism for first generation irreversible BTK inhibitors. In preclinical studies ARQ 531 has demonstrated high oral bioavailability as well as good ADME, pharmacokinetic and metabolic properties. The company plans to initiate a phase 1 trial by the third quarter of 2017. BTK is a therapeutic target that has been clinically proven to inhibit B-cell receptor signaling in blood cancers.

On May 18, 2017 (GLOBE NEWSWIRE) — Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the fields of cancer metabolism and rare genetic diseases, reported that updated clinical data from the fully enrolled, ongoing Phase 2 study (DRIVE PK) of AG-348 in adults with pyruvate kinase (PK) deficiency, a rare, potentially debilitating, congenital anemia, will be presented at the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) taking place June 22-25, 2017 in Madrid, Spain. AG-348 is a wholly owned, novel, first-in-class, oral activator of both wild-type (normal) and mutated pyruvate kinase-R (PKR) enzymes (Press release, Agios Pharmaceuticals, MAY 18, 2017, View Source [SID1234519209]).

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The accepted abstracts are listed below and available online on the EHA (Free EHA Whitepaper) conference website: View Source!*listing=3*browseby=2*sortby=1*media=3*ce_id=1181*label=15531

Oral presentation by Agios:

Title: Effects of AG-348, a pyruvate kinase activator, in patients with Pyruvate Kinase Deficiency: updated results from the DRIVE-PK study
Date & Time: Saturday, June 24, 2017 from 11:30-11:45 a.m. CET
Session Title: Sickle cell disease, enzymes
Abstract Code: S451
Location: Room N109
Presenter: Rachael Grace, M.D., Dana-Farber Boston Children’s Cancer and Blood Disorder Center
Updated data from the DRIVE PK study will be presented at the time of the meeting.

Poster presentation by Agios collaborator:

Title: Ex-vivo treatment of red blood cells from 15 Pyruvate Kinase (PK)-deficient patients with AG-348, an allosteric activator of PK-R, increases enzymatic activity, protein stability and ATP levels
Date & Time: Saturday, June 24, 2017 from 5:30-7:00 p.m. CET
Session Title: Enzymes and sickle cell disease
Abstract Code: P614
Location: Poster area (Hall 7)
Author: Richard van Wijk, Ph.D., University Medical Center Utrecht

Encore presentations by Agios and Celgene:

Title: Enasidenib in mutant-IDH2 relapsed or refractory acute myeloid leukemia (R/R AML): Results of a phase 1 dose-escalation and expansion study
Date & Time: Saturday, June 24, 2017 from 4:00-4:15 p.m. CET
Oral Abstract Session: Targeted treatment of AML
Abstract Code: S471
Location: Hall D
Presenter: Eytan Stein, M.D., Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College

Title: Differentiation syndrome associated with enasidenib, a selective inhibitor of mutant isocitrate dehydrogenase 2 (mIDH2)
Poster Session Date & Time: Friday, June 23, 2017 from 5:15-6:45 p.m. CET
Session Title: Acute myeloid leukemia – Clinical 3
Abstract Code: P215
Location: Poster area (Hall 7)
Author: Amir Tahmasb Fathi, M.D., Massachusetts General Hospital and Harvard Medical School

About Agios
Agios is focused on discovering and developing novel investigational medicines to treat cancer and rare genetic diseases through scientific leadership in the field of cellular metabolism. In addition to an active research and discovery pipeline across both therapeutic areas, Agios has multiple first-in-class investigational medicines in clinical and/or preclinical development. All Agios programs focus on genetically identified patient populations, leveraging our knowledge of metabolism, biology and genomics. For more information, please visit the company’s website at www.agios.com.

About Agios/Celgene Collaboration
IDHIFA (enasidenib) and AG-881 are part of Agios’ global strategic collaboration with Celgene Corporation focused on cancer metabolism. Under the terms of the 2010 collaboration agreement, Celgene has worldwide development and commercialization rights for IDHIFA (enasidenib). Agios continues to conduct clinical development activities within the IDHIFA (enasidenib) development program and is eligible to receive reimbursement for those development activities and up to $95 million in remaining payments assuming achievement of certain milestones and royalties on net sales. Celgene and Agios intend to co-commercialize IDHIFA (enasidenib) in the U.S. Celgene will reimburse Agios for costs incurred for its co-commercialization efforts.

On May 18, 2017 Acceleron Pharma Inc. (NASDAQ:XLRN), a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative therapeutics to treat serious and rare diseases, reported that two abstracts on luspatercept will be presented at the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Madrid, Spain on June 22-25, 2017 (Press release, Acceleron Pharma, MAY 18, 2017, View Source [SID1234519208]). Luspatercept is being developed as part of the global collaboration between Acceleron and Celgene.

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The oral and poster presentations will include efficacy, duration of response, and long-term safety results from the ongoing Phase 2 studies with luspatercept in myelodysplastic syndromes (MDS) and beta-thalassemia. The presentations at the conference will include updated information beyond that included in the abstracts available online on the EHA (Free EHA Whitepaper) conference website. The beta-thalassemia presentation will review results updated from the ASH (Free ASH Whitepaper) 2016 presentation in December and the MDS presentation will highlight results updated from the recent International Symposium on MDS earlier this month.

Oral presentation

Title: Luspatercept Increases Hemoglobin and Decreases Transfusion Burden in Adults with Beta-Thalassemia (Abstract: S129)
Session: Thalassemia
Date: Friday, June 23rd
Time: 11:45 a.m. CEST (IFEMA, Room N105)

Poster presentation

Title: Luspatercept Increases Hemoglobin and Reduces Transfusion Burden in Patients with
Lower-Risk Myelodysplastic Syndromes (MDS): Long-Term Results from Phase 2 PACE-MDS Study (Abstract: P666)
Session: Myelodysplastic Syndromes – Clinical 2
Date: Saturday, June 24th
Time: 5:30 – 7:00 p.m. CEST (IFEMA, Poster Area, Hall 7)

The luspatercept clinical poster and slides from the oral presentation will be available immediately following the presentations at the conference in the "Science" section on Acceleron’s website, www.acceleronpharma.com.

About Luspatercept

Luspatercept is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members in the transforming growth factor-beta superfamily involved in the late stages of erythropoiesis (red blood cell production). Luspatercept regulates late-stage erythrocyte (red blood cell) precursor cell differentiation and maturation. This mechanism of action is distinct from that of erythropoiesis stimulating agents (ESAs), which stimulate the proliferation of early-stage erythrocyte precursor cells. Acceleron and Celgene are jointly developing luspatercept as part of a global collaboration. Phase 3 clinical trials are underway to evaluate the safety and efficacy of luspatercept in patients with myelodysplastic syndromes (the "MEDALIST" study) and in patients with beta-thalassemia (the "BELIEVE" study). For more information, please visit www.clinicaltrials.gov.