On December 30, 2015 Epizyme, Inc. (NASDAQ: EPZM), a clinical stage biopharmaceutical company creating novel epigenetic therapies for cancer patients, reported that the first patient has been dosed in the phase 2 study of tazemetostat in adult patients with genetically defined tumors (Press release, Epizyme, DEC 30, 2015, View Source [SID:1234508645]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The phase 1 dose escalation study in pediatric patients with the same tumor types is also now open for enrollment. The cancers being studied in these trials, INI1-negative tumors, certain SMARCA4-negative tumors and synovial sarcomas, are aggressive cancers that are poorly served by current treatments. The first sites activated for adult enrollment are Northwestern University, MD Anderson Cancer Center and Cincinnati Children’s Hospital and the first sites activated for pediatric enrollment are the Dana Farber Cancer Institute and Cincinnati Children’s Hospital. Additional study sites in the U.S., Canada, Europe and Australia are planned to be added over the upcoming months.

"Life-threatening rare tumors such as rhabdoid tumors, epithelioid sarcomas and synovial sarcomas affect children and young adults who are in need of novel effective therapies since the standard approaches are only marginally useful," said George Demetri, M.D., Director, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute and Professor of Medicine, Harvard Medical School. "We are enthusiastic about evaluating tazemetostat in our patients with these forms of sarcomas since the molecular mechanism is so compelling, especially with the recent identification of mutations in INI1 or SMARCA4 as genetic drivers for these cancers."

"This important study will enroll children with cancers such as malignant rhabdoid tumor, based on unique genetic defects that appear to result in biological sensitivity to EZH2 inhibition," said Susan Chi, M.D., Director of the Pediatric Brain Tumor Clinical Trials Program, Dana-Farber Cancer Institute and Assistant Professor of Pediatrics, Harvard Medical School. "For children with these deadly diseases, tazemetostat potentially represents a meaningful option when other treatments have been exhausted."

"Initiation of the clinical program in genetically defined solid tumors is an important milestone for Epizyme and expands tazemetostat development beyond non-Hodgkin lymphoma," said Peter Ho, M.D., Ph.D., Chief Medical Officer, Epizyme. "We are excited to advance the study of tazemetostat in these patients."

The adult phase 2 multicenter study will enroll up to 90 patients in three cohorts. The first cohort will be comprised of patients with malignant rhabdoid tumor, rhabdoid tumor of the kidney and atypical teratoid rhabdoid tumor, all of which are characterized by INI1- or SMARCA4-negativity. The second cohort will be comprised of patients with non-rhabdoid INI1-negative tumors including epithelial sarcoma, epithelioid malignant peripheral nerve sheath tumor, extraskeletal myxoid chondrosarcoma, myoepithelial carcinoma and renal medullary carcinoma. The third cohort will be comprised of patients with synovial sarcoma in which INI1 is dysregulated by a reciprocal translocation between chromosome 18 and the X chromosome. Patients will be dosed at 800 mg twice daily with tablets taken orally. The primary endpoint is overall response rate (ORR) for patients with INI1-negative tumors and progression-free survival (PFS) for patients with synovial sarcoma. Secondary endpoints include duration of response, overall survival (OS), and PFS for patients with INI1-negative tumors, as well as safety and pharmacokinetics (PK).

The pediatric phase 1 multicenter study will enroll approximately 40 patients in a dose escalation design, followed by dose expansion, with an oral suspension of tazemetostat. The study will enroll patients with the same INI1-negative tumors, SMARCA4-negative tumors or synovial sarcoma as in the adult study. The primary endpoint of the study is safety, with the objective of establishing the recommended phase 2 dose in pediatric patients. Secondary endpoints include pharmacokinetics, objective response rate, duration of response, progression free survival, and overall survival.

INI1-negative or certain SMARCA4-negative tumors are characterized as aggressive cancers with few to no approved treatments today. For example, current treatment of malignant rhabdoid tumors, an INI1-negative tumor, consists of surgery, chemotherapy and radiation therapy, which are associated with limited efficacy and significant treatment-related morbidity. In August, the FDA’s Division of Oncology Products 2 accepted Epizyme’s IND application to study adult and pediatric patients with INI1-negative solid tumors or synovial sarcoma in the U.S.

Interim data from Epizyme’s phase 2 study of tazemetostat in adult patients with genetically defined solid tumors are anticipated to be presented at a medical conference in late 2016.

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 or certain SMARCA4-negative cancers such as malignant rhabdoid tumors and epithelioid sarcomas, 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 INI1-deficient 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 misregulation 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 this program, including clinical trial information for the adult five -arm NHL study, can be found here: View Source

Clinical trial information for the adult INI1-negative tumors, certain SMARCA4-negative tumors or synovial sarcoma trial can be found here: View Source

Clinical trial information for the pediatric INI1-negative tumors, certain SMARCA4-negative tumors or synovial sarcoma trial can be found here: View Source

On December 28, 2015 Immune Pharmaceuticals Inc. (NASDAQ:IMNP) ("Immune") a clinical-stage company developing novel therapies for the treatment of immuno-inflammatory diseases and cancer, reported it has entered into an exclusive license with Atlante Biotech SAS, to the patents and know-how for a new format of bispecific antibodies (Press release, Immune Pharmaceuticals, DEC 28, 2015, View Source [SID:1234508650]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Dr. Daniel Teper, CEO of Immune commented, "This is an important milestone as we make progress with our immuno-oncology pipeline. Our research will focus on the application of this novel bispecific platform to target immune checkpoints. Our plan is to generate additional pre-clinical data with selected bispecific drug candidates in 2016."

The R&D work on the bispecific antibodies will be performed in Immune’s recently established Immunology R&D unit at the Alexandria Center for Life Sciences in New York City, under the leadership of Dr. Boris Shor, Executive Director of R&D, who joined the company from Pfizer Oncology.

In recently presented data, the platform prototype bispecific antibody was shown to retain effector functions and mediate redirect killing of target cells by cytokine induced killer T cells. The bispecific antibody demonstrated direct anti-cancer effects in vitro, as well as in vivo anti-tumor activity and improved survival in a mouse xenograft model of disseminated leukemia. A collaborative European consortium led by Dr. Kadouche from Atlante Biotech, and funded by a European grant developed the novel platform for production of tetravalent IgG1-like bispecific antibodies.

On December 28, 2015 Sunshine Biopharma Inc. (OTCQB: SBFM), a pharmaceutical company focused on the research, development and commercialization of drugs for the treatment of various forms of cancer, reported that it has acquired all of the remaining rights, title and interest in and to all worldwide patents for the Company’s Adva-27a anticancer compound (Press release, Sunshine Biopharma, DEC 28, 2015, View Source [SID:1234508649]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Patent Purchase Agreement executed today provides Sunshine with direct ownership of all issued and pending Adva-27a related patents, which include all rights to this intellectual property worldwide. Prior, Sunshine had ownership of only the U.S. patent.
The purchase price paid by Sunshine for these patent rights was $12,822,499, which will be paid pursuant to the terms of a secured promissory note, with quarterly payments of principal and interest due through December 2020.

About Adva-27a
Adva-27a is Sunshine Biopharma’s lead anticancer compound, a Topoisomerase II inhibitor, small molecule that has recently been shown to be effective at killing Pancreatic Cancer cells, Multidrug Resistant Breast Cancer cells, Small-Cell Lung Cancer cells and Uterine Sarcoma cells (Published in ANTICANCER RESEARCH, Volume 32, Pages 4423-4432, October 2012). Adva-27a is currently in the IND-Enabling stage of development. The original U.S. patent covering Adva-27a was issued on August 7, 2012 under U.S. patent number 8,236,935. The Company is planning Phase I clinical trials of Adva-27a for Pancreatic Cancer and in parallel Multidrug Resistant Breast Cancer to be conducted at McGill University’s Jewish General Hospital in Montreal (Canada).

On December 28, 2015 Epizyme, Inc. (NASDAQ:EPZM), a clinical stage biopharmaceutical company creating novel epigenetic therapies for cancer patients, reported the U.S. Food and Drug Administration’s (FDA) Division of Hematology Products has accepted the company’s investigational new drug (IND) application for tazemetostat for the treatment of adults with diffuse large B-cell lymphoma (DLBCL), the most common type of Non-Hodgkin Lymphoma (NHL) (Press release, Epizyme, DEC 28, 2015, View Source [SID:1234508643]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

An ongoing five-arm registration-supporting, international phase 2 clinical trial assessing the safety and activity of tazemetostat in patients with relapsed or refractory B-cell NHL was initiated in July 2015 (NCT02601950). The IND acceptance will allow the company to enroll DLBCL patients in the United States into this ongoing trial.

"Tazemetostat has demonstrated clinically meaningful anti-tumor activity and an acceptable safety profile in patients with NHL in our phase 1 study," said Robert Bazemore, President and Chief Executive Officer. "We are excited to enable U.S. investigators to gain experience with tazemetostat in DLBCL."

"Patients with relapsed or refractory NHL have a significant need for new treatment options," said Dr. Peter Ho, M.D., Ph.D., Chief Medical Officer, Epizyme. "We believe tazemetostat has the potential to become an important therapy for B-cell NHL patients, both as a monotherapy and in combination, and look forward to extending the ongoing five-arm NHL study to allow access to DLBCL patients in the U.S."

About the Tazemetostat Clinical Trial Program

The phase 2 NHL trial is a five-arm, multi-center, international study that will use a two-stage design to assess the safety and activity of tazemetostat in multiple populations of patients with relapsed or refractory Non-Hodgkin Lymphoma. The study will enroll up to 30 patients in each arm. Patients will be prospectively stratified for EZH2 mutation status and cell-of-origin. The five study arms are enrolling relapsed/refractory patients with:

Germinal center DLBCL with mutant EZH2
Germinal center DLBCL with wild-type EZH2
Non-germinal center DLBCL
Follicular lymphoma with mutant EZH2
Follicular lymphoma with wild-type EZH2
Epizyme expects to present interim data from the phase 2 study in NHL at a medical conference in mid-2016.

In the first half of 2016, the Company also plans to initiate additional clinical evaluations of tazemetostat, including a combination study with R-CHOP in front-line, high-risk patients with DLBCL, and a combination study with a B-cell signaling agent or immuno-oncology agent in B-cell NHL.

In August 2015, the FDA’s Division of Oncology Products 2 accepted Epizyme’s IND application to study adult and pediatric patients with INI1-negative solid tumors or synovial sarcoma.

About Tazemetostat

Epizyme is developing tazemetostat for the treatment of patients with Non-Hodgkin Lymphoma and for patients with INI1-negative solid tumors, certain SMARCA4-negative solid tumors or synovial sarcoma. 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 misregulation 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 this program, including clinical trial information for the adult five-arm NHL study, can be found here: View Source

Information about the company’s Phase 2 clinical trial of tazemetostat in adults with INI1-negative solid tumors, certain SMARCA4-negative solid tumors or synovial sarcoma can be found here: View Source

Information about the company’s Phase 1 clinical trial of tazemetostat in children with INI1-negative solid tumors, certain SMARCA4-negative solid tumors or synovial sarcoma can be found here: View Source