On July 9, 2015 Epizyme reported that it has dosed the first patient in the phase 2 trial of its lead clinical candidate, tazemetostat (EPZ-6438) in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) (Press release, Epizyme, JUL 9, 2015, View Source [SID:1234506199]).

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This five-arm study will enroll up to 150 patients with germinal center diffuse large B cell lymphoma (DLBCL) or follicular lymphoma, stratified into those expressing mutant EZH2 and those expressing wild type EZH2, as well as patients with non-germinal center DLBCL.

"Results from our ongoing phase 1 trial that we presented at the International Congress on Malignant Lymphoma on June 20 show tazemetostat produced durable objective responses in heavily pre-treated patients with relapsed or refractory NHL, with an acceptable safety and tolerability profile," said Peter Ho, M.D., Ph.D., Chief Development Officer, Epizyme. "With the initiation of this phase 2 trial, we look forward to making significant progress in evaluating the potential of tazemetostat in targeted sub-populations of NHL."

About the Tazemetostat Phase 2 Program
The phase 2 NHL trial is a five-arm, multi-center, international study that will assess the safety and activity of tazemetostat in patients with relapsed or refractory non-Hodgkin lymphoma. The study will enroll up to 30 patients in each arm, prospectively stratified for EZH2 mutation status and cell-of-origin, assuming each arm of the study achieves its primary response rate goal in its first stage. The five study arms are enrolling relapsed/refractory patients with:

Germinal center DLBCL with mutant EZH2

Germinal center DLBCL with wild-type EZH2

Follicular lymphoma with mutant EZH2

Follicular lymphoma with wild-type EZH2

Non-germinal center DLBCL

A second planned phase 2 trial of tazemetostat in adult patients with INI1-deficient solid tumors is expected to initiate later in 2015. A phase 1 study in pediatric patients with INI1-deficient solid tumors is also expected to start later in 2015.

The Company also plans to initiate additional clinical evaluations of tazemetostat, including a combination with R-CHOP in patients with DLBCL, and a combination with a B-cell signaling agent or other emerging targeted therapies for B-cell lymphomas.

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 lymphomas, INI1-deficient cancers such as malignant rhabdoid tumors, epithelioid sarcomas and synovial sarcoma; and a range of other solid tumors.

About Tazemetostat
Epizyme is developing tazemetostat for the treatment of non-Hodgkin lymphoma patients and 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 many 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.

Tazemetostat is the second HMT inhibitor to enter human clinical development (following Epizyme’s DOT1L inhibitor, pinometostat, also known as EPZ-5676). The phase 1 study of tazemetostat is ongoing, with additional data expected to be reported later in 2015.

Additional information about this program, including clinical trial information, may be found here: View Source

July 9, 2015 Sorrento Therapeutics and NantBioScience, a majority owned subsidiary of NantWorks reported that they have established a joint venture to focus on the development of ‘first-in-class’ small molecules against targets that have eluded the pharmaceutical industry to date and which may address important drivers of cancer growth including cancer stem cells (Filing, 8-K, Sorrento Therapeutics, JUL 9, 2015, View Source [SID:1234506196]).

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Sorrento will contribute key small molecule programs (lead inhibitors of the proto-oncogenes c-Myc, and the master metabolism regulator HIF-1 alpha, and an inducer of the tumor suppressor cytokine TRAIL) to the joint venture which will be 60% owned by NantBioScience and 40% owned by Sorrento, and funded accordingly.

This joint venture follows on the previously announced acquisition by NantPharma of the rights to Cynviloq, a nanoparticle-based paclitaxel cytotoxic therapeutic, now renamed Nant-paclitaxel, as well as the formation of NantiBody, a joint venture focused on immunotherapeutics. Both entities are affiliated with Dr. Soon-Shiong’s ecosystem of companies at NantWorks.

"Sorrento’s mission is to expeditiously and efficiently bring innovative therapies to cancer patients in need," said Dr. Henry Ji, President and CEO. "This partnership focused on the development of our innovative small molecules will allow us to realize Sorrento’s vision, align our resources on our immuno-oncology and cell therapy assets, and puts Sorrento at the forefront of cancer therapy."

"Treatment of patients with cancer will require a multi-faceted approach involving chemotherapy, immunotherapy, adoptive cellular therapy and next-generation precision medicine platforms," said Dr. Patrick Soon-Shiong, NantWorks founder. "We are committing significant resources to the development of novel and innovative cancer therapies, including small molecules as components of targeted combination therapy strategies. At NantBioScience, we are pursuing the equivalent of the moonshot in the oncology space by developing drugs targeting mutant KRAS, RAL, and now cMyc, and HIF-1 alpha, as well as drugs inducing TRAIL expression and p53 activity. Only by developing drugs for these widely-considered "undruggable" targets do we have a hope of winning our war against cancer. Through this joint venture and the other ongoing collaborations we have with Sorrento, we are focused on transforming cancer therapy as we know it today and provide cancer patients with innovative treatment options for their thus far unmet medical needs."

Eli Lilly’s necitumumab wins FDA experts over (Report, Eli Lilly, JUL 9, 2015, View Source [SID:1234506193]). The committee members have weighed the positives and negatives of a drug that showed only a marginal survival advantage for patients with non-small cell lung cancer. The US FDA will now make a formal decision by the regulatory deadline.

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On July 9, 2015 Tocagen reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to its lead immuno-oncology product, Toca 511 & Toca FC, for the treatment of recurrent high grade glioma, which includes glioblastoma and anaplastic astrocytoma (Press release, Tocagen, JUL 9, 2015, View Source [SID:1234506191]). This treatment will enter a registrational study called Toca 5 later this year in patients with recurrent glioblastoma or anaplastic astrocytoma.

“The granting of Fast Track designation for Toca 511 & Toca FC underscores the urgent need for new treatments for high grade glioma, an extremely deadly and aggressive cancer,” said Harry Gruber, M.D., chief executive officer of Tocagen. “In addition to the excellent safety profile and encouraging median survival we have seen in two separate studies evaluating Toca 511 & Toca FC in patients with recurrent high grade glioma, this designation will help accelerate our development plans to address this unmet need.”

The FDA’s Fast Track program is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need, with the goal of getting important new drugs to patients earlier. Fast Track designation allows for more frequent interactions with the FDA review team, including meetings to discuss the drug’s development plan to support potential drug approval and the opportunity to submit sections of an NDA on a rolling basis as data become available.

About Toca 511 & Toca FC
Toca 511 & Toca FC is an immuno-oncology therapy that will be evaluated in a registrational study to be initiated in 2015 in patients with recurrent glioblastoma or anaplastic astrocytoma. Toca 511 & Toca FC are designed to selectively transform the tumor into a chemotherapy factory while also activating the immune system against the tumor both locally and systemically. Toca 511 is a retroviral replicating vector (RRV) that selectively delivers a gene for the enzyme cytosine deaminase to the tumor. The patient then takes oral cycles of Toca FC, a novel formulation of an antifungal drug, which is converted into the FDA-approved chemotherapy drug, 5-fluorouracil (5 FU). As result, infected cancer cells are selectively killed, subsequently activating the immune system to recognize cancer cells, while leaving healthy cells unharmed. Immune activation locally in the tumor occurs through a combination of mechanisms which leads to breaking of immune tolerance and activation of the immune system selectively against the cancer cells.

On July 9, 2015 Epizyme, reported that it has amended and restated its agreement with Celgene Corporation to extend the research collaboration between the two companies for at least three additional years (Press release, Epizyme, JUL 9, 2015, View Source [SID:1234506189]).

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Under the collaboration, Celgene will have the option to license histone methyltransferase (HMT) inhibitors being developed by Epizyme against three predefined targets.

Under the terms of the revised agreement:

Epizyme will receive a $10 million extension fee from Celgene in return for an option to individually license global rights for two of the targets and ex-US rights for the third target.
Celgene may exercise its option with respect to each of the targets at the time of the IND filing for an additional pre-specified license payment.
Epizyme will be responsible for leading and funding development for each target candidate through phase 1 clinical trials.
Following the completion of phase 1, if Celgene chooses to continue its license for a specific target, it may do so by making an additional pre-specified payment.
Epizyme may earn total potential milestones of up to $610 million on the three targets, including up to $75 million in development milestones and license fees, $365 million in regulatory milestones, and $170 million in sales milestones
Epizyme also may earn a royalty of up to a low double-digit percentage on worldwide net sales for two of the product candidates, and on ex-US net sales for the third product candidate.
Epizyme will retain global rights to the remainder of its pipeline, as Celgene’s option to license ex-US rights for any other preclinical programs will terminate.
In addition, Celgene will retain its ex-US license to, and the companies will continue their ongoing clinical collaboration on, pinometostat (EPZ-5676), a HMT inhibitor targeting DOT1L. Pinometostat is in phase 1 development for the treatment of patients with acute leukemia with alterations in the MLL gene (MLL-r).

"We believe that the extension of our agreement with Celgene will accelerate our goal of developing new therapies that have the potential to help many patients with epigenetically driven cancers," said Robert Gould, Ph.D., President and Chief Executive Officer, Epizyme. "Celgene is a leading company in oncology development and commercialization and we are pleased to continue our partnership on pinometostat and these three exciting novel targets."

The term of this agreement is based on specific development milestones, including the timing of IND filings and completion of phase 1 studies, but will extend for a minimum of three years. In addition, Celgene will no longer have the right of first negotiation on a business combination with Epizyme.

Financial Update

The Company also announced today that, based on its current operating plans, it projects that its cash and cash equivalents will be sufficient to fund operations through at least the end of the second quarter of 2017, prior to including any potential option exercise fees or future milestone payments. This new cash outlook reflects a significant reallocation of resources, implementation of cost savings initiatives, the additional capital provided from the Celgene extension fee payment and the partial exercise of the overallotment option in April from the Company’s March public financing.

"We have increased investment in tazemetostat development, both as a single agent and in future studies in combination with other agents," said Andrew Singer, Executive Vice President and Chief Financial Officer at Epizyme. "This required reprioritizing our pipeline development plans and reducing operating costs. We are excited about the updated data from our dose escalation and dose expansion studies presented at the International Congress on Malignant Lymphoma in Lugano, Switzerland on June 20. We look forward to presenting additional data at the European Society for Medical Oncology’s European Cancer Congress in Vienna, Austria on September 26."

About Tazemetostat (EPZ-6438)

Epizyme is developing tazemetostat for the treatment of non-Hodgkin lymphoma patients and patients with INI1-deficient solid tumors. Tazemetostat is a first-in-class small molecule inhibitor of EZH2 developed by Epizyme. In many 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.

Tazemetostat is the second HMT inhibitor to enter human clinical development (following Epizyme’s DOT1L inhibitor, pinometostat).

Epizyme is conducting a five-arm, multi-center international phase 2 clinical trial that will assess the safety and activity of tazemetostat in patients with relapsed or refractory non-Hodgkin lymphoma. A phase 1 dose escalation and dose expansion trial of tazemetostat is also ongoing, with additional data expected to be reported later in 2015. Additional information about this program, including clinical trial information, may be found here: View Source

About Pinometostat (EPZ-5676)

Epizyme is developing pinometostat, a small molecule inhibitor of DOT1L created with Epizyme’s proprietary product platform, for the treatment of patients with acute leukemia in which the MLL gene is rearranged due to a chromosomal translocation (MLL-r). Due to these rearrangements, DOT1L is misregulated, resulting in the increased expression of genes causing leukemia. Pinometostat is the WHO International Non-Proprietary Name (INN) for compound EPZ-5676.

Epizyme believes that pinometostat was the first HMT inhibitor to enter human clinical development. Epizyme is currently conducting a two-stage Phase 1 study in adult MLL-r patients and in May 2014, initiated a Phase 1b study of pinometostat in pediatric patients with rearrangements of the MLL gene. The adult dose escalation cohorts have completed enrollment, and an adult MLL-r dose expansion cohort is now enrolling patients. Additional information about these ongoing Phase 1 studies can be found here: View Source

Pinometostat has been granted orphan drug designation for the treatment of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) by the Food and Drug Administration in the U.S. and by the European Commission in Europe.

Epizyme retains all U.S. rights to pinometostat and has granted Celgene an exclusive license to pinometostat outside of the U.S.