On July 9, 2015 Genmab reported its licensing partner Janssen Biotech, Inc. has completed the rolling submission of the Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for daratumumab (Press release, Genmab, JUL 9, 2015, View Source [SID:1234506200]).

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The submission is for daratumumab as a treatment for patients with multiple myeloma who have received at least three prior lines of therapy including both a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or who are double refractory to a PI and an IMiD. In May, 2013, daratumumab was granted a Breakthrough Therapy Designation (BTD) in this population. The completion of the submission triggers a milestone payment of USD 15 million to Genmab from Janssen. The milestone was included in Genmab’s financial guidance for 2015, which was updated on May 20, 2015. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

A request for Priority Review has been submitted by Janssen with this BLA. The FDA will inform Janssen whether a Priority Review has been granted by calendar day 60 of their review starting today. If the FDA grants Priority Review the review period may not exceed 6 months from that date.

If daratumumab receives FDA approval, Genmab will receive a milestone payment from Janssen of USD 45 million associated with the first commercial sale of the product in the United States. However, it is not possible to precisely predict the timing of a potential marketing approval and first commercial sale; therefore, this milestone has not been included in the 2015 financial guidance at this time.

"The rapid completion of the BLA submission brings us a significant step closer to the potential regulatory approval of daratumumab," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "Daratumumab received Breakthrough Therapy Designation from the FDA for this indication for multiple myeloma patients who have no other treatment options available, and we are proud that our partner Janssen has completed the submission in record time."
The submission includes data from the Phase II study (Sirius MMY2002) of daratumumab in multiple myeloma patients who have received at least three prior lines of therapy including both a PI and an IMiD, or who are double refractory to a PI and an IMiD. However, safety and efficacy data from the Phase I/II study (GEN501) and safety data from three other studies have also been included in the BLA submission.

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the United States (U.S.), following only leukemia and lymphoma.2 Approximately 26,850 new patients will be diagnosed with multiple myeloma and approximately 11,240 people will die from the disease in the U.S. in 2015.3 Globally, it is estimated that 114,251 people will be diagnosed and 80,019 will die from the disease.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5

About daratumumab
Daratumumab is an investigational human IgG1k monoclonal antibody (mAb) that binds with high affinity to the transmembrane ectoenzyme, CD38, on the surface of multiple myeloma cells. It induces rapid tumor cell death through diverse mechanisms of action. Five Phase III clinical studies with daratumumab in relapsed and frontline settings are currently ongoing. Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma and non-Hodgkin’s lymphoma. Daratumumab has been granted Breakthrough Therapy Designation from the US FDA.

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.