On January 4, 2016 Merck KGaA, Darmstadt, Germany, Pfizer and Syndax Pharmaceuticals, Inc. reported that they have entered into a collaboration agreement to evaluate avelumab*, an investigational fully human anti-PD-L1 IgG1 monoclonal antibody, in combination with Syndax’s entinostat, an investigational oral small molecule that targets immune regulatory cells (myeloid-derived suppressor cells and regulatory T-cells), in patients with heavily pre-treated, recurrent ovarian cancer (Press release, Pfizer, JAN 4, 2016, View Source [SID:1234508657]).

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Avelumab is currently under clinical investigation across a broad range of tumor types by the alliance between Merck KGaA, Darmstadt, Germany, and Pfizer. This is an exclusive agreement between the alliance and Syndax to study the combination of these two investigational agents in ovarian cancer. Syndax will be responsible for conducting the Phase Ib/II clinical trial in ovarian cancer.

"This collaboration with Syndax adds a new dimension to our quest to pursue combination immuno-oncology regimens based on compelling preclinical rationale and the potential to generate clinical results superior to those achieved with either agent alone," said Dr. Mace Rothenberg, Senior Vice President of Clinical Development and Medical Affairs and Chief Medical Officer for Pfizer Oncology.

"Combination therapy is the next frontier in immuno-oncology and a key strategy for the alliance," said Dr. Luciano Rossetti, Head of Global Research & Development of the biopharma business of Merck KGaA, Darmstadt, Germany. "Avelumab as a monotherapy has already shown promising early activity in ovarian cancer in a Phase Ib trial, and through our ongoing research and this collaboration with Syndax, we will hopefully be able to make a real difference to women fighting this complex cancer."

"We are delighted to be working with the alliance to explore the potential benefits of entinostat in combination with avelumab for ovarian cancer patients," said Dr. Briggs W. Morrison, Syndax’s Chief Executive Officer. "The continued interest from leading companies in investigating the potential of entinostat in combination with checkpoint inhibitors reflects positively on the potential mechanism of action of the molecule, and also reinforces our clinical strategy to explore entinostat for the benefit of patients across a broad range of solid tumor indications."

Financial terms of the agreement were not disclosed.

*Avelumab is the proposed International Non-proprietary Name for the anti-PD-L1 IgG1 monoclonal antibody (MSB0010718C). Avelumab is under clinical investigation and has not been proven to be safe and effective. There is no guarantee any product will be approved in the sought-after indication by any health authority worldwide.

About Ovarian Cancer

Globally, ovarian cancer is the seventh most common cancer in women.1 Annually, nearly 239,000 cases are diagnosed worldwide.2 Ovarian cancer may be difficult to diagnose, as symptoms may appear only in the later stages, when the disease has spread beyond the ovaries.2 Outcomes for women with ovarian cancer are generally poor due to most patients presenting with advanced disease.3 The 5-year prevalence of women globally living with ovarian cancer is 22.6 per 100,000.2 Current treatment options for epithelial ovarian cancer may include surgery, radiotherapy, chemotherapy and targeted therapies.4 Women who are unable to undergo treatment with platinum-based chemotherapy, due to resistance or refractory disease, currently have very limited treatment options. Platinum-resistant ovarian cancer is defined as ovarian cancer that recurs within six months of completing primary chemotherapy with a platinum-based medication.5 Platinum-refractory ovarian cancer is defined as ovarian cancer that progresses during treatment with a platinum-based chemotherapy regimen.5 There is still a clear unmet need in ovarian cancer in relation to general disease awareness,2 improving initial investigations in primary and secondary care and novel therapies with demonstrable efficacy.6

About Avelumab

Avelumab (also known as MSB0010718C) is an investigational fully human anti-PD-L1 IgG1 monoclonal antibody. By inhibiting PD-L1 interactions, avelumab is thought to potentially enable the activation of T-cells and the adaptive immune system. By retaining a native Fc-region, avelumab is thought to engage the innate immune system and induce antibody-dependent cell-mediated cytotoxicity (ADCC). In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

On January 4, 2016 MabVax Therapeutics Holdings, Inc. (OTCQB: MBVX), a clinical-stage oncology drug development company, reported that it has received notice from the U.S. Food and Drug Administration (FDA) authorizing the initiation a Phase I clinical trial with HuMab-5B1 as a therapeutic treatment for pancreatic cancer (Press release, MabVax, JAN 4, 2016, View Source [SID:1234508656]).

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The Company filed an Investigational New Drug (IND) application for its lead fully human antibody product on November 30, 2015. Patient enrollment in the Phase I clinical trial is expected to begin at multiple investigational sites in early 2016.

The Phase I trial will evaluate the safety, tolerability and pharmacokinetics of HuMab-5B1 as a single agent or in combination with a standard of care chemotherapy regimen in subjects with metastatic pancreatic cancer. The first cohort of patients will be enrolled in a traditional dose escalation regimen to assess safety and determine the optimal dose of the antibody. A second patient cohort will establish the safety and optimized dose of the antibody when administered with a standard of care chemotherapy. Two additional patient cohorts will be administered the optimized dose of antibody as a single agent, or in combination with a standard of care chemotherapy regimen, for the treatment of patients with pancreatic cancer.

David Hansen, MabVax’s President and Chief Executive Officer, said, "We are delighted with the FDA’s expeditious response to our IND filing. We intend to begin the dose escalation portion of this trial as soon as possible and anticipate reporting early safety assessment and determination of a maximum tolerated dose by mid-year 2016. This significant interim milestone will enable us to move into the combination therapy and monotherapy portions of the trial that we expect will provide important pharmacological data. This milestone could also have a positive impact on our future commercial and corporate development activities."

MabVax plans to file a second IND application for a HuMab-5B1 PET imaging agent and, subject to FDA authorization, will begin this Phase I trial in patients with pancreatic cancer in early 2016. 89Zr-HuMab-5B1, which is the antibody combined with a radio-label as a novel PET imaging agent, has demonstrated high image resolution of tumors in established xenograft animal models, making it attractive as a potential companion diagnostic for the HuMab-5B1 therapeutic product.

"Data generated in the early portions of these two Phase I trials could demonstrate important initial safety, targeting specificity and utility of the HuMab-5B1 antibody in patients with this devastating disease," added Mr. Hansen. "We are excited about the potential applicability of our dual-product development approach in other cancers with HuMab-5B1, as well as with follow-on antibodies under development at MabVax."

About HuMab-5B1:

MabVax’s HuMab-5B1 antibody is fully human and was discovered from the immune response of cancer patients vaccinated with an antigen-specific vaccine during a Phase I trial at Memorial Sloan Kettering Cancer Center. In preclinical research, the 5B1 antibody has demonstrated high specificity and affinity, and has shown potent cancer cell killing capacity and efficacy in animal models of pancreatic, colon and small cell lung cancers. The antigen the antibody targets is expressed on more than 90% of pancreatic cancers making the antibody potentially broadly applicable to most patients suffering from this type of cancer.

On January 4, 2016 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported that it has entered into a $150 million credit agreement, secured by future royalties of ENHANZE products, received only from Halozyme’s collaborations with Roche and Baxalta (Press release, Halozyme, JAN 4, 2016, View Source [SID:1234508654]).

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"This transaction allows us to continue to execute our two pillar strategy supporting the initiation of our phase 3 study in pancreatic cancer, ongoing studies in non-small cell lung and gastric cancers, and start of our planned trial in breast cancer in collaboration with Eisai," said Dr. Helen Torley, president and chief executive officer of Halozyme. "This opportunity for non-dilutive financing further demonstrates how our ENHANZE platform can drive value, and is additive to the $25 million upfront payment from the recently announced licensing and collaboration agreement with Eli Lilly."

The debt transaction is expected to close in January 2016. The financing will be facilitated through investment funds managed by Pharmakon Advisors and Athyrium Capital Management. "We are pleased to partner with Halozyme in this transaction," said Martin Friedman, managing member of Pharmakon Advisors. "We believe Halozyme’s ENHANZE technology adds tremendous value to biologic products as demonstrated by the strength of Halozyme’s collaborations with Roche and Baxalta." As part of the financing structure, Halozyme formed a wholly-owned subsidiary, Halozyme Royalty LLC ("Halozyme Royalty"), which, subject to satisfaction of certain closing conditions, will borrow $150 million at a per annum interest rate of 8.75 percent plus the three-month LIBOR rate. Under the terms of the loan, the three-month LIBOR rate is subject to a floor of 0.70 percent and a cap of 1.50 percent.

On the closing date, Halozyme will transfer to Halozyme Royalty the right to receive certain royalty payments from the commercial sales of Herceptin SC and MabThera SC under Halozyme’s collaboration agreement with Roche and from the commercial sales of Hyqvia under Halozyme’s collaboration agreement with Baxalta. Halozyme will continue to record and report royalty revenues over the term of the loan, using the payments from the collaboration agreements as the source of funds to repay the principal and interest on the loan. Milestone payments received under any current or future collaboration agreements are excluded from the transaction.

Under the terms of the credit agreement, Halozyme Royalty will not be required to apply any of the royalty payments to repay the loan during 2016. All interest accrued in 2016 will be capitalized and added to the outstanding balance of the loan. Halozyme Royalty will only be required to apply 50 percent of royalty payments received in 2017 to make principal and interest payments subject to quarterly caps set forth in the credit agreement. Thereafter, subject to quarterly caps set forth in the credit agreement, Halozyme Royalty will apply all of the royalty payments received to repay outstanding principal and interest on the loan. If royalty payments available to repay the loan are insufficient to pay accrued interest due on any quarterly payment date, the unpaid interest will be capitalized and added to the outstanding principal balance of the loan. Royalty payments received in excess of the quarterly caps will be retained by Halozyme Royalty and distributed to Halozyme. Loan-related expenses will be deducted from the royalty payments before such amounts are applied to the loan or distributed to Halozyme Royalty.

The final maturity date of the loan will be the earlier of (i) the date when the principal amount and accrued interest are paid in full, (ii) the termination of Halozyme Royalty’s right to receive royalties under the collaboration agreements with Roche and Baxalta and (iii) December 31, 2050. Repayment of the loan is the sole obligation of Halozyme Royalty and is intended to be non-recourse to Halozyme Therapeutics, Inc. and its other subsidiaries.