On March 3, 2016 Merck, Pfizer and Verastem reported that they have entered into an agreement to evaluate avelumab*, an investigational fully human anti-PD-L1 IgG1 monoclonal antibody, in combination with Verastem’s VS-6063**, an investigational focal adhesion kinase (FAK) inhibitor, in patients with advanced ovarian cancer (Press release, Merck KGaA, MAR 3, 2016, View Source [SID:1234509356]). Avelumab is currently under clinical investigation across a broad range of tumor types. The Phase I/Ib clinical trial is expected to begin in the second half of 2016. Financial terms of the agreement have not been disclosed.

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"Combination strategies in immuno-oncology offer significant promise for patients in need. Through our collaboration with Verastem, we hope to accelerate our understanding of avelumab and its potential as a combination therapy with FAK inhibition for patients fighting ovarian cancer," said Dr. Alise Reicin, Head of Global Clinical Development at Merck’s biopharma business.

"Through this collaboration, we hope to advance our understanding of how FAK inhibition may complement our development program for avelumab, with the ultimate goal of potentially achieving better outcomes for women with ovarian cancer," said Chris Boshoff, Vice President and Head of Early Development, Translational and Immuno-Oncology at Pfizer Oncology.

"Recent research shows that FAK inhibitors could be beneficial in combination with immuno-oncology agents.1 We are excited to be working with Merck and Pfizer to build upon the early clinical signals observed in patients with ovarian cancer receiving combination therapy with VS-6063," said Robert Forrester, Verastem President and Chief Executive Officer.

FAK is a protein which is often overproduced in tumors, enabling cancer cells to evade attack by the immune system. As reported in the September 24, 2015, edition of Cell, pre-clinical research shows that FAK inhibition can modulate the balance of immune cells in the tumor, increasing the presence of cytotoxic T cells in the tumor and decreasing the presence of immunosuppressive T regulatory cells.1

*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.

**VS-6063 (defactinib) is under clinical investigation and has not be proven to be safe and effective. There is no guarantee any product will be be approved in the sought-after indication by any health authority worldwide.

References
1. Serrels A et al. FAK Controls Chemokine Transcription, Tregs, and Evasion of Anti-tumor Immunity. Cell 2015; 163 (1): 160-73
2. Ferlay J et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: View Source Accessed December 2015.
3. World Cancer Research Fund International. Ovarian Cancer Statistics. Available from: View Source Accessed November 2015.
4. NICE. Ovarian Cancer: Recognition and Initial Management. Available from:
View Source Accessed November 2015.
5. National Cancer Institute. Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer Treatment (PDQ). Available from:View Source Accessed November 2015.
6. Ledermann JA et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO (Free ESMO Whitepaper) clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24(Suppl 6): vi24-32.
7. Ojalvo LS et al. Emerging immunotherapies in ovarian cancer. Discov Med 2015; 20(109): 97-109.

About Ovarian Cancer

Globally, ovarian cancer is the seventh most common cancer in women.2 Annually, nearly 239,000 cases are diagnosed worldwide.3 Ovarian cancer may be difficult to diagnose, as symptoms may appear only in the later stages, when the disease has spread beyond the ovaries.3 Outcomes for women with ovarian cancer are generally poor due to most patients presenting with advanced disease.4 The 5-year prevalence of women globally living with ovarian cancer is 22.6 per 100,000.3 Current treatment options for epithelial ovarian cancer may include surgery, radiotherapy, chemotherapy and targeted therapies.5 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.6 Platinum-refractory ovarian cancer is defined as ovarian cancer that progresses during treatment with a platinum-based chemotherapy regimen.6 There is still a clear unmet need in ovarian cancer in relation to general disease awareness,3 improving initial investigations in primary and secondary care and novel therapies with demonstrable efficacy.7

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 enable the activation of T-cells and the adaptive immune system. By retaining a native Fc-region, avelumab is thought to potentially engage the innate immune system and induce antibody-dependent cell-mediated cytotoxicity (ADCC). In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

On March 3, 2016 Agenus Inc. (NASDAQ:AGEN), an immuno-oncology company developing checkpoint modulator antibodies and cancer vaccines, reported a corporate update and reported financial results for the fourth quarter and year ended December 31, 2015 (Press release, Agenus, MAR 3, 2016, View Source [SID:1234509351]).

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"During the course of 2015, we broadened our capabilities and advanced our portfolio of checkpoint antibodies and diversified vaccine platforms," commented Garo H. Armen, Ph.D., Chairman and CEO of Agenus. "We made a series of strategic acquisitions, in our efforts to speed discovery and development, as well as to improve the quality of our leads and programs. We also validated our portfolio and discovery capabilities through our strategic alliances with Incyte and Merck. Our greatest asset, however, is our team of scientists with their breadth of expertise.

We believe a multidisciplinary approach is critical because the future of cancer therapy will be based on the ability to identify subpopulations of patients that are likely to best respond to specific immuno-oncology (I/O) agents or combinations. This will require tailored combinations of I/O modalities, including antibodies, vaccines and adjuvants, and cell therapies. At Agenus, we believe that we are uniquely positioned in the I/O landscape by having assembled the critical parts of what could be the future I/O ecosystem.

To support all these endeavors, last year we strengthened our cash position through partnerships, a stock offering and a non-dilutive royalty financing, all affording the company a financial runway through the first half of 2017."

2015 HIGHLIGHTS AND CURRENT UPDATES

January: Leveraged in-house resources through a global license, development and commercialization agreement with Incyte Corporation. The alliance initially focused on the development of four CPM antibodies targeting GITR, OX40, LAG-3 and TIM-3, and was expanded in November 2015 to include three additional undisclosed targets. Agenus and Incyte share costs and profits equally for the GITR and OX40 programs, as well as two of the undisclosed programs. Agenus received a $60 million upfront payment, which included a $35 million equity investment. Agenus is also eligible to receive up to $350 million in development, regulatory and commercial milestones across the initial four lead programs.

April / November: Optimized our discovery of antibodies through acquisition of the Celexion, LLC, SECANT yeast display platform and an agreement with IONTAS for an exclusive license to a proprietary phage display library.

May: Raised approximately $75 million through a public offering of common stock.

June: Strengthened management team with the appointment of C. Evan Ballantyne as the Company’s Chief Financial Officer.
July: Acquired rights to antibodies targeting Carcinoembryonic Antigen Cell Adhesion Molecule 1 (CEACAM1), a glycoprotein expressed on T-cell and NK-cell lymphocytes from Diatheva s.r.l., an Italian biotech company.

September: Raised net proceeds of approximately $78 million in a non-dilutive royalty transaction pursuant to a Note Purchase Agreement with an investor group led by Oberland Capital Management, LLC. The investors received our rights to worldwide royalties on future sales of GlaxoSmithKline’s (GSK) shingles (HZ/su) and malaria (RTS,S) prophylactic vaccine products that contain Agenus’ QS-21 adjuvant to repay principal and interest. At its option, Agenus has the right to buy back the loan at any time under pre-specified terms. Agenus also has the right to receive an additional $15 million in cash from the investors after approval of HZ/su by the FDA, provided such approval occurs by June 30, 2018. This financing also allows Agenus to retain any upside from vaccine royalties remaining after the loan terms are satisfied.

December: Secured our own antibody manufacturing capability through the acquisition of XOMA Corporation’s antibody manufacturing pilot plant and an agreement granting Agenus access to Selexis’ cell line development technologies.

December: Expanded our cancer vaccine program by acquiring privately-held PhosImmune Inc., a company with a portfolio of cancer neoantigens based on aberrant phosphorylation of proteins. The acquisition provides Agenus the ability to potentially accelerate the development of novel off-the-shelf and personalized cancer vaccines and is synergistic with Agenus’ AutoSynVax (ASV) vaccine program for targeting patient-specific tumor neoantigens.

December: Advanced first two checkpoint modulator antibodies toward the clinic by submitting Investigational New Drug (IND) applications to the U.S. Food and Drug Administration (FDA) for AGEN1884 (a CPM antibody that binds to CTLA-4) and INCAGN01876 (a CPM antibody that targets GITR and is partnered with Incyte). In January 2016, the FDA cleared both IND applications.

Upcoming 2016 Program Milestones and Events:

Initiation of Phase 1 clinical trials for anti-CTLA-4 antibody candidate (AGEN1884; wholly owned by Agenus), and for anti-GITR antibody candidate (INCAGN01876, partnered with Incyte) in the first half of 2016.

Initiation of Phase 1 clinical trials for one or more additional CPM antibody candidates in the second half of 2016.

Initiation of a well-controlled randomized Prophage clinical vaccine trial in newly diagnosed glioblastoma patients in the second half of 2016.

Initiation of Phase 1 clinical trial with our first ASV vaccine product candidate in the second half of 2016. Agenus’ ASV program targets cancer neoantigens with an autologous synthetic vaccine approach.

Partner (GSK) filing for regulatory approval of its shingles vaccine candidate containing Agenus’ proprietary QS-21 Stimulon adjuvant in the second half of 2016.

Initiation of combination trials with Agenus vaccines and CPM antibody candidates in the second half of 2016.
Continually evaluate additional strategic alliances and partnerships.

Fourth Quarter and 2015 Financial Results

Cash, cash equivalents and short-term investments were $171.7 million as of December 31, 2015.

For the fourth quarter, Agenus reported a net loss attributable to common stockholders of $15.7 million, or $0.18 per share, basic and diluted, compared with a net loss attributable to common stockholders for the fourth quarter of 2014 of $26.0 million, or $0.41 per share, basic and diluted.

The decreased net loss attributable to common stockholders for the quarter ended December 31, 2015, compared to the net loss attributable to common stockholders for the same period in 2014, was due primarily to a $14.8 million decrease in the non-cash charges related to our contingent obligations as well as increased revenue of $6.0 million related to our Incyte collaboration partially offset by increased expenses related to our CPM programs. We recorded non-cash expenses for the quarter ended December 31, 2014 of $6.5 million, due to the fair value adjustment of the contingent purchase price consideration, and $7.7 million related to the fair value adjustment of our contingent royalty obligation. This compares to non-cash income of $623,000 related to the contingent purchase price consideration for the quarter ended December 31, 2015.

For the year ended December 31, 2015, the company incurred a net loss attributable to common stockholders of $88.1 million, or $1.13 per share, basic and diluted, compared with a net loss attributable to common stockholders of $42.7 million, or $0.71 per share, basic and diluted, compared to the same period in 2014.

The increase in net loss attributable to common stockholders for the year ended December 31, 2015, compared to the net loss attributable to common stockholders for the same period in 2014, was primarily due to the advancement of our check point modulator programs, partially offset by the increased revenues of $17.8 million primarily related to our Incyte collaboration; a $13.2 million charge for the acquisition of the SECANT yeast display platform and other license and technology transfer arrangements. We also recorded a total of $13.6 million in non-cash expense for fair value adjustments to our contingent obligations.

During the same period of 2014, the company recorded non-cash expense of $6.7 million due to the fair value adjustment of the contingent purchase price consideration and non-cash income of $2.1 million related primarily to various GlaxoSmithKline vaccine trial results containing QS-21 Stimulon.

On March 3, 2016 Janssen Products, LP reported that it has informed PharmaMar(MSE:PHM) that regulatory authorities in 6 countries have granted 10 new authorisations to sell Yondelis: five for treating relapsed platinum-sensitive ovarian cancer (ROC), in combination with Caelyx (pegylated liposomal doxorubicin), and 6 as monotherapy for treating soft tissue sarcoma (STS) (Press release, PharmaMar, MAR 3, 2016, View Source [SID:1234509347]).

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The six countries that have authorised Yondelis for ROC and/or STS are SaudiArabia, Moldavia, Bangladesh, Brunei, Costa Rica and Kuwait.

As a result, Yondelis is now approved in nearly 80 countries, 31 of which are in the European Economic Area (EEA). The European Commission approved Yondelis for soft tissue sarcoma in 2007, and at the end of 2009 they approved the sale of this
drug in combination with pegylated liposomal doxorubicin for relapsed platinumsensitive ovarian cancer.

In 2015, the U.S. Food and Drug Administration (FDA) gave Janssen Products, LP, the marketing approval for YONDELIS for the treatment of patients with unresectable or metastatic liposarcoma (LPS) or leiomyosarcoma (LMS); and the drug was also approved by the Japanese Minister of Health, Labour and Welfare to Taiho Pharmaceutical Co., Ltd. for the treatment of patients with soft tissue sarcoma.

Yondelis has orphan drug status for soft tissue sarcoma and ovarian cancer in the European Union, the United States, and Switzerland, and for soft tissue sarcoma in Japan and South Korea.

According to the licensing agreement between PharmaMar and Janssen Products, LP, PharmaMar has the rights to sell Yondelis in Europe (including Eastern Europe), while Janssen Products, LP has the rights to sell the drug everywhere else except Japan, where PharmaMar has granted a license to Taiho Pharmaceutical Co., Ltd. for the development and sale of Yondelis.

About YONDELIS (trabectedin)
YONDELIS (trabectedin) is a novel, multimodal, synthetically produced antitumor agent, originally derived from the sea squirt, Ecteinascidia turbinata. The drug exerts its activity by targeting the transcriptional machinery and impairing DNA repair. It is approved in nearly 80 countries in North America, Europe, South America and Asia for the treatment of advanced soft tissue sarcomas as a single-agent and for relapsed ovarian cancer in combination with DOXIL/CAELYX (doxorubicin HCl
liposome injection). Under a licensing agreement with PharmaMar, Janssen Products, L.P. has the rights to develop and sell YONDELIS globally except in Europe, where PharmaMar holds the rights, and in Japan, where PharmaMar has granted a license to Taiho Pharmaceuticals.