On August 6, 2015 Halozyme Therapeutics, Inc. (Nasdaq: HALO) reported the Pancreas Center at the University of California, San Francisco (UCSF) has initiated a clinical research study of Halozyme’s investigational new drug, PEGPH20 in pancreatic cancer patients who are candidates for potentially curative surgery (Press release, Halozyme, AUG 6, 2015, View Source [SID:1234507081]). The trial will be conducted within the UCSF Helen Diller Family Comprehensive Cancer Center.

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The Phase 2 study will investigate PEGPH20 in combination with gemcitabine and nab-paclitaxel (ABRAXANE) in patients with borderline resectable Pancreatic Ductal Adenocarcinoma (PDAC). The study will track the progress of up to 36 patients through chemotherapy and surgical treatment.

PEGPH20 (PEGylated recombinant human hyaluronidase) targets the degradation of hyaluronan (HA), a chain of natural sugars that can accumulate around cancer cells, inhibiting other therapies. By degrading HA, PEGPH20 may increase the access of co-administered chemotherapeutic and immunotherapeutic agents.

"This is a unique study to determine if PEGPH20, when administered in combination with other cancer-fighting drugs, will better prepare patients for surgery," said Margaret Tempero, MD, director of the UCSF Pancreas Center. "We will observe outcomes of our patients to learn if this combination therapy with PEGPH20 could make a difference in potentially curative surgery."

At the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting this year, interim results of the randomized Phase 2 Study 202 clinical study of PEGPH20 with ABRAXANE and gemcitabine showed a doubling of progression-free survival and an improvement trend in overall survival in high HA metastatic pancreatic cancer patients. In addition, the potential risk profile, including the rate of thromboembolic events, were also presented.

"We believe PEGPH20 may improve the effectiveness of co-administered cancer therapies, and both our preclinical data and clinical studies in metastatic pancreatic cancer patients are showing encouraging results," said Halozyme Chief Medical Officer, Athena Countouriotis, MD. "We are very pleased that independent scientists within academia are interested in focusing on the tumor microenvironment and the potential benefits of PEGPH20 in another area of pancreatic cancer."

About HDFCCC at UCSF

The Helen Diller Family Comprehensive Cancer Center at UC San Francisco is a member of the national NCI-funded Cancer Center network focusing on research. The HDFCCC combines basic science, clinical research, epidemiology/cancer control and patient care from throughout the UCSF system. For more information, visit: View Source

About UCSF Pancreas Center

The UCSF Pancreas Center treats patients with a wide range of pancreatic disorders from cancer and benign tumors to pancreatitis. Our team includes specialists in anesthesia, gastroenterology, neurology, nursing, psychology and surgery for the diagnosis and treatment of disease and the management of pain. Our patients also have the opportunity to participate in research to test the latest experimental therapies. For more information, visit: View Source

On August 6, 2015 MabVax Therapeutics Holdings, Inc. (OTCQB: MBVX), a clinical stage oncology drug development company, and The Rockefeller University’s Laboratory of Molecular Genetics and Immunology reported the have entered into a research collaboration agreement to explore the mechanism of action of constant region (Fc) variants of the HuMab 5B1 in the role of tumor clearance (Press release, MabVax, AUG 6, 2015, View Source [SID:1234507079]). The objective is to optimize Fc receptor mediated antibody function.

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The work will be conducted in the Laboratory of Molecular Genetics and Immunology at The Rockefeller University, which is headed by Jeffery Ravetch, M.D., Ph.D. Dr. Ravetch is a leading researcher who unraveled the importance of the antibody constant region (Fc) and described the mechanisms of antibody-mediated effector responses. The Fc portion of an antibody plays a critical functional role by binding to various cellular receptors as well as complement proteins, and it is responsible for recruiting other immune system cells to attack the tumor cell resulting in destruction of the targeted cell.

The Company recently announced that it will file investigational new drug (IND) applications with the U.S. Food and Drug Administration for a HuMab 5B1-based therapeutic product and a next generation PET imaging agent later this year. The Company anticipates initiating Phase I trials in the first quarter of 2016.

David Hansen, President and CEO of MabVax Therapeutics, explained, "Because we are working on a very difficult to treat disease, pancreatic cancer, as our first therapeutic indication, the Company has been initiating research and development programs on next-generation HuMab 5B1-based therapeutic products. These programs are geared toward increasing the potency as well as the antibody-mediated effect of the current product. While we believe that the current HuMab 5b1 product will demonstrate effectiveness in our early studies, the longer term strategy is to bring more potent products to the market in the next few years."

Because the HuMab 5B1 antibody is fully human and recovered from patients undergoing cancer vaccine treatment at Memorial Sloan-Kettering Cancer Center, the Company believes that these antibodies reduce the likelihood of unwanted immunogenicity and cross reactivity. The results from preclinical studies continue to build the body of evidence that makes the HuMab 5B1 product a valuable asset. The Company believes that its unique dual-product development approach – of having both a therapeutic and diagnostic application – is applicable to other cancers utilizing our HuMab 5B1 antibody as well as with follow-on antibodies already under development in our preclinical pipeline.

On August 6, 2015 Vanderbilt University reported that Vanderbilt-Ingram Cancer Center (VICC) investigators and colleagues at several major medical centers have been testing a new targeted therapy that is showing promise for the treatment of a rare tumor that forms in and around joint cavities (Press release, Vanderbilt University, AUG 6, 2015, View Source [SID:1234507070]).

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The study was published in the July 30 issue of The New England Journal of Medicine.

Tenosynovial giant-cell tumors, also known as pigmented villonodular synovitis (PVNS), are rare, locally aggressive tumors that develop in the lining of joints, including knees, hips, shoulders, elbows, ankles and feet. These tumors, which feature painful inflammation, often grow and destroy the joint, leading to joint replacement surgery or even amputation. There is no approved systemic therapy.

The newly designed drug, PLX3397, is a tyrosine kinase inhibitor that blocks interaction between the colony-stimulating factor1 (CSF1) gene and the gene receptor (CSF1R). Expression of the CSF1 gene is elevated in most cases of tenosynovial giant-cell tumor.

Igor Puzanov, M.D.
The multicenter clinical trial, led by William Tap, M.D., at Memorial Sloan Kettering Cancer Center, New York, included a Phase 1 dose escalation study to establish a safe dose of PLX3397. Igor Puzanov, M.D., associate professor of Medicine and associate director of Phase 1 Drug Development, led VICC’s Phase 1 portion of the trial in patients with solid tumors.

Forty-one patients enrolled in the dose-escalation study and 35 patients completed this portion of the study. Patients received MRI imaging at the time of enrollment and every two months to assess the status of their tumors.

The mean duration of treatment with PLX3397, which is given in capsule form, was 70.7 days. Eight of the patients had stable disease and one had a partial response.

A multicenter extension study with 23 patients was conducted to test the safety and efficacy of PLX3397 in patients with tenosynovial giant-cell tumors. Most of the patients had tumors in the knee. Vicki Keedy, M.D., assistant professor of Medicine and clinical director of the Sarcoma Program, led VICC’s effort.

Vicki Keedy, M.D.
In the extension study, 12 of the 23 patients had a partial response for an overall response rate of 52 percent, and seven of the 23 had stable disease. The total rate of disease control (complete response, partial response or stable disease) was 83 percent. Only one patient who already had metastatic disease had disease progression. The median duration of treatment was eight months at the time of data cutoff.

The investigators found that patients generally had a large reduction in tumor burden within the first four months of treatment that persisted over time. The mean decrease in tumor volume score was 61 percent.

Side effects from the therapy included changes in hair color, fatigue and nausea. An elevation in liver enzymes also occurred in half of patients.

Based on this research and a previous study, the authors said it appears tenosynovial giant-cell tumor can be added to the "growing list of oncogene-driven neoplasms that respond to drugs targeting the oncogenic driver."

Patients often develop resistance to targeted therapies and the authors said it will be important to determine if resistance occurs with this new drug, along with the mechanisms that cause treatment resistance.

Plans are underway for additional trials of the new therapy.

Collaborators participating in the study include investigators from Weill Cornell Medical College, New York; University of California Los Angeles Medical Center; Stanford University School of Medicine, California; Evergreen Hematology and Oncology, Spokane, Washington; University of Pennsylvania School of Medicine, Philadelphia; Rocky Mountain Cancer Centers, Denver; Dana-Farber Cancer Institute and Massachusetts General Hospital, Boston; Virginia G. Piper at Scottsdale Healthcare-Translational Genomics Research Institute, Scottsdale, Arizona; Spire Sciences, Boca Raton, Florida, and Plexxikon, Berkeley, California.
Plexxikon provided funding for the study.

On August 6, 2015 Emergent BioSolutions Inc. (NYSE:EBS) reported that its Board of Directors has authorized management to pursue a tax-free spin-off of the company’s Biosciences business into a separate, stand-alone publicly-traded company (Press release, Emergent BioSolutions, AUG 6, 2015, View Source [SID:1234507056]). The spin-off is expected to create two independent public companies with distinct strategic plans, growth strategies, and operational and development priorities.

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The new Biosciences company, to be named at a later date, will focus on providing novel oncology and hematology therapeutics to meaningfully improve patients’ lives. The core technology of the Biosciences company will be its ADAPTIR platform applied to immuno-oncology. Emergent BioSolutions will continue to operate as a global specialty biopharmaceutical company whose core business is focused on providing specialty products for civilian and military populations that address intentional and naturally emerging public health threats.

"The proposed spin-off recognizes that our two operating divisions have evolved into distinct business and investment opportunities. The Biosciences spin-off establishes each as a pure play company with a focused strategy and enables each company to target investors attracted to its business profile," said Daniel J. Abdun-Nabi, President and Chief Executive Officer of Emergent BioSolutions. "This transaction will allow us to accelerate our growth strategy while enabling the new Biosciences company to invest in novel therapeutics in the highly attractive immuno-oncology field. We expect the spin-off to enhance business focus, better align resources to achieve strategic priorities, and unlock significant value for both companies."

Strategic Rationale
Emergent believes that establishing the Biosciences business as a stand-alone public company offers a number of benefits. The spin-off will enable each company to:

tailor business strategies to best address opportunities within its target market,
enhance business focus and better align resources to achieve strategic priorities,
pursue distinct capital structures and capital allocation strategies, and
target investors attracted to its business profile.
New Biosciences Company: A biopharmaceutical company focused on novel oncology and hematology therapeutics to meaningfully improve patients’ lives

The new Biosciences company will consist of certain assets currently in Emergent’s Biosciences division, including:

the ADAPTIR (modular protein technology) platform including bi-specific therapeutics based on Redirected T-cell Cytotoxicity (RTCC), a promising approach within immuno-oncology,

MOR209/ES414, a bi-specific therapeutic for metastatic castration resistant prostate cancer currently in Phase 1 clinical development in partnership with MorphoSys AG, and

a commercial product portfolio consisting of IXINITY, WinRho, HepaGam B, and VARIZIG.

The Biosciences company will be well-positioned to:

establish itself as a "pure play" biopharmaceutical company in the highly attractive immuno-oncology field,
target investments and operations in the development of bi-specific therapeutics using the proprietary ADAPTIR platform technology,
increase awareness of ADAPTIR’s RTCC mechanism of action, and
provide greater visibility into its innovative platform technology and product candidates for potential collaborators.
Emergent expects to provide the Biosciences company with a fixed cash contribution of $50 million to $70 million. Additional sources of cash to support R&D investment will include commercial product sales and partnership funding.

Emergent BioSolutions: A global specialty biopharmaceutical company focused on providing specialty products for civilian and military populations that address intentional and naturally emerging public health threats

Emergent will retain the biodefense marketed products and development programs, platform technologies, and manufacturing infrastructure. Emergent will maintain its headquarters in Gaithersburg, Maryland, biodefense product development facilities in Gaithersburg, Maryland and Munich, Germany, cGMP manufacturing facilities in Lansing, Michigan, Hattiesburg, Mississippi, and Winnipeg, Manitoba, Canada, as well as its CMO fill/finish operations in its Camden site in Baltimore, Maryland. Emergent’s Bayview Campus, also in Baltimore, Maryland, will continue to operate as an HHS-designated Center for Innovation in Advanced Development and Manufacturing. Emergent’s Winnipeg manufacturing facility is expected to serve as primary CMO for some products of the Biosciences company under an arm’s length, long-term manufacturing agreement.

Emergent, with its focus on its core biodefense business, will be better positioned to:

establish itself as a "pure play" company, recognized as a leader in the biodefense and emerging infectious diseases fields,
enhance its financial returns and operating margins through the elimination of biosciences related R&D, sales, marketing and G&A costs, and allow greater flexibility in its capital allocation decisions.

Leadership
As stand-alone public companies, Emergent and the new Biosciences company will have separate management teams and boards of directors. Daniel J. Abdun-Nabi will remain President and Chief Executive Officer and Robert G. Kramer will remain Executive Vice President and Chief Financial Officer of Emergent. Fuad El-Hibri will remain Executive Chairman of the Board of Directors.

Upon completion of the spin-off, Marvin L. White will serve as President and Chief Executive Officer of the new Biosciences company. Mr. White is currently a member of Emergent’s Board of Directors. He is the former Chief Financial Officer of St. Vincent’s Health, a $2.8 billion multi-hospital health system. Mr. White previously served as Executive Director and CFO of Lilly USA, a subsidiary of Eli Lilly and Company, and held other positions in corporate finance at Eli Lilly and Company.

"Marvin brings more than two decades of experience as a senior executive of prominent pharmaceutical and healthcare organizations," said Mr. Abdun-Nabi. "Having worked with Marvin on our board for five years, it is clear that his combination of leadership talents and business acumen will serve the new Biosciences company well as it strives to achieve the promise of its product portfolio and platform technology."

"Having witnessed the development of the biosciences business as an Emergent director, I am excited for the opportunity to grow this business as an independent public company by leveraging its innovative ADAPTIR technology in the highly-desirable immuno-oncology field," said Mr. White. "I look forward to working with the talented team within the new Biosciences company to advance its unique product candidates for the benefit of patients."

Additional details of the board and management team of the new Biosciences company will be provided at a later date.

Financial Guidance
Emergent expects to incur transaction-related expenses of $2 million to $4 million in 2015, which are included in its reaffirmed 2015 financial guidance. The company expects additional costs in 2016 leading up to completion of the spin-off.

Additional Information and Next Steps
The transaction is intended to take the form of a tax-free distribution to Emergent’s shareholders of common stock of a new publicly-traded Biosciences company. The stock distribution ratio and other matters, including the stock exchange on which the new Biosciences company’s stock will be listed, will be determined at a later date. Emergent will continue to be listed on the New York Stock Exchange under its existing symbol "EBS."

More details about the Biosciences company, including pro forma financial information, will be disclosed when the new Biosciences company files a Form 10 registration statement with the Securities and Exchange Commission in connection with the transaction. The initial filing of the Form 10 registration statement is expected to occur in the first quarter of 2016. The transaction is expected to be completed in mid-2016, subject to certain conditions, including the receipt of a favorable opinion from outside tax counsel and private letter ruling from the Internal Revenue Service, execution of inter-company agreements by Emergent and the new Biosciences company, the effectiveness of the Form 10 registration statement, and final approval of the transaction by Emergent’s board of directors.

The transaction will not require the approval of Emergent’s shareholders. Obligations under the 2.875% Convertible Senior Notes due 2021 will remain with Emergent following completion of the transaction, subject to the conversion adjustments provided in the indenture governing the notes.

Emergent may, at any time and for any reason until the proposed spin-off is complete, abandon the spin-off or modify its terms and conditions.

Emergent is being advised by J.P. Morgan Securities LLC, as financial advisor, and by Wilmer Cutler Pickering Hale and Dorr LLP, as legal advisor.

On August 6, 2015 AstraZeneca and Heptares Therapeutics, the wholly-owned subsidiary of Sosei Group Corporation, reported that they have entered into a licensing agreement under which AstraZeneca will acquire exclusive global rights to develop, manufacture and commercialise the adenosine A2A receptor antagonist, HTL-1071, a small molecule immuno-oncology candidate, and potential additional A2A receptor-blocking compounds (Press release, AstraZeneca, AUG 6, 2015, View Source;astrazeneca-and-heptares-therapeutics-enter-agreement [SID:1234507045]).

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AstraZeneca will explore the assets across a range of cancers, including in combination with its existing portfolio of immunotherapies.

Tumour cells have developed mechanisms to evade the immune system, including through the production of a natural molecule called adenosine. By stimulating A2A receptors, adenosine stops T-cells within the immune system from proliferating and reduces their ability to destroy cancer cells. Blocking A2A receptors can therefore promote the anti-cancer response of T-cells within in the tumour microenvironment.

Under the terms of the agreement, Heptares will grant AstraZeneca an exclusive license to research, develop, manufacture and commercialise HTL-1071. The companies will also collaborate to discover further A2A receptor-blocking compounds for development in cancer immunotherapy.

Heptares will receive an upfront payment of $10 million and is eligible to receive additional, significant near term milestone payments based on agreed pre-clinical and/or clinical events. Subject to successful completion of development and commercialisation milestones, Heptares is also eligible to receive more than $500 million, as well as up to double-digit tiered royalties on net sales.

Susan Galbraith, Vice President, Head of Oncology in AstraZeneca’s Innovative Medicines and Early Development Unit, said: "We are pleased to expand our successful collaboration with Heptares into the exciting area of immuno-oncology. By combining the pioneering A2A receptor programme with the strength of AstraZeneca’s oncology portfolio, we hope to develop novel treatments with the potential to transform the lives of patients."

Malcolm Weir, Chief Executive Officer of Heptares, said: "The A2A receptor programme at Heptares has been an outstanding example of our Structure Based Drug Design approach in action, resulting in a novel clinical candidate, HTL-1071, with a highly attractive profile. Heptares is targeting G-protein-coupled receptors that play a key role in cancer biology through the identification of both antibody and small molecule therapeutics. We are delighted to be entering this expanding field by partnering with AstraZeneca, an innovative leader in the field of cancer immunotherapy. This agreement further builds on our successful existing research collaboration."

The transaction is subject to customary clearances under the Hart-Scott-Rodino Antitrust Improvements Act.