Five Prime Therapeutics Provides Update on FP-1039 Clinical Program

On January 11, 2016 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing novel protein therapeutics for cancer and inflammatory diseases, reported an update on GlaxoSmithKline’s (GSK) ongoing Phase 1b clinical trial of FP-1039/GSK3052230, an FGF ligand trap, in patients with squamous non-small cell lung cancer (sqNSCLC) and mesothelioma (Press release, Five Prime Therapeutics, JAN 11, 2016, View Source [SID:1234508729]).

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GSK presented preliminary clinical safety and efficacy data from the Phase 1b trial at the World Conference on Lung Cancer on September 9, 2015. At the time, data from Arm A in treatment-naïve sqNSCLC patients were encouraging, Arm B in second line sqNSCLC had few patients enrolled, and data from Arm C were immature because few mesothelioma patients were then evaluable. Based on preliminary data, GSK and Five Prime have agreed to continue to enroll up to 30 mesothelioma patients at the expansion dose of 15 mg/kg in Arm C of the trial. GSK plans to submit data for presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2016 Annual Meeting in June. The companies have also agreed to stop enrolling the sqNSCLC patient study cohorts given the change in treatment paradigms following approvals of immuno-oncology agents and the increasingly competitive landscape.

"We are encouraged by the preliminary data we have recently reviewed from the mesothelioma arm of the study and look forward to seeing the results as additional patients are enrolled and followed," said Lewis T. "Rusty" Williams, M.D., Ph.D., president and chief executive officer of Five Prime. "The majority of mesothelioma tumors express high levels of FGF-2, so our FGF ligand trap represents a rational therapeutic approach, and patients currently have limited treatment options. If we see similar results once we have full, mature data for Arm C, we will seek to regain rights for FP-1039 in the U.S., Canada and the E.U. from GSK, as mesothelioma could represent a potentially attractive market opportunity for Five Prime."

About the Phase 1b Trial

The Phase 1b clinical trial of FP-1039 is being conducted by GSK and is designed as a three-arm, multicenter, non-randomized, parallel-group, uncontrolled, open-label trial. This clinical trial was designed to evaluate the safety, tolerability, dosage, response rate and duration of response of FP-1039:

in combination with paclitaxel and carboplatin in previously untreated metastatic sqNSCLC (Arm A);
in combination with docetaxel in metastatic sqNSCLC that has progressed after previous therapy (Arm B); or
in combination with front-line pemetrexed and cisplatin in mesothelioma (Arm C), a tumor in which the FGF-2 ligand is overexpressed.

About FP-1039

FP-1039 is a protein drug designed to intervene in FGF signaling. As a ligand trap, FP-1039 binds to FGF ligands circulating in the extracellular space (such as FGF-2), preventing these signaling proteins from reaching FGFR1 on the surface of tumor cells where they would otherwise stimulate cancer cell division and/or angiogenesis. However, FP-1039 does not bind to certain "hormonal" FGFs, including FGF-23, which regulates phosphate levels in the blood. As a result, treatment with FP-1039 treatment has not been shown to cause hyperphosphatemia, a side effect seen with small molecule inhibitors of FGF receptors, which block the activity of both cancer-associated FGFs and FGF-23.

About Mesothelioma

Mesothelioma is a disease with high unmet medical need and high mortality rate. A majority of mesothelioma patients have tumors with abnormally high levels of FGF-2. In preclinical testing, Five Prime observed inhibition of mesothelioma tumor growth with single-agent FP-1039. Mesothelioma is an orphan indication in the United States with a prevalence of about 4,000 patients and incidence of about 3,000 patients. Worldwide, there are a total of approximately 14,000 cases of mesothelioma diagnosed each year.

Eagle Pharmaceuticals and AMRI Announce Agreement to Jointly Develop, Manufacture and Commercialize Parenteral Drug Products

On January 11, 2016 Eagle Pharmaceuticals ("Eagle" or the "Company") (NASDAQ:EGRX) and AMRI (NASDAQ:AMRI) reported that they have entered into an agreement to jointly develop and manufacture several select and complex parenteral drug products for registration and subsequent commercialization in the United States, which will significantly expand Eagle’s portfolio of existing products and product candidates targeting therapeutic areas including oncology, critical care and orphan diseases (Press release, Eagle Pharmaceuticals, JAN 11, 2016, View Source [SID:1234508715]).

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Under terms of the agreement, AMRI will develop and initially provide cGMP manufacturing and analytical support for the registration of the new product candidates. Eagle will be responsible for advancing the product candidates through clinical trials and regulatory submissions.

AMRI will be reimbursed certain costs for formulation activities, process and analytical development and manufacture of regulatory submission batches. Following U.S. Food and Drug Administration ("FDA") approval, AMRI will supply the products to Eagle pursuant to a commercial supply agreement and receive payments based on Eagle’s sales of the products. Eagle will be responsible for U.S. commercial distribution of all approved products, once approved by the FDA.

"As we commercialize our FDA approved products and bring additional products pending approval to market in 2016, this agreement will allow Eagle to expand our portfolio of injectable therapies in a focused and efficient manner by coupling our internal expertise in clinical, regulatory and commercial execution with AMRI’s unique depth of experience with aseptic formulation development, working with complex Active Pharmaceutical Ingredients (API) and handling highly-specialized manufacturing requirements. With this agreement, we expect to more efficiently scale our development infrastructure and speed our market entry with new products, ultimately building long term value for customers and shareholders alike," stated Scott Tarriff, President and Chief Executive Officer of Eagle Pharmaceuticals.

"We are very pleased to partner with Eagle as they look to expand their portfolio of innovative products that address unmet needs. We are very impressed with what Eagle is preparing to bring to market and look forward to playing a key role in the advancement of their product portfolio," said Bill Marth, AMRI’s President and CEO.

8-K – Current report

On January 11, 2016 Shire plc (LSE: SHP, NASDAQ: SHPG) and Baxalta Incorporated (NYSE: BXLT) reported that the boards of directors of both companies have reached an agreement under which Shire will combine with Baxalta (Filing, 8-K, Shire, JAN 11, 2016, View Source [SID:1234508775]). Under the agreement, Baxalta shareholders will receive $18.00 in cash and 0.1482 Shire ADS per Baxalta share. Based on Shire’s closing ADS price on January 8, 2016, this implies a total current value of $45.57 per Baxalta share, representing an aggregate consideration of approximately $32 billion. The exchange ratio was based on Shire’s 30-day trading day volume weighted average ADS price of $199.03 as of January 8, 2016, which implies a total value of $47.50 per Baxalta share.

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The value of the offer, as of Shire’s January 8, 2016 closing ADS price, represents a premium of approximately 37.5% to Baxalta’s unaffected share price on August 3, 2015, the day prior to the public announcement of Shire’s initial offer for Baxalta. This will provide Baxalta shareholders with approximately 34% ownership in the combined company. The parties expect the transaction to close mid-2016.

Shire Chief Executive Officer Flemming Ornskov, M.D., M.P.H., commented:

"This proposed combination allows us to realize our vision of building the leading biotechnology company focused on rare diseases. Together, we will have leadership positions in multiple, high-value franchises and become the clear partner of choice in rare diseases. Our expanded portfolio and presence in more than 100 countries will drive our growth to over $20 billion in anticipated annual revenues by 2020. Our due diligence has reinforced our belief in the combination, and we look forward to welcoming Baxalta colleagues to a shared entrepreneurial, patient-driven culture."

Susan Kilsby, Chairman of Shire, commented:

"Together, Shire and Baxalta create a platform for sustainable innovation, growth and value creation. Shire is an experienced and disciplined acquirer with a track record of delivering shareholder value. Stakeholders of both companies are expected to benefit from the enhanced growth prospects, superior operational scale and efficiency and the strong financial and organizational profile of the combined entity."

Baxalta Chief Executive Officer Ludwig N. Hantson, Ph.D., commented:

"Today’s announcement marks a new path forward for our organization and is a testament to the significant progress we have made in achieving our strategic business priorities. This transaction presents a unique opportunity for Baxalta shareholders, who will receive substantial immediate value as well as an ongoing stake in a combined global leader in rare diseases with strong growth prospects. We bring to Shire a strong portfolio and pipeline of market-leading products, high-quality manufacturing capabilities and a talented global workforce that places patients at the center of everything we do. The combined organization will be well positioned to accelerate innovation and deliver enhanced value for all stakeholders."

Wayne T. Hockmeyer, Ph.D., Chairman of Baxalta, commented:

"We launched Baxalta to focus on purpose-driven performance, sustainable growth, and continuing our leadership in developing treatments for orphan and underserved diseases. While we have made great progress to date and have had a measurable impact across all our businesses, I look forward to joining the board of the combined company to help ensure that we infuse the best of both organizations and foster a new shared culture that has the resources, the passion, and the commitment to continue to make a meaningful difference in the lives of our patients and their families."

Baxter International Chairman and Chief Executive Officer José E. Almeida commented:

"Baxter fully supports the proposed combination of Shire and Baxalta, which will create a major biotechnology company and global leader in rare diseases. Baxter is pleased to support this value enhancing transaction."

Shire will host a conference call for investors and analysts today, January 11, 2016 at 1:30 p.m. GMT / 8:30 a.m. EST / 5:30 a.m. PST. (Details below)

Combination Creates the Global Leader in Rare Diseases with a Sustainable Platform for Future Innovation, Growth and Value Creation

The combination of Baxalta and Shire will create the number one rare diseases platform in revenue and pipeline depth, with best-in-class products in each of the following growing, multi-billion-dollar franchises: Hematology; Immunology; Neuroscience; Lysosomal Storage Diseases; Gastrointestinal / Endocrine; and Hereditary Angioedema (HAE). The combined company will also possess a growing franchise in Oncology, with approved products and innovative compounds in development, as well as a robust late-stage Ophthalmics pipeline.

The combined portfolio will have an expanded range of therapeutic areas with more than 60 programs in development, including over 50 that will address rare diseases and the newly-approved Baxalta products ADYNOVATE, VONVENDI and OBIZUR. Shire anticipates more than 30 recent and planned product launches from the combined pipeline, contributing approximately $5 billion in annual revenues by 2020.

Further, the combined company will benefit from expanded geographic reach across more than 100 countries, with a high-quality commercial organization and world-class manufacturing operations.

Through a balanced portfolio and expanded therapeutic expertise and capabilities, the combination will enhance revenue diversification and optionality for the business, while strong cash flows will increase financial and operational scale. In total, the proposed combination will create a sustainable platform for future innovation and growth, yielding projected near- and long-term value for shareholders.

Leading Franchises, Each with Best-in-Class Products and a Foundation for Sustained Category Leadership in Rare Diseases

The portfolio will include over 20 leading brands and a robust pipeline of expected new product launches with complementary positions across growing multi-billion-dollar franchises:

Hematology

• Baxalta has a well-established hematology portfolio based on its heritage and legacy of leadership in hemophilia. Baxalta offers a comprehensive portfolio of innovative therapeutics, including ADYNOVATE, Antihemophilic Factor (Recombinant), PEGylated, an extended circulating half-life recombinant factor VIII (rFVIII) treatment for hemophilia A which was recently approved in the U.S., and is focused on introducing new treatments for hemophilia and other rare chronic bleeding disorders to further reduce patient burdens

Immunology

• Baxalta is contributing the broadest portfolio of immunoglobulin (IG) products in the industry, most notably the recently launched HYQVIA, a next generation subcutaneous IG treatment for patients with primary immunodeficiency, as well as a pipeline of innovative products across a broad range of potential new indications
Neuroscience

• Shire has over 20 years of experience in neuroscience with a strong, growing ADHD franchise and pipeline, including a new VYVANSE indication for adults with moderate-to-severe Binge Eating Disorder

Lysosomal Storage Diseases

• Shire brings industry-leading capabilities in the development and commercialization of a wide range of therapies for multiple rare and devastating genetic diseases including: VPRIV for long-term enzyme replacement therapy (ERT) for patients with type 1 Gaucher disease; ELAPRASE for patients with Hunter syndrome (Mucopolysaccharidosis II, MPS II); and REPLAGAL for long-term ERT in patients with a confirmed diagnosis of Fabry disease

Gastrointestinal / Endocrine

• Shire’s Gastrointestinal / Endocrine portfolio is built on the strength of its 5-ASA products, LIALDA, for the treatment of mild to moderate ulcerative colitis, and PENTASA, for the treatment of mildly to moderately active ulcerative colitis, and recent additions of GATTEX/REVESTIVE, for adults with short bowel syndrome who are dependent on parenteral support, and NATPARA, as an adjunct to calcium and vitamin D to control hypocalcemia in patients with hypoparathyroidism

HAE

• Shire brings HAE leadership through its currently approved prophylactic and acute therapies, CINRYZE and FIRAZYR, respectively, and—pending completion of the Dyax acquisition—a Phase 3, potentially transformative prophylactic therapy
Ophthalmics

• Shire is focused on building franchise leadership in ophthalmology with the 2016 projected launch of Lifitegrast, contingent upon regulatory approval, for dry eye disease; SHP640 for infectious conjunctivitis entering Phase 3 trials in 2016, and SHP607 for the treatment of retinopathy of prematurity, generating results from its Phase 2 trials which are expected in 2016
Oncology

• Baxalta brings a growing oncology business and a broad platform that positions the combined company at the leading-edge of discovery and development of innovative therapies in hematological and other cancers. The portfolio includes ONCASPAR (pegaspargase), a marketed biologic treatment for acute lymphocytic leukemia, and late-stage, partnered products such as pacritinib, an investigational oral kinase inhibitor for the treatment of patients with myelofibrosis, and ONIVYDE (irinotecan liposome injection) for the treatment of patients with metastatic pancreatic cancer
Financial Highlights

Shire anticipates that it will realize more than $500 million in annual cost synergies (expected to be achieved within the first three years post-closing). These annual cost synergies will be achieved by increasing efficiencies, leveraging the scale of the combined business, aligning to Shire’s lean operating model and optimizing the combined R&D portfolio. Further, Shire expects to generate additional revenue synergies and a combined non-GAAP effective tax rate of 16-17% by 2017. Growth is expected to be accelerated by combining capabilities and establishing a global infrastructure that will include a "best of both" commercial model and a presence in over 100 global markets.

The transaction is expected to be accretive to non-GAAP diluted EPS in 2017, the first calendar year of ownership, and beyond. The combined company is expected to generate annual operating cash flow of $6.0 billion beginning in 2018, underpinning an attractive ROIC that will exceed Shire’s cost of capital in 2020.

Shire has conducted additional tax due diligence, and based on this diligence, Shire and its tax advisor have concluded that a merger with the proposed cash consideration of $18 per Baxalta share will maintain the tax-free status of the Baxalta spinoff from Baxter.

Shire has secured an $18 billion fully underwritten bank facility to finance the combination. The new bank facility has a one year life, with a one-year extension available at Shire’s option. Shire intends to refinance the bank facility through capital market debt issuances in due course. The financing of the transaction has been structured with the intention of maintaining an investment grade credit rating for the combined entity. Shire is committed to de-levering rapidly post-close by deploying free cash flow to repay debt. Shire is targeting a net debt to EBITDA range of between 2.0x and 3.0x 12-18 months post-closing.

Transaction Details

Under the agreement, Baxalta shareholders will receive $18.00 in cash and 0.1482 Shire ADS per Baxalta share. Based on Shire’s closing ADS price on January 8, 2016, this implies a total current value of $45.57 per Baxalta share, representing an aggregate consideration of approximately $32 billion. The exchange ratio was based on Shire’s 30-day trading day volume weighted average ADS price of $199.03 as of January 8, 2016, which implies a total value of $47.50 per Baxalta share.

The value of the offer as of Shire’s January 8, 2016 closing ADS price represents a premium of approximately 37.5% to Baxalta’s unaffected share price on August 3, 2015, the day prior to the public announcement of Shire’s initial offer for Baxalta. This will provide Baxalta shareholders with approximately 34% ownership in the combined company.

Closing

The transaction has been approved by the boards of directors of both Shire and Baxalta. Closing of the transaction is subject to approval by Baxalta and Shire shareholders, certain regulatory approvals, redelivery of tax opinions delivered at signing and other customary closing conditions. The transaction is a class 1 transaction for Shire for the purposes of the UK Listing Rules requiring the approval of Shire shareholders. A shareholder circular, together with notice of the relevant shareholder meeting, will be distributed to Shire shareholders in due course. The parties expect the transaction to close mid-2016.

8-K – Current report

On January 11, 2016 Sorrento Therapeutics, Inc. (NASDAQ: SRNE; Sorrento), an antibody-centric, clinical-stage biopharmaceutical company developing new treatments for cancer and other unmet medical needs, reported that it has formed an exclusive partnership with the world-renowned Karolinska Institutet (KI) in Stockholm, Sweden, to perform cutting-edge immuno-oncology research and to develop new natural killer (NK) cell-based therapies (Filing, 8-K, Sorrento Therapeutics, JAN 11, 2016, View Source [SID:1234508774]).

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Under the agreement, Sorrento will sponsor preclinical and clinical research & development programs focused on NK biology as well as adoptive NK cell therapies and, in return, obtain full rights to the resulting discoveries and developments. The research will be performed at KI, but there will also be an active research exchange with Sorrento R&D in San Diego. A joint steering committee with members from both Sorrento and KI will guide the program activities.

"Given the fact that NK cells were discovered at Karolinska Institutet, it is of course now exciting to take part in the ongoing developments involving these cells in settings of adoptive immunotherapies targeting human malignancies", said Professor Hans-Gustaf Ljunggren, Dean of Research at Karolinska Institutet. "We look forward to teaming up our world-leading NK cell experts with Sorrento’s outstanding scientific team to gain new insights into NK biology and applying these to develop novel cellular therapies."
"We are honored to work with the distinguished KI faculty on discovering and developing new adoptive NK cell immunotherapies", said Dr. Henry Ji, President and CEO of Sorrento. "Through this partnership, Sorrento further establishes its subsidiary, TNK Therapeutics, as one of the premier companies in the cellular therapy space. Building upon the academic and clinical excellence at KI and Sorrento’s expertise in antibody research and development, our partnership will stimulate innovation and may ultimately lead to new ground breaking therapies to improve the lives of cancer patients and their caretakers."

Merck Acquires IOmet Pharma and Expands Immuno-Oncology Development Program

On January 11, 2016 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that it has acquired IOmet, a privately-held UK-based drug discovery company focused on the development of innovative medicines for the treatment of cancer, with a particular emphasis on the fields of cancer immunotherapy and cancer metabolism (Press release, Merck & Co, JAN 11, 2016, View Source [SID:1234508773]). Under terms of the agreement, Merck, through a subsidiary, will acquire IOmet, including its comprehensive pre-clinical pipeline of IDO (indoleamine-2,3-dioxygenase 1), TDO (tryptophan-2,3-dioxygenase), and dual-acting IDO/TDO inhibitors. Based on the transaction, IOmet will become a wholly owned subsidiary of Merck.

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"By harnessing the power of the immune system, we are already witnessing great advancements in the treatment of cancer," said Eric Rubin, M.D., vice president and therapeutic area head, oncology early-stage development, Merck Research Laboratories. "The acquisition of IOmet is a further example of Merck’s commitment to fully realizing the potential of this rapidly evolving field through our existing innovative portfolio as well as the acquisition of promising immunotherapeutic candidates."

"Merck’s leadership in immuno-oncology and expertise in development combined with the potential of our IDO1 and TDO programs creates significant opportunity for us to advance the treatment of cancer," said Alan Wise, Ph.D., CEO, IOmet. "As a company we have benefited from proximity to world class life sciences research including the University of Dundee, an early stage collaborator with us on the IDO1 and TDO programs and from supportive shareholders including the Scottish Investment Bank. We now look forward to joining Merck and feel that this acquisition underscores the shared commitment we have to accelerating our programs to bring solutions to people who need them most."

Financial terms of the acquisition were not disclosed.

About IDO1 and TDO Inhibition

IDO1 and TDO, the rate-limiting enzymes in the pathway that metabolizes the essential amino acid tryptophan, have emerged as key targets for the pharmaceutical industry in the cancer immunotherapy field. Overexpression of these enzymes has been detected in a variety of cancers – including glioma, melanoma, lung, ovarian, and colorectal cancers – and is associated with poor prognosis and survival. IDO1 and TDO overexpression leads to tryptophan depletion and high tumor levels of the breakdown product, kynurenine. This elevated kynurenine/tryptophan (K/T) ratio suppresses the body’s immune response to cancer, thus facilitating tumor progression and metastasis. Extensive preclinical evidence, and emerging clinical data, suggests that inhibition of IDO1 and/or TDO may synergize with, and help overcome resistance to, existing clinical cancer therapies, in particular other immunotherapy-based treatments.

Data involving IOmet Pharma’s novel, pre-clinical IDO1, TDO and IDO1/TDO Dual Inhibitor programs were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in November 2015.