On February 28, 2017 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported that it has expanded its license with Sermonix Pharmaceuticals to include worldwide rights to develop and commercialize oral lasofoxifene. Ligand originally licensed the U.S. rights to oral lasofoxifene to Sermonix in February of 2015, and has now expanded the agreement to include the rest of the world (Press release, Ligand, FEB 28, 2017, View Source [SID1234532255]). Sermonix is focused on breast and ovarian cancer treatment with oral lasofoxifene, particularly an indication in the treatment of advanced Estrogen Receptor positive (ER+) endocrine-resistant breast cancer.

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"Lasofoxifene is an asset with a rich heritage originating at Ligand and with a substantial set of global clinical data. This agreement with Sermonix represents an expansion of our relationship and enables further development of oral lasofoxifene on a worldwide basis," said John Higgins, Chief Executive Officer of Ligand Pharmaceuticals. "This amendment includes an upfront payment, additional commercial milestones and 6% to 10% royalties on ex-US sales and is consistent with our shots-on-goal business model of partnering the development of our assets to create a robust pipeline with limited required R&D spending by Ligand."

About Lasofoxifene and Ligand’s Lasofoxifene Partnerships

Lasofoxifene was discovered through a research collaboration between Ligand and Pfizer that began in 1991. The oral, 0.5 mg form of lasofoxifene tartrate was developed by Pfizer under the trade name Fablyn, and progressed through regulatory approval in the EU. After Pfizer acquired Wyeth and its drug Conbriza (bazedoxifene), a similar SERM program, rights to all forms of lasofoxifene reverted to Ligand in 2011. In 2013 Ligand licensed lasofoxifene to Azure Biotech for the development of a novel formulation targeting an underserved market in women’s health. Also in 2013, Ligand licensed to Ethicor Pharmaceuticals Ltd rights to manufacture and distribute oral lasofoxifene as an unlicensed medicinal product in the European Economic Area, Switzerland and the Indian Subcontinent. Ligand and Ethicor mutually terminated that agreement in early 2017.

On February 28, 2017 Invenra, Inc., a pre-clinical stage bio-pharmaceutical company focused on next-generation therapeutic human antibodies, bispecifics and antibody derivatives, and QIMR Berghofer Medical Research Institute ("QIMR Berghofer"), one of Australia’s largest, fully integrated biomedical research and development centres reported a collaboration to identify and characterize a panel of fully human therapeutic monoclonal antibodies (mAbs) against a novel target that QIMR Berghofer has identified. Financial details of the deal were not disclosed (Press release, Invenra, FEB 28, 2017, View Source [SID1234570589]).

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Invenra’s proprietary platform is based on ultra-high throughput technology allowing function forward screening of full-length antibodies using Invenra’s mAbSeq technology, where antibodies can be directly and quickly interrogated in a multi-plexed fashion with a diverse set of immunotypic and biologically relevant assays. The Invenra technology allows rapid identification of high affinity mAbs with the broadest epitope coverage possible while simultaneously performing direct phenotypic screening to isolate those mAbs with the most relevant biological activity, thus leading to the election of the best lead compounds for further development.

QIMR Berghofer’s Director and CEO, Professor Frank Gannon, said, "We welcome this collaboration and look forward to working with the team at Invenra to advance the characterization and development of novel, effective cancer therapies. At QIMR Berghofer we are strongly committed to translating our research into new and better treatments, diagnostics and prevention strategies."

Roland Green, CEO and president of Invenra, said, "This collaboration is a significant milestone for Invenra as a company and another validation of our innovative technology. We are delighted to be collaborating with the outstanding team at QIMR Berghofer to identify best-in-class antibodies against their novel target. In addition, this collaboration with QIMR Berghofer fits well within our business model, whereby we are partnering with a select group of organizations while continuing to develop our own internal proprietary pipeline of therapeutic product candidates."

On February 28, 2017 MacroGenics, Inc. (NASDAQ:MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, as well as autoimmune disorders and infectious diseases, reported a corporate progress update and reported financial results for the year ended December 31, 2016 (Press release, MacroGenics, FEB 28, 2017, View Source [SID1234517890]).

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"MacroGenics continues to advance its broad pipeline of clinical compounds, including those in our HER2, B7-H3 and PD-1 franchises as well as the many bispecific product candidates based on our DART platform," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "Across our portfolio of proprietary antibody and DART-based oncology programs, we now have initial evidence of on-target engagement, manageable safety and anti-tumor activity. In addition, I am very encouraged by the biological activity observed in subjects treated with MacroGenics’ autoimmune DART molecule, MGD010. We will continue to advance our robust pipeline in 2017, including defining future development strategies for multiple programs based on data expected later this year."

Pipeline Updates

Margetuximab. Recent highlights related to the Company’s Fc-optimized monoclonal antibody that targets the human epidermal growth factor receptor 2, or HER2, include:

Phase 3 Metastatic Breast Cancer Study. The pivotal SOPHIA study is evaluating the efficacy of margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy in approximately 530 relapsed/refractory HER2-positive metastatic breast cancer patients. MacroGenics continues to expect to complete enrollment of this study by late 2018. In addition, in consultation with the U.S. Food and Drug Administration (FDA) and the Committee for Medicinal Products for Human Use of the European Medicines Agency, the patient population eligible for participation in SOPHIA has been further expanded to include ado-trastuzumab emtansine-naïve patients.
Phase 2 Gastric Cancer Study. The Company continues to enroll advanced HER2-positive gastric and gastroesophageal junction cancer patients in its combination study of margetuximab with an anti-PD-1 antibody. Preliminary data from the dose escalation portion of the study, including patients with objective response following progression on previous lines of treatment with trastuzumab and chemotherapy, was presented at the Company’s R&D Day in December 2016. MacroGenics expects to complete enrollment of this study in 2017.
B7-H3 Franchise. MacroGenics is developing a portfolio of therapeutics that target B7-H3, a member of the B7 family of molecules involved in immune regulation. The Company is advancing multiple programs that target B7-H3 through complementary mechanisms of action that take advantage of this antigen’s broad expression across multiple solid tumor types. These molecules include:

Enoblituzumab: The Company continues to recruit patients in multiple ongoing studies of enoblituzumab, an Fc-optimized monoclonal antibody that targets B7-H3. These studies include one monotherapy study expanded to include additional bladder and prostate cancer cohorts and two combination studies with either an anti-CTLA-4 mAb (ipilimumab) or anti-PD-1 mAb (pembrolizumab). In addition, two monotherapy Phase 1 studies were recently initiated: a study for children with various solid tumors, including neuroblastoma, and an investigator-sponsored study in men with localized intermediate and high-risk prostate cancer in the neoadjuvant setting.
MGD009: This DART molecule targeting B7-H3 and CD3 is being evaluated in a Phase 1 study across multiple solid tumor types. Adverse events have been manageable to date and initial signs of antitumor activity have been observed, as previously disclosed at the Company’s R&D Day in December 2016. The Company expects to establish the dose and schedule for MGD009 administration as well as initiate dose expansion cohorts in 2017.
MGC018: The Company is conducting Investigational New Drug (IND)-enabling activities to support an IND application for this anti-B7-H3 antibody drug conjugate (ADC) in 2018. The Company will feature a poster presentation on MGC018 at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April.
PD-1-Directed Immuno-Oncology Franchise. MacroGenics is advancing several PD-1-directed programs, which will enable both a broad set of combination opportunities across the Company’s portfolio and provide further differentiation from existing PD-1-based treatment options. The first of these are:

MGA012. The Company’s Phase 1 clinical study of its proprietary anti-PD-1 monoclonal antibody was initiated in November 2016. With anti-PD-1 therapy becoming a mainstay of cancer treatment across multiple tumor types, MacroGenics believes MGA012 will be the basis for combination therapy with several of the molecules in its pipeline.
MGD013. MacroGenics is developing the DART molecule, MGD013, to provide co-blockade of two immune checkpoint molecules expressed on T cells, PD-1 and LAG-3, for the potential treatment of a range of malignancies. The Company has completed IND-enabling studies and plans to submit an IND for MGD013 in the first half of 2017.
Additional DART Clinical Programs. Additional DART molecules in Phase 1 clinical development include flotetuzumab (CD123 x CD3, also known as MGD006 and S80880); MGD007 (gpA33 x CD3); MGD010 (CD32B x CD79B); duvortuxizumab (CD19 x CD3, also known as MGD011), which is being developed by Janssen; and PF-06671008 (P-cadherin x CD3), which is being developed by Pfizer. At its R&D Day in December 2016, MacroGenics provided an in-depth update on its portfolio of proprietary, clinical DART programs. The Company highlighted the promising features of these DART molecules, including on-target engagement, manageable safety as well as preliminary evidence of biological activity. Updates on three of these programs for which MacroGenics leads development include:

Flotetuzumab. MacroGenics continues to recruit patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in the U.S. and Europe in the Phase 1 study of flotetuzumab. The Company expects to establish the dose and schedule as well as initiate dose expansion cohorts for this study in 2017. In late 2016, the FDA granted orphan drug designation to flotetuzumab for the treatment of AML.
MGD007. MacroGenics continues to recruit patients with colorectal cancer in the Phase 1 study of MGD007. The Company expects to establish the dose and schedule for this study in 2017.
MGD010. During the fourth quarter of 2016, MacroGenics completed the Phase 1 study of MGD010 in healthy subjects. This DART molecule is being developed for the potential treatment of autoimmune disorders. The Company plans to report updated clinical pharmacodynamic activity results from this study in 2017.
Corporate Update

New Board Members: In January 2017, MacroGenics announced the expansion of its Board of Directors from six to eight members and the appointments of Karen J. Ferrante, M.D., and Scott Jackson to fill the newly created vacancies. Dr. Ferrante, a hematologist-oncologist, most recently served as Chief Medical Officer and Head of Research and Development at Tokai Pharmaceuticals. Mr. Jackson served as Chief Executive Officer and as a member of the Board of Directors of Celator Pharmaceuticals, Inc. until its acquisition in July 2016.
Commenced Build-out of GMP Manufacturing Suite: In January 2017, the Company began the expansion of its manufacturing capacity by commencing the construction of a GMP suite in its headquarters building in Rockville, MD to support larger-scale clinical and commercial manufacturing.
2016 Financial Results and Cash Runway Guidance

Cash Position: Cash, cash equivalents and marketable securities as of December 31, 2016, were $285.0 million, compared to $339.0 million as of December 31, 2015.
Revenue: Total revenue, consisting primarily of revenue from collaborative agreements, was $91.9 million for the year ended December 31, 2016, compared to $100.9 million for the year ended December 31, 2015. Revenue from collaborative agreements includes the recognition of deferred revenue from payments received in previous periods as well as payments received during the year.
R&D Expenses: Research and development expenses were $122.1 million for the year ended December 31, 2016, compared to $98.3 million for the year ended December 31, 2015. This increase was due primarily to increased activity in the Company’s preclinical immune checkpoint programs, including MGD013 and MGA012, MGD014 (funded by NIAID/NIH) and the initiation of two Phase 1 clinical trials combining enoblituzumab with other compounds. These increases were partially offset by decreased manufacturing costs for margetuximab.
G&A Expenses: General and administrative expenses were $29.8 million for the year ended December 31, 2016, compared to $22.8 million for the year ended December 31, 2015. This increase was primarily due to increased staff, recruiting costs and stock-based (non-cash) compensation expense and patent expense.
Net Loss: Net loss was $58.5 million for the year ended December 31, 2016, compared to net loss of $20.1 million for the year ended December 31, 2015.
Shares Outstanding: Shares outstanding as of December 31, 2016 were 34,870,607.
Cash Runway Guidance: MacroGenics expects that its current cash, cash equivalents and marketable securities, combined with anticipated funding under its current strategic collaborations, should fund the Company’s operations through late 2018.

On February 28, 2017 Portola Pharmaceuticals, Inc. (NASDAQ:PTLA) reported a corporate update and reported its financial results for the fourth quarter and year ended December 31, 2016 (Press release, Portola Pharmaceuticals, FEB 28, 2017, View Source;p=RssLanding&cat=news&id=2250316 [SID1234517893]).

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"We are working towards gaining approval of both betrixaban, our investigational oral Factor Xa inhibitor, and andexanet alfa, our investigational antidote for oral Factor Xa inhibitors, in the United States and Europe over the next year," said Bill Lis, chief executive officer of Portola. "Each has the potential to become the first product approved for their respective indications and both are highly anticipated by the medical community. We are confident in the robust clinical data for both products, and are focused on addressing the regulatory risks that remain."

Recent Achievements, Upcoming Events and Milestones

Betrixaban – an oral Factor Xa inhibitor anticoagulant in development for extended prophylaxis of venous thromboembolism (VTE) in acute medically ill patients with risk factors for VTE; designated Fast Track status by the U.S. Food and Drug Administration (FDA)

The FDA accepted the New Drug Application (NDA), granted priority review, and established a Prescription Drug User Fee Act (PDUFA) action date of June 24, 2017
FDA informed Portola at the mid-cycle review that it does not plan to schedule an Advisory Committee meeting to discuss the NDA
The European Medicines Agency (EMA) validated the Marketing Authorization Application (MAA) under a standard 210-day review period; the Committee for Medicinal Products for Human Use (CHMP) opinion is expected by the end of the year
AndexXa (andexanet alfa) – a Factor Xa inhibitor antidote in development for patients treated with a Factor Xa inhibitor when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding; designated a Breakthrough Therapy and an Orphan Drug by the FDA

Expanded the existing agreement with Daiichi Sankyo; Portola received a $15 million upfront payment and is eligible to receive up to an additional $10 million upon meeting certain milestones; upon AndexXa’s approval, Daiichi will be eligible to receive a capped royalty
Resubmission of the Biologics License Application (BLA) is anticipated in the second quarter of 2017
Continued to enroll patients in the ongoing Phase 3b/4 ANNEXA-4 Study in patients with acute major bleeding; the Data and Safety Monitoring Board (DSMB) successfully completed its third review
Cerdulatinib – an oral, dual Syk/JAK inhibitor in development to treat resistant or relapsed hematologic cancer patients

Continued to enroll patients in a Phase 2a study evaluating the safety and efficacy of cerdulatinib in patients with relapsed/refractory B-cell malignancies who have failed multiple therapies
Entered into an exclusive worldwide licensing agreement with Dermavant Sciences for the development and commercialization of cerdulatinib in topical applications beyond oncology; Portola retains full rights to all non-topical formulations of cerdulatinib, including oral formulations
Corporate

Entered into a $50 million loan agreement with Bristol-Myers Squibb Company and Pfizer Inc. for continued development and clinical studies of andexanet alfa
Entered into a $150 million royalty agreement in the first quarter of 2017 with HealthCare Royalty Partners in exchange for a tiered, mid-single-digit royalty based on worldwide andexanet alfa sales
Fourth Quarter and Year-End Financial Results
Collaboration and license revenue earned under Portola’s collaboration and license agreements with Bristol-Myers Squibb Company and Pfizer, Bayer Pharma and Janssen Pharmaceuticals, Daiichi Sankyo and Dermavant Sciences was $13.7 million for the fourth quarter of 2016 compared with $4.4 million for the fourth quarter of 2015. Collaboration and license revenue for the year ended December 31, 2016, was $35.5 million compared with $12.1 million for the year ended December 31, 2015.

Total operating expenses for the fourth quarter of 2016 were $68.9 million compared with $70.7 million for the same period in 2015. Total operating expenses for the fourth quarter of 2016 included $7.9 million in stock-based compensation expense compared with $6.8 million for the same period in 2015. Total operating expenses for the year ended December 31, 2016, were $305.1 million compared with $239.2 million for 2015. Total operating expenses for the full year ended December 31, 2016, included $30.4 million in stock-based compensation expense compared with $22.9 million for 2015.

Research and development expenses for the fourth quarter of 2016 were $56.0 million compared with $59.8 million for the same period in 2015. Research and development expenses were $246.9 million for the year ended December 31, 2016, compared with $200.4 million for 2015. The increase in R&D expenses was primarily due to increased program costs to advance andexanet alfa of $64.7 million, including a $27.3 million one-time charge to write off certain prepaid manufacturing costs and increased program costs to support cerdulatinib and early research programs of $3.8 million, partially offset by decreased program costs related to betrixaban of $22.0 million following the completion of the APEX clinical trial enrollment.

Selling, general and administrative expenses for the fourth quarter of 2016 were $12.9 million compared with $10.9 million for the same period in 2015. Selling, general and administrative expenses for the year ended December 31, 2016, were $58.2 million compared with $38.9 million for 2015. The increase in SG&A expenses was primarily due to increased headcount-related costs, commercial launch preparation activities and business development-related costs, and costs associated with professional and accounting fees of $2.0 million.

For the fourth quarter of 2016, Portola reported a net loss of $53.8 million, or $0.95 net loss per share, compared with a net loss of $66.1 million, or $1.23 net loss per share, for the same period in 2015. Shares used to compute net loss per share attributable to common stockholders were 56.5 million for the fourth quarter of 2016 compared with 53.6 million for the same period in 2015. Net loss for the year ended December 31, 2016, was $269.0 million, or $4.76 net loss per share, compared with a net loss of $226.5 million, or $4.36 net loss per share, for the same period in 2015. Shares used to compute net loss per share attributable to common stockholders were 56.5 million for 2016 compared with 52.0 million for 2015.

Cash, cash equivalents and investments at December 31, 2016, totaled $318.8 million compared with cash, cash equivalents and investments of $460.2 million as of December 31, 2015.

2017 Annual Financial Guidance
For the fiscal year 2017, Portola expects total GAAP operating expenses to be between $323 million and $344 million. For the fiscal year 2017, Portola expects total pro-forma operating expenses to be between $290 million and $310 million, excluding stock-based compensation. These expenses will be primarily for manufacturing of both andexanet and betrixaban, support of ongoing clinical trials and preparation for the potential commercial launches of betrixaban and AndexXa.

Non-GAAP Financial Projection
This press release and the reconciliation table included herein include a non-GAAP projection of 2017 operating expenses, excluding stock-based compensation. A reconciliation to projected GAAP 2017 operating expenses is provided in the accompanying table entitled "Reconciliation of GAAP to Non-GAAP Projected Operating Expenses." Portola management believes this non-GAAP information is useful for investors because it provides information about the Company’s ability to independently fund and advance its operations with existing capital resources. Share-based compensation is not an expense that requires cash settlement, and therefore, the Company excludes these charges for purposes of evaluating our ability to fund future operations.

On February 28, 2017 Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) reported that the U.S. Food and Drug Administration (FDA) has approved XERMELO (telotristat ethyl) 250 mg as a first and only orally administered therapy for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy (Press release, Lexicon Pharmaceuticals, FEB 28, 2017, View Source [SID1234518219]) . Carcinoid syndrome is a rare and debilitating condition that affects people with metastatic neuroendocrine tumors (mNETs) . XERMELO targets the overproduction of serotonin inside mNET cells , providing a new treatment option for patients suffering from carcinoid syndrome diarrhea. This new treatment is now available by prescription and will be in select specialty pharmacies beginning March 6, 2017.

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"Today’s approval of XERMELO represents a shift in the treatment paradigm of carcinoid syndrome diarrhea for cancer patients who are inadequately controlled by SSA therapy, and until now, have had limited options to manage this debilitating condition," said Lonnel Coats, Lexicon’s president and chief executive officer. "We are proud to have discovered and developed this ground-breaking orphan drug, and it is an honor to make it available for the thousands of patients currently suffering from this condition who wish to lead a more routine life with fewer incidences of severe diarrhea."

Carcinoid syndrome is a rare condition that occurs in patients living with mNETs and is characterized by frequent and debilitating diarrhea that often prevents patients from leading active, predictable lives, as well as by facial flushing, abdominal pain, fatigue and, over time, heart valve damage.

"The approval of XERMELO establishes a new treatment option for patients with carcinoid syndrome diarrhea that is inadequately controlled by SSA therapy," said Matthew H. Kulke, M.D., TELESTAR primary investigator, director of the Program in Neuroendocrine and Carcinoid Tumors at Dana Farber Cancer Institute and Professor of Medicine, Harvard Medical School. "Inhibition of tumoral serotonin production represents a novel approach for patients with this condition. Studies have shown that XERMELO can reduce the debilitating effects of carcinoid syndrome diarrhea and has a favorable efficacy and safety profile in patients who currently have limited treatment options."

About XERMELO

Discovered using Lexicon’s unique approach to gene science, XERMELO is the first and only approved oral therapy for carcinoid syndrome diarrhea. XERMELO targets tryptophan hydroxylase, an enzyme that mediates the excess serotonin production within mNET cells.

Lexicon has built the in-house capability and infrastructure to launch and market XERMELO in the U.S., where it retains all commercialization rights. Lexicon also retains rights to market telotristat ethyl in Japan. Lexicon has established a license and collaboration agreement with Ipsen to commercialize telotristat ethyl in Europe and other countries outside of U.S. and Japan. For more information about XERMELO, please visit www.xermelo.com.

XERMELO Important Safety Information

Warnings and Precautions: XERMELO may cause constipation which can be serious. Monitor for signs and symptoms of constipation and/or severe, persistent, or worsening abdominal pain in patients taking XERMELO. Discontinue XERMELO if severe constipation or severe persistent or worsening abdominal pain develops.
Adverse Reactions: The most common adverse reactions (≥5%) include nausea, headache, increased GGT, depression, peripheral edema, flatulence, decreased appetite, and pyrexia.
Drug Interactions: If necessary, consider increasing the dose of concomitant CYP3A4 substrates, as XERMELO may decrease their systemic exposure.
For more information about XERMELO, see Full Prescribing Information at www.xermelo.com.