On October 13, 2015 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 that it held its first R&D Day and provided an in-depth review of the Company’s broad portfolio of product candidates and technology platforms (Press release, MacroGenics, OCT 13, 2015, View Source [SID:1234507712]). Special guest speakers included Charles Drake, M.D., Ph.D., Professor of Oncology, Urology and Immunology, Johns Hopkins School of Medicine, and Holbrook Kohrt, M.D., Ph.D., Assistant Professor of Medicine (Oncology) at Stanford University Medical Center.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The team at MacroGenics continues to make significant advances in realizing our mission to create breakthrough biologics and life-changing medicines," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "Our growing and advancing pipeline now includes eight product candidates in clinical development across a wide range of indications in solid and hematological malignancies, as well as autoimmune disorders. Today’s R&D Day allowed us to provide an update on our Fc-optimized antibodies, margetuximab and enoblituzumab, our five DART molecules in the clinic, additional programs that we have not previously disclosed and the evolution of our multi-specific targeting platforms."

Program Updates and Highlights:

Margetuximab. MacroGenics today provided details about its ongoing SOPHIA Phase 3 clinical study of margetuximab, the company’s Fc-optimized, HER2-directed monoclonal antibody in patients with metastatic breast cancer. The Company also highlighted activity of margetuximab as single agent in patients with gastric cancer from its recently completed Phase 1 study, and a planned Phase 1b/2 study evaluating the combination of margetuximab with an anti-PD-1 antibody.

B7-H3 Franchise. MacroGenics highlighted its industry-leading franchise related to therapeutic targeting of B7-H3, a member of the B7 family of molecules involved in immune regulation. The Company is developing three product candidates that engage this target through complementary mechanisms of action and take advantage of this target’s broad expression pattern in multiple solid tumors.

Enoblituzumab (MGA271). The Company provided an overview of initial data from its ongoing Phase 1 monotherapy clinical study of enoblituzumab, an Fc-optimized monoclonal antibody. To date, enoblituzumab has been well tolerated in patients and has shown encouraging, initial single-agent activity, including tumor regression in multiple, heavily pre-treated patients. In addition, evidence of T-cell immunomodulatory function has been observed in patients treated with enoblituzumab. The Company continues to enroll patients in additional monotherapy Phase 1 study cohorts as well as in two combination studies with either ipilimumab or pembrolizumab. Data from the ongoing monotherapy study will be presented in a late-breaking abstract session at the 2015 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting on November 7, 2015.

MGD009. MacroGenics disclosed that MGD009, a Dual-Affinity Re-Targeting (DART) molecule targeting B7-H3 and CD3, has entered into a Phase 1 study in patients and is being evaluated across multiple solid tumor types. MGD009 is designed to target tumors expressing B7-H3 as well as recruit and expand T cells at the tumor site. MacroGenics retains worldwide development and commercialization rights to MGD009.

B7-H3 Antibody-Drug Conjugate. MacroGenics also presented pre-clinical data on an antibody-drug conjugate (ADC) program targeting B7-H3. The Company is evaluating several toxin/linker combinations to induce direct killing of B7-H3-positive tumor cells.

DART Platform. MacroGenics provided an overview of the advantages and versatility of its DART platform for bispecific targeting. The Company also provided a summary of the five DART molecules currently in clinical development, including MGD006 (CD123 x CD3), MGD007 (gpA33 x CD3), MGD011 (CD19 x CD3), MGD010 (CD32B x CD79B) and MGD009 (B7-H3 x CD3). In addition, the Company disclosed for the first time two DART molecules that it expects to advance into clinical development in the first half of 2017. These two product candidates include the following:

MGD013. MacroGenics is developing MGD013 to provide co-blockade of two immune checkpoint molecules co-expressed on T cells, PD-1 and LAG-3, for treatment of diseases spanning a wide range of solid tumors and hematological malignancies. The Company presented pre-clinical data on an Fc-bearing DART molecule directed against these targets. In addition to MGD013, MacroGenics is generating and evaluating multiple other candidates that target a range of immune regulators using its DART and Trident platforms.
MGD014. MacroGenics presented pre-clinical data on MGD014, an Fc-bearing DART molecule that targets HIV-infected cells and CD3. MGD014 is being developed to eliminate latent HIV infection in patients treated with continuous anti-retroviral therapy (cART) alone or in combination with latency-reversing agents. MGD014 will be developed under a contract recently awarded by the National Institute of Allergy and Infectious Diseases for up to $24.5 million. This is the first infectious disease DART program planned for clinical testing.

Trident Platform

MacroGenics presented its Trident tri-specific platform, extending the Company’s leadership position in multi-specific antibody-based targeting. Trident molecules have an antibody-like structure with three specificities that enable novel mechanisms of action by recognizing up to three separate antigens in different, customizable conformations.

On October 13, 2015 Pfizer reported that this Breast Cancer Awareness Month, it and the Union for International Cancer Control (UICC) are proud to announce the recipients from the Seeding Progress and Resources for theCancer Community: Metastatic Breast Cancer Challenge (SPARC MBC Challenge), a first-of-its-kind initiative to address the unique challenges facing women with metastatic breast cancer worldwide (Press release, Pfizer, OCT 13, 2015, View Source [SID:1234507711]). In total, 20 organizations from 18 countries have been selected to receive grants amounting to $760,000 (USD) in funding provided by Pfizer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Launched on World Cancer Day in February 2015, the SPARC MBC Challenge received significant interest with over 80 applications submitted by organizations in 46 countries, reflecting the urgent need for improved services and support for women with metastatic breast cancer. Due to this high level of interest, Pfizer increased its funding of the initiative from $500,000 (USD) to $760,000 (USD) to support additional projects.

The SPARC MBC Challenge aims to empower advocacy groups, hospital networks, support groups and other organizations worldwide as they initiate projects to close the gap in information, support, awareness and policy between metastatic breast cancer and early disease, as well as help reduce the number of women diagnosed at the metastatic stage of breast cancer.

"Globally, there are wide disparities in the diagnosis, management and care of metastatic breast cancer, a disease that is clinically complex, emotionally burdensome and socially misunderstood," said Professor Sanchia Aranda, president-elect, UICC. "We are hopeful this program will help us to fulfill our mission of promoting greater equity in access to comprehensive breast cancer services, and we are thrilled with the community’s response to the SPARC MBC Challenge and the number of applications submitted to support projects that can greatly impact the lives of women living with this diagnosis."

Awardees were selected through a competitive application process overseen by an external, multidisciplinary selection committee formed by UICC and chaired by Dr. Fatima Cardoso, director of the Breast Unit of the Champalimaud Cancer Center in Lisbon, Portugal.

Each awardee will receive either a campaign grant ($20,000 USD) or a network grant ($60,000 USD). These grants will be used to fund projects in support of women with metastatic breast cancer worldwide, including projects in low-income countries, such as Uganda and Haiti, where women are frequently diagnosed at a more advanced stage of breast cancer than women in developed nations.1,2

"Our partnership with UICC on this initiative represents our commitment to the hundreds of thousands of women worldwide who are living with metastatic breast cancer," said Liz Barrett, global president and general manager, Pfizer Oncology. "This initiative helps bring us one step closer to the day when metastatic breast cancer patients around the world may have access to the care and support they need, regardless of their location or socio-economic status."

"One particularly valuable component of the SPARC MBC Challenge is that it will also provide mentorship support to the awardees and enable networking and sharing of best practices among the organizations," said Professor Aranda. "We look forward to following the progress and results of all awarded projects that were selected to address the challenges facing the MBC community globally."

Among the awardees is Associação Mama Help, an organization based in Portugal that will be creating an online resource center in the Portuguese language to provide information and support to women living with metastatic breast cancer. Additionally, Uganda Women’s Cancer Support Organisation (UWOCAO), will implement a project in partnership with the Uganda Cancer Institute to identify the challenges faced by women with advanced breast cancer in Uganda and help increase awareness of their unique needs among advocates, caregivers and policymakers. Based on this understanding, the organization will seek to develop new tools, services and policies to address their needs and to ultimately help increase access to supportive care and improve quality of life for women with metastatic breast cancer.

On October 13, 2015 NewLink Genetics Corporation (NASDAQ:NLNK), a biopharmaceutical company at the forefront of developing and commercializing novel immuno-oncology product candidates to improve the lives of patients with cancer, reported that a peer-reviewed article in Cell Reports offers new insight demonstrating that the tumor indoleamine 2,3-dioxygenase (IDO) pathway is a central regulator of both local and systemic immunosuppression and resistance to immunotherapy in melanoma (Press release, NewLink Genetics, OCT 13, 2015, View Source [SID:1234507710]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The paper also reports that indoximod, NewLink Genetics’ wholly owned IDO pathway inhibitor, reversed tumor-associated immunosuppression in pre-clinical melanoma models and that there is a "strong rationale" for therapeutic targeting of IDO as one of the central regulators of immune suppression. The paper, titled Tumor-Expressed IDO Recruits and Activates MDSCs in a Treg-Dependent Manner and authored by Rikke B. Holmgaard, Dmitriy Zamarin, Yanyun Li, Billel Gasmi, David H. Munn, James P. Allison, Taha Merghoub, and Jedd D. Wolchok, was published on line and appears today in the October 13, 2015 issue of Cell Reports.

Rikke B. Holmgaard, Ph.D., lead author of the paper and Research Associate, Memorial Sloan Kettering Cancer Center, said, "We learned that IDO mediates local and systemic immune suppression in murine tumor models by means of other immunosuppressive cells, such as MDSCs and Tregs, and by upregulating other immunosuppressive mechanisms mediated by MDSCs, such as arginase 1, iNOS, and immunosuppressive cytokines. In so doing, IDO makes tumors grow faster and become less responsive to immune checkpoint therapy, such as PD1/CTLA4. Thus, adding IDO inhibition may be one of the key elements of combination therapies for strong, durable anti-tumor responses."

Jedd D. Wolchok, M.D., Ph.D., Chief of Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center, Associate Professor of Immunology and Microbial Pathogenesis at Weill Cornell Medical College, and co-author of the article, added, "This data further demonstrate IDO as one of the key immune checkpoint targets and show that indoximod can block the expansion of suppressive myeloid cells and recruitment of MDSCs to the tumor microenvironment that mediate local immune suppression. It prevents activation of Tregs that mediate systemic immune suppression in a mouse model and enhances the antitumor activity of combination anti-CTLA4 and anti-PD1."

David H. Munn, M.D., Professor of Pediatric Hematology and Oncology at Georgia Regents University and co-author of the article in Cell Reports, added, "This research not only sheds additional light on the mechanism of IDO expression in tumors but also shows how indoximod can enhance anti-tumor responses when combined with other checkpoint inhibitors."

"This important work, both in animal studies and in analyses of human melanoma samples, by leading scientists in immuno-oncology validates our view of the central role IDO inhibition and indoximod may play in tumor immunosuppression," said Charles Link, M.D., CEO and Chief Scientific Officer of NewLink Genetics. "It also points to the potential for IDO inhibitors like indoximod to overcome that immunosuppression and enhance anti-tumor responses."

Indoximod is in Phase 2 clinical trials for breast cancer, prostate cancer, melanoma and glioblastoma multiforme as well as in Phase 1b/2 clinical trials for pancreatic cancer.

The authors’ analysis of tumor samples from 36 melanoma patients found that myeloid-derived suppressor cells (MDSCs) were increased in IDO+ tumors. This suggests that IDO recruits and activates such cells through activation of regulatory T cells (Tregs). The authors found greater tumor growth, as well as resistance to immune checkpoint blockade, in the tumors overexpressing IDO. Treatment of the mice bearing tumors overexpressing IDO with the IDO pathway inhibitor indoximod reversed this tumor-associated immunosuppression by decreasing the number of MDSCs and Tregs and stopping their suppressive capability.

On October 13, 2015 Johnson & Johnson (NYSE: JNJ) reported sales of $17.1 billion for the third quarter of 2015, a decrease of 7.4% as compared to the third quarter of 2014 (Press release, Johnson & Johnson, OCT 13, 2015, View Source [SID:1234507708]). Operational sales results increased 0.8% and the negative impact of currency was 8.2%. Domestic sales decreased 0.6%. International sales decreased 13.7%, reflecting operational growth of 2.1% and a negative currency impact of 15.8%. Excluding the net impact of acquisitions, divestitures and hepatitis C sales, on an operational basis, worldwide sales increased 5.6%, domestic sales increased 7.7% and international sales increased 3.8%.* Earlier today, the Company also announced its Board of Directors has approved the repurchase of up to $10 billion of the company’s common stock.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Net earnings and diluted earnings per share for the third quarter of 2015 were $3.4 billion and $1.20, respectively. Third quarter 2015 net earnings included after-tax intangible amortization expense of approximately $0.4 billion and a charge for after-tax special items of approximately $0.4 billion. Third quarter 2014 net earnings included after-tax intangible amortization expense of approximately $0.3 billion and a net gain for after-tax special items of approximately $0.4 billion. A reconciliation of non-GAAP financial measures is included as an accompanying schedule. Excluding after-tax intangible amortization expense and special items, adjusted net earnings for the current quarter were $4.2 billion and adjusted diluted earnings per share were $1.49, representing decreases of 9.4% and 7.5%, respectively, as compared to the same period in 2014.* On an operational basis, adjusted diluted earnings per share increased 1.2%.*

"New and core products drove solid underlying growth for Johnson & Johnson in the quarter," said Alex Gorsky, Chairman and Chief Executive Officer. "Consistent with the plans we’ve laid out for the year, we’re focusing our portfolio and are advancing our innovation agenda to expand our leadership position in key categories while seeking new opportunities for growth. Our dedicated employees are committed to improving healthcare and making a difference in the lives of patients and consumers worldwide."

The Company increased its adjusted earnings guidance for full-year 2015 to $6.15 – $6.20 per share. The Company’s guidance excludes the impact of after-tax intangible amortization expense and special items.

Worldwide Consumer sales of $3.3 billion for the third quarter represented a decrease of 7.7% versus the prior year, consisting of an operational increase of 3.1% and a negative impact from currency of 10.8%. Domestic sales increased 8.9%; international sales decreased 15.7%, which reflected an operational increase of 0.4% and a negative currency impact of 16.1%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 4.0%, domestic sales increased 8.9% and international sales increased 1.5%.*

Positive contributors to Consumer operational results were sales of over-the-counter products including TYLENOL and MOTRIN analgesics and ZYRTEC allergy medications; international feminine protection products; AVEENO and NEUTROGENA skin care products; and LISTERINE oral care products.

During the quarter, the divestiture of the SPLENDA low calorie sweetener brand to Heartland Food Products Group was completed. This completes the divestiture of products within the nutritionals business.

Worldwide Pharmaceutical sales of $7.7 billion for the third quarter represented a decrease of 7.4% versus the prior year with an operational decrease of 0.3% and a negative impact from currency of 7.1%. Domestic sales decreased 4.5%; international sales decreased 11.1%, which reflected an operational increase of 5.5% and a negative currency impact of 16.6%. Excluding the net impact of acquisitions, divestitures and hepatitis C sales, on an operational basis, worldwide sales increased 10.1%, domestic sales increased 11.5% and international sales increased 8.5%.*

Worldwide operational sales growth was driven by new products and the strength of core products. New product sales growth was negatively impacted by lower sales of OLYSIO/SOVRIAD (simeprevir) due to competitive entrants. Strong growth in new products include INVOKANA/INVOKAMET (canagliflozin), for the treatment of adults with type 2 diabetes; IMBRUVICA (ibrutinib), an oral, once-daily therapy approved for use in treating certain B-cell malignancies, or blood cancers; XARELTO (rivaroxaban), an oral anticoagulant; and ZYTIGA (abiraterone acetate), an oral, once-daily medication for use in combination with prednisone for the treatment of metastatic, castration-resistant prostate cancer.

Additional contributors to operational sales growth were SIMPONI/SIMPONI ARIA (golimumab), biologics approved for the treatment of a number of immune-mediated inflammatory diseases; STELARA (ustekinumab), a biologic approved for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis; INVEGA SUSTENNA/XEPLION (paliperidone palmitate), a once-monthly, long-acting, injectable atypical antipsychotic for the treatment of schizophrenia in adults; CONCERTA (methylphenidate HCI), for the treatment of attention deficit hyperactivity disorder; and PREZCOBIX/REZOLSTA (darunavir/cobicistat) for the treatment of human immunodeficiency virus (HIV-1).

During the quarter, the U.S. Food and Drug Administration (FDA) granted Priority Review for the Biologic License Application for daratumumab for the treatment of double refractory multiple myeloma. Additionally, the FDA approved EDURANT (rilpirivine), in combination with other anti-retroviral agents, for treatment-naïve adolescent patients aged 12 to 18 years with human immunodeficiency virus-1 (HIV-1) infection, as well as an update to the SIMPONI ARIA (golimumab for infusion) label to include improvement in both physical and emotional measures of health when treating moderately to severely active rheumatoid arthritis. In the U.S., a supplemental new drug application was submitted to the FDA for IMBRUVICA (ibrutinib) for use in treatment-naïve patients with chronic lymphocytic leukemia. In addition, Marketing Authorization Applications were submitted to the European Medicines Agency for paliperidone palmitate once-every-three-months formulation for the treatment of schizophrenia and daratumumab for the treatment of patients with relapsed and refractory multiple myeloma. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has granted an accelerated assessment of the daratumumab Marketing Authorization Application.

Worldwide Medical Devices sales of $6.1 billion for the third quarter represented a decrease of 7.3% versus the prior year consisting of an operational increase of 0.9% and a negative currency impact of 8.2%. Domestic sales increased 2.0%; international sales decreased 14.8%, which reflected an operational increase of 0.1% and a negative currency impact of 14.9%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 1.3%, domestic sales increased 2.0% and international sales increased 0.8%.*

Primary contributors to operational growth were sales of ACUVUE contact lenses in the Vision Care business; endocutters in the Surgical Care business; sales of biosurgicals and international energy products in the Specialty Surgery business; and electrophysiology products in the Cardiovascular Care business.

In October, subsequent to the third quarter, the Company announced the completion of the divestiture of its Cordis business to Cardinal Health for an approximate value of $2 billion.