New York, NY, United States
New York, NY, United States

ImClone Systems Incorporated is a formerly independent biopharmaceutical company dedicated to developing biologic medicines in the area of oncology. It was founded in 1984 and has its corporate headquarters in Bridgewater, New Jersey and its research headquarters in New York City. On October 6, 2008, it accepted a $6.5 billion acquisition offer from Eli Lilly and Company, and became a fully owned subsidiary of Eli Lilly and Company on November 24, 2008. Prior to the acquisition, it was traded on the NASDAQ stock exchange under the symbol IMCL. In 2014 the use of the ImClone brand name was retired and the former ImClone research and manufacturing sites were renamed Eli Lilly and Company. Wikipedia.

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Mazur M.T.,Imclone Systems | Seipert R.S.,Imclone Systems | Mahon D.,Imclone Systems | Zhou Q.,Imclone Systems | Liu T.,Imclone Systems
AAPS Journal | Year: 2012

With the growing commercialization of therapeutic monoclonal antibodies developed for the treatment of various diseases comes the need for increased analytical scrutiny of the impurity components contained within such drug products. Traditionally, relatively low performance and throughput analytical techniques were employed for elucidating the product-related breakdown components derived from the original molecule, including N-terminal Edman sequencing and matrix-assisted laser desorption time-of-flight (MALDI-TOF) mass spectrometry. Although N-terminal sequencing provides a definitive starting point of an unknown breakdown product, the resolution and mass accuracy of MALDI-TOF instruments are often insufficient for unambiguous sequence characterization. Described here is the implementation of existing advanced analytical technologies, including high-performance mass spectrometry (LTQ-Orbitrap XL-ETD) and a chip-based nanoelectrospray autosampling robot (TriVersa NanoMate), for the thorough identification and characterization of breakdown products derived from a force-degraded monoclonal antibody. Many anticipated breakdown products were identified, including Fab fragment (48,325 Da) and heavy chain polypeptide hydrolysis product (15,521 Da). Using high-resolution collisionally induced and electron transfer dissociation methods, additional identifications were made with specific localization of unpredicted modifications. As examples, a modified Fab fragment (N- and C-terminal cyclization, 47,902 Da) and a hydrolyzed free light chain impurity components (23,191 Da) were identified with a high degree of confidence (E value, <1e-5). This work describes the approach for top-down characterization of breakdown products and is readily applicable to additional monoclonal antibodies (mAb) characterization experiments, including charge isoform characterization and aggregate analysis, for a more thorough understanding of therapeutic mAb drug products. © 2012 American Association of Pharmaceutical Scientists.

Ulanet D.B.,University of California at San Francisco | Ludwig D.L.,Imclone Systems | Kahn C.R.,Harvard University | Hanahan D.,University of California at San Francisco | Hanahan D.,Ecole Polytechnique Federale de Lausanne
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

The type 1 insulin-like growth factor receptor (IGF-1R) tyrosine kinase is an important mediator of the protumorigenic effects of IGF-I/II, and inhibitors of IGF-1R signaling are currently being tested in clinical cancer trials aiming to assess the utility of this receptor as a therapeutic target. Despite mounting evidence that the highly homologous insulin receptor (IR) can also convey protumorigenic signals, its direct role in cancer progression has not been genetically defined in vivo, and it remains unclear whether such a role for IR signaling could compromise the efficacy of selective IGF-1R targeting strategies. A transgenic mouse model of pancreatic neuroendocrine carcinogenesis engages the IGF signaling pathway, as revealed by its dependence on IGF-II and by accelerated malignant progression upon IGF-1R overexpression. Surprisingly, preclinical trials with an inhibitory monoclonal antibody to IGF-1R did not significantly impact tumor growth, prompting us to investigate the involvement of IR. The levels of IR were found to be significantly up-regulated during multistep progression from hyperplastic lesions to islet tumors. Its functional involvement was revealed by genetic disruption of the IR gene in the oncogene-expressing pancreatic β cells, which resulted in reduced tumor burden accompanied by increased apoptosis. Notably, the IR knockout tumors now exhibited sensitivity to anti - IGF-1R therapy; similarly, high IR to IGF-1R ratios demonstrably conveyed resistance to IGF-1R inhibition in human breast cancer cells. The results predict that elevated IR signaling before and after treatment will respectively manifest intrinsic and adaptive resistance to anti - IGF-1R therapies.

Protein biopharmaceuticals, such as monoclonal antibodies (mAbs) are widely used for the prevention and treatment of various diseases. The complex and lengthy upstream and downstream production methods of the antibodies make them susceptible to physical and chemical modifications. Several IgG1 immunoglobulins are used as medical agents for the treatment of colon, breast, and head and neck cancers, and at least four to eight isoforms exist in the products. The regulatory agencies understand the complex nature of the antibody molecules and allow the manufactures to set their own specifications for lot release, provided the safety and efficacy of the products are established in animal models prior to clinical trials. During the manufacture of a mAb product, we observed lot-to-lot variability in the isoform content and, although the variability is within the set specifications for lot release, made attempts to gain mechanistic insight by isolating and characterizing the individual isoforms. Matrix-assisted laser desorption/ionization (MALDI) and liquid chromatography (LC)/mass spectrometry (MS)/MS analyses of the isolated isoforms indicate that this variability is caused by sialic acid content, as well as truncation of C-terminal lysine of the individual isoforms. Sialidase and carboxypeptidase treatment of the product confirm the observations made by MALDI and LC/MS/MS.

Belardi V.,University of Pisa | Gallagher E.J.,Mount Sinai School of Medicine | Novosyadlyy R.,Imclone Systems | Leroith D.,Mount Sinai School of Medicine
Journal of Mammary Gland Biology and Neoplasia | Year: 2013

Obesity and the Metabolic Syndrome are associated with multiple factors that may cause an increased risk for cancer and cancer-related mortality. Factors involved include hyperinsulinemia, hyperglycemia, hyperlipidemia and IGFs. Insulin resistance is also associated with alterations in the levels of proinflammatory cytokines, chemokines, adipokines (leptin, adiponectin) that may also be contributing factors. The insulin family of proteins is ubiquitously expressed and has pleiotropic effects on metabolism and growth. However insulin, IGF-1 and particularly IGF-2 have been identified as tumor promoters in multiple studies. Mouse models have focused on insulin and IGF-1 and their receptors as being involved in tumor progression and metastases. The role of the insulin receptor as either mediating the effects on tumors or as compensating for the insulin-like growth factor receptor has arisen. Its role has been supported by preclinical studies and the importance of insulin resistance and hyperinsulinemia in obesity and early diabetes. Since the focus of this review is the insulin-family we will focus on insulin, IGF-1 and IGF-2. © 2013 Springer Science+Business Media New York.

Novosyadlyy R.,Imclone Systems | Leroith D.,Mount Sinai School of Medicine | Leroith D.,Haifa University
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2012

Numerous lines of evidence indicate that insulin-like growth factor signaling plays an important role in the regulation of life span and tumor development. In the present paper, the role of individual components of insulin-like growth factor signaling in aging and tumor development has been extensively analyzed. The molecular mechanisms underlying aging and tumor development are frequently overlapping. Although the link between reduced insulin-like growth factor signaling and suppressed tumor growth and development is well established, it remains unclear whether extended life span results from direct suppression of insulin-like growth factor signaling or this effect is caused by indirect mechanisms such as improved insulin sensitivity. © 2011 The Author.

Huggenberger R.,ETH Zurich | Ullmann S.,ETH Zurich | Proulx S.T.,ETH Zurich | Pytowski B.,Imclone Systems | And 2 more authors.
Journal of Experimental Medicine | Year: 2010

The role of lymphangiogenesis in inflammation has remained unclear. To investigate the role of lymphatic versus blood vasculature in chronic skin inflammation, we inhibited vascular endothelial growth factor (VEGF) receptor (VEGFR) signaling by function-blocking antibodies in the established keratin 14 (K14)-VEGF-A transgenic (Tg) mouse model of chronic cutaneous inflammation. Although treatment with an anti-VEGFR-2 antibody inhibited skin inflammation, epidermal hyperplasia, inflammatory infiltration, and angiogenesis, systemic inhibition of VEGFR-3, surprisingly, increased inflammatory edema formation and inflammatory cell accumulation despite inhibition of lymphangiogenesis. Importantly, chronic Tg delivery of the lymphangiogenic factor VEGF-C to the skin of K14-VEGF-A mice completely inhibited development of chronic skin inflammation, epidermal hyperplasia and abnormal differentiation, and accumulation of CD8 T cells. Similar results were found after Tg delivery of mouse VEGF-D that only activates VEGFR-3 but not VEGFR-2. Moreover, intracutaneous injection of recombinant VEGF-C156S, which only activates VEGFR-3, significantly reduced inflammation. Although lymphatic drainage was inhibited in chronic skin inflammation, it was enhanced by Tg VEGF-C delivery. Together, these results reveal an unanticipated active role of lymphatic vessels in controlling chronic inflammation. Stimulation of functional lymphangiogenesis via VEGFR-3, in addition to antiangiogenic therapy, might therefore serve as a novel strategy to treat chronic inflammatory disorders of the skin and possibly also other organs. © 2010 Huggenberger et al.

Gerald D.,Imclone Systems | Chintharlapalli S.,Eli Lilly and Company | Augustin H.G.,University of Heidelberg | Augustin H.G.,German Cancer Research Center | Benjamin L.E.,Imclone Systems
Cancer Research | Year: 2013

Anti-VEGF pathway therapies primarily target immature blood vessels in tumors. However, emerging approaches to combine with targeted therapies impacting the later stages of remodeling and vessel maturation are expected to improve clinical efficacy by expanding the target vessel population. The angiopoietin/Tie ligand/ receptor system is a prototypic regulator of vessel remodeling and maturation. Angiopoietin-2 (Ang2) appears to be a particularly attractive therapeutic target. In fact, the experimental proof-of-concept showing improved efficacy when VEGF and Ang2-targeting therapies are combined has been solidly established in preclinical models, and several Ang2-targeting drugs are in clinical trials. However, rational development of these secondgeneration combination therapies is hampered by a limited understanding of the biological complexity that is generated from agonistic and antagonistic Ang/Tie signaling. This review discusses recent mechanistic advances in angiopoietin signaling, particularly in light of the recent study published on REGN910 and summarizes the status quo of Ang2-targeting therapies. In light of the clarified partial agonist function of Ang2, we propose that clarity on the expression profile of the angiopoietin ligands and Tie1 and Tie2 receptors in subsets of cancer vessels and cancer cells will provide clearer hypotheses for more focused rational clinical trials to exploit this seminal pathway and improve current antiangiogenic therapies. © 2013 American Association for Cancer Research.

News Article | March 10, 2015

Hope to See You Thursday at “New York’s Life Science Disruptors” The weather is warming up just in time for a little disruption in New York biotech. Come join us and celebrate the respite from the deep freeze: our latest event, “New York’s Life Science Disruptors,” will kick off Thursday afternoon at 5 pm at the Alexandria Center for Life Science in East Manhattan. We’ve brought together a great lineup some of New York’s most influential biotech leaders for some candid, interactive talks you’ll be able to take part in. Tickets are going fast, but you’ve still got a few days to register here. Some of the names you’ll see: —George Yancopoulos, one of the co-founders of Regeneron Pharmaceuticals (NASDAQ: REGN). —Sam Waksal, the former CEO of ImClone Systems and an executive at New York’s Kadmon. —Two of the key folks—Thong Le and Misti Ushio—that have brought Seattle’s biotech startup machine, Accelerator Corp., to the Big Apple. —Acorda Therapeutics CEO Ron Cohen and CNBC biotech reporter Meg Tirrell, who will each moderate some of our chats. Catch you all on Thursday in Manhattan.

- Industry veteran to lead development of optimized programs for Iomab-B including initiatives targeted at patients, physicians and payors designed to support clinical development and pre-commercialization efforts - Mr. Price brings three decades of marketing and strategic leadership experience in the oncology field with most recent experiences in immunotherapy focused on hematology at Merck and antibody-based therapeutics at Imclone Systems NEW YORK, Feb. 21, 2017 (GLOBE NEWSWIRE) -- Actinium Pharmaceuticals, Inc.  (NYSE MKT:ATNM) ("Actinium" or "the Company"), a biopharmaceutical company developing innovative targeted therapies for cancers lacking effective treatment options, announced today that Steven Price has been appointed to the newly created position of Vice President, Clinical and Commercial Strategy. In this role, Steve will initially focus on pre-commercial efforts including strategic planning and product messaging for Iomab-B, increasing awareness for Iomab-B, further developing relationships with the physician community, and supporting clinical trials for Actinium’s current and future clinical programs. He will also be in charge of pre-commercial activities for Actimab-A and Actimab-M. “I am incredibly honored to join Actinium at this point in the Company’s evolution and excited to be working with a strong and committed team”, said Steve Price. “The data to date for Iomab-B and Actimab-A are very impressive and suggest these drug candidates have the potential to improve patient outcomes in disease indications with high unmet needs. I look forward to leveraging my experience and relationships to further enhance the profiles of Actinium’s drug candidates to the hematology and bone marrow transplant community while positioning them for future success.” Most recently, Steve was at Merck as Global Disease Lead, Hematology where he focused on Keytruda, an anti-PD-1 immuno-oncology antibody. In this position, Steve served as commercial lead on the product development team responsible for maximizing physician acceptance, KOL development, market penetration and new indication launch uptake. Further, he developed the marketing program ahead of product launch before implementing at the regional level and guiding regional teams in a new indication launch. Prior to Merck, Steve consulted to pharmaceutical and biotechnology companies on product pre-launch strategies, pre-market evaluations, developing and implementing marketing strategies, and KOL development. Previously, Steve worked at Imclone Systems, now a wholly owned subsidiary of Eli Lilly, as Associate Vice President, Global New Products Strategic Marketing. At Imclone, Steve was the commercial lead for 10 antibody therapeutics where he was responsible for all commercial aspects of the New Product Pipeline. In addition, Steve was Vice-chair of the Hematology council where he reviewed assets and advised on the development of new compounds. Steve has also worked as National Director of Sales and Marketing at Enzon Corporation and as Marketing Director at Immunex Corporation until it was acquired by AMGEN. Sandesh Seth, Executive Chairman of Actinium Pharmaceuticals said, “Steve’s hiring represents another significant step in Actinium’s growth and one that I am most excited about. Steve brings to Actinium a significant amount of knowledge and experience specific to hematology and also has deep relationships that he curated in his 30 years in this field. I look forward to working with Steve and the rest of the Actinium team in building a great company that is focused on improving outcomes for patients.” Actinium Pharmaceuticals, Inc. is a biopharmaceutical company developing innovative targeted therapies for patients with cancers lacking effective treatment options. Actinium's proprietary platform utilizes monoclonal antibodies to deliver radioisotopes directly to cells of interest in order to kill those cells safely and effectively. The Company's lead product candidate Iomab-B is designed to be used, upon approval, in preparing patients for a hematopoietic stem cell transplant, commonly referred to as bone marrow transplant. A bone marrow transplant is often the only potential cure for patients with blood-borne cancers but the current standard preparation for a transplant requires chemotherapy and/or total body irradiation that result in significant toxicities. Actinium believes Iomab-B will enable a faster and less toxic preparation of patients seeking a bone marrow transplant, leading to increased transplant success and survival rates. The Company is currently conducting a single pivotal 150-patient, multicenter Phase 3 clinical study of Iomab-B in patients with relapsed or refractory acute myeloid leukemia (AML) age 55 and older. The Company's second product candidate, Actimab-A, is currently in a multicenter open-label, 53-patient Phase 2 trial for patients newly diagnosed with AML age 60 and over. Actimab-A is being developed to induce remissions in elderly patients with AML who lack effective treatment options and often cannot tolerate the toxicities of standard frontline therapies. In addition, Actinium is developing Actimab-M, which is being studied in patients with relapsed or refractory multiple myeloma in a Phase 1 clinical trial. Actinium is also utilizing its alpha-particle immunotherapy (APIT) technology platform to generate new drug candidates based on antibodies linked to the element Actinium-225 that are directed at various cancers that are blood-borne or form solid tumors. Actinium Pharmaceuticals is based in New York, NY. To learn more about Actinium Pharmaceuticals, please visit and to follow @ActiniumPharma on Twitter please visit, This news release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause actual results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential, or financial performance. No forward-looking statement can be guaranteed and actual results may differ materially from those projected. Actinium Pharmaceuticals undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.

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