Xechem International Inc. (fka XKEM)

[foxwoodsfan]

Cosmid Corp, LLC Cosmid Corp is a biopharmaceutical company that owns the worldwide patent rights to COS-103, currently being developed in the U.S. to treat Sickle Cell Disease (SCD). COS-103 is an orphan drug and may help meet a substantial medical need in the treatment of SCD, especially in children.
COS-103 is a reformulation and significant improvement of an existing drug (NIPRISAN) sold outside of the United States. The National Institute of Health Sickle Cell Disease Reference Laboratory has evaluated more than 800 candidate drugs sent from researchers, universities and companies. The most effective drug with minimal adverse effects had been NIPRISAN. COS-103 has been shown to be more potent.
Sickle cell disease (SCD) is a hereditary blood disorder, affecting 90,000-140,000 people in the United States and Europe (Primary Market) and tens of millions of people worldwide (Secondary Market). In the US, those with SCD have an average mortality in their 40s, a poor quality of life, and high medical costs. Existing therapies are inadequate; therefore COS-103 will be a major breakthrough for this orphan disease.
Wednesday, September 16, 2009

Key PeopleCosmid Corp's mission is the clinical developement of orphan drugs to improve the lives of children and adults with serious or life-theatening diseases. Management & Directors

Robert A. Swift, PhD – Founder, Chief Executive Officer. Dr. Swift is a biotechnology entrepreneur. Prior to founding Cosmid, Dr. Swift’s most recent position was Chief Oversight Officer at Xechem International, a biopharmaceutical company. Dr. Swift was a Senior Scientist at Eli Lilly, a Biotech Analyst with Hanifen Imhoff, Director of Research for Life Sciences at Unterberg Towbin, and a Co-Portfolio Manager for Origin Capital, a healthcare sector hedge fund. Dr. Swift received a Ph.D. in Biochemistry from Michigan State University, a M.B.A. in Finance from Indiana University and a B.A. in Chemistry and Biology from Coe College.



Swami Nathan, PhD – Chief Science Officer. Dr. Nathan is co-inventor of COS-103. He is a Visiting Scientist at Rutgers University. He is responsible for the research and development of botanicals for Cosmid and the manufacturing of COS-103. Dr. Nathan was Head of Microbiology for Xechem International prior to joining Cosmid. He received a Ph.D. in Industrial Microbiology from the University of Madras, India.



Peter Kalinka, Ph.D. – Director Dr. Kalinka is an expert in international drug development of Biological drugs especially in the field of Biosimilars. His expertise spans early drug development, CMC, pre-clinical and clinical (Multiple Sclerosis, Hepatitis, Oncology) through to regulatory filing (FDA CDER, CEBER, EMEA, Health Canada and Kosheisho). Dr. Kalinka was a pioneer in the evolution of Biosimilars and was responsible for the development and successful filing of the first Biosimilar in History (Omnitrope, Sandoz). Dr. Kalinka is presently the Head of the Biopharmaceuticals Division within Apotex Inc., Canada. He is also CEO of Tiburon Bio Consulting GmbH a German drug development-consulting firm and is in the faculty of the Johns Hopkins University, Advanced Academic Programs. Dr. Kalinka served as CEO of Accelsiors Ltd., an Eastern European CRO; Head of Clinical Development at BioPartners, Switzerland; Head of the Biologics Division at Novartis Generics, Austria; Product Manager Immunology at Ares Serono, Switzerland; Senior New Project Manager and Project Manager at Sandoz, USA; Head of New Business Development and International Project Manager at Sandoz-Biochemie, Austria. Dr. Kalinka received his Ph.D. from the University of Innsbruck, Austria and held a post-doctoral position at the Institute of Pharmacology and Toxicology at the University of Innsbruck Medical School. He started his career in the Pharmaceutical Industry when joining Sandoz-Biochemie in 1989 where he was directly responsible or involved in the development of more than 30 drugs and biologics of which 7 are presently marketed internationally.



Carolyn C. O’Reilly – Clinical Trial Project Manager. Ms. O’Reilly is an expert in drug development from pre-IND through NDA. Prior to joining Cosmid, she was the Director of Clinical Operations for Advanced Biologics, where she implemented Phase I to Phase IV studies for pharmaceutical and biotech companies, e.g. Johnson and Johnson, Biodel, Schering-Plough, Centocor, Daiichi-Sankyo. She has served as CRA Department Manager for Chromedica and worked with numerous biotech and pharmaceutical companies, including Glaxo and Pfizer on Phase I to Phase IV projects and she has worked as a CRA in all major therapeutic classes. Ms. O’Reilly received his B.A. from Colorado Women’s College.

Larry Gold, Ph.D. – Director. Dr. Larry Gold is the founder, Chairman of the Board, and Chief Executive Officer of SomaLogic. Prior to SomaLogic, he also founded NeXagen, Inc., which later became NeXstar Pharmaceuticals, Inc. In 1999, NeXstar merged with Gilead Sciences, Inc. During nearly 10 years at NeXstar, Dr. Gold held numerous executive positions including Chairman of the Board, Executive VP of R&D, and Chief Science Officer. Before forming NeXagen, he also co-founded and served as co-Director of Research at Synergen, Inc., a pioneering biotechnology company later acquired by Amgen, Inc. Since 1970, Dr. Gold has been a professor at the University of Colorado at Boulder (CU). While at the university, he served as the Chairman of the Molecular, Cellular and Developmental Biology Department from 1988 to 1992. Dr. Gold is a member of the National Academy of Sciences since 1995. Dr. Gold also serves on the board of directors of BioForce Nanosystems, BT Pharma, CompleGen, MicroPhage, and the scientific advisory board of Archemix.
Clinical Advisory Board

Toshio Asakura, M.D., PhD Dr. Asakura is a Professor of Pediatrics, Division of Hematology, Children’s Hospital of Philadelphia (CHOP). Dr. Asakura is Director of the Sickle Cell Disease Reference Laboratory. He received a Ph.D. in Biochemistry from the University of Tokyo and an M.D. from Kyoto Medical College.



Peter Gillette, M.D., PhD Dr. Gillette is a Assistant Professor of Medicine and is the Director of the Adult Sickle Cell Program, Kings County Hospital State University of New York (SUNY-Brooklyn) Health Science Center at Brooklyn. He received his M.D. from the University of Chicago.


Kathryn Hassell, M.D. Dr. Hassell is a Professor of Medicine, Division of Hematology at the University of Colorado Health Science Center (UCHSC) and is the Director of the Colorado Sickle Cell Treatment and Research Center at UCHSC. She received a M.D. from the University of Minnesota.



Kwaku Ohene-Frempong, M.D. Dr. Ohene-Frempong is Professor of Medicine, Division of Hematology, Children’s Hospital of Philadelphia (CHOP). Dr. Ohene-Frempong is the Director of the Comprehensive Sickle Cell Center at CHOP. He received a M.D. from Yale Medical School.







Content copyright 2009. Cosmid Corp. All rights reserved.






Sickle cell disease (SCD) is an autosomal recessive blood disorder affecting 50,000-100,000 people in the United States (Brawley et. al. 2008). In the US, those with SCD have an average mortality in their 40s and aggregate direct hospital costs in excess of $500 million per year (Steiner and Miller 2004). In addition to the increased mortality of the disease, patients often experience a reduced quality of life, suffering frequent episodes of severe bone pain, vaso-occlusive crises, and hospital admissions, reducing their ability to participate in physical activities, affecting their social and economic advancement and producing a fear of early death (Artiz et al. 2009).
The only disease-modifying drug is the anti-cancer drug hydroxyurea (HU) that was approved for use in adult patients with SCD in 1998. A multicenter clinical study showed that approximately 44% of patients on HU therapy had an annual reduction in the rate of painful episodes (Charache et. al. 1995). HU has clearly helped some patients, but not all patients respond to it. HU can be poorly tolerated causing various undesirable side effects, including dose-limiting myelosuppression, and requires frequent monitoring for the life-threatening side effects which have limited its use (Platt 2008). Research over several decades has shown little progress in the development of additional disease modifying agents. Therefore, safer and more effective therapeutic antisickling agents are needed to treat patients with SCD, particularly children, which is the focus of this grant application.
In SCD, the altered beta globin protein of hemoglobin (ßS-globin) has decreased solubility when not bound to oxygen and can self-polymerize forming long rigid deoxy-Hb S fibers inside the red blood cells (RBCs) that result in a rigid sickle shape, hence the name sickle cell disease. Under conditions of low partial oxygen pressure, a condition found in capillaries, the RBCs sickle and can block capillary blood flow. The deformed RBCs can cause an increase in blood viscosity and the altered RBCs can interact with vascular endothelium causing inflammation and occlusion of larger blood vessels.
The interruption of blood flow causes infarctions and ischemic necrosis in tissues and organs (Steinberg 1999). If such occlusions take place in organs such as the brain or lungs, the patients may die. Cumulative ischemic tissue damage and fibrosis can result in chronic pain, and over 50% of SCD patients experience chronic pain (Smith et. al. 2008). SCD pain can last from a few minutes to days or even weeks requiring hospitalization. Splenic sequestration, common in children, is one of the most serious complications and is second only to infection as a cause of death in infants with SCD. Stroke is one of the most devastating aspects of SCD and is most prevalent in childhood and adolescence, where it is estimated that 11% of SCD patients under the age of 20 will have a stroke (Adams et. al. 1998). Recently, it was reported that one third of adult SCD patients have pulmonary arterial hypertension (PAH), which may worsen with age and be a prognostic indicator for early death (Gladwin et. al. 2004).
In an attempt to find new therapeutic agents, various drugs are being tested in clinical trials though to date the results have been disappointing. Some drugs increase the affinity of Hb for oxygen (Cerami 1978; Arya et. al. 1996), delay or inhibit deoxy-HbS polymerization (Eaton and Hofrichter 1983). Some drugs promote hydration/prevent dehydration of RBCs or increase vasodilation, e.g. nitric oxide (NO) or its inducers (Head et. al 1997), or some drugs reduce adhesion of the RBCs and white blood cells (WBCs) to the endothelium (Schechter and Gladwin 2002), e.g. a p-selectin receptor blocker. A trial testing a p-selectin inhibitor recently failed. Some drugs being tested work by inducing the production of more fetal hemoglobin (HbF) similar to the mechanism of hydroxyurea. Short chain fatty acids (Atweh et. al. 1998), azacitidine (Vidaza) or its deoxy derivative decitibine (Dacogen) have shown some promise in increasing HbF (Gilbert et. al. 2004). These drugs, however, cause epigenetic changes by altering the acylation and methylation of DNA and may be inappropriate for children as they might disrupt a child’s genetic developmental program. Increasing the hydration of RBCs with magnesium or blocking the Gardos channel in RBCs has been tried (De Franceschi et. al. 1997; Ataga et. al. 2008) and though increasing the hydration of RBCs is a mechanism of action for reducing sickling, these drugs have not shown a clinical benefit.


References

Adams RJ, McKie VC, Hsu L. et. al. Prevention of a First Stroke by Transfusions in Children with Sickle Cell Anemia and Abnormal Results on Transcranial Doppler Ultrasonography. N Engl J Med. 339:1 5-11 1998.

Brawley OW, Cornelius LJ, Edwards LR, Gamble VN et. al. National Institute of Health Consensus Development Conference Statement: Hydroxyurea Treatment for Sickle Cell Disease. Ann. Int Med. 148:12 1-10, 2008.

Artz N, Zhang J., and Meltzer D. Physical and Mental Health in Adults Hospitalized with Sickle Cell Disease: Impact on Resource Use. J. Nat. Med. Ass. 101:2 139-144, 2009.

Ataga KI, Smith WR, De Castro LM, Swerdlow P, Saunthararajah Y, Castro O, Vichinsky E. et. al. Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia. Blood 111:18 3991-97.

Atweh GF, Sutton M, Nassif I, Boosalis V, Dover GJ et. al. Sustained Induction of Fetal Hemoglobin by Pulse Butyrate Therapy in Sickle Cell Disease. Blood 93:6 1790-97 1999.

Cerami A. Review of the Development of Cyanate as a Drug in the Treatment of Sickle Cell Anemia. Ann. NY Acad. Sci. 538-544 1978.

Charache S, Terrin ML, Moore RD, et.al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med. 32:1317-22 1995.

De Franceschi L, Bachir D, Galacteros F, et al. Oral magnesium pidolate: effects of long-term administration in patients with sickle cell disease. Br J Haematol. 108:284-289 2000.

Eaton WA and Hofrichter J. Hemoglobin S Gelation and Sickle Cell Disease [Review]. Blood 70:1245-66 1987.

Gilbert J, Gore SD, Herman JG, and Carducci MA. The Clinical Application of Targeting. Cancer through Histone Acetylation and Hypomethylation. Clin. Can. Res. 10:4589-96.

Gladwin MT, Sachdev, V, Jison ML, Shizukuda Y, Plehn JF et. al. Pulmonary Hypertension as a Risk Factor for Death in Patients with Sickle Cell Disease. N Engl J Med. 350: 9 886-895 2004.

Head AC, Brugnara C, Martinez-Rolz R, Kacmarek, et. al. Low Concentrations of Nitric Oxide Increase Oxygen Affinity of Sickle Erythrocytes In Vitro and In Vivo. J. Clin. Invest. 100:5 1193-98 1997.

Schechter AN, and Gladwin MT Hemoglobin and the Paracrine and Endocrine Functions of Nitric Oxide. N Engl J Med. 348:15 1483-5 2002.

Smith WR, Penberthy LT, Bovbjerg VE, McClish DK, Roberts JD et. al. Daily Assessment of Pain in Adults with Sickle Cell Disease. Ann. Intern. Med. 148:2 94-101 2008.

Steinberg, MH. Management of Sickle Cell Disease. N Engl. J. Med. 340:13 1021-1030, 1999.

Steiner, CA and Miller, JL Sickle Cell Disease Patients in U.S. Hospitals, 2004 HCUP Statistical Brief #21. December 2006.

Content copyright 2009. Cosmid Corp. All rights reserved.

Publications and LinksPublications


Asakura TA, Chen Q, Nathan S, Tripathi P, and Swift, RA. Improvement of the mass production of Nicosan™/XICKLE™, an herbal medicine that contains strong antisickling agents. Sickle Cell Disease Association of America, 36th Annual Meeting (New Orleans, LA September 2008).

Asakura TA, Swift, RA and Chen Q NIPRISAN reduced the precentage of reversible sickled cells in the blood of 100% human Hb S mice and prolonged their survivial time to longer than one year . Sickle Cell Disease Association of America, 37th Annual Meeting (Orlando, FL September 2009).

Awodgan AO, Wambebe C, Gamaniel K, Okogun JJ, Orisadipe AT and Akah PA. Acute and short-term toxicity of NIPRISAN in rats I: a biochemical study. J. Pharm. Res. Dev. 1:1 39-45 1996.

Cordeiro NJV, Oniyangi O Phytomedicines (medicines derived from plants) for sickle cell disease. http://www.cochrane.org/reviews/en/ab004448.htm

lGamaniel K, Amor S, Akah PA, Samuel BB, Kapur S, et. al. Pharmacological Profile of NIPRD 94/002/1-0: A Novel Herbal Antisickling Agent. J. Pharm. Res. Dev. 3:2 89-94 1998.

Iyamu EW, Turner EA, Asakura T. In vitro effects of NIPRISAN (Nix-0699): a naturally occurring, potent antisickling agent. Br J Haematol. 118:1 337-43 2002.

Iyamu EW, Turner EA, Asakura T. Niprisan (Nix-0699) improves the survival rates of transgenic sickle cell mice under acute severe hypoxic conditions. Br J Haematol. 122:6 1001-8 2003.

Nathan S., Tripath P, Wu QL and Belanger FC Nicosan: A Phytomedicinal Treatment for Sickle Cell Disease In: African Natural Plant Products: New Discoveries and Challenges in Chemistry and Quality, Juliani, H.R., Simon, J.E.,Ho, C.T. (Eds). ACS Symposium Series, American Chemical Society: Washington, D.C., 2009.

Swift RA, Nathan S, Tripathi P, Chen Q, and Asakura TA. Research preview on improving NICOSAN™/XICKLE™, a phyto-medicine for the treatment of Sickle Cell Disease. Sickle Cell Disease Association of America, 36th Annual Meeting (New Orleans, LA September 2008).

Wambebe C, Barngboye EA, Badru BO, Khamofu H et. al. Efficacy of NIPRISAN in the Prophylactic Management of Patients with Sickle Cell Disease. Cur. Treat. Res. 62:1 26-33 2001.

Wambebe C, Khamofu H, Momoh AF, Ekpeyong M, Audu BS et. al. Double-blind, placebo-controlled, randomized cross-over clinical trial of NIPRISAN in patients with Sickle Cell Disorder. Phytomedicine 5:4 252-61 2001.


Links


American Family Physician – Sickle Cell Disease in Children
http://www.aafp.org/afp/20000915/1309.html


Center for Disease Control and Prevention, Sickle Cell Disease
http:// www.cdc.gov/ncbddd/sicklecell

eMedicine – Sickle Cell Disease
http://emedicine.medscape.com/article/205926-overview

Medline Plus by National Library of Medicine and NIH
http://www.nlm.nih.gov/medlineplus/sicklecellanemia.html


Medicine Net - Sickle Cell Disease
http://www.medicinenet.com/sickle_cell/article.htm


National Heart Lung and Blood Institute
http://www.nhlbi.nih.gov/health/dci/Diseases/Sca/SCA_WhatIs.html


Sickle Cell Disease Association of America
http://www.sicklecelldisease.org


WebMD
http://www.webmd.com/a-to-z-guides/sickle-cell-disease-topic-overview


World Health Organization Report by the Secretariat A59/9 Sickle-cell anaemia 2006
http://apps.who.int/gb/ebwha/pdf_files/WHA59/A59_9-en.pdf


Content copyright 2009. Cosmid Corp. All rights reserved.



Dr. Robert Swift
Cosmid Corp, LLC
970.206.4402 Phone
970.377.9554 Fax
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