Nuvelo
Encyclopedia
Nuvelo Inc. was a biopharmaceutical
company engaged in the discovery, development and commercialization of drugs for acute cardiovascular disease
, cancer
and other debilitating medical conditions. On January 27, 2009, the company was acquired by ARCA Biopharma, Inc. in a reverse takeover
transaction.
and had approximately 60 employees. The Company’s development pipeline included:
In addition, Nuvelo had research programs in leukemia
therapeutic antibodies
and Wnt signaling pathway
therapeutics to expand its drug pipeline and create additional partnering and licensing opportunities.
technology. Hyseq’s genomic
platform was used to develop gene based therapeutics
and diagnostics. At the rate of more than 1,000,000 human DNA samples analyzed per month during 1997, Hyseq was a large partial human gene sequence database
with over 5,000,000 sequences. The HyX platform had five core technologies:
This technology led to collaborations and partnerships with companies and academic institutions including Affymetrix
, PerkinElmer
, Aurora biosciences, Amgen
, Genetastix, Agilent Technologies
, Callida Genomics, Aspen Institute
, University of California at San Francisco, Celera Diagnostics, Surromed, Variagenics, Sequenom
, Archemix, Amgen
and Bayer
. The company also created revenue by out-licensing their technologies with other companies.
Dendreon was paid an upfront fee of $4.0 million with an additional $23.5 million if all development and commercialization milestones are achieved. In addition, royalty payments were structured.
In July 2006, the collaboration was expanded in that Archemix became responsible for the discovery of short-acting aptamer
s targeting coagulation cascade
for use in acute cardiovascular procedures. Nuvelo was responsible for the development and commercialization of any products discovered.
The deal was structured with a $50 million upfront payment and milestone payments totaling $385 million ($165M in development milestones and $170M in sales and commercialization). Although many of these milestones were never achieved, in 2006 a total of $28.9M was billed to Bayer under their cost-sharing agreement.
In February 2003, Hyseq merged with Variagenics giving birth to “Nuvelo Inc.” to further development of drug “alfimeprase.” This drug therapy was developed against peripheral arterial occlusion or “Leg Attack” disease and was approved as orphan drug
status. This accelerated the clinical development of alfimeprase.
. Bayer was collaborating with Nuvelo on late stage studies on alfimeprase. After Nuvelo’s failure in these studies, Bayer closed the deal in June 2007. However, Nuvelo was optimistic and continued the trial with alfimeprase. However, in March 2008, Nuvelo’s phase II trial failed to meet endpoints, thereby forcing Nuvelo to discontinue the trial. The company laid off forty employees and restructured the organization. Also, Dr. Michael Levy, Executive Vice President, Research and Development left the company.
Nuvelo’s share price plummeted eventually to less than $1 and received notification from ]NASDAQ. Despite this, Nuvelo was able to show positive proof of concept for NU172 in August 2008. Following this, Nuvelo was merged with ARCA Biopharma Inc. on September 26, 2008 forming a late stage cardiovascular biotechnology company. ARCA biopharma focuses on developing genetically targeted cardiovascular therapies, with lead candidate drug Gencaro, a beta blocker
and vaso-dilator. It was Nuvelo’s genetically targeted technology and cardiovascular drug development that interested ARCA Biopharma in acquiring the company.
According to the merger
agreement, Nuvelo issued new shares of its common stock to ARCA stockholders and assumed the outstanding option
s and warrant
s involved. Novelo CEO
Ted Love took a seat on the board of the combined business and Arca CEO Richard Brewer became CEO of the new business. The option and warrant holders were expected to own 67% of the combined company’s common stock and Nuvelo stockholders 33% of the new company.
Biopharmaceutical
Biopharmaceuticals are medical drugs produced using biotechnology. They include proteins , nucleic acids and living microorganisms like virus and bacteria where the virulence of viruses and bacteria is reduced by the process of attenuation, they can be used for therapeutic or in vivo diagnostic...
company engaged in the discovery, development and commercialization of drugs for acute cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
, cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
and other debilitating medical conditions. On January 27, 2009, the company was acquired by ARCA Biopharma, Inc. in a reverse takeover
Reverse takeover
A reverse takeover or reverse merger is the acquisition of a public company by a private company so that the private company can bypass the lengthy and complex process of going public...
transaction.
The company
Nuvelo, Inc. was located at San Carlos, CaliforniaSan Carlos, California
San Carlos is a city in San Mateo County, California, USA on the San Francisco Peninsula, about halfway between San Francisco and San Jose. It is an affluent small residential suburb located between Belmont to the north and Redwood City to the south. San Carlos' ZIP code is 94070, and it is within...
and had approximately 60 employees. The Company’s development pipeline included:
- Alfimeprase, a direct-acting fibrinolyticFibrinolysisFibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...
in Phase II development for the treatment of thromboticThrombosisThrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
-related disorders, including acute ischemic stroke and catheter occlusion. - NU172, a direct thrombinThrombinThrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss...
inhibitor in Phase IClinical trialClinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
development for use as a short-acting anticoagulantAnticoagulantAn anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
during medical or surgical procedures. - NU206, a preclinical candidate for the treatment of chemotherapyChemotherapyChemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
and radiationRadiationIn physics, radiation is a process in which energetic particles or energetic waves travel through a medium or space. There are two distinct types of radiation; ionizing and non-ionizing...
therapy-induced mucositisMucositisMucositis is the painful inflammation and ulceration of the mucous membranes lining the digestive tract, usually as an adverse effect of chemotherapy and radiotherapy treatment for cancer. Mucositis can occur anywhere along the gastrointestinal tract, but oral mucositis refers to the particular...
and inflammatory bowel diseaseInflammatory bowel diseaseIn medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
.
In addition, Nuvelo had research programs in leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
therapeutic antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
and Wnt signaling pathway
Wnt signaling pathway
The Wnt signaling pathway is a network of proteins best known for their roles in embryogenesis and cancer, but also involved in normal physiological processes in adult animals.-Discovery:...
therapeutics to expand its drug pipeline and create additional partnering and licensing opportunities.
Start-up phase and core competency
Nuvelo was initially founded as Hyseq in August 1992 and based on DNA arrayDNA microarray
A DNA microarray is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome...
technology. Hyseq’s genomic
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
platform was used to develop gene based therapeutics
Gene therapy
Gene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...
and diagnostics. At the rate of more than 1,000,000 human DNA samples analyzed per month during 1997, Hyseq was a large partial human gene sequence database
Database
A database is an organized collection of data for one or more purposes, usually in digital form. The data are typically organized to model relevant aspects of reality , in a way that supports processes requiring this information...
with over 5,000,000 sequences. The HyX platform had five core technologies:
- Labeled DNA probes
- DNA arrays of samples and probes
- Software-driven modules like Gene Discovery, HyGnostics and HyChip
- Industrial robots to screen DNA probes
- BioinformaticsBioinformaticsBioinformatics is the application of computer science and information technology to the field of biology and medicine. Bioinformatics deals with algorithms, databases and information systems, web technologies, artificial intelligence and soft computing, information and computation theory, software...
software for information management
Transition towards therapeutics
Applications that were developed making use of the genomic platform included gene identification, expression analysis, polymorphism screening and diagnostic testing. The company strategy was to exploit this platform technology to enter gene discovery and to eventually produce therapeutic drugs.This technology led to collaborations and partnerships with companies and academic institutions including Affymetrix
Affymetrix
Affymetrix is a company that manufactures DNA microarrays; it is based in Santa Clara, California, United States. The company was founded by Dr. Stephen Fodor in 1992. It began as a unit in Affymax N.V...
, PerkinElmer
PerkinElmer
PerkinElmer, Inc. is an American multinational technology corporation, focused in the business areas of human and environmental health, including environmental analysis, food and consumer product safety, medical imaging, drug discovery, diagnostics, biotechnology, industrial applications, and life...
, Aurora biosciences, Amgen
Amgen
Amgen Inc. is an international biotechnology company headquartered in Thousand Oaks, California. Located in the Conejo Valley, Amgen is the world's largest independent biotech firm. The company employs approximately 17,000 staff members. Its products include Epogen, Aranesp, Enbrel, Kineret,...
, Genetastix, Agilent Technologies
Agilent Technologies
Agilent Technologies , or Agilent, is a company that designs and manufactures electronic and bio-analytical measurement instruments and equipment for measurement and evaluation...
, Callida Genomics, Aspen Institute
Aspen Institute
The Aspen Institute is an international nonprofit organization founded in 1950 as the Aspen Institute of Humanistic Studies. The organization is dedicated to "fostering enlightened leadership, the appreciation of timeless ideas and values, and open-minded dialogue on contemporary issues." The...
, University of California at San Francisco, Celera Diagnostics, Surromed, Variagenics, Sequenom
Sequenom
Sequenom is a manufacturer of DNA massarrays, based in San Diego, California, United States. The MassARRAY platform is used for SNP genotyping, methylation detection and quantitative gene expression analysis. Sequenom also manufactures clinical tests, such as SEQureDx, a noninvasive prenatal test...
, Archemix, Amgen
Amgen
Amgen Inc. is an international biotechnology company headquartered in Thousand Oaks, California. Located in the Conejo Valley, Amgen is the world's largest independent biotech firm. The company employs approximately 17,000 staff members. Its products include Epogen, Aranesp, Enbrel, Kineret,...
and Bayer
Bayer
Bayer AG is a chemical and pharmaceutical company founded in Barmen , Germany in 1863. It is headquartered in Leverkusen, North Rhine-Westphalia, Germany and well known for its original brand of aspirin.-History:...
. The company also created revenue by out-licensing their technologies with other companies.
Partnerships
In the early days of Nuvelo, when they were called Hyseq, there was a great deal of partnering activity. This was due to their business model which centered on their high-throughput sequencing platform. The company simply partnered or licensed out any novel discovery that did not fall into their desired disease space. Listed below are some of the material collaborations that the company undertook.Dendreon
Nuvelo obtained the worldwide rights for all indication of rNAPc2 and other rNAPc molecules owned by Dendreon Corporation.Dendreon was paid an upfront fee of $4.0 million with an additional $23.5 million if all development and commercialization milestones are achieved. In addition, royalty payments were structured.
Amgen
In October 2004, Nuvelo obtained the worldwide rights to develop and commercialize alfimeprase from Amgen in exchange for future payment to Amgen as negotiated under their initial deal.Archemix
In January 2004, the company signed a 50/50 agreement with Archemix.In July 2006, the collaboration was expanded in that Archemix became responsible for the discovery of short-acting aptamer
Aptamer
Aptamers are oligonucleic acid or peptide molecules that bind to a specific target molecule. Aptamers are usually created by selecting them from a large random sequence pool, but natural aptamers also exist in riboswitches. Aptamers can be used for both basic research and clinical purposes as...
s targeting coagulation cascade
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
for use in acute cardiovascular procedures. Nuvelo was responsible for the development and commercialization of any products discovered.
Bayer
January 2006, Nuvelo partnered to develop Alfimeprase. Bayer was to commercialize the drug outside the United States. Nuvelo retained commercial rights in the United States market and was to receive ROW royalties ranging from 15% to 37.5%.The deal was structured with a $50 million upfront payment and milestone payments totaling $385 million ($165M in development milestones and $170M in sales and commercialization). Although many of these milestones were never achieved, in 2006 a total of $28.9M was billed to Bayer under their cost-sharing agreement.
In February 2003, Hyseq merged with Variagenics giving birth to “Nuvelo Inc.” to further development of drug “alfimeprase.” This drug therapy was developed against peripheral arterial occlusion or “Leg Attack” disease and was approved as orphan drug
Orphan drug
An orphan drug is a pharmaceutical agent that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease...
status. This accelerated the clinical development of alfimeprase.
Failure
Early stage clinical trials for alfimeprase with NU206 (R-respondin protein) and NU172 (short acting thrombin inhibitor) were promising and were approved by the FDAFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
. Bayer was collaborating with Nuvelo on late stage studies on alfimeprase. After Nuvelo’s failure in these studies, Bayer closed the deal in June 2007. However, Nuvelo was optimistic and continued the trial with alfimeprase. However, in March 2008, Nuvelo’s phase II trial failed to meet endpoints, thereby forcing Nuvelo to discontinue the trial. The company laid off forty employees and restructured the organization. Also, Dr. Michael Levy, Executive Vice President, Research and Development left the company.
Nuvelo’s share price plummeted eventually to less than $1 and received notification from ]NASDAQ. Despite this, Nuvelo was able to show positive proof of concept for NU172 in August 2008. Following this, Nuvelo was merged with ARCA Biopharma Inc. on September 26, 2008 forming a late stage cardiovascular biotechnology company. ARCA biopharma focuses on developing genetically targeted cardiovascular therapies, with lead candidate drug Gencaro, a beta blocker
Beta blocker
Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...
and vaso-dilator. It was Nuvelo’s genetically targeted technology and cardiovascular drug development that interested ARCA Biopharma in acquiring the company.
According to the merger
Mergers and acquisitions
Mergers and acquisitions refers to the aspect of corporate strategy, corporate finance and management dealing with the buying, selling, dividing and combining of different companies and similar entities that can help an enterprise grow rapidly in its sector or location of origin, or a new field or...
agreement, Nuvelo issued new shares of its common stock to ARCA stockholders and assumed the outstanding option
Option (finance)
In finance, an option is a derivative financial instrument that specifies a contract between two parties for a future transaction on an asset at a reference price. The buyer of the option gains the right, but not the obligation, to engage in that transaction, while the seller incurs the...
s and warrant
Warrant (finance)
In finance, a warrant is a security that entitles the holder to buy the underlying stock of the issuing company at a fixed exercise price until the expiry date....
s involved. Novelo CEO
Chief executive officer
A chief executive officer , managing director , Executive Director for non-profit organizations, or chief executive is the highest-ranking corporate officer or administrator in charge of total management of an organization...
Ted Love took a seat on the board of the combined business and Arca CEO Richard Brewer became CEO of the new business. The option and warrant holders were expected to own 67% of the combined company’s common stock and Nuvelo stockholders 33% of the new company.
External links
- SEC Filings
- http://phx.corporate-ir.net/phoenix.zhtml?c=109749&p=irol-news&nyo=4
- http://phx.corporate-ir.net/phoenix.zhtml?c=109749&p=irol-newsArticle&ID=800821&highlight=
- http://phx.corporate-ir.net/phoenix.zhtml?c=109749&p=irol-newsArticle&ID=377600&highlight=
- http://pharma.immunodefence.com/2006/12/nuvelo-plunges-79-on-drug-test.html