Bio Sidus S.A., founded in 1983, has become a leading developer and supplier of world-class biopharmaceutical products to 30 countries throughout Latin America, Asia, the Middle East, Africa and Eastern Europe. It achieves annual turnover of around US$40 million (€28.7 million) and is a global leader in sales of biosimilar recombinant human erythropoietin (EPO) and other cutting-edge biogeneric products.
The fast-growing enterprise, which already operates according to the highest international standards, plans to enter the European, North American and Australian markets in the next few years, and Marcelo Argüelles, Bio Sidus’s
President, is currently looking for partners to help the company achieve its goals in these markets. Bio Sidus excels at delivering high quality biopharmaceuticals at affordable prices.
History of innovation
Bio Sidus has been expanding its activities over the years. In 1980, the original pharmaceuticals company, Sidus, branched out into cutting-edge biotechnology activities, including cell cultures, genetic engineering and protein purification.
Since the launch of our first product in 1990, we have manufactured and sold more than 60 million drug product units in emerging markets, with more than 75% of our revenues, for fiscal year 2008, derived from sales outside Argentina, and approximately 40% from sales outside Latin America.
Bio Sidus’s proven expertise in Biotech manufacturing methods has resulted in a wide range of biopharmaceuticals, which include Interferon alfa 2a, Interferon alfa 2b, Filgrastim and Somatropin, all produced through bacterial fermentation; and Epoetin, Lenograstim and Interferon Beta 1a, produced through mass cell culture. The company also counts on a robust pipeline of product candidates in different stages of development.
First EPO developed in Latin America
Bio Sidus launched EPO in 1990, the first recombinant human protein fully developed and manufactured in Latin America. To date, Bio Sidus has launched seven recombinant proteins currently distributed in Argentina and abroad. Continuing to innovate, Bio Sidus now has more than 10 biomolecules in its pipeline, and continues to conduct groundbreaking research in transgenic animals and gene therapy.
High-tech facilities to meet international standards
Bio Sidus has two manufacturing sites in the city: the 6,200 sq m Almagro plant, which focuses on manufacturing active pharmaceutical ingredients; and the 5,000 sq m Bernal plant, which specialises in fill-finish, freeze-drying and packaging operations.
In early 2008, to increase capacity for its fast growing biogenics projects, Bio Sidus acquired a 12 hectare manufacturing site with a 12,000 sq m facility to be refurbished to produce bacterial fermentation and mass-cell-culturederived biomolecules, which will help Bio Sidus meet growing demand for such products in the US and EU markets. This facility will be operative in late 2010.
Guiding principles: safety and security
Safety and security are guiding principles for Bio Sidus, whose research, development and manufacturing facilities are all strictly controlled to ensure that all activities meet the highest quality standards. The Bio Sidus Quality Assurance System includes regular internal and external audits and inspections and exhaustive process validation.
Groundbreaking research and development
Bio Sidus is developing new technologies for the high-yield and cost-effective production of recombinant proteins for pharmaceutical applications. Aiming at the optimal expression system for each product, Bio Sidus develops the production of recombinant proteins in bacteria, mammalian cell lines, yeast and transgenic animals.
One of Bio Sidus’s advances is the development of transgenic cattle to obtain recombinant human proteins for therapeutic use.
Transgenic animals to produce human proteins
Bio Sidus has concluded the development of human growth hormone obtained from the milk of cloned transgenic cows, achieving a high yield of the target protein at a convenient manufacturing cost. Bioequivalence of this protein has been conducted in healthy volunteers versus a reference somatropin product available in the market. The results have been satisfactory and the efficacy clinical trial in children with growth retardation has been scheduled for late 2009. This is the last step in the regulatory process to obtain the necessary authorisations to market the product.
The current herd of cattle transgenic for human growth hormone is made up of 30 hGH-producing cows.
Another target protein has been the bovine growth hormone which has successfully been expressed in the milk of cloned transgenic cows. This method of production results in a recombinant protein substantially similar to recombinant bovine growth hormone produced using bacterial fermentation. We currently have four cows that are producing recombinant bovine growth hormone in their milk and we are in the process of selecting a founder animal. The target market for this product is the dairy industry in countries where it has been approved for use aimed at increasing milk production, including Mexico, Brazil and the United States.
Finally, we have applied this manufacturing method to the obtention of human insulin. We have developed a genetic construction that encodes for an inactive human insulin precursor and we have generated eight transgenic cows with this gene. This strategy has been adopted to prevent potentially fatal side effects in the host transgenic cow. The human insulin precursor that was expressed in the milk must be further purified and enzymatically cleaved resulting in a biologically active recombinant human insulin product suitable for use in humans. As our transgenic cows reach sexual maturity, we will start the milking process to assess the presence of insulin precursor in their milk and to conduct the selection of the founder animal based on the level of expression and quality profile of the target protein. After selecting a founder animal, we will begin the development of the production process, as well as stability assays and preclinical studies. We have applied for patent protection in the United States for our production process of recombinant human insulin.
Clinical trials testing gene therapy for cardiac conditions
Angiogenesis and muscle regeneration using the vascular endothelial growth factor. Vascular endothelial growth factor (VEGF) is a protein that stimulates the growth of blood vessels. We have developed technology to generate naked plasmids containing the VEGF human gene in conditions suitable for administration to humans (i.e., pharmaceutical grade) with the aim of injecting these plasmids into the heart muscle in patients with perfusion disorders. This plasmid would be inserted in the patient’s myocardiocytes to cause the patient’s cells to produce the VEGF protein in order to generate new blood vessels. The resulting contribution of more blood and consequently, more oxygen, to the heart muscle would improve its function. We conducted preclinical trials in animals and we have observed a successful reperfusion of areas of ischemic tissues in the heart of these animals and also tissue regeneration with no toxic or undesirable side effects associated with this treatment.
Following very positive preliminary results we started Phase I clinical trials, GENESIS I, in humans involving ten patients conducted at the Fundación Favaloro, the major cardiological centre in Argentina. The naked plasmid is administered through a catheter that injects it directly into the ischemic area of the heart muscle of the patient. We have observed a significant improvement of cardiac function in all of them, diminishment of angina, increase of the ejection fraction, and no adverse effects or serious side effects throughout patient follow-up.
New clinical trials include Phase II plasmid injection in no-option patients with chronic ischemic heart disease; Phase II coronary artery bypass grafting combined with direct injection of plasmid in myocardial territories non amenable to surgical revascularisation in patients with severe coronary heart disease, and a Phase I/II in severe limb ischemia.
Bio Sidus White Genome Project
Yet another groundbreaking initiative for Bio Sidus is the White Genome Project, which aims to isolate, identify and characterise Antarctic bacterial strains for further sequencing of the complete genome.
In collaboration with the Argentine Dirección Nacional del Antártico, we have developed research aimed at the isolation and characterisation of certain microorganisms from the Antarctic territory that are particularly adapted to extreme temperature. We have isolated and identified a novel species, Bizionia argentinesis and have sequenced its full genome, among some 400 strains of Antarctic bacteria, characterised for living in a temperature range of 1 to 5 degrees Celsius. These microorganisms, have the potential for significant industrial applications in the field of “cold enzymes” for industrial processes.
Additionally, some of the projects we are working on include a collaborative agreement for the production of a Human Papillomavirus vaccine for emerging countries, and broadening the scope of our pharmaceutical dairy project to obtain a mastitis free line of transgenic cows and a herd of cloned transgenic cows for the production of therapeutic monoclonal antibodies.
With its impressive track record, Bio Sidus is well prepared to succeed in new markets in the coming years, and offers outstanding opportunities for partners in the EU and the US.