February

With trepidation from industry, a new chemical regulation in the EU called REACH (Regulation (EC) No 1907/2006) was published in late 2006. The Regulation, which came into force in June 2007, is expected to have a major impact on those chemical and associated industries worldwide that manufacture and/or import chemicals, preparations and articles to the EU. Before REACH, the EU legislative framework for chemicals was fragmented with different rules for new and existing chemical substances and the requirements were generally considered by governments to be inadequate for protecting human and environmental health. REACH brings together all existing EU legislation and is arguably the most comprehensive and far-reaching system of chemical regulation worldwide.

Basic elements of REACH

In brief, the basic elements of REACH are Registration (by industry), Evaluation (by the new European Chemicals Agency, the ECHA), Authorisation (and possible restriction) of Chemicals. The extent of the obligations placed on industry varies depending on the chemical tonnage manufactured in, or exported to, Europe, and on the hazard properties of the chemical substance. Substances alone, in preparations or in articles are affected.

There are exemptions from many or all of the provisions of REACH. Some substances being structurally simple and benign are exempted (and listed in the Annexes to the Regulation). Other chemicals or preparations already regulated are exempt, the most relevant example being substances used in medicinal products within the scope of Regulation (EC) No 726/2004 or Directive 2001/83/EC. Such substances are exempted from registration, evaluation, authorisation and downstream user obligations and information supply in the supply chain (Article 2 of the Regulation). This exemption applies to active and non-active ingredients in regulated medicinal products.

For those phase-in (existing) substances falling within the scope of REACH, the first administrative action for industry will be to pre-register their substances. This will take place in a six-month window starting 12 months after entry into force (June 2008 to December 2008). The subsequent registration procedure requiring submission of data and dossiers is to be carried out over a period of 11 years. The first deadline is for substances imported or manufactured at tonnages above 1,000 tonnes per annum or substances already classified as dangerous over 100 tonnes per annum or CMR category 1 or 2 substances over 1 tonne per annum. Subsequent deadlines in 2013 and 2018 are for lower-tonnage, less hazardous substances (above 100 and 1 tonne, respectively).

It is important to note that the registration process is based on the principle of one substance, one registration (OSOR). Therefore, firms that pre-register the same substance will be encouraged to work together to register jointly the substance and to share data.

The final, and arguably the main driver for REACH, is concerned with the authorisation or restriction of substances. Substances of very high concern (SVHC)(1) cannot be used or placed on the EU market without a specific authorisation granted from the ECHA. In some circumstances, restrictions will apply and some substances, based on their risks to humans and the environment, will be banned.

There are other obligations that REACH places on firms such as information in the supply chain and classification and labelling requirements.

One final, important point is that only EU-based firms or organisations can participate as registrants under REACH. Those firms outside the EU that import to the EU have a choice to nominate their importer to undertake the responsibilities imposed by REACH, or they can appoint a third party (which can be any organisation, including a consultancy firm) as their ‘Only Representative’ for managing their responsibilities. The duties of the ‘Only Representative’ are outlined in the Regulation.

General provisions for intermediates

REACH has identified three categories of intermediates. Non-isolated intermediates (intermediates not intentionally removed from synthesis/manufacturing equipment) are exempt from the provisions of REACH. However, on-site isolated intermediates (not meeting the criteria of a non-isolated intermediate, with manufacture taking place on the same site) and transported (between other sites) isolated intermediates attract registration obligations. Isolated intermediates, if manufactured or imported in excess of 1 tonne per annum, do benefit from reduced registration requirements if the registrant confirms that they are manufactured and used under strictly-controlled conditions, otherwise a full (standard) data package and registration dossier is required. Finally, intermediates are not subject to authorisation, although there is the possibility of restrictions, listed in Annex XVII of the Regulation.

Confidential business information (CBI)

One of the major issues with intermediates is the release of confidential business information (CBI). This includes not only the manufacturer, method of manufacture, and use and composition (impurity profile) of the intermediate, but may also include information on the testing establishment (if in-house, this may reveal the source of the intermediate). Although a concern for the industry, the combination of existing measures in place and action by the registrant should ensure confidentiality.

Existing measures include the option for companies to opt out of joint registration (submitting common parts of the dossier separately), given appropriate justification. Public disclosure of the information submitted in the registration dossier to the ECHA can be restricted, provided adequate justification is provided. For example, this can be restricted to total tonnage bands, study summaries, trade names and IUPAC name.

Voluntary measures taken by companies can add to these provisions. The process of pre-registration, mentioned above, involves the electronic submission of information to the ECHA, such as: name of substance, name and address of registrant, deadline for registration and tonnage band, name of other substances for which available data is appropriate for read-across. To keep the name of the registrant confidential, companies within the EU can appoint a Third Party Representative to submit the pre-registration information (and the registration dossier) on behalf of the manufacturer. It is important to do this at the pre-registration phase. Firms outside the EU can appoint either their importer or an Only Representative to fulfil the REACH obligations. Unlike the Third Party Representative, this involves greater liability. Nevertheless, this can conceal identity. The Third Party or Only Representative can participate in discussions with other registrants for the purposes of data sharing. There is also the option, in the case of multinationals, of having their EU legal entity undertake the various tasks, however, this might not preserve anonymity.

Data-sharing

Under REACH, data-sharing between registrants of the same substance is mandatory. Specific procedures have been introduced to enable data-sharing prior to registration. Following pre-registration, those companies that have submitted information on the same phase-in substance will be made aware of each other to facilitate communication, data-sharing and joint submission, if appropriate. Although, potentially, sharing of data may appear to compromise CBI, this is not the case. If data are shared and compensation agreed, only access to the data is granted (unless otherwise agreed between parties). Companies cannot be forced to provide copies of reports or even full summaries. Endpoints need to be shared for reasons of conducting risk assessments and these endpoints will be disclosed to the public, eventually. Therefore, that information within reports that might be considered confidential is preserved. After 12 years from the date when studies are submitted for registration, summaries will be made freely available for public use.

Information sources

EU Commission, Member State, industry and consultancy firm websites are awash with information on REACH. Arguably, there is too much information afforded to the indiscriminate seeker of knowledge. Two worthwhile sites belong to the European Chemicals Agency (http://ec.europa.eu/echa/reach_en.html) and the UK Health and Safety Directorate (http://www.hse.gov.uk/reach/helpdesk.htm). The Commission has now published several thousand pages of guidance documents (interestingly called RIPs: REACH Implementation Projects). The quality of the information in these documents is increasing and notable documents are those concerned with Pre-Registration and Data Sharing (RIP 3.4), Guidance on Registration (June 2007) and Guidance on Intermediates (June 2007).

(1) A SVHC is defined as being a CMR (carcinogen, mutagen, reproductive toxin) category 1 or 2, PBTs (persistent, bioaccumulative or toxic), vPvBs (very persistent, very bioaccumulative) or substances of equivalent concern and included in the candidate list for Authorisation.

FURTHER INFORMATION
Dr Louis Wyness
TSGE
Concordia House
St James Business Park
Knaresborough
North Yorkshire HG5 8QB
United Kingdom
Tel: +44 1423 799633
Fax: +44 1423 797804

Internet Links:
Email: louis.wyness@tsgeurope.com
Web: www.tsgeurope.com

Argenta Discovery recently announced that it had entered into a fee-for-service collaboration with Antisoma in which scientists from the two organisations will work together to develop improved molecules for Antisoma’s programme of telomere targeting agents (TTAs). Antisoma will utilise Argenta’s expertise in medicinal chemistry, computer-aided drug design, molecular biology, biochemistry, assay development and in vitro screening during the course of the collaboration. Financial terms of the deal were not disclosed, but the agreement does provide options to expand the relationship.

Argenta also recently entered into an alliance with NeuroSolutions Ltd to gain preferential access to specialist electrophysiology and hERG testing services and expertise. The collaboration will enable Argenta to provide its contract research clients with an expanded assay development and screening resource, either as part of an integrated drug discovery programme, or as a stand-alone service.

Dr Christopher Ashton, chief executive officer of Argenta Discovery, commented: “Argenta has been looking at ways of enhancing its biochemistry and in vitro screening capabilities. We have entered into this collaboration with NeuroSolutions to provide Argenta with dedicated access to specialist electrophysiology and hERG screening services, offered by a leader in the field. Argenta has a number of contract research programmes in the pipeline for 2008 which will benefit from NeuroSolutions’ support and expertise. This alliance will enable Argenta to provide assay development and compound screening services across an even wider range of small-molecule gene families.”

Small-molecule discovery agreements

In December, ChemDiv Inc signed a collaborative discovery research agreement with US company Siwa Biotech Corporation in which ChemDiv will initiate a high-throughput screen for small-molecule inhibitors of tyrosylprotein sulfotransferases. The collaboration provides Siwa Biotech with access to ChemDiv’s expertise in chemistry systems and lead discovery.

In another recent development, Graffinity Pharmaceuticals established its second drug discovery collaboration with Pfizer in which Graffinity will provide Pfizer with access to its proprietary, fragment-based screening technology for use in screening drug targets. Graffinity will receive technology access fees and payments for follow-up chemistry for the generation of novel small-molecule hits against a number of drug targets.

Discovery agreement for cancer therapeutic antibodies

Oxford Genome Sciences (UK) Ltd (OGeS) has entered into a strategic collaboration with Amgen to discover, develop and commercialise novel therapeutic antibodies for the treatment of cancer. This new collaboration will enable OGeS to further strengthen its pipeline of fully human therapeutic antibodies in cancer based on the target discovery capabilities of its OGAP® database.

OGeS and Amgen will jointly discover novel antibodies for the treatment of cancer. The companies will generate fully human antibodies using Amgen’s XenoMouse® technology, which was acquired through its acquisition of Abgenix. These antibodies will be raised against the novel druggable targets that OGeS has identified through the OGAP database. OGAP has been developed into the world’s largest cancer protein database to discover novel clinically relevant drug targets and diagnostics.

The agreement covers up to six oncology programmes. Amgen will have the right to select up to three programmes, while OGeS will retain rights to the remainder. Once Amgen has produced the initial antibody leads, OGeS will carry out the initial preclinical assessment of each antibody programme.

Dr Christian Rohlff, CEO of OGeS, commented: “I am very happy to be collaborating with Amgen in our effort to discover and develop novel fully human antibodies for the treatment of cancer. I am confident that by using our complementary expertise we will be able to develop a promising and valuable pipeline of antibodies. This significant new deal, together with our existing Medarex collaboration, further underpins OGeS’ transition from a target discovery to a product development company and is an important step in our ambition to become a key player in the field of therapeutic antibodies for the treatment of cancer.”

OGeS’ new collaboration with Amgen follows a previous agreement that the company signed with Medarex and Biosite which means that the company now has access to the two leading technologies that are used to generate fully human monoclonal antibodies as it works to develop its own product pipeline of cancer therapeutics and diagnostics.

GPCR screening agreement

Multispan and Promega have recently agreed to co-develop assay tools for G-protein coupled receptor (GPCR) screening. The companies will combine Multispan’s GPCR cell lines and Promega’s bioluminescent technologies to create optimised GPCR screening protocols. The first tools will support cell lines and the cAMP-Glo™ Assay for quantification of signal. Additional tools will be developed for cell-based assay detection. The companies say this combination of validated biologic components with the most sensitive and dynamic luminescence assay detection technology for high-throughput screening will provide increased speed and efficiency in GPCR drug screening.

“Pre-optimised protocols will reduce assay development times, from months to days, helping deliver better GPCR targeted drugs faster,” said John Watson, marketing director of pharma/biotech at Promega. “Our suite of assay tools can be combined with Multispan’s validated GPCR cell lines to provide turnkey solutions for drug discovery scientists. Bioluminescent tools developed at Promega are routinely used to profile small-molecule compounds, study druggable targets such as GPCRs, nuclear hormone receptors, proteases and kinases, and assess cell viability and cytotoxicity.”

Integrated offering supports biologics development

NextGen Sciences has formed an alliance with Paragon Bioservices, Inc, a provider of contract research and manufacturing services in support of developing biologics. The alliance expands the portfolio of both companies with the ability to offer existing and future customers an integrated offering including molecular biology, protein production, proteomics, functional assay development, biomarker discovery and monitoring. NextGen Sciences says that this alliance extends its commitment to expand its fee-for-service offering in strategic partnerships in addition to adding new capabilities in-house, such as its protein biomarker monitoring services introduced in November 2007. The companies have agreed to co-market each other’s fee-for-service offerings, thus allowing client companies to choose a one-stop-shop for all their gene-to-protein needs.

Systems biology consortium

Elan Pharmaceuticals has joined GeneGo Inc’s MetaTox Consortium, which is focused on developing systems biology tools for safety assessment of small-molecule compounds and biological therapeutics. This effort includes the expansion of the existing tools in the MetaDiscovery™ platform with toxicity ontologies, developing ‘knowledge-based’ predictive models (functional descriptors), manual reconstruction of toxicity pathways in human and relevant preclinical model species, and the development of simplified workflows for analysing and reporting systems toxicology data. These tools will enable the members of the Consortium to leverage their diverse molecular toxicology data in an integrated ‘systems’ perspective that has not been available until now. The Consortium will propose the deliverables, to be voted on and prioritised by the members, and GeneGo will then develop and deliver the agreed-upon content and software with members’ input. All the members joining to date have said that they could not perform this amount of work internally for the membership fee, which, GeneGo says, helped to justify the business model.

“Despite the increasing deployment of new technologies probing the molecular basis of chemical toxicity, too many investigational drugs still fail in clinical trials due to human toxicity unseen in preclinical safety assessment,” said Dr Richard Brennan, director of toxicology at GeneGo. “The Consortium, which includes representatives from industry and from FDA, believes that part of the problem lies in a lack of appropriate data analysis tools to properly integrate the multiple data types generated by data-rich omics technologies, and to convert findings from cell-based and animal models into meaningful human risk-assessments.

“We will focus on developing novel predictive models, while expanding our knowledge-base of toxicity information, and developing new software for omics data analysis in a systems biology perspective. Alongside GeneGo’s expertise in identifying and mapping differences in human and model-species biology, these tools will facilitate a better assessment of the potential for human toxicity from preclinical tests, increasing the quality of, and confidence in, new compounds going into clinical trials. They will also contribute to understanding the causes of failure for compounds that drop out of trials, or are withdrawn from the market, for safety reasons, allowing these liabilities to be screened out of follow-up molecules,” he said.

Lead discovery technology contract extension

Genedata, a provider of in silico solutions for drug discovery, has announced a multi-year contract extension for the use of the Genedata Screener® lead discovery product suite with pharmaceutical manufacturer Nycomed. Genedata will create a global scientific computing infrastructure for the lead discovery and drug research programmes at Nycomed sites worldwide.

Independent of instrumentation, technology, volume or location, Genedata Screener will enable the interdisciplinary teams at all sites to rapidly capture, visualise, analyse and manage large volumes of assay data. Low to ultra-high throughput screens, single-point assays or complex high content screens can be performed in association with Screener. The effective combination of these findings with data from other corporate sources, accessible through Screener’s viewing tools, will provide Nycomed scientists with information they need to enhance their lead finding processes.

In January, DSM Pharma Chemicals, a business unit of DSM Pharmaceutical Products, entered into an enzyme supply agreement with German company IEP to enable fast and secure scale-up of chiral alcohol manufacturing based on IEP enzymes. DSM Pharma Chemicals has secured access to IEP alcohol dehydrogenases, which are screened at IEP, as well as to the supply of IEP enzymes at commercial scale. DSM can either source the enzyme from IEP or produce the enzymes in its own enzyme manufacturing facilities located in Delft, The Netherlands; Capua, Italy; and Seclin, France.

Founded in 1962, Ash Stevens Inc (ASI) is a contract research organisation focused on low-volume, high-value APIs produced using the company’s more than 40 years experience in chemistry, process development, materials, and quality requirements of products. ASI’s corporate offices and research facilities are housed in the Detroit Research Park, Michigan, USA, and has six research laboratories and support facilities.

The company’s customer base includes both the private sector and the US Federal Government. Services include chemical research and development, support of clinical trials through synthesis of drug candidates, and manufacturing of APIs post-regulatory approval. This support has led to approvals on APIs in many areas including oncology. The company was recently approved to manufacture the active ingredients in Velcade, Vidaza and Clolar. With these approvals, it now has 11 FDA-approved drug substances in its portfolio.

“We support all facets of chemistry manufacturing and controls preparation related to APIs, including structure elucidation, specifications development, methods validation, and drug substance stability, as well as preparation of documentation for submission,” says Dr Stephen A. Munk, the company’s president and CEO.

“Ash Stevens had been a long-time Government contractor and one of the compounds that we were developing with the National Cancer Institute, Fludarabine Phosphate became interesting commercially. The company followed that drug to the market and we continue to support the brand, Fludara, 17 years after approval! That initial approval re-focused our investment programme to ensure that we continue to modernise our operations in line with current pharmaceutical and GMP thinking. That was a major driver for our 2000-2003 plant upgrade and expansion.”

Investment in process development and drug manufacture

ASI’s process development and drug manufacturing facility is located in Riverview, Michigan. The 28,000 sq ft facility now houses nine chemical drug development and production laboratories, three full-scale production areas, as well as two analytical laboratories for quality control. Projects at this facility typically involve cGMP manufacture of material for toxicological and clinical studies through to commercial production after approval of the drug product. Major production equipment includes glass-lined batch vessels (up to 500 gallons), hydrogenation and other pressure vessels, centrifugal, nutsche and Rosenmund filter-dryer equipment, and vacuum and convection tray drying ovens, plus barrier isolation systems.

Last October, ASI announced that it had recently brought two new Rosenmund filter-dryers and a 100-litre pilot plant with cryogenic capabilities online at Riverview, representing an investment of more than $2.5 million. The large filter-dryer, a 0.3 cubic metre unit, is equipped with glovebox technology to facilitate handling of air-sensitive materials and to enable safe handling of Category 3 and 4 potent materials at plant scale. The smaller filter-dryer, a 0.03 cubic metre unit, is designed to be used with the company’s new cryogenic pilot plant which has the capability of maintaining temperatures as low as -80°C and can operate seamlessly to 200°C. The new systems are modeled an ASI’s process laboratories with pocket filters and vessels using the same geometries as those found in the main plant.

“These new capabilities facilitate the rapid scale-up of processes to support product requirements throughout clinical development and post-launch,” says Munk. “It’s our mission to translate client discoveries into new products to help seriously ill people. By upgrading our facilities with scaleable systems and assuring rapid product supply, we are investing in our customers’ success in the form of faster drug approvals.

“Ash Stevens thinks in detail about specifications not only from a technical perspective but from a regulatory perspective. Often, while things might make chemical sense, specifications are inadequate from a regulatory perspective. We additionally have a real understanding of pharmaceutical needs and timelines and are able to help optimise material management issues with our clients. This allows us to be nimble and ensure that material of adequate quality is available quickly for toxicology work while we prepare for the clinical side of the programme.”

Niche product manufacture

ASI’s products are sold globally and the company has been audited by a large number of Ministries of Health including in Europe, Japan, Korea, and Australia. The company produces APIs for both large pharma clients (for Fludarabine Phosphate and Clofarabine) as well as emerging pharma clients. Munk says its flexible, robust systems allow it to work efficiently with a variety of clients:

“Many in our industry have the same physical infrastructure as Ash Stevens. What distinguishes Ash Stevens is the depth of our systems and our understanding of the needs of pharmaceutical companies in contrast to the needs and requirements of organisations focused mainly on chemicals. This is reflected in the large number of New, Innovator, and Developed Chemical Entities that we were recently approved to produce – three in a period that has seen less than 100 for the entire world.”

Munk says ASI’s capacity is well suited for niche products, as its largest vessels are 500 gallons: “This limits our ability to deliver many metric tons quickly but we are a very nimble organisation and understand the very tight timelines for ensuring the survival of our client companies. Since we also have a lot of ‘Big Pharma’ regulatory and manufacturing experience, our systems are robust enough to meet the depth and demands of larger pharma clients as well.”

Level playing field

Munk is very positive about the company’s future: “Chinese and Indian companies will ultimately need to comply with tougher regulatory standards and that will level the playing field in terms of price,” he says. “Wages are also rising in those parts of the world, but I feel the financial advantage that producers from that part of the world enjoy is largely driven by the cost of regulatory compliance.

“I think that the outlook for competent contract research and development organisations is very positive going forward. We are certainly positive for the future and continue to invest in our business. We brought low-temperature capabilities online last year and purchased new, contained isolation technology – filter-dryers with glovebox technology. We have just completed commissioning of a new 400 MHz NMR. Emerging pharmaceutical companies will continue to be formed with exciting concepts from academic laboratories as well as licensing from Big Pharma as they realise that they cannot pursue all of the great opportunities that they have before them. There will be opportunities for those organisations to realise value from products that do not fit their company objectives and that will create opportunities for new companies to take up the challenge of converting those ideas into products.

“I think that it is a great time to be in the contract R&D/manufacturing environment. Those with a good understanding of pharma needs and the financial resources to invest will thrive as outsourcing grows in importance for Big Pharma as well as new companies whose business model does not include a full complement of chemical development and manufacturing expertise,” he concludes.

FURTHER INFORMATION
Dr Stephen A. Munk
Ash Stevens Inc
5861 John C. Lodge Freeway
Detroit, MI 48202
USA
Tel: +1 313 872 3621
Fax: +1 313 872 6841

Internet Links:
Email: samunk@ashstevens.com
Web: www.ashstevens.com

Bangalore, India-based Syngene International Private Limited is an internationally-known custom research company with multi-disciplinary skills in synthetic chemistry and molecular biology. Leveraging the convergence of information technology and biotechnology, Syngene conducts high-value R&D in early-stage drug discovery and development for a diverse global clientele.

A subsidiary of Biocon Limited, one of India’s premier biotechnology companies, which was established in 1978, Syngene provides customised R&D services to pharmaceutical and biotechnology companies on a strong platform of intellectual property protection. Syngene was established in 1994, and operates state-of-the-art facilities, employing highly-qualified researchers.

Biocon and its two subsidiary companies, Syngene International Ltd and Clinigene International Ltd, form a fully integrated biotechnology enterprise, specialising in biopharmaceuticals, custom research, clinical research and enzymes. With successful initiatives in clinical development, bioprocessing and global marketing, Biocon delivers products and solutions on a global basis. Many of these products are FDA- and EMEA-approved. Biocon launched the world’s first recombinant human insulin, INSUGEN, in November 2004 using Pichia expression and India’s first indigenously produced monoclonal antibody BIOMAb-EGFR.

Research partnership with BMS

In March of last year, Syngene entered into a research partnership with Bristol-Myers Squibb (BMS) to provide R&D services for discovery and early drug development to BMS. Under the agreement, BMS is significantly increasing the scope of its relationship with Syngene to further develop integrated capabilities in India in medicinal chemistry, biology, drug metabolism, and pharmaceutical development. Syngene is partnering with BMS through a dedicated research facility at Biocon Park, Bangalore, which is planned to ultimately house more than 400 scientists to help advance BMS’s discovery and early drug development. Leveraging the current global demand for biopartnering, the alliance aims to provide cost-effective growth and access to top scientific talent in India.

“We are delighted to announce this one-of-a-kind discovery research partnership with Bristol-Myers Squibb, a recognised global healthcare leader,” commented Dr Kiran Mazumdar-Shaw, chairperson of the Biocon Group “The new research facility will mark a significant step forward in our evolution as a valuable partner to the global pharmaceutical industry.”

“Bristol-Myers Squibb has been a valued customer of Syngene since 1998. This enhanced partnership with Bristol-Myers Squibb heralds a new phase in Syngene’s advancing capabilities in providing high-end services in discovery research,” added Dr Goutam Das, Syngene’s chief operating officer.

“This broad expansion of R&D in India will allow us to grow competitively while maintaining our industry-leading position in productivity and innovation,” commented Elliott Sigal, MD, PhD, chief scientific officer, and president of the Pharmaceutical Research Institute, Bristol-Myers Squibb. “Through this partnership with Syngene, Bristol-Myers Squibb will continue to access world-class talent to deliver and grow our robust product pipeline.”

Research facilities

Following the announcement of the parnership, Syngene and BMS conducted a ground-breaking ceremony for their new research facility at Biocon Park. Dr Francis Cuss, senior vice president of the Pharmaceutical Research Institute, Bristol-Myers Squibb, laid the foundation stone. Dr Mazumdar-Shaw,and Dr Das were also present.

The research facility at Biocon Park is located in the Bommasandra Industrial Area - Phase IV. Syngene opened its own new research centre at Biocon Park in October 2004. The state-of-the-art facility occupies over 50,000 sq ft and is ISO 14000 compliant, employing over 200 scientists. The research centre offers capabilities in niche areas of synthetic chemistry, molecular biology and custom synthesis.

International agreements

In September 2006, Syngene and Innate Pharmaceuticals AB, based in Umeå, Sweden, concluded a cooperation agreement to jointly develop, manufacture and market virulence blockers to counteract bacterial diarrhoeal disease. Virulence blockers are a new class of drugs that could become an alternative to antibiotics. Virulence blockers disarm certain bacteria, rendering them incapable of causing disease, without affecting the body’s normal bacterial flora, thus reducing the risk that the bacteria will develop resistance to the drug.

Diarrhoeal diseases are one of the biggest factors in the global disease burden. There is an extensive medical need for drugs to treat diarrhoeal diseases, which affect over one billion people worldwide every year. Clinical studies of therapeutic effect are being conducted and a candidate drug is being developed to the stage of a limited Phase II study in patients with diarrhoeal disease. Syngene will carry out further clinical studies enabling the virulence blocker to be registered as a drug for the treatment of bacterial diarrhoeal disease. Innate Pharmaceuticals will have European marketing rights, while Syngene will have rights to other parts of the world market. Each company will receive royalties on the sales conducted by the other.

Innate Pharmaceuticals was formed in 2000 to create a commercial platform for the research taking place at Umeå University and Karolinska Institutet in Stockholm, Sweden. The company has developed and applied for patents for a number of chemical substances to counteract bacterial infections, that is, for virulence blocking substances. Innate Pharmaceuticals and Syngene have been working together on several projects over recent years.

In August 2004, Syngene entered into a contract research agreement with the Novartis Institutes for Biomedical Research, Inc to carry out research projects to support new drug discovery and development. Novartis is just one of the leading multinational pharmaceutical companies that form part of Syngene’s client portfolio in this area.

“We are delighted and proud to work with Novartis. This alliance is yet another step in our evolution as a valuable partner to the global pharmaceutical industry and further enhances Syngene’s ability to conduct world-class research,” commented Dr Mazumdar-Shaw.

Commenting on the agreement, Dr Jeremy Levin, global head, strategic alliances at the Novartis Institutes, said: “We have an aggressive programme to seek the best collaborations worldwide. Our desire is to develop strong alliances with world-class scientific programmes in India, and the relationship with Syngene, and its parent Biocon, offers such an opportunity.”

Ranjit Shahani, country president, Novartis Group in India, added: “India has a huge diaspora of talented scientists and chemists and these arrangements are pushing the globalisation frontier in R&D in pharmaceuticals to a new level. Partnerships such as this devolve and optimise lead times and costs to the final advantage for the patient. A robust patent regime will only encourage more such collaborations in the future.”

FURTHER INFORMATION
Syngene International Limited
Biocon Park, Plot No 2 & 3
Bommasandra IV Phase
Jigani Link Road
Bangalore - 560 099
Karnataka
India
Tel: +91 80 2808 3156
Fax: +91 80 2808 3150

Internet Links: Email: bd@syngenintl.com
Web: www.biocon.com/syngene.asp

Last December Pfizer and Adolor Corporation established an exclusive worldwide collaboration to develop and commercialise novel compounds, ADL5859 and ADL5747, for the treatment of pain.

Plethora Solutions was founded in 2003 to develop new treatments for urological disorders affecting both men and women and has built a well-balanced product portfolio, targeting male sexual health, ur

“iNovacia’s drug discovery services to biotech and pharmaceutical companies are supported by a strong chemical library, the application of biophysical tools and its long experience in drug develop