CONTRACT RESEARCH Collaborations based on Enantia’s broad range of capabilities
Collaboration 1: A US pharmaceutical company developed a new indication for one of its existing drugs. The existing synthetic procedure for small-scale production was not cost-effective for larger-scale production of this chiral API.
Enantia was selected amongst a list of major US and European CROs, based on the excellent technical proposal, according to client feedback. An FTE-based contract was signed with the IP generated belonging entirely to the sponsor. After six months, a patent application was filed by the sponsor for a new and cheaper way to prepare the API.
Collaboration 2: A European fine chemical company had developed a process to
different approaches to improve solubility and enantiomeric resolution, and solve purification problems.
Enantia developed the first process based on co-crystallisation technologies in 2004 when this was a topic discussed only in academic circles. This was a process to develop a chiral resolution for a molecule where the classical diastereoselective salt crystallisation was not possible as the target molecule was unable to form salts. The co- crystal approach was an elegant and cost- effective one that was successfully scaled-up later on and used at the larger scale. “This was the compelling event that made us realise the tremendous opportunity of applying co- crystal technology, not only to prepare pharmaceutical co-crystals to shape and improve physicochemical properties, but also to apply it to solve process chemistry challenges in an effective way,” says Feixas. “Co-crystallisation techniques can offer much cheaper options for resolution of chiral molecules and purification of achiral and chiral molecules, especially when these molecules are unable to form salts. For example, it is possible to potentially avoid costly chiral column chromatographies and use a simple co-crystallisation step.”
International collaborations Enantia has established a number of close international collaborations over the past three years: “Due to confidentiality reasons, we are unable to comment on the majority of our clients,” says Feixas. “However, we have collaborations not only with tier 1 and tier 2 pharmaceutical and fine chemical companies but also with smaller biopharmaceutical companies in a number of European countries including Switzerland, Italy, France and
prepare an API and this included a classical racemic resolution. The originator’s chemical process and the resolution were patent- protected by two independent patents, the latter expiring a few years after the process one. One way of resolving the intermediate at a low cost would allow the sponsor to reach the market a few years before the competition.
Enantia pre-evaluated the case and took the project on at its own risk. Seven months later, Enantia delivered to the client a new patentable, high-yield, high ee diasteromeric co-crytsallisation process that provided the chiral intermediate at a competitive cost, allowing the circumvention of the resolution patent.
Austria. However, the USA, due to the euro/dollar exchange rate, is a difficult market to penetrate, although we are making progress. For the next two to three years, Enantia is poised to consolidate existing collaborations and grow the number of collaborations.”
Pharmaceutical project preferred partner
Set up on the basis of a strategic alliance between four Spanish pharmaceutical companies (Almirall, Esteve, Palau Pharma and Proteomika), the NEOGENIUS project will run for four years with a total budget of €15.4 million with the objective of discovering and developing new painkilling medicines for patients suffering from osteoarthritis. Enantia was selected as the custom synthesis provider to support the drug discovery activities of the consortium. One outcome of the project was the development by Enantia of a new chiral ligand, MaxPhos, which when complexed with rhodium is used to promote a number of enantioselective hydrogenations. This catalyst is particularly stable, very active and affordable. Currently, a number of customers are already using it at pilot scale and achieving highly satisfactory results, the company says.
Future projects and technology developments
Enantia is promoting co-crystal technologies in all areas where it can be applied, and at the same time working to provide a holistic approach to solid forms: “It is a fact that in the past a good part of our efforts have been in the development of co-crystals but we also want to have a broader, more ‘lateral’ offering. For this we recently acquired a spray-dryer rig
in order to be able to offer capabilities in amorphous forms,” says Feixas. “On the chiral technologies side we are committed to exploring and expanding the MaxPhos family using different metals, chemical transformations and ligands, and we are committed to developing new, greener chemistry. We recently developed some industrial conditions for a particular oxidation process that allows the use of non-chlorinated solvents, a fact not reported in the literature for that type of oxidation, and using milder conditions.”
Another key aspect of the company is its commitment to keeping abreast of new technologies and trends in the pharmaceutical industry, and it recently opened a new department dedicated to the custom synthesis of particularly highly valued polymers. This new department allows Enantia to enter new areas with direct applications in nanotechnology, drug delivery and solar cells, to name but a few. “The Spanish economy faces a number of challenges, and this has had an impact on some of Enantia’s projects,” says Feixas. “Fortunately, Enantia has a healthy financial situation and this allows the company not to be wholly dependent on services and to develop our own technologies. This allows us to undertake projects at our own risk, and later successfully commercialise them with our national and international clients. The fact that our client base is becoming less dependent on the Spanish market has made the effects of the Spanish economic climate less severe. Even in this difficult local environment, Enantia has expanded its facilities with a new lab for medicinal chemistry projects. “Although faced by a challenging global economic environment, we believe that as a company we are well placed for further growth. Co-crystallisation services are becoming increasingly important to our clients and partners and this new technology combined with our existing services and innovative business model means we are in an excellent position to enjoy continued success,” concludes Feixas
Further information Dr Joan Feixas, Enantia, SL C/ Baldiri Reixac, 10 Barcelona 08028 Spain Tel: +34 93 403 48 37 Fax: +34 93 403 48 38
Internet links Email:
info@enantia.com
Web:
www.enantia.com March/April 2012 sp2 Inter-Active 21
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48