Open-access drug discovery database launched

The Wellcome Trust has announced the launch of ChEMBLdb, a database that contains chemogenomic data on over 520,000 small molecules.

The lowdown: In July 2008, the Wellcome Trust awarded a 5-year, UK£4.7 million grant to transfer chemogenomics data from the publicly listed company Galapagos to the European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL–EBI) (Nature Rev. Drug Discov. 7, 789–790; 2008). At that time, EMBL–EBI planned to incorporate the collection into its open-access data resources for biomedical research. The database now contains over 2.4 million records of the effect of the 520,000 small molecules on biological systems (http://www.ebi.ac.uk/chembldb/). The data include information about how small molecules bind to their targets, how these compounds affect cells and whole organisms, and information on the absorption, distribution, metabolism, excretion and toxicity of the molecules. It is hoped that this carefully curated database will overcome some of the challenges that other public databases of chemogenomics datahave faced, such as variations in the way different chemists draw the same chemical structures. Alongside the launch of ChEMBLdb, EMBL–EBI also released SARfari (SAR meaning structure–activity relationship), an integrated resource of sequence, compound and screening data from various sources on protein kinases.

Developers mop up Pfizer's unwanted drugs

Durata Therapeutics and The Medicines Company will develop two drugs that Pfizer has decided not to continue developing, and Debiopharm will help Pfizer in the late-stage development of a third agent.

The lowdown: Towards the end of December 2009, Durata Therapeutics announced that it had acquired Vicuron Pharmaceuticals from Pfizer. Durata Therapeutics was formed by a venture capital syndicate that plans to complete the late-stage development of the glycopeptide antibiotic dalbavancin, which was acquired through the deal. Pfizer had submitted a new drug application for dalbavancin for the treatment of complicated skin and skin structure infections (CSSSIs), but received an approvable letter from the FDA in December 2007. At this time, the FDA's advisory committee on anti-infective drugs was considering whether non-inferiority trials were acceptable for such indications and, if so, what margin of efficacy would be acceptable. Unfortunately, the approvable letter requested additional non-inferiority clinical trial data and, in September 2008, Pfizer reported that it would withdraw its US and European regulatory applications for dalbavancin. Now, Durata Therapeutics plans to complete an 18-month Phase III trial to show non-inferiority to other antibacterial drugs in severe CSSSI. The financial terms of the acquisition were not disclosed.

Also, in December last year, The Medicines Company announced that it has acquired Pfizer's APOA-I Milano, which was in preclinical development for the potential treatment of atherosclerosis. As part of Pfizer's strategy to out-license agents that it no longer wishes to pursue, The Medicines Company will pay an upfront fee of US$10 million for APOA-I Milano and will receive additional payments upon the achievement of certain clinical, regulatory and sales milestones up to a total of $410 million. Pfizer will also be eligible to receive royalty payments on worldwide net sales.

Finally, on 7 January 2010, Pfizer announced that it had entered into a co-development agreement (on undisclosed financial terms) with Debiopharm to conduct a Phase III trial of tremelimumab, a fully human monoclonal antibody specific for cytotoxic T lymphocyte-associated antigen 4, for the treatment of unresectable, stage IV melanoma. In April 2008, Pfizer discontinued a Phase III clinical trial of tremelimumab after the Data Safety Monitoring Board showed that the trial would be unlikely to demonstrate superiority of the drug to standard chemotherapy. Analysis of the clinical trial data revealed an undisclosed biomarker that could be used to identify patients who are most likely to respond to the agent, which will be used to select patients for the new Phase III trial.

Novel risk-sharing fund supports Phase III clinical trials

Paul Capital Healthcare (PCH) has provided up to US$100 million to SARL (P3D), a company recently established to assist in the management and funding of Phase III clinical trials in the European Union (EU).

The lowdown: Since PCH was established in 1999, the investment fund has closed more than 38 investments in the health-care arena and now manages $1.6 billion in assets. This capital has enabled PCH to offer investments that help manage the financial risks of drug development. Now, by supporting P3D, PCH is helping companies to share the financial risk of late-stage clinical development. There is little information available about P3D, but the company has announced that it has already signed an agreement with an undisclosed pharmaceutical company. P3D will assist in the management and funding of Phase III clinical trials of an approved product, with the aim of expanding the product's indications. If successful, P3D will receive development and regulatory milestone payments and a share of product royalties and sales revenues from the pharmaceutical company. Importantly, P3D will help companies to navigate clinical trials in the EU. These can be complicated to undertake owing to different interpretations of the 2004 Clinical Trials Directive by individual EU member states.