COPENHAGEN—Nuevolution, a Danish lead discovery company,announced in September that it has entered into a drug discovery collaborationwith Novartis. Per the agreement, Nuevolution will apply its proprietaryChemetics drug discovery technology to identify novel small-molecule leadsagainst drug targets of interest to Novartis. The Chemetics platform usesinnovative DNA labeling to allow fragment-based drug screening at a largescale.
Nuevolution will screen its multimillion member, diversefragment-based screening libraries for hit identification. Through the design,synthesis and screening of target focused Chemetics follow-up libraries, the partieswill also work together to perform hit-to-lead optimization.
"This collaboration will complement our ongoingsmall-molecule drug discovery efforts and hopefully lead to the discovery ofnew small-molecule leads against drug targets of interest to Novartis," saysJeffrey Lockwood, a spokesman for Novartis Institutes for BioMedical Research."We were attracted by Nuevolution's Chemetics drug discovery technology, andits promise as a means to generate new small molecule leads against ournominated targets."
Under the agreement, Nuevolution will receive an upfronttechnology access fee payment, research funding and milestone payments ascandidate compounds progress through preclinical and clinical development andonto the market. In addition, Nuevolution is eligible to receive royalties onthe commercial sales of approved products. Further financial details of theagreement with Novartis were not disclosed.
Nuevolution is using its libraries and screening techniquefor screening internal targets as well as targets of significant interest topartners, which is proving attractive to a number of pharmaceutical companies.Alex Gouliaev, CEO of Nuevolution, says the company invented Chemetics, amethod that allows the company to generate ultra-large chemical libraries forscreening. A typical library size is 20 million to 250 million compounds. Thissummer, Nuevolution reached a milestone of sorts—passing the 1-billion mark ofinteresting small-molecule compounds for screening.
"The technology allow us to process millions of compounds inone screening using only picomoles of screening material and only micrograms oftarget material, while screening our libraries that are each tens to hundredsof fold larger than any conventional Big Pharma library, which is typicallyonly 1 to 5 million compounds in size," notes Gouliaev. It typically takes oneor two technicians four weeks to prepare a library of this size once allmaterials for the library has been obtained. All molecules in our librarybecome attached to a piece of DNA during its synthesis. The DNA will carry theinformation about chemical composition and conditions used for generating themolecule attached to it."
In the screening, all molecules are screened as one mixtureagainst the target of interest, and the most potent ligands are identified fromthe mixture. The technology also can be applied to targets spanning a widerange of disease areas, adds Gouliaev.
"The technology offers a brute-force screening approach totargets, which has been shown to be highly valuable for the identification ofligands to tough targets such as protein-protein interaction targets," Gouliaevnotes. "We believe and have observed that the brute force approach does lead tointeresting results when other conventional methods have failed."
The output from Nuevolution's screening is a set ofsequences, where some sequences will be observed more often than others.
"Those that are observed the most often represent the mostpotent ligands. Our Chemetics technology also allows us to address off-targetactivity—to identify straight from the screening library, ligands which arepotent against the target of interest, but do not have or have significantlyreduced activity against related targets," Gouliaev points out.
The Novartis deal is just the latest collaborative agreementfor Nuevolution. Gouliaev notes that Nuevolution does enter intofee-for-service arrangements, but only accepts agreements in which its partnerwill be significantly committed to the collaboration programs.
"We have entered into agreements with different scope andfocus with Lexicon Pharmaceuticals, Merck & Co. and GlaxoSmithKline," notesGouliaev. "We believe that partnerships are key to optimally harvest the valuesresiding in the technology, where we offer access to millions of smallmolecules for screening and our partner's offers access to biological targetand disease expertise."
The GSK agreement relates to a number of patentedtechnologies for rapid synthesis and DNA-tagging of hundreds of millions ofchemically diverse drug-like, small-molecule compounds and the efficientscreening of these, facilitating the identification of potent drug leads. Thesetechnologies were developed by Nuevolution and Praecis Pharmaceuticals, awholly owned subsidiary of GSK.
In April, Nuevolution announced that Merck agreed to proceedto the second phase of a collaboration agreement initiated in June 2008 toapply Nuevolution's proprietary Chemetics drug discovery technology to identifynovel small-molecule leads against several drug targets. By entering the secondphase, Merck gained access to a new multimillion member proprietary library ofsmall-molecule drug candidates.