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MorphoSys Unveils Next-Generation Antibody Technology Ylanthia®


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MorphoSys AG has unveiled its next-generation antibody technology Ylanthia®. The technology was presented to an audience of specialists at the 2011 Antibody Engineering and Antibody Therapeutics Conference in San Diego.

MorphoSys expects Ylanthia to set new standards for therapeutic antibody generation in the pharmaceutical industry over the next decade and beyond. Commercial application will commence in 2012.

"Ylanthia takes antibody technology beyond current methods, among which our HuCAL platform is perhaps the most successful representative," commented Dr. Simon Moroney, Chief Executive Officer of MorphoSys AG.

Dr. Moroney continued, "We believe that the success story of therapeutic antibodies can be substantially expanded if certain current limitations can be overcome. Ylanthia addresses many issues currently limiting the success of this class of drugs. This innovative platform will open up attractive commercial opportunities for us as it delivers a stream of new antibody drugs both for ourselves and our partners."

There are two major reasons why existing technologies limit the successful development of therapeutic antibodies. First, many antibodies fail in development due to poor biophysical properties, which render the molecule "not developable".

If the antibody cannot be manufactured, or its properties make it difficult to handle, chances of successful commercialization are slim. Second, failure to generate antibodies against all regions or "epitopes" of a target may lead to highly promising disease targets being overlooked.

Lack of diversity in antibody generation means that putative targets often are not fully "interrogated" with antibodies intended to probe their role in disease processes. The Ylanthia technology was specifically conceived and designed to overcome these limitations.

Ylanthia comprises a large collection or "library" of human antibodies. A guiding principle underlying the design and construction of the library was to ensure that the library is of the highest possible quality. Features which distinguish Ylanthia from other technologies include:

• Size and heavy/light chain pairing: Ylanthia is the industry's largest known antibody Fab library, comprising over 100 billion distinct, fully human antibodies. Ylanthia uses 36 fixed, naturally-occurring heavy and light chain framework combinations, which translates into unprecedented structural diversity. Great care was invested into the antigen binding site design. The library's diversity is expected to result in antibodies against previously inaccessible target molecules and unique epitope coverage.

• Biophysical properties: Antibody frameworks were pre-selected for expression levels, stability and aggregation behavior. A shift towards higher stability and stress tolerance will increase shelf life and serum stability of resulting antibody products, making them more cost-effective to produce and administer. A higher solubility in turn opens up the path for more convenient ways of administration, to the benefit of patients.

• Optimization: When needed, antibodies from the Ylanthia library are optimized using MorphoSys's proprietary Slonomics® technology, which MorphoSys obtained through its 2010 acquisition of Sloning BioTechnology. Ylanthia thereby distinguishes itself in a central respect from HuCAL, which relies on a modular gene design and pre-formed cassettes for antibody optimization. Slonomics enables optimization of Ylanthia antibodies with unprecedented speed and flexibility.

"In Ylanthia, even more than in previous technology generations, quality was built into the antibody library itself," commented Dr. Marlies Sproll, Chief Scientific Officer of MorphoSys AG.

Dr. Sproll continued, "By engineering out the very flaws that lead to delays in antibody programs, we expect Ylanthia to result in higher overall success rates and shorter timelines in antibody drug development. By offering unprecedented functional diversity, Ylanthia will allow us to fully interrogate disease targets, to deliver unique drug candidates, and potentially even to re-visit "false negatives" - targets which were overlooked when worked on with other technologies."

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