Antibody rival drawing investors to Molecular Partners

The company announced today that it has raised CHF18.5m (€11.3m) in Series A financing, having caught the eye of several US and European venture capitalist firms.

Dr Christian Zahnd, CEO of Molecular Partners believes their platform technology offers several advantages over traditional antibody therapies, whilst maintaining their specificity and target affinity.

The novel binding proteins that attracted the new investors have been dubbed Designed Ankyrin Repeat Proteins (DARPins), which is one of several new classes of therapeutic proteins set to take on antibodies in the biopharma market.

Molecular Partner's DRP technology has also drawn plaudits from outside the investment community, having previously won the 'Swiss Technology Award 2005'.

Two of the investor companies will also now have representatives on the board of directors, bringing their industry expertise with them.

One of those new directors, Dr Francesco de Rubertis of Index Ventures, said he is "convinced" the company can go on to build a "broad pipeline of attractive therapeutic assets" .

"We are very impressed by the long-standing track record and the deep understanding of the antibody space our investors bring to the table, thus bringing much more into the company than the strong financial backing," said Zahnd.

DARPins comprise a single protein structural motif that is repeated several times and linked by a peptide loop.

The structural units then stack together to form an elongated molecule.

Zahnd explained in an interview that Molecular Partners can use different structural units in a single molecule and therefore generate proteins that can bind to several targets at once.

Repeat proteins are found naturally in jawless vertebrates where they can induce the adaptive immune system, just like antibodies in humans.

The proteins also play an important role in the innate immune system of humans, animals and plants.

This led Molecular Partners to investigate the possibility of designing repeat proteins that can mediate a specific protein-protein interaction.

The company was originally formed in 2004 as a spin-off from Professor Andreas Pluckthun's group at the University of Zurich, Switzerland.

According to Zahnd, DARPins bind to their protein targets with affinity in the single-digit nanomolar to picomolar range, which the company said is comparable to the strength of antibody binding.

For example, one DARPin the scientists discovered binds to cancer target HER2 in the low picomolar range, which, according to Zahnd, is stronger than Genentech and Roche's Herceptin (trastuzumab) binds to the same target.

GlaxoSmithKline's (GSK's) Tykerb (lapatinib) also binds to HER2 but to the intracellular tyrosine kinase domain of the receptor.

The company has since generated several libraries of repeat proteins, which it claims can bind to a diverse set of targets, including cell surface receptors, cytokines, proteases, kinases and viral coat proteins.

The most advanced library is based on ankyrin but other subclasses occur, such as leucine-rich repeat (LRR) proteins, tetratricopeptide repeat (TPR) proteins and armadillo repeat proteins.

Zahnd explained that Molecular Partners currently has three internal drug discovery projects and although he was currently unwilling to disclose their targets or indications, he did reveal that the research is at the lead optimisation stage and that he hopes at least one potential drug will make it into the clinic by the end of 2009.

As well as being able to bind to "over three or four," targets at once, Zahnd went on the say that the molecules have other advantages over other protein therapeutics, such as they are more stable and easier to make.

As well as its internal programmes, Molecular Partners has also penned alliances with Bayer-Schering - against an unspecified cancer target - and with Roche, where both the indication and target remain undisclosed.

Several other classes of compound could rival traditional antibodies as the therapeutic protein of choice in the future.

Among these are domain-antibodies or 'mini antibodies', which GSK has invested it through its acquisition of Domantis, and Ablynx's nanobodies.

Both of these classes of molecule recently entered Phase I clinical development.

Zahnd said that the major difference between DARPins and these mini-antibodies is that the former are not based on antibody folds - they are totally different structurally.

A third type of molecule that could take some of the market share away from antibodies is aptamers.

Archemix has developed a process for discovering and producing the synthetically-derived short nucleic acid sequences (oligonucleotides).

Aptamers bind to specific target sequences of DNA disrupting interactions between proteins, much like antibodies.

However, because they are chemically synthesised they are much less expensive to make than antibodies.

DARPins are not just limited to the therapeutic market, however.

They can also be used as tools for drug discovery and intracellular target validation, for example as detection agents in ELISA, and in protein knock-down experiments.

They have also been used in co-crystallisation to elucidate the structure of relevant protein targets.

A second alternative use is in the field of diagnostic tests, where the affinity and specificity of the molecules makes them useful, much like their antibody rivals.

However, the company is currently focussing on therapeutic applications of the molecules with industry partners, with the diagnostic and biotechnology uses mainly attracting collaborations with academic groups.