Overcoming Challenges In The Development Of Peptides And Oligonucleotide Therapeutics

By Ed Miseta, Chief Editor, Clinical Leader

Dr. Hanjo Hennemann, co-founder and chief science officer, Nexigen GmbH

At the 2013 Oligonucleotide & Peptide Based Therapeutics Congress, Dr. Hanjo Hennemann, co-founder and chief science officer of Nexigen GmbH, will speak on Overcoming Delivery Challenges in Peptide and Oligonucleotide Therapeutics. Dr. Hennemann is a founding member of Nexigen and has served as managing director and head of research since the company’s founding. Previously he was principal investigator at the research center caesar, Bonn, where he established the basis for the technology and the foundation of Nexigen. We spoke with him about the potential for peptides in the treatment of cancer and other diseases.

Ed Miseta: Why are we seeing an increase in the attention being paid to peptides?

Hanjo Hennemann: The Big Pharma and biotech companies, for the last decades, have been working mainly on small molecule drugs. The reason is there are hundreds of sensitive proteins which you can attack with these drugs. However, this is only about ten percent of the available disease modifying target proteins. About ninety percent of all the proteins which are relevant and which are highly interesting for the drug development community cannot be accessed by small molecule drugs. This led to more attention being paid to therapeutic antibodies, which now comprise the top ten blockbuster drugs in oncology.

Unfortunately if you look at which proteins are accessible by this type of drug class, you end up at only around seven to eight percent of all disease-relevant proteins. If you add small molecule drugs and therapeutic antibodies together, you have access to less than twenty percent of the disease-relevant target proteins.

The question is, what do we do with the remaining eighty percent of the target proteins? I believe this is the reason why another class of drugs, siRNAs or Antisense, have gained so much attention over the last years. The promise was that this would allow us to reach virtually any protein relevant for disease. Up until now, that promise has been difficult to fulfill.

The fact that there have been billions of dollars spent to overcome technical hurdles in the field indicates that there is a tremendous need in accessing the remaining eighty percent of disease-relevant proteins, which cannot be readily attacked by common drug classes.

Miseta: Is this what helped open the door for cell-permeable peptides?

Hennemann: I believe so. What these difficult-to-access proteins have in common is they are mainly intracellular and they do not have any enzymatic activity. Small molecules recognize enzymes quite easily, and therapeutic antibodies only recognize proteins on the surface, which is outside of the cell. Peptides generally have quite good abilities to bind specifically to a variety of proteins including non-enzymatic proteins, but they need to get inside of cells, which they usually don’t do.

Cell permeable peptides solve this issue of getting the drug in, which makes this a promising drug class. There has been success with this drug class, and with an investment of millions rather than billions. There is hope that in using cell-permeable peptides, the success rate may be higher and the overall cost in order to get it to work may be less. That is creating a lot of interest because in drug development the main problem is getting the drug to work as fast as possible, with the lowest attrition rate and at adequate costs.

Another advantage of peptide drugs is they have a very specific binding, so they don't bind everywhere. Because of this specific binding, side effects which arise from binding to other proteins may be reduced. And remember too that peptides have been in successful development for decades. One very well-known peptide is insulin, and there are many successful peptide drugs in the diabetes field.

Miseta: Are there other companies having success with peptides?

Hennemann:  There are companies working on different strategies to make peptides cell-permeable. One company in the Boston area, Aileron Therapeutics, is doing quite well with their permeable peptides. Xigen, a Swiss company, is also doing good work with peptides. And there are other companies that do not specialize in cell-permeable peptides but which do have these products in their portfolios.

Miseta: All working with peptides but taking different approaches?

Hennemann: Exactly. Different platforms and different indications, but they're all synthesizable. You can manufacture them completely chemically, which is a real advantage. They all appear to be able to modulate intractable target proteins.

Miseta: Can you discuss any signs of success at this time?

Hennemann: Yes. There are several stages in the development of these drugs. First you develop a platform, which enables you to identify such drugs. Then you use the platform to identify the first generation of these drugs. Our drug was successful in a cell culture model, and was advanced to animal testing. It was able to significantly inhibit the growth of tumors in animal models, which was an important milestone in our development of cell-permeable peptide therapeutics.

Miseta: Looking forward, where do we go from here?

Hennemann: The next step will be to move into the pre-clinical testing phase, which is needed to register for clinical testing.

Our approach is also generally applicable. This is not an island approach, which only works with a very specific protein class, or with a very specific disease mechanism, or with a specific indication. It can probably work on cancer or other disease indications where such peptides can be applied. I think that this is quite a valuable extension of the arsenal of available drug classes.

Cell-permeable peptides will be very valuable NBEs for other companies as well, especially drug developers trying to access hidden treasures which are not yet accessible with common drugs.

For more information on the Oligonucleotide & Peptide Based Therapeutics Congress: http://www.globalengage.co.uk/oligos-peptides.html