Well, it's been a while since I've written about Covagen, and I see they have two conjugations of antibodies with Fynomers (FynomAbs) in clinical trials already, and it looks like this is with their partner Mitsubishi Tanabe Pharma Corp.
The conjugation makes sense, the molecular weight of the Fynomers would probably mean they don't around long enough in the body to be clinical useful, but an antibody conjugate can take advantage of the bodies antibody recycling systems and thus stick around longer. This is probably also an approach that will be strongly considered by the other alternative scaffold company Molecular Partners (and yes indeed, here are their notes only they are selling DARPins as a tag to increase the half-life of other molecules by targeting the DARPin to serum proteins or as fusion proteins).
I wonder if Fynomers will show up as a drug on its own, without the antibody conjugation. That is the promise after all of alternative scaffolds, antibody-like specificity but cheaper and easier to make. Right now the most successful approach appears to be making bispecific antibodies.
Showing posts with label alternative scaffold. Show all posts
Showing posts with label alternative scaffold. Show all posts
Sunday, May 11, 2014
Tuesday, September 25, 2012
Polyphor
Founded in 1996, Polyphor is a company in Basel developing drugs only slightly larger than small molecule drugs and their focus is on the disruption of protein-protein interactions. These kinds of interactions are more difficult to disrupt because of the shape of the interaction. Usually, to disrupt an enzyme, you need a small molecule that can slip into the active site. However, protein-protein interactions are typically bigger and may require a larger drug to disrupt. Protein therapeutics such as DARPins and antibodies are good at targeting protein-protein interactions, but their larger size has a cost. It may be difficult to design a drug that can enter cells, cross the blood-brain barrier, or can be taken orally.
Polyphor participates in partnerships with companies to develop their small therapeutics against the clients chosen targets. The most recent annoucement has been a partnership with Boehringer Ingelheim (who recently shut down virology research in Montreal Canada).
Polyphor also develops their own compounds against drug targets and have several in clinical trials, with the most advanced in phase II. They are also clearly moving forward with clinical trails since they have a job posting for a clinical development project manager.
Polyphor has two technologies, MacroFinder and PEMfinder. MacroFinder is a synthetic system to develop libraries of rings, sounds like combinatorial chemistry to me. PEMfiner is based on PEMs, developed by Prof. J. A. Robinson at the University of Zurich (yes, Zurich has not only federal ETH but also their own university). PEMs are cyclic peptides with specific short structural motifs (such as a hairpin turn), and it appears that Prof. Robinson has developed the Pseudomonas aeruginosa inhibitor that is currently in clinical trials at Polyphor. The peptide portion of PEMs can first be developed using phage display, and then the peptide sequence transfered to their synthesis platform. I guess at that point the PEMs are cyclized (and are not cyclized during phage display).
Polyphor participates in partnerships with companies to develop their small therapeutics against the clients chosen targets. The most recent annoucement has been a partnership with Boehringer Ingelheim (who recently shut down virology research in Montreal Canada).
Polyphor also develops their own compounds against drug targets and have several in clinical trials, with the most advanced in phase II. They are also clearly moving forward with clinical trails since they have a job posting for a clinical development project manager.
Polyphor has two technologies, MacroFinder and PEMfinder. MacroFinder is a synthetic system to develop libraries of rings, sounds like combinatorial chemistry to me. PEMfiner is based on PEMs, developed by Prof. J. A. Robinson at the University of Zurich (yes, Zurich has not only federal ETH but also their own university). PEMs are cyclic peptides with specific short structural motifs (such as a hairpin turn), and it appears that Prof. Robinson has developed the Pseudomonas aeruginosa inhibitor that is currently in clinical trials at Polyphor. The peptide portion of PEMs can first be developed using phage display, and then the peptide sequence transfered to their synthesis platform. I guess at that point the PEMs are cyclized (and are not cyclized during phage display).
Tuesday, September 4, 2012
Molecular Partners
Molecular Partners is in the news recently for striking a 62 million dollar deal with Allergan so I decided to do some research about this company.
Molecular Partners is another alternative scaffold biotechnology company and their fold of choice are the ankyrin repeat proteins based on work done by Andreas Plückthun at ETH in Zurich. These designed ankyrin repeat proteins (DARPins) are small, well produced in E. coli and can be engineered to reach high affinities. Molecular Partners has freedom to operate and a business model that is a combination of internal drug developments and partnerships with pharmaceutical companies. On their webpage, Molecular Partners claims their patents cover DARPins and other repeat proteins, without going in to the patents (yet) I speculate this includes modular leucine-rich repeat proteins which has also been investigated by Andreas Plückthun. What I like about the DARPin is the modular structure, and how you can increase potential binding area with the addition of more ankyrin repeat motifs, but at the cost of increased size.
As with Covagen Fynomers, DARPins can be strung together to create molecules with multiple specificities. The recent deal with Allergan includes MP0260, a DARPin with two specificities, although the structure of the compound is not divulged. Bi-specific binders seems to be the buzz word as of late, and a place where alternative scaffold proteins have an opportunity to shine, given the challenges of developing bi-specific antibodies, not impossible, just more challenging than genetically encoding the different blocks together. Currently Zymeworks is a company working on building bispecific antibodies.
The collaboration with Allergan has also lead to Molecular Partners' most advanced lead, in phase I/IIa clinical trials. This is one of the more advanced of the alternative scaffold proteins currently in clinical trials. I'll write more about that later one day.
More information about Molecular Partners and Allergan can be found in this EvaluatePharma article.
Molecular Partners is another alternative scaffold biotechnology company and their fold of choice are the ankyrin repeat proteins based on work done by Andreas Plückthun at ETH in Zurich. These designed ankyrin repeat proteins (DARPins) are small, well produced in E. coli and can be engineered to reach high affinities. Molecular Partners has freedom to operate and a business model that is a combination of internal drug developments and partnerships with pharmaceutical companies. On their webpage, Molecular Partners claims their patents cover DARPins and other repeat proteins, without going in to the patents (yet) I speculate this includes modular leucine-rich repeat proteins which has also been investigated by Andreas Plückthun. What I like about the DARPin is the modular structure, and how you can increase potential binding area with the addition of more ankyrin repeat motifs, but at the cost of increased size.
As with Covagen Fynomers, DARPins can be strung together to create molecules with multiple specificities. The recent deal with Allergan includes MP0260, a DARPin with two specificities, although the structure of the compound is not divulged. Bi-specific binders seems to be the buzz word as of late, and a place where alternative scaffold proteins have an opportunity to shine, given the challenges of developing bi-specific antibodies, not impossible, just more challenging than genetically encoding the different blocks together. Currently Zymeworks is a company working on building bispecific antibodies.
The collaboration with Allergan has also lead to Molecular Partners' most advanced lead, in phase I/IIa clinical trials. This is one of the more advanced of the alternative scaffold proteins currently in clinical trials. I'll write more about that later one day.
More information about Molecular Partners and Allergan can be found in this EvaluatePharma article.
Tuesday, August 21, 2012
Covagen
Covagen is a small, private company, located in Schlieren, close to Zurich in the Bio-Technopark and was founded in 2007 by Dr. Dragan Grabulovski and Dr. Julian Bertschinger.
Covagen is using the ‘alternative scaffold’ based on the human Fyn SH3 domain which they call Fynomers. Fynomers are part of the next step in drug development, an attempt to shrink the size of antibodies while at the same time maintaining high specificity and affinity. Development of this alternative scaffold started in the Prof. Dr. Dario Neri group at ETH. ETH is one of two Swiss federal technical Universities and also home of another alternative scaffold, the DARPins from Prof. Dr. Andreas Plückthun which have been spun off to Molecular Partners, also in the same Bio-Technopark.
Anyway, back to Covagen and Fynomers. With such a small domain, it is easy to string several together and development multi-specific binders, which is exactly what they have done with their bispecific TNF/IL-17A inhibitor. In December of 2011 they moved forward into preclinical development with this compound.
Three dimensional SH3 structure. Image generated from 4AFQ in the pdb database using PyMol.
Covagen is using the ‘alternative scaffold’ based on the human Fyn SH3 domain which they call Fynomers. Fynomers are part of the next step in drug development, an attempt to shrink the size of antibodies while at the same time maintaining high specificity and affinity. Development of this alternative scaffold started in the Prof. Dr. Dario Neri group at ETH. ETH is one of two Swiss federal technical Universities and also home of another alternative scaffold, the DARPins from Prof. Dr. Andreas Plückthun which have been spun off to Molecular Partners, also in the same Bio-Technopark.
Anyway, back to Covagen and Fynomers. With such a small domain, it is easy to string several together and development multi-specific binders, which is exactly what they have done with their bispecific TNF/IL-17A inhibitor. In December of 2011 they moved forward into preclinical development with this compound.
Three dimensional SH3 structure. Image generated from 4AFQ in the pdb database using PyMol.
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