YEDA-XL-Protein GmbH Agreement

One of the potential uses of PAS-YNSα8 is for treating inflammatory diseases, in particular of the central nervous system. An example is multiple sclerosis (MS), a devastating chronic, progressive immune disease of the central nervous system that can eventually lead to paralysis. Among the drugs today used to treat MS are those based on interferon-beta (IFN-beta).
 

Weizmann Institute scientists developed a novel, highly active interferon variant, YNSα8. This modified IFN was engineered to bind much more tightly to the interferon receptors. The result is a very potent molecule, which shows a gene activation profile and biological activities that surpass any naturally existing interferon.

 

Together with scientists at XL-protein, the activity of PAS-YNSα8 was boosted by extending its half-life in the body using PASylation® technology. PASylation involves the genetic fusion of the therapeutic protein or peptide with a non-structured, expanded polypeptide made of the small amino acids Pro, Ala and Ser (PAS).
 

In a study that appeared in the Journal of Biological Chemistry and was led by Dr. Daniel Harari and Prof. Gideon Schreiber at the Weizmann Institute, it was found that the in vivo half-life of PAS-YNSα8 was increased10-fold in comparison to standard interferon. Most importantly, the PASylation did not interfere with the biological activity of this potent IFN; this has been a common technical problem for other methods of extending drug circulation. In a head-to-head comparison with conventional IFN-beta, this long-living superagonist conferred highly improved protection from disease progression in a mouse model of human multiple sclerosis, despite being injected four times less often than IFN-beta and at one-sixteenth of the dosage.
 

"We are excited by the pronounced therapeutic effect of our PASylated IFN superagonist, which was not accompanied by any observable immunogenic side effects in mice,” said Prof. Schreiber. “Our studies suggest that this potential drug could be safe and might provide clinical benefit surpassing that of IFN-beta, all this with a significantly reduced number of injections and lower dosage. We hope it will soon be possible to check the effectiveness of our molecule in clinical trials in humans.”
 

“The biological potency and bioavailability of this novel IFN-based molecule is remarkable. Improved receptor binding, achieved by advanced protein engineering, in synergy with the half-life extension provided by our PASylation technology, will result in more effective and less frequent dosing for the benefit of patients," said Prof. Arne Skerra, CSO of XL-protein and co-author of the study. "We are pleased to forge this business alliance with a renowned partner such as YEDA to commercialize this potent biological drug candidate," added Claus Schalper, CEO of XL-protein.