I also think Roche / Genentech like to drag their feet and just take the cheap research, it's over 3.5 years now for little money and the final date stretches out to the 5 year mark. Same as the last deal they had cpp's and the blood brain barrier were hitting all the goals and looked the goods but then they just did it better themselves and passed it back at the 5 year mark.
Roche / Genentech have signed I think 3 maybe 4 deals targeting pseudomonas aeruginosa the last few years and they paid quickly big up fronts big milestones that monster the little one they signed PYC on - I don't think they'd be dragging feet if they were convinced. PA has always been the hot target though it was the focus of Mediimune / Astrazenca in the old $100M deal and likely what Cubist was eying first up when they opened the books.
From Feb 2012 Technical Presentation...
Cell-based screening using phage display
Phylogica has conducted a direct, cell-based screen to identify Phylomer® peptides which have activity against bacteria involved in multidrug resistant nosocomial infections.
To identify peptides which bind to bacteria, a phage display library of 51 million Phylomer® peptides was selected sequentially by biopanning on live Acinetobacter baumannii, a species of bacteria involved in nosocomial infections. A total of 101 Phylomer® peptides were obtained which bound to A. baumannii. These peptides were used to design a series of 280 overlapping synthetic peptides, which were then tested for antimicrobial activity (Figure 7).
Figure 7: Selection of Phylomer® peptides inhibit the growth of bacteria.
Several of these Phylomer® peptides (shown in blue) could inhibit the growth of bacteria as well as or better than known antimicrobial peptides (shown in brown) at an equivalent concentration or Ampicillin which was tested at two different concentrations.
Bactericidal activity was confirmed in live cell plating assays, in which 100% of bacteria were killed in the presence of Phylomer® peptides at nM to low μM concentration. The active Phylomer® peptides were divided into the rapid bactericidal, slow bactericidal and bacteriostatic/delayed bactericidal peptides. Rapid bactericidal activity occurred within 5 minutes of co-incubation and was observed for 3 out of 14 active Phylomer® peptides.
Assessment of mammalian toxicity by red blood cell haemolysis showed no measurable toxicity for 7 of the active Phylomer® peptides (a selection of peptides shown in Figure 8)
Blue text indicates potent activity on 50 different clinical isolates of A. baumannii, including multiresistant strains MHC10 = the minimum concentration required for >10% haemolysis
Minimal Inhibitory Concentrations (MIC) for complete inhibition of growth (μM)
Figure 8: Antimicrobial activity and toxicity profiles of Phylomer® peptides
The screen resulted in the isolation of 14 Phylomer® peptides with potent antimicrobial activity against the gram-negative bacterium A. baumannii. Further characterisation showed that biopanning the Phylomer® library had produced a diversity of antimicrobial peptide with varying degrees of cross-activity against the gram-positive bacterium S. aureus (Figure 8). Phylomer®s were identified from this screen, which were more potent than the well-characterised natural antimicrobial peptide tachyplesin, which has an MIC against A. Baumannii of 1.75μM. Pilot experiments with the most potent Phylomer® peptide Ac14s3 showed high antimicrobial activity at low nanomolar concentration against clinical multi-resistant bacterial isolates. An antimicrobial Phylomer® has also shown activity in vivo in an animal model of pneumonia.
And this passage taken from the 2012 Annual Report...
Medimmune
The collaboration with MedImmune, the worldwide biologics unit of AstraZeneca, was announced in August 2010. The overall aim was to use our Phylomer®#libraries to discover novel antibiotic agents to treat various bacterial infections.
The key target organism is multi-drug resistant Pseudomonas aeruginosa, which is a major cause of hospital-acquired infections and is also the main cause of lung problems in Cystic Fibrosis sufferers.
We were delighted to have screened our Phylomer®#libraries and to have identi!ed drug candidates with antimicrobial activity against the target organism Pseudomonas aeruginosa, as well as candidates that also have activity against other important pathogens such as Acinetobacter baumanii, Klebsiella and Staphylococcus aureus. Phylogica is working on the optimisation of these peptides.
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