Armagen BearDownAZ, as you may recall, Armagen's BBB drug transport platform targets the insulin receptor as the dominant receptor for the transport of drugs across the BBB. Interestingly, Armagen's technology also targets the LRP-1 and transferrin receptors but, clearly, at lower performance levels.
Armagen uses a portion of a monoclonal antibody (MAb) fused with a therapeutic such as an LSD enzyme. They refer to the monoclonal antibody as HIRMAb, standing for human insulin receptor monoclonal antibody. Using HIRMAb, Armagen claims they can build fusion proteins with enzymes, monoclonal antibodies, siRNA and other therapeutics. I have not found a more detailed description of the MAb that they fuse with the therapeutics.
It appears that the fragment of MAb that they use in their platform is very large. The molecular weight of the fusion protein that they tested in a MPS IIIb study was 320 kDa. The enzyme was N-sulfoglucosamine sulfohydrolase, (SGSH) or sulfamidase, that has a molecular weight of about 60 kDa. That suggests a very heavy transport vehicle with far greater complexity compared to xB3, which if I recall comes in at less that 2 kDa. In fairness, I have never done further research to determine how small a fragment of their HIRMAb that Armagen has developed. I cannot see any reference in Armagen's literature to a peptide or a peptide-sized structure similar to what Bioasis can boast. To me, this means that Armagen may have more difficulty manufacturing fusion proteins of sufficient clinical quality and at the low costs such as Bioasis anticipates with xB3.
With respect to the delivery of efficacious doses, Armagen claims delivery of about 1% of the dose in an MPS IIIb study. I suspect it is similar for their other fusion proteins. There may be other data existent but my recollection is that Bioasis has shown various delivery capabilities ranging from 4% of dose to 6% and more. Clearly, Bioasis can delivery several times as much to the brain as Armagen can.
Over the years, Bioasis published a corporate presentation on its website. I think the last version was in late 2015. In it was a table of molecules and their relative uptake to brain. This table could be misleading because the the numbers are not drug delivery quatities but the brain uptake of the underlying molecules used as drug vectors. Some molecules such as glucose and morphine were presented for reference. The units of uptake were described as "Kin (x10-6 mL-1/s-1/g-1)." Since all the numbers in this list use the same units, we just need the numbers for comparison.
Glucose: 9500 Kin (x10-6 mL-1/s-1/g-1)
Melanotransferrin (p97): 640 (xB3 should be of a similar or larger number.)
Morphine: 200
Aprotinin: 160 ( Angiochem's Angiopep-2)
Insulin Receptor: 100 (Armagen's HIRMAb)
Implicit in these numbers is the capability of p97 (xB3) to deliver 6 times or more of a drug dose across the BBB as Armagen's HIRMAb can deliver (640 to 100), and as suggested above, with lighter, more easily and cheaply manufactured fusion proteins.
We also know that xB3 has exceptional pharmacokinetic (PK) and other attributes such as quick delivery, long half-life, no apparent negative effects on the payload, and such. I haven't tried to determine how Armagen performs in these areas, but given xB3's exceptional performance, Armagen is in a tough race to beat us. The large size of the transport vehicle may also cause earlier breakdown than xB3 but that is only speculation on my part.
As with Angiochem, I long ago stopped viewing Armagen as a serious competitor to Bioasis. That said, Armagen signed a deal in 2014 with Shire for $11 million up front and a potential $225 million overall. Armagen recently completed a Phase II with its MPS I program and is looking at a Phase III trial. If they are successful, they will beat us to market with a drug delivered by receptor mediated transcytosis. In the end, however, xB3 may be able to achieve more flexible doing with better pharmacokinetics so I have no worries about Armagen beating us on that front.
But as I recently noted, our competitors are staying away from the big diseases and their potentially huge commercial values. Denali and Armagen are starting out with LSDs. Angiochem started out with brain tumours, but by transporting paclitaxel, not Herceptin, Avastin or Rituxan, the big-revenue MAbs in the cancer business.
I don't think our "competitors" can deliver to the brain the quantities of drugs with such favourable PK and manufacturing (cost) characteristics as Bioasis may be able to do. Ultimately, if xB3 continues to succeed, I don't think these other companies will be able to compete with us.
jdstox
ps: You can find some of the Armagen numbers and information that I referenced in an MPS IIIb study
found here.
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