If you did not appreciate the
value the pharmaceutical industry has come to place on the HBsAg knockdown
concept for achieving a functional cure for chronic Hepatitis B (HBV) infection,
the last two days will have woken you up.
Yesterday, ISIS Pharmaceuticals reported that it had received a $7M milestone payment related to the development of an antiviral RNaseH
development candidate (ISIS-GSK3Rx, aka ISIS-HBVRx) which, although undisclosed for competitive reasons, hasgot to be for HBV. And today, Tekmira publicly announced that
they will file an IND for an HBV-RNAi candidate in 2014 while hinting at the
partnering potential of such a treatment candidate.
Arrowhead Research is thus not
alone in their efforts any more.
Coincidentally, Arrowhead reported today the completion of their
enrollment of the phase I single-dose, healthy volunteer study with ARC520,
their DPC-delivered candidate for chronic HBV.
Accordingly, the dose escalation was able to run through all the
pre-planned 6 dose cohorts up to the top dose of 2.0mg/kg.
Apparently, there were no signs
of significant dose-related toxicities. The
only finding of concern among the 36 volunteers, 24 of which received drug, was 2 cases of lightheadedness
of uncertain clinical relevance. As
these occurred at the highest dose, it seems that the company suspects that it could have
been drug-related although the study remains blinded for follow-up.
A dose of 2mg/kg without any
serious adverse events or dose-limiting toxicities is a great start for DPC
delivery technology. This is especially
the case when one considers that the single-molecule subQ version of DPC that I
hope will form the basis for the upcoming pipeline candidates, except for the
next one perhaps, will be much more potent than the two-molecule version
of intravenously delivered ARC520 based on the non-human primate data presented at last year's OTS meeting.
With 2mg/kg of ARC520, I further believe that HBsAg knockdowns of over 90% are likely. The biggest challenge going forward with this
program will be setting a knockdown goal and getting the dose and dose frequency right.
For more about increasingly lively HBsAg knockdown
for the treatment of chronic HBV, please follow my HBV Knockdown Blog.
Also today: Tekmira and
Arrowhead Research Rapidly Filling Pipeline
In addition to chronic HBV,
Tekmira further disclosed development plans for candidates addressing Marburg
infection, alcoholism, hypertriglyceridemia and severe orphan glycogen
disorders. The presentation made clear
that the company has not sat on its hands since the settlement with Alnylam and
is close to having at least 4 drug candidates in active clinical development by early
2015 (TKM-PLK1, TKM-EBOLA, TKM-ALDH2, TKM-HBV).
Meanwhile, previously $200M
market cap Arrowhead Research has succeeded with a $60M private placement
without having had to offer a discount.
In my opinion, this reflects the broadened investor interest in the space and makes Arrowhead an even better investment as it can
now, freed from financial constraints, immediately pursue some of the
attractive liver targets with best-in-class solutions and beyond.
Wondering whether we are in an
RNA Therapeutics bubble? Then I suggest
you get my OTS 2013 meeting report.
Dare I say that oligonucleotide therapeutics is a more capable and
exciting technology than monoclonal antibodies already? At least if you believe orphan diseases are
the way to go in today's pharmaceutical drug development, there is no doubt about it coming
out of the meeting.
2 comments:
No discount? Well, if you 'discount' the selldown the day before the pricing, I guess not. Surely no one would short a stock to get themselves a better deal in a financing. Not in this day and age.
Their P1 trial for safety study was not very convincing. It was based on a single dose which is not reliable. We will not know about its safety profile until they start P2a multiple dose study.
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