As you will probably know already, Regulus Therapeutics surprised us this
week with the sudden departures of both their CEO and CSO. These two individuals also happened to be the
insiders selling major positions in the stock earlier this year just days ahead
of critical data to be released on their lead clinical candidate, RG-101 for
the treatment of HCV ('Reading the tea leaves on Regulus insider sales').
While this would be a good reason for what looks like a sacking of the company’s two key executives (especially since
the exodus came as a pair), for investors the all-important question is whether
it is also related to bad news that we do not know about yet. Most importantly, does this also have anything to do
with the failure to report the viral resistance analysis which had been promised
to us for the EASL meeting in April?
It is this analysis that will determine whether the miR-122
inhibitor can facilitate 4-week treatment regimens which must be the goal for
this asset. This is because RG-101 is
the only serious long-acting agent out there in the HCV drug development arena
and 4 weeks of oral, short-acting antivirals do not seem capable of getting rid
of the virus.
If there was no resistance to RG-101, based on the available
data RG-101 given on week 4 would add ~6 weeks to deep viral suppression to
the treatment regimen, in a way resembling a 10-week oral regimen which have much higher
odds of viral clearance.
If viral resistance (and not waning drug levels as I am assuming) played a role in the rebounds
seen in the single-dose study, then this would not necessarily be the
case. I say ‘not necessarily’ because
even then, the risk of developing viral resistance to RG-101 should be much lower when given in
combination with other agents as is the plan.
Take-home: I remain cautious (but not short any more)
prepared to take advantage of another bout of panic selling that could come
with the release of the resistance analysis.
The quality of the new leadership to lead the exciting microRNA platform
will also indicate whether Regulus can finally live up to its original promise.
Long-term, whether precipitated by the insider sales or not, the changes should be good as morale at the company from what I can tell had been low.
PS: in more positive news, Regulus Therapeutics today reported
that a first-in-man study with their second most advanced microRNA Therapeutic,
RG-012 for the kidney-related orphan disease Alport Syndrome, has begun dosing.
