Regulus Therapeutics Declares MicroRNA Therapeutics Bankrupt

Once considered a new star on the biotech firmament, the most prominent microRNA Therapeutics company is going from bad to worse fast.  

Last week, Regulus Therapeutics announced that both of its clinical programs in Alport’s Syndrome and autosomal dominant polycystic kidney disease (AKPKD) had been voluntarily halted for financial and preclinical reasons. Instead, the company will now try to renegotiate the Alport deal with Sanofi and use its remaining resources to focus on a preclinical program for HBV.

Management not in control

The program pauses follow a string of other setbacks over the last 3 or so years. Most prominently, it discontinued a highly promising candidate for the treatment of HCV due to safety questions and having been a few years too late to a highly competitive game.  A slow early advancement of that miR-122 program was partly to blame for this.

After that, it has been one delay after another for various programs.  Partner AstraZeneca e.g. returned a liver-targeted metabolic program and the Alport's program has been hit by multiple delays and trial reconfigurations.

If this was not sufficient proof that managing a biotech company has been well above the paygrades of the multiple executive teams that have come and gone over the years, running out of cash in this genetically-focused biotech bull environment is simply unacceptable.  Even if microRNAs may have lost its early luster as targets for particularly complex diseases, I had thought that having exclusive access to the huge IP portfolios of parent companies Ionis and Alnylam for microRNA Therapeutics purposes would provide a powerful backstop when it came to accessing fresh capital.

With a market cap of less than $40M and last week’s ‘we’ve-run-out-of-cash news’ I was obviously wrong…

Chasing a 'safe' target

Since microRNAs which typically have a range of biologically meaningful targets are thus promising for treating particularly diseases of complex causes and manifestations, I would have thought that with the genetics gold-rush that we are now witnessing in neurology, not least because of antisense drug SPINRAZA, there would be much interest in Regulus Therapeutics there.

I understand that HBV is becoming a hot area again, with the skyrocketing valuations of Arrowhead, Dicerna, and Arbutus suggesting that high rates of functional cures are just around the corner.  Going after HBV with a microRNA, however, would seem like a surprising choice though given that in terms of direct antiviral activity, a microRNA approach should pale in comparison to the RNAi competition.  You would therefore think that Regulus is considering a immune reactivation-related microRNA target for HBV, but it is not clear to me which model they would be basing this on.  

Hey, management, at least show us some data to hang our hats on when you sell a preclinical concept as your future.

Or does choosing HBV betray that they have lost all confidence in their ability to deal with the biological complexity of microRNAs, instead seeking safety in just measuring simple viral knockdowns?

After the quasi-demise of microRNA diagnostics leader Rosetta Genomics, there is now the real prospect that the therapeutics counterpart will equally go belly-up soon.  In order to avoid that, Regulus needs new, confident management first and foremost as the main task now is to make the case for microRNAs as therapeutic targets.  Where are all the boastful biotech executives when you need them?