Here’s What to Look out for in Regulus’ Upcoming Interim Release

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Just as has many of its biotech peers, Regulus Therapeutics Inc. (NASDAQ:RGLS) has had a tough start to the year. The company started 2016 with a market capitalization of a little over $420 million. At yesterday’s close, the market valued it at $323 million – a 30% decline across the period. In February, however, Regulus will report data from a phase II study of its lead candidate, RG-101, which the company is currently trialing in a hepatitis C indication.

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Promising results would likely inject some upside momentum into Regulus, and could quickly close the gap on it’s 2016-open cap. Ahead of the release, here’s a look at how the drug works and what we should be looking for in the data.

First, a quick primer on Hepatitis C. It’s caused by the HCV virus, and unlike it’s A and B counterparts, there is no available vaccine. The condition generally doesn’t show any symptoms for a number of years, while it quietly attacks the liver – it’s the number one cause of liver transplants in the US. There are a few available treatments, none of which are 100% effective. Lead symptoms include cirrhosis, liver failure and liver cancer.

RG-101 is what’s called GalNAc-conjugated anti-miR that targets miR-122. Sounds pretty complicated, but its just jargon. GalNAc-conjugation simply refers to the delivery method of the drug – in this case it’s a formulation intended for injection under the skin. miR refers to microRNA (not to be confused with mRNA). Think of it like this: mRNA is a long strand that expresses a particular pattern of genes. Normally, a ribosome will pass along the strand, producing and secreting proteins as it goes. microRNA acts a regulator of this process – it binds to a particular region of the mRNA strand (after first binding with a protein, but we don’t need to go into this bit) and blocks the ribosome from its continued path along the mRNA strand. This either stops it from producing any more of the protein that that particular strand codes for, or holds the ribosome in a position that means it continues producing a particular protein (which one depends on the position of the microRNA). mir-122 is a microRNA that stimulates HCV replication by binding to RNA expressed by the HCV virus. RG-101 attaches to mir-122, stopping it from attaching to HCV RNA, and in turn, (theoretically, at least) can be used to halt HCV replication.

If there are already treatments available, why is Regulus spending money developing this one? Well, the current SOC is a combination of an antiviral drug called Pegasys and ribavirin. This combination is generic and – in turn – cheap, but it is frequently innefective (for unknown reasons) and is notorious for its long list of adverse side effects. We won’t list them in this piece as it wont make for very entertaining reading, but those interested can see a full list here. If Regulus can bring a treatment to market that is effective and safe, it could quickly dominate the hepatitis C space, at least in developed nations that can afford the drug, and therein lies the company’s incentive.

Which brings us nicely to what we want to see from a data perspective. There will be two numbers that stand out in the data – the first, a mean viral load reduction (MVLR) figure and the second, a below the limit of quantification (BLOQ) number. Regulus hasn’t told us exactly how many patients it has enrolled on the trial, and with this being an interim analysis there is every chance that the total number will change between now and topline anyway, but with the MVLR figure we are looking for a reduction in at least 85-95% of patients. If the company produces this or higher, it should be considered positive. BLOQ we want as high as possible. In the phase I for this indication, 65% of (9 out of 14) patients had a viral load BLOQ, which essentially means the virus has gone (almost) completely. If we get a replication of this 65%, or higher, ideally, then again it should be looked at as positive.

As a side note, these numbers rely heavily on safety and tolerability data also being positive. Regulus is targeting a market dogged by adverse events, and so a safe candidate could be justification for an FDA green light even if efficacy is sub-par.

Data is due mid-Feb, so keep an eye on the company’s press release section here for the update. Beyond that, topline should come in about twelve weeks time.

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