Myokardia Inc (NASDAQ:MYOK) just announced topline from its lead cardiovascular trial, and alongside the data, reported it intends to carry the drug under investigation into a phase II before the year draws to a close. The FDA granted the drug orphan designation back in May, and as it moves through the development process, it looks set to be the primary driver behind Myokardia’s open market valuation. With this in mind, and ahead of the phase II initiation, let’s take a look at the drug in question in an attempt to figure out what to watch going forward.

So, the drug. It’s called MYK-461, and it has a target indication of a condition called symptomatic obstructive hypertrophic cardiomyopathy (oHCM). oHCM is a sub type of a wider, and extremely prevalent, condition called hypertrophic cardiomyopathy (HCM). In the heart, a balance between two types of filament, myosin and actin (one thick, one thin respectively) dictates the ability of the muscle to contract. In patients with HCM, there is a relative imbalance, and the walls of the left ventricle (primarily) thicken. This on its own has some relatively mild symptoms (and some more severe, in some instances), and affects somewhere in the region of one in every five hundred individuals in the US. It can develop into oHCM, however, and this variation is far more serious. oHCM happens when the thickening results in what is essentially a blockage in the left ventricle – it obstructs (as the name suggests) the ability of the heart to pump blood out of the ventricle, and this can have some serious issues, including a vastly increased risk of death by cardiac arrest or stroke. There are no currently approved drugs available to treat oHCM, and more often that not surgery is required to alleviate the obstruction. The surgery (generally what’s called a septal myectomy) isn’t particularly risky – it’s been a standard procedure for nearly 25 years – but it’s invasive, and requires a general anesthetic; something that a physician will always seek to avoid if possible. In short, it’s an unmet need, and the FDA has quantified this unmet need with the orphan designation.

So what does MYK-461 do? It allosterically modulates the above mentioned cardiac myosin. This means (simplified) it changes the shape of the myosin to alter its functionality. The main aim of the modulation is to reduce left ventricular contractility, and in doing so, alleviate the obstructive nature of the HCM. This reduction in left ventricular contractility will likely be the primary endpoint in the upcoming phase II (although we’ve not yet got confirmation on this, but it’s a logical assumption) and was one of the secondary points in the just reported phase I data. While there wasn’t too much insight on offer from the very small sample of HCM patients that had an LVOT obstruction in this just completed trial (only two patients total), the drug showed some degree of efficacy, and this should lead nicely into the upcoming phase II. The thing to understand going into the next trial, and as data starts to hit press, is that the drug only has to have a marginal impact on contractility to have a large impact on the severity of the condition itself. Researchers at Myokardia suggest that even if the impact is as small as a 5% decrease in contractility, it would justify the drug becoming available as a first line treatment in this indication. That is, assuming safety and tolerability hold firm across the development process.

So, going forward, what are we watching out for? Well, efficacy is the next big thing. Preclinical and small sample phase I data has hinted at a positive result, but we won’t really know whether the drug stands a chance until the company puts it through its paces in the upcoming phase II. As we’ve said, this is set to initiate before the close of the year, and interim/topline post initiation is going to be the next major upside catalyst.

Before then, the company is set to hold what it calls an R&D day, and we should find out a little more about the data just reported, and the structure of the next trial. That’s scheduled for the fall. The takeaway? A slow burner, but worth watching.