Reverse-engineering cardiovascular R&D
CEO: Tassos Gianakakos
Based: South San Francisco
Clinical focus: Heart failure
The scoop: There's a well-worn path for companies developing drugs for cardiovascular disease: find a promising molecule, get it through proof-of-concept and then write a check for a huge Phase III program and hope for the best. If all goes well, you might have a blockbuster on your hands; if not, you just wasted billions of dollars on some interesting subpopulation analysis. That cumbersome model is often prohibitive for venture-backed biotechs, for whom costly outcomes trials are simply impossible. One such company is taking an entirely different approach, attacking the scourge of heart failure by targeting one orphan-like population at a time, using the rare disease model to build the case for its pipeline.
What makes MyoKardia Fierce: Another product of the Third Rock Ventures startup factory, MyoKardia is taking a precision medicine approach to cardiology. The company's big target is heritable cardiomyopathy, a rare and lethal genetic disorder in which patients have a defect in the proteins that help control cardiac contraction, making heart muscles either too big or too small. In keeping with Third Rock's guiding ethos, MyoKardia got started not with a single promising drug candidate but with a deep dive into disease biology, CEO Tassos Gianakakos said, taking time to build its own registry of cardiomyopathy genetic data and figure out the biological mechanisms behind the disease.
From that came MYK-461, a Phase I treatment for hypertrophic cardiomyopathy, or HCM, which results in oversized cardiac walls that put a serious strain on cardiac function. The disease affects about one in every 500 people, Gianakakos said, and MyoKardia believes it will need only a few hundred patients to eventually demonstrate MYK-461's promise in a pivotal trial. Behind the lead candidate is a preclinical drug for dilated cardiomyopathy, or DCM, in which the heart walls become dangerously thin and put patients at risk of sudden cardiac death. That program is on track to enter the clinic in 2017, Gianakakos said, ahead of a third project that targets a subgroup of HCM patients.
While going the rare-disease route decreases some of the risks of drug development, cardiovascular R&D is still a major undertaking, and MyoKardia knew from the outset it would need some external expertise. The company brought in Sanofi ($SNY) in 2014 in a deal that paid out $45 million up front and promised up to $200 million more, giving the French drugmaker ex-U.S. rights to the three aforementioned programs. In exchange, MyoKardia gets financial support that will keep things moving through 2018, and the biotech has retained control of development through Phase I.
Having Sanofi around will come in handy if MyoKardia's approach can be applied to the much larger indication of heart failure. Such an undertaking would considerably change the risk dynamic, Gianakakos said, but if MyoKardia can consistently demonstrate proof of concept in rare cardiomyopathies, one of those big, old-fashioned Phase III programs could become the next natural step. And for that, you need Big Pharma.
In the meantime, MyoKardia is pressing ahead with its pipeline, partnered and otherwise. This week, the company filed to go public with an $86 million placeholder IPO value. The plan, MyoKardia said, is to extend its runway and keep digging into the genetic drivers of cardiovascular disease. Gianakakos, interviewed before the filing, said his company is first and foremost a platform biotech, focused more on its underlying science than any single project.
"We have an integrated research capability that efficiently generates targeted molecules, and each one has backup compounds," he said. "We're doing it the old-fashioned way, not taking any shortcuts. Eventually one of our molecules will make a big difference for patients."
Investors: Third Rock Ventures, Sanofi, Casdin Capital, Cormorant Asset Management, Perceptive Life Sciences and BridgeBio
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-- Damian Garde (email | Twitter)