Little Milo wrestles for gene therapy spotlight


You’ve probably never heard of Milo Biotechnology. 

Run by a virtual staff of one, financed by relatively small grants and based in Cleveland, far away from the biggest life sciences hubs, Milo has few of the calling cards that high-profile companies routinely play for attention. But over the past few years the virtual biotech--helmed by a "volunteer" CEO and guided by two noted clinical trial investigators--has run or launched three small human studies on an AAV gene therapy for follistatin demonstrating an important snapshot of efficacy in strengthening patients suffering from rare, debilitating diseases that spur progressive muscle loss. And they’re coming to a crossroads, looking to strike off into a pivotal study to prove that the tiny biotech can succeed in a field where one industry giant just failed. 

That won’t be easy, but interviews with the principals involved and an advanced look at their latest study results indicate that the privately held Milo may well be one biotech worth watching closely as it carefully picks its way through a clinical minefield of potential safety and efficacy hazards.

Their second study is being cited in a presentation by Jerry Mendell on Friday afternoon at the American Society of Gene and Cell Therapy annual meeting in Washington, DC. Mendell, last seen making an impassioned--ultimately unsuccessful--plea to win the support of an FDA panel for his small, 12-boy study for Sarepta’s ($SRPT) Duchenne muscular dystrophy drug eteplirsen, will note that 6 patients with sporadic inclusion body myositis (or sIBM) demonstrated an average improvement in a 6-minute walking test (6MWT) of 46.5 meters, while a control group of patients not treated declined, as expected, by 38.5 meters over a similar time period. A subgroup of untreated controls--matched by age and gender--experienced a similar decline.

This study follows a similar 6MWT of patients with Becker muscular dystrophy, a closely related disease to Duchenne. According to the study abstract last year, two patients improved their 6-minute distance by 58 meters and 125 meters, respectively. The third patient in that cohort showed no change. In a second cohort, patients 05 and 06 received 6 × 10(11) vg/kg/leg, improving their 6MWT by 108 meters and 29 meters. Patient 04 showed no improvement.

Not only has Milo’s treatment proven to be effective in hitting myostatin in small but telling human trials, says CEO Al Hawkins, but it’s also demonstrated downstream effects in damping down inflammation. Milo also started a 6-patient study for Duchenne a little more than a year ago, though there’s no readout available yet on that trial.

Milo was co-founded by a close colleague of Mendell’s, Brian Kaspar, an investigator who also co-founded AveXis ($AVXS), another gene therapy company. Hawkins, meanwhile, is an experienced venture investor who’s been contributing his time in managing a company with no staff and no private investors. 

Milo has had key support from some of the influential patient advocate groups in the field, most particularly the Duchenne Alliance. Kaspar is also an associate professor at Nationwide Children’s Hospital, an active player in gene therapy research which has been responsible for making Milo’s treatment.

Milo got started 5 years ago, working around a big idea outlined in a variety of academic research projects, which indicated that follistatin could be a very effective way to block myostatin. If you block myostatin, a protein that blocks the growth of muscle cells, you get muscle growth in mice. The same basic theory drove Novartis ($NVS) to back an ambitious program for bimagrumab, an antibody approach licensed from MorphoSys which failed a pivotal test for sIBM earlier this year. Bimagrumab won the FDA’s "breakthrough" drug designation. Its supporters had assigned a peak sales value to it of $4 billion a year. The same target also inspired the startup Scholar Rock, which has its own take on sIBM in preclinical work.

But Milo may be the only outfit with a gene therapy for follistatin 344 that’s delivered by an AAV vector into muscles--if you count out Elizabeth Parrish.

Parrish runs a startup called BioViva. And last fall she made a controversial claim to have treated herself with a gene therapy for follistatin to reverse muscle loss due to aging. Muscle wasting is a common characteristic of aging, but you’ll find that Milo and others in the field are closely concentrating on rare diseases to prove that they have a product that works safely and durably for specific diseases. And Parrish had trouble winning over support--or credibility--for her bizarre self-treatment experiment.

For Milo, the past 5 years have been a long, slow passage in search of credibility and support.

“We were criticized it wouldn’t be safe and well tolerated, back in the day,” Kaspar tells me. But now they have treated 19 patients in total with no adverse events to report as well as evidence of extended efficacy. Milo got started before gene therapy became a darling on Wall Street, and it plans to profit from the experience of other companies in rare diseases, like Sarepta, which was blistered in an FDA review for failing to run the larger, controlled studies that regulators repeatedly insisted would be needed for an approval.

“We’ve been afforded that time to run the studies without the pressure of investor expectations,” says Kaspar. “When we started, our thinking was that we could run this and be thoughtful of the clinical data, let it mature. That sets us apart from companies struggling to raise funds.” That should bode well now, he hopes, as the company scouts for some investment cash to run the kind of pivotal study in Becker’s that can win over regulators.

How much money? How many patients in the next trial? Those are all issues that have yet to be hammered out, says Hawkins. Kaspar allows, though, that given Sarepta’s experience at the FDA, you can almost assume that a good pivotal study design will require a control arm. 

The smaller you are, the less money you have, the more profitable it can be in learning from others. And Milo is out to leverage every advantage it can in preparation for the next big stage of development.