Honorable Mention: AveXis

Fierce 15

Looking to create a gene therapy approach to a devastating disease that is the number one genetic killer of infants in the world

CEO: Sean Nolan
Based: Bannockburn, IL
Founded: 2010
Clinical focus: A gene therapy candidate for the treatment of spinal muscular atrophy (SMA) Type 1

The scoop: AveXis’ focus is on spinal muscular atrophy, or SMA, which can affect up to 10,000 children around the world. The disease has four types, but AveXis is focusing on Type 1, the most severe: Around 90% of children born with this type never see their second birthday, and in their short lives will never sit, crawl or walk. Right out of the gate, these children have a poor quality of life, and the disease takes hold rapidly, with most ending up on a ventilator before dying.

What makes AveXis Fierce: As with many of this year’s Fierce 15 companies, AveXis is going after this devastating disease--which has no treatments, with palliative care the only means of looking after these kids--with gene therapy. SMA Type 1 occurs when a protein, known as SMN, is not produced sufficiently, because they are missing the SMN1 gene. Without this gene, you don’t have the protein and without this protein, the motor neurons die as do other key tissues, such as muscle.

Sean Nolan, CEO of AveXis, says that gene therapy is in his eyes the best approach to defeating this disease. “It all goes back to the biology of this condition,” he explains. “SMN1 is a gene we all have, but with SMA Type 1, you essentially don’t have it, or it is defective. So what we do is I think quite elegant. We’re able to place a fully functioning, human SMN gene into the nucleus of target cells and that becomes the primary producer of the SMN protein. So we are addressing the root cause of biology of the disease with gene therapy. This is a very different approach to others that are in the clinic.”

The treatment is currently in Phase I with 15 patients, with all 15 having been dosed with AVXS-101. In its most recent data update over the summer, AveXis reported that they have had no deaths, with Nolan saying that the motor function is “very, very strong; … all of our kids have had increases in motor function where you would expect significant decreases. We’ve got kids with threshold scores above anything ever seen before. And on top of this, a quarter of our kids in the therapeutic dose cohort are into the normal range as measured by the standard scale to assess motor function.”

When the company also looked at other key areas such as pulmonary function and nutrition, Nolan says here too they are seeing strong results. “That’s why we’re so encouraged by what we’ve seen even at this early stage thus far,” he said. “And the field is clearly encouraged as well, and the data is bringing in investors like Roche’s venture arm, T. Rowe Price and Deerfield. These data speak for themselves, they’re dramatic, and we’re seeing the benefit of that.”

AveXis also believes that its approach is industry-leading. James Goff, VP of investor relations and communications at the biotech, said: “The way that the construct of the vector itself is I think truly innovative. We’ve built features into the construct of the vector that are designed to do a number of things. Notable among them is the durability of the effect from this therapy, and second is the rapid onset of the effect. So we’ve got a rapid solution to a rapidly deteriorating disease, which is essential. And the other really innovative element, which was a discovery made in the lab of Dr. Brian Kaspar [the biotech’s CSO], where he found that this vector, AAV9, has the ability to cross the blood-brain barrier. That is the real breakthrough as that’s what showed that we could effectively target the CNS and the key motor neuron cells where we needed to target the therapy.”

AveXis' approach, armed with technology licensed from ReGenX, works as a one-time treatment. There is a one-hour infusion and that’s it--and it can also be done locally to patients. This is a step up from the recently approved gene therapy from GSK known as Strimvelis (that works very differently to AveXis’ treatment), for the rare childhood condition ADA-SCID (a.k.a bubble boy syndrome), which can take up to three months for treatment and currently can only be given to patients in Milan, Italy, where it is manufactured.

AveXis is taking several different approaches to the manufacturing side, using both CMOs and developing in-house new methods to create this treatment from its new facility in Chicago. “GSK has lots of elements to its gene therapy, but ours is in some ways more straightforward as we can ship it to the hospital where it can be administered through an IV,” Nolan explains.

Nolan also envisions going beyond SMA Type 1, adding that he hopes their platform can be used in other diseases in the CNS area.

The company went public earlier this year but as a private company up until February, FierceBiotech made an exception to our private biotech rule and added AveXis into our winners' circle, given both the cutting-edge tech and the rare, devastating disease area the company is aiming to treat. 

Investors: T. Rowe Price-managed funds, Deerfield Management, Roche Venture Fund, Venrock, Janus Capital, RA Capital and Foresite Capital

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Honorable Mention: AveXis