Today, Ultragenyx is chugging along on the gene therapies it picked up in the Dimension buyout, as well as developing Crysvita for a second indication. (Michael Gaida/Pixabay)

IPO year: 2014
Raised: $121 million
Share price at IPO: $21
Valuation: $436 million
Close Aug. 30, 2019: $54.47
Change: Up 159%

When Emil Kakkis, M.D., Ph.D., founded Ultragenyx Pharmaceutical in 2010, it had two employees: Kakkis and his secretary. In the years since, the company has swelled to more than 700 employees, pushed two rare disease therapies past the FDA and pulled off a $121 million IPO—out-raising its initial goal of $86 million.

In late 2013, the company had planned to sell 4.8 million shares for a price between $14 and $17 but ended up selling nearly a million more than that—and at $21 per—in January 2014.

At the time, Ultragenyx had four midstage programs, including a pair of enzyme replacement therapies and an antibody it had recently acquired from Kyowa Hakko Kirin designed to treat X-linked hypophosphatemia (XLH), a rare genetic disease that causes rickets.

One of those enzyme replacement therapies became Ultragenyx’s first approved drug in November 2017. Dubbed Mepsevii, the drug won an FDA green light to treat children and adults with mucopolysaccharidosis VII, a lysosomal storage disorder caused by a deficiency of the beta-glucuronidase enzyme. Over time, the disease causes a particular type of sugar molecule to build up in connective tissues and cause damage throughout the body.

RELATED: Ultragenyx up on XLH drug's phase 3 success

As for the XLH candidate, it was eventually christened Crysvita and earned its FDA nod in April 2018. It was the first treatment for a group of rickets patients who wouldn't respond to vitamin D therapy. Ultragenyx markets Crysvita in the U.S., Canada and Europe, while Kyowa Hakko Kirin sells it elsewhere.

Along the way, Ultragenyx inked an R&D pact with Takeda worth up to $65 million, teamed up with Arcturus on mRNA treatments for rare diseases and snapped up Dimension Therapeutics to get its hands on a pair of rare disease gene therapies.

The Dimension deal didn't come without a fight, and nor did it come cheap. Regenxbio had already agreed to acquire Dimension for $86 million in August 2017, but Ultragenyx swooped in a month later, offering $138 million—a whopping 358% of Dimension’s share price as of Aug. 24, the day before Regenxbio announced its deal. Ultragenyx won out, ultimately forking over $151 million for Dimension and its programs in ornithine transcarbamylase deficiency and glycogen storage disease type 1a.

Ultragenyx has run into its share of setbacks, too. In early 2017, a small molecule drug, UX007, missed the mark in a phase 2 study of glucose transporter type 1 deficiency syndrome (G1DS), which is linked to epileptic seizures and movement impairment. A phase 3 failure followed, and Ultragenyx ended up axing the program in G1DS. It's still developing UX007 for long-chain fatty acid disorders.

A phase 3 candidate for the muscle disease GNE myopathy met the same fate in August 2017, after it failed to beat placebo at improving muscle strength and function. Ultragenyx’s swift decision to can that program freed it to focus on drugs with better prospects—and one of those drugs was Mepsevii.

RELATED: Ultragenyx snags option on antisense startup GeneTx

Ultragenyx’s latest M&A move was to snag an option to acquire GeneTx, which plans to start testing its treatment for Angelman syndrome in the first half of 2020. With eyes on the clinic, the company picked up $20 million from Ultragenyx, which will also pitch in strategic and clinical expertise during the run-up to an IND.

Under the deal inked last month, Ultragenyx may pull the trigger on buying GeneTx up to 30 days after the FDA accepts the IND. If it wants to hold off until it sees phase 1/2 data, Ultragenyx will have to pony up another $25 million to extend its option.

Now, Ultragenyx is chugging along on the gene therapies it picked up in the Dimension buyout, as well as developing Crysvita for a second indication in tumor-induced osteomalacia, a bone-weakening disease typically caused by small endocrine tumors. It recently submitted a New Drug Application for UX007 in a group of genetic disorders that keep the body from converting long-chain fatty acids into energy.

Ultragenyx, like its peers on this list, pulled off a successful IPO and translated those dollars into marketed drugs. But what sets it apart is that it continues to work at its pipeline and sell its products as a standalone company.

And from the looks of it, Ultragenyx plans to keep going it alone. The company recently promoted Erik Harris from head of North American commercial operations to the long-vacant role of chief commercial officer, showing it's still serious about its sales and marketing ops. And Kakkis himself told FierceBiotech this summer that Ultragenyx is doing what it can to hold onto its entrepreneurial spirit and fight off the bureaucracy that can kill innovation at larger companies.

To keep the innovation flowing, Ultragenyx has set up a translational research team that manages the early-stage pipeline. Any employee can come up with an idea, pitch it to the group and get it funded from a separate budget. Like a small biotech raising venture funding, a group working on such a project can grow and eventually become part of Ultragenyx’s portfolio. 

“We purposely allow them to do kind of crazy things and make mistakes. … We are incredibly proud of this kind of environment; it keeps a small-company feel," Kakkis said.


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