One of the newest arrivals to Ireland’s thriving life sciences sector is the US company Aerie Pharmaceuticals. It will shortly begin commercial production at a newly constructed state-of-the-art facility in Athlone.
Founded in 2005, Aerie specialises in the discovery, development and commercialisation of novel treatments for glaucoma, the disease that can cause irreversible vision loss, as well as for retinal diseases and other diseases of the eye.
The company’s lead product is the Rho kinase inhibitor, netarsudil which is approved and marketed as Rhopressa in the US and recently approved in Europe as Rhokiinsa. It is a once-daily eye drop to reduce elevated intraocular pressure (IOP) in patients with glaucoma or ocular hypertension.
In the US, the company also launched a fixed-dose combination of netarsudil and the prostaglandin analogue, latanoprost. (Rocklatan is a a once-daily eye drop to reduce IOP in patients with open-angle glaucoma and ocular hypertension.
How it came to be
“The company was founded by a leading ophthalmologist, David L Epstein, and Casey C Kopczynski,” said chair and CEO Vicente Anido Jnr.
“Epstein was chair of the Department of Ophthalmology at Duke University and had spent his research career looking for better ways to treat glaucoma.”
Biotech start-up veteran Kopczynski joined with Epstein to develop a new class of medications to transform the therapeutic area.
“David’s idea was that the best way of treating eye disease was to understand the underlying cause and target that,” Anido added. “He understood that the cause of glaucoma was damage to the trabecular meshwork, which is the primary pathway for fluid to drain from the eye.
“The damage causes the fluid to back up, thereby increasing pressure and ultimately damaging the optic nerve. None of the drugs treating glaucoma at the time were specifically designed to treat this underlying cause.”
Those conventional treatments lowered pressure by either reducing the amount of fluid being produced or increasing the outflow through a secondary drain. None treated the disease mechanism.
“David tried several different compounds and eventually settled on a class of drugs known as rho kinase inhibitors which work at the molecular level to open up the trabecular meshwork and allow fluid to start flowing again,” Anido said.
The next step
Having identified the class of drug, it was then necessary to find one that would work in a once-a-day dose.
“They looked at two candidates and the second one worked better for a longer duration. They identified it in 2013 and it became netarsudil,” Anido said.
“It took eight years before they made all the necessary adjustments to the chemical structure to get to this compound. They spent $75m and a lot of sleepless nights worrying before they succeeded. It was all about keeping the company afloat up until then.”
Anido joined the company in 2013 at the point when it was setting out on its clinical development and commercialisation journey. It had been decided in 2012 to raise funds through floating the company on the public markets and an expanded board was required.
Anido had extensive industry experience, including as president and CEO of ISTA Pharmaceuticals and president of the Americas Region for Allergan, and joined Aerie as executive chairman in April 2013.
Within a few months, there was a decision to restructure the management of the company and Anido took on the CEO’s role as well.
The big break
Clinical trials followed. “We were successful with Rhopressa studies and after a lot of hard work we got it approved in late 2017 and launched in the US in 2018,” said Anido. “In parallel, we had been looking at the fixed-dose combination with latanoprost, providing two drugs in one bottle to address all of the outflow pathways.”
That became Rocklatan. “We got that approved by the US Food and Drug Administration (FDA) in March 2019 and the two drugs are now on the market in the US.”
The decision to expand overseas was taken very early. “Unlike many pharma companies of our size, we chose not to partner outside the US,” Anido noted. “We opened an office in Dublin and moved our intellectual property (IP) to Ireland. Any IP created outside the US is located in Ireland.”
Manufacturing was top-of-mind early on. “We realised demand for our drugs could be quite large and there are not too many contract manufacturers in the ophthalmic space. So, we decided to build our own facility,” he said.
Role of IDA Ireland
And that’s when first contact with IDA Ireland was made. “There was just one line in our 200-page SEC filing document which talked about contract manufacturing organisations and said we were thinking about building a manufacturing facility somewhere in the world well known for pharma manufacturing, like Ireland”, he recalled.
“Someone in the IDA Ireland research department picked up on that and within 24 hours of filing I got a phone call from them asking if they could come out and see us in California,” he added. “That’s what started the relationship. I told them they should promote that researcher. We have since invested more than $70m in Ireland.”
Visits to Ireland followed. “The IDA took our manufacturing and finance people around to visit sites to show them what was available. They also introduced them to banks and other service providers and gave us details of the training and other support they could provide. The team came back and said they saw a site in Cork and a site in Athlone that they liked. Athlone had a building which had been constructed by the IDA as a showcase for the industry.”
He continued: “When they told us about that, it was an easy one for me. I had experience of Athlone going back to the 1980s when Elan was just getting started. They were a CMO for a company I worked for in the US. We were their first client. I visited Athlone on a number of occasions and got to know the culture and ecosystem there. It’s a great central location and we decided that was where we were going to plant our flag. We now have more than 70 people working in Athlone and a further seven in the Dublin office.”
Its first Irish hire
Athlone site director Barry Ivin was the company’s first hire for the Irish manufacturing facility. He says the availability of the building was critically important. “This was part of the IDA strategy of building advanced facilities in regional locations to attract technology investments,” Ivin noted. “This allowed us to avoid a greenfield investment and took a lot of the risk away. Athlone is centrally located with a strong industry cluster coupled with a supporting infrastructure of contractors, laboratories, and so on.”
Setting up the facility is a key element of the company’s strategy. “We like to control our own destiny,” Ivin added.
Initial design work for the facility began in March 2017 and progressed at what Ivin describes as an “extraordinary rate”. “We completed the building last year and hope to begin commercial production and supply in early 2020. We have 70 people working here at the moment and that will increase to 90 to 100 at full production.”
Talent availability was another factor in Ireland’s favour. “We are a small organisation with not-quite 400 people in total and we put a huge amount of time and effort into hiring the right people,” Ivin explained.
“Our people have an average of 17 to 18 years’ industry experience and more than 95pc have a third level qualification, with more than 80pc educated at a degree level or higher. Like anything, if you are clear on what you want and work hard enough you will get it.”
“The truth is that there is more pharmaceutical manufacturing talent available here than in the US or northern Europe.
“Good people are hard to find anywhere in the world, but we have worked very hard to put together an attractive proposition to compete with leading companies in the industry. Because of Athlone’s location, we can attract staff from a very broad catchment area. West Dublin is less than one hour from the plant and Galway is within 45 minutes.”
Anido said the Athlone facility is meeting all targets. “We passed our first set of inspections with the HPRA earlier this year and came through with a clean bill of health.
“We have submitted our prior approval supplement to the US FDA and will be inspected by that agency early next year. With luck we should be supplying product from the facility for the US market by the beginning of 2020. We filed for approval for Rhopressa in Europe in 2018 and received marketing authorisation in November 2019. With that approval, we were able to file Rocklatan with the European authorities in December 2019.”
In Europe, the drugs will be known as Rhokiinsa and Roclanda, respectively.
Ireland also boasts another advantage which had not been immediately apparent, according to Anido. “Something we found out early on and that other companies don’t realise is that not only is it more advantageous to supply Europe from Ireland, but it is also better to supply Japan from Ireland. This is due to the strength of the work Ireland has put in around the world in agreeing tax treaties. Ireland has a better tax treaty with Japan than the US does. That’s a benefit we hadn’t initially factored into our assumptions.”
He is happy with the relationship with the IDA. “They have been really good at explaining all the benefits to the point that we are already looking at expanding the footprint in Athlone by adding more space. Although we will use some contract manufacturing as a backup, we don’t expect to do our own manufacturing anywhere other than Athlone.”
The future looks bright for Aerie and its Irish facility. “Like any small company starting out, we will have our growing pains,” Anido noted.
“Some pipeline drugs will win out and some will not, but we hope to have enough shots on goal to have a healthy pipeline to fuel the growth of the company. In Europe we are about two to three years behind the US in terms of product releases. We will be able to shorten that gap now that we have our own manufacturing facility in Ireland. A lot of states in the US could benefit from the Irish model in terms of attracting investment and dealing with unemployment. Few other organisations have done this as successfully as the IDA.”