Inside stories of coronavirus battlers Aerogen, Hibergene, Open Orphan and Nearform

Irish companies are on a voyage of discovery in their pivotal role in the fight against Covid-19

Brian Carey and Conor McMahon
Sunday April 26 2020, The Sunday Times

Ireland was placed sixth last week in a list of nations ranked on their response to the Covid-19 crisis in terms of innovation. The league table was compiled by StartupBlink, a Swiss-Israeli company that collates data on start-ups; the United Nations-backed Health Innovation Index; the Moscow Agency of Innovations; and partners such as tech database provider Crunchbase.

While the Republic has punched above its weight largely because of multi- national medical device firms, Enterprise Ireland says more than 100 of its client companies are responding to the crisis. Here, we step inside four Irish businesses that are seeking to make a material contribution in the fight against the deadly spread of Covid-19.

image: A quarantine room at hVivo’s unit in London – TOLGA AKMEN

Aerogen

John Power, the chief executive of Aerogen — Ireland’s largest indigenous medical device company — was in Washington DC during St Patrick’s week. He was a guest of Enterprise Ireland at the American Ireland Fund gala dinner on March 11, and was due to visit the White House reception the following day. The event was cancelled.

Power had spent the previous week in San Francisco and Texas, visiting hospitals and ventilator-maker customers. At the time, fears of a coronavirus pandemic were not a big concern, but by the time he arrived back in Ireland, “everything changed”, says Power. “My feet have barely touched the ground since.”

Aerogen’s technology is at the forefront of the fight against Covid-19. It is based on a vibrating mesh membrane that deliver drugs to the lungs with a high degree of precision and safety. The company supplies its nebulisation technology to the world’s leading ventilator makers, such as GE Healthcare, Medtronic, Hamilton Medical, Philips Healthcare and Maquet.

Aerogen mostly operates under an integrated partnership, where its brand is carried on the side of machines, similar to the Intel Inside branding on laptops. Aerogen also manufactures its own stand-alone nebuliser systems.

Using its technology, drugs can be administered without opening the ventilator breathing circuit. This is critical in minimising the risk of infection to intensive care unit (ICU) staff and contamination of other patients in ICU drug reservoirs. As the
inventor and only maker of closed-aerosol, drug-delivery technology, Aerogen has been swamped.

Power says the company received the same volume of orders in two-and-a-half weeks leading to up to the Easter weekend as it did in the first six months of 2019. His company supplies 75 countries.
“It was crazy. It’s like health authorities were doing the opposite of what supermarkets were telling people not to do with toilet paper: stockpiling,” says Power.

The clamour came from ventilator makers, distributors and hospital groups. “We couldn’t meet the demand on the basis of first in, first served — it wouldn’t have been ethical.”

The company “pushed back” demand and asked each customer to justify orders on a hospital-by-hospital basis. “Every Aerogen nebuliser we ship can have an impact on someone’s life,” says Power. “I didn’t want to get to a situation where we were looking at our product sitting on shelves in one hospital when there were shortages in others.”

Power decided to supply customers in smaller volumes but on a more frequent basis. With multiple customers in many countries demanding his product, it was a hugely complex task.

Aerogen manufactures through two key partners: Molex in Shannon and M&M Qualtech in Galway. Molex is due to close its Shannon plant at the end of this year. Power visited Molex boss Joe Nelligan in Chicago. Understanding the critical nature of Aerogen’s product, the two companies are ensuring that key manufacturing will stay under Aerogen’s control in Shannon after the end of the year.

Power praised the “commitment and flexibility” of his manufacturing partners. Both factories have been working “on a 24-7 basis”, he said.

At Aerogen HQ in Galway, three temporary packing lines have been installed. Volunteer accountants, scientists and administrators have been taken from offices and development labs and put to work on the production lines. Social distancing means shift crews must be kept apart on the lines.

“We’ve been trying to rapidly ramp up production when the world around us was shutting down,” says Power.
A key component supplier in California was locked down, so Power got letters from the relevant health and safety authorities and multinational ventilator maker to get it reopened. “We’re a very small part of their business, yet they opened up to help us make our product.”

Aerogen generally uses passenger airline cargo to send its product across the world and to import component supplies. The company had to get a tool mould from China via air freight and send finished products back to China and India. In the past month, freight costs have grown up to sixfold, as it has been hard to find space on planes.

Despite rising costs, Aerogen has not put up prices. “I don’t know of any genuine medtech company that has,” says Power.
The company’s revenues have risen at 30% per annum in recent years. This year, growth will be at least 50%, with Aerogen shipping three million units.

“Everybody is running flat out and the costs of everything you do are higher,” says Power. “We’re lucky, of course, to have the business, but with this awful pandemic it’s certainly not how you would choose to grow.”

Aerogen is also partnering with drug companies in clinical trials for eight Covid-19 treatments, including hydroxychloroquine — cited by Donald Trump as a “miracle cure”. Partners include the World Health Organisation, the Bill & Melinda Gates Foundation, and the National Institute of Health in America.

The focus is directed toward meeting demand for Covid-19 patients and drug trials. Aerogen and other Galway medtech companies, such as Medtronic and Palliare, are working with NUI Galway and University Hospital Galway to adapt equipment and produce accessories that enable a greater range of respiratory support equipment.

Aerogen shipped five of its ICU ventilators, used in research and development, to the hospital.

Staff have been pulled off speciality projects — “which has been very hard,” says Power. Aerogen is developing an aerosol-delivery treatment for premature babies, but the phase 2b trial has paused.

Power says people assume a health emergency will generate huge windfall profits for medtech. ICUs are cost centres for hospitals, he says, whereas elective surgery units are profit centres. ICU budgets are squeezed, and even highly engineered and innovative products such Aerogen’s do not command the same premium as stents or orthopedics.

Profit and margin have never been Power’s main motivation. “If somebody is admitted to an ICU with Covid-19, three things will determine the outcome. One is the care-givers, two the ventilator, and three the system used to deliver the drugs to treat the patient. It is an enormous privilege for us all to be part of that.”

HiberGene

Seamus Gorman, chief operating officer of Sandyford medtech company HiberGene expects its rapid diagnostic test for Covid-19, which is at the validation stage, will be launched “imminently”.

The company, which develops molecular tests for infectious diseases, first explored the possibility of developing the test in January with partners in China.

After completing a feasibility study, HiberGene successfully applied for €1m from the European Commission’s Horizon 2020 research and innovation fund.

Gorman said the test, Hg nCoV19, will be faster than those in use. It is expected to deliver results within an hour.

Most molecular tests in hospitals and labs use polymerase chain reaction technology and require extraction reagents, which are in short supply globally.

“What makes HiberGene’s test different is the sample handling,” says Gorman. “We’ve developed our own sample preparation buffer that’s part of the test kit, so no sample extraction is required. It offers a rapid turnaround and avoids the need for extraction reagents.”

HiberGene, which employs 21 people, plans to manufacture and develop the tests in Ireland. Gorman says it initially plans to produce 6,000 a week; this is expected to rise to 40,000 a week. After deploying tests in Ireland, the company intends to roll them out to other markets. “It’s a global opportunity and a global challenge,” says Gorman.

Open Orphan

Cathal Friel, the chairman of Open Orphan, calls hVivo his “lucky acquisition”. HVivo specialises in viral study models and testing the efficacy of vaccines. The company owns a 24-bedroom quarantine clinic in London.
The AIM-quoted Open Orphan bought hVivo “because it looked cheap”, says Friel. About £113m (€130m) has been invested in the clinic, viral testing models and a universal flu vaccine. While structured as a merger, Open Orphan in effect bought hVivo for £13m. It was an “unloved company” in an unfashionable corner of the pharma services sector, according to Friel — but not any more.

“In truth, in the past number of years there hasn’t been a lot of money spent on developing vaccines — it’s been all talk and no action,” he says. “In the past six weeks, suddenly, being a world leader in viral studies and testing has become a very interesting place.”

Last week Open Orphan announced its involvement in an antiviral treatment trial for Covid-19 with Russian pharma outfit Nearmedic International. It is in talks with eight pharma firms about using its facilities to mount a “human challenge” study on potential vaccine candidates. As such, it could play an integral part in bringing a vaccine to market quickly.

Normally, the efficacy of a vaccine candidate is tested in field studies, where the treatment and a placebo are given to thousands — or even tens of thousands — of people. Reseachers monitor those who get infected and how they react.

These phase III field studies are complex and time-consuming, and often the longest part of a vaccine’s development. With Covid-19, the focus of the health authorities and the public is to suppress the natural spread of the virus, which may frustrate the field study.

With a human challenge study, a small sample of people, perhaps 100 to 150 , are given the vaccine candidate or a placebo. All subjects are then infected with an attenuated strain of coronavirus a month later, and monitored in a quarantined environment for 10 days. Nir Eyal, director of the centre for population-level bioethics at Rutgers University in New Jersey, told Nature publication that human challenge studies could “greatly accelerate the time to approval and potential use” of a coronavirus vaccine.

The hVivo clinic has a virology laboratory and is one of only two such private facilities in Europe.

Friel said volunteers would be selected from the lowest-risk, healthiest cohorts. The clinic will have access to a full array of antiviral treatments, if necessary. “Over a three-month period, we can have 140 patients tested,” says Friel.

An ethical concern exists about challenging humans with even a weakened strain of a potentially deadly virus. Eyal says society lets “humans volunteer to do risky things” all the time. “We let people volunteer to be emergency medical services during this period. That significantly elevates their risk of getting infected.”

HVivo placed the call for volunteers for a coronavirus trial on its flucamp.com site on March 4. It has received 54,000 replies. “On a normal week we might get 20 to 40 volunteers,” says Friel. Volunteers get £3,500, but Friel says the motivation is not monetary. “It’s almost like contributing to the war effort.”

image: NearForm’s Cian Ó Maidín is developing a contact tracing app – NICO KAISER

NearForm

The Tramore tech firm NearForm is an unlikely recruit in the campaign against the virus. It was enlisted by the HSE to develop an app — CovidTracker Ireland — to help with contact tracing.
Founded by Cian Ó Maidín and Richard Rodger in 2011, NearForm specialises in developing software for large companies and counts IBM, Intel, Microsoft and The New York Times as clients. It employs 160 people, with offices in the UK and America.

A spokesman for the HSE, which is overseeing the app project, has said the technology will be “a key element of the next phase of Irish national public health response” to Covid-19.

The app will help the HSE identify individuals who may have come into contact with people with confirmed cases of the virus. Users will be able to track their symptoms every day.

Privacy is likely to be a key issue. The HSE has said the app will run on a voluntary, fully opt-in basis, and the timeline of its rollout will be determined by the results of security and product testing.

“When ready, the Department of Health and the HSE will formally launch the app with clear instructions on how to download and use it,” said the HSE