Atriva Therapeutics GmbH was working on an active ingredient to inhibit flu viruses. What made you decide to use this as a basis for developing a COVID-19 drug?
 
Based on our knowledge of flu viruses, it made perfect sense to ascertain whether our general approach could also produce successful results with COVID-19. ATR-002 has a special and unique mode of action. It attacks the structures in the host cell that are important for the replication of this entire family of viruses – referred to as RNA viruses – including both the flu virus and the SARS viruses that cause COVID-19. On the one hand, our drug has a proven antiviral effect, making it impossible for the virus to replicate due to the absence of the necessary cellular apparatus. On the other – and this is its unique feature – it influences the immune system in such a way as to prevent the dreaded excessive immune response that leads to a significantly increased release of cytokines and can be even more fatal for COVID patients than for those suffering from flu.  
 

When did you learn about the new virus and when did you start developing a drug to treat COVID-19?

The world’s number one market for antivirals besides the USA is China. The close scientific contacts we’d established with Chinese partners and companies because of our flu drug meant we were already aware in January of the severity of the outbreaks in Wuhan. We then began testing at our labs in February and, eight weeks later, we were certain that ATR-002 is also effective against SARS-CoV-2. We started preparing for the clinical trial back in midMarch and got in touch with Professor Martin Witzenrath from Charité, Europe’s largest hospital specialising in pulmonology and infectious diseases.
 

Did you receive any special support to speed up the development of a COVID-19 drug?

Government funding naturally focused on vaccine research to start with. Perceptions are now changing, though, and support is being extended to treatments with the aim of reducing the extremely high mortality rates being seen at hospitals. These were totally unexpected and exceeded our worst fears. Two months ago, hardly anyone would have thought it possible that we would have up to 1,000 daily deaths. Nobody predicted how the pandemic would take hold. The risk of making mistakes is huge. Germany has continued to fare better than many others, but we mustn’t throw that away now. A threestep approach is required. First of all, we must minimise contact and optimise personal protection. The second and most important step is the vaccine. And thirdly, we need treatments to minimise the number of serious cases so that our healthcare system continues to cope. The Ministry of Health has now realised this. Amongst other things, we’re obtaining a loan from the European Investment Bank (EIB) that will provide Atriva with up to 24 million euros for the development of our drug to combat COVID-19.
 

When will it be possible to treat regular patients with ATR-002?

Ever since we announced the start of the phase II trial, we’ve been receiving calls from patients and their families asking for treatment. Regrettably, we’re still having to ask them to wait, but we’re endeavouring to have the drug available to patients by the end of this year. The initial patients selected for the trial at Charité are to be given ATR-002 in January, as soon as we have the stamp of approval. We’re expecting to treat around 30 patients per week given that hospitals currently have more than enough to do without clinical trials. Despite this, Professor Witzenrath has allocated a doctor and a study nurse specifically for this purpose. We estimate that we’ll have treated the requisite 220 patients by the end of the second quarter of 2021. We’ll then need to keep them under observation for a period of 90 days, during which we’ll see whether or not the drug is effective.  ATR-002 is now starting to be administered to sick people. A total of 1,000 patient years is normally required to establish a drug’s safety, but that’s more difficult to insist on in an emergency situation such as this. Nonetheless, the risk-benefit analysis must be totally convincing and all questions raised by the responsible authorities must be answered.
 

How important is it to develop highly effective antiviral treatments for the global pandemic?

According to experts, the southern hemisphere is at particular risk of experiencing a third wave once the colder months return there. And we’ll be unable to vaccinate the entire population as quickly as we would like. If, for example, this more infectious virus mutation from the UK becomes widespread, having 60 per cent of the population vaccinated won’t be sufficient. We’ll need to achieve a level of 90 per cent – despite the current vaccine scepticism … Other risks are also constantly emerging, including tropical diseases such as dengue fever and hantavirus. The warmer the climate becomes, the more Europe, too, will be affected by diseases of this kind, so we need to find highly effective antiviral treatments as quickly as possible