Atriva Therapeutics – a new take on influenza antivirals

In September 2023 a privately held German drug development company called Atriva Therapeutics announced that it was going to go public via a reverse takeover of Biocure Technology. That company, whose stock is traded on the Canadian Securities Exchange (CSE: CURE), will now move away from developing CAR-T therapies and biosimilars to working on a small molecule antiviral and immunomodulatory treatment of severe influenza infections. The reverse takeover is expected to close by end of March 2024.

Pitt Street Research, the parent company to Stocks Down Under, has been commissioned to evaluate this new opportunity, and our research is available at pittstreetresearch.com. We commend it to you. Atriva is currently raising US$15m to move its lead compound forward as a public company, and if this is of interest to you, the contact details of the company are below.

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Introduction to Atriva Therapeutics

Atriva’s lead drug candidate, which has made it to the mid-stage Phase 2 of clinical development, is zapnometinib, a pill that people with a severe influenza infection can take which has the potential to blunt the infection and, importantly, prevent the patient’s immune system from going into overdrive in a way that could be harmful and maybe even deadly. ‘Big deal’, we hear some of you saying. ‘We have vaccines for influenza and have had them for decades. Moreover, since the turn of the Millennium there have been influenza antivirals. So why would we need another antiviral?’ 

The answer to that question is that vaccines don’t always work well. Indeed, seasonal efficacy is generally less than 60% and can sometimes be as low as 10%. And when it comes to the antivirals, they don’t tend to work all that quickly, are indicated only for early-stage disease, and can lead to the development of drug resistant virus variants because they target the pathogen directly. Add these factors together and you’ve got a partial explanation of why America averages something like 35,000 ‘influenza-associated’ deaths a year, and the global figure is close to 400,000 deaths. That’s the unmet medical need that Atriva believes it can address with its zapnometinib candidate. 

Zapnometinib

Zapnometinib was discovered around 2015 by scientists at the University of Tubingen in Germany. Professor Stephan Ludwig had noticed that many of the cell signalling pathways that are activated in cancer cells are also activated in host cells used by the influenza virus for replication. He hypothesised that drugs blocking such pathways would therefore indirectly act against influenza infections, thereby avoiding the resistance issue you get when you target the virus directly. A breakthrough came when he used a Pfizer drug candidate called CI-1040 to block a cellular signalling pathway involving MEK (a seronine/threonine kinase), demonstrating the reduced ability of influenza to replicate inside host cells. Ludwig and his Atriva co-founders later showed, in the lab, that a metabolite of that drug worked even better, and that metabolite ultimately became zapnometinib. 

Before Atriva could study zapnometinib in influenza in humans, the Covid-19 Pandemic arrived in 2020, providing a different, albeit somewhat unexpected, RNA virus infection to clinically test the drug against. Atriva’s experience with Covid-19 was encouraging as well as frustrating. The company was able to run a Phase 2 study of zapnometinib in severe Covid-19 patients, but that had to be cut short because of the emergence of the Omicron virus variant and a lack of severely diseased/hospitalised patients in late 2021. However, even with small patient numbers, the study still found a trend towards significance in terms of an improvement of clinical severity status at day 15 versus placebo, which suggests that zapnometinib works as expected against RNA viruses. 

So what now?

Atriva is now preparing zapnometinib for clinical studies in patients hospitalised with a severe influenza infection, and that’s what the current reverse takeover and capital raising is all about. The company hopes to be back in the clinic in influenza by the second half of 2024. First will be a challenge study in healthy volunteers, where those volunteers are infected with a version of an influenza virus and then treated with zapnometinib to demonstrate the drug’s antiviral activity and immunomodulatory capacity. After this challenge study will come the Phase 2b trial in patients hospitalised with severe influenza. This study can straddle both hemispheres to recruit patients wherever influenza infections are rising. 

The immunomodulatory capability of zapnometinib is important because in severe cases of the flu, cytokine production by the immune system to fight the infection can grow out of control. Such a ‘cytokine storm’ can damage organs, especially the lungs and kidneys, and even lead to death. When Atriva looked at its drug in vivo in Covid-19 it found that the expression of pro-inflammatory cytokines had been reduced.  

Atriva believes that zapnometinib and other candidates in Atriva’s portfolio can be useful against other RNA viruses such as hantavirus, Respiratory Syncytial Virus (RSV) and Dengue fever. In January 2022 the FDA granted zapnometinib Orphan Drug designation for the treatment of hantavirus infections. 

There’s still upside left

As we noted above, Atriva is currently raising US$15m to take zapnometinib into the forthcoming clinical studies in influenza. This company has raised more than EUR40m in capital since its 2015 founding, with backing from venture capital, the European Investment Bank, and the German government. So, Atriva and its science has been through some serious due diligence over the last seven years. This latest transaction comes at a time when sentiment towards biotech and medical devices has been crunched by a two-year bear market. However, the upside is significant: Roche made US$709.5m from Tamiflu in 2015, a mild flu year, but in 2009, during that year’s H1N1 swine flu outbreak, sales skyrocketed to US$3.2bn. If you’re interested in the current capital raising, please get in touch with CEO Christian Pangratz by emailing [email protected]. 

Disclosure: Pitt Street Research owns shares in Biocure Therapeutics. Also, the company was paid for the evaluation research it published at pittstreetresearch.com.