Thomas Cueni - Director General, IFPMA

EF: As a partner in the AMR Action Fund, could you elaborate on the inspiration behind the fund?‍

TC: The inspiration came from an analysis of the current situation. Some progress has been made in One Health, treating veterinary medicine as the science closest to antimicrobial resistance, but since 2014, no advances have been made. In 2015, Lord O'Neal came up with a report for the G7 meeting hosted by David Cameron, but since more big pharma companies haven't continued with antibiotic research, currently, there are no new revelations. The few biotech companies with promising products that managed to get approval went into administration, with Achaogen and Melinta being the most famous examples. Achaogen was listed on the Nasdaq, and its value was over a billion dollars; they were marked for priority approval by the FDA and suddenly dropped because the investors knew there was no market.

There have been studies in Germany of 10 million people dying due to AMR by 2050. A recent study published last year reported that 1.4 million had already died, and 5 million indirectly. Jim O'Neal's trajectory is even higher than mine. In the previous eight years, we have had several G7 and G20 statements and commitments, but not much has happened. The NHS in the UK did a subscription model pilot, which was well thought-out and positive. They plan to do something similar in Japan, and something similar is being done in Sweden. The Pasteur Act in the US would be game-changing, but it didn't pass at the end of last year. Pasteur is key in two respects; it provides money to companies who succeed with the subscription model and brings money to the hospitals for drug reduction. Drug reduction is necessary to face the MR problem, and we must deal with environmental discharge manufacturing and One Health. If we succeed, new antibiotics are still needed because bacteria have developed.

I remember a call to action conference the UK co-hosted with Ghana and Norway. The previous year, the G20 agricultural ministers agreed to ban the industrial use of antibiotics for gross stimulation in industrial settings, which was a step forward. A year later, in a G20 meeting in Cordoba, Argentina, sadly, the agricultural ministers went back on it, possibly influenced by the big meat-producing countries (Argentina, Brazil, and the US). Other than myself, Dame Sally Davis, the big name in AMR worldwide, and GEM are looking into the data, and both believe that something must be done; we need a new industry. The need for a realistic chance of progress on required incentives led to the creation of the AMR Action Fund, and the industry must be the first mover rather than stay on the sidelines. The industry collectively, twenty-plus companies, put together a billion dollars. A few CEOs invested significant money because they believed the industry needed to move. The immediate results gave us respect and credibility; we launched the fund in July 2020; I had been in Japan in February for investment-related business with Japanese companies and got five of six to co-invest. We had Dr. Tedros from the WHO, the Danish Minister of Health, and Yench Bahm from Germany. We had a similar launch in Tokyo and a third launch in Lausanne with two senators behind the fund. It triggered a reaction within the industry to do something, and two years later, the fund was up and running. So far, the fund has made three investments, the first, Venatorx, second, Adaptive Phage, and the third, BioVersys, which is Swiss, with the first European product. DOD Investment Bank, the Wellcome Trust, and the WHO participated in the co-creation team, giving us credibility because the two latter are involved with public health.‍

EF: How did you convince them to participate? What was your pitch to them?‍

TC: The Wellcome Trust and WHO had worked for years on the subject but had not progressed much. The WHO had been in discussion with the European Investment Bank on a 500 million Action Fund, but they never got the money. In our case, more than 90% of the money comes from the industry. The Wellcome Trust is on the board, independent of the investors. From the beginning, it was crystal clear that no money would go to big pharma, and it didn't need to be explicitly stated. Some biotech startup companies don't have the money to move into clinical trials phase two, let alone phase three, as it is very costly and partners are needed. For example, BioNTech required Pfizer in vaccines, and Moderna needed Lancet. Partners are necessary to market, meaning the business model hasn't changed much. It is important to find solutions to help a company avoid the destiny of Achaogen.

Last February, I was in Brussels, invited by the Netherlands and Hungary for a mission event to appear before the European Commission. I appreciate that the Commission and HERA believe in the need for incentives. There is an excellent study from the OECD on stemming the tide of antimicrobial resistance for just a few more dollars. No company has the same kind of return as immuno-oncology, and we can't justify investing in something when there is no return. We have a channel access provision because if we do have new antibiotics, we need them to be available where required. The challenge is to ensure they are stewardship, for example, in multi-drug resistance TB. J&J has teamed up with global TB to ensure it is getting to the countries that most need it, namely developing countries, and only supplied to certified hospitals to have the assurance that it will be used appropriately.‍

EF: Is it the case that a substantial amount of money is being invested in tech companies and the stock exchange, even though many of them lack profits, while unicorn companies, despite their potential, have yet to generate income?‍

TC: Some have turned out to be a huge success; eleven vaccines were approved in the flu vaccine project, while Covax has only three vaccines. We must share what is most effective, and 85% of the Covax vaccines in 2021 came from four companies, Pfizer, AstraZeneca, Moderna, and J&J.‍

EF: We know you to be an avid reader; if you had to recommend three books to understand the value and impact of innovation, which would they be?‍

TC: Baumol is a classic; I have quoted him; he makes a beautiful distinction between scientists in Russia: discovery is not the same as innovation; innovation turns discovery into industrial innovation. I love William Baumol because it is a classic of how the growth machine in the free market is innovation. My second recommendation since COVID-19 is The Vaccine, by Joe Miller. He is a journalist, the Frankfurt correspondent of the FT, who initially didn't plan on writing a book. Clive Cookson told him to think about it a year into the pandemic, and he met with Ugur Sahin and asked him if he was willing to help him. Today there are WHO announcements everywhere to the effect we will have MRA capabilities, and many hubs are working in this direction; Brazil, South Africa, where it started, and Korea. I already mentioned the 2023 MRA trials; getting the gist of the basics of MRNA doesn't mean you can create a vaccine.

The people from BioNTech were a little miffed early on when the government wasn't interested in them. They were interested in another company CureVac, which never got approval because they missed the 50% efficacy, whereas the BioNTech vaccine efficacy was 95%. Before the pandemic, a certain president of the US was interested in buying CureVac because he was convinced it would be the first vaccine company and wanted to bring it to the US, which was not well-received in Germany. The German government gave a few hundred million to CureVac, but they failed. I was told they then had a better second-generation vaccine with GSK. But Joe Miller's book is very interesting in this respect, and Baumol was right; it is about the industrial application of innovation and its use. It is translational science from the lab to creation. Interestingly, Moderna is very positively referred to by Jeremy Ferrard in Spike on how the virus information got out, although it is a bit parochial on British politics.‍

EF: If you had to create a startup to impact the health sector tomorrow, what would you do and why?‍

TC: I know business and public relations very well, but I’m no scientist. I think life sciences are very exciting, especially for an open-eyed scientist. I have used "The Legend of the Princes of Serendip" as an example of walking through life open-eyed. Some biotech companies do that; BioNTech wasn't into anti-infectives but oncology. They had a flu plan with Pfizer, but their main activity was oncology. They had a leader who had written and published many scientific papers. He wrote a report in January about a virus. He called the chairman of his board and an executive committee meeting over a weekend and told them they had to do a total reassessment of our priorities, a light-speed turnaround, as he called it. His chairman was shocked; he had met with JP Morgan three weeks before to procure funding for their ambitious oncology clinical trial program. It shows that if you are open-eyed, you will see new opportunities.

There is a book published over twenty years ago by Barry Werth titled "The Billion-Dollar Molecule" about Vertex Pharmaceuticals, and it is hilarious, irrational, and unstructured. Vertex was controversial for splicing some of their drugs, but they were game-changers. A former senior MSD scientist and a Harvard medical professor looking to develop the first billion-dollar molecule designed to improve on Ciclosporin, which was the first drug that helped heart and kidney transplants, as until then, heart transplant patients died within days. Then a Japanese company, Fujisawa, which today is part of Astellas, had a product called FK506. It was potentially more effective than Ciclosporin but much more toxic, so it never quite made it. Joshua Boger, the founder of Vertex, then decided to create a better product than FK506. They took out its toxicity and achieved the million-dollar molecule.

The first drug they came up with was an HIV antiviral, which they managed to license to what then was Glaxo. The first big money he got was from the head of Chugai, a Russian company today. I mention these cases as a result of being open-eyed and having the capacity to change, clearly the case with Hugo Sahin. A young scientist on my team is seriously into the microbiome. Some believe many CNS diseases or Alzheimer's could come from the microbiome. My young scientist is from Istanbul, the son of Bulgarian-Turkish parents. He is not wealthy but is a top graduate of Istanbul University; he went to Cambridge and then came to Switzerland with a postdoc grant from the Swiss Science Foundation. He prepared my briefing papers for the MNRA and maps for a talk I gave at the Tokyo University of Science and Technology.