Webinar: Creating a New Generation of Antibiotics

Emma Ross

Good morning and thank you for joining us for this webinar on Creating a New Generation of Antibiotics. We’re here today to discuss the threat of antibiotic resistance, what the problems are with the availability of effective antibiotics, what strategies are being pursued to reinvigorate the pipeline, and what more needs to be done to ensure we have a reliable armoury of antibiotics that we will need, to enable Doctors to effectively treat bacterial infections that are increasingly outsmarting antibiotics in a way that’s threatening lives.

We have with us today four speakers who are at the centre of efforts to protect us from this phenomenon. Laura Piddock is a Professor of Microbiology at the University of Birmingham, who has been at the forefront of antibiotics research, and is Director of Scientific Affairs of the Global Antibiotic Research and Development Partnership, GARDP, a non-profit drug developer. We also have with us today Thomas Cueni, who is CEO of the International Federation of Pharmaceutical Manufacturers and Associations, which represents large, research-based pharmaceutical companies worldwide. The focus of his tenure has been on the industry’s action on antibiotic resistance. Kevin Outterson Co-Directs the Health Law Programme at Boston University. He also serves as the Founding Executive Director and Principal Investigator for CARB-X, a $500 million international public-private partnership to accelerate global antibacterial innovation. Jim O’Neill is a renowned Economist who coined the term BRICs to describe big emerging economies. He’s currently Vice-Chair of the Northern Powerhouse Partnership and Chair of Chatham House. Since leaving government in September 2016, having been Commercial Secretary to the Treasury, Jim moved to the crossbenches of the House of Lords. He led a very famous independent review into antimicrobial resistance for David Cameron from late 2014 to September 2016, and he remains focused on this challenge, and that report is considered a landmark in the field globally.

Just a bit of housekeeping first, before we move onto our speakers. This webinar is on the record and is being recorded. The video will be available to corporate members on a private YouTube channel afterwards, and this is part of the Business in Focus Series for Chatham House. Please do ask questions. We’re using the ‘Q&A’ function in Zoom to ask questions. First of all, each speaker will outline their point of view for a few minutes before we start engaging in a Q&A. So, Laura, I’d love to start with you, if you could start by putting the problem in context for us and give your perspective on untreatable infections and how certain we are about what’s going on and why treatments are so important.

Professor Laura Piddock

Thank you, Emma. So, it may seem strange that I’m going to start my comments about tackling antibiotic resistance by talking about COVID, but I think it’s really relevant to us today to be able to ground the knowledge that we all now have about COVID and its relevance towards tackling antibiotic resistance. So, COVID is a single virus, and so it causes a single infection, in the same way as that it’s a single virus that causes chicken pox, a single virus that causes Ebola. When we talk about these, we never talk about tackling all of these viruses at the same time, but that’s exactly what we do when we talk about antibiotic resistance, and we group together many different bacteria and many different drug resistances. Although it’s not simple, it is actually much easier to focus on single infections.

So, we’re all well aware of tuberculosis. This is an antibiotic-resistant infection in many parts of the world, and this also is caused by a single bacteria, a single cause, but, in addition to TB, there are millions of infections worldwide by other drug-resistant bacteria. So, the antibiotic resistance pandemic is with us, and it’s with us now. The difference with COVID is that the impact of this pandemic has not been hugely felt by those who live in high-income countries, and this is because we’ve got considerable choice of the antibiotics that the healthcare professionals can use, and there’s access to these antibiotics. Even with this, there are still tens of thousands of untreatable infections each year in each of the high-income countries.

So, why don’t we really know about them? How come we’re not aware of this in the same way as we’re aware with COVID? Well, it’s quite simple. Unlike COVID, many of these deaths by infection are hidden, and, if they’re documented, they usually record it as due to something else, such as cancer, or sepsis. So, if people realised how many deaths were caused across the world, I believe they would act much more quickly, and the WHO will shortly start a global surveillance project where mortality data will be collected, and this will show the real size of the problem. In my view, I believe it will be as high or higher than the current global mortality figures for COVID. But why are we going to wait until those figures are available? I really don’t think we need to, and, like many people over the last ten years, we have started to see action.

But it’s important to say that, unlike COVID, which is a new disease, we know an awful lot about antibiotic resistance and ways of tackling it, and there are many promising opportunities to develop new treatments, but the world needs to act together, in partnership, to develop these so that they reach the patients who need them, and this joining together is, I believe, the missing part of the puzzle to truly tackling antibiotic resistance. It’s important to note that there’s few vaccines to tackle antibiotic resistance and, even so, it may not be possible or even desirable to use this approach for all antibiotic-resistant infections, and this is because many bacteria an important part of our microbiome, the so-called good bacteria. But the bacteria that often cause infections in the lungs or blood are often those same bacteria, they’re just in the wrong place, and when in the wrong place, they can cause a deadly infection.

So, new treatments are really the best hope, and the science about antibiotic resistance is much more advanced than it is for COVID, and we have the wherewithal to do this now. Unfortunately, the drug discovery, research and development pipeline and how it is funded has been divided into segments. Sometimes, different sectors can also appear pitted against each other, but the only way we can contact – conquer antibiotic resistance across the world is to link all parts of the pipeline with every actor working together, and, yes, this still needs more funding. And this is not just because we need to develop the drugs, but we need to make them available and accessible everywhere. Most new drugs are only approved for use in Europe and North America, but, worryingly, in the case of antibiotics, one was only approved for use in the USA, really restricting access to it.

But we’re a global community, so what happens anywhere in the world can happen to anyone. COVID’s shown us this, and antibiotic resistance travels too, and, in fact, it has done. One of the big antibiotic resistances that trouble healthcare professionals today originated in the USA, another one originated in Asia, and these have all spread globally. So, to protect us all, we need to make sure that new treatments are manufactured and distributed throughout the world. We could also think about maybe, if we’re making these new treatments, or making old treatments available, they should be available to the priority populations, in the same way as we were talking about COVID and prioritising for those most at risk, such as the elderly. The priority populations for antibiotic resistance are frequently children and babies. So, we need to really work together to make not only the new drugs approved where they can be used but give access to them.

So, I’d like to just say a few words about the Global Antibiotic Research and Development Partnership, GARDP, a not-for-profit drug developer whose mission is to provide treatments for bacterial infections and make them available to everyone, and to do this by filling gaps that no other will. So, much of the current work is focused on clinical development of a new treatment for drug-resistant gonorrhoea, and we’re doing this in partnership with a small company called Entasis. Our latest clinical programme is a new drug for serious bacterial infections in adults in hospitals and, ultimately, we hope this will be a route to a new treatment to treat bacterial sepsis in children and babies, and this programme is in partnership with another small company called [inaudible – 12:21].

And the third example of our work is in discovery research, where three Japanese pharmaceutical companies have shared large chemical libraries, which we’ve used to screen for activity against drug-resistant bacteria. We’re already having success, we’ve identified some really interesting new chemicals, and these could form the basis of future new treatments.

So, to finish my remarks, we need to work together, and we need to make sure there’s enough funding to do this. If we do not act now and tackle the antibiotic resistance pandemic, we could end up in the same situation as we are with COVID, where, in many parts of the world, the only way to tackle it is good hygiene, social distancing, and restricting our activities, and I think we’re all too aware of the huge impact that this has on our economies. Thank you.

Emma Ross

Thank you, Laura, that’s a great introduction to the rest of the discussion. Thomas, can I ask you now to give us the pharma industry perspective, why it’s such a difficult dilemma for the industry, and what it’s doing in this effort, and where you think this needs to go?

Thomas Cueni

Thank you very much, Emma, and I’m delighted to be on this panel, in particular since GARDP, as well as Jim O’Neill and Kevin Outterson, played a role in the creation of the AMR Action Fund. When you look at – Laura referred to COVID-19. Now, COVID-19 was the pandemic we were, sort of, waiting for, but we didn’t know what it was, and we didn’t know SARS-CoV-2 until January 10. AMR, we have known for more than ten years, and we have seen in the several reports published in 2014, which Jim O’Neill did for the David Cameron Government, you know, the frightening impact AMR could have.

My first meeting with Lord O’Neill, we didn’t know each other at that time, [inaudible – 14:26] and he gave me a bit of a dressing down ‘cause, after I gave my usual industry talk about what the industry was doing, he said, “Oh, stop pestering, you know, get on with it. Everybody agrees with the market entry reward, everybody agrees with the billion-dollar cheque for novel antibiotics,” and I had the guts to push him a little bit back and said, “You are suffering from one slight confusion. Signing a statement of G7 or G20 is not the same as signing a billion-dollar cheque.” Unfortunately, I was right, and, six years, you know, after his report was published, we know from the World Bank OECD, Jim O’Neill, the staggering cost of AMR, the impact on health, the impact on our economies, but nothing had happened.

Now, we have had a few more meetings since then and he pushed me, same as Sally Davies, in terms of, for God’s sake, the industry is to blame because companies are getting out of AMR. Now, the reason companies, many companies, quit antibiotic research is there’s no market. Actually, as Kevin Outterson once told me, the worst which can happen to a company, a biotech company, which makes it to the market, which has even gotten a priority review by the FDA, they lost more money by getting on the market than if they would have just, you know, killed their research, because there is no market, and staying on costs more money than the research and development costs.

Now, short, you know, answer to the question about the pharma industry is, I felt frustrated, as many others, that we didn’t see policy change, but also, I felt a responsibility for the industry because industry was seen as not living up to societal expectation, and not living up to the public health needs. Now, they could market arguments why this happened, but, at the same time, this is a huge public health challenge, and we were a bit concerned, when we were ready to go public on the AMR Action Fund, that it all would be drowned in COVID-19. We had a pleasant surprise because what we saw is that Politicians as well media reacted extremely well, that the industry was willing to invest in something where there is no money, but there’s a huge public health problem.

And I think, when you look at the unique properties of this AMR Action Fund, it is not just companies still invested in antibiotic research and, when you look at the statistics on antibiotic research, it’s still about two thirds to 80% of the R&D is spent from the private sector. But by and large by just four and five companies, therefore being able to raise money from 23 research-based pharmaceutical companies, most of them never were in the antibiotic business, some of them gave up, I think it’s quite an achievement. Raising a billion dollars we believe is more than move the needle, it is potentially a gamechanger because we benefited upfront. We talked to Kevin Outterson, John Rex GARDP, WHO, EIB. We had all their business plan analysis, we knew that you can actually, in the field of antibiotic research, achieve a lot.

We are confident that, thanks to what CARB-X and the REPAIR Impact Fund and the Fleming Foundation, basically did, there’s more into – in early research and discovery research, but, after that, there was the ‘valley of death’, therefore our focus is really on clinical development. We were told by all the experts, “Don’t waste your money too fast on late-stage development,” because, as we know from WHO and others, there isn’t that much there, but they are interesting molecules in the early development stage.

I think the second element which is crucial, this is not to make money. I think all my investors, from the industry side, would be absolutely over the moon if they get their money back. They want to get their money back because otherwise we would fail. We would not succeed in bringing to the fore real, novel antibiotics to the market, but the focus is driven by WHO priority list of pathogens and CDC priorities, which means it’s public health and it’s not making the money.

And, last but not least, I think and I hope, and I’m pretty sure that Jim O’Neill and Kevin will confirm that, it will be a drop in the ocean and a waste of money if we do not succeed to trigger the debate, which is so much needed on policy reform and change, on making antibiotic research something exciting, but also sustainable and viable. And what I think is unique to this, when you look at blended financing, it’s normally public money de-risking private investment, and we flipflopped it to some extent. It was private sector being the first move, I think very much responding to the call from Jim O’Neill and others, and now, we need support from all the stakeholders to drive the debate about policy change. What we will do is make sure that the money is well invested, and science dominates in public health and not the concern about, do we get the money back? Thank you.

Emma Ross

Thank you, Thomas. I just had a follow-up question on that. Can you expand a little bit about what the Action Fund will do? I’ve heard you said 23 companies have put money into it. What exactly will they do? Is this a new pharmaceutical company that’s co-owned by various companies? Does it mean that companies won’t do anything more outside of this context? Is this Action Fund going to be enough to solve the problem, from the pharma industry’s point of view?

Thomas Cueni

The last one is the easiest and fastest to answer, no. The money would be wasted drop in the ocean if we don’t see policy change in the next few years. The earlier one, I think what’s important is the fund is not an excuse for companies to quit, quite the opposite. The fund will not subsidise research from Big Pharma companies like GSK, like Pfizer, MSD, Roche, you know, who else, Sanofi, who are still in the business of doing antibiotic research. It wants to invest probably in clients of Kevin Outterson, it wants to invest in companies who are faced with the ‘valley of death’ because there’s no money. Venture capital has pretty much quit the area; therefore, the fund will invest for taking an equity stake in small companies, give them advice, and I think that’s really important. We have heard many times from experts like Kevin Outterson, like Sally Davies, it’s not just about money.

You also need the skillsets of Big Pharma therefore the notion is about an engaged owner fund. You would get expertise, so these companies will get expertise on how to run a clinical trial. You will get expertise from Big Pharma, which is pretty, you know, knowledgeable about what to kill, which projects not to develop, because you can waste a lot of money if you develop a compound, which is actually not worth developing. You will get support for regulatory science because small companies don’t have the regulatory expertise, and you may also get, for these small companies, support in scaling up manufacturing, and support how to get on the reimbursement list of, for example, US hospitals, so the chance of getting the money back is somewhat better. Therefore, it is about the money, but it’s also about the skillsets which only Big Pharma has.

Emma Ross

Okay, thank you for that, Thomas. Kevin, I wanted to bring you in now to follow-up on that, and where you’re situated in this whole picture, and what you see is going on and is needed going forward.

Kevin Outterson

So, thank you for the opportunity to speak. It’s early here in the morning in Boston, but I’m glad to do it. A transformational couple of months of my life was spent at Chatham House, as a visitor, and it was really excellent work that laid a foundation for a lot of what I do now in the world of antibacterials.

All of us, you know, we have a goal. We all think that we must continually create new generations of antibiotics. Because of the evolution of bacteria, we can’t say we’re done and walk off, like we might if we had a perfect cure for heart disease, or, you know, many other human conditions. For antibiotics, we need to continue to innovate because the bacteria continue to evolve. If COVID has hit the world like this tsunami, you know, coming as a surprise to most people, and quickly rising to the level of mass devastation, if COVID is a tsunami, based on viruses, antimicrobial resistance is more like a glacier. It moves more slowly, but let me tell you, you know, it continues griding away unrelentingly. Glaciers can level mountains, given time. It’s going to destroy everything in its path is what a glacier will do and so, we really need to be on this problem. Think if you were in charge of maintenance for the Chunnel, keep at it every day, you hope that your task is never urgent because you’ve messed up if you have an urgent maintenance need on the Chunnel. Since we’re fighting bacterial evolution, we have to be at this all day, every day.

Recently, we’ve seen signs of extreme trouble. Not only do people like the CDC, and the ECDC, and all the professional societies ring alarm bells, and WHO, saying that the pipeline is thin, the people are dying, that we’re not replacing antibiotics that are being lost due to bacterial evolution, but we see alarm bells in the market. Since April of 2019, not that long ago, five out of the last 14 antibiotics approved by the US FDA, and that’s an entire decade’s worth of antibiotics, five out of 14, have been through bankruptcy or the equivalent since April of 2019. In nine of those drugs, nine out of the 14 were not commercially available in a country like Sweden as of June of 2020. So, this is not an access problem that’s – you know, we’re worried about Africa or, you know, Asia or something, high-income countries in Europe are lacking access.

And the companies that, for any normal biotech, you get to FDA approval, it’s a time for celebration, you know, people open the champagne. If you’re a biotech with antibiotic, five out of those 14, a third of the pipeline, more than a third of the pipeline, for the last decade, you know, a decade of work, and what they’re rewarded with is the bankruptcy or its equivalent, mainly because, if you create a great antibiotic, Doctors don’t want to use it very much, and, if you create a tremendous antibiotic, they don’t – they want to use it even less. They want to put it behind glass and save it for the future, and that’s great for public health, it’s a disaster for the small companies.

So, I promised everyone that I would not be just negative, but I would be positive and focus on promising developments. I lead CARB-X, I view that as a positive development. We’re non-profit, we’re founded at Boston University, we support preclinical antibacterial R&D worldwide, and preclinical, so we end at the end of the Phase I trials. In short four, you know, short years, we’ve built the world’s largest preclinical pipeline, actually, for the reasons Thomas stated, larger than all of the large pharma companies combined, which is kind of frightening when you consider that – you know, how long we’ve been around. We’ve been gratefully supported by three governments, the United States, the United Kingdom, and Germany, and two foundations, the Wellcome Trust, and the Bill & Melinda Gates Foundation. We’ve put – so far, 68 projects we’ve agreed to fund, the 68th we announced just a few minutes ago. We’ve put – committed $250 million at this moment to the 68 projects, and we have many projects and additional funding following.

As was mentioned, also, we don’t just fund with money, these are small companies. Typically, they’re less than 15 people. They don’t have the depth and breadth of a large drug company. They need technical experts as well, and we provide experts that we’ve retained, so that it’s not at any cost to the company, so that they’re able to get done the projects they need. More than 90% of our projects are highly innovative, they’re new classes, new mechanisms of action, non-traditional antibiotics, and more than 90% of the companies are small and medium-sized enterprises. The median size is actually 15 employees.

I’m encouraged by GARDP in the work that they’re doing. They’re picking up projects and work that, you know, nobody else would, honestly, and particularly the – focusing on the ability for companies to license their product and to make sure that it’s available in the rest of the world. The project that they’re dealing with in Texas, for example, would not be done but for GARDP. And I’m very encouraged by the Action Fund because CARB-X ends at the end of the Phase I human trial, and I was concerned. Where was the private money? Where was the expertise that would pick up and cover the Phase II and Phase III clinical development and take it to approval? The Action Fund is – will be part of the answer for that.

I’m also greatly encouraged by the UK pilot project. You may not know this, but the United Kingdom Government, and National Health England in particular, has been working for a couple of years to develop what’s called a subscription plan. This gets around the problem, I mentioned, that a great antibiotic is never used. How does a company need to make money if its technology is never utilised until maybe a decade later, after the patent’s expired? The answer to that is the linkage. Let’s not pay based on the volume of antibiotics used immediately, but let’s pay based on the value to society. And so, one way to think about that is the subscription plan.

A country, England, paying a set fee for an antibiotic, say £10 million per year, without regard to how much of it is needed in any given year. Maybe only five people need it, maybe 1,000. Hopefully, the fewest, but, nevertheless, the country gets access to the antibiotic, that’s the subscription, and the company gets steady revenue, and there’s no pressure whatsoever to overmarket or to overuse the project in the meantime. That’s a live project, it’s a pilot being worked on in the Department of Health and Social Care and the – and NICE and National Health England. It couldn’t have happened without Dame Sally Davies’ leadership, for which we’re all grateful.

The United States has taken notice. There’s a bill in Congress now, co-sponsored by a Republic and a Democrat in Congress and in the US Senate. If you follow US politics, it’s rare these days to have a bipartisan consensus, but the PASTEUR Act takes essentially this English idea and develops a subscription model in the United States for antibiotics, as well. So, a lot of good things happening. We need good things happening because the problem is a glacier, the problem is important, and we must act, even if it’s not as a crisis at the exact moment, in the same way that COVID is. It’s the sort of thing that, if we let it get away from us, ourselves, our children and our grandchildren will call us to account.

Emma Ross

Thank you, Kevin. I do have a follow-up question for you, but, before that, I just wanted to remind the audience, please do submit your questions through the ‘Q&A’ function, and we’ll be getting to them shortly, so please bring it on. Kevin, I wanted to just ask you about this glacier versus tsunami thing, and it’s asking you to do a little predicting, maybe a little bit unfair, and I can ask others this, as well. But, with a tsunami, we’ve been – we’ve known a tsunami is coming at some point, a very acute situation, and we’ve been judged to be ill-prepared for that and disaster. With a glacier situation, how optimistic do you feel that we will do what’s needed to get ready for a glacier, or how do you see that we’re going to get the commitment we need on a glacier? Are you seeing signs that we are, that it’ll be sustainable? Are these just little steps that may, kind of, fade when we’ve got a lot of demands, economic demands, on recovery after COVID? Do you think this is a goer?

Kevin Outterson

You know, when you’re talking about things like bridge maintenance, or, you know, the Chunnel example, or keeping train tracks, you know, in a state of repair, or motorways, you don’t put that up to a – you know, a public opinion poll every month to make a decision whether you do that maintenance work. You need a commitment from government, understanding that this is a preparedness issue, this is an infrastructure issue, and it deserves the same, sort of, steady, continuous, sustainable investment that we give to other things that are in those categories. So, we can use public opinion to get to that point, but I don’t think that public or Politicians will sustain their intensity on this issue for decades, and so we have to build something that’s more robust than that.

The bacteria will sustain their activity for decades. I’m a little more worried about our attention span. So, that’s why, you know, the Action Fund, it’s interesting, there’s two primary goals. One is to bring these two to four antibiotics to market. The second goal is a structural, long-term, sustainable fix to the way that antibiotics are paid for, because that’s the sort of long-term solution that’s required.

Emma Ross

And for your CARB-X graduates, is the Action Fund the home for all of them, or – and where are they going afterwards?

Kevin Outterson

Our scope is a little broader, we also include prevention and diagnostics, and the Action Fund is really focusing on therapeutics. There’s still a market for the – you know, for the thera – for the diagnostics and for prevention for vaccines, and so, you know, the Action Fund is focusing where the market is most damaged. And so, certainly, we hope that the presence of the Action Fund will mean that CARB-X graduates, and obviously they can look at companies that have never been affiliated with CARB-X as well, we’re non-profit either way, so we have no economic stake in it. But it’s hopeful that many of those will find a home in the Action Fund, and it’s interesting that two of the companies that are working now with GARDP in later stages, in clinical stages, also are companies that we have supported in preclinical stages, in some cases with different projects. So, you know, we have an interesting ecosystem in which CARB-X is doing some really work, really built on the foundation of all the basic funding done at universities, through Medical Research Councils, and NIH, and folks like that. And we now have some structures being developed for the clinical phases, and what’s needed is a reform to the way that societies pay for the antibiotics. We get that piece into place and I’m very optimistic.

Emma Ross

Okay and that’s a good note. Jim, can I ask you now to reflect on this and add anything to this discussion, your perspective…

Jim O’Neill

Hmmm hmm.

Emma Ross

…having heard, as well as put it in the context of the review?

Jim O’Neill

Thank you, Emma. Let me try to be brief, so there’s more time for questions for everybody, ‘cause I know many have a hard stop at 1:00. So, first of all, I want to just, from my perspective, tell all the corporate members here what a real privileged treat they have got, having Laura, Thomas, and Kevin on here, because I know a lot of people, around this space, even though I don’t know anything about it, and these are three of the people that are right at the cutting edge of this dilemma about new drug supply. So, it was a pleasure for me to listen to them all, and I deliberately asked Emma that I could go last rather than first, and so I want to emphasise that.

Second thing to say is, as hopefully you all know as well, in my role as Chair, I am a major driver or nagger of the House to be a leader in what I call profit with purpose, about business going forward, and I think, particularly in a post-COVID world, business needs to evolve even more to understand its broader licence to operate than just profit. And linked to what I just said about the three of them, you heard specifically from Laura and Kevin that they are not for profit and, very interestingly, Thomas made it rather clear that the one billion fund that he’s pioneered and driven is one that’s not expected, by other participants, to get money back. And I will congratulate Thomas again here, in front of this audience, that, yes, indeed, I nagged and rudely irritated him in front of many others for quite a few years, and it’s – it is very good that the industry has shown some response.

And as Thomas himself emphasised in particular, in order to solve the supply part of the problem, we do need what Kevin talked about with the UK initiative and the PASTEUR initiative to be real. And I am particularly intrigued by this PASTEUR Act that Kevin briefly talked about, because, from what I understand of the magnitudes there, the UK is not sufficiently large enough for this to matter on a global basis, from what I can see, to get pharmaceutical companies to respond. But I think, given the size of the US and the monies that I understand, partly directly from Kevin, this could be a very important development.

And, in that regard, I do find myself slightly more hopeful than I would have been a year or two ago, and, jumping to what I was going to say as my last point, I was very fearful that COVID and everything that goes with it would completely diminish the focus on antimicrobial resistance, but it clearly, as evidenced by what you’ve heard here, it has not. And I love Kevin’s glacier versus tsunami, I’m going to steal that off you, Kevin, I’m afraid, and so, I will credit it with you when I do – if I do write something about it. I think it’s a perfect analogy for what ultimately will be, as Laura made clear, and it seems to me the numbers sadly are going this way, it will definitely be, if we don’t solve this, something that is going to kill a lot more people than COVID-19.

The only other thing I would like to emphasise for now is that – as often, when there’s any discussion about antimicrobial resistance, virtually the whole focus is about new antibiotics as a – I’m taking for granted that a number of listeners or viewers are aware of this, but, alongside the 29 recommendations our final written report made in what was May 2016, they covered ten broad areas, which I rather perhaps, in the minds of some, churlishly, occasionally, describe as the Ten Commandments of AMR, getting market entry rewards and therefore unlocking the incentives for Big Pharma to take these early stage initiatives and ‘valley of death’ initiatives to market is one of those. And it is very important and for me to emphasise again here the permanent solution, which, in itself, makes it even more tricky for pharmaceutical companies, is for us to permanently reduce the demand for these things and as I’ve often said, we need to stop treating them like sweets, or, to American audience, like candy. And, in that regard, let me just finish quickly because I think it’s very good that Kevin’s Barder initiative is focused on diagnostics ‘cause I continue to believe the role of diagnostics in helping diminish the unnecessary use of antibiotics is huge.

And linked to one of the questions I saw in the chat earlier, to my slight surprise, in the developed world, there has been some progress in agricultural usage. When we finished our review and made our recommendations, I would have not have believed, four and a half years ago, what I’m about to say. But, in the US, there has been a reduction in the amount of usage of antibiotics for feeding animals, and the UK has made significant process. And what is particularly interesting, and maybe it’s, again, in a profit with purpose context, I know, because of my strange role in all of this, that the major supermarket chains that are present in the UK, which includes American ones, are actively working on their own initiative to progress this further, as they obviously find some commercial or broader reason to position themselves as being responsible about this issue with their customers.

So, there are some encouraging signs. I don’t want to give the wrong impression that this is anything like job done, because, as evidenced in a piece I just received coincidentally over the weekend, published in Prospects in the States by Sam – authored by Sameer Kadri and Helen Boucher, talking about the number of people that die from AMR in the States, and they revi – it refers to CDC numbers published in 2013, which, at the time, and we used this in our reviews, are 23,000 a year, just in the US, that is now estimated, in November 2019, at being just under 36,000. But as I hadn’t realised at the time, but I checked with Kevin before it was known to others is that, actually, looking back, the number then was 44,000, and that almost definitely means, given the quality of data analysis in the United States, the 700,000 number that we used as our base globally was almost definitely significantly in excess of one million people a year. And, in that regard, it is definitely comparable to the tsunami of COVID, and we need to – just as in climate change, there has been some response to things like the slow creep of melting glaciers, we need to do the same in this space, and I’ll stop there.

Emma Ross

Okay, thank you, Jim. I’m going to open it up to audience Q&A now. Just as a reminder, if you put your question in the Q&A, I will see if you would like to speak your question, request the microphone, to give you the option of asking it yourself. I’m going to go to the most upvoted question first, and that’s from Robert Yates. Rob, please indicate whether you would like to take the microphone, it’s yours if you’d like it, to ask the question that you’ve written in.

Robert Yates

Yes, please, I’d be delighted to, and thank you very much, Emma, and thanks to the wonderful panel, I’ve learnt so much this morning. I’d like to ask about the role of the state. You know, we’ve been talking a lot about the role of the private sector and academia, but the role of state and policymakers, you know, how vital is – it is we get this on the radar of policymakers. So, what specifically would be the ask of, say, an incoming policymaker, say the – you know, the elevator pitched to an incoming President Biden about what – you know, what should be the one, two, three that he should do, and how do you think that we can raise our game in getting more political champions? They’re pretty rare. I mean, David Cameron was, but, at that level, there are very few Politicians really interested in this. So, tactically, how do we do better at getting the Politicians involved?

Kevin Outterson

I suggest we take Dame Sally and clone her as quickly as possible, in as many company – countries as possible. If every G20 country had Dame Sally running about, I think we’d be…

Jim O’Neill

They’d be petrified.

Kevin Outterson

Yes, they’d be petrified, but we’d get something done.

Professor Laura Piddock

So, recently, several of us had a letter published in a national newspaper in the UK, in The Telegraph, requesting that there should be a Minister for antibiotic resistance, or actually called it Antimicrobial Resistance, made it slightly broader, within the UK. But, again, within other countries, as well, because, if there was somebody with this as a portfolio, then this would keep this on the political agenda for the future, so we wouldn’t need to clone Dame Sally.

Jim O’Neill

So, quickly, Emma, one of the saddest consequences of the never-ending nonsense of British politics inside the Conservative Party is exactly this. David Cameron, in his poor judgment about holding a referendum, and he – and I occasionally still talk to him about it, has still no idea that the momentum with him being a G7 leader at the G20 table that gave, and it’s a serious issue, much more broadly, about aspects of British governance and our voice in international affairs that a lot of leaders of other countries are still rather confused and shocked as to why, four years later, not only have we decided to leave the EU, but why this very powerful voice we had about antimicrobial resistance has just suddenly gone.

And I spend quite a bit of time, and have been doing hopefully with some consequences, over the past three months talking to Treasury officials about it again, in a way that they have not wanted to do in the interim period before that. But we – to go to the first part of Rob’s question, the ask would be to make sure that this PASTEUR Act that Kevin touched on gets through Congress, because, at least for the supply of new antibiotics, from what I understand, I’m not sure Kevin would even describe it as a complete gamechanger, but it feels to me, you know, in that ballpark. Thomas would probably have a big view on it, too.

Thomas Cueni

If I may, Emma?

Emma Ross

Go ahead, Thomas.

Thomas Cueni

I basically want to address three asks. One is, I think it would really be important, the UK has an opportunity, you are hosting G7 next year, this should be top of the health list, because it’s something where you need momentum and, in slight, you know, nuance from Kevin’s praise for the UK pilot, I’ve said publicly that, if you ask York University and NICE to give a proper value to a novel antibiotic, you’re more likely to err on the conservative side than really to come up with the incentives you need, which means you really need incentives and something [inaudible – 49:49] not just from the UK, but other countries. But the second element, which is often forgotten is, you also need to give a proper value for quality, mature antibiotics.

When you look at the BBC documentary, I think it was last year, Vets are expensive, antibiotics are cheap, it was about use or abuse of antibiotics in industrial agriculture in China, it hit the mark. We really need to also be concerned about sustainable supply of mature, quality generic antibiotics. And, last but not least, I think this is a bit of Sisyphus. G20 Agriculture Ministers in 2018 agreed unanimously to forego or ban the use of antibiotics for gross stimulation in indus livestock and, by 2019, they’d gone back on that, and, if I’m not mistaken, the three main drivers for reversing the decision were countries with no interest in agriculture, such as Argentina, Brazil, and the US and, honestly, that’s a bit embarrassing.

Emma Ross

Laura, is there anything you wanted to add to that before we move onto the next question?

Professor Laura Piddock

Well, responding to anim – use of antibiotics in animals produced for food, the WHO had an expert group meeting in the late 1990s, and that resulted in the EU banning the use of antibiotics for growth promotion in animals in 2004, and this had a big impact. At that meeting in Geneva in the late 90s, there were numerous other countries, including the USA, China, and various others, and there was a will to do this. Unfortunately, the way that animals are reared for food production in different countries is not the same, and so what works in certain European countries has not been transferrable to these other countries, and, quite simply, antibiotics are used as a substitute for poor hygiene, and it’s an animal welfare issue. And so, this still needs to be tackled, but possibly in a different way to the way we originally thought in the 90s. Simply taking these drugs away may well end up making the food chain more expensive, and there are a lot of implications here.

Intellectually, personally, I believe we shouldn’t be using the same chemical classes of antibiotics in animals and people, and I think, if we could move towards that, that would be a big move, because we know that certain types of drugs used in animals are very different to those used in people, and they have very little impact on antibiotic resistance infections in people. So, we need to make a – start being a bit more precise over what we want to stop in that sector.

Emma Ross

Okay, thank you very much. I’m going to go to a question now from Stella Howell, and her microphone’s not working, so I’m going to read it out. It’s also been upvoted, and this is for you, Laura. She’s asking if you could please elaborate on what you mean that COVID virus causes a single infection. What is a single infection?

Professor Laura Piddock

Okay, so, perhaps a better word would be, say, a single disease. So, it’s a – one virus, one disease. When we talk about antibiotic resistance, there are lots of different types of bacteria, and so it’s not one cause, one disease, so that’s the big difference. So, scientifically and intellectually, it’s easier to tackle something that is just of a single cause. With antibiotic resistance, there are many different types of infections or diseases.

Emma Ross

So much more complex to tackle.

Professor Laura Piddock

Yes.

Emma Ross

Okay, thank you. I think, hopefully, that’ll be okay for you, Stella. The next question is from Adam Zerda. Adam, would you like to answer your question live? Ask…

Adam Zerda

Sure, thank you, and hopefully you can hear me. I’ll keep it brief, since I know we’re getting close to end of time, but one of the clear lessons from the COVID pandemic has been just the importance of prevention and diagnosis. All of the focus now is on vaccines to try to keep us as safe as possible and, in the meantime, we’ve been focusing on testing and isolating and preventing the spread of the disease amongst those who have it. Do you see the role of vaccines and diagnostics as a result becoming more of a focus when it comes to drug-resistant infections, so that we contain and prevent the spread of some of these resistant infections, rather than simply focusing, or entirely focusing on restocking the armoury, as I put it in the question? Thank you.

Jim O’Neill

And I’m happy to start briefly on that. I hope so, Adam. I mean, I – as I said, you know, new drugs is just one of the ten areas we focused on and I think were broadly brought in, so you have a whole load of supply interventions and a whole host of demand reducing interventions. And, in that regard, actually, the washing hands was, in the sense, you know, as everybody here knows, one of Sally Davies’ great things is – was the whole notion of washing your hands in warm, soapy water to Happy Birthday twice became embedded in one of our recommendations, which is better hygiene. And, as Rob Yates knows so well from his own initiatives on these broader areas with the emerging countries, one hygiene being seriously adopted in the likes of India and across Africa having enormous impact on reducing so many aspects about the demand for this stuff. And I’ve – as I’ve already said, and here, you know, I find myself in this, sort of, spirit of never letting a crisis to go waste. The whole role of technology and data that’s been escalated by this crisis, I’d, sort of, almost intellectually take for granted will accelerate the role of diagnostics across the board in the health industry, and it – that is hugely important in the battle of fighting AMR.

Professor Laura Piddock

If I…

Emma Ross

Thank you.

Professor Laura Piddock

…could jump in.

Emma Ross

Oh, go ahead. Go ahead.

Professor Laura Piddock

Just to say that certain programmes are co-developing antibiotics with a diagnostic. So, gonorrhoea as an example of that, find are leading the development of a rapid test to diagnose gonorrhoea, drug-resistant gonorrhoea, indeed, and so then you would know whether you need to use a new drug that’s developed to tackle that infection, or if the infection is actually susceptible to old antibiotics and you could use those. Clearly, one of the key things we still want for community or GPs, or even the individual over-the-counter, is a rapid test to even tell you if your cough, cold, earache is even of bacterial cause, because, if it’s not, if it’s a virus, an antibiotic will not work. And that’s really important to remember with COVID because pretty much every patient worldwide who’s gone into hospital with COVID has been given an antibiotic, sometimes several, as soon as they’ve gone in the hospital, and we don’t know how big a role that’s had in actually reducing the impact of COVID. We all think it’s horrific at the moment, but perhaps without the widespread use of antibiotics, it could have been even worse.

Emma Ross

Thank you. I was really hoping to get through all the questions, but, unfortunately, we are a minute and a half away from closing, and, as we’ve got a hard stop because of their commitments after that, I’m afraid we’re going to have to wrap it up. So, thank you all for joining us, and thank you all of you speakers for all the great information and fabulous conversation back and forth, actually, and for the audience for joining us, and I’m sorry we didn’t get to the last few questions. But hopefully, that’s been informative for you, and thank you all, and have a great rest of the day.

Jim O’Neill

Let me say again…

Thomas Cueni

Thanks a lot.

Jim O’Neill

…Laura, Thomas…

Thomas Cueni

Bye.

Jim O’Neill

…and Kevin, thank you so much for joining us.

Thomas Cueni

Yeah.

Emma Ross

Thank you.

Professor Laura Piddock

Thank you.

Thomas Cueni

Thank you.

Professor Laura Piddock

Goodbye.

Emma Ross

Bye.

Thomas Cueni

Bye.