CARB-X: Accelerating Global Antibacterial Innovation to Combat Resistance

CARB-X: Accelerating Global Antibacterial Innovation to Combat Resistance

CARB-X: Accelerating Global Antibacterial Innovation to Combat Resistance

Caroline Duell, Director Media & Communications, MTPConnect
Andrew Bowskill, Director Stakeholder Engagement Queensland, MTPConnect

Guest: Richard Alm, PhD, Chief Scientific Officer, CARB-X

00:02  Richard Alm
So upfront, I mean, I’ll say that CARB-X would love to have been accelerated in Australia supporting obviously the Australian ecosystem but also, you know, the Western Pacific as well, because I think there are things going on in New Zealand that we don’t hear about enough. And so I do think an accelerator in this area, you know, geographically this area would be, you know, exceptionally beneficial both to us and CARB-X, but also to the, you know, the greater ecosystem within Australia.

00:45  Caroline Duell
Hello and welcome to the MTPConnect podcast. I’m Caroline Duell, our guest on today’s podcast is Richard Alm. He’s the scientific officer at CARB-X, the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator, which is based at Boston University. CARB-X is a global nonprofit partnership focused on supporting antibacterial research. Richard joined CARB-X following almost 20 years working in drug discovery in large pharmaceutical infection R&D teams and spending some time at a small, antibacterial biotech company. He obtained his Ph.D. in microbiology from the University of Adelaide, and prior to joining industry he held two postdoc positions in the AMR area, one in Australia and one in Canada. It’s a great pleasure to welcome you to the podcast, Richard.

01:35  Richard Alm
Thank you. So happy to be here.

01:38  Caroline Duell
My co-host today is Andrew Bowskill. He’s MTPConnect’s Director of Stakeholder Engagement for Queensland and co-chair of AAMRNET Australia’s Antimicrobial Resistance Network. Hi, Andrew.

01:51  Andrew Bowskill
Hi, Caroline.

01:52  Caroline Duell
Okay, so Richard, you’re originally from Adelaide. Welcome home. What brings you back to Australia for this trip.

02:00  Richard Alm
Yeah. So it’s actually an interesting story. I think that’s one of the positives from out of COVID I guess is the ability to work remotely. And I came back after obviously not being out of travel for two years. I came back for the Lorneinfection meeting in February and presented at that and actually caught up with some people I had used to work with I knew that were happy to see me in person and then spent a couple of weeks. My family’s all still in Adelaide and then when I went back I was given the opportunity from the CARB-X management, whether I wanted to work remotely from Australia for a couple of months and do some outreach as our new funding was coming. And so I came back in May for a little surprise visit to test whether I could function at three in the morning, because obviously the time difference is hot. So I came home for a surprise visit for Mother’s Day, and then came, I guess, early July, and I’ll be here for a couple of months.

03:01  Caroline Duell
Oh, that’s great. Great news. And well, tell us more about CARB-X and how the organization that you’re working for came about and how did you end up there?  It’s a long way from Adelaide.

03:14  Richard Alm
It is. So I am. So first of all, CARB-X. So CARB-X was founded in 2016. It came out of really President Obama’s executive order around combating antibiotic resistant bacteria. And so the order was to make an accelerator and it was competitively bid. And the BU team, led by Kevin Outterson, won the grant from BARDA, which is from the Department of Health and Human Services in the US government, and then raised money from Wellcome Trust. And then three other partners joined shortly after, the governments of Germany and the UK, as well as the Bill and Melinda Gates Foundation. So we have five funders and the initial investment was for five years. So that went through to sort of like 2021 and we’ve just been renewed. So BARDA has just put in another 300 million over ten years and Wellcome Trust has put in, I think 70 million over three. So that’s good news. And so yeah, CARB-X is a very unique model. Uh, funds early, early-stage product development from sort of hit to lead through to first time in human clinical trial on a completely non-dilutive basis. And I’ve been in Boston, based in Boston now for I guess 26 years. So originally I did my PhD in Adelaide and then went to University of Victoria in Canada to my first postdoc with a with an expat Australian who’s chair of the department there he was out of Melbourne and then I came back to the IMB in Queensland to do a second postdoc for three years. And during that time the professor that I was with in Victoria, Trevor Trust, he had been funded by Aster at the time and he got asked to set up a research satellite in Massachusetts. And so he invited me back and that was in 96. And so I said I’d go back for a couple of years and I’m still there. I worked for AstraZeneca for almost 20 years in various roles and responsibilities from early target ID through to support of clinical products. And then when infection sort of ended at AstraZeneca, that was 2015. They exited out of the space and spun out Entasis Therapeutics. I actually went to a small startup company then called Macrolide Pharmaceuticals, where we were just four people at the start. So that was kind of exciting, completely different to having the infrastructure of the Big Pharma. But during that time I was the principal investigator on our CARB-X grant. And so then when that company pivoted away from infection, as a lot of companies unfortunately are doing, it was a chemistry based platform company. They pivoted to awards rare diseases. I reached out to some colleagues that I had known from AstraZeneca that were at CARB-X to see what opportunities were there. And I joined CARB-X then in 2019. So I’ve been there ever since.

06:18  Caroline Duell
What a journey. And you talk about that many companies are moving away from this type of research. So why the focus on AMR for CARB-X and what are the particular challenges for antimicrobials that make an organization like CARB-X so necessary in this research space?

06:38  Richard Alm
Overall, I mean, developing a drug in any therapeutic area is expensive. Developing an antibacterial drug as a therapeutic is equally as expensive, but it’s got some unique challenges to it. One is that you can spend all this time and, you know, estimates are up to $1.3 billion to get a drug from, you know, a compound from the start all the way through to registration. You spend all this money, you know, developing a drug through face to face through clinical trials. And then at the end of it, if it’s approved, the doctors and the regulators say that’s really good. But then the doctors say, well, we want to keep that until we really need it. And so then there’s no revenue for it. And so you spend all this money developing this drug and then it’s put on the shelf until the doctors really need it. And so there’s no income. I think some of the other challenges are when you do the clinical trials, most clinical trials are done as a noninferiority. And so you go against, you know, the standard of care or best available therapy. And so you’re looking for a noninferior. So, you know, worse than that. And so you actually don’t get a claim typically of superiority. And so then the perception I think is, well, you know, I can take a $5 generic or I can take your branded drug, why wouldn’t I take the $5 generic? And so I think the non-inferiority status of how you develop a drug is challenging. And I think then the third dagger, if you like, is that most antibiotics are only taken for 7 to 10 days typically because then the infection is either cleared or the patient has succumbed. And so you don’t have that lifelong your return visits, if you like, if you like, if you’re on a cholesterol or blood pressure medication, you have repeat you have the repeat customer usage concept, whereas with antibacterials you don’t even though a good antibacterial can extend your life by, you know, up to seven years, if you get an infection, a bad infection as a child that’s usually done in the first 7 to 10 days. And then you don’t think about it again. So I think all those challenges together make the profit margins very, very difficult, which is why a lot of countries and I know Australia is also looking at this and looking at pull incentives as well as push incentives. And so CARB-X is an example of a push incentive where governments are giving money and organizations are giving money to increase the amount of pre-clinical work that is ongoing to make sure that there’s a pipeline of products that can be developed and are innovative enough to get around the emerging resistance. But then there’s also a need to fix the other end. And that is, you know, big company, you know, you need big companies to or some big organizations to actually develop the drugs through the expensive phase two and phase three trials and then commercialize them. And I think the way to do that is some sort of reimbursement or, you know, pull incentive. And so different ones are being trialed. And I know Australia is looking at some of the different options there as well, which is great. I think Sweden and the UK have got pilots going and hopefully the PASTEUR Act in in the US will get approved by Congress and that will, you know, put in some sort of strength to the ecosystem so that companies will come back and reinvest in the development of antibacterials because I think they need needed.

10:00  Caroline Duell
CARB-X is an accelerator. Can you tell us how that model works in this marketplace?

10:05  Richard Alm
I’ve never seen a funding model quite like this. So we as in CARB-X, it’s a competitive grant based organization. So we when we have a funding round, the fund has set a size and scope of the funding round. And then we call for applications from all around the world. And it’s a competitive application process. To give you an idea, since 2016, we’ve had I think 1163 applications and funded 90 to 92 projects. So that’s around 8% or something. So it’s quite difficult. I think the good thing that I’m actually proud of at CARB-X, is that even if programs get through to the later stages of the application and don’t get funded, we still provide them with expert feedback from our you know, suite of advisors to help them improve their project. So even if they don’t get funded, they still get, you know, really good feedback on, you know, this is not only what would have helped you in this application, but this is what would help you in your project going forward. So hopefully they can still take that project forward and reapply. And we have had companies come back, reapply and then get funded. So that sort of supports that that notion works. So then once a company is contracted with us, we set up a series of negotiation rounds where we will negotiate a statement of work and we build a what we call a support team around them. Some of the companies we fund, a lot of them are very small, you know, less than ten people, some of them. And so they don’t have all of the expertise and all of the disciplines that they need to take a, you know, compound from hit to lead through to phase one. They don’t have the clinical or the regulatory expertise. And so what CARB-X has done is assembled a panel, if you like, a group of experts in the different areas that we fund. And we will bring those experts to bear. And they will sit on these support teams and work with the companies on a regular basis to add that scientific support around them. So we obviously give them non-dilutive funding, but we also give them a lot of, you know, technical and business development expertise as well as they try and build their company.

12:28  Caroline Duell
I understand, is over $300 million of funding invested into these projects that you’re working with at the moment. That’s a huge boost to the sector all around the world. It takes a lot of money to get an early stage project or a startup company, you know, sort of phase one, really. How much investment is required for these projects?

12:55  Richard Alm
Yes, that’s an interesting question about how much it costs. And obviously, there are some nuances there. CARB-X funds, therapeutics, preventatives and diagnostics. So depending on what pillar you’re of, that of what modality you’re in will have different costs. And also depends where you start. I will also say that, you know, some of the modalities we support like bacteriophages don’t have to do as much toxicology as a small molecule. And so those costs aside, so there’ll be a range of costs. But I would say for your average therapeutic program, if you are if you’re if you’re a company or your organization has multiple assets where some of the infrastructure can be deployed and costed against, you know, different assets, probably 25 to 30 million would probably be the minimum to get you through to, you know, phase 1, first time in human evaluation involved is, that that will depend on how strong your pharmacology package is or whether you pick up any toxicological signals in preclinical studies that you need to then follow up and do you know, more rigorous, tough studies before you progress. But that’s about how much it costs.

14:08  Caroline Duell
You just mentioned phages, and I know this is an interesting area of research around bacterial resistance. Can you just sort of, I guess, explain why antibacterial resistance is such a challenge at the moment?

14:25  Richard Alm
I mean, people have been talking about antimicrobial bacterial resistance for a long time. I think what some of the most pivotal data has come out earlier this year where the large Gram study from IMPE was done actually looked at the burden of attributable mortality to just the resistant part of antimicrobial resistance not just not from bacteria infections but from the resistant infections. I think the numbers like globally, it was like 1.27 million people died due to that were directly attributable to resistant bacterial infections. If you look at those that are associated, you know, associated with bacterial infections, with resistant bacteria infections, the number is almost 5 million. And that’s what they couldn’t attribute it, but it was associated. And that’s the equivalent of, you know, like a jumbo jet crashing every 37 minutes or something, you know, for a year, which, you know, if that was happening, people would pay attention. And yet I think a lot of attention because unlike COVID, which was a very rapid pandemic and very acute antimicrobial drug resistance is a slower moving pandemic. And it’s coming. And a lot of the last resort drugs are now resistances against those. And it’s going to get to a stage, unfortunately, if we’re not careful where simple surgeries, you know, hip replacements, you know, things like that are going to suddenly become, you know, a death sentence. Because if you get an infection, there’ll be nothing to treat it. And so simple surgeries, cancer treatments, all of those things and all those procedures, where we take the presence of an antibiotic for granted, are someday going to become a challenge as the resistance gets worse. And I think as especially in the Gram-negative bacteria as some of the resistance mechanisms have become so widespread, people have either resorted to colistin, which is a very old nephrotoxic drug, that people are still working out how to dose appropriately. It doesn’t get to all body sites as a last resort because that’s the only thing that most things are sensitive to. And now there’s resistance to colistin that is circulating through several mechanisms. And so people have been going back to your question about bacteriophages, the use of bacteriophages has been around for quite a while, mostly in Eastern Europe. I think it’s been picked up again by Western countries. And there’s a lot of activity now about treatment of severe infections with bacteriophage or bacteriophage cocktails, either empirically or personalized, where they will take an individual patient’s infecting bacteria and screen it against panels of bacteriophage and say, this bacteriophage will kill your bacteria. So we’ll dose you with that. And there’s been, you know, a lot of individual case reports where that has been successful. And I think the choice that infectious disease doctors have now is do we do we continue with it on this patient by patient basis or is there potential to move bacteriophage therapy into more of an empiric treatment regimen where you can use a cocktail against a certain pathogen and give it empirically without having to screen against individual patients, you know, isolates. And so I think the field, the bacteriophage therapy field is still working out where best to place it. You know, do you do it in combination with antibiotics? What’s the cadence of dosing? And some of those questions, I think, need to be answered in a randomized clinical trial format where you can robustly ask those clinical research questions. It’s very hard to get those answers when you’re doing one patient at a time. And each patient is very, you know, different. And so there are companies now that are doing, you know, randomized trials with bacteriophage. And I think some of that data will be, you know, will be very useful in directing the field as to where exactly is the best place for these phages to fit into the armamentarium of the infectious disease doctor? I have no doubt they will. The question is, where will they be best deployed?

18:42  Caroline Duell
So there is so many efforts and levels of research involved in this challenge of tackling anti-bacterial resistance. And you are working with a number of these projects, do you feel like you’re really working against the clock here?

19:01  Richard Alm
I do. In many regards. It takes a long time to develop a drug. I think it can take years and then it you know, a project can fall over for reasons that you don’t even predict. I mean, most people think it’s either not going to work or it’s not going to be safe. But there are other reasons that you know, projects can fall over and some of them, unfortunately, aren’t even for science. Some of them are for business reasons. The company might pull out and then try and re-license the asset to someone else and you’ve got to then spend the time to try and, you know, package the data up and find a buyer. So there’s a lot of things that can happen and go wrong between starting a project and getting it even into phase one, which is where CARB-X funds into so as you see all these, you know, rising levels of resistance, you do feel like you’re racing against the clock because it’s only getting worse, it’s not going to get better. And stewardship and infection control that hospitals are putting in place are slowing it down. And they should, you know, continue those policies because they make a huge difference. But, you know, little things like educating the public when and how to take antibiotics is also really important. And that’s all part of stewardship to try and slow down because it is inevitable. Bacteria replicate really frequently. And so evolution takes over and resistance occurs.

20:31  Andrew Bowskill
So you mentioned that CARB-X is a supporter of early stage projects and you’re one of the only financial supporters of those projects. And I’m just wondering, and a lot of those projects, as you called out earlier as well, come from really small organizations or even researchers, and that is still within a medical research institute or in academia. How can they be sort of poached to in development and product development? And what sort of things do you look for in a project to support those researchers and those small companies?

21:11  Richard Alm
First of all, I shouldn’t underestimate the value of research that a lot of governments put in through their funding for basic research. Because basic research is vitally important. CARB-X is a little bit different in that we fund product development research. So we don’t fund basic research at all. And so when we look to fund a program, when the applications come in, we look for applications that have a vision of where they’re going and who, what patient population they want to treat and how they want to get there. And so I think one of the biggest shifts between a lot of academic groups and, you know, to do the basic research over to product development research is really that. And that would be my strongest advice would be if you want to pivot from, you know, from basic to applied research is really think about who do you want to treat and how are we going to treat them because those questions asked early help you frame and design your preclinical research such that you answer those key questions. I think a lot of academic groups and a lot of academic applications, we see that the basic science is there, but they have no idea how to apply that to a clinical development program. So certainly when we have funded academic groups, we have had a couple of grants in Australia with the University of Queensland and what we looked for there was the ability to take that basic science but also have a product development mindset to it. And we always look for, is there an exit strategy? So either the groups that we fund have to have an exit strategy. Is it to out-license the product to certain stage to a group that will continue to develop it, which means that the group that are doing the work initially have to have the mindset to do the right experiments and ask the right questions so that it’s attractive to be out licensed, or are they going to spin out a company and do they have the capacity and the business development expertise around them to do that? And in the case of the group at Queensland, obviously UniQuest has played a role in that in several examples and so that made their application, you know, stand out.

23:40  Andrew Bowskill
So if you are a researcher, if there’s a researcher listening to this and that in an MRI or in academia at the moment, would you think that there’s an advantage for them to spin out into a small company? And if so or not, what do you think are the key attributes of a successful spin out?

24:06  Richard Alm
I think the most successful thing you can get with a small company is the people. I think having worked in both large and small organizations, the smaller the organization, the more important the people are and the way the people interact with each other. And if you’ve got a company of thousands, you interact with your small teams, but not necessarily with everyone in the company. When you’ve got a small company, you interact with everyone. And so that that dynamic and that culture is really, really important. From a scientific standpoint I think if an academic researcher at an MRI as is looking to say, spin out a company, I think they obviously need to get a story down of how their program, their product or future product is going to impact, you know, the health systems and the patients because they’re going to have to go and pitch that and raise money and raising money in this space is is difficult. CARB-X works on a cost share basis so our grants at the moment, some of the existing grants are at a 90/10 contribution. So we’ve been CARB-X has been supplying 90% of preclinical research to 10% cost share from the companies. I think the funders have now moved that to 70/30, which is where it was before COVID. But I mean that’s still a huge boost to them to get 70% non-dilutive money. But you can still have to raise those other funds. And so you have to have a story that you can go out and speak to investors and convince them that your vision is worth them investing in. And a lot of the well, most of the, you know, VC firms that have extremely good due diligence and they know the systems and the ecosystem that they want to invest in. And so you have to have a clear vision and a clear path to get there to warrant these people putting in their money because they want a return on their investment. So I think clear strategy, start with the patient in mind because that’s ultimately where you’re going to get because the VCs are not going to fund basic research, they’re going to fund they want to get to an inflection point where the product can be further developed or or sold off and they can, you know, recoup money on their investment. And so you have to have a clear path towards commercialization.

26:42  Andrew Bowskill
CARB-X has a global accelerator network with various organizations around the world. I was wondering if you could please tell us a bit more about that network and how it works and what those accelerators provide?

26:56  Richard Alm
Yeah, so we have, we have I think now we have six or seven accelerators, some of them are very, very like specialized. Like we have one fund, the foundation for innovative new diagnostics that helps our diagnostics portfolio. And that’s all they do. They do diagnostics. And then we have say C-CAMP in India, which they are an accelerator that goes out in the ecosystem within India and actually sort of encourages and draws out some of the science that is going on in some of the institutes in India and makes them aware of CARB-X. And I will say that since C-CAMP came on board the quality and the number of applications in our funding rounds from Indian institutions has grown dramatically, both in number and in quality. And so I think having an accelerator in a region where, you know, this is what CARB-X is looking for, this is how you can make a competitive application. This is, you know, and coach those groups, especially that are coming out of academia, how to make compelling applications is a key role of a pre award accelerator. The other aspect where we use the accelerators is post award. Some of the accelerators have specific technical expertise that will you know, bring into these support teams. Some of them have good access to regulatory, you know, regulatory agencies in Europe and so they can help if your plan is to, you know, to go in and file in Europe, they can help set up and facilitate interactions with European regulators. And so beyond the you know, once you’ve been awarded a CARB-X grant, these accelerators can also help accelerate, hence the name, but then can also, you know, help further the progress of your program by bringing in expertise and opening up doors and facilitating interactions where a small company might find it difficult. And the accelerators can do that. And so I think of the accelerators as two halves, the ones that help potential applicants frame a better story to get funding, but then also support companies in their portfolio, in the CARB-X portfolio that have been funded. How they can accelerate that by opening doors and creating networks beyond that and both play an important role to make sure there’s a robust pipeline both in the ecosystem as a whole, but in the CARB-X portfolio. Yeah. Specifically.

29:40  Andrew Bowskill
Right. And so and currently there’s no AMR accelerator in Australia nor for that matter in the Western Pacific region. And so you’re aware of the work that AAMRNET has been doing while we’ve been exploring how we could establish AAMRNET as the AMR accelerator here. So it’s the sorts of things that we’ve been doing is engaging internationally, raising awareness about Australia’s capability and capacity and building on its reputation as a single contact point for AMR R&D here in Australia. And we’ve also collaborated with therapeutic innovation Australia on their pipeline accelerator voucher scheme. And thank you for your input and being part of that assessment process on that one. So we just announced the awardees yesterday I think along with TIS. So that’s really exciting. And we’ve also been working with the same team that you support at University of Queensland to hopefully bring the ICARe antimicrobial drug development course to Australia next year, hopefully. And what do you see as the next steps for AAMRNET to get established as Australia’s AMR accelerator and possibly be integrated into the CARB-X global network?

30:56  Richard Alm
So upfront, I mean I’ll say that CARB-X would love to have an accelerator in Australia supporting obviously the Australian ecosystem, but also, you know, the Western Pacific as well because I think there are things going on in New Zealand that we don’t hear about. So I do think an accelerator in this area, you know, geographically this area would be, you know, exceptionally beneficial both to us at CARB-X, but also to the, you know, the greater ecosystem within Australia. And we have two accelerators in our network, the DCIF in Germany as well as C-CAMP in India that are funded from local governments. I mean, I think it would be it would make sense for the Australian Government to understand and recognize the risks that AMR play for the Australian population and see the development of an accelerator as a real investment, not just to develop and encourage and formalize some of the AMR research that’s going on in Australia. And I will say that even in my short time back here a couple of times this year, I wasn’t aware of how much AMR research was going on in Australia. So it’s really pleasing to see and I’m in the AMR field and so for me to see how much there is here that I didn’t know about that needs to get exposed to the world. I mean Australia has, you know, a very good history of doing, you know, good medicinal research and to get that out in such a valuable field as AMR is important. And I think an accelerator would help do that and raise it to an international stage. From a CARB-X perspective, obviously having an accelerator here to understand what CARB-X is looking for, each of our funding rounds and knowing who to contact in all the different research centers and supporting them to put in applications. I mean, the CARB-X grants are fairly large. I think, you know, most of them are on our website, so I won’t put the numbers up, but people can go and look. I mean, but they are significant. And to be honest, even if the development of an accelerator, you know, got one or two of these research grants into Australian, you know, scientific research, that would be more than the cost of funding an accelerator for a decade. So from that point of view, it would be money well spent for the government to step up and put in money to establish a, you know, a bona fide accelerator. And I think the other benefit, you know, just talking now specifically within the CARB-X sphere, a lot of our companies, as you mentioned in the beginning, Bug Works is doing their phase one in Australia. Australia has a reputation for having phase one units that are very good and we’ve had several of our companies within the CARB-X portfolio come and do their trials in Australia, but that’s in the Post Award accelerator. That’s where, you know, if companies are now progressing towards that stage, the connections could be made and the benefits could be directly applied to those companies from members of an accelerator, and that would only help the ecosystem within the clinical research arms of Australia as well. So I think there are multiple benefits of having an accelerator. I think somehow to harness all of the work that’s going on. Australia’s a big country. I think. But there’s, you know, there’s stuff, there’s a lot of stuff going on over in Perth from Brisbane down to Victoria. I mean that’s a lot of geographical area to cover to try and harness all that knowledge and all that, you know, in a central facility, if you like, or a central part of knowledge would be very, very useful, not just for CARB-X grants, but there are other granting bodies, less demand non-dilutive, but there are other, you know, international granting bodies that will, you know, give grants as well. And so it wouldn’t have to you know, it wouldn’t obviously be tied just to supporting CARB-X. It would be able to help these groups get funding from, you know, a lot of other sources as well. But all I can say is we would love to welcome an Australian accelerator into our stable.

35:08  Andrew Bowskill
So great news. Thank you.

35:11  Caroline Duell
You mentioned companies coming to Australia to run their early clinical trials. Why is Australia such a good destination for this type of clinical trial program?

35:25  Richard Alm
Few reasons come to mind. One is obviously, I think the quality of the data that comes out and the access to, you know, rapid assembly of cohorts and then, you know, robust data is obviously what companies look for in terms of their timelines if companies are also fighting against the clock because, you know, the burn rate of finances for small companies is quite quick. So the quicker you can do a clinical trial and not have it drag on, the quicker you get your data. And to be honest, the end of phase one is a very good inflection point for infection companies because you’ve got that preclinical pharmacology, you’ve now got human exposure. If you’re above the know how, you can work out a therapeutic index. And then that’s a really good inflection point to then try and get additional funding to do phase two and three. So I think speed and quality of data is one. The Australian Government also gives a, you know, a tax incentive rebate, which I think a lot of companies, especially the smaller companies, find very attractive. I mean I hear even working in the US, the Australian, you know, phase one companies will do little webcasts and webinars over their advertising themselves. So it’s not just in the therapeutic area of infectious diseases, it’s, you know, it’s a lot of different therapy areas that companies are coming to Australia to do. The early clinical research.

36:47  Andrew Bowskill
You mentioned the CARB-X has supported a couple of projects in Australia already. You talked about the gang at UQIMB and Bug Works have set up an Adelaide’s. There’s also SpeeDx in Sydney. What do you think that Australia and Australian researchers can do to be even more successful when it comes to accessing CARB-X or any other international funding for that matter?

37:15  Richard Alm
So projects that we have funded here, I’ll take SpeeDx to start with. I mean their platform technology is excellent. You know, the program we’re funding is a gonorrhea and chlamydia diagnostic that also picks up resistance very quickly. Obviously the point of care diagnostics for STIs is really important just because of the patient population, you need that out so very quickly. Their technology was quite impressive and they had a path on how to turn their assay platform technology with another partner into a product. The Queensland group had a program when they first came to us that was looking at a product that could kill colistin resistant bacteria. We spoke about colistin earlier as colistin resistance is increasing in the Gram-negative bacteria, something that could kill colistin resistant bacteria is obviously really important because that resistance is only with the amount of usage that colistin is getting now, that resistance is going to spread. They also came in with a very unique proposal around low and low- and middle- income country capability building, which one of our funders, GAMRIF, which is the UK government arm of our funding, is particularly interested in in LMIC or low- and middle-income country applications. And so they fund studies or portions of programs that are directly applicable to LMICs. And so the Queensland group came in with a very unique way of trying to build capability built in, in some of the LMICs. And the UK Government liked that proposal and that was, that was their second, their second grant was to work around how you could use some of their molecules as potentially agents against colistin resistant bacteria with widely available drugs that are already on the market in LMICs and potentiate. So you can repurpose those and reuse them and make them active again. But also with that, they tied in some capability building to help the LMICs researchers understand their problem and how to do molecular epidemiology on site. And that’s now I think if you help but rather than do things for groups like that if you teach them how to do it and they can do it themselves, that brings a lot more value to the whole world really. And so there are two very different programs that we funded here in Australia. When the funders of CARB-X set the scope of the funding around, it’s fairly narrow and will be hopefully announcing our new funding round soon. You know, read those and then I would encourage people within Australia to if you have a program that fits that, you know, reach out to some of the companies within Australia or within the CARB-X portfolio and say, you know, what is it like? We have companies that learn from each other, we have company only webinars, meetings where we will bring out companies together so they can learn from each other. And so that’s a different type of network. But we’re all in this together. And ultimately, as even when I work for AstraZeneca, if your child or your mother gets sick, you don’t really care which company has made the drug that saves their life. I think we owe it to ourselves as a society to make sure that, you know, we help each other be successful. And I think especially in an area where such devastating infections can take the life of someone, we need to help each other. And so, you know, one other thing that we’ve been doing at CARB-X just in the last couple of years, we call them portfolio acceleration tools. If we see several companies dealing with the same issue, we bet we will actually sponsor an activity that brings in data that we can share with those companies, but also to the greater ecosystem. Because, you know, that’s part of what CARB-X is about, is making sure that patients get access to drugs. And if we support the companies that develop them or we support the ecosystem that can develop them outside of our funding, that’s equally important to society. You know, help get off my soapbox now. But I think that that’s really important. And too often companies like don’t share data and then, you know, it’s seen as a competitive advantage if another company has to spend years and years to, you know, go down the same path to find out that, you know, that’s a toxic molecule that’s going to cardiovascular toxic problem or whatever. Whereas we talked about earlier, we’re racing against the clock here. And if you can shave off a couple of years by sharing some data, publishing it, talking to people that are in the same field, you know, I think the time for that level of competitiveness in this field is gone. I think we need to work together. And so I would encourage any applicants in Australia to, you know, speak to the Queensland group or whatever and find out, you know, what they thought CARB-X, what, you know, what they put into their applications and yeah, come to us with the best app application you can generate with this is the patient population we want to treat and this is how we’re going to treat them. This is our vision.

43:07  Andrew Bowskill
It’s a really important point, I think. Yeah. I mean, collaboration is the key, certainly MTPConnect, we stand up there and say, you got to collaborate, you’re going to collaborate, right. And that the whole message of what are we doing this for in the first place? And that’s to ensure patients have access to the right.

43:27  Richard Alm
And I think that shouldn’t be forgotten. There’s the old saying it takes a village to raise a child? I think that’s where AMR research is now. And there’s so many big companies that got out of it. You know, so many little companies are doing the lion’s share of the work now. And they all would benefit from the knowledge. And, you know, the other thing with the big companies leaving the space is that you’re losing a lot of that institutional knowledge. And you mentioned, you know, the eyecare costs that you’re hoping to bring down here next year. I mean, I think part of that is to train the next generation of antimicrobial drug discoveries, because, you know, when old people like me stop, you know, if there’s no one to teach the next generation, then that’s going to have to be relearned. And unfortunately, we don’t have time to relearn how to make, you know, good antimicrobial drugs. And so the continuity of institutional knowledge of how to do it needs to be passed on.

44:31  Andrew Bowskill
And it’s a good segue to the next question, actually. It’s about young people and how can we get more young Australians involved in raising awareness around AMR?

44:44  Richard Alm
So interesting question said you mean young researchers so they research it or just young people in general to be aware of the risks of AMR?

44:55  Andrew Bowskill
I think that everyone needs to be more aware of the threat that AMR poses and in the future. I mean, if we’re running out of antibiotics and to think that someone can’t get chemotherapy or a hip replacement or whatever is, is just incredibly frightening to bear if you stop and think about it. But so yeah. So but yeah, I mean, obviously we need young researchers to get involved as well to try and overcome this. And it’s a village, as you say.

45:30  Richard Alm
I think in terms of general population, I think one of the most important things is the precision of communication. I think COVID has taught us that, you know, populations as a whole can understand scientific principles if they’re communicated fairly clearly. And, you know, unfortunately, COVID has been there’s been good examples and bad examples of that, of how to communicate. But I think if you ignore the bad examples and some of them were quite bad, there were several really good examples of how to talk to the global population, you know, within your country of this is what an infectious disease is, these are the risks, this is how to help. And I think that precision of communication, honest and transparent, is the best way to go. And I think that more and more drug resistant bacteria need to be included in that conversation just at a population level. I think the challenge there is, because it is unlike COVID, it doesn’t affect you so acutely. It’s easy to ignore and, you know, kick the can down the road and, you know, let the next administration worry about it because it’s not our problem. And so I think in terms of the general population, it’s all about you don’t need to put fear into it, but I think you need to be realistic and honest and precise in your communications. That’s for the general population. I think in terms of, you know, if there are researchers going on and you know, where they can choose their career, I mean, microbiology, I’m biased but microbiology is, I think, a fascinating career, working with things you can’t see and watching them evolve and change and adapt basically in real time is is fascinating. And so I think what I’d like to see, you know, some universities I know some are doing this and I applaud them for it is to blend that basic lecture series of microbiology into biotechnology. And how can you turn that basic knowledge into, you know, translate that into medical research? I think the more that you can, you know, not just go to the textbooks and say, learn this remotely, you know, and just, you know, memorize this, memorize this, but actually take that information and translate it and run biotechnology courses or bioengineering or whatever to show students at an early part of their career, maybe as a, you know, undergraduates as to this is how what you’re learning today can be applied, I think gives them a lot of focus and a lot of, you know, excitement about how they could make an impact. And so if you can encourage undergraduates to see how, you know, basic textbooks can really be translated into products, can help the population they will develop technologies that we can’t even think of yet. And so but they need to early on, I mean, when I went through undergraduate, it was, you know, you just learn about bacteria and that was it. It was only really when I ended my postdoc that I was lucky enough to get into industry and see how it’s not just your single discipline. I mean, all through my academic training, it was really just molecular microbiology and that was it. It was only when, you know, you get to a company and you see all these other disciplines, you know, the pharmacology and the biochemistry and the toxicology and how they can all come together and work together. And you have experts from all these different disciplines sitting in the room working on the same problem. Again, it comes back to that collaboration. You all have that singular focus of what can I do with my specific expertise to make this product move forward safely and effectively. That level of broadness in undergraduate would have been a huge advantage to me, rather than taking, you know, six or seven years to come across it. You know, I think for universities or early researchers now, students to get exposure to how other disciplines play a role and what you want to do and how you want to apply I think is important.

49:52  Andrew Bowskill
It’s exciting to think what’s possible in the future, that’s for sure. It really is as scary as AMR is and it’s exciting to think what solutions we can come up with, the new generation can come up with as well. So we can’t talk about anything and we have already a little bit without bringing up the impact of COVID 19 and how the pandemic tested our responsiveness and preparedness around the world to tackle a global crisis in a short term. How do you think the world is currently set to fight against AMR and how can we in Australia be more involved in the global effort?

50:29  Richard Alm
I mean watching it, it was surreal in the States for two years watching COVID evolve because as a microbiologist slash virologist, there was nothing that happened that was surprising. I mean, it was the spread of a, you know, respiratory viruses. It can’t be stopped. And so, you know, I think the speed at which some of the treatments and vaccines came online was breathtaking. Knowing how long it takes to develop those normally. And, you know, I’ve heard people say, well, why did it happen so quickly? It wasn’t done robustly, which is frankly completely untrue. I think one of the biggest things was that because there was money given to the companies that were developing it, you could run trials in parallel without waiting for that, you know. Do I reinvest? Look, let me look at the data. Do I reinvest? Because the money was there? You could do things much faster, which, you know, I’m not saying that that will happen in every case in the AMR, but certainly the availability of funds drives innovation. There’s no question about that. We saw that with COVID. I think as horrific as COVID has been, I think it’s also taught us about preparedness and hopefully put the world on notice that, you know, some of these things, you know, are going to happen again. And how do we prepare, I think with all the molecular testing capability that’s now been deployed around the world to low and middle income countries and to, you know, all different regional centers, I think to have that capacity now to pivot that towards AMR detection and AMR diagnostics would be incredibly useful for both from a surveillance as well as a, you know, just a diagnosis standpoint, but also from a surveillance aspect. If some of that molecular technology that testing can be pivoted towards AMR would be tremendously useful. So I’m hoping that that happens. I think, you know, Australia did really well early on in COVID. I mean I was obviously because my family’s here, I was watching it, I was really impressed at how coordinated Australia was compared to, you know, what was going on in the US at the time, which was, you know, not as coordinated. At some point you get that, you know, that pull of well at which point do you open up again? And I think every country struggled with that. But overall, I think the organization of Australia during COVID was exceptional. I mean, when you come in, you have the sign in QR codes and the contact tracing and the earlier, there was nothing of that in the States. And so, you know, Australia should be really proud I think, of how they handled it and you know, early on and set up those things. In terms of AMR pivoting to that, I think as I said earlier, there is a lot of AMR research going on in Australia. I think having that coordinated and put together to help, not just locally, you know, within Australia but also globally because we do live in a global world. I think that’s one thing COVID has definitely taught us is we’re all so interconnected that it’s not a one country problem. And I don’t think AMR is either. But I do think that the government needs to understand that access, all governments, not just the Australian Government, that access to good antimicrobials is what’s going to prevent an outbreak. And so if you have an outbreak and you don’t have a good antimicrobial, you may not be able to. I mean, the vaccines and stuff came for COVID in, you know, in 12 months they repurposed some antivirals very quickly. I don’t know whether if you had a drug resistant bacterial outbreak that was that widespread, that you could repurpose another drug because they’re already resistant to it. And so I think understanding that you need a consistent pipeline is one of the hardest things it seems to for people to comprehend that you have to prepare years in advance and you need that. You can’t just say, okay, there’s, you know, there’s 20 products in phase one to phase three now that are moving through. If we get three or four drugs out of that will be good because those drugs will you get resistance to those drugs fairly easily. And if you’ve got nothing to replace them, it takes it takes a decade to build that pipeline. And so that’s where CARB-X is really focused, is trying to make sure that there is a sustainable pipeline there with things going into clinical development on a regular basis so that we’re never caught out. And so I think the governments of the world to realize that having a pipeline is what’s important and not just, you know, a drug on the shelf today.

55:38  Andrew Bowskill
It’s a really interesting and unique challenge that AMR sort of poses for the world.

55:45  Caroline Duell
So, Richard, what’s next for CARB-X, given your newly announced funding? What’s the horizon looking like now?

55:51  Richard Alm
Yeah, so we were really proud to get to get the new BARDA Award, which was announced July 1st. I think that was $300 million commitment over ten years, which, you know, I think shows their commitment, you know, to a longer term horizon and Wellcome, which was our another one of our original funders. They came in with more funds as well. I think very shortly within the next few months, hopefully we’ll announce how the scope of our new funding rounds and then we start again with the applications. Some of the discussions we’ve had internally already is, where are the gaps in, you know, in the, the global portfolio as well as our portfolio? What, where are the real gaps? And I think anyone that follows this space can look fairly quickly and say, well, it would be good to have more oral drugs. I think a lot of the drugs are IV based. I think some of the oral drugs that are used commonly, the resistance is getting so high to those that they’re becoming less and less useful. And so to have some good oral drugs for some indications, especially for indications that could be treated out of the hospital. At the moment, if you get a drug-resistant bacteria, even for something as simple as a urinary tract infection, you have to go into hospital to get an I.V. drug. And because there is no oral alternative. And so then you’re now paying hospital costs and the burden on the health care system, you know, at a time when the bed may be better used for someone else, you’ve got someone in there with imminently what would be a treatable outpatient infection if you had an appropriate oral drug. And so I think, you know, there’s an area that I think, you know, I’d like to see more and more attention paid to, you know, getting some oral drugs obviously that hard. I’m not saying they’re easy to develop, but there are things like that that I think hopefully will be, you know, the focus going forward of trying to fill some of the gaps that are in both our pipeline and in the global preclinical pipeline.

58:07  Caroline Duell
Well, we’ll be watching with interest. Richard, thank you so much for joining us today. It’s been a fascinating conversation with you about the challenges of antibacterial research and the work of CARB-X. It’s great to have you back in Australia for a little while and we look forward to staying in touch.

58:25  Richard Alm
Yeah, thank you so much. It’s been lovely.