Host: Ethan Rhee
Guest: Su Chiang, PhD, Senior Alliance Manager, CARB-X
00:11 Ethan Rhee
Welcome to the first episode of season two of the Antibiotic Resistance Awareness podcast. I’m your Ethan Rhee. In season two, I hope to bring you more interviews from those who are directly involved with antibiotic resistance. Today’s episode, we will be interviewing Dr. Su Chiang, who is a senior alliance manager at a global nonprofit partnership that accelerates antibacterial products to address drug resistant bacteria. The organization is called CARB-X and it stands for combating antibiotic-resistant bacteria biopharmaceutical accelerator. I would like to welcome Dr. Chiang to the podcast. Hello, Dr. Chiang, thank you for taking time out of your busy schedule to join me on my podcast. Could you give us a brief introduction on your background and career?
00:54 Su Chiang
Yeah, absolutely. Hi, Ethan. Thank you very much for inviting me to your podcast. And thank you for spreading the word about antimicrobial resistance or AMR for short. It’s a very important problem, and I think it’s really important for everyone to know that each of us has a role to play. So thank you so much for doing this. So about me, I started my career with a bachelor’s degree in biochemistry followed by a PhD in molecular microbiology studying Vibrio cholerae. That’s the bacterium that causes cholera. I then did postdoctoral work on mycobacterium tuberculosis, which is the bacterium that causes tuberculosis, before moving into research roles that were away from the lab bench. Initially, I worked on a program funded by NIAID. That’s the National Institute of Allergy and Infectious Disease, that provided research and development resources to researchers across the United States. And then I worked in a university tech transfer office, helping academic researchers move their discoveries into product development and towards commercialization. And then in 2018, just over four years ago, I joined CARB-X at Boston University.
02:11 Ethan Rhee
When I was researching topics for my next podcast episodes, I came across various articles talking about how antibiotic companies were going bankrupt, and that there has been a steady decline in antibiotic discovery, as when I connected with CARB-X I wanted to learn more about why these antibiotic companies are facing these challenges. Could you explain how CARB-X fits into this scenario?
02:31 Su Chiang
Sure, I’d love to. First, there are a couple of points that I’d like to start with to help explain why it has been so difficult to make new antibiotics. Personally, I think most of us, I certainly did for you know, an embarrassingly substantial portion of my career, I think most of us take antibiotics for granted. They were the first wonder drugs, you took them and your bacterial infections were cured. Not that you got a little bit better, not that you lived a few months longer, but people were cured by antibiotics, and they would otherwise have died. Today, antibiotics enable modern medicine, risky procedures like chemotherapy, dialysis, and organ transplants are all much safer procedures because antibiotics are available. And we got used to this situation in the mid 20th century. And we’ve largely forgotten how bad it is when there are no effective antibiotics. So how do antibiotics stop working? Right? And to a first approximation, as soon as patients start taking new antibiotics, bacteria find ways to evolve and escape the activity of those drugs. That’s a natural process that the bacteria undergo to survive. Unfortunately, it means that our existing antibiotics are becoming less effective against bacteria, and we are not developing enough new antibiotics to replace those.
03:59 Ethan Rhee
So if new antibiotics must continually be made to address antibiotic resistance, why has there been a decline in antibiotic discovery?
04:06 Su Chiang
Well, first, funding is a huge problem. You may have heard the number quoted that on average it takes a billion US dollars and more than a decade for a company to develop a new antibiotic. Unfortunately, we as a society, globally, have been under investing for decades in antibacterial research. And as a result of that there’s much less money going into antibiotic R&D compared to for example, cancer. Second, once new antibiotics are approved by regulatory agencies, like the FDA, for example, doctors will reserve them, they’ll save these new antibiotics for situations in which older antibiotics don’t work. This is called stewardship and it’s essential for public health, because it helps to slow the spread of antibiotic resistance. The problem is, while it’s essential for public health, it’s financially disastrous for companies. With low sales volumes and payment policies that don’t reward the true value of antibiotics, it’s difficult for companies to recover the R&D costs that went into creating those new antibiotics. So companies in this area, they can and they do go out of business, even if they succeed in getting a new antibiotic approved. Now, there are efforts ongoing around the world to fix these broken economics of antibiotics. But until that gets done, we need to keep innovation and development going so that the pipeline isn’t empty. And that’s what CARB-X helps to do. So, as you mentioned, CARB-X is a nonprofit. It’s a global nonprofit. It’s based at Boston University. It was founded in 2016. And we have been funded by the US, the United Kingdom and the German governments, the Wellcome Trust, and the Bill and Melinda Gates Foundation. We believe we’re the world’s most scientifically diverse early development pipeline of antibacterial products. And our purpose is to get life-saving products for patients into the pipeline. We support product developers from anywhere in the world who are creating new drugs, new vaccines, rapid diagnostics, and other types of products that address antibiotic resistance. And we take a comprehensive approach, because while antibiotics cure bacterial infections, vaccines help prevent them, and the best infections are the ones that we never have. And as you may have discussed elsewhere in the podcast, as we learned during COVID rapid diagnostics are critical to help slow the spread of disease and rapid diagnostics would help doctors to test at a single medical appointment whether a patient has a bacterial infection, and if so, which antibiotics would be effective.
07:01 Ethan Rhee
I really find stewardship and access to be important and preserving new antibiotic discoveries. In my previous research and interviews, I found that antibiotic stewardship is an effort to gauge and improve how antibiotics are prescribed by clinicians and used by patients. The CDC website says that this is a critical way to effectively treat infections, protect patients from harms caused by unnecessary antibiotic use, and combat antibiotic resistance. Can we talk about that?
07:27 Su Chiang
Yeah, absolutely. This is very important. As mentioned earlier, stewardship means saving antibiotics for situations in which doctors are confident that they will work. And this is in order to slow the development of resistance. This means not using new antibiotics if older ones can cure the infection effectively. And it means using existing antibiotics only when appropriate. I think you’ve mentioned this before, that antibiotics don’t work against viral infections, so they should never be prescribed or used for viral infections. On the other hand, patients who need antibiotics should get them and that’s access. Unfortunately, all over the world, there are patients who are not getting the antibiotics that they need, particularly in low- and middle-income countries. And the goal that we have to achieve is to balance stewardship and access so that vital products are available to patients who need them anywhere in the world, while also slowing the spread of antibiotic resistance to preserve these drugs for future generations.
08:38 Ethan Rhee
So how does CARB-X support this? I see that you developed a Stewardship and Access Guide.
08:44 Su Chiang
Yes, CARB-X and our international partners developed a guide to help our product developers create their own stewardship and access plans so that when they get their antibacterial products to market they can achieve what we call access not excess, for these essential medicines. So an ideal stewardship and access plan must be developed. Or I should say, ideally, the stewardship and access plan should be developed when their product enters pivotal clinical development, meaning that it’s getting pretty close to regulatory approval. And the plan should outline how the company will ensure responsible stewardship and appropriate access in low- and middle-income countries.
09:27 Ethan Rhee
Okay, so as I understand it, companies funded by CARB-X have contractual stewardship and access obligations. So what happens if they can’t meet those obligations?
09:39 Su Chiang
Right. Well, we are all in this together. So responsibility for stewardship and access is shared by companies, governments, funders, industry, health professionals, patients, everybody. And if an individual company can’t meet its stewardship and access obligations, then the Wellcome Trust, which is one of our funders, has access rights that are modeled after the US by dual rights. And very roughly speaking, this means that the Wellcome Trust can step in to help ensure access in low- and middle-income countries, if a CARB-X funded company isn’t able to meet its stewardship and access obligations on its own.
10:25 Ethan Rhee
I see. I saw on your website that there’s quite a list of CARB-X graduates, how are they doing after graduating from the program?
10:33 Su Chiang
We’re very excited that many of our graduated programs continue to progress towards commercial launch. And in fact, two diagnostic products that we supported are now on the market in Europe and seeking FDA approval for the US market. And these are from T2 Biosystems, and from Specific Diagnostics. Specific Diagnostics, which was a private US company, was actually acquired in 2022 bybioMérieux, which is a global leader in in vitro diagnostics. And that was super exciting for us. On the therapeutic side, I’ll just briefly mention two products that are currently in advanced clinical development, post CARB-X. The first is a product called VE303, from Vedanta Bioscience. This is a live biotherapeutic. It’s a mixture of eight bacterial strains that is intended to restore the gut microbiome and prevent recurrent Clostridium difficile infections. This is in phase two clinical trials. And the other product I wanted to mention is called GSK 3882347. This is from GlaxoSmithKline. It’s an orally available small molecule drug that prevents E. Coli from binding to the wall of the bladder. And this is in phase one clinical trials for preventing recurrent urinary tract infections caused by E. coli.
12:00 Ethan Rhee
And those are some interesting names. Well, I think that the work that CARB-X is doing is so unique, and so important, and making sure we have the necessary tools to continue fighting antibiotic resistance. I read that CARB-X has received over 1160 expressions of interest from companies or institutions located in 40 countries in just the first five years. Where do you see CARB-X 10 to 20 years from now?
12:30 Su Chiang
That’s a long time to be looking into the future. So you know, it would be fantastic if economic and societal incentives align, and the antibiotic ecosystem becomes fully self-sustaining on a global basis. Bacteria evolved to escape our medicines, and that’s never going to end. So we have to evolve our efforts. And we’ll never be able to stop either. What CARB-X’s specific role will be over the next decade or two is not something that I’m able to predict. But I can say that we’re always looking to understand what are the most urgent clinical needs, what has gone well, and what could be done better in our own processes. And after the first five years, we’ve implemented targeted funding calls to focus our investments on the most critical gaps in clinical care. We are building portfolio-wide efforts so that we can have benefit across multiple projects. And we’re working with partners to shorten the path between good ideas and real world solutions for AMR. So while I can’t, I really can’t answer your question in any detail, I can say that we will be here doing this as long as we’re needed. And as long as we’re able to.
13:54 Ethan Rhee
Thank you so much Dr. Chiang for joining us here and sharing your knowledge and expertise. We’ve learned so much and I hope to continue as part of the younger generation to keep antibiotic resistance on their minds as they’re navigating through the healthcare system. We hope CARB-X can continue to grow and accelerate important companies discovering AMR products.
14:16 Su Chiang
Thank you so much, Ethan. It’s been a pleasure.
14:18 Ethan Rhee
Thank you.
14:25 Ethan Rhee
I want to thank Dr. Su Chiang for joining us and a special thank you to Robin Berghaus for helping me get connected with Dr. Chiang for this interview. That is the end of this episode. And don’t forget to click the follow button on Spotify and follow me on Instagram at ARA.podcast. Thanks for listening. This is Ethan Rhee for Antibiotic Resistance Awareness podcast. And that’s a wrap.