The roller coaster of antibiotic development

The roller coaster of antibiotic development

The roller coaster of antibiotic development

Lance Price, PhD, Professor, George Washington University
Matthew Wellington, Public Health Campaigns Director, PIRG

Erin Duffy, PhD, Chief of Research and Development, CARB-X

00:14  Matt Wellington
Hey everybody. Welcome to another episode of Superbugs Unplugged. My name is Matt Wellington, I’m the public health campaigns director for PIRG, one of your hosts. And I am joined here by Dr. Lance Price of the Antibiotic Resistance Action Center. My other host for the podcast. Hey, Lance, how’s it going?

00:31  Lance Price
I’m sick.

00:33  Matt Wellington
Yeah, everybody’s sick. My daughter has a pretty nasty case of the croup right now. I don’t know what caused it. I understand that is a side effect of other things like RSV. So who knows what’s going on there. But yeah, things kind of suck right now in terms of illness. They really do. It’s.

00:51  Lance Price
They do. Do you take her outside, too? That fresh air is supposed to help with croup.

01:01  Matt Wellington
Yes. We took her outside this morning a little bit, and she was in her brand-new snowsuit. She’s 14 months old, so she’s running around and walking and we have a snowsuit that’s too big for her. So we have to roll up the sleeves and the legs. And so she looks like an absolute balloon. It’s hilarious. But she was like running around the backyard with her little sunglasses on. It was great. Yeah, but she sounds terrible. It’s kind of scary.

01:28  Lance Price
I’m sorry. It’s very stressful.

01:29  Matt Wellington
Yeah. Did they get you sick or did you get sick on your own?

01:33  Lance Price
Oh, my daughter likes to cough right into my face. It’s pretty awesome. So if you’re yawning, she’ll cough into your mouth. It’s awesome.

01:44  Matt Wellington
Ruby takes her little finger and just kind of puts it in my mouth and twirls it around a little bit. That’s one of her favorite things to do.

01:53  Lance Price
Yeah, kids are gross.

01:55  Matt Wellington
They really don’t understand. Yeah, it’s tough for all daycare classes now. Right now, pretty much.

02:05  Lance Price
I’m excited. I mean, despite being sick, I’m really excited about Erin Duffy, our guest. But you’ve got some news first, don’t you?

02:14  Matt Wellington
Yeah, I’ve got some, some news to share on the antibiotic resistance front. So as we record this episode today, the FDA just came out with their latest report on antibiotics sales to agriculture. It’s the ADUFA report and it’s pretty underwhelming, to be honest. There’s that one less than 1% decrease in the sales of medically important antibiotics to meat producers from 2020 through 2021. So not much of a change at all in either direction. And, you know, that’s been the case pretty much since 2015 when the FDA took the steps. They took on growth promotion and increasing veterinary oversight. After they did that, there was a slight, you know, good decline in sales until 2017. And since then, it’s actually slightly increased, you know, from 2017 through 2021. So it just highlights that the FDA’s approach is not exactly effective right now for reducing antibiotic use for the long term on farms. There’s no, as far as I can tell, no targeted, you know, approach for reducing the use of these drugs. So of course, we’re urging the FDA to take the lead there and to, you know, take some lessons from the European Union. That’s they’ve been able to basically have sales of antibiotics to veterinary medicine in the last ten years. And they did it through setting targets and measuring against their progress. So we are definitely urging the FDA to take a similar step. But yeah, not much, not much else in the report other than not much has changed.

03:56  Lance Price
Are you ever, every time I hear it, I always want to say ADUFA. I don’t know. It’s just got a funny name.

04:02  Matt Wellington
Animal Drug User Fee Act. Yeah, I do feel it’s a very ridiculous outcome.

04:09  Lance Price
Did we ever talk about how from 2016 to 2017 there was this huge jump in therapeutic use? So you see this, you see this, you know, apparent. Well, you see a definite drop in total amount, but then it looks like there’s this big just a shift in what they were calling a bunch of drugs. Right. So they were saying, oh, yeah, these weren’t after all, these weren’t for growth promotion, these were for disease prevention.

04:40  Matt Wellington
Well that’s a good distinction too, you said therapeutic use and the FDA considers disease prevention a therapeutic use, but we do not. To us, therapeutic use means treating disease and disease. You know, preventing disease brought on by industrial farming conditions to me is not a therapeutic use. But we agree to disagree with the FDA on that one. But you’re right, you know, it’s just we see it as, you know, a shift in the labeling. And I think they did tackle the low hanging fruit on antibiotic misuse in their previous actions, but have not really done much of anything since then. So that’s antibiotic resistance in the news, not to be a bummer. But we do have an upbeat episode. We go it was quite a roller coaster. We talk about antibiotic development, we talk about how antibiotic resistance affects lower and middle income countries differently than high income countries. But ultimately we end on a positive note. So even though I have been a little bit of a bummer in my introduction here, I encourage folks to listen to the full episode because you’ll definitely have some hope at the end of it. And we have a special guest joining us, Dr. Erin Duffy. She is the chief of research and development at CARB-X, a global biopharmaceutical accelerator for the discovery and early development of products to prevent, diagnose and treat bacterial infections. So folks might remember we had the executive director of CARB-X, Kevin Outterson, on our previous episode. So Dr. Duffy is his colleague and she is going to take us through some of the more scientific pieces of what CARB-X does. So stick around to hear that episode. But we’re going to take a break right now. We’ll see you when we get back.

06:21  Laura Rogers
Hi, this is Laura Rogers, deputy director of the Antibiotic Resistance Action Center. If you like what you’re hearing, could you do us a favor and rate review and subscribe to the podcast? We really appreciate it. Now, let’s get back to the episode.

06:34  Matt Wellington
Hey, everybody. Welcome back from the break to another episode of Superbugs Unplugged. I’m here with Dr. Lance Price, and Dr. Duffy is our special guest for today. Hey, Dr. Duffy, thanks for joining us.

06:45  Erin Duffy
Hi. Thank you for having me. Happy to be here.

06:48  Matt Wellington
Of course. And so we were lucky enough to chat with one of your colleagues, Kevin Outterson from CARB-X pretty recently. So hopefully our viewers have a little bit of a primer on what CARB-X is. So I wanted to start with just your background. Can you tell us a little bit about yourself?

07:05  Erin Duffy
Sure. So again, Erin Duffy, I am the head of research and development here at CARB-X. I am a chemist by background, trained formally at Yale and spent a little bit of time at Pfizer doing drug discovery right out of a postdoc. But then the meat of my career was actually with a small company founded as Rib-X Pharmaceuticals that became Melinta Therapeutics, a pure play antibiotics company, where our goals were to discover, develop new antibiotics. We did that over about 17 and a half years. And then unfortunately, and I suspect this is going to be part of our conversation once we launched our first antibiotic and commercialized it, we ran into some challenges, market headwinds, which required us to close the research and development shop to focus on market products. And so I left there in 2019 and joined CARB-X.

08:10  Matt Wellington
Awesome. You’ll have to be patient with me with the chemistry it is the only class that I did not do super well on in college, so.

08:18  Lance Price
I didn’t even know chemists could speak. So this is really awesome to microbiologists. You know, we had a lot of competition with us.

08:27  Matt Wellington

08:27  Lance Price
What’s pure play?

08:29  Erin Duffy
Oh, sorry. Pure play. Meaning that we were, which is pretty true of most biotechs, we were solely focused on the development of new antibiotics, not, you know, and oncology agents or whatever, whatever. But we had a foundational technology out of Yale that actually was the subject of a Nobel Prize mid-stream in our company in 2010. Not that I won it, but the founders did. And that was to describe at the atomic level what one of the most prolific targets for antibiotics looked like. And that then allowed us to use that and design new antibiotics against it.

09:09  Lance Price
And I thought you said parallel play. You know, I can see my daughter’s nursery from here and they do a lot of parallel play and I just didn’t know that. I was just imagining chemists all trying to like, you know, almost like shared workspace. Okay.

09:25  Erin Duffy
I’m sorry to disappoint you, but yeah.

09:29  Matt Wellington
Well, I definitely am curious to hear about the challenges, the market challenges. You mentioned before I asked that, as I said, hopefully our listeners are already primed with what CARB-X is, but can you just give us a little bit of what CARB-X is and what we’re all about.

09:43  Erin Duffy
Sure. Absolutely. So I’m sure Kevin told you this, but I’ll remind you what the acronym means, which is combating antimicrobial-resistant bacteria biopharmaceutical accelerator. Those last words are what make the X. And long story short, we are a project at Boston University School of Law that is funded by three international governments. So the U.S., the UK and the German government, as well as two foundations including the Wellcome Trust and the Bill and Melinda Gates Foundation. We’ve been given to date just about $800 million to deploy for the support of companies that are designing and developing new antibiotic attacks, new vaccines and other preventatives against bacterial infections and new diagnostics.

10:36  Matt Wellington
So one thing that and lots of the things Kevin said stuck with me from his interview is that we titled that episode “King of Analogies” because he was just throwing them about left and right. One thing that I came away with was it sounded like CARB-X is doing what I would consider like letting all the flowers grow, right? So it seems like you’re kind of open to every and all approaches to addressing antibiotic resistance, but you all have the strategic goal, like, are you thinking ten years from now we want to have three antibiotics developed, four diagnostic tools in place X, Y and Z? Or is it just throwing spaghetti at the wall, seeing what sticks, which if it is, that’s totally fine. I’m just curious if there is that strategic. Here’s what we want the next ten years.

11:24  Erin Duffy
Yeah. So I’m not the queen of analogies except maybe bad ones, so I’m not going to go there. But I would say that it has evolved. So when Kevin was first awarded this grant in 2016, I would say it was more of the spaghetti on the wall, which is I don’t think Kevin had any idea if ten people would apply, 100 people would apply, 1000 people would apply. And so they had very broad calls of, you know, we do fund only through active funding calls. We can talk about that. If you want to have a very broad, just bring us stuff that might be relevant for antimicrobial resistance. And then as we’ve matured, we’ve built some portfolio analysis tools so that we can look at, you know, the landscape of pathogens and infections that they cause and where we’re heavily invested and where we’re not well invested. And you know what? What sorts of things are in that box, how mature they etc. And then that has allowed us to refine for what we look at. And I think probably the best expression of that is this year in October we launched the first what we’re calling omnibus solicitation or funding call since 2019, and we publish three funding themes and there are very specific funding themes. The first is we’re looking for new oral therapeutics for a variety of infections. The reason for that is all those antibiotics that you know and probably have used with your children. I know you’ve both mentioned young children, things like Zithromax, Augmentin, you know, these are products that are being eroded because of resistance in the community. And so we’re looking to replace those with new antibiotics. So that was one call. The second call was for vaccines, maternal vaccines for neonatal sepsis. Not a huge problem in high income countries, but a massive problem in low middle income countries. These vaccines are very hard to develop. And then the final set of themes was for gonorrhea. And this was a broad based. If you have something for gonorrhea, whether it’s a treatment, a preventative or a diagnostic, we want to hear from you. And this was after a careful analysis of what where the holes are in our current portfolio and where the needs are in the world.

13:55  Matt Wellington
Yeah. Lance, you’re going to jump in.

13:57  Lance Price
Yeah. I mean, no, that’s really exciting. So for the neonatal sepsis, is that primarily E. coli? I know we have a lot of that. And I mean there are E. coli strains that cause neonatal sepsis. You see that in the U.S. But I don’t know about low- and middle-income countries or is it other organisms?

14:16  Erin Duffy
Yeah. So actually, there’s a pretty neat study that was done called BARNARDS. This was work out of Oxford University, Tim Walsh’s lab, supported by the Gates Foundation. And what they found pretty contemporary study was a predominance actually of Klebsiella pneumonia. So if you were to rank pathogens from sort of most likely to cause and do cause neonatal sepsis down, it would sort of go like Klebsiella pneumonia, and maybe said that five more times. And then in fact, E. coli, Acinetobacter baumannii and Staph aureus actually as well. So those are the four main pathogens.

15:01  Lance Price
Tim is amazing, Tim Walsh I mean, this guy.

15:05  Erin Duffy
You could have.

15:06  Lance Price
Him on the show at some point.

15:07  Erin Duffy
I know you do. You do. You do. He’s terrific. Yeah.

15:12  Lance Price
So discover MCR1and then also New Delhi metallic protease. Yeah. Wow. Okay so the end.

15:22  Matt Wellington
Man of the year, Lance gushed about his favorite scientists.

15:25  Lance Price
Oh well he’s an amazing guy. So the oral antibiotics make sense and vaccines. Awesome. And then yeah, the gonorrhea. Let’s talk about gonorrhea a little bit. It’s one of my favorite topics. So super resistant strains now and nearly pan resistant, right?

15:45  Erin Duffy
Yeah, absolutely. You know, there’s you know, we always talk about resistance to classes, but in fact, in the case of gonorrhea, we’re not just down to one class that is effective. We’re down to one antibiotic in one class, and that is the cephalosporin, very old. And it’s an IM injection. It’ll make you think about it if you have to get the injection. But even there, particularly in low- and middle-income countries, the resistance rates are certainly concerning.

16:18  Matt Wellington
So you’ve mentioned lower and middle income countries a few times now. And I know when I was looking at some of the background on your work, CARB-X talks about antibiotic resistance and the burden primarily falling on LMICs. So how does that come into play? You know, obviously we use antibiotics in the U.S. We’ve talked about antibiotic resistance in the US context, but how is it different in LMICs? What are the different challenges? What does it look like?

16:46  Erin Duffy
Oh, well, you know, so I mean, it’s frightening, frankly, is how it looks. But so this year in actually January, I think late January of this year, a really amazing paper was published in The Lancet that sort of commonly known as the GRAM paper. And there for the first time described what the burden looks like worldwide. And also then mortality and morbidity, morbidity associated with bacterial infections. And, you know, the numbers are staggering in and of themselves and I’m sure you talked about that with Kevin, but if you were to plot where those infections happen, they’re not here. Okay? So they are all in low middle income countries. It’s really alarming. And even more alarming than that is the disproportionate burden on children of babies, particularly neonates. It’s shocking.

17:42  Matt Wellington
And what because we did have one of the researchers of that study on the podcast several months ago, and I’m trying to remember what he told me in the interview was partly it’s that it’s just a lack of access to antibiotics in those countries. Is that your take as well, or are there other things coming into play with resistance factors, or is it the case that these people with infections could be easily treated if they happen to live in the United States with these infections? Or is there something else happening?

18:13  Erin Duffy
Well, certainly it is true that access is a major, major, major driver. And that’s because, you again, the health care system is very different. I mean, if you’re a woman who is pregnant and delivering a child, you might drive for two days to go to a place that certainly doesn’t look like any hospital that you or I would ever come into contact with. And so it’s just the levels of the health care system are different. The access to these antibiotics, as you said, is very low, but then also the misuse of antibiotics that we can get drives resistance. And so it’s sort of all of that combined. You know, actually earlier I think Lance mentioned, you know, New Delhi metallo-beta-lactamase, why you think it’s called that because the first patient who showed up with it was from New Delhi. That’s how these things are named. And so anyway, it’s all three of those factors, I think.

19:12  Lance Price
I think, you know, the other thing I was so happy to see your focus on the LMICs, too, is that, you know, we talk about antibiotic resistance undermining modern medicine all the time, right? So that’s, you know, one of the messages that seems to resonate with people. But in low- and middle-income countries, I mean, the antibiotic is modern medicine. And if that fails, you die, right? So that $5 antibiotic doesn’t work. You don’t, you don’t hook people to hundreds of thousands of dollars’ worth of equipment. Right. I mean, so that’s the thing that really strikes me is that these are modern medicine and they’re failing. And so, yeah, well, tell us, how do you when you think about diagnostics, when you think about drugs, how do you know? What is it you’re looking for to support that specifically helps in that context?

20:07  Erin Duffy
Yeah, it’s a great question. You know, and I think it’s so much easier for better or for worse, to have this conversation now. Three years almost. Exactly. And to, you know, COVID, because if you if you roll the clock back to, you know, I believe in May of 2020, if you had a respiratory infection and suspected you might have COVID, you couldn’t get a test, you couldn’t figure out if you had it, there weren’t therapies and there weren’t vaccines. You know, so this is terrifying and it’s sort of the same here. So but in the low and middle income country setting, you need all of these things, but you definitely need a diagnostic. But that diagnostic needs to be, you know, cheap available at the lowest levels of the health care system. So it’s going to be, you know, a blunt instrument. But at least to say, you know, bacterial and maybe, you know, idea what it is and some resistance markers so that you can properly treat, you know, is critical. But then having the right antibiotics or at least enough options for antibiotics once you understand what that is, is key. Now, of course, the third part of this and again, you know, we have code to thank for this is prevention, because you know, the best infection is the one you actually never get. And so if we had good bacterial vaccines available, that I think would be a game changer in low and middle income countries.

21:39  Matt Wellington
I want to ask you about the diagnostics. So what you described that tool where, you know, it says here’s the here’s what the infection is or roughly what the infection might be resistant or not resistant, does that even exist in higher income countries? Like does that is that something physicians have access to here in the U.S.?

21:57  Erin Duffy
At the highest levels of the healthcare system, you know, for different syndromes? And when I say syndromes, I mean infections. Right? And for you have to think about sample types as well. But yes, there are these big systems and then you have these cartridges that you swap in and out. And so it depends. But certainly there are infections for blood sorry, diagnostics for bloodstream infections. After you take the blood and you culture it and say growing the bacteria, then identifying it and saying to what it is susceptible can be done. But that’s at your highest levels of the health care system and it’s not available with all of the infections types and sample types and, you know, whatever that you want. So for instance, in gonorrhea, you know, we have this call. Turns out that it’s really difficult to measure bacteria and things like vaginal swabs and urine. Partially that’s a collection problem. But anyway, so there’s a lot of work to be done and bacterial vaccine and bacterial diagnostics. Now, the good news is for respiratory diseases, we had so many groups, small companies, big companies who dove in to the COVID world in 2020 kind of stopped what they were doing to develop tests for all levels of the healthcare system. Well, those people, you know, they’ve made some really interesting products and now we have the ability to pool them in and hopefully get them excited about what else they can build and build it for, you know, bacterial infections.

23:39  Matt Wellington
Yeah. I mean, the COVID tests amazed me. I just took one this morning. Ready took a little swab, little piece of cardboard and in 15 minutes I knew to a degree whether or not I had COVID. Yeah. So that’s the idea, right? It’s something super simple, cheap that physicians can use. I guess one follow up question I have is how we’re talking about like COVID in particular, you know, versus virus who knows how many potential bacterial infections. So how would you narrow it down in a test like that? Would you develop it for the top three bacterial infections? You might find it in a region. How would that work?

24:19  Erin Duffy
Yeah, it’s a good question. So, I mean, typically these things are more syndrome focused and by that I mean, okay, this is for respiratory tract infections. Okay. And then, you know, you’ll hopefully be able to have enough on the test to be able to determine what the key pathogens. So you’re looking for the key pathogens that cause that syndrome. You know, so, you know, we talked in the case of neonatal sepsis about, you know, the big four, if you’re talking about a lower respiratory infection, you know, a deep pneumonia infection, you know, you’re talking about, you know, things like Klebsiella pneumoniae. We mention that Pseudomonas, staph aureus, you know, it’s a similar grouping. So you’re going to look for that. And then, you know, depending on the sophistication of the tool and again, at what level it sends, that’s where you get into the nitty gritty of. Okay. And it also is carrying X marker where X is something about resistance.

25:20  Lance Price
So I’m curious about the economics of, say, a diagnostic for low- and middle-income countries, because it’s my understanding is that one of the big barriers to bringing new point of care diagnostics into places like the United States is this unpredictable reimbursement. Right. So, you know, if there’s not clear reimbursement, then a doctor’s not going to order it. And if the doctors aren’t going to order, then nobody’s going to produce it. Right. So it seems like the technologies are out there. There needs to be the effort, the investment. And so my understanding of CARB-X is that you do the push piece, so you have this non-dilutive funding at the beginning. But then and you know, we talked a lot with Kevin about, you know, pull incentives, but how would that work in low- and middle-income countries? How would you pull?

26:17  Erin Duffy
Yeah. No, I think these are excellent questions. I’m definitely not the expert to answer these questions, but I will say that that certainly if you’re talking specifically about diagnostics groups who think a lot about this are a group that we work with quite closely called Find. And I don’t know if you’re aware of them, but you know, Geneva based, you know, very big focus on diagnostics for low-income countries across the board, including antimicrobial resistance. But then also the lead at CARB-X of our diagnostics portfolio is a woman called Betsy Wonderly Trainor, super energetic. You know, a really bright gal. And recently she was part of a convening group at the National Academies of Science to start grappling with these questions of reimbursement for diagnostics. So it’s conversation, but it’s certainly something I would say in a less well developed than, for instance, the PASTEUR Act that I’m sure Kevin spent some time talking with you about for treatments.

27:26  Lance Price
Well, I think if anybody can solve this, it’s somebody named Betsy Wonderly Trainor.

27:30  Erin Duffy
I think. Really. I mean, honestly, no, she’s terrific. You know, she’s had a quite a long history of both development and deployment of diagnostics for emerging diseases, including in low- and middle-income countries. So she’s very passionate about it, super connected and really trying to make a difference.

27:55  Matt Wellington
I feel like this is a good, good time. So if you don’t mind, let’s go back to your personal experience with Melinta, right? So we’re talking about the push and pull incentives, the market challenges. Can you give us the details of what happened with the antibiotic at Melinta? Because I think it’s always helpful to have the stories to go along with the principles at play here. So walk us through what happened.

28:19  Erin Duffy
Sure. So I’ll tell you the long version and then we can cut it to the short version.  We have to roll the clock back a little bit. So around 2005 or 2006 at the latest, we actually brought this antibiotic. So our technology, it was all focused on the ribosome, which is, as I mentioned earlier, prolific target for many antibiotics. And we had put our first products that were new ribosomes targeting antibiotics into first in human clinical trials and they were moving along. But we’re a small private company and the investor said you should bring in a more advanced product so that you can get on the market faster. And of course that will allow us to continue to reinvest in R&D. Seems smart. So we brought in this fluoroquinolone that we named delafloxacin, and it’s in the same class as Cipro. Everybody’s heard of Cipro, but it had a better resistance profile and arguably put clinically a better safety profile. And it had been in the hands of Abbott Laboratories, you know, big organization who were developing it. But what happened was around that time there was a company, big company called Aventis, now Sanofi, and they had an antibiotic that was meant to replace Zithromax. It was called Ketek and it was put on the market. And then some idiosyncratic liver toxicity started showing up. And mind you Zithromax is used in kids, your kids, you know, and earaches and bronchitis and sinusitis. And so, these things need to be really safe. So that was a problem. And it really served to shut down the regulatory path for people developing community-based antibiotics. So Abbott got out, gave it back, gave delafloxacin a send back to the people who had created it, which was a Japanese pharmaceutical company. And then we licensed it from them and then we pivoted it towards hospital infections so that we could move it on a regulatory path. But this took some time. Okay? And then we were just about to start. We just finished our Phase two program, which is the first time you demonstrate efficacy in people for the infection you’re trying to cure in 2010. And at that point, the FDA released new guidelines for certain paths towards approval, and that was one of them. And so that caused us to stop. And, you know, because we’re ready to jump into phase three with a plan. So we had to back that up a little bit and took some time. Okay, I’m telling you all this because time is important with the drug, because all those years that you have delays, just eat the patent clock off of your marketing product. Okay. So fast forward 2012. We were trying to raise money in an initial public offering to do those Phase three pivotal trials with delafloxacin. And there was something that was being discussed in Congress called the GAIN Act, which was generate antibiotic incentives now, and the whole story behind that was they recognized that all these companies had a big pause because of Ketek and what happened in the regulatory environment and realized that many of these products would launch after their patent clock had expired. Okay. Not really a great economic story if you think about it. Okay. But GAIN passed and we went and we did our clinical trials. And in 2017, we gained approval. So great. Great approval of our antibiotic. At the same time, we did a reverse merger with an antibiotic company that had run into some challenges with their product that the FDA, this company was called Sempra. They were public and had money but problems and we were not public and needed money to build a marketing team. So was a married match in heaven. So approval of the antibiotic reverse merger. Now we’re a public company, so it’s not bad about that and it’s great. But then we made this decision, which seemed like a really smart decision, which was, well, delafloxacin is meant for the hospital. So you’re going to build a sales force. Why not send those people in with more than one antibiotic in their back? And so we bought three other antibiotics from a company, the medicines company, who decided to divest themselves of antibiotics. I think because of the market conditions. And so now here we are, we have four antibiotics that are on market, two that are launching both important antibiotics and two that have been on the market for a while. It was great and we took on a little debt in addition to the money that we got from the reverse merger to do that. But we were off. We thought this was great. But then the reality of the market conditions that came in and over the next three quarters, the amount of revenue that we received over the four antibiotics was not enough to sustain them on the market. Incredibly. And so that’s when we made the decision in the, I guess, the fourth quarter of 18 to close the research and development shop and find a home for those assets, which we did the preclinical assets, and then to really focus on what we could do to move these antibiotics forward again in oncology company with four branded products for a minute, having this, probably can’t imagine it can you. And so anyway, so then. R&D was closed and then that following year, 2019, in the fourth quarter, actually Melinta filed for Chapter 11 bankruptcy protection. Now, there’s a good news story to that. I have to say, let me just cap this by saying that was sort of the nadir, but now Melinta was brought out of bankruptcy by the group from whom they took the debt, Deerfield and Melinta as a going concern. They’re a focus company with multiple products, including the ones that I mentioned. And so they’re back in business and looking to build, which I think is a good sign.

35:00  Matt Wellington
That was quite a journey. So I think.

35:03  Erin Duffy
Sorry about that.

35:06  Matt Wellington
Reminded me of like it almost was like I felt like there should be like a Hulu documentary special made about this quite, quite a story as you were telling the story, a couple of things stood out for me. You said market conditions several times. You talked about the sales force and it just paints the perfect picture about how the current drug development structure just it does not work for antibiotics. If we want to keep antibiotics effective, it just does not work. You know, sales based on volume, which a company needs, it literally just will not work for antibiotics if we want to keep those drugs effective for the future. So that stood out to me quite a bit.

35:46  Lance Price
Yeah. So I wonder, Erin, how does that of somebody who came out of this, you know, for profit drug world now you’re working with CARB-X. I mean is that shaken your sort of vision of how markets work. I mean what is that Yeah. How does that experience sort of shape your thinking?

36:11  Erin Duffy
Yeah, I mean, it’s a good question. I you know, I guess I’m here because I, you know, I, I believe like, I think we all do that the world needs these products. And, you know, there’s this is a challenge. It’s a different challenge than the scientific challenges that I’m used to tackling. But, you know, somebody has to do this stuff. And thankfully, we have people who are behind us. So we’re curating that pipeline for when. And you know, there are others, including, you know, Kevin, who are working on the how. And I think both need to come together. It’s a puzzle, you know, would have been easy. I’ll tell you to just go to a different therapeutic area. Sadly, when we closed the R&D shop, I had 25 colleagues with whom I worked in New Haven, Connecticut, and I’m proud to say that all of them were gainfully employed shortly after we closed the R&D site. Not a single one of them in antibiotics, not a single one. Okay. So it’s easy to retreat. But I think, you know, we all know we need these things. And I do believe fundamentally smart people and passionate people will help us figure out the other side of the equation.

37:30  Matt Wellington
But it is so clear to me, especially after hearing the story in detail, like it’s a policy problem, obviously there’s a science problem that you’re dealing with, but at the end of the day, it’s a policy problem. We have to figure out the policies that will make this system work. So thank you for sharing the story with us. So I guess pausing for a second, is there anything you wanted to discuss, Dr. Duffy, that we haven’t touched on yet? Because I actually I feel pretty good about where we’re at right now. Lance I don’t know. Is there anything else you wanted to discuss?

38:03  Lance Price
Oh, I could talk for hours. We could do like we could do one of those long podcast recordings. But no.

38:12  Matt Wellington
Yeah. So on your end, Dr. Duffy, anything you feel like you were really burning to talk about that we didn’t ask you?

38:19  Erin Duffy
You know, I think sensing that, that I think we’re still trying to figure out, frankly, because you’re right, it is a policy problem, okay? The science of science. And, you know, I mean, we can tackle hard problems, but the question is, how do you get the non scientists in the world to go yeah, I get it. I mean, it’s good. And I say that because, you know, I think we’ve tried various things. You know, we talk about antibiotics underpin all modern medicine. That’s true. But you know, it’s not at the level that people worry about, know people worried when they felt there were no therapies for COVID. People worried in the eighties and nineties about getting HIV. Okay. So they were activated and motivated and I guess I’m curious to know, you know through all of this if you think there are ways to reach people. I mean we’re talking this obvious podcast hopefully it’ll be out there but how do you make how do you make you know like the gal who’s sitting right now at the dry bar having her hair done, listening to this podcast, because that’s what you do, listening to the dry bar, I think, you know, But like we need to do something about that, you know.

39:44  Matt Wellington
I mean, my, my take and it is a core part of our audience, the salons and barbershops. So we get a lot of play with Superbugs Unplugged there. But my take on the public facing piece of it is if I just sit here and really think about it, I can come up with three immediate family members who have had drug resistant infections. All of them are a little bit different, you know, difference in severity. But one of them was fatal. One of them was nearly fatal. And I think most people, when they really think about it, antibiotic resistance has touched them directly or their loved ones directly, and they don’t even really know that. And I think partly it’s because it’s always couched or, often couched in a larger medical problem. Right. So, you know, a cancer patient surviving cancer and then unfortunately dying from a drug resistant infection is just part of a larger story. And so I think it’s up to folks like me, I’m a non-scientist full disclosure. I’m a non-scientist. So it’s up to people like me, I think, and other advocates to work with physicians in those patients to help tease those stories out and have those physicians tell their stories. But the actual patients tell their stories, too, you know, and we do that every day. I have a great farmer that I work with because we work a lot in agriculture here and trying to reduce antibiotic use there. And he talks about how he had MRSA infection. And I guess his doctor, he was upset with his doctor for not starting antibiotic treatment sooner. And his doctor had a great conversation with him about why he didn’t make that decision, because he doesn’t want to spur antibiotic resistance unnecessarily. And it totally changed this guy’s life. He changed how he produces animals based on it. He switched from a conventional model to now raising his animals without antibiotics. So I think it’s up to I think it’s really about helping physicians to talk about this in a way that is public facing and is understandable to the public, not as just this kind of ambiguous medical problem. And then people me to, you know, put a megaphone in front of them and get it in the media and understand how people understand that if they really think about it, this has already affected them. You know, I think the amoxicillin shortage, I know that’s not necessarily about antibiotic resistance, but it’s giving us a glimpse of what the world will look like without antibiotics. And that has been on headlines all over the country. Right? Amoxicillin shortage. People are freaking out for good reason. What I think we need to do is connect the dots that, yes, and if we don’t act on this soon, you’re going have a lot more to freak out about.

42:19  Lance Price
I think, too, it’s you know, as we see E. coli getting more and more resistant, this is going to become a salon conversation because you’re going to see urinary tract infections that are very, very difficult to treat. And so unfortunately, I mean, I think it’s a crisis. It’s going to lead people to start to feel that. Yeah, unfortunately.

42:45  Erin Duffy
Yeah that’s really good point in the urinary tract infection you know touches so many sort of different levels of people. Right. But you’re you know, to your point about, you know, a lot of young women have, you know, what are, you know, non-complicated urinary tract infections. But we also have not again, because, you know, these markets have not been attractive. We haven’t had a lot of innovation for new oral antibiotics for urinary tract infection. You have a college girl let’s say, gets urinary tract infection. Pretty sure she doesn’t think she’s signing up for 14 days of intravenous antibiotics because all the ones that are oral unfortunately don’t work anymore. So these are all these funny things that seem like, you know, just I’ll just go get an antibiotic. But you can’t.

43:36  Matt Wellington
I mean, gonorrhea, right? Talking about college kids, that’s something to worry about. Not. Yeah, yeah, yeah. So I think I think we just have a lot more work to do to penetrate the public’s consciousness, which is a really hard thing to do. And to Lance’s point, I think unfortunately it often takes a crisis to do it right.

43:55  Lance Price
I think we’ve also, you know, we’ve had 70 years of, you know, faith in technology that’s been reaffirmed whenever there was a new antibiotic. Right. So, you know, we as a society, we’ve been taught to disregard this issue. And what I don’t think that most of society sees is that pattern is coming to a quick change, you know, and.

44:20  Erin Duffy
Know it’s true. You know, I was reading, I don’t know. could have been yesterday, could have been two weeks ago. But there was an article, I think it was in the Wall Street Journal about infrastructure aging where, you know, water treatment and distribution is concerned around the country. Right. Because we haven’t invested in this stuff. Nobody buys a house or rents an apartment thinking I’m not going to have safe water to drink. Right. Nobody in. Okay. People in low- and middle-income countries do, but not in the U.S. Right. But antibiotics are like that water. You don’t think about it. You don’t think when you go to have a, you know, a filling or, you know, to have a hip or a knee replaced or any anything else that, you know, what if what if I get an infection and there’s an antibiotic that works against it? Nobody even thinks about it. Your doctors don’t talk to you about it. You know, you just expect it’s there.

45:13  Lance Price
Yeah, but I mean, I think Matt and I are. We’re going to crack this, you know this. And I don’t really know. I mean, I, I, you know, I listen, there’s a, there’s a podcast that I listen to The Drive and it’s, you know, about longevity. And you know, personal health and how do you, you know, what are the things that you can do to hedge your bet and try to live a little longer? And I think about this all the time. We should be on that podcast because this is what’s going to pull the rug out from under people, right? Because as we get older, you know, no matter how well we’ve taken care of ourselves, we get more and more susceptible to infections. And, you know, I think that this could I don’t want to end on such a negative thing.

45:57  Erin Duffy

No, it’s not. Negativity, actually, which is that, you know, coming back to CARB-X and I mean this as sincerely as I can say it, it is remarkable to me how many high-quality researchers doing really innovative stuff are out there and remain active in this field. Okay. And that’s why we’re here, is to pull that energy and pull what they’re doing. The situation will be fixed. I think, you know, there will be a policy fix. There has to be. And thanks to these people today, 92 different companies and hopefully counting more soon, they’re making it so that the stuff will be there when the policy is fixed. And I think that’s an important message. It’s not like, you know, everybody packed up shop and went somewhere else.

46:46  Lance Price
And people like you, thank you for staying in the fight.

46:50  Matt Wellington

46:50  Erin Duffy
Yeah, I’m honored to do it. It’s good fun.

46:54  Matt Wellington
Well, I think that’s a good place to end. High note. Thank you, Dr. Duffy, for. For joining Lance and I. This has been great. Both said the interview with Kevin and you, I think this is a really great one-two punch to tackle, you know, drug development and antibiotic development and what it’s going to take.

47:12  Erin Duffy
I really appreciate it, and I hope you feel better Lance. Thank you. I look forward to listening. And thanks again.

47:21  Matt Wellington
All right. See you.

47:22  Erin Duffy
Take care.

47:23  Matt Wellington