Thanks everyone for coming back. We have Iterum Therapeutics, ITRM, Corey Fishman, CEO is with us, once again, and we just got off with Immutep and the oncology side, and it's amazing to me valuations and talk about the value of checkpoint inhibitors. Then you go to the other side, which is my favorite area, infectious disease. It's like you can't buy a valuation. I don't understand it. It's just as important as anything, that's as important in oncology. People should be paying attention to ID. Iterum has done some incredible things by potentially getting the first oral carbapenem approved for uncomplicated urinary tract infections, had a successful phase III that read out. It was a repeat trial earlier this year, early January, if I recall.
It's been through a lot of ups and downs, and here we are, very close to potential approval. There was an AdCom just recently, and we could talk about that, but here to provide an update on where Iterum is, is Corey. So thanks for joining us, Corey. Maybe give us a little bit of an overview.
Sure. Absolutely
... of the company and yourself.
Yeah, thanks for having us, Jason. We appreciate it, and it's been a long road for Iterum, but we feel really good about where we are. We are developing, as you mentioned, the first oral penem that might be approved for uncomplicated urinary tract infections. We actually have our PDUFA date upcoming here in about 10 days, October 25th. So we're getting to the wire, and we're very excited about it for a number of reasons. And really, the most important reason is because we know there's a tremendous antimicrobial resistance crisis going on, and we believe sulopenem can play a very important role in helping to stem that crisis. And, you know, I'd be happy to talk more about that with you and as we go on.
Maybe, maybe you can give everybody an overview of penems, right? And how important they were, they've been. There have been a lot of attempts at going oral. It's been IV. Obviously, there's a bunch of IVs that are out there, but it's you and there's one other that that's out there that we're aware of that's a-
Sure
... had success.
Yeah, it's a great point. Penems have been really the stalwart of infection treatment for over 30 years, but primarily as IVs. So there's been imipenem, meropenem, ertapenem, a number of penems. Extremely potent, extremely safe, but again, only as IVs. And it's been quite difficult for companies to develop the oral version of those penems. I know a number of them have tried. This one we actually licensed from Pfizer. So Pfizer was able to figure out the science and the chemistry behind it, and we were able to get the rights to the product. And we think that's incredibly important because it really can change where you're treating these patients now, right?
Uncomplicated urinary tract infections are treated in the community, and therefore, this is an opportunity to put a drug into that treatment paradigm, which is efficacious and safe, and most importantly, doesn't have any resistance. And unfortunately, the situation of the orals in that space as we speak, most are extremely old, and most have a significant amount of resistance that has driven over time, and it's eroding the efficacy. And because they are as old as they are, it's really got a number of challenges for those orals. So we are very excited to be able to potentially be into that mix. You mentioned one other oral penem. There is another company developing an oral penem for complicated urinary tract infections, which would likely be used in the hospital setting. So-
What is the standard of care? What I mean, what do patients, if and, like, maybe start with the size of the market. It's huge.
Sure.
And then maybe there's the series of antibiotics that they can get.
Absolutely. So the market is quite large. We estimated over forty million prescriptions annually for uncomplicated urinary tract infections. And the way it works is patients show up at a physician's office, present with symptoms, and are treated empirically. Now, this is, again, out in the community. This is not in the hospital. This is in primary care docs, in OB-GYNs, in ERs, et cetera. So these folks are showing up and getting an empiric treatment. The challenge that exists today is most of those drugs that are being prescribed are quite old, have a lot of resistance, and have some safety challenges that make them suboptimal. The challenge a physician has, unfortunately, today is they don't have any other choices. There's been nothing new in this space for over 20 years in terms of approvals.
Just recently, there was one other drug approved, but it is not yet marketed, so you're talking about a physician situation where they don't have any other choices, and they go with what they know. The challenge is, oftentimes, that doesn't work well, and if you don't get the drug and the bug matched correctly, then you're in a situation where it could become a more serious infection, and you could end up, especially if you're an elevated-risk patient, in the hospital, and everybody wants to avoid that. That's really the worst outcome of all, is having an uncomplicated UTI devolve into something much more serious.
Not that, I don't want to open old stuff, but it doesn't matter now because the PDUFA is in a week or whatever, right? So, but to your point of the effectiveness of Sulo, can you go back to the first phase III, where there was some issues with regulators, but the trial was fine, more or less, right? ... and then, so you got a comparison in that trial that I actually think is of value, even though the trial, obviously, you had to redo it. With the REASSURE trial, you got a different comparator, but now you have actually more data that supports Sulo's use, right, for this indication?
Correct. So the first trial was Sulopenem versus Cipro. And what we had recommended was Sulo versus Cipro, full stop. And what the agency said at the time was, "We'd really like you to break it into two pieces, a piece where those are resistant patients to Cipro, and a piece where those are susceptible patients to Cipro." So we did that. We did the trial. We were successful in showing superiority to Cipro in the Cipro-resistant population. We did not show non-inferiority to Cipro in the susceptible population because of an unusual microbiologic, I call it an anomaly, it's called asymptomatic bacteriuria, and that simply means that there's a trace element of pathogen remaining in a patient's urine at the test of cure. We happen to have more of that than Cipro did, and therefore we didn't meet that criteria.
However, on the overall basis, Sulopenem versus Cipro, we were non-inferior, which is exactly what you would expect. Then, when we ran the second study, we decided to change it, and of course, had a SPA agreement with the FDA, to change the comparator to, Augmentin, a beta-lactam, which is a similar class as us, and we ran, the study. We had excellent results in not only the susceptible group, we showed we were not, not only non-inferior to Augmentin, but we were also statistically superior in that susceptible group. So we, we had some really great results, and I think, I think by showing that, we've given the agency a lot of comfort.
If you read their briefing book documents for the advisory committee, they come out and say, "You've got two adequate and well-controlled studies." And so I think the opportunity now is to hopefully get an approval in the next couple of weeks, and then figure out the, you know, the appropriate patients for treatment. That's gonna be critically important. We agree with that, and we've always said that, as you well know, for years, we've been saying, "This drug is really tilted toward elevated-risk patients," because it is a penem. It is very potent, but it can make a very significant difference in treatment, where you know you're going to have a very good result, and you really want it in those patients that are a little bit higher risk.
But that's a lot of people.
It is.
Right, so maybe run us through those numbers of, of how big-
Sure
... that population really is.
We estimate, as I mentioned, there's about 40 million prescriptions, and of that, about two-thirds are elevated risk. And when we say elevated risk, Jason, what we mean are people that are women that are over 65, that have diabetes, that have another comorbidity that's impacting their immune system, or that have had a history of recurrent infections. So those lumped together are the, what we call, elevated-risk patients, and there's roughly 27 million of those in the market as well. And so those are the folks we're most concerned about because I think those are really the ones, if you have a mismatch in bug and drug in terms of treatment, you could end up with some much more severe challenges on the patient outcomes.
That's really where we've been talking for many years now about targeting Sulopenem, is for those elevated-risk patients.
So there was a lot of talk during that AdCom. So it was. It's funny. So when that AdCom, the stocks fall, so you put the press release out and write in the news an update, and it is very, it's as benign as it could possibly be. But we get a lot of calls, people, like, they don't understand why there was no voting question. Like, well, there's not always a voting question. You just don't hear about it all the time. But there was a lot of discussion about antibiotic resistance that are out there, resistant microbes, and such. Can you walk us through that AdCom and what it really means?
Sure. Yeah, I think there's a couple things that it, within that question. I think the first is really to take some time and talk about antimicrobial resistance, and what's been going on, and how, importantly, how to try to stem that. So I think the first thing, just to note, if we just go back in history, is since the 1940s, when antibiotics were discovered, there has been resistance to antibiotics over time. It's just a naturally occurring phenomenon. Unfortunately, these pathogens are smart, and they know how to change over time, so they're not impacted by some of these drugs.
The next thing that's really interesting is, if you have a physician treatment perspective that talks about the right antibiotic for the right patient, the right dose, the right duration, all of that's incredibly important in treatment of in stemming the rise of antimicrobial resistance, and that's really gonna be important. It continues to be kind of a beachhead for physicians in terms of treatment. The other thing that would be awesome would be point-of-care diagnostics, a rapid point-of-care diagnostic. Unfortunately, there isn't one available. We don't see one on the horizon for the community, and therefore, it makes empiric treatment kind of required. The other piece that's gonna be very important as we go forward are continued development of new antimicrobials, and the challenge with that, as you well know, is most of the larger companies have stopped developing antibiotics.
There are some who still sell them, but most have stopped developing them, and that really puts the burden on smaller companies, and it puts the, a significant financing challenge around that. Because ultimately, smaller companies have, you know, lesser resources, and it's just much more challenging to be coming out with antibiotics, especially to your point earlier, when the market doesn't see tremendous value in them, irrespective of how successful they are. The last piece I would talk about is kind of the government impact here, and there's been some really positive stuff.
In 2012, as you know, Congress enacted the GAIN Act, and that was generating antibiotic incentives now, and that was really great for a number of companies, because what that did was said, "If you qualify as a qualified infectious disease product, then you get two incentives." The first is five additional years of data exclusivity for an NDA, which takes your total to 10 years, and the second was you got an expedited review of six months versus the standard 10 months. So that was fantastic. The challenge has been in the last decade. There's been a significant cry from industry and others for real economic incentives from the government. Been a lot of talk about that in Congress and various government agencies, but unfortunately to date, nothing has come of that. So-
What about the PASTEUR Act? Because we just heard yesterday that that act might actually get passed, if you could believe something gets done these days, might actually be signed into law before the end of this year for a variety of reasons, for companies that are phase III or later commercial stage. Is that something that Iterum could possibly take advantage of or is exploring at least?
Yeah, for sure. It's on the horizon, and we're certainly hopeful. There's been other projects as well. There's been a priority review voucher kind of discussion, where antibiotic companies that have commercial drugs would get a kind of a incentive voucher to be able to help them in the financing world. That hasn't had a lot of traction as of yet, but certainly if PASTEUR Act does pass, that would be great, and that would be something that would be valuable for everyone.
Some of the things we were talking about that yesterday was is because they do still get things done down there. I know it's been a crazy time politically, but you know, one side seems to be very adamant about having things that are U.S.-based, stockpiling here, we make it here, and the other side has some issues with drug pricing, and now being able to control pricing and getting those drugs to people that need them. And so it seems like everybody wins, and the people who really could win are ultimately might be Iterums of the world.
Agreed. And it's really important because the deep down in our guts feeling is if we don't find some way to incent antibiotic companies like Iterum, it's gonna be really hard for people to continue to develop new drugs, and that'll be terrible. I mean, just terrible. We know all the statistics around antimicrobial resistance and what it's expected to do, you know, kill literally thousands of people over the coming years. It would just be very, very difficult for companies to continue to try to raise capital, privately or publicly, because there's so little appetite. And I think...
I'm hopeful that something like Sulopenem can change that perspective, much the way that something like Cubist with Cubicin did early on, you know, a number of years ago, which is show that you can get out there for the right patients, that physicians will use this for those right patients and really see that you're making a difference. And if you can do that, I think then there's a different pathway available with regard to financing, and I think that's incredibly important for the industry in that regard.
There was an article earlier in September about they're expecting forty million deaths by 2050. It's a long time, but not that long from now, from superbugs.
Yep.
I mean, they can't publicize the need for new antibiotics any more than they do, so I don't... I'm trying to figure out, you know, what's gonna change.
That really is sort of the crux of the issue, right? There are agencies that continue to be supportive, folks like BARDA, but just like everything else, they have a limited pool of funds, and unfortunately, when you know, when things come along that are super serious in their mind, like COVID, you know, it gets sort of pressed to the side, antibiotics do. But ultimately, there are some places where there's still funding pools available, but it's not enough. It's not enough to keep these companies going.
We've seen, unfortunately, a few companies go out of business in the antibiotic space over the last five years, and it's really challenging, and it makes it a very difficult conversation for people because they don't want to invest in antibiotics because they don't see a future, but it's kind of the vicious circle, right? If we don't get some antibiotics out on the market, doing well, and investors can see a pathway to saying, "Okay, this makes sense for me to be in," well, then, of course, they're not gonna invest. But if you're not gonna invest in the first place, no one's gonna develop the drug.
So part of the theme of that AdCom you had mentioned is kind of how do you focus on the right population for you? There's some concern, right? I mean-
Yep.
How do you control for some doctor, wherever they are, use you know doing empiric therapy and saying, like, "Hey, this new antibiotic come out, I'm just gonna use it?
... Well, it really is an incredibly important issue, and one that we are completely aligned with the AdCom and the FDA on, which is we want this to get to the right patients. So let's start at the beginning. We would potentially, if we get approved, be approved for uncomplicated UTI, full stop. We're not approved for anything else. We're not approved for things we did studies on, you know, uncomplicated urinary tract or complicated intra-abdominal, and so we'd be very, very happy and comfortable to say to physicians, "That's not it," right? Our ability to influence that is really what we talk to physicians about, and it would only be about uncomplicated UTI, and it would only be if we do get approved and get a label, whatever is within the bounds of the label.
I think the guideline folks also have a good role to play here because they're able to say to physicians, "Here's how you should be thinking about treatment." Now, do community docs pay as much attention as hospital docs to those? Some might, some probably don't. So it's really gonna be incumbent upon the physicians themselves, with some education, to be able to say, "These are the patients we wanna go to," and as an example of that, when we were doing this a few years ago and thought we were on the road to an approval, we developed a website to talk directly to physicians about their specific zip codes and what resistance rates are in those zip codes, so at least we're helping to educate on, "Okay, you're in an area where there's almost no resistance? Super cool.
That's great." Or, "You're in an area that's really high resistance. You've really gotta think carefully about how you're treating." So those are the kinds of things I believe the educational pieces that can really help that process as well.
Do you think, we had said, you know, the expectation is that you get a uUTI approval, kind of full stop, right? So, do you think that there's any potential that the label gets narrowed, or is it based on, like, "Hey, you should use this for... It's indicated for people, you know, with certain risk factors?
Yeah. Look, that's always a potential, and even in that case, again, if that were to be the case, we're very comfortable with where we believe, and I think we're pretty well aligned based on what we heard at the AdCom and heard from FDA there as well, with where we would want to treat, right? We, we have said all along, you, you know, you've heard this from us, we have said we are not the drug to treat the healthy, young, first-time, uncomplicated UTI patient. That's not necessary. Don't use us. So right there, you know, again, I'm, I'm very comfortable saying, "That's for someone else." But when you look at other patients and, and what they look like, I think there's a definite need. The advisory committee themselves, as you heard, said, "Look, we think there's a need for this in the market.
We're just concerned about resistance," and I wanna just share one little story about resistance because I think people believe that as soon as you use a drug, there's gonna be a substantial amount of resistance in the market, and I don't believe that's gonna be the case, and I'll tell you. For example, Cipro's been out almost 40 years. Bactrim's been out 50 years, right? So this isn't, "I came out yesterday, and now I'm sitting at a 20% resistant rate." For Cipro, as an example, we were able to dig up some old data from the 1980s and 1990s, made a few assumptions. They did about $100 million of sales when they launched Cipro in 1987 in their first year. They had five indications when they launched, including uncomplicated UTI.
The volume, based on our estimate of what pricing is, is about five million scripts in their first year. If we look at that compared to, like, a Sulo over a 10-year timeframe, in that first 10 years, we estimate Cipro volume is about 50 times the volume that we would do with Sulo. And most importantly, at that point, 10 years from launch, if you looked at some of the data that was out there, E. coli in ambulatory patients in the U.S., the resistance rate was between 1% and 3%. So I just wanna put it out there so people understand, I don't believe that this is going to be something that you use it, and all of a sudden, you've got this terrible problem for Sulopenem.
I think there's a different perspective, and that's part of why we feel pretty good about saying, "Look, this is for the right patient, full stop." There, there's no question, it's gotta be used in the right patients. But when we hear things like, "It's gonna come out, and it might impact other drugs, you know, other penems," it's, it's a possibility, but I think it's a very, very low-risk possibility that happens anytime soon.
What do you think the kind of appetite for pharma is in terms of bringing on board new antibiotics? Not, maybe not paying for the development, like for Iterum. You guys have already... You're done. We saw them do something with Spero, with GSK, for a complicated, separate. We've seen Scynexis do an antifungal and get that license for VVC, not dissimilar from a UTI-
Mm.
you know, very, very big indication. So there's opportunities there. Do you think pharma's kinda incentivized a little bit to kind of wade back into antimicrobials generally, and then is there an opportunity for Iterum... to get a partnership?
Yeah, I think there is, and I'll tell you why, particularly in Sulo's case. You know, our if we do get approved, our priority will be to go out and find a partner of some sort. It's been our priority since the board gave us that mandate earlier this year, hasn't changed, and we will redouble efforts on that. Having said that, based on current prescribing of uncomplicated UTI oral drugs, those physicians that are prescribing the most are primary care-type physicians, are urologists, are OB-GYNs, and emergency room. So when you think about it, this is a very typical, bigger pharma kind of product. I can say that with a lot of comfort, because I've done the analysis of all products in the U.S. over $50 million in sales, who prescribes them?
And not surprisingly, outside of specialty, derm, ophthalmology, rare disease, and oncology, all those other groups, diabetes, pain, neurology, urology, you know, vaccines, women's health, are predominantly prescribed by those physicians. Our message to bigger pharma would be, it's not about an antibiotic, so it's not like I'm jumping into the antibiotic space, as much as it's about physician type, and do I see those docs today? Are they prescribing our drugs? Do we have people that are talking to them, and can I put this into the bag? I think that's an easier sell, and I think it makes a lot of sense for bigger pharma, particularly if it's an approved drug, right? To your point, you're not paying for the development, but you're also... You get rid of that regulatory risk, and I think there is a...
I do think there's a good place for the drug in someone's hands like that, who's got those products that are being prescribed by those types of physicians.
The key to this, 'cause we're running out of time, is that PDUFA, everyone. It's 10 days from now or-ish, right?
Yep.
Um, so-
That's right
... and just quickly, the cash runway is it-
Yep.
It's-
We've got cash that'll get us into next year, so through the PDUFA, and then through a few more months, and then we're, you know, working on opportunities to continue to extend that as well.
Right, and the goal here is to get Sulo to maximize shareholder value in a way. If it's approved, get a partnership, or sale, or otherwise.
That is absolutely what we wanna do. Correct.
So in our view, lower risk, but you know, we have to wait for the PDUFA in 10 days. So we're excited about that, but we're out of time, so thank you so much, Corey-
Awesome.
... for coming on.
Thanks for having us, Jason.
I'd be happy to post PDUFA.
Awesome. Sounds great. Thank you.
Take care.
Bye-bye, now.