Annual JP Morgan Healthcare Conference. My name is Tess Romero, and I'm one of the senior biotech analysts here at JP Morgan. We're pleased to welcome to the stage Upstream Bio, and presenting on behalf of the company, we have President and CEO Rand Sutherland. Rand, over to you.
Hello everyone, Tess. Thank you so much for the kind introduction. It's a real privilege to be here today and to share our story among all the innovation that's happening at this conference. It's really an exciting time for our industry. So I'm very pleased today to share our story at Upstream Bio. Thank all of you for being here. And with the requisite disclaimers, I will move into maybe a little bit of an overview about who we are and what it is that we're doing. And I think it's fair to say that at Upstream, we're a dedicated team focused on a single mission, and that is to develop an antibody called verecitug for severe respiratory diseases. Now, what is verecitug? Well, it's the only known drug in development that targets the receptor for thymic stromal lymphopoietin, or TSLP.
TSLP, as I'll share with you in a moment, is an important mediator of a number of different diseases, and we actually have generated some very interesting data to suggest that we have a nicely differentiated profile for this molecule. Now, the provenance of the molecule is actually quite interesting. We did not discover it. We are developing it, having acquired it outright from Astellas, who discovered the antibody actually in a collaboration with Regeneron. So the molecule is a fully human IgG1. It's a product of the Regeneron antibody discovery platform, and as I will share with you in a moment, it has very differentiated pharmacology that we believe could translate to an important and differentiated clinical profile. What we've learned so far from our clinical trials to date is that our antibody very quickly and for an extended period of time occupies 100% of free TSLP receptors.
That translates to a pharmacological profile that is marked by potency. And that potency has actually allowed us in our phase 2 programs in both severe asthma and chronic rhinosinusitis with nasal polyps to evaluate dosing intervals as infrequently as every 24 weeks. So I'll show you on what basis we made that decision. And I'll also show you real data that we believe provide proof of concept in asthma. And we'll show you some differentiated data on both fractional exhaled nitric oxide and blood eosinophils to support that. On that basis, we've actually moved into phase 2, both in severe asthma and in CRS with NP. And also on the basis of emerging data that suggests a role for TSLP and COPD, we will actually be initiating a phase 2 program in COPD in the second half of this year.
Now, that's an important catalyst for us, but I think data are always the most important catalysts. And so what we will be providing in the second half of this year are the top line phase 2 data from our CRS with NP trial. And about a year from now, the top line data from our phase 2 trial in severe asthma. And it's important to know that all of our phase 2 studies have been designed not as exploratory trials, but as potentially definitive studies that could serve as an important part of a BLA registration package. And that's following a very well-trodden regulatory path in these diseases. I'll just say that we've got a great team who have been doing this kind of work for a long time. I'm very proud to be part of the team.
And we were also very happy to have a successful IPO towards the tail end of last year that has given us great funding. We are actually funded into 2028. That will get us through the two catalysts that I mentioned and allow us to really get our COPD program well along. Now, I talked about our multiple ascending dose trial in patients with asthma demonstrating proof of concept. And I will go into those data, but suffice it to say, when you sort of take what we've learned about the molecule and you stack up our attributes versus potential competitors in tezepelumab, Dupilumab, and Mepolizumab, what you see is that by virtue of targeting the receptor for TSLP, we're able to dose this drug either every 12 weeks or every 24 weeks in clinical trials.
We are able to do that actually in an injection volume that is very competitive. Even our largest dose, 400 milligrams, can be administered in two milliliters subcutaneously. And when you look at the data from our program, what you see is the effect on FeNO is actually superior to that observed with tezepelumab or dupilumab. Of course, IL-5s do not traditionally affect FeNO, and so there's no effect with mepolizumab. And also important to note, we are not an eosinophil depleter. And yet, despite that, we have an effect on eosinophils that also appears to match or potentially exceed that observed with tezepelumab as well. Because we're targeting TSLP, we don't anticipate being restricted on biomarkers.
That has been a feature then that has allowed us in our phase two programs to move forward without restriction, again, in severe asthma, CRS with NP and COPD as well. I mentioned the catalysts. I won't reiterate them again, but they are important and they are coming, and they are coming on time. The leadership team is great, both on the executive side, but I think even more importantly on the functional leadership side. We've got people who have really been doing this for a long period of time, despite the fact that we're small and relatively young. We are stocked with talent and we are focused on execution. We really plan to continue to getting this medicine as far forward and potentially to patients.
I won't spend a lot of time on TSLP because I know many of you understand what TSLP is, but suffice it to say that it's an alarmin, which is a type of cytokine, and it's produced at the epithelial surface in the skin, the gut, and the lung. We've decided to go after respiratory diseases, but that sort of breadth of expression actually gives you a sense of where this drug could potentially go from the standpoint of therapeutic areas, and what's a very unique and I think nice feature of TSLP is not only does it aggregate type two signaling, but because of its breadth of effect, it also has an effect that could be viewed as sort of down-modulating type one inflammatory pathways and also potentially fibrosis as well.
There's really, I think, good human genetics and actually human disease biology that have validated, and even into the commercial space with Tezspire, TSLP, and a lot of these diseases, and so we want to be able to leverage that biology, but then also take advantage of differentiation to potentially bring an even more efficacious and preferential medicine to patients. As I mentioned, we're focused on respiratory because we think that this is actually the sort of nexus of reduced risk, highest probability of success, actually highest degree of unmet need, and therefore highest potential commercial opportunity, but as I mentioned, there are a number of potential other disease states where the biology has been validated in one way or another and where over time we could potentially consider going forward, so let's turn to the data because I think these are what matter.
I would just say that our data come not just from the preclinical space, but also from phase 1 studies. All of the preclinical work and actually the phase 1 single ascending dose study were conducted by Astellas before we acquired the molecule. We've now taken it forward from the multiple ascending dose trial and forward. What you can see is that, not counting the folks in our phase 2 trials, 120 patient participants have actually received this drug so far. What we've learned is that the drug is generally well tolerated. It has a very predictable and reproducible pharmacokinetic profile, which is great and has been very helpful in terms of planning and dose selection. It's quite available subcutaneously. As I mentioned, we're going forward with a subcutaneous presentation. There's been nothing in the way of clinically meaningful immunogenicity thus far.
Importantly, the profile of this molecule is marked by rapid, substantial, and sustained effects on disease-associated biomarkers. Now, the data from the phase 1 single ascending dose trial in healthy volunteers actually put on the table very early in the clinical life of the program, the fact that this drug could potentially be dosed at least every 12 weeks, if not potentially every 24 weeks. It was really those data that then led to the design and conduct of a multiple ascending dose trial, which was placebo-controlled, was actually randomized and blinded, and really performed in a way that was designed to give us a really broad data set to help us understand how this drug might or might not work. If it did, how might we take it forward from the standpoint of dose selection?
Importantly, this MAD study was conducted in patients with asthma, all of whom were, because this was a signal-seeking study, required to have evidence of Type 2 inflammatory tone as manifested either by blood eosinophils or FeNO concentrations and there was a range of background therapies, but all of these patients did in fact have asthma and were enrolled in the study. Again, in four different cohorts, six receiving per cohort active drug, two placebo, with the regimens that you see here, ranging from a 25 milligram single dose all the way up through 100 milligrams dosed every four weeks. The primary objective, of course, was safety and tolerability, but we were able to obtain very useful pharmacodynamic and pharmacokinetic data as well. First, importantly, from the standpoint of safety, the safety and tolerability profile seen here is very consistent with other agents in the class.
The class writ large noted for actually fairly bland safety. There is nothing here that was concerning, nothing that required discontinuation of the drug or subject participation, and importantly, nothing that prevented us from moving forward into phase two with these doses and dose regimens. Now, I mentioned the reproducibility of the pharmacokinetic profile and what we're showing you here are the modeled curves from the phase one SAD overlaid with the individual points from the phase one multiple ascending dose trial.
And what you see here across healthy and patients, participants with disease, is that actually the profile is quite reproducible with perhaps the exception, actually notably that at the higher dose regimens further out, that there's actually a bit more drug available on board than would have been predicted, sort of helping push us even further to understand that Q24 week dosing could actually be an opportunity here as well. But what really got us excited were the pharmacodynamic data. I'm showing you two different things here on the left of the slide. You're seeing receptor occupancy data going from 100% of receptors being available sort of at the top and 0% of receptors being available at the bottom. You see a black line showing the effect of placebo, which is no effect.
But with all doses administered, what is observed is that at two weeks, there is 100% receptor occupancy. And that with all doses except for the 25 milligram single dose, that effect or that occupancy of the receptor persisted for up to 24 weeks after the final dose. Now, even with that low dose single administration of 25 milligrams, you see an effect for 12 weeks. So these are really quite durable effects from the standpoint of receptor occupancy. And then if you just move to the right, what you see is a very similarly durable effect when it comes to the disease biomarkers of blood eosinophils and FeNO. Now, these both probably represent different things. Eosinophils may be representing a bit more of systemic type 2 tone with FeNO, really because it's produced in the airway epithelium, reflecting airway inflammation.
And what you see with both of these and really very much overlapping both the kinetics and the magnitude of effect with these different dose regimens, reductions of blood eosinophils essentially to normal circulating concentrations and reductions to approximately normal of FeNO as well, recognizing that there's some variability in starting concentrations. Now, just to contextualize these data a bit, we sort of stood them up against what's been reported in the tezepelumab development program and with the important caveat that we're comparing data from a phase one multiple ascending dose trial to data from the phase two and phase three programs from Tezspire.
What we see is that when we look at the absolute change in parts per billion of FeNO across these three different dose regimens, we saw between a 28 and 47 parts per billion reduction in FeNO, which when translated to percent reduction from baseline equated to about a 51 to 54% reduction in FeNO, and when you look at these versus what was observed in the Tezspire program, you see that the absolute magnitude of reduction there was about 17 parts per billion with a percent versus baseline change of about 25% reduction as well, so at a very high level and sort of qualitatively, quantitatively looking at comparability versus Tezspire, it appears that there's evidence here of an effect that is at least, if not greater than that observed with tezepelumab.
And we were then able to take those data and actually use them to do fairly sophisticated PK and PD modeling to really understand how our potency and how that observation we made about receptor occupancy then translated to dose selection for our phase two trials. And so what we're showing you here are the results of that modeling and comparing it against the outputs from the tezepelumab program. And what you see when we calculate the EMAX, which is essentially the calculated maximal effect of verecitug on FeNO. And when we compare that versus tezepelumab, you see that our EMAX is calculated at 43.4% compared with around 28% observed with tezepelumab.
But I think most importantly, and when you look at the EC50 and the EC90, so these are the concentrations of drug required to achieve an either 50% or 90% maximal effect on FeNO, you see that our concentrations are 0.008 or 0.07 micrograms per ml, which are approximately 300-fold lower than required for tezepelumab. So this is a very strong sign of the potency of our molecule. These data were very helpful to us in terms of being able to do robust modeling and dose selection for phase two. And on the basis of these data, we were actually able to select two doses for our phase two program in severe asthma. We're taking forward 100 milligrams q12 weeks and 400 milligrams q24 weeks in that trial.
Now, what you see here is that we've shown the sort of population predicted drug concentrations for both of these dose regimens, and we stack them up against the EC90 for FeNO. And what you see is that very comfortably 100 milligrams q12 keeps drug concentrations above the EC90 for the entire 48-week period that we modeled here. And in the case of 400 milligrams q24 weeks, the same is true with perhaps the exception of like the last couple of days of that 24-week dosing interval. And that's important to note because that two days may or may not matter, but we'll find out in our trials. Importantly, however, we have used the EC90 for FeNO as our threshold for efficacy here. And that's a very conservative way to look at this. Normally, you might use an EC50.
Had we chosen the EC50, we would be well above that for the entire period with both of these dose regimens. So our going-in hypothesis actually in the severe asthma program is that these two doses and dose regimens may not be distinguishable from each other. We'll see what happens, but we're working hard to get the data and see what's true and what isn't. Now, as I mentioned, we've got these two clinical programs underway.
I think in the interest of time and maybe because we'll discuss a little bit about this in the Q&A, I won't get into the details in great depth other than to say again that both of these have been designed with sufficient power with the right endpoints such that if they are positive trials, they will give us a reasonable basis to go to the regulators and have a discussion about including these trials as potentially one of two registrational studies. And I would also note that we fully intend to take the same approach with our COPD program in which we intend to dose the first patient in the second half of this year. So again, just as a reminder, the nasal polyps program will read out top line data in the second half of this year. Recruitment's going well, and we feel very good about that commitment.
Similarly, with severe asthma, which we intend to read out in the second half of next year. I think just maybe quickly to wrap things up, these are large markets that we are looking to address. Biologic sales in severe asthma and major markets are still growing despite the fact that there are now six biologics approved for this indication, and it's projected that there will continue to be growth at approximately 6% through 2032 in severe asthma with sales maybe exceeding $12 billion, and you might say, well, there are already six drugs on market. Is there really an opportunity here?
It's been really interesting to observe this market and watch it sort of maybe evolve over time because what has become clear is that even though there are efficacious biologics available, that there still is a lot of opportunity in terms of penetration and the ability to treat patients who need to be treated with biologics who are not yet receiving them. And a very interesting feature of this market has been that when new differentiated and efficacious drugs come to market, they actually can take substantial share. I think all you have to do is look at the Tezspire launch to recognize that that's true. And when they take that share, they don't really do it by eroding the share of others. They do it by driving penetration.
And so we believe that this will be a feature of the market that will continue to be operative for a substantial period of time. And it's also one, by the way, that we would look forward to the COPD market as well, recognizing that that's a much younger market now with Dupixent only having been within the last few months approved in the United States for the treatment of COPD. So we think there's substantial commercial opportunity here for differentiated assets. I've shared with you our data and the rationale for why we believe we could be differentiated. And I've shared with you that we're doing the trials to understand if we are differentiated. So we're looking forward to reading these out, and I think it's an exciting time for the company. We are not just using our belief here.
We're using data, and we're actually using the results of market research to help inform our understanding, and just working from the bottom up, we know that the TSLP mechanism is an attractive mechanism of action. It's differentiated in a number of ways that are clinically meaningful from IL-4/13, from IL-5, from IgE, and so from the standpoint of just prescriber preference and understanding of this mechanism, there is a strong understanding and a high preference for it as an attractive mechanism of action, and then when you move up and you just test, for example, the performance of a Tezspire-like efficacy profile, but then add to that q12 or q24 week dosing, we see that that's very attractive to prescribers and also very much supported by payers as well.
And I think probably most importantly, something that patients are really excited about because the ability to take a drug maybe two or four times a year versus every two or four weeks is a big difference for patients. And so our base case for differentiation, I think, is extended dosing. We've showed you the reason to believe there with even a TSLP class-like effect. But we do believe that there's an opportunity for an upside here that could potentially involve even a higher degree of efficacy because of the potency of our molecule and because we're targeting the receptor. So all forward-looking statements. We have to do the work. We need to read these trials out, but we're excited to see what we will show there.
Having already said what I was going to say about COPD, with the exception that it's an even bigger market than severe asthma, I will finish there and, Tess, happy to chat further. Great. Thank you, Rand. You talked just now about how verecitug is the only therapy currently in development targeting the TSLP receptor and not the ligand. Why is that? And can you briefly maybe orient the listeners to the history around the target? Sure. Let me get this on now. All right. There we go. It's hard for me to exactly answer why because we're not in the heads of everybody making decisions, obviously in all the companies. I think there have been previous programs, or at least one program that we know of targeting the receptor. That was Roche's program. We also know that that program was terminated in phase one.
The reasons for that have not, to my knowledge, been publicly disclosed, but I think suggest, given the phase of termination, that there could be a number of important limiting approaches there with that program that do not appear to apply to us. As you've sort of already alluded to, it is important to note that we are the only drug in development targeting the receptor. Everybody else is going after the ligand, and we're doing some very interesting work at Upstream trying to understand the why behind why this makes a difference, and there's some very interesting observations that we've made about relative expression of the receptor versus relative expression of the ligand, which indicate that there's a lot less receptor being expressed than ligand.
We've also observed that there appear to be differences in turnover of these two targets as well with a much slower rate of refresh, if you will, of the receptor as a target than of the ligand. So we're working on these data and we'll be publishing them, but it suggests that it's simply hard to get enough drug on board for enough of a period of time to really sop up enough of the ligand to have an effect that's similar to what we observe.
So maybe we'll move stepwise through the readouts here. Oh, question? Yeah, but I have some way after. Okay. Go ahead. Thank you. Thank you very much. Uncertain.
I was wondering, given your really high potency and reasons we've seen or we're guessing from past failures in atopic dermatitis, what criteria are we watching for internal or external for potential indication expansion there?
Yeah. So the atopic dermatitis question is a really interesting one. And you've seen, I think, even over the last few weeks, other companies in licensing assets targeting TSLP and deploying them in AD. We have looked very carefully, to the extent that we can, to the data from Amgen's two robustly designed and executed phase two programs in atopic dermatitis with tezepelumab, both of which were negative. And it concluded that those trials were robustly negative. Now, it's interesting that that was the observation given the genetics and sort of human disease biology that would suggest a strong role for TSLP in atopic dermatitis.
So we don't quite understand why that turned out the way it did, but it does lead us to believe that the biology there may be a little more complex than simply just TSLP, TSLP, TSLP. So we are not pursuing AD at this point in time. We are not pursuing other indications at this time, not for similar reasons, but just because right now we're focused, we're resourced, not constrained, but we have enough resources to do the work that we're doing, but not to go after other indications. So we'll be focusing on severe respiratory diseases for now. As we move forward and as our sort of book of business and resources change, we may consider either other dermatological diseases or potentially gastrointestinal diseases as well, including eosinophilic gastrointestinal disease. Okay. Great. Yep.
So moving stepwise here, I thought maybe we'd start with CRSwNP just because it's data expected this year. Rand, you alluded a little bit here, but how is enrollment going and how should we think about when you could complete enrollment to meet that guidance?
Yeah. So enrollment's going very well. We're not specifically communicating where we are right now, but we have committed to read these data out by the end of the year, and we will do so. Okay. How was the trial designed to optimize its chance for success? Well, I think it's been interesting. Even over the course of the last few years, the regulatory guidance, at least in the U.S., for CRS with NP has evolved. And so we are taking that into account.
And so the first thing to do is design your trials in a way with endpoints that not only are meaningful to payers, patients, and physicians, but also to regulators. So it sounds obvious, but that's important to do. We have also really, again, designed these trials in a way that they are sufficiently powered to detect effects that are not only clinically meaningful, but are clinically meaningful from a contextualization standpoint versus the potential competitors. And so this has really been designed as a very robust, potentially registration-enabling trial. And I think we're in a good place to have it read out positive or negative in a way that will be robust.
Okay. Can you quantify, put any numbers around that for us? Yeah.
I mean, let's just say that if you, for example, look at the label for Dupilumab, there's about a two-point change in the endoscopic nasal polyp score that was reported there. We think that that's probably relatively a floor for efficacy that we would want to see to be competitive. I mean, there's a little bit of room around that. We've powered to be even a little bit more robust than that. So I'm not going to put specific numbers on it because it's also a question in the field about the dynamic range of the nasal polyp score versus some of the other endpoints in this disease. But we are well positioned to read out, if positive, a competitive profile from that standpoint.
What were your impressions of Amgen's phase three readout in November for Tezspire and the indication?
What are you monitoring for in the fuller results?
Well, we were left wanting more, which hopefully we're going to get sometime in the next couple of months, maybe even. We don't know, but there are conferences early in the year that would make sense for a readout there. We were happy to see sort of their top line notification, and that's reassuring, I think, for patients that this is a tractable pathway. Of course, their secondary analysis from their asthma program already had suggested that. And we've seen with Dupilumab and others that modulating this biology can really lead to significant clinical benefit in these diseases. So we're excited to see what they've done. We're excited to learn from it. And it should provide yet another very nice way to contextualize our data. Okay.
Switching gears now to severe asthma, similar question that I asked for CRSwNP, how is this enrolling and how should we think about timelines to data?
Also enrolling well, also on track to readout when we have committed.
Okay. Can you characterize your expectations a little bit more around what constitutes good data and what would be a home run?
Well, good data, I mean, we don't always talk about this in these kinds of settings, but high-quality data from well-conducted, carefully monitored clinical trials where the team is very much on a daily basis engaged with sites and with CROs is actually really important. It's something that we've put a lot of effort to as a company and really feel very strongly about. So we want data that are interpretable. We want data from trials, as I mentioned.
We've taken the same approach with severe asthma as with NP and well with COPD in terms of robust trial design. And again, I think I sort of showed you a competitive context, which included Tezspire, Dupixent, Nucala. We need to be in that range for efficacy. And we also potentially need to differentiate on dosing interval as well. So we would not see lesser efficacy necessarily being worth the trade-off of an extended dosing interval there.
Okay. Okay. I guess I could think another question we often get is how to think about the evolving competitive landscape here just because there are so many products and companies out there that are looking to develop new products in the space. So how do you think about that?
How much time do we have? It's a pretty complex landscape. It's evolving every day in the case of today, even every hour.
And so we've sort of gone back to first principles. So what is the mechanism of action? We are differentiated from everybody else based on mechanism of action. We've shown you the data from prosecuting the target the way that we have, and we will see what those mean from a clinical efficacy standpoint. So the fact that we're able to do that means that we are progressed to a point and have done it in a way that has allowed us to not just sort of make claims, but make claims and share plans on the basis of data. And that's because of the maturity of the programs. And so I think the second thing to look at is just where is company A versus B?
We feel very good about where we are in the long-acting TSLP space, not only because of our MOA and our data, but because of how and how quickly we're executing. That's another thing. I think then you can sort of separate the landscape. Again, everybody else is targeting the ligand. Some are doing it with purported extended dosing. Now, in most, if not all cases, that is achieved through Fc engineering, which is a different approach that we're taking. That approach may have differentiated durability versus us, and that durability may or may not extend to both durability of pharmacodynamic effect and durability of clinical effect. We think it's important when appraising other programs to look at that.
Moving away from long-acting agents, there's a whole universe of short-acting monospecifics that are in phase one development in healthy volunteers, in some cases in airways disease, in some cases in atopic dermatitis. There are also multi-specifics. We're following those closely. Right now, we feel pretty good about where we are and what kind of data we're going to read out and how re-risking and hopefully de-risking those are in terms of understanding the profile of the molecule as it moves forward. We're working hard to move as well and as quickly as we can to understand if we have a medicine for patients here.
Moving along here, what are the key considerations that we should be thinking about around designing a phase two study that's optimized to succeed in COPD? Yeah, so that's a great question.
Actually, the Tezepelumab data that were reported at ATS last year in COPD were really helpful in that regard. We've also obviously very carefully looked at Dupixent's data in COPD as well. I think what we've learned, and it wasn't a surprise, is that these biologics potentially can be transformative in these diseases, and it'll be really great. I mean, I was an asthma physician, pulmonary physician at the start of my career, and this will transform the treatment of COPD, Dupixent. I think that the same will be true in biologics more broadly construed once we have good data. What do we have to focus on there? We still have to focus on exacerbations. We still have to focus on symptoms and lung function. Again, we need to go after what matters to patients, physicians, and payers, and what will support robust regulatory interactions.
So looking at, for example, annualized exacerbation rate is going to be very important. Now, what's been very interesting is the discussion and debate around what's the right eosinophil cut point in COPD and how do you think about that. And again, we could talk about that for a long time, but we think it's pretty important, I think, to tie ourselves to the data from Amgen and from that proof of concept study, which indicated really sort of a bit of a line at 150 eosinophils and up in terms of efficacy, but still leave oneself the opportunity to explore lower eosinophil counts and the potential for pushing that threshold down. So we're not at the point yet where we're fully communicating our design, but it will look at important and meaningful endpoints and try to take advantage of what we know to date about the biology.
When do you think you'll be able to come to us about the design or inform the street with respect to how you're thinking about it? Well, I think by the time we dose our first patient, we would be ready to do that, and that would be in the second half of this year.
Fair, so I mean, I think you alluded to a lot of this or some of this in your prepared remarks here. But in each of the core indications, what does your market research suggest drives market share higher or lower for a new biologic entrant in the space? What are the key similarities and differences across these couple of focus areas that you have at the company?
Yeah, it's a good question. I'm not sure we've done the full conjoint to test the interaction of all of these different things.
Assuming base safety, which is critical, you really have in our sort of paradigm a trade-off or not between comparative efficacy and dosing interval. The way we went about asking our questions with our market research was really to put sort of, again, a Tezspire-like efficacy profile in front of folks and then pair that with a Q12 or Q24 week dosing regimen, and when we did that, it was clear that there was a lot of value associated with extending the dosing interval in a way that maintained a very high degree of efficacy. The way we did that was stepwise, so most of the value came from going to, say, Q4 to Q12 weeks. There is incremental value associated with going to Q24 weeks.
And they're sort of soft data, but with that kind of profile, even 50% or greater of NRx was selected by the folks we talked to in terms of a preference profile. So it seems to be very attractive. That work was done before the landscape, I think, has evolved in ways that we've been discussing before we saw the readout from Depemokimab in asthma. So this is a rapidly evolving space, but we do think that a high degree of efficacy with extended dosing interval is a very valuable value proposition.
Okay. And any comments you'd make specific to the CRSwNP or the COPD populations, maybe CRSwNP? Yeah, so just in terms of which aspect? I guess what patients and prescribers are really looking for. Yeah.
I think in NP, it's interesting because part of the treatment paradigm for NP has been a lot of sort of experience at the patient level, first with inefficacious medical therapy, then potentially having to go to surgery, which is very difficult, very painful, often associated with a high degree of recurrence, and then after that, being eligible for biologics trials, and now I would say highly efficacious biologics, so actually, we think it's interesting. That's the population that needs to continue to be studied, but we do think there's an opportunity for the treatment paradigm to change such that having to go through surgery before being eligible for a biologic may not necessarily be the right thing for all patients.
Now, we are not testing this in our trials, and the field writ large needs to work on this and sort of look at what's appropriate from the standpoint of practice patterns. But if you benchmark existing epidemiology and existing sort of patient eligibility data to that kind of environment, but then look down the road and ask, okay, if that changes and more patients become eligible and don't have to go through surgery first, there may be an opportunity to expand patient eligibility and really get more patients access to these drugs, which remove this horrible feeling of having your head completely full, allow you to smell, allow you to breathe, allow you to sleep, a lot of things that are really very miserable experiences for patients.
So this is what all the trials look at from the standpoint of endoscopic data, nasal congestion score, and other sort of patient-reported outcomes. So we think following that paradigm is really important. Also in COPD, I think this is a case where, unlike what we've seen in other programs where history of smoking and active versus historical smoking may potentially be drivers of efficacy, that is not a signal thus far that's been seen with TSLP. So we're looking at a broad population from that standpoint and again, want to get to the patients with frequent exacerbations and most severe disease. Okay. Maybe I'll just conclude with a financial question.
What is your cash runway? Oh, through 2027.
Through 2027 into 2028. And after the IPO pro forma, about $500 million on hand. Okay. And that supports the milestones that you've laid out.
That will support the readout of our phase two in CRS with NP in the second half of this year, the readout of our severe asthma program in the second half of next, and the dosing of our first patient and execution of our COPD program starting the second half of this year.
I think that might be a good place to leave it. Thanks, everyone.