Mannkind Corporation 0 Earnings Call

Good afternoon, and welcome to the MannKind Corporation conference call to discuss the phase I-B results for nintedanib DPI. As a reminder, this call is being recorded on July 29th, 2026, and will be available for replay on the MannKind Corporation website shortly after this call for approximately 90 days. This call will contain forward-looking statements. Such forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from these expectations. For further information on the company's risk factors, please see the Form 10-Q for the period ended March 31st, 2026, this morning's press release, and the slides prepared for this presentation. Joining us this morning are Michael Castagna, Chief Executive Officer, and Dr. Wassim Fares, Senior Vice President and Therapeutic Area Head, Respiratory. I'd now like to turn the conference over to Mr. Castagna.

Thanks, operator, good afternoon, everyone. Thank you for joining us for this focus update on nintedanib DPI. I'll begin with the IPF opportunity and why we believe this program can create meaningful shareholder value over the coming years. Dr. Fares will review the clinical data, including our phase I-B results, as well as a history of the program leading into our global phase II now underway. I'll return with a few closing thoughts before we open up the call for questions. Let me start with the broader context. At the beginning of the year, we laid out three major catalysts. We have now delivered on all three through July. The Afrezza pediatric indication is now approved, expanding the population we can serve and creating a growth opportunity. We're excited about the early days of launch, and we'll provide more details on our next week's earnings call.

FUROSCIX ReadyFlow is approved, reducing administration from hours to seconds while supporting broader adoption and operation in health systems, as well as a lower cost of goods. Two approvals in a single year is a lot for a company of any size, let alone ours. Which brings me to nintedanib DPI. When we called this update, we've completed the third catalyst on this page, and it's the one we spent the last seven years to get to this point. There's an urgent need for new effective therapies in IPF, and we believe lung-targeted delivery is the best approach that addresses the tolerability barriers that are holding today's therapies back. For us, our phase I-B data is the key clinical de-risking step for the entire program, and it's the reason we wanted to walk you through the history and the full picture of where we are today.

Let's begin with the opportunity. The first is that our phase I-B study demonstrated safety and tolerability in patients with IPF. That's a dataset we haven't had, and I'm proud to say there were no serious adverse events, no GI issues, and no patient discontinued. Dr. Fares will take you through the details shortly, but I'd summarize it this way: The tolerability questions we and our investors have cared about, including inhaled anti-fibrotic therapy in the lungs, are precisely the questions this study was built to address, and the results give us the confidence to advance this program forward. Our global phase II is underway, and we are actively progressing site activations, and we expect enrollment to continue to increase as we progress through 2026. I want to spend a minute why we're investing here. It's because IPF is a category that's already been commercially validated.

We don't have to establish a disease state. These are approved therapies on the market today. Ofev has generated more than $4 billion in global revenue just in 2025. I hear Jascayd is off to a fast start, approaching $2 billion in their first year of launch. You have a blockbuster precedent in a disease with roughly 100,000 IPF patients in the U.S., a population that unfortunately continues to rise year after year. Beyond IPF itself, there's a larger adjacent segment of patients with pulmonary fibrosis, more broadly, interstitial lung diseases that can lead and progress to fibrosis. The market does not need to be created. The disease burden is clear. The treatment category is established. The unmet need remains substantial and unchanged, and that combination creates an opportunity for a targeted inhaled delivery.

Let me be a little more specific about the challenge we face because it's not a problem of efficacy. nintedanib works. We don't question that. It's the first drug to really show what it can do to help patients. The problem is patients can never start therapy because they know the side effect profile or they don't stay on therapy. Three out of four IPF patients are not on an approved anti-fibrotic therapy, despite the fact that 80% face the risk of death within five years of diagnosis. Among those who do start, published discontinuation rates run as high as 50%, and current therapies carry major tolerability challenges. Our aspiration was to take a proven molecule, change its route of administration to solve this unmet need created by the standard of care.

nintedanib DPI is designed to deliver drug directly to the deep lung where fibrosis occurs while bypassing the GI tract and reducing systemic exposure. The GI adverse effects associated with oral nintedanib are the reason so many patients stop or never want to start. Reducing systemic exposure is the mechanism by which we hope to change the treatment experience. We believe this approach has the potential to improve efficacy and tolerability, which may support long-term adherence. This thesis has recently been proven out by the data released on inhaled pirfenidone, as well as TYVASO's TETON 1 and 2 trial, all of which show that targeted lung delivery therapy does drive efficacy in IPF.

With these phase I-B results, we have more confidence in our program and why this targeted approach will have an impact on patient outcomes. The reason we believe we can execute on this thesis is the platform underneath it. Technosphere technology provides highly efficient delivery of a dry powder through a small portable device that we call Dreamboat. The FDK microparticles at the core of our technology drive rapid uniform distribution deep into the lung with extensive throughout the lung tissue. Often I get asked, "Can they inhale a dry powder? Will they receive the product?" The answer is yes. If air is flowing, our powders are going into that area of the lung. It's already been validated on two FDA-approved products, Afrezza and Tyvaso DPI. For us, that changes the CMC and drug device risk profile of a program like this considerably.

We're not simultaneously trying to prove a new delivery technology and a new molecule and a therapeutic hypothesis. We know how to formulate this on our platform. We know how to manufacture at scale. We have real-world data experience in how patients use our inhalers day in and day out. For a chronic disease where patients may be on therapy for years, the practical characteristics of the device, the portability, the fast inhalation, are not a footnote. They are part of whether a therapy gets used at all. One technical point worth understanding is the versatility of the platform. A Technosphere particle and the products that we make are mostly FDKP based carrier with a small percentage of active drug, as you can see here.

Technosphere powder has now been used in more than 50,000 patients, a substantial base of experience with the carrier itself before we ever even put nintedanib on it. This gives us ability to really understand where our particles go, how they are formed, and how patients can tolerate them across multiple diseases. I also want to address a question we get regularly, which is whether patients and prescribers will adopt a dry powder inhaler. We have a case study from our own experience in the inhaled treprostinil market, where DPI today has grown to 80% of the market since launch. Patients have demanded this, patients have enjoyed it. In this pulmonary population, many of them elderly, many of them with compromised lung function, the DPI format has become the dominant way the therapy is delivered.

I'm not going to claim that history will repeat itself automatically in IPF. It does tell us something important about behavior. When a dry powder option offers a genuinely better experience than the alternative, clinicians prescribe it and patients demand it. Those dynamics give us confidence in the commercial logic behind the nintedanib DPI, assuming we deliver the clinical profile we're working towards. With that said, let me turn it over to our clinical data. I'm pleased to introduce you to Dr. Wassim Fares, who joined us a little over three years ago to lead our respiratory therapeutic area. Dr. Fares is a board-certified pulmonologist with more than 18 years of running respiratory clinical development programs in PAH, IPF, from early-stage studies all the way through phase III and post-approval. He has spent a career on serious, rare lung diseases across both academic medicine and biopharma.

He understands the challenges patients face, how to develop drugs, and how to get these to patients in the quickest way possible. Thank you, Dr. Wassim, for joining us today. I will turn it over to you.

Thank you, Mike. Good afternoon, everyone. Before starting the clinical program in humans, we conducted multiple animal studies to characterize the pharmacokinetics, pharmacodynamics, and safety of nintedanib dry powder inhalation. In these preclinical studies, which included five non-GLP, GLP stands for Good Laboratory Practice, and three GLP studies, lung concentrations were at least 100-fold higher than plasma with minimal systemic exposure. We did 28-day toxic studies in two different species and a six-month repeat dose study. These studies showed no clinical toxicity. They established a wide safety margin, which was the pharmacokinetic and safety foundation we needed to move into humans. Since then, our clinical program has advanced from first-in-human healthy adult volunteers to patients living with IPF.

We published the results of the healthy volunteer study along with the preclinical studies earlier this year. We are reporting today the results of INFLO-1, the phase I-B study that showed safety and tolerability of nintedanib DPI in patients living with IPF. We are now enrolling in INFLO-2, our global phase II study for patients with IPF. In less than two years, the program has moved from first-in-human dosing to a global phase II study, which we are very proud of. The team has done an exceptional job with this progress. In the next few slides, I will go into more detail into each of these studies in humans. Starting with the first-in-human study. It used a standard stepwise design. Part A evaluated single ascending doses from two to eight milligrams. After formal safety reviews, Part B evaluated twice-daily repeat dosing over seven days.

The objectives were safety, tolerability, and pharmacokinetics, not efficacy. We wanted to know whether we can deliver enough exposure in the deep lungs where IPF pathology is, whether exposure increased predictably with dose, and whether repeated delivery into the airways produced any signal of concern. nintedanib DPI was safe and well-tolerated over seven days in healthy adults with no safety signals, no serious adverse events, and no study drug discontinuations. We observed mild reversible cough, typically after the first dose, without worsening on repeat dosing. We did not observe the systemic adverse events commonly associated with oral nintedanib, including diarrhea, nausea, vomiting, or headache. This was a short study in healthy volunteers, so it cannot establish chronic tolerability. It provided the first human evidence that the formulation behaved as intended and supported advancement into patients with IPF.

Before I remind you of our PK data that we published earlier this year, I want to highlight the importance of nintedanib Cmax, which supports a lung-targeted approach. Published preclinical work shows that peak lung concentration, that is Cmax, is more important to nintedanib's anti-fibrotic activity than total exposure over time, that is AUC. In those models, brief high concentrations were sufficient to inhibit fibrotic pathways, while additional ongoing exposure beyond the peak did not add much. That creates a rational fit for inhaled delivery. Achieve a high, brief concentration in the lungs while limiting prolonged systemic exposure. Our human pharmacokinetic data are consistent with efficient drug lung delivery. For inhaled nintedanib to reach the blood, it must go through the deep lungs first, including alveoli, pass through the lung interstitium, where IPF pathology is. Then cross to the blood.

Plasma levels are an excellent surrogate of how much drug is delivered to the deep lungs. To orient you to this figure, our PK data are on the left. The ones on the right are published data from a nebulized nintedanib formulation. At comparable doses, nintedanib DPI produced plasma Cmax values approximately six to eight times higher than published values for nebulized nintedanib. This is a cross-study comparison, not a head-to-head trial, and it should be interpreted accordingly. What it shows is that the Technosphere formulation is delivering drug efficiently to the deep lungs with an immediate plasma peak. Let's turn to the study most relevant to today's update. INFLO-1 was a randomized, double-blind, placebo-controlled phase I-B study in 27 patients living with IPF across 10 sites in the U.S.

Patients received one of two active regimens or placebo over seven days, with formal safety review by the sponsor, us, and an external Data and Safety Monitoring Board before dose escalation. The study was designed to assess short-term safety, tolerability, and pharmacokinetics. The gating question was simple: Can a fibrotic lung tolerate repeated administration of nintedanib DPI? The answer from this study was a clear yes. The safety profile was clean. There was no drug-related diarrhea, nausea, or vomiting. As you know, these are the major adverse events that limit the use of oral nintedanib. There were no bronchospasms, no changes in oxygen levels or respiratory rate, and no study drug discontinuations or dose reductions. This is a meaningful de-risking step as we move into phase II. Let me address cough directly, because it is the most common question about delivering a powder into fibrotic lungs.

Approximately 60% of patients living with IPF who received active drug in this study had no cough. Roughly 90% had either no cough or only a mild, that is Grade 1, cough adverse event, and none had a severe cough. When cough occurred, whether in this study or in our other studies using Technosphere technology, it generally followed the first dose and did not worsen with continued dosing. There were no discontinuations, no dose reductions, and there was no correlation between cough and powder mass. The observed pattern is consistent with prior experience across our Technosphere platform, where clinical data from approved products show less than 3% discontinuation due to cough. The extent of patient exposure also matters. Let me orient you to this figure. Magenta color reflects exposure in our trials with nintedanib DPI. Gray color reflects reported exposure by a nebulized nintedanib formulation.

On the left, it shows exposure in healthy volunteers. On the right, it shows exposure in patients living with IPF. Across INFLO-1, we administered around 448 inhalations of nintedanib DPI to patients with IPF. I'm not talking about exposure in healthy volunteers. I'm talking about patients with the target disease, idiopathic pulmonary fibrosis. Contrast this with what has been reported with a nebulized nintedanib formulation. We could find that only six doses were given to patients living with IPF, one dose per patient for six patients with IPF. As you know, exposure and clinical experience in patients with the target disease are very important. With that exposure to nintedanib DPI, we saw no difference in spirometry between active drug and placebo, which use an empty cartridge. For clinicians evaluating an inhaled therapy in a compromised lung, that is an important pulmonary safety observation.

This provides an impressive early safety database in the target population using a carrier already experienced by thousands of patients living with ILD through Tyvaso DPI in PH ILD. With that strong foundation, let me turn to phase II. INFLO-2 is a randomized, double-blind, placebo-controlled global study that will enroll 210 patients with IPF. The 12-week control period evaluates two active regimens against matched placebo, followed by a 24-week open label extension. At the end of that trial, we will have safety and efficacy data in patients with IPF over a nine months period. The primary objective is safety and tolerability with forced vital capacity, or FVC, as the key efficacy endpoint. Importantly, the study includes patients who are untreated, that is, they are not on background IPF therapies, as well as patients who are on stable background therapy of pirfenidone and/or Jascayd.

That design reflects the evolving IPF treatment landscape and preserves our ability to understand nintedanib DPI, both as an alternative first-line anti-fibrotic and as a potential backbone for combination therapy. With that, I'll turn the call back to Mike.

Thanks, Wassim. Let me close how we think about the value here. First, on patent protection, we've built a layered patent estate specific to nintedanib DPI in combination use with the longest dated protection extending to 2046. Underneath the product estate sits the platform itself with more than 1,400 patents enforced worldwide. I'd like to add one point beyond patents. Manufacturing this powder at scale is genuinely complex, and that complexity adds a practical barrier to entry. We've spent 35 years building the capability to make it at scale, and it isn't something a competitor can quickly stand up. Nintedanib DPI is designed to be delivered in seconds and give patients lung-targeted delivery without the nebulizer burden or the systemic adverse events associated with oral therapy.

Our Technosphere particles are already validated in two FDA-approved products used in the adult population, including elderly individuals with compromised lung function. This overlap is within our target population is really relevant to where we're going. We also have experience in this clinical setting, and our platform has demonstrated safety and tolerability in patients with underlying lung diseases. Tyvaso DPI is approved in PH and PH ILD, which includes patients who also live with IPF in some cases. nintedanib is the gold standard in this disease, but the GI burden of the oral caps how much it can be used. I've never believed the ceiling on this molecule was scientific. It's always been tolerability, and that's been going on for over a decade. At the same time, IPF is moving towards combination treatment as more options become available.

We've seen the same progression across other chronic conditions, including respiratory disease, where monotherapy comes out and establishes a category, new mechanisms enter, and combination therapies follow. This is further evidenced as we look at the data just recently presented in TETON 1 and 2 that showed using combination use in IPF got additional effect size for patients. Our thesis is that a well-tolerated, seconds-long inhalation nintedanib can become the backbone of future regimens. If patients are going to receive multiple therapies, the foundation needs to be effective, practical, and something they can remain on. That is our strategic thesis, not a demonstrated outcome, but it explains why we've designed our phase II the way Dr. Fares described it, preserving the ability for combination approaches as well as monotherapy. Finally, I want to zoom out because nintedanib DPI isn't our only exposure to this market.

We have three shots on goal when we look at the IPF landscape, all of them running on our proven platform aimed at large underserved market. Nintedanib DPI is the asset we fully own. Tyvaso DPI through our partner United Therapeutics is approved today with potential future expansion in IPF. We recently announced in partnership with United Therapeutics, the ralinepag DPI that is progressing towards IND. Each of these programs draws in the same formulation science, the same manufacturing base, and the same clinical experience delivering dry powder into compromised lungs. The scientific and operational learnings from any one of these carries into the others, and we're applying a large single capability across the same market, multiple angles from our leading asset as well as our partner programs.

None of this guarantees clinical or commercial success, it means we have a shot to make this very successful to help patients. With that said, operator, I'm going to turn it over and open it up for Q&A.

Thank you. At this time, if you would like to ask a question, please click on the raise hand button, which can be found on the black bar at the bottom of your screen. When it is your turn, you will receive a message on your screen from the host allowing you to talk, and then you will hear your name called. Please accept, unmute your audio, and ask your question. We will wait one moment to allow the queue to form. Our first question comes from Ben Burnett with Wells Fargo. Please unmute your line and ask your question.

All right. Hi. Hello. Can you guys hear me?

Yeah. We can hear you.

Hi, this is Tien-Chieh calling in for Ben. Congrats on the data, team. I really appreciate the color that you provided on peak and comparison versus the nebulized nintedanib. Just curious, have you guys conducted any analysis or comparison versus the oral one? How does it look like?

I think going back to our animal talks, our animal program is probably where we would compare to oral. In humans, we've not done that because we're not trying to match plasma PK per se. The data on plasma is out there publicly on oral, so there was no need to redo that work.

Got it. Thank you. Another follow-up is, now that you have this new data set, how did that change your thinking around expectation for the phase II data, whether it's safety or efficacy? Any updated thoughts over there?

I don't think it changes. We started the phase II in parallel at-risk, knowing that this result will come out somewhere in the middle or before we started the trial. It doesn't fundamentally change anything. If anything, it gets us more excited to go faster. That's really what we're evaluating is now that we have 100% confidence on lung. The number one question we get is cough tolerability. Can patients who IPF do this? I think we can clearly say this after over, what, about 50 patients and hundreds of doses. We feel very comfortable going forward. We're trying to see how we can accelerate this as quickly as possible.

All right. Thanks. Thanks a lot. Congrats again on the data.

Thank you. Our next question comes from Olivia Breyer with Cantor.

Please unmute your line and ask your question.

Hey, good afternoon. Thank you guys for the questions. I want to drill down a little bit more on the adverse event data. I don't know how much more granular you can get or if you're planning to provide an events table at some point. Maybe just on the cough, can you characterize whether that 10% cough rate, was it all deemed treatment related? For those 60% with no cough, is that just no cough whatsoever or just no worsening cough from baseline? I also wanted to ask, it sounds like you saw a cough almost immediately after the first inhalation in those patients that did have it. Was any of it transient, or did it resolve over time? Just trying to understand the comments made around it mostly not worsening. I've got a couple follow-ups, if you don't mind.

Great, Olivia. I'll give some comment, I'm going to turn over to Wassim to give further dialogue. The first I want to say is the cartridges are 10 to 20 milligrams in powder per episode. We're talking about every time you gave an administration, you might have gotten one cartridge and two cartridges. Think about the powder load and the incidence of the number of cartridges. I'll let Wassim talk about the data behind the cough as he's closer to it. Wassim. Hi, Olivia. Good to hear from you.

As you mentioned, 60% did not have cough reported as an adverse event. What that means, if they had cough as a baseline, it did not get worse. It was cough related to IPF. If they did not have cough, it did not cause cough. That's one of the questions. I think the first question was we would report more details about this study in our coming scientific conference. The others, the 40%, the remaining 40% who had reported cough were deemed related to the study drug. Yes. Three-quarters of those were mild. Most of them were also transient. It was like an irritation after the first inhalation for most of these patients. Did I miss any of the questions, Olivia?

Olivia, did we get all your questions? You might be on mute.

Sorry. Can you guys hear me?

Now we can. Hello? Yep.

Okay, perfect. We hear you.

Yeah, just to clarify on that final 10%, that is cough, right? Is how you guys are characterizing that? 30% mild, 10% moderate?

Yes. Yeah. 30% had grade 1 mild, 10% were moderate.

Olivia, this is very subjective on cough, right? If you want versus a continued cough could make a difference. They were all mostly transient. I think that's what's most important. These are not adding a huge burden to the patient. They're mostly a reaction after inhalation.

Okay. Wanted to ask on your PK data, if you're achieving 6 to 8 times higher plasma exposure than nebulized nintedanib, how are you thinking about the balance between maximizing lung exposure and then obviously minimizing systemic exposure, just given that, I know one of the major goals of the inhalation approach is to avoid some of those dose-limiting toxicities that we've seen with the oral therapy?

Yeah, I think a couple of questions came in on the adverse event table today, I would say there's not much there to get excited about to want to share that. There's really nothing there. It's not like we're hiding something that we saw that you didn't hear about. Sorry, the question was what The PK PK, sorry.

What I was going to say is it's 5% bioavailable from the oral. When you think about what we were trying to do is take that 5% bioavailable and put it directly into the lung. We have a long way to go to worry about hitting near plasma concentrations of what an oral nintedanib will get through the absorbed GI tract. We've done the tox studies. We found we can go pretty high on dosing. There's a pretty high level of safety margin here that we're well below, and we're nowhere near a critical threshold of causing side effects in the systemic system or even lung issues, I'd say.

We feel pretty good that those levels are. We're happy to see them, number one, and it just is reinforcing our technology, which we really believe adds consistency in delivery, and that's something, we could develop nebulizers if we thought they were better, and we did in the case of clofazimine, if you recall. We always know that our technology delivers consistent, deep lung penetration where you're getting most of the powder into the lung and you're not losing it in the oral cavity, in the throat, and the GI tract. You're getting most of it into the lung tissue. That's really what our technology's about, and that's really what I thought you could see here when you can see we're getting to the deep alveoli, we're getting picked up in the blood, and we're showing the demonstration of that technology.

As Wassim said, getting through that lung interstitial layers shows up in the plasma, and that's what you should be confident in with our technology.

Okay. Thank you, guys. Appreciate it. Congrats on the update. Thank you.

Our next question comes from Roanna Ruiz with Leerink. Please go ahead and unmute your line and ask your question.

Hey, guys. You have Ryan on for Roanna. Thanks for taking our questioning. Congrats on the update. Maybe just two from our end. How do you guys expect this seven-day safety cough data to translate into a longer 26-week and eventually a 52-week trial? Do you think the seven days provides a good benchmark for what we would see on this AE profile moving forward? My second one is just curious on the phase II, so about your expectations for the two different dose arms. I believe it's four mgs twice a day and two mgs four times a day. Are you expecting differences in safety and efficacy between those two, given the total dose is relatively similar? Just curious your expectations there. Thanks. Yeah. The first thing I'd say, Ryan, is we're very thankful we have thousands of patients from all the trials we've done over the 30 years showing that the cough is usually transient.

It's immediate after the inhalation. It usually gets dramatically reduced after the first week. For us, the first seven days are actually the most important when we think about a long-term program, because even you took Afrezza, where we spent $75 million doing a multi-thousand-patient trial. The first seven days, you see one out of four patients have a cough. It drops to less than 3%, 5% at the end of 30 days. The cough here doesn't get worse with time. The powder loads aren't going up with time. Patients could have down-dosed in this trial if they were having trouble with cough or tolerability. Not one person did in either phase trial.

I do believe the first seven days are enough for us to project out in the trial. We didn't see any major concerns or major patient tolerability issues that give us concern. I do think that's predictive. I don't know if, Wassim, you have any.

Yeah, I agree. It's consistent with our prior data where the cough starts early on and it doesn't really get worse over continued exposure.

Yeah. Thank you. That was true in the patients who even did have cough, right? We didn't see it get worse. If anything, the first dose was their challenge and it got better each one. Then the expectations you're asking, which I think is a great question on, do we expect a difference in the four milligrams twice a day or two milligrams four times a day? The answer is, given the levels we're getting with each of our doses, no. If Cmax really does have a certain critical threshold, maybe we'll see a slight difference in the four milligram where you might get a higher Cmax. What we're really testing here, because theory in animal models and cellular models don't always translate to humans, is we really don't know on the nintedanib. Nobody does. We do want to make sure we're covering the frequency of receptor engagement, the Cmax of receptor engagement, as well as matching up what's out there in the standards of care.

We fully expect TYVASO to do an incredible job in IPF, and we want to make sure that that's going to be out there used four times a day, that our product can potentially be used right next to it four times a day. That's really the key of that second arm there. QID is making it easy for the patient to remember when to take their drugs. My background's in HIV, where people were taking 20, 30 pills a day, three different drugs. It's very hard for patients.

How do we design things early so that when the data reads out, it's meeting the standards of care that are out there at that time? We think that's critical. We hope both work. We may find out one works better than the other, or they're both comparable. I don't expect from what we saw any differences in cough or tolerability so far. Our seven-day data would indicate we should be confident in tolerability of either dose, but we'll be curious about efficacy as much as anything Awesome.

Congrats again. Thank you, Mike.

Our next question comes from Brandon Folkes with H.C. Wainwright. Please unmute your line and ask your question.

Hi, thanks for taking my question. Maybe just a follow-up on the cough question. Granted it is a small patient population, but in the patients where you did see mild to moderate cough, was there any potential trend or emerging trend in disease severity or any other patient baseline characteristic? Thank you. I'm going to turn that one to Wassim.

Thanks, Brandon. Again, the sample size is small, as you know. Within that sample size, there were no specific characteristics or trend that would differentiate or predict who's going to have a cough or not.

Thank you, Brandon. Next question.

Our next question comes from Yung Zong with Wedbush. Please unmute your line and ask your question.

Hi, good afternoon. Thank you very much for taking the questions, congratulations on the data. The first question is, I wanted to confirm, did you see any FEV1 decline in any of the treated patients in the study? The second question is, looks like while the study did not enroll patients who have had exposure to oral nintedanib, looks like the ongoing phase II study is also having the same criteria. I assume probably don't have any impact on the potential label in the future, but just curious, is that the same approach that the nebulized program is also taking in terms of patient enrollment? What kind of impact do you think that criteria will potentially have on the pace of patient enrollment? Thank you very much. Yeah.

I'll try to take these one at a time. In the FEV1, this data will all be shared at a future scientific conference. I think Wassim presented somewhere in one of the slides that the difference between placebo, which was an empty cartridge, and our active powder was no difference in pulmonary characteristics. We'll share more of those details at a conference, but that's all I can say for now. The next one was around exposure to oral. I can't remember. People couldn't be on the nintedanib, but they could've had it in the past?

They could have had it previously, currently they're not on it or they were never on oral nintedanib in our trial.

Yeah. Some patients could have tried oral nintedanib in the past. They just couldn't be actively on it because we didn't want to add to the burden of any potential side effects and really look at a clean profile here. That is true in our standard trial. It's actually one of the major reasons we went ex-US, is because we wanted to be able to be used on the background of standard of care and/or naive patients. We think a placebo-controlled trial really can't go for 52 weeks in the U.S., or even 26. We got to the lowest we could, which is 12, and that's acceptable so far outside the U.S., and we're working with the FDA to get that acceptable here. They could have previous exposure to nintedanib. They just can't be on active nintedanib.

Within our trial, they could be potentially on Tyvaso or Jascayd, and some of the newer agents, we'll be moving that in any protocol changes going forward. Those will be options. We plan to have roughly 75% on some kind of background therapy at some point, and probably 25% truly naive. That is different than the competing program out there. I believe they're going after only naive patients not on background therapy. Those are two different characteristics. I don't think one's right and one's wrong. We'll see if they impact either company's enrollment. I think this is a tough population to find for trials, and we're going to do our best to get this done as quickly as possible.

Great. Thank you. Thank you.

Our last question comes from Gregory Renza with Truist Securities. Please unmute your line and ask your question.

Hi, guys, it's Anish on for Greg. Congrats on the data today and for taking our question. Mike, at the top of the call, you mentioned you guys have been following too long and studying this asset and opportunity for a while. Even though this is phase I-B data, I feel like this question is relevant. Do you see nintedanib DPI primarily as a switch play for Ofev-intolerant patients as a first-line alternative or an add-on that enables combination with other anti-fibrotic? Where do you see the initial commercial point of entry, just given the clean GI profile and compelling nature of the data to date? Thank you so much. Yeah.

I think there's a lot that's going to change over the next 3 to 5 years while this program's going through development. If you ask me in general, I would say I believe nintedanib is the major background treatment in most clinical trials. I believe it will continue to be the first choice for patients and doctors. Jascayd may make that a little bit different. We're seeing very fast uptake there. It's too early for me to see the data to say is that coming 100% naive or switch patients. I would say that product is not as efficacious, but it's way more tolerable and you're seeing that fast uptake on tolerability, where people would rather take a more tolerable product and have something than nothing, right? I think that's good for patients. I see nintedanib being used as the background.

I see DPI as becoming a predominant choice if the data pans out the way we expect. Because patients really do not tolerate the oral, and if they do tolerate it's through a lot of sacrifice. It's through a lot of the IMODIUM they take and other tricks and diet. That they're doing everything they can to maintain that drug because they want to preserve as much life and lung function as possible. I think when they have an alternative to all that lifestyle, they will take it. Now, not every patient has that experience, and not every patient struggles. Those patients, if they're happy, they'll stay on what they're doing. Dry powders, we'll be the first to say, are not for every patient every time, but the large majority of patients can tolerate them and will tolerate them.

We believe this will be a foundation opportunity. My guess is we'll get a good share of naive patients, we'll get a good share of intolerable, and we'll get a good share of patients who tried nintedanib and have been stopped for whatever reason. We see this as a large opportunity. It mostly will be used in combination by the time this gets to market, as we see this being a combination market, which is why we are studying it in different dosing regimens. We're excited, and we're excited by the category, and we're excited that The number one question we get is cough, and that was such an important topic to get out there today, as well as all the background data we've generated, because people, we've not been always as fluent on this one and sharing with shareholders.

We wanted to take today to dedicate the background that we've done, the time we've been working on this, and the insights we have. Hopefully that summary today is helpful for shareholders and ultimately investigators and patients.

Thanks, guys. That concludes the question and answer portion of today's call.

I will now hand the call back to Michael Castagna for closing remarks.

First, I'll say thank you to everyone for joining. We've had quite a few calls and data readouts and updates the last six weeks, and we have one more with an earnings call next week. Then we have September investor meetings kicking off. A lot of great things happening here at MannKind, and we just have never been more excited about the direction we're going, the number of patients we can help, and where the shareholders should hopefully start to see the growth they've been waiting for. I want to thank the patients and investigators in INFLO-1 and as we kick off INFLO-2. This data doesn't exist without them. Our clinical data and manufacturing teams and clinical teams have been working really hard to make this program hit the timelines we set out for. The first-in-human global phase II is off and running.

We're looking forward to updating you as enrollment progresses. We'll talk to you all on the earnings call next week with additional questions. Feel free to email our IR inbox and we'll talk to you soon. Have a great afternoon, and thank you again for joining today.