Great. Good morning, everyone. Welcome to the RBC Capital Markets Global Healthcare Conference in 2025. My name is Greg Renza, one of the senior biotech equity research analysts. To kick off the day, we're very pleased to have MannKind with us. Look forward to a chat with the CEO, Michael Castagna, as well as the CFO, Chris Prentiss. All right. Sorry about that. Guys, we've got an eventful year for MannKind. I know we just reported not too far off from the first quarter, a lot in the pipeline, a great deal with DPI. Maybe, Mike, we can just have you kick it off for those who aren't familiar with MannKind, just a brief overview and introduction to the company, the Afrezza franchise, the United Therapeutics collaboration, as well as really what is an emerging and exciting pipeline.
Yeah, for those who are not familiar with MannKind, it's 34 years in the making. It's been a long journey for many people. It's an inhalation platform that started out as a diabetes insulin, inhaled insulin, as many of us know us for. In 2017, we started funding some of the pipeline assets. In 2019, we pivoted to orphan lung disease while we waited for the pediatric data readout on Afrezza. Over the last five, six years, we've been building up the TYVASO DPI franchise with UT. We launched a trial into nontuberculous mycobacterium. We got an inhaled version. We had pirfenidone and nintedanib. We moved one of them forward and killed the other one. We have a few other things that we haven't disclosed yet.
The company's continued to evolve and really thinking about how do you best utilize the platform to make a difference in people's lives and make sure you get fair price points as we saw, you know, me too drugs weren't going to get the pricing in the future than they used to years ago.
Yeah. And of course, MannKind is predicated on the proprietary inhalation technology, the dry powder. How do you believe that these technologies are positioned to have an impact in pulmonary diseases like PH, like the orphan lung diseases that you're talking about, as well as, of course, the diabetes space?
Yeah. When I'm a pharmacist by training, when you're dispensing drugs, you do not think about one inhaler being different than another inhaler and the powders are the powders. I did not appreciate that when I got to MannKind. As I have come to appreciate the technology and how the inhaler itself has a very easy ability for people with lung disease to inhale, you know, the velocity of the powders in other devices really causes either the cough or you lose a lot of drug in the administration process or nebulizers. I think our dry powder technology delivers more drug down to the lungs and deep lung tissue than most dry powders, which get stuck in the back of the throat, the upper airways. There is a big difference in just dry powder technologies that we stand out.
I would just say from an investment viewpoint, you know, a lot of the dry powder companies have not survived. People just have nebulizers, which are not that differentiating probably because they do not have something unique or the infrastructure to scale a dry powder. I think that is where our founder, you know, dream big and built big. We have a large facility we have seen in Danbury. It is scalable. It has been FDA approved. You can add additional drugs onto the platform as we have been. I think from that perspective, it is a unique platform that delivers really good drug concentrations. The novel excipient that most people do not realize is our own. That is really our secret sauce that is not as easy as people think probably to manufacture and scale and creates competitive opportunities for us to continue to build out more.
Yeah. Maybe just talking about that effort of commercialization and just realizing the value with TYVASO DPI, maybe talk, Mike, about the value that you've really harnessed from DPI, from TYVASO with respect to the royalty sale last year, how you view the value and really, frankly, what could translate to an underappreciation and how this is monetized and how you're actually bolstering the manufacturing support.
Yeah, I guess it was about almost two years ago in June, we kicked off a royalty monetization because our stock we felt was undervalued. At that time, the royalty was not disclosed. We thought, okay, let's just sell 10% of our royalty rights to put some valuation as a backbone to the company. Those offers came in and we announced January of 2024, $150 million transaction for 10% of the royalty that we received. That just hedged the risk mainly because we wanted cash on the balance sheet to pay down our convertible debt and also just to put a fair value out there. Since then, the royalty came out publicly what it is. It makes it easier for investor calls. What that did is fundamentally just de-risked the company a little bit.
As you can see, a year later, we paid off most of our debt over last year. The company, you know, that was a goal of ours five years ago was to be debt free. I'm proud to say we sit here today, one year left, and we have $35 million left in debt. I think from the royalty side, that really helped us deliver the company while it provides additional cash flow to fund the pipeline. That is really what we always felt was going to happen as we were moving our preclinical assets through animal models. We said by the time they get to phase two, three, we should have enough money coming in to pay for that and be independent as opposed to giving up rights like we had to back in 2018 for TYVASO. We felt it was a good partner.
UT has been a great deal for everybody and patients especially. Now as you look forward, like you would want the upside of 201, you want the upside of 101. We really don't want to give those up as that's to me how our shareholders can see a lot of value.
Yeah. Let's go there. Let's go to 101 and nintedanib as you're really fueling the pipeline and building a capability set in MannKind that is really, frankly, a turnaround. That's a natural progression of what you've done with the company in the last several years. Specifically, what does 101 do? What problems is it solved for in NTM lung disease just over current standards of care?
Yeah, for those who do not know NTM, it is a very rare lung disease. It is often misdiagnosed, patients either through infectious disease or pulmonologists for years. In the U.S., there are about 100,000 patients. In Japan, there are about 100,000 patients. It is very endemic because it lives in the soil and the water and the moisture and humidity. Think about those types of countries, Japan, Hawaii, Florida, it is prevalent there. From an infrastructure, you do not need a large infrastructure to commercialize it. From an unmet need, there is only one drug ever been approved. Most of the people know Insmed has done a great job at just building out, I will say, ARIKAYCE during a really tough time during COVID. Now that they are through that cycle, you can really see it accelerating growth in Japan, a little bit in Europe and U.S.
For us, everything else has unfortunately not made it to phase three at this point. We are the last one standing from a clinical development perspective. Everything else has failed or died or got unfunded in the last year. We expect to be the next launch in NTM. We have a nebulized version of clofazimine. It's in trials now. We have a dry powder version. We're working on that. Hopefully, we'll advance pretty soon. We're starting out in our factory population just like our case, moving it up. The summit need is pretty large because our case has quite a few side effects and administration burden. One of the things we were trying to solve for was patient out-of-pocket costs with one month of therapy, two months off, less cleaning, less hassle for the patient.
Additionally, clofazimine is a drug that we know works, but it has organ accumulation, skin discoloration, and QT prolongation. Some pretty severe side effects in the oral formulation. By cutting the dose down, putting it directly into the lung, we think really can deliver a far better experience for the patient and hopefully efficacy. So far in Japan, enrollment's taken off. It's really done. We just increased the cap for Japan so they can enroll more. That's going ahead of expectations. In the U.S., we're at ATS this past week. That'll be somewhere we're focused on. U.S. is picking up the last few months of that.
Yeah, you disclosed some of the enrollment updates. As far as the randomization is going, just walk us through the ICoN-1 study, some of the design and how it is certainly global and the efforts you're making to make that push.
For this, if you guys haven't followed this disease, many drugs take a long time and sometimes they don't make it because the companies run out of money. Before we really push forward the second, the oral powder and then other earlier indication, we had to make sure the first trial was going smoothly. Honestly, it's going smoothly. We're going to advance hopefully other opportunities to scale the NTM business faster in terms of clinical development. The trial itself is about 180 patients. The first 100 will be evaluable after six months of treatment. We expect to hit that 100 patient enrollment for evaluable patients, which is important. Some patients will be enrolled, but they won't have a baseline sputum. We find out about 20% won't count towards the end. We need about probably 120 to get to 100.
We should hit that mark by the end of the year and then call it sometime mid. Sometime during Q3, we should get the sputums, and then that'll tell us the size of the trial, meaning has it been scaled properly or do we need a few more patients? The good and bad news is that the enrollment is going. If we need a few more patients, we're going to let it keep enrolling. We should be okay assuming things are in the right direction and be able to lock down the trial late next year and then file 2027.
Okay. Great. You're mentioning being at ATS. I know there's probably lots of learnings that you're pulling with the company. Maybe if you could just share some of your insights and takeaways from the recent events.
Yeah. I mean, I thought we'd hear a little bit on the IPF space, not allowing the NTM. There was one patient conference. There was an NTM conference before ATS every year. The good news is there are 160 some patients there hearing about MannKind. A lot of excitement for us in that community. Within ATS, obviously, TYVASO gets a lot of showtime, DPI with UT. For us, clofazimine, we had a clinical team there meeting all the investigators and a lot of the U.S. opportunity to reposition the trial for them to get back top of mind. These guys are busy. We want to make sure they need to focus on our trial in the U.S., get that going. That has been part of our focus.
The 201, we didn't publish anything there yet for present, but we'll start to release that data in the coming year.
Okay. Maybe just walk us through the rationale with 201 and IPF, certainly a challenging indication, many failures with your novel formulation. How are you framing that up for folks?
On 201, for those who don't know, it's an inhaled version of Ofev. Ofev has severe diarrhea, unfortunately, in the morning to talk about. But it's a drug. It's the only two drugs approved for IPF. We looked at both pirfenidone as well as nintedanib. We felt the pirfenidone had either would require a long nebulization or a lot of dry powder. We just didn't think that was worth the development. There was no rationale to really put both of these drugs together from overlapping toxicities in our minds. We moved the Ofev one, killed the pirfenidone. You know this is one that we really do believe the fibrosis is in the lung and trying to get better lung penetration, deeper lung penetration could help hopefully the patient population faster. Within that, we've not released all the data.
The veterinarians keep asking us about dosing and efficacy. When I say about MannKind is we've gotten several drugs approved. We've developed 40 formulations. We have a good guesstimate of moving from one space to another. We could always be wrong as these are difficult. I would say, you know, I know Arava failed and two and a few others this past year. I think we have a good platform, pretty predictable dosing levels that we get in. We're able to see this weekend, honestly, the levels of avalance that nintedanib program. Seeing where they're putting their data out there and their confidence and duration, we feel very good about ours. We have a much higher plasma than they did in duration of that.
We feel whether it's our high dose or mid dose or even low dose, we have a good opportunity to hopefully have a good shot on goal there.
Yeah. Okay. All right. Great. I want to talk Afrezza, just another commercial engine for you. Before that, maybe just a little bit on the manufacturing platform and just the technology, the potential just beyond these indications. You've spoken, Mike, about how you're taking sort of a very judicious approach. You're doubling down on the right indications where it makes sense. Talk to us about how you're evaluating expanding the pipeline. It's even a good way to weave you in, Chris, as you're thinking about capital allocation. As you've joined about a year now in MannKind, you've joined with a lot of potential ways to sort of use the cash that you're generating. How are you framing up that, basically that matrix of determining what to go after, how to partner, and how to commercial or how to develop?
Yeah. I think one of the big questions for us is do we expand beyond? Do we go into COPD? Do we go into asthma with the inhalation platform and the pros and cons of that? I think as you look at TYVASO's success, obviously these patients have comorbidities. They have COPD, they have IPF, they have ILD. We think seeing our technology continue to work well in that population and tolerate it gives us more and more confidence that we can look in other areas that we were not normally going into. We cannot go into PH because UT owns that space exclusively. I think from a company perspective, there are another three to five assets we are working on in the pipeline. Once we move us to a stage we are comfortable, we will disclose those. We are not running out of ideas yet.
I do think we'll start to evolve to NCEs and start to look for more targets early stage and start to move those through because as you want to think about IP long term and launching drugs in 2040 and 2038, we got to start thinking about that today, unfortunately. I feel very good about our platform and our launches over the next three to five years. As you think about 2033, 2035, what else can you start to move? That's really what we're spending a little bit of time thinking about now.
Sure. Great. Chris, I'll let you talk about allocation.
Yeah. I think for us, you know we're just sitting with a great balance sheet. To have approximately $200 million of cash at the end of the quarter and as Mike said, just our $35 million of debt remaining, it leaves us in a really strong position. For us, obviously trying to progress the pipeline as quickly as we can, that's our first priority. We just, we'll get to it in a second here, but just what a great opportunity with Afrezza, with a pediatric indication to be able to bring new life to a brand that's been approved for 10 years now.
Maybe, Chris, as you think about the manufacturing and the MannKind capabilities, how are you framing up some of the global pressures when it comes to the supply chain, when it comes to tariffing impacts? Where does MannKind and your facility stand with that?
Yeah. Obviously, nervous days as you continue to evaluate and guess what's going to come through next. For us, we manufacture Afrezza, TYVASO DPI, as well as our pipeline assets are all manufactured in Danbury, Connecticut. That puts us in a really good position to be able to manage through. As we look at some of our key raw materials, such as insulin, such as our proprietary excipient that Mike mentioned, those are all exempt from tariffs at this point. There will be some small impacts on ancillary products or pieces of our product, but overall, we're able to manage this really well.
Great. Great. Let's talk Afrezza. You certainly mentioned going back to the roots of MannKind. Just talk, Mike, about how this franchise is really evolving and sort of met your expectations commercially, but also with the data that you've been generating. How has it been used to support the growth and what's your vision going forward?
Yeah. I think what people misunderstand about Afrezza is we didn't have the capital in my first four or five years. Then we had COVID. We were just waiting for peds data. We have not really invested as much as people think to really commercialize an asset like this. It required a lot of work in terms of redosing the trials, getting the label changed, getting pediatrics. That was not well funded in the beginning years I got here. It took a long time to get things moving. The good news is all those things are done. Now it's how do you scale it? In the last two, three years, we were investing for profitability, not growth.
Yeah, we were still growing at $7 million-$10 million a year, but we were not growing as fast as shareholders would like or myself included in that. Now that we have the capital, now that we have fixed the balance sheet, we are looking to grow it faster. Now we hired a President in January. I think the manufacturing facility can handle a lot more dosing. From a capacity perspective, we just got India's last clearance. That was the last milestone. We will be in Danbury tomorrow, just planning how to get the supply ready for India. Within the U.S., I feel like the pediatric side, gestational, there is the exercise study kicked off. There is type one, there is type two.
Afrezza is a brand within a brand as you think about how many patients it can help and the millions and millions of people that suffer from high sugars and lack of control. It's still a huge unmet need. If people's sugars were in great control, we wouldn't be as excited about Afrezza's opportunity. In my nine years as CEO, all we've done is move the population from a Medtronic device to a Tandem device to an Omnipod to Beta Bionics. Why do they keep switching? Because they're not doing well. Otherwise, that would still be the only original device that was promised to be like an artificial pancreas. Has the technology gotten better? Yes. Have A1Cs dramatically improved in this country? No. We as a society are spending billions of dollars for CGM and pumps and all this technology on patients.
The patient just wants good sugar control. I do think our trial that we just released last year showed you do not need an insulin pump, that you can safely switch off if that is what you want. If you want a pump, that is fine. We do not judge. You do not need one. I think that is not what patients are being told. A lot of our work going into the second half of this year and next year is making sure patients have a choice to their care that they pay for. Today we are not offered as a choice. That is one of the things we have to work on, scaling up our sales force, working with the societies to make sure that the tools that are out there for patient new information are all including inhaled insulin as an option for patients.
Because when you get there, it's here's insulin pumps, here's a pen, here's a vial. Even the state laws are getting changed to include inhaled insulin. We got Medicare, they've all included inhaled insulin. I think that's one of our main focuses is to make sure we're set up. Patient access and the payer side. We offer low cash price so if someone really needs it. We try to remove the payer barrier. I think we've done a decent job. The doctors will still perceive there to be a barrier, but that's because they've not either met our reps or prescribed it. That's part of what we're working on, is making that whole process as possible and getting ready for kids.
For us, it's really the, if you ask me, the pediatric opportunity is really what we're focused on right now. Yes, we'll grow a little faster in adults, but I think the inflection comes with kids.
Yeah. Yeah. I have always admired how you take a very deliberate approach historically when you go to market, but you have also taken a test and learn. As you are doing efforts in the field force, you are collecting data, you are seeing what works, you are seeing what does not, and you are never afraid to make those shifts accordingly and to double down on what works. I trust peds is no exception.
No. I mean, we're excited about peds. I mean, I've met several big failures in pediatrics last past year just as we get our data and say, "Hey, what's your reaction?" People's number one reaction when they see the lung function data was the most important because there's such an overhang on safety in the lung that if there was any signal in kids, I think we were dead. And there was absolutely no signal. In fact, the rapid acting arm did worse in lung function tests than the Afrezza arm, which again, you're like, "Why?" And then I read an article this weekend in Diabetes Care, how even in adults, patients with CHF and heart disease have lower rates of FEV1.
I'm like, "Well, we got to go back and look at our type two trials and understand, was there a correlation there?" The data is still evolving, but I think the safety profile of this product, which has been its biggest overhang, I would say after 10 years on the market, we feel very good about the safety. Going into kids, going into gestational and some of these other areas, we think just helps build out that user case and experience with the product.
How are you characterizing the potential top line impact with peds?
Yeah. So we've said, I think we want a Q1, Q4 earnings to happen in Q1, that if Afrezza had the opportunity to get to over $200 million from where we are today, I think we finished last year at $65 million-ish. Peds, every 10% share is about $150 million in revenue. It does not take a lot of kids to really think about this as a billion-dollar opportunity. Obviously, we do not think it is going to do a billion, but can it do a couple hundred million more top line? I think the answer is yes. We think there is a real possibility here. We will be hopefully 12 months or so from launching that very soon.
Yeah. You touched on India, but maybe the Afrezza opportunity outside of the U.S. perhaps doesn't receive the spotlight it could deserve. Maybe just walk us through how you think about Afrezza, the partnership, the Cipla partnership, the top line contribution even from those markets outside.
I mean, for me, we've already paid for FDKP. We've already paid for a lot of insulin. The factory itself needs to produce more. Some of this is just recouping our cost or spreading our fixed cost amongst more millions of cartridges. India, you won't make a lot of money, but at least if we can get back some of the cash we've already outlaid. India's got 80 million people with diabetes. There's a lot of excitement there, a lot of awareness already, believe it or not. I think from that perspective, yes, we'll make some money. There's a lot of people. If it launches well, I think we'll do okay and it'll be a nice addition. It also, we're starting to have an imbalance for countries, which we've never had.
Having someone, a country in Europe, I just got talking to Chris in another country in Asia, ask us if we would sell a tender, would we make Afrezza available? The answer is yes, we will. I think as that news spreads, right, we'll get more and more. It's like the snowball effect, right? Yeah, that happens. Now Europe, with the most favorite nation, I think that's something we'll watch closely because obviously insulin's a lot cheaper outside the U.S. We can't sell it for $15 a month as much as I'd love to. We won't be in business. I think just that's one of our focuses of the new data was how do we get more people to go? How do we improve time in range? How do we improve outcomes, right?
Not just give you a crappy outcome, but improve that outcome. I think that's the value proposition of Afrezza, right? You're paying for an insulin pump just to fix the profile of insulin. That's costing $5,000 or $10,000 patient costs. When you think about the cost of insulin, it's not just the insulin, it's the device, it's the supplies, it's the syringes, pens, needles, everything else that you need that honestly society doesn't think about. We do spend billions of dollars on those things as well.
Yeah. Great. Great. We just have a minute left. I just want to open it up to the audience if there are any questions for Mike and Chris, the MannKind team. We're good. Guys, great to see you. Congrats on the progress.
All right. Thank you, Greg, for everything and look forward to the rest of this year and finishing up strong.
All right. Thank you.
Thank you, everyone.