All right, let's kick off our next session. It is my pleasure to host Mineralys Therapeutics. Here with me, Jon Congleton and Adam Levy, CEO and CFO of the company. Gentlemen, welcome.
Good.
Always a pleasure to be hosting you guys for these events.
Yeah. Appreciate the opportunity.
The weather's looking good this year.
What's that?
The weather's looking good this year compared to the first time we hosted, where we remember that there was a hurricane-
Hurricane
that went through.
We were talking about that earlier, yeah.
I have a lot of questions to ask, but before we go through that, I'll turn it to you for opening remarks.
Yeah, no. We're very excited about 2026 and the opportunity in front of us. As we noted, the NDA for lorundrostat was submitted late last year. The PDUFA date was declared in March of this year, that PDUFA is Dec 6. Interactions with the FDA standard course. We continue to feel very positive about the opportunity, the approval. We're using this year to continue to prepare for a successful launch of lorundrostat. Have built out our market access team, our medical affairs team, we've optimized. Obviously look forward to bringing lorundrostat to, frankly, the 20 million patients in the U.S. that could benefit from it significantly in lowering their BP and their cardiovascular risk.
Fantastic. Recently, you guys announced a deal with Tanabe, where you guys ended up buying the IP rights and to lorundrostat and also all the royalty obligations. It'd be great if you can go over the terms and the commercial milestone obligations related to this deal.
Absolutely. We had the opportunity to buy back the royalties from Tanabe for $200 million up front and $100 million in future potential commercial milestones. The future milestones are based on certain thresholds, we believe that they will be totally paid for by the savings in the royalty.
I see. Okay. You guys mentioned that this transaction is accretive to investors. I think a lot of investors took it the other way, given how the stock reacted when it came out. Just walk us through how this transaction came about, and why do you believe it's accretive to investors?
Yeah. The feedback we've gotten from investors has been very positive on the transaction. It was really opportunistic. It came up as Bain Capital had acquired Tanabe, they were looking to monetize assets that they viewed as non-core. They saw this potential future stream of cash flows as non-core to them, they looked to sell it, we were in the right place at the right time and had the opportunity to buy it at a value that was attractive to us. When we look at the return on investment, we believe that it's quite attractive, with the cash flows that would come in versus the $200 million up front, it looked like a great investment for us.
Right. I see. Okay. What was your assumption, given the deal size of that $300 million, that went into the modeling of how you guys came up with that price?
We looked at our base case model, high case, low case, did some analysis, looked at not only what the returns were, but also what we thought would be reasonable for us, given that we're cash flow negative. We also have other investments that we want to make in R&D, it was really driven more by the market opportunity than us modeling it. We offered something that we felt was attractive, it worked for them, we made a deal.
I see. Okay. Got it. Some investors saw what you guys did with this deal, and then you guys had to end up raising $150 million to do equity and then another $500 million debt facility, which is the first time that you took on such large debt. They saw it as you guys are giving up on BD. Is that a fair statement?
It's really unrelated to business development. We've been thinking about how we capitalize the company for quite some time. We've thought about the range of options to fund, whether we would do additional equity, debt, maybe convertible notes, sell a royalty, this really matched how we look at our cash flows going forward. Even though it's $500 million committed, we only brought in $100 million up front. We have additional tranches. The next tranche is available at FDA approval, then that'll be $150 million additional. There's another $250 million available to us at certain commercial thresholds that's really at our discretion. We can pull it if we want, but we're not required. This was a good way to put us in a position where we're funded, but reduce the cost of capital versus equity.
I see. Okay.
I think, if I can add, if you're a fundamental believer in the value of lorundrostat, which we are, getting uncapped royalties back at what we thought was a fair deal makes a ton of sense for us, it is not incongruent with the BD strategy because it's fundamentally the value of lorundrostat. To me, there was a congruence to it that fit the strategy that we've proclaimed forever with lorundrostat.
Sure.
Building value on our own and enabling and being open to partnering.
Right. Was this royalty buyback inspired by some of the partnership discussions that you guys have? I mean, can this expedite those efforts?
The royalty buyback was opportunistic. It was something that Bain and Tanabe put up for sale, and we had the opportunity to acquire it. That said, whether we're alone or with a partner, or if someday a company wanted to acquire us, it builds value in any case by consolidating those cash flows and increasing the profitability of the business.
Right. Yeah, no, that makes a lot of sense. Now we're waiting for the PDUFA date.
When do you expect to hear from the FDA regarding the proposed label, when does that negotiation process typically start?
All the way towards the back half of the year, probably in Q4. Typically, a couple of months before the PDUFA date, is when we'll begin negotiating the label, it's when we'll begin to talk about any kind of post-marketing commitments. I think looking at the baxdrostat data label, we feel very confident in some of the common themes that'll be there, also some of the differentiating points. All of that'll be part of Q4 activities.
Q4. Okay. Got it. You guys recently presented data from LAUNCH-HTN at the ESH conference.
Where you compare patient with CKD and those without CKD among a pooled 800 patients treated with a 50 mg dose. What are some of the key highlights from that study, why is it important from a commercial perspective or from a future development perspective?
Yeah. This was data presented by Manish Saxena, who is one of our PIs in Launch-HTN. It's post-hoc analysis, so in fairness to that. He wanted to look at the difference in response within Launch-HTN for subjects that had CKD and those that did not. Using, I think it's KDOQI-related criteria, specifically around albuminuria
which was not part of the inclusion criteria, we had over 1,000 subjects. I think we had between 80 and 90 subjects that met that definition of CKD. Looking at response to lorundrostat on blood pressure reduction, there was no change whether the patients had CKD or not. Nice effective reduction in BP. Looked at safety. There was no incidence of hyperkalemia in the non-CKD population. I think just 2% in those that were defined as CKD by albuminuria. The ones that had albuminuria at baseline over the 12-week period saw a 55% reduction in albuminuria. UACR is a really nice surrogate for-
a drug that may provide renal protection. If you see a reduction in UACR, that's conferring a level of protection of the kidney. That's very congruent to the Explore-CKD data that we released last June. In that study, we showed over just a four-week period of time, safe reduction in BP and about a 31% absolute reduction in UACR. Very congruent to that. Why that's important is as we go out and talk to physicians that are treating uncontrolled and resistant hypertension and ask the question, what attributes matter to you? Lowering blood pressure is always number one. Doing so safely is always number two. Having a benefit on proteinuria is always a top five attribute that if they can make their ideal antihypertensive, it would have an effect on proteinuria.
We've now seen in two separate data sets that you can safely reduce blood pressure and provide a benefit on the kidney. That becomes relevant because if you think about third and fourth-line patients, these are patients that are not just uncontrolled or resistant hypertension patients in isolation. They have other comorbidities that are related to that decades of uncontrolled BP, being able to confer that benefit beyond just blood pressure reduction to the patient and the offering that lorundrostat can provide for them.
Yeah, you're right. I think the UACR, you guys saw a 52% reduction.
Yeah
Or people-adjusted reduction at the 12-week. What's the implication of this? How do you use this, leverage this from a commercial setting to help drive uptake? What does it mean for you to think about CKD as a future indication or future development opportunity?
I think to the latter part, it de-risks a CKD program if we were to choose to go there. I think it's also fair to say that coming at the CKD market from the venue of hypertension, we're going to be able to provide value to patients at launch with a hypertension label. Even though this is really nice data, it doesn't mean we're going to have an indication for the treatment of CKD per se. Again, there's such overlap. I think 2/3 to three-quarters of all CKD patients have uncontrolled or resistant hypertension. A quarter of hypertension patients have CKD. These are not independent disease states. These are overlapping.
If you talk to any nephrologist who's treating a CKD patient who has uncontrolled resistant hypertension, they will say the number one goal is get blood pressure under control, because that will confer a benefit and provide kidney protection. This data with the label for hypertension, I think, will enable us to go and speak to those physicians who are dealing with uncontrolled and resistant hypertension in a population with CKD. Use lorundrostat for the control of blood pressure, but be able to do so with confidence that they can do it safely and that they are likely to see a benefit on proteinuria. It actually enables an opportunity to have physicians use lorundrostat in that setting and do so on the background of an SGLT2. We know that there are programs under development with ASI and SGLT2 and CKD.
We're certainly going to be able to compete within that space for those that are uncontrolled and resistant hypertension.
I see. Okay. Got it. Let's go into the hypertension market. I asked you guys, how do you think payers will manage lorundrostat fine setting. I remember in the past when I asked you this question that you felt like the third line is pretty fair game.
you could have access to it. In the last call, you guys mentioned that the fourth line is the optimal entry point. That's where you would go in, build, I guess, benefit and establish benefit there before you would move into the third line setting at some point.
Right.
When people hear that, it sounded like there may not be an opportunity to third line because who knows how long that takes.
Right
to establish the benefit. Is there a path to that third line, what does that look like?
Yeah. As we do market research with physicians, there's high demand in third and fourth line.
Yep.
As we do research with payers, the access entry point is probably a little bit quicker for fourth line. It doesn't mean that third line is not something that's available. It's a little bit dependent upon plan, upon payer. I think the point I was trying to make is the fourth line, if I combine access and demand, that's the easy entry point. It doesn't mean the third line won't be used. It doesn't mean the physicians won't be prescribing it. It just means the access aperture is going to be a bit broader for the fourth line. Again, the demand is clearly there. We anticipate third line use. The fourth line, just based on our current research with both payers and physicians, I think is where it's really going to take off. Then with that success build into the third line very quickly.
That demand will progressively open up the aperture from an access standpoint.
I see. What's that timeline look like? Is it years? Is it months? What does it look like?
No, I think it begins at launch.
Yeah.
Again, I hate to use this aperture, but it progressively opens up with that demand. Some of it's based on book of business.
Yeah
Is it commercial, is it Medicare? Some of that is plan specific. I think both markets, that uncontrolled and resistant, are going to be in play immediately. I just think that fourth line, there's a bit of a broader open lens.
I see. Okay. Got it. Basically, optimal from a point that it's easier to access those patients immediately and then. It doesn't mean that.
I think there's going to be a.
You wouldn't use it in third line.
I think you're going to see the drug used in both lines of therapy. I just think the access barrier is going to be a lot lower at fourth line.
I see. Okay. Got it. In that fourth line optimal entry point, what would the step edits look like? Would that include like an MRA or such as spironolactone as part of the process? What do the patients have to do to get on lorundrostat?
Yeah, I think there is a growing appreciation. It's already there in the medical community. I think it's growing within the formulary, and those are manned by physicians and PharmDs, that aldosterone is the emerging target that's not addressed properly right now. That spironolactone is the only one that's there. For the five years that I've been involved in Mineralys, the natural question that you just asked is what about MRA? What about spironolactone step through? Progressively, the feedback has been, we're not going to make you step through an MRA. A, the use in hypertension is exceptionally low. B, these formulary decision-makers understand the difficulty that patients have in staying on that drug-
Right
having a successful outcome with that drug.
Because of the titration to it too.
Well, I think it's titration. I think it's not just off-target effects like gynecomastia, infertility, anorgasmia, but it's also to push dose to get more efficacy, you push the rates of hyperkalemia. It's just for a lot of reasons, it's just not used. I think what has progressed as our pivotal data read out and as we now have market access team members out in front of the field is it'll be for that fourth-line setting. It'll be a step through three drugs. It'll be a look back in their EMR. Step through three drugs, but kind of indiscriminate what those drugs are.
There will just need to be evidence that a patient has a history in the last six to nine to 12 months of being on three drugs or more, failing to get to goal, and that is in essence the check the box for the step edit. There's likely to also be a PA to label. For I think the vast majority, that'll be an electronic PA, so that's, I think both of those are going to be fairly low hurdles because if we think about the volume of patients, roughly 10 million patients that are going to have within their existing EMR that experience base. It's a quick look back, check, step edit, and access to lorundrostat.
I think, I don't know if this is on your mind, but I think where we've seen baxdrostat price, based on the research we've done, I think that's a reasonable price point that they've identified that fits within that utilization management based on the research that we've done.
Yeah. No, I have some questions on that too. How long would that process take when you go do the step edit, do you think, before they can get on lorundrostat?
I think it's going to be variable by plan. I don't know if I'd want to hazard a guess at maybe a 30-, 60-day period, but it's going to be variable by the plan.
Yeah.
Yeah.
I see. Okay. Another key point that I think we discussed before was that the ongoing PBM reforms where the rebates are now being completely passed due to the plans. It used to be that the PBMs have some financial incentives to use branded medications like lorundrostat or ASI, maybe even ahead of some of these generics or parity to generics, because they can have some of the rebates, they can keep some of the rebates. Now that's been passed through and kind of shift some of the incentives away from that. How do you think, just given that dynamic, how does it affect when you think about getting it on the formulary, thinking about competing with these generics, with these payers?
I think the old model there were two incentives for PBMs, one was the retention, their portion of the rebate that they retained. There was, in fairness to PBMs, there was another incentive, that was trying to identify good clinical value to their customers, ultimately. Creating access to novel innovations that could help their constituent customers' populations address whatever medical need. In this case, getting their blood pressure under control. That's always an element of the PBMs within this context. It's not just give us the rebates, but it is providing good service and good value from a clinical standpoint to their constituents.
I think if we look at the model now, that clinical value piece still sits there as a supposition that if there is true innovation, given the fact that half the patients in the U.S. cannot get to goal that are treated, that becomes part of that clinical value prop. What has shifted is the rebate transparency has pushed that through, what has emerged for that are these service-based fees as a percentage. Whether it's an admin fee, a data fee, there are new fees that have emerged that are a bit more transparent, it's kind of from one hand into another hand. There are still elements, from a PBM standpoint, that they'll derive value from having a branded asset introduced into a market that's purely generic right now.
I see. When we look at PBMs, they often use these preferred and exclusive contracting tactics, especially when multiple players come into the market with similar drugs. This happened, we saw that with the PCSK9, obesity now, and also many others. Are you expecting this to be the case for ASIs as you launch lorundrostat with baxdrostat already out there, and then how are you preparing for this scenario?
Yeah, I think we put our market access team in place in Q1 of this year. We're doing what's called PIE, pre-approval information exchange, so that these payers are aware of our timing, our clinical value proposition, the unmet need, and how we're thinking about positioning lorundrostat, which is in that third-line later setting. To your point, I think payers like to have, from their standpoint, multi-source of new innovations like this. Having two is kind of an ideal setting for them. I don't know that they necessarily drive and force for a preferred. I think it's more of, from a sponsor standpoint, do we want to move to a preferred setting? If we want to do that, then there's going to be a cost related to that.
Our going-in position is really going to be more about how do we ensure fair access, parity access we'd be fine with. We're somewhat interpreting as we make some assumptions about our launch plan that AstraZeneca may come in with a parity kind of position as well, as opposed to anybody who wants to move to a one of one, then you're going to have to buy into that preferred state and offer more rebate. I think from our standpoint, it's more about let's create profitable access, let's look for parity, and then let's create opportunity for physicians and patients to choose.
Going back to my previous question about the PBM reform, do you see because of that incentive shifting away from these PBMs, do you also see that there's a shift in terms of how they're managing it, and maybe less use of these preferred exclusive type of contract?
No, I think there's still the opportunity through other rebate structures to create preference if one chose to do that.
Again, there's a potential slippery slope with that as far as risking your margin in doing that. I think our goal again is how do we create equitable fair access for when physicians and patients choose lorundrostat, and keep it in a parity position so it is at the choice of the physician as opposed to a forced choice from the payer.
I see. Okay. You mentioned, I think last time that the sales force, usually you would hire them typically around 90 days before launch, and obviously you can't just post these positions at 90 days before launch because there's a whole process of hiring them, making the offer, negotiate, background checks, notice periods, and stuff like that. How many sales do you foresee needing for that initial launch? Then how soon do you have to really get the ball rolling with that?
The actual number we haven't disclosed yet, and that's predominantly just for a level of competitive insulation, and we're just not willing to signal yet to AstraZeneca, who's in the market right now, how we plan on doing our go-to-market model and our sales force size. As I noted, we've put our market access team in place in Q1. We've optimized our size of our MSL, medical science liaison team in Q2 of this year. We're beginning to put our sales leadership team structure in place right now, as you know, there's head of sales, the next level and next level of management, sales territories.
We're confident in the timing that we have, the positions that we've put in place right now, the positions we're recruiting for, that all of that enables 90 days prior to that PDUFA that we could have the vast majority of our targeted sales force in place in that timeframe. That gives us time for those reps to get acclimated to their geography, meet their customers, do all the proper training, begin to do some of the disease ed communication that's allowed pre-approval, up to and including coming soon communication.
Right. I see. Okay.
With the goal ultimately being on upon PDUFA that we can quickly pivot to full commercial launch.
Right. Okay. Baxfendy recently approved on May 18th with a list price of $500 per month. This was higher than what we were expecting, I think some of the market were expecting. What is your impression for that price given sort of the sensitivity around drug pricing at this point? Have you tested that price range, and how do payers would react to that price, do you think?
Yeah. I think that that price fits within the research we've done, the one-on-one dialogues our team is having right now. It's not a specialty tier, which was one of the key points. If the net price for an ASI would've fallen in the specialty tier, then that would've greatly restricted access. This is a non-specialty tier price point, just at WAC, let alone what the net would be. I think with the position of the drug later in treatment, not 1st line, not even second line, but third line or later, with the step edits that I identified earlier, I think that price point, coupled with what will eventually be the rebate percentages, fits well within the research that we've seen. Now, will that be the exact price that we land on?
That's part of what we'll continue and analyze through the course of the next six, seven months. I think it was a reasoned price.
Right.
I don't think it narrows that $20 million third and fourth line patients that we've talked about in the past. I think that fits within that population based on the research we've done.
Mm-hmm. How have you been hearing how payers are looking at Baxfendy at this point?
It's early days.
Like in your PIE discussions, does it get-
Yeah
brought up?
It's very early days. Obviously, the price point just got communicated in the last couple of weeks, but I don't know that there's been any surprises. I don't know that there's been any shock around the price point. I don't know that we have seen a great deal to date on the contracting strategy. That'll be something that'll unfold over the next couple of months.
Right. Okay. Got it. Basically, still aligns to what you said earlier about the fourth line being the optimal entry for them also at that price point.
I think the payers view this transformative class, and I think that's a fair statement to say. I think they've been impressed with the clinical value proposition. I think they're viewing both lorundrostat and baxdrostat similarly, as it relates to access for fourth line, and in some cases, with some payers, third line as well.
Okay. Got it. I want to shift gears to some of the partnership questions, and then later on, the Baxfendy's label. From a partnership perspective, you guys have been talking about exploring potential partnerships for some time now. Now with the December PDUFA date fast approaching, are there any key uncertainties and risks that are sort of holding things back? I'm just kind of looking at the macro environment, and potentially how payers are managing this class, maybe you want to seek clarity on that. From that partnership point for your ongoing discussion with partnerships, are there things that are holding back, do you think?
No. We've shared that we're always open to having dialogues about increasing the value of lorundrostat by definition Mineralys through partnering. Open to the point of acquisition if it made sense. Fundamentally, we've been driving to ensure that we have a successful launch in the United States. I think what I can share within those dialogues with partners, there's an appreciation of the value proposition of lorundrostat, the appreciation for the value of the ASIs as a class, and an appreciation for the market size. I don't know that any of the macro elements I would characterize as limiting. I think it boils down to the value proposition writ large. I think, like I said, there's a true appreciation for that.
Right. I see. Throughout this year of discussion with strategic, how would you characterize sort of that interest level throughout this period of time? Is it similar since you guys started? Is it becoming there's higher interest now or lower interest now?
I think return of large pharma to cardiometabolic. I was the first hire when Mineralys was put together, through the licensing of lorundrostat. This was late 2020, early 2021. Maybe a handful of pharma were really focused on cardiometabolic. I think today, and I think part of it is due to the success that Novo and Lilly have generated with the GLP-1s in the anti-obesity space. I think today the vast majority of pharma have returned to this space and appreciated not only the market opportunity, but the unmet need. You and I have talked in the past. Just go to The Lancet's Global Burden of Disease study. Three of the top eight drivers of loss of life or loss of quality of life are kidney disease, stroke, and heart disease. What underpins those two are cardiovascular, like blood pressure, and metabolic, like diabetes or obesity underpinning that.
I think there's clearly a return of interest to this space and an appreciation for the significant value opportunity.
I see. Okay. With that PDUFA fast approaching, after a certain time period, there may not be enough time for a partner to come in to properly prepare for lorundrostat's launch or be able to participate in that label discussion. Is there a window that closes for a potential strategic to come in ahead of the PDUFA? Or do you see these ongoing discussions would go past PDUFA?
Yeah, I appreciate the question. I don't know that I hold that there's a window. I think at any time it could be right for us, it could be right for a partner. That's why, and I'll pick on a word that you used there, properly. It goes back to what we did with the proof of concept. I think we properly ran a proof of concept. I think we properly ran a pivotal program that put together a very robust NDA. Last year and into this year, I think we're doing all of the things. If you were to blind Mineralys and put in any big pharma name, you would see what we're doing to prepare for a successful launch of lorundrostat looks the same. The investments in market access, the investments in medical affairs, the readiness for sales force.
All of that supports two things. One, us generating value with lorundrostat as Mineralys and to go it alone. Two, enables a partnering or potentially even acquisition at any point because any pharma could look and say, "You are doing everything that we would do.
Legitimately. That may sound bold for a small biotech, but the team is loaded with experienced commercial, med affairs, market access, commercial manufacturing staff.
Yep.
We're ready to enable successful launch, again, whether it's in our hands or that of a partner.
Okay, got it. Let's spend the rest of the time on Bax-C HTN label after it came out. It looks interesting in a way that we did not see the Bax24 data in there.
Right.
At least the efficacy portion.
Right.
We saw some safety portion, but not the efficacy. What is your impression of that label, and how do you think lorundrostat can differentiate?
I think it did two things. It affirmed some assumptions that we had. The indication was very straightforward, and it's broad, right? Inadequately controlled blood pressure on top of background meds. The outcomes claim, as anticipated by the guidance, was in there. Lowering BP lowers risk of stroke and MI. I think the monitoring was actually a little bit more liberal than I thought it would be. It said establish a baseline and then periodically check. It did not delineate time, bring back in two to four weeks. I would presume that those will be pretty common languages within an approved lorundrostat label. To your point, the Bax24 is part of safety, but not part of the efficacy, and the BaxHTN data, as published, was represented in that label. That's where I think there becomes the opportunity for differentiation.
Specifically, if LAUNCH-HTN as a base case is the only clinical data set that gets into our Section 14, then we know the absolute and placebo-adjusted change is greater than what was demonstrated with baxdrostat in that study. Advance-HTN, we think, is a highly informative, very rigorous study that we're going to make arguments for during those negotiations should be a part of the label because it's very informative for the truly confirmed uncontrolled resistant hypertension. That could become part of a differentiation aspect as well.
There was also a statement saying that there was no clinical benefit established for eGFR less than 45. Although the label does not restrict the use of these patients.
Right
Do you believe the payers would have some statement for you guys because you did study these patients?
Yeah. That could also be a point of differentiation. We did Explore-CKD down to eGFR of 30. We made it part of our label application. It'll be part of our negotiations, whether that's in Section 14 or acknowledged in special populations down to eGFR 30. That said, our market access dialogues hasn't indicated that the payer's going to be looking at an eGFR cutoff specifically.
I see. Okay. Well, fantastic. We're out of time. I've probably gone through less than half of the questions I prepared for you guys. We got to do it again some other time.
Absolutely.
Thank you so much. It's been a pleasure hosting you guys again at the GS conference.
No, always a pleasure to be here and appreciate the invitation.
Any final remarks?
No. Look, it's been too long. It's been 20, 25 years since there's been true innovation in this space. I think the ASI is the right medicine at the right time. The medical community is keyed up in looking at aldosterone as an untargeted driver of cardiorenal metabolic. I think they're excited about ASIs. We're very excited about the clinical profile that we've developed over the last five years and the commercial opportunity to really help improve the lives of millions of patients that I think will engender significant value for shareholders of Mineralys.
Great. Thanks, guys.
Yeah. Thanks.
Thanks everyone.