Milestone Pharmaceuticals, Inc. Aktie

Hello, and welcome to the Annual Meeting of Shareholders of Milestone Pharmaceuticals, Inc. Please note that today's meeting is being recorded. If you participate in today's meeting and disclose personal information, you will be deemed to consent to the recording, transfer and use of same.

If you disclose personal information of another person in today's meeting, you will be deemed to represent and warrant to Computershare and the corporation that you first obtain all required consents for the disclosure, recording, transfer and use of such personal information from all appropriate persons before your disclosure. During the meeting, registered shareholders may submit questions or comments at any time by clicking on the Q&A tab.

It is now my pleasure to turn today's meeting over to Joe Oliveto. Joe, the floor is yours.

Good morning. I'm Joe Oliveto, the Chief Executive Officer of Milestone Pharmaceuticals. Welcome to all of you to Milestone's 2026 Annual Meeting of Shareholders. As you know, we are hosting our annual meeting through a virtual online platform. We believe this affords us the opportunity for continued engagement with our shareholders regardless of location. With that in mind, I want to thank you all for taking the time to join us.

While the meeting is virtual only, registered shareholders will have the opportunity to ask questions or make a comment online during the Q&A portion. I'd like to caution you that forward-looking statements may be made during this meeting or the question period following the meeting, and actual results could differ materially from forecasts, projections, estimates, expectations or conclusions in such forward-looking statements.

You may find additional information about the material factors and assumptions that could cause actual results to differ in our most recent annual report on Form 10-K and subsequent SEC filings.

Before I call the meeting to order, I would also like to take the opportunity to encourage you to review the rules of conduct for the meeting, which are posted in the virtual meeting platform. I'd also like to introduce you to the members of the Milestone Pharmaceuticals Board. In addition to myself, they are Stuart Duty, Seth Fischer, Lisa M. Giles, Joseph C. Papa, Andrew Saik, Michael Tomsicek and Robert J. Wills, PhD, who is the Chair of our Board. I'd like to thank our Board members as well as the members of our management team for their dedication and willingness to serve.

All of our Board members are present at this meeting as well as Amit Hasija, our Chief Financial Officer; and David Sandoval, our General Counsel and Chief Compliance Officer. I would also like to introduce Gregory Tremlin of PricewaterhouseCoopers LLP, the company's auditors, who are available to respond to appropriate questions; and Ryan Sansom and Paul Alexander of Cooley LLP and Jeremy Brisset of Stikeman Elliott LLP, the company's legal counsel.

The meeting will now officially come to order. We will proceed with the formal business of the meeting as set forth in your notice of annual meeting and proxy statement. After the formal part of the meeting, shareholders who are attending this meeting with a valid 15-digit control number may submit questions or comments for the Q&A portion of the meeting through the text box located in the virtual meeting screen.

Please note that this meeting is being recorded. We kindly request that shareholders limit their questions to one topic per question and to one question per shareholder. Questions from shareholders will be grouped by topic and one representative question will be read aloud before the appropriate milestone individual answers as time permits.

As noted in the meeting -- I'm sorry, as noted in the annual meeting rules of conduct, we will only answer questions that are relevant to the meeting and the proposals presented. We will not accept ballots, proxies, revocations or changes after the closing of the polls. If you have already submitted your vote by proxy and do not wish to change your vote, you do not need to vote now and your shares will be voted as previously instructed. If you intend to vote and have not already done so, you must submit your vote online now in order for it to be counted. If you have not voted, I encourage you to vote online now.

Will the Secretary please report at this time with respect to the mailing of the notice of the meeting and the shareholders' list?

I have at this meeting a complete list of the shareholders of record of the company's common shares as of April 15, 2026, the record date for this meeting. On May 1, 2026, a notice of Internet availability of proxy materials was deposited in the Canadian Postal system to registered shareholders of record at the close of business on April 15, 2026.

At this time, I would like to introduce Steve Gilbert, a representative of Computershare Investor Services, Inc. I am appointing Mr. Gilbert to act as Inspector of Election at this meeting. Mr. Gilbert has taken and subscribed the customary oath of office to execute his duties with strict impartiality. We will file this oath with the records of the meeting. Mr. Gilbert's function is to decide upon the qualifications of voters, accept their votes and when balloting on all matters is complete, to tally the final votes. Will the Secretary please report at this time with respect to the existence of a quorum?

I've been informed by the Inspector of Election that proxies have been received for 76,322,487 of the 119,637,391 common shares outstanding on the record date, which represents approximately 63.79% of the total number of outstanding shares. This constitutes a quorum for the meeting today, and we may now carry out the official business of the meeting.

The first item of business is the presentation of the company's audited consolidated financial statements for the year ended December 31, 2025. A copy of such financial statements is available on the company's profile on SEDAR and EDGAR. A copy of such financial statements has also been made available per the notice of Internet availability of proxy materials mailed to all shareholders of record at the close of business on April 15, 2026.

We will now proceed with the formal business of this meeting. After all of the proposals have been described, we will answer any questions related to the proposals submitted online. As a reminder, we ask that any comments or questions during this portion of the meeting pertain only to these proposals. Please submit any questions as soon as possible for our review. The polls will be open to voting after we go through the matters to be voted on.

There are 4 proposals to be considered today by the shareholders. The first proposal up for vote is the election of 8 nominees for director to hold office until the close of the 2026 Annual Meeting of Shareholders or until their successors are duly elected or appointed or until such directors' earlier resignation or removal. In accordance with the provisions of our bylaws, shareholders are required to provide advanced notice of their intent to nominate candidates for directors.

No shareholders submitted such notice. Therefore, I declare the nominations for directors closed. The nominees for director are Stuart M. Duty, Seth Fischer, Lisa M. Giles, Joseph Oliveto, Joseph C. Papa, Andrew R. Saik, Michael Tomsicek and Robert J. Wills, PhD.

The second proposal up for vote today is the appointment of PricewaterhouseCoopers as the independent registered public accounting firm of the company to hold office until the close of the 2027 Annual Meeting of Shareholders and the authorization of Milestone's Board to fix PwC's remuneration.

Apologies, I do want to go back to the first proposal. There was an error. It was to hold office until the close of the 2027 Annual Meeting of Shareholders, not the 2026 Annual Meeting of Shareholders.

The third proposal up for vote today is the amendment of the company's 2019 equity incentive plan as amended to increase the number of shares authorized for issuance by 6,800,000 as described in the proxy statement relating to this meeting.

The fourth proposal for vote today is the advisory vote on the compensation of the company's named executive officers as described in the proxy statement.

Shareholders have been asked to vote on an advisory basis on the following resolution: Resolved that the shareholders of Milestone Pharmaceuticals, Inc. approve on an advisory basis, compensation paid to the company's named executive officers as disclosed in its proxy statements for the 2026 Annual Meeting pursuant to the compensation disclosure rules of the Securities and Exchange Commission, including the compensation tables and narrative discussion.

Voting today is by proxy and electronic ballot. Each common share is entitled to one vote. We will open the voting for registered shareholders and duly appointed proxy holders momentarily. The electronic ballot should automatically open on the virtual meeting platform. Shareholders who have submitted proxies or who have previously voted via the Internet or by phone and who do not wish to change their vote do not need to take further action. Their prior votes will be counted automatically.

The polls will remain open for approximately two minutes.

We will now review if there are any questions submitted about the proposals before we open the polls. As a reminder, we will only review and answer questions at this time that pertain to the relevant to the meeting and the proposals presented.

Please note that our discussion today may include forward-looking statements, and our actual results may differ materially from those discussed here.

David, are there any questions?

I confirm there are no such questions. As noted earlier, to ensure I confirm there are no such questions.

Joe, over to you.

Okay. We will now proceed with the voting portion of the meeting. Will the secretary please open the polls for voting.

Yes.

[Voting]

The polls will be closing in 30 seconds. The inspector of election will not accept any votes once the polls close.

The time is 11:13 a.m. Eastern Time, and the polls are now closed for voting. We will take a moment now for the inspector of elections to tabulate the votes.

We have the preliminary results of the voting once available.

Will be available momentarily.

The Inspector of Election has provided us with preliminary results and confirmed that we have received the necessary votes required to pass the following: each of Stuart M. Duty, Seth Fischer, Lisa M. Giles, Joseph Oliveto, Andrew R. Saik, Michael Tomsicek, Joseph Papa and Robert J. Wills, Ph.D., has been elected as a director to serve until the close of the 2027 Annual Meeting Shareholders or until their successors are duly elected or appointed or until such directors' earlier resignation or removal.

The appointment of PwC as the auditor of the company to hold office until the close of the 2027 Annual Meeting of Shareholders and the authorization of the Milestone Board to fix PwC's remuneration has been approved.

The company's 2019 equity incentive plan as amended, which increases the number of shares authorized for issuance by 6,800,000 is approved.

The resolution concerning the advisory vote on the compensation of the company's named executive officers is approved. A full tally of the votes will be published in a current report on Form 8-K, which will be filed with the Securities and Exchange Commission within the next four business days.

Thank you. With no further business, I hereby adjourn today's meeting. We will now entertain applicable questions from shareholders or proxy holders posted in the virtual meeting platform.

Okay. It appears there are no additional questions. To conclude, thank you again for your attendance at today's meeting and for your continued support of Milestone Pharmaceuticals.

This concludes the meeting. You may now disconnect.

Ladies and gentlemen, good morning, and welcome to the Milestone Pharma First Quarter 2026 Earnings Conference Call. [Operator Instructions] As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Michael Wood of LifeSci Advisors. Please go ahead.

Thank you, operator. Good morning, everyone, and welcome to the Milestone Pharmaceuticals First Quarter 2026 Financial Results and Business Update Conference Call. Earlier this morning, the company issued a press release providing an overview of its financial results for the quarter ended March 31, 2026, and recent corporate highlights. The release can be accessed on the Investors and Media section of the company's website, milestonepharma.com.

Before we begin, I'd like to remind you that some of the information presented on this conference call contains forward-looking statements under the securities laws. These forward-looking statements involve substantial risks and uncertainties that could cause actual clinical programs, future results, progress, timing, performances or achievements to differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties associated with Milestone's business and factors that could cause or contribute to such differences are described in detail in the company's filings with the SEC, including in the Risk Factors section of the annual report on Form 10-K for the year ended December 31, 2025, filed with the SEC on March 20, 2026.

Speaking on the call today will be Joseph Oliveto, President and Chief Executive Officer of Milestone; Lorenz Muller, Chief Commercial Officer; and Amit Hasija, Chief Financial Officer and EVP of Corporate Development. In addition, Dr. David Bharucha, the company's Chief Medical Officer, will also be available on the call during the Q&A session. So with that, I'll turn the call over to Joseph Oliveto. Joe, please go ahead.

Thank you, Michael. Good morning, everyone, and thank you for joining us today. This is an exciting day as it represents our first analyst call reporting on our first ever quarter or, more accurately, partial quarter of sales since the commercial launch of CARDAMYST for acute episodes of paroxysmal supraventricular tachycardia or PSVT.

Today, our prepared remarks will highlight 3 advances or updates since our last quarterly call. First, we'll provide our thoughts on the launch of CARDAMYST. Second, we'll discuss the initiation of our Phase III pivotal trial for etripamil for patients with atrial fibrillation and rapid ventricular rate or AFib-RVR. And lastly, we'll provide an update on our financials from our CFO, Amit Hasija.

Let's start with the launch. To recap, CARDAMYST, the brand name for etripamil, was approved by the FDA on December 12 as the first and only rapid-acting self-administered prescription therapy for acute PSVT episodes in adults. Following approval, we immediately mobilized our launch plan. We quickly engaged our distribution channels such that CARDAMYST became readily available through retail pharmacies by the end of January. We then began promotion of CARDAMYST in earnest in mid-February, including the deployment of our national sales force of approximately 60 sales representatives. Launching within 2 months of the approval was an aggressive goal that we successfully met in Q1.

Now a little less than 3 months since the launch, we're excited to share the emerging themes we've observed so far. Cardiology health care providers across the board, including physicians, nurses, nurse practitioners and physicians' assistants are consistently responding positively to CARDAMYST. It seems clear to us that the HCP audience we've engaged so far quickly understands the value that CARDAMYST brings to the patients with SVT due to its safety profile and ease of effective self-administration. Insurers continue to collaborate with us on pathways to coverage with the goal of adding CARDAMYST to their formularies.

A great example of this is our earliest major win, Express Scripts National Formulary coverage. Express Scripts is one of the 3 major pharmacy benefit managers, or PBMs, which when combined with the other 2 major PBMs account for more than 80% of commercially covered lives in the United States. Perhaps most gratifying for us is the positive initial feedback we are receiving from the patient community and specifically those patients who received CARDAMYST. We gain these insights of patient experiences through our ongoing patient engagement activities, our social media monitoring and through physicians and nurses feedback, much of which is in the form of unsolicited text, calls and e-mails.

The stories take the form of 2 flavors. The first being those patients who've used CARDAMYST and have had a positive experience during an event, but also interestingly, stories from some patients who relay excitement simply from having obtained CARDAMYST from their pharmacy and not even having used it yet. These patients describe having an increased sense of preparedness and security for when their next event will occur. All of these patient stories are a very valuable reminder of why we do what we do.

So I'll hand it over to Lorenz to provide some additional details on the launch.

Thank you, Joe, and thank you to everyone joining us this morning. Building on Joe's overview, I will provide more color on our commercial rollout and sales progress of CARDAMYST in the first part of the year. Given that it's so early in the launch, I'll break total scripts out by month, which demonstrates steady progress month-over-month.

Moving forward, we plan to report total prescriptions, unique health care practitioner writers and unique patients as quarterly figures. Through the end of April, we've captured approximately 600 total prescriptions. Specifically, February generated approximately 100 prescriptions and March was around 200, totaling approximately 300 prescriptions in our first partial quarter. In April, we're reporting around 300 scripts, or as many as the previous 2 months combined. Our data indicate that these prescriptions were written by over 400 unique health care professionals for approximately 560 unique patients.

Our last key metric that we are reporting today and we will continue to report quarterly is lives covered by commercial insurance. With our early Express Scripts win announced at the end of March, we conservatively estimate that 25% of all commercially insured patients have quality coverage for CARDAMYST.

Now for some perspective on what these numbers mean and why they're important at this early stage. In terms of prescription volume, while it's too early to forecast trends definitively, we are pleased to see data showing steady month-over-month growth. As Joe mentioned, prescriber reception has been very positive, which we see as a validation of the core value proposition for CARDAMYST. With both a well-established calcium channel blocker mechanism and a safety profile supported by robust clinical data, we believe that these first scripts written by our target providers tell us that prescribers see CARDAMYST as an important and needed solution for their patients with PSVT.

As I said, through the end of April, over 400 unique prescribers have written approximately 600 total prescriptions for CARDAMYST. We view this breadth as a strong leading indicator of the appeal of CARDAMYST among providers. When a new therapy like this is adopted across a relatively wide physician base from the onset rather than just a narrow group of early adopters, we believe it signals that the value is clearly resonating broadly. Thus, we are building a strong, receptive foundation of prescribers who, as coverage expands and their familiarity with CARDAMYST increases, should increase their prescribing depth over time.

I will add that many of these prescriptions are coming from physicians who have met with one of our sales representatives only a few times. This is important as we believe in pharmaceutical launches, early trial after 1 or 2 interactions is a positive signal about the strength of the clinical story and a physician's interest in the product. This is something our commercial teams specifically aspire to from the onset, and we believe it reflects the compelling nature of the profile of CARDAMYST and its value proposition. As our reps build frequency and deepen their relationships through repeat visits, we have every expectation that this will be a driver of growing prescription patterns.

Now to the third metric, coverage. On March 31, we announced that Express Scripts, one of the nation's largest pharmacy benefit managers, added CARDAMYST to its commercial national formularies. I want to highlight the importance of this earlier than predicted success. This is the first contracted formulary acceptance of CARDAMYST by a major payer.

In the landscape of commercial drug launches, getting a major PBM formulary placement within the first quarter of a launch is a significant achievement. We see this as clear validation of the clinical and economic value to payers, particularly in terms of our clinical data, illustrating the potential of this drug to reduce health care utilization, including emergency department visits and hospital admissions.

The Express Scripts coverage decision means that we now have approximately 1 in 4 commercially insured lives covered. We believe most of that coverage is quality coverage, meaning patients are more likely to be approved at the point of sale rather than navigating an overly onerous prior authorization process and we will be able to refill a prescription multiple times to treat subsequent episodes of PSVT.

We are actively negotiating with other major PBMs and health plans. And while I won't get ahead of any specific decisions, we are committed to continuing to expand contracted coverage, and we expect further announcements as those discussions progress.

So to summarize where we stand across our 3 key metrics, the breadth of new prescribers and early physician acceptance gives us confidence that we are gaining traction. We are building momentum, and we will continue to plan for an acceleration in prescription volume as our launch progresses. These measurements of growth will be driven by increased promotional frequency with our target physicians, continued pull-through from our first major coverage win and additional anticipated positive coverage decisions.

I'll now turn the call back over to Joe to update on progress in our clinical development program.

Thank you, Lorenz. I'll turn now to the next major advancement for milestone and for etripamil. Namely that we have initiated our Phase III trial for atrial fibrillation with rapid ventricular rate or AFib-RVR named ReVeRa-301. This ReVeRa Phase III registration trial is based firmly on the successful performance of etripamil in our AFib Phase II study.

In that trial, patients on etripamil demonstrated a statistically significant and clinically meaningful reduction in their ventricular rate compared to placebo and also showed symptomatic improvement. The design of our Phase III AFib study, ReVeRa, uses the same approach of patient self-administration of drug and operational study conduct as our successful Phase III trials in PSVT.

Specifically, the Phase III AFib ReVeRa study is a double-blind, placebo-controlled, event-driven trial in which the patient will self-administer the drug outside of the health care setting. The study employs the same 70-milligram dose and repeat dose regimen that is already approved for CARDAMYST for SVT and many of the operational conduct components are the same as those that were used in the SVT program.

Regarding status, we are labeling clinical study drug. We have begun contracting with key clinical research sites with whom we've had successful experience from our PSVT trials and have completed contracting with several. We're actively recruiting additional trial sites in several geographic regions with a focus on the U.S. and the trial has been posted on clinicaltrials.gov. We expect to enroll our first patient into this trial in the second half of this year and look forward to providing further updates as the ReVeRa-301 study advances this year.

I will now turn the call over to Amit for a financial update.

Thanks, Joe. We have a strong balance sheet, including approximately $184 million in cash, cash equivalents and short-term investments as of March 31, 2026. This compares with $106 million at December 31, 2025. We believe our cash balance provides sufficient runway to support both ongoing CARDAMYST launch activities and our operations into the second half of 2027, including the execution of the ReVeRa-301 study.

The higher cash number is primarily the result of $75 million cash payment we received in January in connection with our royalty purchase agreement with RTW, as well as approximately $19 million in net proceeds from ATM sales and Series A warrant exercises that took place during Q1. Our operating cash burn during Q1 was approximately $23.7 million. Product revenues in the first quarter of 2026 were $0.2 million.

R&D expense net of tax credits was $3.3 million in the first quarter of 2026 compared to $5 million in the first quarter of 2025. The decrease compared with the prior year was primarily due to a decrease in the outside service costs related to drug development and research. G&A expense was $4.8 million in the first quarter of 2026 compared to $5.2 million in the first quarter of 2025. The decrease was primarily due to lower professional costs, partially offset by an increase in personnel costs.

Commercial expense was $15.8 million in the first quarter of 2026 compared to $10.4 million in the first quarter of 2025. The higher commercial expense was primarily a result of additional personnel costs, professional costs and other operational costs related to the launch of CARDAMYST. Net loss for the first quarter of 2026 was approximately $26.1 million or $0.20 per share compared to $20.8 million or $0.31 per share in the first quarter of 2025.

I will now turn the call over to Joe for some concluding statements.

Thank you, Amit. As we reflect on the quarter, we are proud of the early execution of our launch and the progress we are making in establishing CARDAMYST as a novel treatment for PSVT. While we're still in the early stages, the initial indicators we are seeing give us confidence in the opportunities ahead with the PSVT launch and with our AFib-RVR Phase III clinical development program. Our focus remains clear: driving disciplined commercial launch execution, including expanding payer access, advancing our clinical development program and managing our resources responsibly.

We believe these priorities position us well to continue our momentum over the course of 2026 and beyond. Thank you again to our team and our shareholders for your continued support.

That concludes our remarks, and we will now open the call to questions.

[Operator Instructions] We take the first question from the line of Ritu Baral from Cowen.

I wanted to ask about the 400 unique prescribers and sort of the first Rxs, NRxs that have come in. Can you talk about the mix of prescribers at this point and how you expect that sort of evolution of the mix, especially as you continue your commercial targeting? And how do you think that, that will sort of reflect downstream on the percentage of patients -- I'm sorry, the mix of patients that you end up getting?

And then according to our calculations, while you have mentioned that you're giving away free drug, it doesn't look like you've given away that much free drug. Can you talk about sort of the receptivity of that program, and has sort of bridging programs been offered and will that continue to be a part of the 2026 effort?

Yes. Great, Ritu. Great to hear your voice. Thanks for listening in on the call. And maybe I'll start a little bit, particularly with the prescriber mix and ask Lorenz to comment a little further on what that means for downstream as we're thinking about it now. And then also Lorenz to give a little bit more color on how much free drug we're giving away and how we think about that going forward.

So we've always said that this is primarily driven by clinical cardiologists. That's where the majority of these patients live in terms of their management. We always thought that EPs, electrophysiologists, could be a bigger writer in the first year, primarily because we don't have or are not expecting a lot of refills in the first year. So that was our guidance before launch.

And I would say we're largely seeing that. So far, we've seen approximately 50% of the scripts to date written by cardiology and about 25% written by electrophysiology. The other 25% is really a combination of nurse practitioners, physicians' assistants, a few PCPs, really not many at all and just an other bucket that are not classified in our data.

So it seems to be playing through with how we've thought about it prelaunch with the idea that while electrophysiologists are writing only 25%. Currently, that's a big number relative to where they'll be over the long haul, and they're influential, as you might be aware. So it's good to have that prescribing behavior because those are the folks that will be called by cardiologists asking about the drug. They're important to P&T committees, they're important guidelines, all those types of things.

Lorenz, maybe if you want to comment a little further on how you see downstream going and then move over to the free drug program.

Sure. Happy to do that. Ritu, thanks for the question. So Joe is exactly right in that we expected the majority of early scripts to come from cardiology and maybe favor electrophysiology somewhat as the thought leaders. Over time, we would expect to continue to see the majority of our prescriptions coming from cardiology, clinical and interventional cardiology. Electrophysiology will continue to use it, but their use case is more focused on bridging patients to an ablation. And so there wouldn't be as much reuse of the drug, assuming those ablations were successful.

So I think over time, we will see 2 dynamics. One is the percentage of cardiology scripts that is written by clinical cardiologists and interventionalists will increase relative to total, including EPs. And I do think the second dynamic over time is we will start to see more APPs, so nurse practitioners and physicians' assistants. As practices get comfortable that the cardiologists in that practice or cardiologists are comfortable prescribing the drug, which we are seeing evolve relatively quickly, APPs will become more the day-to-day managers of these patients and the prescribers.

I also think, finally, over time, so measured in years, not months, I do think primary care will start to adopt more, although they only represent roughly 1/3 or 1/4 or 1/3 of the prescribing population. What we're seeing is early on is primary care that look more like cardiologists than true primary care. And I do think over time, primary care will also start to write more because they're seeing some of the younger patients where they don't have -- they only have -- the only form of cardiovascular disease those younger patients have is PSVT.

To your second question on free drug quantities, our goal in the launch has always been to ensure that when a script comes in, that the payer is notified that there's demand there because that helps us ultimately convince payers that there is demand and therefore, that they want to cover the drug and make themselves -- avail themselves of those rebates.

So we don't just provide free drug right out of the gate. We go through the process and then the pharmacist and/or the physician, the office have to fill out the paperwork for prior auths or medical exception, which is where most of the scripts come through ahead of coverage. And only where those prior auths or medical exceptions are not granted, do we then come in primarily with assistance.

So I would say I was pleased to see that we are week-over-week seeing growth in the number of scripts that are actually filled. And that is in part a sign of expanded coverage, meaning the ESI coverage decision win, but also somewhat our ability to now convert patients, meaning at the end of the chain, if they don't pass medical exception, we are there to catch that patient and allow them to use the drug.

So this is more sort of like true bridging rather than like a sampling effort. Is that correct?

Yes, I think that's accurate, Ritu, yes.

We take the next question from the line of Ted Tenthoff from Piper Sandler.

Congrats on the nice first quarter launch. Lorenz, always appreciate all the detail and color that you provide. My question has to do with the ReVeRa-301 and just a sense of -- I know you're just starting and just kicking it off, but walk us through a little bit more in terms of the patients that you're enrolling and maybe what our expectations should be in terms of how long it might take to enroll the study?

Sure. I'll handle this. Of course, if there's any further questions, David Bharucha is on the line. So very importantly, and just a reminder for the audience is atrial fibrillation is a huge market. Current estimates about 10 million patients with atrial fibrillation in the U.S. alone and growing. Expectations are that this number will increase in the short term here.

And very important to realize that we are looking for patients that have AFib are characterized with AFib and importantly, are characterized with AFib and events of rapid ventricular rate. These are events above 100 beats per minute and commonly last for some time and are very importantly, symptomatic to the patient. The ultimate value prop for CARDAMYST, Ted, is really to help resolve that elevated rate, bring it down towards a more normal rate, doesn't have to get all the way to normal and reduce symptoms.

And by doing that, we should enable the patient to manage these episodes at home and not have to go to the emergency department for most commonly IV calcium channel blockers like IV diltiazem. That is the value prop. We want to follow that in this study. So very importantly, we're looking for patients that have a history of AFib with rapid ventricular rate, ideally more elevated rates and very importantly, symptomatic rates.

So that's what's really the driver for this study in the patient population we'd like to see. We believe that the study should -- well, it is powered at 90% to deliver 0.05 based on really the second endpoint, which is symptomatic improvement. We believe that powering it that way should deliver a successful results with a total size of somewhere in the range of 150 to 200 total events. And we believe that, that study should take around 2 years from start from our first patient enrolled to data.

That's our current estimate. There's a lot of variables in there, but it's driven primarily off of our experience with our PSVT program, our experience with our Phase II program in AFib and trying to triangulate around what we saw in both of those programs both with the AFib experience in the emergency department, but also operationally the PSVT program in the outpatient setting.

So it will be -- also it will be sized similar to our PSVT programs in the sense of multi-country, multisites ranging up to 600 patients enrolled in the funnel, if you will, to deliver that 150 to 200 total AFib-RVR events.

We take the next question from the line of Mohit Bansal from Wells Fargo.

Congrats on all the progress. I want to dive a little bit deeper in the Express Script formulary decision. Can you remind us what kind of prior auth is required to make it available for the patient? And then if I do the math on like number of prescriptions and then the sales you are reporting, it seems like pretty high, almost $800 per script number.

So is that, Lorenz, like you said, that you are trying to make sure that payers do see it and you are not providing free drug just yet. Is that the reason why the gross to net seems to be really good here?

Yes. I think those maybe are questions for Lorenz to provide color. What I'm hearing, Mohit, is you really want to know about ESI coverage and what that looks like in terms of how quality is it and what's the prior auth process was the first question. And then the second question, let me just make sure I got it correctly. Are you calculating something like $800 per script? Is that what I heard?

Yes. So basically, like $238,000 divided by the 300 script number that you provided. So just trying to calculate it via that.

Okay. Well, maybe I'll ask Lorenz or Amit to help out with that one as well. So Lorenz, maybe you could start with the ESI number.

Sure. Yes. So ESI is one of the 3 big pharmacy benefit managers, right? It rolls up under Ascent. And so by signing a contract with them and getting coverage, that allows, as I mentioned on the call, about 1 in 4 commercially insured patients to have coverage for the drug.

And that means all the plans that ESI administers a pharmacy benefit for will now have the ability to make a coverage decision and then fill the drug without all the different steps that I mentioned in the previous question from Ritu, which is an onerous prior auth process or medical exception, things that take time and requires a lot of work on the part of the physician or the pharmacy to populate.

With Express Scripts, I mentioned that we think the majority of that will be what we call quality coverage. I can't say all of it because there's a lot of different benefit designs under ESI and not everyone opts into the offer, but we have confidence that the majority will. And our definition of quality coverage is essentially that the -- it's not onerous to prescribe the drug and get it filled, meaning the physician's office doesn't have to do a ton of paperwork, in some cases, no paperwork in order for the product to be able to be filled at the pharmacy. And that there is the ability for the patient to refill the drug a number of times.

Most patients have more than one episode a year. And so they want -- if they have success with the drug, which we are hearing anecdotally from patients, they are, they'll want to go back and get a refill, and we don't want it to disproportionately limit the amount of product that a patient can get, but we also understand that payers in a launch here might be concerned about a patient using this 30 or 50 or 80 times a year, which we're not expecting to see.

So again, quality coverage is limit the amount of prior auth paperwork to as little as possible. And ideally, anything that's required is adjudicated at the pharmacy and not requiring the doctor or the doctor's office to fill a lot of paperwork and also that the quantity limits aren't overly draconian. So we're happy if a patient can have up to 6 or 12 fills in a year. Although in a launch year, as we've said, we expect most patients to use this a couple of times.

On the second part of the question, by the way, I was taking note. I think, Mohit, the confusion is we had announced on the earnings call that we have around about $200,000 in net sales and that that's coming from 600 prescriptions, not 300. So I think the math you did was a little bit off in terms of the dollars per prescription. It is, in fact, a little bit lower than the range we've often quoted of $500 to $1,000, but that's because we're in the first quarter of launch, and we are seeing a lot more use of denial conversion or where medical exceptions aren't going through, we do want those patients to have access to the drug.

So we expect that number to increase steadily over the next few quarters to get into the range of what we've reported previously.

We take the next question from the line of Tiago Fauth from Raymond James.

I just want to talk a little bit more about the acceleration in prescription volume, right? So you are seeing that steady pace of adds -- an increase in adds. I'm curious, and again, it hasn't been that long, but the Express Script agreement, can we expect to see some degree of acceleration relative to that? Does that quality coverage actually could increase the pace of net adds?

And then I have a follow-up just in terms of the depth of prescribers and the patient journey. Question here is mostly about the ramp for the launch, right? So what are some of the key levers that will lead a physician to prescribe to more patients and for a patient to actually utilize this more than once a year. I know there's probably a cap there. But again, depth of prescribing and also the utilization per patient, what are some of the levers early in the launch? I understand, but just trying to think about this the longer term.

Okay. So Tiago, great for jumping on here and for the questions. Again, I'll start, Lorenz. I don't know if I caught all those questions at the end. I might have to ask Tiago to come back to a few of them. But certainly, ESI -- and remember, Tiago, we got that right at the end of the quarter, so right at the start of April. So these first quarter numbers are really all without any coverage pretty much or very, very little coverage, whatever you get initially out of the gate.

So remember that is the first thing. We do see coverage in general and then ESI is a good early win is providing 2 things. One is obviously a little better pull-through once a script gets to the pharmacy and that paperwork, as Lorenz said explained, having to be a lot less, if any, to be able to actually see the script show up and actually get filled. So that's the first part.

And then the subsequent kind of intangible that is just the reality these days is physicians will write if they know that there's less hassle factor. It's funny. I've been out in the field now too handfuls of times. And very consistently, you're ending the call with how do I get it? Is it covered? Is it in Epic? That type of stuff. What pharmacy has it? And is it covered and what have I got to do? And what does my staff have to do is a real question.

So it's an intangible, but I can't help but believe that with coverage, and we are very cognizant of not wanting to put too much burden on these offices with the idea of turning them off. A doctor has to write 2 or 3, 4 pieces of paperwork for a patient and then they don't get it, that can frustrate them. So we're very sensitive to not having that happen. And getting that coverage. And at the end of the day, we think that as we get coverage and less of that paperwork has to happen, it's going to result in more initial scripts.

So it's just in the back of the physician's mind. So yes, to acceleration. However, remember, Express Scripts, while a big payer, it's 1 of 3 on the commercial side. And remember, about half of our population is commercial, about half of the population is Medicare. So think of it as like half of the 25% that we reported for the total target addressable market in terms of coverage so far. So a ways to go on that front.

So that was a lot on that. Lorenz, maybe you can move on to the second and third questions.

Yes, I will. And I'll just add one other thing on the acceleration. You were focused a lot, Tiago, on the coverage part of acceleration. And we certainly think broader coverage will be for the reasons Joe mentioned, a driver of acceleration. But the other one is promotional response, right? Our reps have been out there now for a couple, three months. They've seen a lot of their customers only once or maybe twice.

And as they get more frequency on those customers and as they reach more of the customers in the rather large territories that they have, we do expect that to result in more prescription writing. And that's a little bit of answering to the second part of your question, which you were asking about 2 parts, as I heard. One was what are the tactics or the levers where target physicians will write more than they're currently doing. Most of our physicians based on the numbers we reported this morning, have written a script, although about 25% have written more than that.

And then the second part was how are we going to drive utilization of the patient where they fill more than one script. And both of those will happen over time. And they're related to both the physicians' awareness and willingness to trial, which we're seeing, but then translating the willingness to trial to usage where they use it on more patients and where patients actually come back after they've had a successfully treated episode. or where they ask for a second script to be filled even before they have a first episode because they want to have access to the drug.

So with the payers being willing to give patients, say, more than one dose at a time, we do believe patients will go in and fill a second or a third script in order to be able to have the drug on them, in the office, at home, in close proximity. So when they have that unexpected episode, they can treat it quickly.

So I think all of that, the answer is time and effort for us to continue to drive promotional response, getting in front of HCPs, prescribers and making sure they're aware and trialing in appropriate patients. And then we do think over time, as patients have a successful experience with the drug, we've seen this already in some of the anecdotal social media listing we've been doing. They'll come back to the docs say, "Hey, that really works for me. Could you write me another script? I'd like to refills." That's sort of a dynamic. We will also accelerate our adoption.

We take the next question from the line of Brandon Folkes from H.C. Wainwright.

Congrats on all the progress so far. Maybe just 2 for me. Can you talk about how you're thinking about targeted DTC spend going forward here? And then last year at your Commercial Day, you provided a lot of really insightful detail on how you envisioned the launch. Can you just talk about if the launch is tracking sort of within all those expectations? Anything there that you see different today? Obviously, Express Scripts coming on very early on. But yes, just put in context how you see the launch today versus sort of how you framed it last Feb.

Sure. Again, I think I'll just provide a high level. And then, Lorenz, these are really questions for your insights. I would say with regard to targeted DTC spend, hopefully, what came across in our plans before we got the approval, Brandon, was we're trying to be very thoughtful around how to use the dollars and use them in areas that are really going to drive the most bang for the buck.

And things like targeted DTC or what we call DTP, direct-to-patient as well as even things like nonpersonal promotions to physicians. Everyone is aware, we have about 10,000 targets. I'm pretty sure everyone is aware that we're not going to get to all those targets. There are no C physicians in our target call base. And that lends itself to nondirect promotion or what we call nonpersonal promotion. So these are ability to get the message and the information to these offices that we can't have our reps come in on, right?

And it takes a little longer to get to those offices. But the thought is behind both of these tactics, if you will, is let's make sure we have enough coverage and enough general awareness through the more routine routes of our sales representatives and working through the coverage system before we really start driving patients into the office. So it's always been very tailored that way, and we still expect that to happen.

We are, though, having pilots in those areas such that when we are ready to turn on the spigot, if you will, and open up spends on those areas, we know where and how to spend it. So that's the general philosophy of how we're approaching these things. But Lorenz, maybe you can provide a little bit more color specifically to the DTC spends that Brandon is talking about.

Sure. So we've always said that this is a patient-driven market. And we still -- everything we're seeing in the launch so far suggests that, that was a correct assessment. And so it's really a question of timing rather than -- so it's not if, but it's when. And what I mean by that is you don't want to drive patients, this is in any therapeutic area into the HCP office or into a prescriber office if the prescriber is not aware of the new drug, right? That always becomes problematic. It's one of the reasons why DTC ads are not allowed in the launch year, meaning television.

So what we're doing is to be compliant with that, which we believe, which we agree with, is we've done some pilots, as Joe alluded to, which are really primarily targeting tools that are already in doctors' offices, whether they're wallboards or whatever that is, to be able to generate some awareness amongst patients and see if we can actually raise awareness amongst patients through those tactics. So they're not expensive, but there are things that are very scalable.

So if we invest in that and we do it for a period of 2 or 3 months and we see a positive ROI, then we'll know we can do more of that later this year or starting next year to drive patient awareness because we're very confident that if a patient is aware of a new treatment for SVT since there's no competition out there, they will likely go into the doctor and ask for it. And where they do ask for it, more than likely it will be granted.

Then more broadly in terms of patient activation, so that was just awareness generation tactics. But in terms of actually doing kind of the customer relationship marketing, building educational resources and then capturing patients by advertising for them and then building a relationship with them and marketing to them. So the classic direct-to-patient type tactics.

We are in the process of building those capabilities, and we expect to bring them online in a time frame, whether it's later this year or early next, where we have sufficient awareness and trial amongst cardiology that they're not going to be surprised that a patient is coming in to ask for the drug and certainly won't be irritated by that. So that's kind of how we think about the staged rollout of a very important and long-term tactic that I think will drive business, which is patient activation.

In terms of the second part of your question, Brandon, around what are some of the -- how is the launch tracking from our view? You kind of captured the 3 broad areas. So we think about payers, we do think we're a little bit ahead of what we were expecting with the early win from ESI.

And we -- nobody asked about how we're doing with the other big payers, but we are in active discussions and are pleased with what we're seeing in terms of level of engagement, right? You can't get to a contract, you can't get to coverage if the payers don't want to talk to you. And I can confidently say we are talking to all the major payers, both the commercial ones, which is the big 3 PBMs as well as the Medicare payers where we're setting ourselves up to be within the consideration set for formulary decisions in 2027.

So there -- I'd say we're ahead of plan. In terms of cardiologists and HCP reception, we are hearing very positive feedback and Joe and I have seen it when we've been out in the field ourselves in terms of the profile of the drug. People seem very happy with the efficacy and the safety data. It doesn't take very long when you're in the field as a rep or as one of us going out to get the doctor to say, "Okay, I get it." This looks really interesting. Yes. And then you start talking about what kind of a patient and when am I going to be able to write this.

I can say we've mentioned earlier in the pre-approval that we were targeting around 10,000 doctors. We currently have engaged with about 1/3 of those doctors, meaning a sales rep has been in there one or multiple times to actually get in and talk and make them aware of etripamil. And you heard me earlier, so that's -- think about it as around 3,000 or 4,000 doctors that have actually been engaged with a sales rep. And you heard earlier that we have around 400 writers. So we're seeing north of a 10% prescribing rate for the people that we've reached.

And this early in the launch, 2 to 3 months in, we're actually quite pleased with that metric. We expect it to obviously grow as we get more reach and as we get more frequency on these customers. But that's an early metric that I think is a sign of, that the launch is tracking as we hoped it would.

And then the patient response is the third area that's very important. All we've heard at this point is anecdotal from social media listening about how patients are responding to the drug. Not many patients have gotten a prescription and actually use the drug given the nature of the episodes, but some have. And so far, that response has been overwhelmingly positive. And so that's a very good sign that patients are having good experience. They're going to report that back to their doctor and then they're going to get refills.

Congrats on the launch progress to date.

We take the next question from the line of Dennis Ding from Jefferies.

This is Georgia on the line for Dennis Ding. A quick question on the commercial strategy and launch. You mentioned many of the early prescriptions are coming from just 1 or 2 rep interactions. Can you provide more detail on just how many touch points you're seeing on average today and how you expect that to evolve as the launch matures to hit those 10,000 docs you just spoke about? And any plans for a sales force expansion to do that?

And then relatedly, are you seeing differences across prescriber segments such as the EPs versus the cardios in terms of the number of interactions required to drive initial and repeat prescribing? And then finally, when would you expect your sales force to reach max productivity?

Okay. Yes. I think some of these, Georgia, will be a little tough just given how early we are, especially when we want to talk about repeats. Really, we're just in the initial stages there. But Lorenz, a host of good questions for you to speculate on, I would say, some of these things.

Fair enough. Thanks, Georgia, for the questions. So in terms of the early prescriptions, yes, you're correct. We know many of our customers have seen a sales rep once or twice, although a number of them have seen them dozens of times. It really very much varies in terms of the access. So it is definitely too early to be able to calculate promotional response.

We can get an anecdotal feel for, wow, that doctor got one detail and they wrote a script, and we saw that a number of times, right? So that's very promising and suggests that it's not complicated to understand how to use this drug, and there don't appear to be any concerns about new mechanisms or safety concerns or any of that, that would limit a doctor based on an initial encounter or two with a sales rep to be willing to write the drug and actually follow through with getting it filled.

So that feels pretty good early on. But you're right, we will, over time, want to get doctors not only to reach more customers than the ones we've already reached, so go beyond the roughly 1/3 of our targets that we've reached and get to a higher number and then also get more depth, which would result in it being more top of mind, which means that each doctor would end up writing for more than one patient over time.

In terms of sales force expansion, our strategy at launch is still valid, which we thought is we're going to go out with a sufficiently sized sales force, our 60 reps, where we can confidently demonstrate demand, but not get ahead of coverage. So what we don't want to do is make a number of -- a larger number of physicians frustrated by the fact that they can't get scripts filled and then decide they're not going to write until we have broader coverage. So we felt like that was the rightsized sales force to be able to go out with.

And as we do gain coverage, this has always been the strategy, focused on commercial first, but over time, next year, we hope to get some Medicare coverage. That will be the time to consider expanding the sales force. But you also heard me say earlier that we're also going to be thinking about ramping up patient activation. And so it's going to have to be a responsible decision around what gets the biggest bang for the buck.

So later this year, we'll have a better sense of the promotional response for our existing promotion. In other words, how much do we pay for a rep and how many scripts does that rep generate? And we'll also have a sense from some of the pilots about how effective patient activation is. If we market to a patient, we identify them and market to them, will they actually go in and get a script. And we can measure all that because they're largely digital tactics. And based on that, we'll make a decision probably later this year or early next year around where do we put the resource, which one gets the bigger bang for the buck. So it's going to be ROI driven in terms of how we expand the commercial effort, and it's not just focused on the sales force.

You also asked about any differences in promotional response from cardiologists versus electrophysiologists. And again, it's too early to calculate that from data. But again, having been out in the field, Joe also alluded to the number of times he's been out. The use case and the discussion with an EP is a little different than with a cardiologist, and we've trained our reps to be able to accommodate that. But we're not necessarily seeing any incremental resistance to prescribing and/or any overly enthusiastic prescribing differences between cards and EPs.

It's just that how they think about using the drug is a little different. A cardiologist is more likely managing a newly diagnosed patient that doesn't want an ablation or an existing patient that is dissatisfied with existing therapies. And the EP is more thinking about how to use the drug potentially on a patient that they're queued up and waiting for an ablation.

And your last question is around -- on sales force productivity and maximizing that. And again, it's too early to calculate that, but conventional, let's call it, wisdom or experience would suggest that when you deploy a new sales force, you need at least 3 to 6 months before they can get out to all of their customers, to get to their reach targets and also get sufficient frequency on their customers to get them on whatever adoption path that particular customer is on.

So I'd suggest that second half of this year is what we'll have a better sense of that. And that's also when we feel like we can start to calculate promotional response, which would drive some of the investments that I mentioned earlier in this answer.

I think there's one thing to add, Georgia, is the difference, at least from my experience being in the field now, it's hard to get through a discussion with an electrophysiologist about CARDAMYST for PSVT with them not wanting to bring up atrial fibrillation and they, almost to a person, do.

And we know that. We know that it's driven largely by the fact that their ablations in atrial fibrillation are not nearly as successful as they are in SVT. And it provides a nice bridge for us then to have that discussion with them with our medical team. We refer them over to the medical side of the house and the clinical side of the house to be able to engage them around what we're doing on the development and the Phase III program for AFib. So that's the other main difference between the 2 groups, cardiology and atrial fibrillation. We want to be super compliant and make sure we drive the message home that this drug is for PSVT. It's approved there. There's a high medical need there.

To Lorenz's point, we do talk about the right patients. Maybe it's that patient getting a bridge to an ablation or that patient who's trying to decide on their ablation. That's the discussion. But it really is obvious that they're really looking forward to our development in AFib and that gets them excited and gets our clinical team excited.

Ladies and gentlemen, as there are no further questions from the participants, I would now hand the conference over to the management for their closing comments.

Thank you, operator, and thank you all to the investors who called in today and those who listened in. And I appreciate all your interest in Milestone and look forward to updating you as the launch progresses. Have a great day.

Thank you. Ladies and gentlemen, the conference of Milestone Pharma has now concluded. Thank you for your participation. You may now disconnect your lines.

Good morning, ladies and gentlemen, and welcome to the Milestone Pharmaceuticals Fourth Quarter and Year-End 2025 Corporate Update Conference Call.

[Operator Instructions]

As a reminder, this conference is being recorded. I will now turn the call over to your host, Michael Wood of LifeSci Advisors. You may now begin your conference.

Thank you, operator. Good morning, everyone, and welcome to the Milestone Pharmaceuticals Full Year 2025 Financial Results and Business Update Conference Call. Earlier this morning, the company issued a press release providing an overview of its financial results for the year ended December 31, 2025, and recent corporate highlights. The release can be accessed on the Investors Media section of the company's website, milestone pharma.com.

Before I begin, I'd like to remind everyone that some of the information presented on this conference call contains forward-looking statements under the securities laws. These forward-looking statements involve substantial risks and uncertainties that could cause actual clinical programs, future results, progress, timing, performances or achievements to differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties associated with Milestone's business and factors it could cause or contribute to such differences are described in detail in the company's filings with the SEC, including in the Risk Factors section of the earnings report on Form 10-K for the year ended December 31, 2025, filed with the SEC today.

Speaking on the call this morning will be Joseph Oliveto, President and Chief Executive Officer; Lorenz Muller, Chief Commercial Officer; Amit Hasija, Chief Financial Officer and EVP of Corporate Development. In addition, Dr. David Bharucha, the company's Chief Medical Officer, will also be available during the Q&A session. So I'd now like to turn the call over to Joseph Oliveto. Joe, please go ahead.

Thank you, Michael. Good morning, and welcome, everyone, to our 2025 year-end earnings call. December 2025 marked a transformational event for Milestone Pharmaceuticals with the FDA approval of CARDAMYST, etripamil nasal spray for paroxysmal super ventricular tachycardia or more specifically for the conversion of SVT to normal sinus rhythm in adults. Milestone is entering an exciting new phase of growth as we focus on bringing this important new therapy to patients and building a strong commercial franchise.

The FDA approval of CARDAMYST was the culmination of years of clinical development and scientific commitment. And as such, I'd like to reiterate my appreciation and thank all the people who help make this happen. This includes the clinical trial investigators and clinical support staff, our partners who conducted the various clinical, manufacturing and regulatory programs. The patients who participated in the studies and, of course, my colleagues here at Milestone, who put in the hard work and dedication to bring us to where we are today.

We see the FDA approval of CARDAMYST as a foundation for value creation. Let me expand on what I mean. First, our commercial team is now executing on the launch of CARDAMYST, the first new therapeutic option in 30 years for more than 2 million patients with PSVT. Our goal is that this new product will become a trusted and essential tool for health care providers and their patients. Our commercial strategy this year is focused on driving new patient starts and achieving commercial coverage, which, if successful, is expected to accelerate prescription growth. The strategy also includes ensuring patients have a good initial experience with CARDAMYST.

We were successful in having CARDAMYST available in the market in late January, approximately 6 weeks after approval, and we began our promotional launch a few weeks later by mid-February. While we're only about a month or so into the launch, we are very encouraged about the initial feedback from prescribers, and Lorenz will be providing more details than what we are seeing regarding the launch later in this call.

Second, we believe the FDA approval of CARDAMYST will enable us to leverage our comprehensive clinical data and seek marketing approvals in other parts of the world. The regulatory process here in the U.S. is seen as the gold standard, and we believe that having an FDA approval adds to the credibility of CARDAMYST. We filed a Marketing Authorization Application, or MAA, for etripamil nasal spray or TACHYMIST, as it will be known in Europe in the fourth quarter of 2025.

We announced the EMA's acceptance of that application in January, and we are engaged with the reviewers, and we expect that review and the decision from that review to occur in the first half of 2027. Moving on to our finances. Milestone Pharmaceutical is well capitalized, and we are reporting today a strengthened balance sheet that we believe supports the successful launch of CARDAMYST and provides us with expected operating runway into late 2027. We are reporting a pro forma estimated cash figure of $200 million. This includes the year-end audited cash and cash equivalents and short-term investments, plus the funds we received in early 2026, and from the RTW royalty payment, exercises of a portion of the warrants from our last financing and the sale of shares through our ATM program.

The figure does not include estimated burn to date in Q1. Amit Hasija, our CFO, will provide the details on our financials later in the call. And lastly, we've recently enhanced our leadership team with the addition of David Sandoval to the position of General Counsel and Chief Compliance Officer. David has an established track record with more than 15 years, leading legal and compliance functions across the life sciences sector. We believe this experience will be extremely valuable as we scale our operations and build the infrastructure to support long-term growth.

With that, I'd like to turn the call over to Lorenz for some additional color on the launch.

Thank you, Joe. And thank you to all of you for joining us this morning on our update. From a commercial perspective, we're excited to be underway bringing CARDAMYST or etripamil nasal spray to patients who have not had a new treatment option for literally decades. CARDAMYST is the first FDA-approved self-administered therapy specifically designed for acute PSVT treatment. Many patients with PSVT often rely on emergency departments for acute care. CARDAMYST is an intranasal treatment option supported by robust efficacy and safety data that patients can administer themselves at the onset of symptoms. Our commercial strategy is focused on targeting high-prescribing cardiologists, electrophysiologists and advanced practice providers who manage PSVT.

With our sales force of approximately 60 representatives, we are targeting around 10,000 providers who we estimate will manage half of the 1 million patients with PSVT who will receive treatment for their condition in 2026. In support of these efforts, we have also been proactively engaging with payers to demonstrate the value proposition of CARDAMYST for PSVT, including the potential to reduce costly emergency department visits and hospital utilization. We believe the PSVT market represents a clearly defined opportunity within cardiovascular specialty pharma. And our commercialization plan is designed to drive early trial and usage and achieve broad coverage while establishing a durable franchise in acute arrhythmia management.

So let me now update you on the positive momentum we're seeing in the market during these early stages of the launch of CARDAMYST. Overall, we are confident and excited about the first few months since the approval, driven by 3 achievements. First, as Joe said, we make CARDAMYST conveniently available to patients through retail pharmacies across the country within 6 weeks of FDA approval. Second, we hired, trained and deployed our national sales force within 2 months enabling them to start delivering thousands of details per week by the middle of February.

And finally, we have ample evidence that ahead of contracted coverage, our investments in reimbursement support are all online and functioning as we had intended, helping providers to write and patients to fill prescriptions. These early achievements are important because they directly support the 3 pillars of commercial success that you've heard me talk about in the past. And those are making CARDAMYST easily accessible and affordable for patients making CARDAMYST easy to prescribe for providers and limiting the need for payers to actively manage the use of CARDAMYST.

So let's now drill down into the actual launch. While it's still very early, what we are seeing at this stage supports our confidence, prescriptions are being written, wholesalers are ordering replenishment product and patients are walking out of pharmacies with CARDAMYST in hand, strongly suggesting that retail distribution is working. On the demand generation side, our sales force is delivering well over 1,000 engagements with targeted providers each week showing that they can get in front of high-value customers just a month into the promotional launch. In this first month of promotion, we've seen over 150 prescriptions filled generated by over 100 unique prescribers.

Most of the prescriptions filled to date are new patient starts and have been written by providers who are targeted by our sales force. We believe that these numbers give us an early indication that our sales operations have good initial functionality. In the future, and as our promotional efforts progress, I will continue to report on prescriptions and prescribers, including total prescriptions, unique prescribers and new patient starts as well as update on contracted coverage by payers.

On the coverage front, as I mentioned a few minutes ago, we have data to indicate that our reimbursement support architecture is working, even without contracted coverage in place yet. Prescriptions are being written, prior authorizations are being prepared, medical exceptions are being submitted, and there has been inbound activity on our reimbursement support line. The investments we made to help facilitate script fulfillment early on at launch are working in the way we design them. As an example of this, I want to share an anecdote of a nationally known electrophysiologist whose name you would all recognize. wanted to prescribe CARDAMYST for one of his patients. His first 2 attempts to fill the prescription at retail pharmacies failed were once he tapped into milestone support services with the help of his local sales rep he was able to get the patient CARDAMYST that same day. For each successful case study, however, there are at least an equal number of examples where we know of demand from a doctor, but the normal rigors of insurer controls block or delay access to the patient receiving the drug despite the physician's desire for their patient to have it.

We continue to work on pull-through of these scripts, both by supporting physicians office staff with assistance in completing the prior authorization or medical exception paperwork and of course, by working toward gaining coverage. This natural dampening of prescription fills and buildup of prescriptions in queue for eventual filling is fully within our expectations based on our extensive prelaunch interactions with payers. Let me give you some details of the support systems we have in place to help patients in advance of contracted coverage.

CARDAMYST launched with the support of a patient assistance platform as we continue to negotiate with insurers for formulary placement and coverage. The program provides benefits verification, reimbursement support and co-pay assistance for eligible patients with commercial insurance that covers CARDAMYST, reinforcing Milestone's commitment to making CARDAMYST affordable for patients who need it. So in summary, our strategy in this launch year is to demonstrate that there is real demand for CARDAMYST.

To achieve this, we will continue to focus on ensuring that physicians want to and can prescribe CARDAMYST. Patients can access and afford the product and payers can see real demand building in the marketplace. While we are now about a month into launch, it's too early to comment on trends or identify durable patterns, especially because we do not yet have contracted coverage in place. So we are encouraged by what we are seeing, but not extrapolating yet from very early launch data. We see the current period as being informative but not yet representative.

In the coming months, we expect prescription volume to increase and commercial coverage to expand over time with more meaningful progress in the back half of the year, and that should further support the launch trajectory.

I'll now turn the call over to Amit to review the financials.

Thank you, Lorenz. We recognized $1.5 million in milestone revenue in the fourth quarter and full year 2025. There is no revenue comparables in 2024. That full year revenue reflects a milestone earned under our license and collaboration agreement with Corxel following FDA approval in the U.S. for CARDAMYST in PSVT. R&D expense, net of tax credits, was $5.5 million in the fourth quarter of 2025 compared to $3.9 million in the fourth quarter of 2024. For the full year R&D expense was $18.1 million compared to $14.4 million in 2024. The year-over-year increase was primarily due to higher consulting and outside services costs, partially offset by lower personnel-related costs.

G&A expense was $5.1 million in the fourth quarter of 2025 compared to $4.0 million in the prior quarter. For the full year, G&A expense was $17.3 million compared to $16.7 million in 2024. The increase was primarily driven by higher outside service costs and higher personnel costs. Commercial expense was $8.2 million in the fourth quarter of 2025 compared to $4.4 million in the fourth quarter of 2024. For the full year, commercial expense was $28.3 million compared to $11 million in 2024. This increase primarily reflects additional personnel costs, professional costs and other operational costs associated with preparation for the launch of CARDAMYST. Net loss for the fourth quarter of 2025 was $17.4 million or $0.16 per share compared to $12.4 million or $0.19 per share in the fourth quarter of 2025.

For the full year, net loss was $63.1 million or $0.75 per share compared to $41.5 million or $0.67 per share in 2024. As of December 31, 2025, we had $106 million in cash, cash equivalents and short-term investments. On January 12, 2026, we closed the sale of the royalty interest under our royalty purchase and sale agreement with RTW and received $75 million in cash in exchange for the royalty interest in CARDAMYST. Subsequent to year-end, we also raised approximately $10.9 million in net proceeds through our previously announced at-the-market offering program and received a further $8 million in net proceeds to the exercise of warrants.

Taking these additional funds into accounts gives us a pro forma cash number of approximately $200 million. We believe this supports a successful launch of CARDAMYST and provides us with expected operating runway into late 2027.

I'll now turn the call over to Joe Oliveto for some concluding statements.

Thank you, Amit. We at Milestone Pharmaceuticals believe we are well positioned at a pivotal moment. With CARDAMYST, we have the opportunity to change paroxysmal supraventricular tachycardia is treated in powering patients with a self-administered option, reducing reliance on emergency department care and establishing leadership in acute cardiovascular therapy.

That concludes our prepared remarks, and we'll now open up the call to questions.

[Operator Instructions]

Our first question today is coming from Ritu Baral from TD Cowen.

This is Athena Chin on for Ritu Baral. A couple of questions on the CARDAMYST launch. How has feedback been to date between the different prescribers that you're targeting? And where are you seeing the most adoption? And on Coverage, what are the leading reasons for coverage denial.

Yes. Great to hear you, Athena. Thanks for taking the time to hear the update. And with regard to prescribers, we're actually seeing a broad mix across cardiology, electrophysiology. And as Lorenz had mentioned, specifically in the script, the APPs who are the nurse practitioners and physicians' assistants. I think we've guided even before the approval that we thought that the APPs would be a key group for this product. They're very engaged with the patient and hearing from the patient even between visits.

So we're seeing a breadth across those specialty groups. And then I think your second question was reasons for coverage denial. It's a bit of a mix right now, and it's early days, I would say. So each plan is -- basically just has a basic kind of block until review, I would say, is what we're seeing most. And what that translates to is a lot of paperwork for confirmation that this could be a patient that could be applicable for CARDAMYST. Extra paperwork on do they have PSVT? Have they had events? Have they visited the emergency, those are some examples of what we see, and those were expected.

Your next question today is coming from Ted Tenthoff from Piper Sandler.

Great. Congrats on the launch really, really extending time for the company. Picking up on that last question, how long is it taking for reimbursement to kick in. And what is Milestone doing to kind of make sure patient get drug in that delay period? How does that work for -- are they getting drug and it's just they then have to kind of fight to get it paid for.

And then secondly, when it comes to supply, what can you tell us about manufacturing supply and sort of how that side of the business is looking?

Yes. Great questions, Ted. Great to hear voice. How long is an interesting question when you're only launch for a week -- for a month or after you only have 4 weeks of data. And Yes. So I would say the example of that Lorenz gave is a great one, right? They tried twice and then they engage the system and then once you engage the system, we've seen scripts filled within days. We've seen scripts filled within weeks and 4 weeks in, we've seen a few scripts not filled yet. We're still working on them. So there is this natural dampening, again, I think we even targeted and signaled to the Street what it is for the industry, which is before you get approval and you have to go through medical exceptions, the benchmarks tell us that more than half of the scripts are not filled, okay?

So that is the benchmark that we have in our head and we're trying to beat that, obviously, with our programs, which dovetails into the second part of your question, which is what are we doing. So we have the patient support system, we do have our sales representatives guide largely the APPs and the office managers that, that's available to them. But remember, we're out there also trying to build awareness of the drug. So we're trying to do all this in the same calls and repeat calls. We have co-pay assistance programs, both in the form of co-pay cards, which give us a little bit more data on how these patients are doing and whether they're getting the drug or not. We also have electronic systems at the pharmacies where we're yet to see the data on. That data has just lagged by a good month or so. So we haven't seen any of that data yet.

So compartmentalized with the question and the uncertainty around how long it takes is we just need time for these data sets to come in. A lot of them are informed if it is on a case-by-case basis, which I don't want to get into with the investors. But that's the value of what we're doing now, having 3 or 4 different programs online allows us to see on a case-by-case basis, which ones work in which areas of the country and then allows us to be prepared to like move the dial on different programs depending on what we see.

That's very helpful. And then the last question was just on supply. Thanks Joe.

Yes. No, supply, we're still in -- we're well prepared. We still have supply left over even from the R&D efforts. So those batches are available and being pulled through and out into the market. And we've already gotten on to a routine cadence of next batches going forward. So all working well on the supply side.

Next question today is coming from Brandon Folkes from H.D. Wainwright.

Congrats on all the progress. A few from me, understanding it's very early on in the launch, but I thought I'd ask this. Given it is early, do you have any sense of when CARDAMYST has been described currently, what it is replacing. Is it the pull in the pockets? Is it newly diagnosed patients? Just any color there would be helpful.

And then maybe secondly, I'll just ask this with it because granted. I don't know how much data you have at this stage. But in terms of early real-world feedback, have you heard of any patients having an episode post having CARDAMYST. And if that has happened, has it worked as anticipated?

Yes. Great questions. I don't have great feedback on a specific patient group that's getting it. It is broad. We have heard of -- so there's not going to be any trends here, but some examples, we have heard of patients getting it before an ablation. We've heard of patients getting yet just as a routine course of they've been waiting for it. And those patients, as we've mentioned before approval, Brandon run the gamut, 2/3 of them are on background medications. A fair number of them have fill in the pocket, in their purse or in their desk draw, whether they use it or not is a question mark. So we've heard all those examples.

But again, too early to say anything that's leading per se right now. I think we're very bullish on the fact that this drug can be used across a whole host of patients, and it really depends on what the APP or the physician believes is best for them.

Your second question is really interesting, we're waiting to hear from those patients of having used it and the excitement we know we're going to get. We know that because we heard it from the clinical trials. I will say, though, we have, as you can imagine, we do pretty heavy social listening out there. So we're on top of what's being said, if you will, on the various pages that these patients talk about and our support group also speaks to patients. Now I don't have that data, but I do, on the social media side, have really uplifting beliefs because even before they treated with CARDAMYST, there was just excitement to get it.

And remember, Brandon, we always talk about there's 2 burdens for this condition. One is when you're in it and your heart is going 200 bps a minute or so, and you're feeling it and you have those symptoms. The other burden is when you're not in a condition, but you know there's one coming. You just don't know when, what you're going to be doing and how bad it's going to be. That's the piece that these patients on the social chat wards are really I think speaking to the fact that they have it and they have, if you will, this comfort or peace of mind to have something. That's been uplifting from -- even -- we saw some of this before we even announced the drug was available. We saw patients getting the drug and being excited about simply having it. I've never had that in my career.

Very helpful. Do you mind if I just sneak 1 more in. Just on sort of reimbursement. Can you remind us of your contracting strategy here. Do you expect a contract early on in the launch ahead of perhaps significant demand? Or given the strength of where your balance sheet is today, are you thinking of perhaps creating significant demand through the patient assistance program and then contracting a little bit later in the launch where you have that demand to put in front of payers. Thank you.

Thanks, Brandon. Our strategy has been very clear. We want to drive to coverage because no matter how many programs we put in place until we get coverage, it is a natural dampening as we identified before, more than half of your scripts don't get through. That's the industry benchmarks. We would like to get out of that world as soon as we can and be reasonable about obviously the types of contracts we put in place. Our strategy is clearly focused on commercial first. We think we can get those first. And we're very actively engaging payers right now for both commercial and Medicare. It's just the natural lead time for Medicare are longer. So we've always guided to Medicare being more of a 27 type of achievement and commercial starting in '26. We don't guide exactly to when it will start because there are a lot of things outside of our control.

But what I will say is we're very encouraged by the discussions we're having with those commercial plans, they are within expectations of what they told us before we got the approval. Remember, we've had 2 years of engagement with these plans, showing them the budget impact models, and it's just a matter now of getting on their schedules. But no surprises from what we can see so far, again, early, early days -- on anything related to how they're thinking about the product.

[Operator Instructions]

Out next question is coming from Dennis Ding from Jeffries.

This is Anthea on for Dennis. And congrats on the progress so far. I wanted to follow up on the prior question regarding contracting strategy. Could you talk a little bit more about what does good formulary positioning look like for CARDAMYST. And how much rebate pressure should we expect you push for broader access? And then separately, what is the patient mix in terms of coverage in terms of commercial versus Medicare?

Great. Great to hear you, Ani. Thanks for taking the time out today. So with regard to what good coverage looks like for us, we view it and we've guided pre-approval, and we still guide to -- we want pretty open access, things like prior off to label and attestation of the patient being treated for PSVT, that's expected type of coverage. We would like to see that would be good. We've also guided the Street to -- the biggest question for payers is not at all the medical need. They see that clearly. They see the benefits of this to their plan. The biggest question they have is how often will it be used by the patient. And we've provided guidance that this is a drug that's used a handful of times per year. They just may want some comfort there. So we've heard of and we would expect good coverage to include at least in the launch year or 2, quantity limits and not onerous ones like but ones that would prevent it from being used instead of 5 times per year being used 50 times a year, right?

That's what they want to avoid. So quantity limits prior off the label is kind of the standard down the fairway type of coverage we've got it to. And again, that's an average. There will be some plans that are more harsh and some plans that are more open, but that's an average good quality coverage for us with standard pay-to-play type of discounts.

With regard to the commercial and Medicare breakdown, roughly think of it as 50-50. It's about 50%, under 65% and about 50% over 65%.

We reach end of our question-and-answer session. I'd like to turn the floor back over to Joe for any further closing comments.

Well, I really -- this is our first earnings call since the approval, and we're reporting on, I guess, the period before we actually launch. So it is early days, but I'm really excited, I'm really thankful for all of the people that have called in here in support of the company, and I want to really just convey that we're super excited to be now doing earnings calls going forward. We'll look forward to updating you on a quarterly basis, as Lorenz had said on how the launch is going and the progress of the company. So with that, I wish everyone a great rest of the day.

Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time, and have a wonderful day. We thank you for your participation today.

Greetings. Welcome to Milestone Pharmaceuticals CARDAMYST FDA Approval Call. [Operator Instructions] Please note, this conference is being recorded.

I will now turn the conference over to Michael Wood at LifeSci Advisors. Thank you. You may begin.

Thank you, operator. Good morning, everyone, and welcome to Milestone's conference call and webinar to discuss the FDA approval of CARDAMYST nasal spray. On a Friday evening, the company issued a press release on the approval. This can be accessed on the News & Events page of the company's corporate website at milestonepharma.com.

During today's call, the company will be making certain forward-looking statements. I will refer you to the safe harbor statement here on Slide 2. A description of potential risks and uncertainties can also be found in today's press release and on the company's latest SEC disclosure documents.

The agenda for today's call is outlined here. Joe Oliveto, Milestone's President and CEO, will begin with opening remarks, including covering the basics of the product label. He will be followed by Dr. David Bharucha, the company's Chief Medical Officer, to discuss the clinician's perspective relative to the medical need. Lorenz Muller, Chief Commercial Officer, will then talk about the launch plans and Joe will conclude before we open the call up to questions. Also, Amit Hasija, the company's Chief Financial Officer, is with us today and will be available to answer questions during the Q&A session.

So with that, I'll turn the call over to Joe to begin. Joe, go ahead.

Thank you, Michael. Good morning, everyone. And of course, thank you for joining us today. We're really excited to announce the FDA has approved CARDAMYST nasal spray for the treatment of PSVT. This approval means that for the first time the more than 2 million Americans who live with this unpredictable and very disruptive condition will now have access to a rapid-acting treatment they can use outside of the health care setting. Many of these patients we have interacted with over the years have expressed to us how having such an option provides them with the ability to better manage their condition, in turn, allowing greater control over their daily lives. CARDAMYST is, in fact, the first new therapeutic option for patients with PSVT in more than 30 years, and we couldn't be happier for those patients who have been waiting.

Shown here is the approved indication statement. The full package insert can be accessed via this link through the Milestone website. We're very happy with the label we received from the FDA, which meets and, in some cases, exceeds our expectations. It reflects the strength of the clinical program with no major surprises to what we were expecting. I'll take a moment to show the primary presentation of clinical efficacy and safety.

The primary efficacy presentation includes a Kaplan-Meier curve showing the conversion over 5 hours for the pivotal RAPID trial. The statistics, including the impressive p-value for the primary endpoint at 30 minutes are displayed with the graph. This presentation is highly supportive of portraying multiple aspects of the drug's efficacy data, including both the speed of conversion displayed at the beginning of the curve and the persistent effects of conversion over 5 hours. Presentation is also flexible in that it allows us to highlight any particular aspects of the display in our promotional materials.

For example, this slide is a potential for trial of efficacy that focuses in more clearly on the primary end point the RAPID trial, the conversion period over the first 30 minutes, amplifying that section of the curve. From this view, it is easier to portray that CARDAMYST converts twice as many patients by 30 minutes and converts patients 3x faster as measured by median time to conversion. So the 5-hour curve provides excellent support for both messages, speed and durability as well as the flexibility to highlight messages with multiple different views.

We're especially excited about how clean the label looks from a safety and tolerability perspective. For any investors who've been following the CARDAMYST story through its development, these data should look very familiar. There are no surprises in the label. Giving CARDAMYST as a calcium channel blocker, what is most important to health care providers regarding safety includes blood pressure reductions AV nodal blocks and syncope. What you see on the left-hand side of the slide is that the label conveys that only 0.4%, that's less than 0.5% of patients experienced hypotension and only 0.1% of patients experienced syncope with no patients experiencing AV nodal blocks of type 2 or greater.

To the right is the presentation of the most common adverse events, those occurring greater than 5% in the CARDAMYST Group. There are only 5 AEs listed and those AEs are largely combined to the local site of administration and nose in face. The data is portrayed across the double-blind studies within the clinical development program. This characterization of tolerability is extremely consistent across the whole of the development program data, including other open-label studies that have been presented multiple presentations and publications. Precautions are portrayed in the label around the potential for a etripamil, again, as a calcium channel blocker to affect blood pressure and AV nodal conduction. Patients are instructed to be seated when they dose themselves and to not dose themselves more than 2 doses within a 24-hour period, all of which is very appropriate and expected and helpful in our view, for the ultimate protection of the patients.

Transitioning to commercialization, our vision for the commercial success of CARDAMYST is very simple. Towards the bottom of the slide, make it easy for patients to use, make it easy for prescribers to write. And thirdly, and relatedly, price it and support it such that there is limited reason for payers to want to control it or to certainly overly control utilization.

Regarding payers, before we get the payers, I will ask David, our CMO, who's also an electrophysiologist and manage these patients and continues to engage with his peers to provide thoughts on what CARDAMYST could offer to busy practitioners. So let me just say a word about payers and the patients. So regarding payers, we have spent significant time educating payers on PSVT on the already published CARDAMYST data, including both the clinical profile and the reduction in emergency department use that we observed in the clinical trials. We've provided them with modeling tools so that they can evaluate within their own populations in order to estimate cost offsets that CARDAMYST could potentially provide for their budgets. The payer feedback from these interactions provides us the confidence we have an offering that will allow plans to cover the product without significant managing the utilization of CARDAMYST.

Lorenz will review our pricing and how it fits into our market access strategy.

So now let me say a word about patients and the medical need from their view. We feel very strongly that PSVT is a patient-driven market. For patients, let's remember, CARDAMYST was prospectively designed from day 1, literally from the time it was envisioned on a whiteboard to be a patient-centric product. Patients will have CARDAMYST with them in their pocket, their brief case, purse, [indiscernible], et cetera, and patients themselves will decide when to use CARDAMYST. We believe and patients have expressed to us that having such an at-the-ready option provides them with the potential for living life with less reliance on the emergency department, which is currently their only approved option while experiencing an event.

Less reliance on the emergency department means less disruption to their daily lives and in turn, alleviates the anxiousness that many patients often feel between events or episodes, and they often are thinking about when the next episode occurs and what they'll be doing. What if it happens while I'm driving the kids? What if it happens during an important day at work or I'm on a plane or I'm on vacation, right? What will I do? Can I get to resolve it? Will I have access to the emergency room? All of these questions and thoughts are going through their mind, not only in an event, but when they're making life choices. Very much like a migraine patient thinks about having their medication available to them during their next migraine or asthmatics think about having their rescue in available to them.

We believe that with PSVT, many of these patients will be thinking about and have CARDAMYST top of mind as to having that available whenever or wherever they have their next event. It's clear to us that the ability to empower patients to take better control over their PSVT attacks is a highly attractive benefit that many patients have expressed to us and the feedback is especially encouraging when it's received relative to patients who experience CARDAMYST in the clinical trials, be it feedback directly from the patients or through their clinical investigators and study staff.

With that, let me turn it over to David, who will provide views on the medical need and the benefits that CARDAMYST can offer to busy cardiology practitioners.

Thank you, Joe. I also want to say how happy I am by FDA approval of CARDAMYST and by this opportunity to make this self-directed treatment available to patients and health care professionals. Speaking as a cardiology arrhythmia specialist, I'll comment on the medical need after my having seen thousands of patients with PSVT, and I'll make several points.

First, the patient experience has been problematic. Second, from a physician perspective, there's been an unmet need due to limited tools up until this point. Third, the basics of etripamil, now CARDAMYST, offer a simple and efficient solution to those previously unmet needs. First, PSVT or paroxysmal supraventricular tachycardia occurs suddenly, usually without warning and inevitably at a really bad time when a patient is in the middle of their everyday activities. It prevents them from engaging at a fear that they may have a symptomatic arrhythmia episode without the means to stop it and physicians up until now have not had an effective acute-acting drug to equip these patients with it.

Second, shown in the lower part of the slide, PSVT commonly has disabling symptoms of palpitations, shortness of breath, lightheadedness, even chest pain and certainly marked anxiety. I use the word disabling deliberately. These are not nuisance symptoms. Although PSVT is not severely morbid, patients in the moment don't feel that way.

Next point. For physicians as well, there's been truly an unmet need here. What's been available up until now? Well, limited treatments that are poorly effective, invasive or inconvenient. So moving from left to right on the current slide, options that have been available to physicians have been chronic oral medications such as calcium channel blockers or beta blockers. These, even when given at high doses are not very effective in preventing episodes. And it really doesn't make a whole lot of sense to take a medication every single day for an episodic condition. Patients are exposed to the side effects, the hassle of a daily drug. That would certainly give me pause before recommending this -- that type of approach. So since chronic oral dosing isn't very effective, quite simply, it's not worthwhile.

Another preventative option is ablation, a catheter procedure performed by electrophysiologists. I performed many ablations myself and have guided many more patients as to whether they were good candidates. Ablations are generally safe and are often curative. However, they're invasive and carry some procedural risk, and they're not for everyone. In fact, research indicates that only 15% of eligible U.S. patients do end up having one. Bottom line, they're preventative. They can't get a patient out of an acute jam. For acute treatments, a pill-in-pocket approach is used by some prescribers, mostly because they simply have had nothing else to offer. A pill in pocket is when an HCP may prescribe taking a onetime dose of an oral calcium channel blocker or a beta blocker. However, the pharmacokinetics of oral therapies are simply not suited to the acute rapid conversion of PSVT.

On the slide's right most panel, emergency visits. When each of these options fail, patients often end up in the emergency department and even hospitalized with all the inconvenience, time and costs that are associated. Now certainly, no physician wants their patient to end up in the emergency department, especially for something that could be handled at home. And so it really needs to be emphasized CARDAMYST as a patient-directed self-administered therapy is very much in line with what physicians have been seeking. To sum all this up, a cardiologist would much rather have a patient self-treat themselves at home with a proven therapy rather than having them end up in the emergency room.

The other bottom line, patients continue to experience disruptive episodes despite the therapies that have been available to them. CARDAMYST, summarized on the next slide, directly addresses this burdensome need. It's a short-acting calcium channel blocker with clear activity as early as 5 minutes after self-administration. The CCB mechanism of action is well understood, time tested and already trusted by health care professionals. This familiarity, I believe, will lead to a low barrier of use and is strongly supported by our labeled safety data.

This drug, also a new chemical entity and with patent protection extending to 2042, offers an important package. It's portable, can be administered on demand. It has a fast onset and is well tolerated. It has been extensively studied with self-administration in an outpatient setting, leading to our robust clinical data set, which led to this approval. As Joe has already summarized, CARDAMYST label supports its favorable safety profile, which I believe will give providers assurance in prescribing the treatment. This label provides Milestone with a really strong basis for communicating efficacy, safety and tolerability.

So Lorenz, if you could update us all on how -- and all that Milestone is now doing to deliver this treatment to PSVT patients and to the health care professionals who care for them.

Thanks, David, and good morning, everyone, and thanks for taking the time this morning to learn about the exciting approval of CARDAMYST and our launch plans for bringing this to the patients that so desperately need a new therapeutic option for treating their PSVT. My mandate this morning is to give you a quick overview of the market opportunity as we see it and then talk a little more detail about some of our key launch strategies, tactics and success metrics.

As I've shown you in the past, the PSVT market dynamics are quite stable. So while we continue to learn about the market, our go-to-market plans are largely the same as earlier this year. And as I will focus -- and as such, I will focus my comments today on a couple of quick reminders on the market opportunity, but then focus your attention on some new approval-enabled information like sales force targeting and pricing.

So let me remind you that in the United States, there are about 2 million patients with the diagnosis of PSVT and that those patients are costing the health care system at least $5 billion a year, driven largely as is represented on this slide by emergency department visits, hospital admissions and ablations. Importantly, about half of the diagnosed patients in the U.S. are seeking treatment in the health care system each and every year because of the burden of their disease.

What excites me about the commercial opportunity for CARDAMYST is represented on this slide. An ideal market for me is one where there's no anticipated branded competition, giving us both 100% share of voice and lower rebate pressure because we won't be negotiating against anyone for preferred formulary position. Physicians in market research have repeatedly told us that they're both very familiar with L-type calcium channel blockers and impressed with the robust data supporting CARDAMYST and as a result, express a low barrier to prescribing. And we believe all of this will result in strong demand generation and the ability to obtain quality coverage initially amongst the 50% of patients that are commercially insured.

So let's dig in a little deeper into how we will get at this opportunity. This slide represents the 2 million patients that have a diagnosis of PSVT in the United States. Of those, as I mentioned earlier, about half are being annually treated, and those are being managed by around 40,000 health care providers. That actually would be a large sales force to be able to deploy against all those doctors. Fortunately, for us, this market is concentrated where roughly half of those patients or 500,000 patients are being managed by only 10,000 health care providers. The majority of those, no surprise, are cardiologists.

So you can see here around 8,000 clinical and interventional cardiologists and 1,500 electrophysiologists are managing over 90% of those patients. Interestingly, there's around 500 primary care physicians that look and act a lot like cardiologists that are managing an incremental 40,000 patients. Together, these 10,000 health care providers represent the prescriber targets in our launch year, which can be engaged by about 60 sales representatives. This concentration of patients with PSVT is the reason we chose an initial sales force size of 60 reps. We believe this sales strategy will enable us to demonstrate robust demand in a launch year while also being good stewards of the company's resources.

Next, I want to remind you of the vicious cycle of PSVT, define our target addressable market and show for which type of patients physicians tell us they'll prescribe CARDAMYST. You can see on the right side of this slide, the distribution of disease burden in PSVT in terms of episodes. The larger box in the middle represents our target addressable market of approximately 50% of patients with PSVT who experience multiple burdensome episodes per year and seek treatment for those episodes. On the left side of the slide, you can see the various use cases where physicians have reported wanting to use CARDAMYST. Of note, you can see that docs want to use CARDAMYST as either an add-on or switch therapy for patients on chronic prophylaxis, patients using off-label pill in pocket and patients receiving no treatment. Electrophysiologists report wanting to use CARDAMYST either as bridge therapy in patients they plan on ablating or as an alternative -- attractive alternative option for those patients whom they cannot convince to have an ablation.

Let me now quantify for you the physician stated adoption for CARDAMYST. On the left side of this slide shows physician reported current treatment of patients with PSVT from market research with 250 cardiologists. As you can see, physicians report a desire to prescribe CARDAMYST to around 2/3 of their patients who are currently receiving pill-in-pocket therapy. A little less than half of their patients that are receiving chronic prophylaxis with calcium channel blockers and beta blockers and a little over half of their patients receiving no treatment, which results in an almost 50% stated adoption for CARDAMYST.

Let me now switch gears to talk about our market access strategy, which is focused on product accessibility and affordability. Payers have repeatedly reported to us that they're not actively managing PSVT currently. And as long as we rationally price the product, they are open to putting it on a Tier 2 or Tier 3 formulary, especially for commercial books of business. And a lot of that motivation is driven by the potential for quantifiable cost offsets. As I reviewed a minute ago, coverage would result in physicians having an easier time prescribing because it would result in less onerous utilization management, meaning in many cases, just a prior authorization to label and potentially some quantity limits. And prior to achieving coverage, Milestone will offer reimbursement support in the form of health care provider assistance in pursuing medical and/or formulary exception and in select cases, even denial conversion for patients whose claims have been rejected.

On the patient side, we have committed to retail distribution to make the drug broadly accessible without the limitations of having to go through specialty pharmacy, and we will offer robust co-pay mitigation in the form of a pay no more than $25 program for commercially insured patients. Also, Milestone will support patients with different nurse educator programs that will both help patients use CARDAMYST correctly and provide them with periodic refill reminders.

Finally, I want to announce today that we've chosen a WACC or wholesale acquisition cost price for CARDAMYST of $1,649 per prescription, which aligns with net revenues to milestone of between $500 and $1,000 per prescription. We've chosen this price in part because of the value prop that CARDAMYST represents relative to the other treatment modalities, which insurance companies must reimburse, whether it's emergency department visits or hospitalizations or ablations. When we have presented this price to payers, it has been well received because they see it in the context of a budget impact model where we show a modest impact in terms of per member per month increase. And by modest, I mean a PMPM impact of pennies and not dollars associated with putting CARDAMYST on formulary for both commercial and Medicare books of business.

Our strategic objectives for CARDAMYST in the launch here are relatively simple. We plan on focusing on driving provider awareness, trial and usage and establishing and maintaining broad and high-quality access and affordability. We're going to assess our performance by tracking and reporting weekly prescriptions and week-over-week prescription growth. On the access side, we'll be tracking and reporting on the percent of insured lives for which we have negotiated coverage over time as well as describing the quality of that coverage in terms of any utilization management that payers mandate.

So in summary, our launch year goals are to get prescriptions written and filled. We're confident that we will achieve significant demand generation because our initial sales force deployment covers 50% of the annual potential because patients with PSVT are going to physician offices every week to receive treatment and because physicians are comfortable prescribing CARDAMYST for a broad array of patients because of their familiarity with our mechanism of action and the robust efficacy and safety data behind CARDAMYST. Of course, it's also very important to get prescriptions that are written filled.

And so as I mentioned, we're committed to retail distribution, and we have invested in comprehensive provider and patient support programs that will facilitate compliant prescription fulfillment, both pre and post insurance coverage. And finally, we believe we can get relatively rapid formulary placement among target payers because we have no branded competition and therefore, not a lot of rebate pressure and an attractive health care resource utilization value proposition.

Thanks very much for your time and attention. I'll now turn the call back over to Joe Oliveto for some concluding comments.

Thank you, Lorenz. I really do want to underscore the significance of our announcement today. The FDA approval of CARDAMYST is a very prideful day, represents an important inflection point in the evolution of milestone, marking our transition to a commercial organization. The FDA approval also represents a huge step forward towards achieving our mission of providing relief to patients suffering from PSVT by providing what we believe will become the new standard of care.

Before I open for questions, the journey to develop CARDAMYST from a whiteboard idea to a drug and really the first new drug intervention in over 30 years for patients dealing with PSVT has taken the dedication of so many. I want to take a moment to thank all those people who have made the approval possible to my colleagues here at the company and our development partners responsible for the literally thousands of decisions, activities and for really portraying the grit needed to achieve and to succeed together as one team.

I really want to thank the patients and their families who participated in our studies and provided their guidance and put their trust in us, who at the start, milestone was really an unknown company to them. I want to thank our clinical investigators and health care providers who worked on the program and generated really such impressive clinical data. And I want to thank our investors who have really supported us throughout this journey. We're grateful to all for your dedication, commitment and helping Milestone realize this important achievement.

Cherry, I'd like to open the line for questions now.

[Operator Instructions] Our first question is from Ritu Baral with TD Cowen.

Just a couple on my front on -- more on the payer side. One, very briefly, if you could give us the Medicare commercial split as you see it right now. But the bigger questions are 2. In your payer conversations, what are your current expectations for prior auth before coverage? Is there any requirement for like documentation of events, documentation of a certain number of events that translates to severity? And then I have a quick follow-up.

Thank you, Ritu. And Lorenz, I think those are right down your fairway.

Thanks, Joe. Yes, Ritu. So the split between -- for patients with the diagnosis of PSVT is roughly 50-50 between commercially insured and Medicare. It's actually 45% commercial, 45% Medicare and then about 10% Medicaid and other. And that's important because that allows us to demonstrate demand in a large group of commercial patients that are just going to be easier to get coverage for in terms of a time standpoint and where we can co-pay mitigate to make the drug more affordable.

To the second part of your question, so because we don't have coverage today at the approval date, we will have a program for pursuing medical exception, formulary exception. And we don't expect that process, by the way, to require documentation of rhythm strips for PSVT and attestation from a physician is more than likely sufficient. And then as we gain coverage, though obviously, medical exception, formulary exception will no longer be necessary. And as I mentioned on the call, we are expecting some mild prior auths to label to ensure CARDAMYST is being prescribed on label and also potentially some quantity limits to ensure that at least until payers have real data in their plans, that there is an overuse of the drug for patients that might have daily or weekly episodes.

Yes, if I can double down on that, you asked about severity. Even for interventions like ablations, there is no prior auth to severity or anything like that. You could literally have one event and go for an ablation. So we really don't have that anywhere in our thinking.

Very helpful. And a quick follow-up. What do you guys expect for time lines to formulary inclusion and sort of more standard coverage and uptake?

Yes. So while I'm sure Lorenz would love to boast what we think, we're going to keep that to ourselves for now and not give guidance on formulary acceptance and coverage. We really do believe -- we believe we'll get good coverage, right? As Ian mentioned, Tier 2, Tier 3, not specialty tier for the majority of plans. But we're going to hold the expectations of a little bit the when to ourselves and really start reporting and see how it goes.

Our next question is from Ted Tenthoff with Piper Sandler.

Sincere congratulations, a long winding road, but your persistence for these patients is notable and finally rewarded. So sincere congratulations. I wanted to get a little bit clearer -- a little clarity on 2 issues. One, I know you said that it would be available in retail pharmacies in the first quarter. Can you give us any more sense what that means? Is that early in the new year? Does it kind of depend regionally where you roll out? What outreach to physicians goes in hand with that in terms of making them aware of availability?

And then secondly, on price, I appreciate the color both with the WACC and the price per patient, which has been very consistent. What are the factors that kind of go into that? I think the biggest being if they use 1 or 2 doses per episode, but how should we be thinking about that price revenue to you guys in a little bit more detail?

Okay. Thanks, Ted. And maybe I'll take the first one and ask Lorenz to take the second one. Really, the critical path to having access to drug for patients in our view, is primarily having sales representatives hired, trained and in the field. We're giving guidance as to really mid-Q1. We know that, that's a little bit wide. But given that we're right here at the end of the year in December and are essentially making offers this week, we have sales reps identified of the 60. We're very close to the full 60 identified. We will be making sales offers this week. And just the time it takes through the holidays to get them on before they can start being trained. There's a little bit of a variable that we're not exactly sure of yet.

But certainly, mid-Q1, we should have sales representatives trained with materials in the field and the channel fill will also come in mid-Q1. So we feel strongly that we'll have it in mid-Q1. You probably won't see revenues probably until the end of the quarter, if not Q2, is our expectations.

And then maybe I'll ask Lorenz to provide you some answers and a little bit more color around the price that you had asked about and the factors that go into how to think about net sales and the number of doses per episode.

Yes. Thanks, Joe. So there was 2 variables you were focusing in on, Ted. One was the number of doses that we might model per episode that a patient would use. And then secondarily, the number -- our estimates on the number of episodes per year that a patient would treat with. Is that correct?

No, I'm just more asking at a high level where -- what goes into the variability in that revenue differential between $500 to $1,000 for you guys.

All right. Sure. So if you think about net sales, when you launch a drug, you don't have coverage and you achieve coverage over time. And I mentioned during the formal remarks that we would have some level of denial conversion for patients and co-pay mitigation to help patients afford their drugs. Those are typically higher early in the launch than later. And so that would eat into our net revenues or net sales price because we're helping patients to get the drug. Once coverage is achieved, a, it's easier to get the product covered. There's less prior authorization. Ritu asked about what we did with medical exception and whatnot ahead of time. So those are the main factors that sort of lead to perhaps a lower gross to net earlier in launch in a launch year and even the entire year. And then as you get into a second and third year after launch, you get more to a steady state.

But I do want to address the question on doses per episode and episodes per year because we also think a driver of net sales in aggregate in terms of demand is going to be how many times do patients refill a drug. We do expect at steady state in the second or third year on the market as patients are on drug and are rolling into each subsequent year that the average patient would use etripamil a handful of times. We model 4 to 6 times a year. But earlier in a launch, because of the dynamics of getting a prescription and then waiting for that episode to happen and then treating yourself and then getting another -- getting a refill, we actually model between 1 and 2. So at most 1 refill a year in a launch year on average. So I would just moderate expectations on how many refills. In terms of metrics, you heard me say earlier, we're looking at the new-to-brand, new patient starts as a key driver and that week-over-week script growth and not so much refills as a driver of net sales in the launch year.

Thanks, Ted. And let me just add one other comment just to the first part of the question Lorenz answered. These are full net revenues where when we say $500 to $1,000, these are not net sales to post payer. So it has the payer rebates and things like that, which are very mild to moderate rebates. It also includes distribution costs to the wholesalers, includes COGS. So those are full net revenues to the company when we give that $500 to $1,000. So full -- all those variables are in there.

Our next question is from Zhengxi Sun with Wells Fargo.

This is Zhengxi for Mohit Bansal. So congrats on the approval. I just have a couple of questions, if I may. So my first question is, of the 3 segments you guys mentioned in terms of cardiologists, electrophysiologists and primary care, is there any one of the segments that are prescribers where the heavy lifting will be relatively low and they can come on board faster than others?

Yes. I think I'll ask Lorenz to expand. But certainly, the ones who know most about the product right out of the gate is the electrophysiologists, right? They are the thought leaders. They're very heavily engaged in our program and have provided advice to us. They're very prominent on formulary decisions. They are a smaller group. So they've -- many of them are aware through our publications, which are highly oriented towards their publications that they read.

So I would say the ones that know it best out of the gate are going to be the electrophysiologists. And as Lorenz had said, there are clear use cases for them to use it around their ablation procedures commonly. So we view the first year sales to come disproportionately, I would say, relative to peak year sales from electrophysiologists. But then over time, as cardiology learns about this from their electrophysiology colleagues as well as their peers that are close to the program, and there's just more of them, really, the lion's share of the scripts will come from cardiology, not electrophysiology.

I have a follow-up -- sorry.

Lorenz, do you need to add on that?

I was just going to add that we've done also early adopter analysis to know within cardiology, within electrophysiology, even within primary care, like who are likely going to be the earlier prescribers that basically adopt new branded products across all different use cases. And so we will obviously be targeting those when we first launch. And I'll remind you, our sales management team has been in the field now for 6 or 8 months. They were on board even back in March. And so they've been going out and engaging customers, profiling offices, disease state education. So they have a good sense within their regions, who are going to be the physicians and the health care practitioners that are more receptive to adopting early. And so that will also drive some of our early targeting activities.

And I have a follow-on question, if I may, that can you guys help us to understand the royalties to the RTW for the next few years? It seems like you guys have 7% until $500 million peak sales, but then there's a 2.5% additional number based on the sales target. I'm just wondering, could you guys help us to clarify that?

Sure. I'm really going to ask Amit, if he's on the line, to take you through the royalty with RTW.

Yes. And there's usually a slide in our deck that kind of go through this a little bit. You might need to go to the footnotes. But you're correct in the way that you described it. There's a 7% royalty at the kind of lowest sales threshold. Because of some of the delays, we will have that additional premium. So the way we model it is 7% plus the 2.5%. So 9.5% all-in royalty for the, I guess, foreseeable future, we're not really guiding on future revenues, but I would model that 9.5% in at least for the first year or 2.

Our next question is from Brandon Folkes with H.C. Wainwright.

Congratulations on the approval. Maybe just for me, can you elaborate on the refill process for patients? When prescribers write the initial script, can they write for a refill or a certain number of refills? How easy is it for a patient to get a refill? What is the process? Do they need to come in? Is this something once they have a documented diagnosis of PSVT, it's the telephone consult -- or just any color on that process would be helpful. And then just is that going to differ significantly initially when they potentially are processed as medical exceptions? Or could they get an exception for a number of refills versus maybe later on when you have broader coverage?

Lorenz, do you want to take that for Brandon?

Sure. Happy to. Brandon. So the refill process, and we will be promoting for this is a physician, if they're comfortable with the drug, can write a prescription and then indicate the number of refills because this is that kind of a therapy like a chronic oral in that way, where you would expect some refills, patients have ongoing episodes. And eventually, doctors have told us they want to have patients have access to the drug so they can treat themselves quickly. So ideally, they have one in the -- at home, in the office, in the car, that kind of thing.

Having said that, you're correct, medical exception, formulary exception, every process is a little different. So in some cases, they may allow only one prescription and no refills. In other cases, depending upon the forms and everything and the actual approval that comes ahead of coverage, there may be the ability to get 1 or 2 refills. And some physicians are going to be comfortable writing refills right out of the gate because it is a calcium channel blocker. It's a mechanism they're very familiar with, early adopters typically are more like that. And then others are going to be more cautious and they'll write a script with no refill, ask the patient to call them back once they treated an episode, find out how they did and then they'll be comfortable writing refills. So we don't expect it to be a high bar, but there may be a little bit of slow ramp-up. And again, that's why I alluded to earlier, we're modeling between 1 and 2 doses per year per patient in the launch year.

Congrats again on the approval.

Our final question is from Dennis Ding with Jefferies.

This is Georgia on the line for Dennis. I wanted to understand a little bit more about the different like segments that you stated and which you expect to flip first or that might move faster than others between like the pill in pocket and the chronic meds and the bridge or alternative to ablation and just how your strategy may be different or the same as you move each?

Yes. Georgia, I'll start, but again, ask Lorenz based on the research he's seen to articulate that. And obviously, if David has an opinion based on his interactions. But I'll start with -- it's a great question because we have seen and heard from physicians that they see it useful in all cases. A reminder, 2/3 of our patients in our clinical trials were on background calcium channel blockers or beta blockers and still at events. So clearly, one of the things we're proud of is the drug can be used on top of existing therapies and would be a very natural add-on.

But Lorenz, maybe you can provide a little bit of color on what you've heard from the physicians relative to your market research.

Yes. Joe, it's very consistent with what you just said. Physicians, once they understand the product profile, have a low bar of prescribing. They're essentially asking us who would I not use this in rather than who would I use it in. So they're really just looking for contraindications, which, as you've heard from the label, are relatively minimal. So pill in pocket to us is the absolute floor of the market because there's no reason you wouldn't write a script for CARDAMYST if you had offered pill in pocket to a patient given that the profiles of the 2, although we don't make direct comparisons is very obvious to clinicians.

And I'll add, importantly, in terms of the type of target patient that we would deploy our sales force against when a physician asks, love the idea of the drug, who should I use it into one of our sales reps. Newly diagnosed patients that have more urgent need to find a therapy that they are comfortable with. Patients with a history of ED visits representing sort of a higher burden of disease. Those are -- and they might have a pill-in-pocket script. They might be on prophylaxis. They might be in queue for ablation. But in all cases, they represent a higher disease burden. And so those are the patients that we would ask physicians to get initial experience in. And then over time, like with many drugs, they'll broaden that experience to just about anyone who asked for it, just given the nature of this drug and the lack of therapeutic options once a patient is in an episode.

Yes. And David, can I ask you, David, to specifically provide a little color on when you're preparing for an ablation, this idea of a bridge to ablation and removing background meds, why do you -- why would -- explain what a bridge to an ablation is from the view of an electrophysiologist. That's something we hear over and over again.

Sure, Joe. A couple of quick points. The first is before an ablation is performed, the idea is a patient has to come off all of their background therapy that could theoretically or practically interfere with the ablation. And one of the goals of ablation is to measure the cardiac conduction system and to induce the arrhythmia itself, and that can be challenging to do if a patient still has some background therapy on board. So the basic idea is whether a patient is on background therapy with an AV nodal blocker or certainly on background therapy with an antiarrhythmic drug to wash those drugs out by stopping them, let's say, several days or perhaps a week in advance. That leaves the patient vulnerable to potential events right in the couple of days before their planned ablation. So for all those reasons, patients may need a bridge in order to make it to the ablation without having breakthrough symptoms.

The other idea of a bridge is that patients often go for ablations when their background therapy isn't working. So the last thing an electrophysiologist wants to do is to recommend an ablation, describe that background therapy really isn't working because it often does not and then have patients have a couple of episodes in a couple of days or a couple of weeks while they're waiting for an ablation.

The last point to make to you, Georgia, is that you asked about the type of patient that this might be prescribed for. I just want to underscore what Joe and Lorenz has already said. This is a simple calcium channel blocker. Cardiologists or even primary care doctors are very used to prescribing calcium channel blockers for all sorts of entities. Now in this particular entity, PSVT, background therapy doesn't work tremendously well, but physicians are very used to prescribing it. So they would be -- so the idea of having CARDAMYST, a readily available calcium channel blocker whose acute administration and rapid onset of action has been extensively studied already to prescribe that. It's just -- it's not going to be, I think, a complex decision in that person's mind, be relatively straightforward. This is a simple solution with a drug or a drug class, excuse me, that is -- physicians are very well accustomed to.

There are no further questions at this time. I would like to turn the floor back over to Joe for closing remarks.

Well, I'd like to just thank everyone for spending the time to listen in today to our update, and I'd like to wish everyone a great rest of the day and a happy holiday season. Take care, everyone.

Thank you. This will conclude today's conference. You may disconnect your lines at this time, and thank you for your participation.