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Edited Transcript of MIST.OQ earnings conference call or presentation 13-Aug-19 12:00pm GMT

Q2 2019 Milestone Pharmaceuticals Inc Earnings Call

Aug 14, 2019 (Thomson StreetEvents) -- Edited Transcript of Milestone Pharmaceuticals Inc earnings conference call or presentation Tuesday, August 13, 2019 at 12:00:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Eleanor Barisser

Milestone Pharmaceuticals Inc. - IR, Argot Partners, LLC

* Joseph Oliveto

Milestone Pharmaceuticals Inc. - President and CEO

* Francis Plat

Milestone Pharmaceuticals Inc. - Chief Medical Officer

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Conference Call Participants

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* Chris Howerton

Jefferies LLC - Analyst

* Ritu Baral

Cowen and Company - Analyst

* Ted Tenthoff

Piper Jaffray & Co. - Analyst

* Leland Gershell

Oppenheimer & Co. - Analyst

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Presentation

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Operator [1]

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Good day, ladies and gentlemen, and welcome to the Milestone Pharmaceuticals midyear 2019 regulatory update call. As a reminder, this call is being recorded.

I would now like to introduce your host for today's conference, Eleanor Barisser.

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Eleanor Barisser, Milestone Pharmaceuticals Inc. - IR, Argot Partners, LLC [2]

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Thank you, operator. Good morning and thank you for joining us for our midyear regulatory update conference call. Delivering prepared remarks on today's call will be Joseph Oliveto, President and Chief Executive Officer. Joining Joe for the Q&A session will be Dr. Francis Plat, Chief Medical Officer; Lorenz Muller, Chief Commercial Officer' and Tim Maness, Vice President of Finance.

Please note that the focus of today's call will be the etripamil program regulatory update announced this morning. For an overview of Milestone's second-quarter financial results, we ask that you please refer to this morning's press release or 10-Q filing.

This is Milestone's first conference call since the closing of the Company's IPO in May. As such, the Milestone management team would like to inform investors of the Company's planned general practice of hosting conference calls in conjunction with key corporate updates, such as today's regulatory news, and not solely for the purpose of discussing quarterly financial results.

Before we begin, I would like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the risk factors section of the Company's most recent quarterly report on Form 10-Q and other reports filed with the SEC.

Any forward-looking statements represent the Company's views as of today, August 13, 2019, only. For your convenience, an audio replay of today's call will also be available on our website shortly after the call.

With that, I would like to turn the call over to Milestone's CEO, Joseph Oliveto. Joe?

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [3]

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Thank you, Eleanor, and thank you to everyone for joining us today. For those of you who may not be familiar with Milestone, the last few months have certainly been an exciting time for us.

With the successful completion of our initial public offering in May, we are well on our way to delivering on our mission of bringing new treatments to patients living with episodic cardiovascular conditions. Our team has been initially focused on the indication known as paroxysmal supraventricular tachycardia, or PSVT.

PSVT afflicts approximately 2 million people and results in at least 600,000 healthcare claims every year in the US alone. Patients experiencing a PSVT episode may feel palpitations, while heart rate increases dramatically, sometimes exceeding 200 beats per minute. The condition commonly causes great distress for patients and their family members and can result in emergency department visits or hospitalizations that add significant cost to our healthcare system.

Our lead candidate, etripamil, is a potent and short-acting calcium channel blocker that has the potential to become the first self-administered rapid onset nasal spray designed to terminate episodes of PSVT wherever and whenever the episodes occur. And without the needed oversight of the emergency department visits that currently available options require.

Results from our Phase 2 trial showed that 87% of PSVT episodes were stopped within 15 minutes of using etripamil 70-milligram dose versus just 35% of placebo-treated patients. And it was these results that served as the foundation for our ongoing Phase 3 program.

By way of background, our pivotal Phase 3 program of etripamil in PSVT consists of three distinct trials designed to support potential regulatory filings in the US and EU. These trials include one pivotal double-blind randomized efficacy trial known as 301 as well as two open-label safety studies, referred to as NODE-302 and NODE-303.

We recently held a productive meeting with the FDA to discuss several proposed changes which we view as potentially optimizing to our ongoing Phase 3 program. We are very pleased with the outcome of our interactions with the Agency, which I will be reviewing in today's call.

I'd like to start with the news regarding NODE- 303. NODE- 303 is our open-label safety trial which will primarily evaluate the safety and tolerability of etripamil 70 milligrams self-administered by the patient without medical supervision and similarly to how it is envisioned to be used commercially. The trial is a global study and will seek to assess up to 1,500 patient events in patients who did not participate in either of our other Phase 3 trials, NODE-301 or NODE-302.

Based on a review of the safety data to date from the ongoing Phase 3 trials, we approached the FDA requesting to initiate NODE-303 with two noteworthy protocol components. First, to allow the study to enroll a similarly broad patient population as the ongoing NODE-301 study, including in that population older patients as well as patients on concomitant beta blockers and calcium channel blockers.

And the second noteworthy protocol component was to allow patients to begin the study and treat their PSVT episodes whenever and wherever they occurred. And without the need for an in-office test dose of etripamil, which is currently used in NODE-301 study. We are pleased to report that we received agreement from the FDA to proceed with this study as requested. And we expect to begin enrolling patients in NODE-303 before the end of the year.

What is more, based on the Agency's early review of the Phase 3 interim safety data for assessing our NODE-303 request, the FDA has also expressed its willingness to consider an overall safety database of less than 1,500 PSVT patient events that they had previously guided us to and which matches the ICH guideline. We believe that this not only is indicative of etripamil's safety profile in the clinical setting so far, but could potentially result in reducing the overall size required of the NODE-303 trial to support an NDA filing.

While we are encouraged by this news, we also note that the program is still in the relatively early days with respect to the total safety database exposure. And as a result, we will continue to plan for sizing NODE-303 to enable the overall safety database of 1,500 patient events for the program. We look forward to providing further granularity on potentially reducing the size of NODE-303 and guidance on an NDA filing timeline as the exposure database continues to grow.

Let me now turn to NODE-301. NODE-301 is our ongoing Phase 3 double-blind placebo-controlled trial evaluating the efficacy and safety of etripamil in terminating PSVT episodes in the outpatient setting. The FDA previously agreed that the trial could serve as a single efficacy study for potential approval and that remains our current plan.

NODE-301 is designed as an event-driven trial. In this trial, we enroll and randomize up to 500 patients to receive either etripamil or placebo in a 2 to 1 ratio. We provide this study drug to the patients and send them home from the office prepared to treat their events when they occur. The study is completed when it reaches 100 confirmed PSVT events.

In addition to the 100 total event requirement, the powering of the study also requires a minimum number of events in each treatment arm: 50 for etripamil and 30 for placebo. Remember, it is randomized 2 to 1, hence the difference.

To avoid potential randomization imbalances, the study calls for an unblinded third-party statistician to review the data as the study approaches 100 events in order to ensure the minimum target number of events occur in each group. With this study tracking ahead of our initial projections, we took the opportunity of the planned FDA meeting to request an increase to the number of adjudicated events in NODE-301 from 100 events to 150 events, a change that addresses several goals.

First, it eliminates the need for the unblinded third-party review of the data, which satisfies a previous request we received from the European Medicines Agency, or EMA, to remove this unblinded review. From a statistical standpoint, upsizing the trial to 150 events significantly decreases the chance of randomization imbalances impacting the study reaching the minimum number of events in each group. With this change, our program now allows us to align under both the FDA and EMA guidances.

The second benefit is that upsizing the study allows us to collect more double-blind randomized data, which better enables subpopulation and pharmacoeconomic assessments, both of which will potentially enhance our understanding of etripamil's commercial profile. And lastly, upsizing the trial enhances its powering.

We also requested and received agreement from the FDA to continue collecting blinded results for patients who have been randomized in NODE-301 but have not yet experienced an event when the 150 events have accrued and the study is stopped. These additional event data will be collected between the time at which the study reaches 150 adjudicated events and until the majority of the remaining patients experience an event.

These data will be analyzed separately as a secondary data set, which we will refer to as NODE-301B, B as in boy. The primary benefit of the 301B addition is the program's ability to generate further double-blind comparative data that will strengthen the safety database and add to subpopulation and pharmacoeconomic analyses and future potential publications and do so in an efficient manner.

Stated more simply, we invested significant efforts in consenting and randomizing patients, packaging the drug for double-blind comparative data. And we thought why not maximize the value of that work to support our eventual NDA filing and future publications.

As with NODE-301, any NODE-301B patient who successfully completes dosing of etripamil in a PSVT event will also be eligible to enroll in our open-label NODE-302 safety extension trial for the treatment of future events.

Based on our progress and experience with the study, we believe that even with the study's increased size, a top-line NODE-301 study readout in the first half of 2020 is still expected. Importantly, while the NODE-301 study will be modestly more expensive than the original plan, there will be no meaningful impact to the total clinical program cost across all studies due to other efficiencies that are gained across the program.

Taken together, we are extremely pleased with the outcome of this meeting with the FDA and the progress of our pivotal program, all of which reflects on the hard work of our skilled and dedicated team. I would also like to thank the physicians and clinical study teams for all their hard work on the NODE-301 study to date. And of course, I'd like to especially thank the patients who have put their faith in the study and in Milestone.

We firmly believe we are well positioned for continued success in the execution of our etripamil pivotal program in PSVT and look forward to updating you on our continued progress in the coming months. Thank you all for your continued support as we work towards achieving our mission of bringing new treatments to patients living with episodic cardiovascular conditions.

With that, I will close the prepared remarks and open up the call for questions.

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Questions and Answers

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Operator [1]

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(Operator Instructions) Chris Howerton, Jefferies.

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Chris Howerton, Jefferies LLC - Analyst [2]

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Hey, good morning. Thanks for the update and hope all is well with you guys. For the first question, I guess, just so I fully understand it, the initial plan was that you want to kind of make sure that you have the minimum event number for each arm. And the change in the upsizing essentially just gives you the confidence that you will meet that minimum number without a statistical adjudication. Is that the basic rationale?

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [3]

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You got it, Chris. Exactly.

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Chris Howerton, Jefferies LLC - Analyst [4]

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Okay, got it, got it. And so when you think about the regulatory path in the EMA, will the NODE-301 trial serve as a single efficacy trial in that territory as well? Or is that still an open discussion with the EMA?

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [5]

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Great question, Chris. And yes, we were very pleased to hear from the EMA when we met with them that a single pivotal efficacy trial could serve as grounds for approval in European Union, as it does in the US with the FDA. So we are aligned on that point as well.

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Chris Howerton, Jefferies LLC - Analyst [6]

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Excellent, okay, great. And maybe just another one in terms of the conduct of the NODE-301 trial. And kind of any information or color you can give us around the event rate or the things that give you confidence that you will still be able to meet that deadline in the first half of next year for top-line results?

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [7]

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Right. Also a common question and a great question. We continue to have confidence, and we would obviously thought twice about making this change should our recruitment rates not have been there for our ongoing program.

But in fact, as you are well aware, Chris, and many of the investors are, we are changing the paradigm here. Going into our Phase 3 program, there was perhaps a little bit more uncertainty around our program than you might otherwise have for Phase 3 because we simply did not have other studies to point to, whether they were ours or others. There just haven't been anyone doing work in this area.

So with that uncertainty, we went into this program with our best estimate. And now, with the randomization rates and event rates coming in, we are seeing that we are actually ahead of our initial projections and continue to have confidence that we will be able to deliver now the 150 events in the first half of 2020. Whereas before, we were thinking we were going to need that period of time to deliver the top-line data with only the 100 events. So it is because we are ahead of schedule on randomization and event rates that we are able to have that confidence.

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Chris Howerton, Jefferies LLC - Analyst [8]

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Awesome. Okay, well, great. And then maybe the other one. I think that I have some ideas, but I'd love to hear your thoughts as well is in terms of what the implications are for the 303 design modifications and the lack of the requirement for the test dose and potentially on the patient population. How does that change your view of the commercial opportunity if at all?

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [9]

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Great question, Chris. I don't know if I would characterize it as changing our view but more confirming our view. Our product profile for etripamil has always been -- and etripamil is designed to be used with a moniker of safety to be used broadly by patients with PSVT events.

And our profile does not have restrictions for any subgroups or any major subgroups. For example, we expect it to be utilized in elderly patients. We expect it to be utilized in patients that are taking other AV nodal blocking agents, such as calcium channel blockers or beta blockers.

However, while we have that in our profile, we do need to confirm that in data. And I would say that this preliminary review of the interim data by the FDA gives us confidence that based on what we have seen so far, the drug is on the right path. Not seeing any particular issues with regard to those populations. So I would characterize it as we are on path to meet our profile rather than changing any views.

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Chris Howerton, Jefferies LLC - Analyst [10]

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Got it. Okay. All right. Well, thank you so much for the updates and look forward to the continued progress.

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Operator [11]

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Ritu Baral, Cowen.

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Ritu Baral, Cowen and Company - Analyst [12]

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Good morning, guys. Thanks for taking the question and the updates. If you had to rank order the reasons behind why the trial is enrolling faster than previously expected, if you had to rank order screening rates, randomization rates, and event rates, like what is the most important driving factor here?

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [13]

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Great question, Ritu, and you are hitting on a little bit of the uncertainty that we had going into this. We had a fair number of variables that we had to manage.

I would say in general, the two drivers behind really us being ahead of schedule are -- and you mentioned screening rates. I would really characterize it as this test dose assessment and potential to screen out patients. And there, we are seeing very low screen-out rates from the test dose. Meaning that patients are tolerating the open-label jug quite well in the office and almost all of them are rolling into the double-blind randomized.

And we had expectations that that screen-out rate would be a lot higher. So that is a major draw to us being able to --

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Ritu Baral, Cowen and Company - Analyst [14]

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Sorry to interrupt. So should we assume that that was kind of like a low-single-digit screen failure rate for the test dose?

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [15]

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It is low-single digits.

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Ritu Baral, Cowen and Company - Analyst [16]

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Got it. Thanks. Sorry, keep going.

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [17]

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So that is one aspect that would be towards the top of the list. We are hitting on all cylinders on getting sites that are finding patients and finding the right patients. Meaning that patients are having episodes a little bit more frequently than we expected.

So for those of you who are close to the story, you know that we have done quite a bit of market research in this field. We estimate that patients have on average or a median number of about a handful to two handfuls of episodes per year; the median being in the range of six to eight.

And we are actually finding when you think about that, you think about a patient having, for our study, maybe four events per year, of which we capture one. We are actually starting to have those events earlier and capturing those first events.

So it is a bit of execution play, where we are doing well. And we are seemingly getting the better patients that are having more events and quicker events. This is all as a result of hard work of our team and being on top of it. And it really going to I think what are superstar sites that really get the protocol and are doing a good job helping us identify the correct patients.

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Ritu Baral, Cowen and Company - Analyst [18]

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And to confirm, your sort of patient interest, patient input rate is at least what you expected? Obviously, it has ramifications for patient prevalence.

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [19]

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Yes, it is. It is better that what we expected in the sense that there are sites that are enrolling a lot of patients. We generally use averages and linear expectations because of all the variables at play and you can wrap yourself around the axle on this. But we do have sites obviously where we miss and haven't enrolled anyone, but the majority of our sites are enrolling patients, with some real superstar sites.

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Ritu Baral, Cowen and Company - Analyst [20]

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Got it. And then the second question. You mentioned that upsizing the events gives you additional powering on some key subpopulation analysis and key pharmacoeconomic analyses. Can you give us a little more detail on the most important subpopulations and why? And which pharmacoeconomic analyses you were referring to in particular?

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [21]

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Right, great question. So the subpops that we typically think about and have on our minds here for this study are common across all studies. They are typical demographics. With regard to PSVT, we really would love to understand if there is age differences in terms of events and results. So in addition to age, there is gender.

We like to think about those patients that are on concomitant medications and other AV nodal blocking agents versus those that aren't. Identifying the subpopulations of PSVT, whether it is AVNRT or AVRT, will be interesting. And those are the subpopulations of interest, I would say.

Again, exactly what it will mean for our drug, we are not sure. Maybe our hope is that it works equally well across. But it will be interesting to advance the field because there just simply is not much out there. And I think we aspire to be a leader in PSVT, and having a more robust study with more double-blind data will allow potential for greater populations in those subanalyses.

With regard to pharmacoeconomics, the study is not powered to show differences, so I just want to set expectations there. It had not been powered; even with an increase to 150, it is not powered to show differences. But we do feel that increasing to 150 as well as putting 301B on now and keeping that as double-blind randomized just gives us more chance of seeing signals.

The important ones we would look for there include interventions. Are there hospitalizations, are there trips to the emergency department, do they intervene with adenosine? Those are the big ones.

Would be also important to understand how patients feel about their use of the drug. So patient satisfaction questionnaires, which are embedded in our study, have a better chance with more double-blind randomized patients. Those are the main areas. Quality of life measures as well as real hard outcomes in terms of medical use of the system.

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Ritu Baral, Cowen and Company - Analyst [22]

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Great. Thanks for taking all the questions. I will get back in the queue with my others.

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Operator [23]

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Ted Tenthoff, Piper Jaffray.

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Ted Tenthoff, Piper Jaffray & Co. - Analyst [24]

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Great. Thank you very much and thanks for the update. Joe, just want to make sure. Did you actually say what percentage of patients have been enrolled? And to this concept of kind of getting patients who have events earlier, remind me. Once they have one event, they go into the open-label study; it is not like they can be counted more than once in the 301, right? Thanks.

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [25]

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Great questions, Ted, and I will take the second one first and confirm that you are correct. Once they have one event in 301, they are -- they get treated. We take their data and they are then out of the 301 study and they roll into the open-label extension called 302.

We collect further data on those patients, but it is not attributing to, if you will, the total safety data set in terms of one patient having two events counts once. So it is per patient, if you will.

With regard to the percentage enrolled, we have not actually identified that or given details on that. I can say, though, and this was predefined with the FDA when we had our end of Phase 2 meeting that we would approach the FDA when about half of the 301 study was completed.

So that will give the investors a feel as to where we are. We went to the FDA recently and we had about half the events under our belt, so about 50 events. So that would give a sense as to where we are without really getting into the details of specific numbers.

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Ted Tenthoff, Piper Jaffray & Co. - Analyst [26]

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That's super helpful. I appreciate the additional color.

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Operator [27]

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Leland Gershell, Oppenheimer.

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Leland Gershell, Oppenheimer & Co. - Analyst [28]

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Hey, good morning, Joe. Thanks for taking my questions and for the good update. I wanted to ask with the 301 data still on track for first half of next year, then the safety study seeming like that may go a bit faster, given your comments, just want to ask if you could maybe qualify for us a bit the NDA and approval timing following the 301 data with 303 filling in. If that could be moved up from prior expectations or how we should think about timelines until approval. Thanks.

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [29]

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Right. Outstanding question and one we are spending a lot of time on internally here, Leland. So here is how we are thinking about it. We have not provided guidance specifically to an NDA filing. We have guided our analysts and our investors that our expectation was that study 303 would run through 2021. That is with it needing to go to the full amount, however many patients that we would need in 303 to enable a total safety data set of around 1,500.

So that was the guidance. That remains our guidance. Even though this is -- we are cautiously optimistic about the FDA willingness to consider something less than 1,500, we want to caution the investors that this is still pretty early in the game in terms of the amount of exposure we have had so far. So we are going to maintain that 303 still runs to the size needed to get us to 1,500 and that would run through 2021.

Now, we will want to update the investors after we get 303 started and get some experience of 303 recruitment under our belt. 303 is in territories we have not experienced yet outside of North America. Both Europe and Latin America is where that study will be conducted, so we do want to get some experience there before we articulate more firm timelines on an NDA filing. And in general, just get more safety data under our belt before we can articulate what the size of the safety data set would be.

So we view those as coming out similarly. I don't have an exact time as when we would update you. But we will continue to assess the progress of the study and look to do it when we feel comfortable that we have our hands around both of those numbers.

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Leland Gershell, Oppenheimer & Co. - Analyst [30]

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Got you. And then just one more, if I may. As you are now going to expand the scope of the safety study and include elderly patients, older patients, patients who may be or have been more reluctant to, let's say, go for ablations and would prefer a pharmacologic intervention but who also may be on many more concomitant meds -- calcium channel blockers, other cardiac active medications -- if you could just again qualify for us what the picture looks like for those older patients in terms of what you see in terms of the meds they are coming on with that may also affect their cardiovascular system. Thanks.

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [31]

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Right. So I will just reword a little bit of the question and then refer to my colleague, Francis, to articulate the concomitant meds that we are seeing with the elderly patients. But we are not opening up to more patients that are elderly or different patients. We have these patients already in NODE-301. We have elderly patients and we have a good percentage of our patients being elderly and/or those on concomitant medications.

The difference is now that given the data we have so far, we are comfortable and FDA is comfortable enrolling these patients without first testing them in the office. And the things we focus on most, as we do with every patient, is AV blocks and blood pressure drops. And we are just not seeing those in this population.

So just want to make sure everyone is on the same page. We are not really opening up to a broader population. We are maintaining the same population without the, if you will, training wheels or safeguards of the test dose. But Francis, can you comment on perhaps concomitant medications or more medications that the elderly may come with?

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Francis Plat, Milestone Pharmaceuticals Inc. - Chief Medical Officer [32]

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Yes, certainly. The safety in 301 is overall very positive and the test dose actually went very well. And as we said, we had very few patients who were not randomized after the test dose, including those patients who are higher than 70 years old and have concomitant medication, especially beta blockers and/or calcium channel blockers.

And when we take the overall safety, including the episode and the administration of the drug by the patients at home, we have no worrisome symptoms, no drop in blood pressure, and no concerns concerning arrhythmia and/or AV block. So basically, the safety is very positive for the overall population, including the elderly population with or without concomitant medication.

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [33]

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And Leland, I will just add lastly, the 301 study is representative, if you will, of also elderly patients having the host of other meds that we all know that they have. So there is no exclusions there; we are very open. And our goal here is really just to match how we expect this jug to be used commercially, which is with very few guardrails or exclusions.

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Leland Gershell, Oppenheimer & Co. - Analyst [34]

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Great. Thanks for the clarification. It's very helpful.

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Operator [35]

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(Operator Instructions) Ritu Baral.

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Ritu Baral, Cowen and Company - Analyst [36]

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Hey, guys. Thanks for taking the follow-up. One more trial conduct question. I know that you guys somewhere in the protocol will be adjudicating the patient events just to make sure that they are true PSVT events. Is that happening real-time or is that sort of adjudication of the true event something that happens after [data dose block]? Remind me again.

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [37]

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Yes, so it's in between. It is not real time; they are batched, if you will. And then when the adjudication committee comes together, they review a series of patients in a batched format and will update us as to whether those patients are truly characterizing their event and it is a true PSVT.

So we are down the path there. We are very happy with how these patients are characterizing their events. We do have some who mischaracterize or misdiagnose and it is not true PSVT. That is valuable for us because in the real world, that will happen. We want to see the safety on those patients.

But we are again below our expectations and assumptions with how many are misdiagnosing. So that is actually another area that gets us to true PSVT events quicker than we had originally assumed.

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Ritu Baral, Cowen and Company - Analyst [38]

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Got it. So basically by the time you lock the database and you count your events, you won't lose any events to classification of real or adjudication, put it that way.

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [39]

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Correct. And that batching could be something that causes us to go -- in the past, would have caused us to go a little bit above 100 events. In this case, that batching may cause us to go a little bit above 150 events. We will try to have the committee meet a little bit more regularly as we get towards the end, but we are not worried if we go over by a couple events.

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Ritu Baral, Cowen and Company - Analyst [40]

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Got it. And can you remind me, do you have any plans on changing the maximum number of doses in 302 and 303? I believe one of them is like 7 max and the other was 11 max. Any changes to that?

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [41]

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We are not changing them. I will just provide the actual numbers. 302 enables up to 12 dosing events. And then NODE-303, which is the upcoming trial, open-label safety, we enable the patient to use the drug four times on four events.

And then our expectation -- it is not that we don't want to keep providing the drug to patients, but the thought was four events would be an appropriate amount of data for the safety data set. There is no requirement, I will remind you, for repeat use in our data set. It is informative information for the Agency.

But after their four events, they have the opportunity to roll into. Our expectation being [a means] patient program where they will have access compassionately use.

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Ritu Baral, Cowen and Company - Analyst [42]

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Got it. And then last question. Can you just confirm that Europe didn't have any other suggestions for the 301 trial design? Or are there potential other small protocol changes to either 301, 302, or 303 that they requested?

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [43]

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The EU always has plenty of suggestions. I would classify them as not of the importance and rigor and definitiveness as this one. This one they were really focused on and hit on a few times. The other ones were taken account of and some incorporated into the protocol and some not. But we did not include every suggested change that the Europeans had.

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Ritu Baral, Cowen and Company - Analyst [44]

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But nothing that would jeopardize the acceptability of the current 301 study?

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [45]

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That is our interpretation and expert review, yes.

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Ritu Baral, Cowen and Company - Analyst [46]

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Got it. Okay, thanks for taking the follow-up.

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Operator [47]

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I am currently showing no further questions at this time. I would like to turn the call back over to Joseph Oliveto for closing remarks.

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Joseph Oliveto, Milestone Pharmaceuticals Inc. - President and CEO [48]

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Thank you very much, operator, and thank you to everyone again for taking the time out. We know it is earnings season. We know you are all busy, so really appreciate you guys following the story and continuing to support Milestone as we move forward here. Thank you very much. Have a great day.

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Operator [49]

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Ladies and gentlemen, this concludes today's conference. Thank you for joining and have a wonderful day.