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Edited Transcript of MDCO earnings conference call or presentation 30-Oct-19 12:30pm GMT

Q3 2019 Medicines Co Earnings Call

PARSIPPANY Nov 15, 2019 (Thomson StreetEvents) -- Edited Transcript of Medicines Co earnings conference call or presentation Wednesday, October 30, 2019 at 12:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Christopher J. Visioli

The Medicines Company - CFO & Treasurer

* Goutham Krishna Gorti

The Medicines Company - VP & Head of IR

* Mark Timney

The Medicines Company - CEO & Director

* Peter Wijngaard

The Medicines Company - Executive VP & Chief Development Officer

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Conference Call Participants

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* Akash Tewari

Wolfe Research, LLC - Director of Equity Research & Senior Research Analyst

* Biren N. Amin

Jefferies LLC, Research Division - MD and Senior Equity Research Analyst

* Chris Shibutani

Cowen and Company, LLC, Research Division - MD & Senior Research Analyst

* Dae Gon Ha

SVB Leerink LLC, Research Division - Associate

* Jay Olson

Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst

* Jessica Macomber Fye

JP Morgan Chase & Co, Research Division - Analyst

* Joel Lawrence Beatty

Citigroup Inc, Research Division - VP & Analyst

* Kyuwon Choi

Goldman Sachs Group Inc., Research Division - Equity Analyst

* Madhu Sudhan Kumar

Robert W. Baird & Co. Incorporated, Research Division - Senior Research Analyst

* Mayank Mamtani

B. Riley FBR, Inc., Research Division - Research Analyst

* Tazeen Ahmad

BofA Merrill Lynch, Research Division - VP

* Umer Raffat

Evercore ISI Institutional Equities, Research Division - Senior MD & Senior Analyst of Equity Research

* Yasmeen Rahimi

Roth Capital Partners, LLC, Research Division - MD, Senior Research Analyst & Co-Head of Biotechnology Research

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Presentation

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Operator [1]

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Greetings. Welcome to The Medicines Company Third Quarter 2019 Earnings Call Webcast. (Operator Instructions) Please note that this conference is being recorded.

At this time, I'll turn the call over to Krishna Gorti, Vice President, Investor Relations. Please go ahead, Krishna.

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Goutham Krishna Gorti, The Medicines Company - VP & Head of IR [2]

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Thank you, Rob. Good morning, everyone, and welcome to The Medicines Company's Third Quarter 2019 Earnings Conference Call. I'm joined today by our Chief Executive Officer, Mark Timney; our Chief Financial Officer, Christopher Visioli; our Chief Development Officer, Peter Wijngaard.

Earlier this morning, we issued a press release reporting our third quarter 2019 financial and operating results. The press release is available in the Investor & Media Relations section of our website.

Before we begin, I'd like to remind you that our discussion during the call will include forward-looking statements that are subject to risks and uncertainties that could cause actual results to differ materially from those indicated by those forward-looking statements. Additional information regarding these risks and uncertainties is discussed under the forward-looking statements legend in this morning's press release as well as in our periodic reports filed with the Securities and Exchange Commission, which can be obtained from the SEC or by visiting the Investor Relations section of our website.

During today's call, we will also discuss certain financial measures that were not prepared in accordance with the U.S. generally accepted accounting principles. Please refer to this morning's press release for a reconciliation of these non-GAAP measures to the most directly comparable GAAP financial measures.

With that, I'll now turn the call over to Mark. Mark?

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Mark Timney, The Medicines Company - CEO & Director [3]

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Thank you, Krishna. Good morning, everyone, and thank you for joining us today. Before I discuss the quarter, I'd like to remind us all of why we're here. Well, more than 47,000 people worldwide will die today as a result of the world's #1 killer, cardiovascular disease. Atherosclerotic cardiovascular disease, or ASCVD, is the leading contributor to morbidity and death and its root cause cumulative exposure to elevated LDL-cholesterol is also the most readily modifiable risk factor. We are aligned with the increasing recognition by thought leaders of the importance of addressing cumulative exposure to LDL-C. Patient management should consider both lowering LDL-C levels and keeping them low for the remainder of one's life.

Despite the widespread availability and use of proven LDL-lowering therapies, notably statins, many people with ASCVD are still not meeting treatment goals. We know from our research that health care professionals around the world are concerned about the inability to get and maintain patients on therapy, and they are seeking different ways to achieve durable and potent LDL-C reductions that address cumulative exposure to LDL-C.

As the first and only LDL-C therapy that would be administered by a health care professional twice yearly, we believe that inclisiran is a game-changer that addresses 2 critical unmet needs: first, additional LDL-C lowering is needed so that ASCVD patients consistently reach their goal and avoid cardiovascular events; and second, underlying this first need is poor patient adherence to LDL-C-lowering therapy. Based on the exceptional data presented so far, we believe inclisiran is well positioned to address this significant unmet need in ASCVD, setting the stage for substantial commercial opportunity and shareholder value.

We continue to make steady progress, keeping a sharp focus on highly disciplined execution, and we believe the existing cash provides us with runway into the second half of 2020 and enables significant strategic financial flexibility.

Now let me focus on a very busy and exciting third quarter with a performance that was defined by flawless execution. I'll begin with our clinical development program where we successfully completed inclisiran's pivotal Phase III LDL-C-lowering trials. Each of those 3 studies met all primary and secondary endpoints showing durable and potent efficacy with twice-yearly dosing of inclisiran and excellent safety with no treatment-related liver or renal laboratory abnormalities.

At the European Society of Cardiology meeting in Paris in September, we presented the results from ORION-11, inclisiran's first pivotal Phase III clinical study. In ORION-11, twice-yearly dosing with inclisiran sodium 300 milligrams met all primary and secondary efficacy endpoints as well -- and was well tolerated and demonstrated an excellent safety profile.

For the primary endpoint, inclisiran delivered placebo-adjusted LDL-C reductions of 54% at day 510 and demonstrated time-average placebo-adjusted LDL-C reductions of 50% from days 90 through 540. The overall adverse event profiles of the placebo inclisiran-treated groups in ORION-11 was similar with no treatment-related hepatic or renal abnormalities. The results of the ORION-11 trials support the unprecedented potential of inclisiran to deliver assurance to clinicians and patients that LDL-C can be lowered in a sustained fashion over the long term with an infrequent dosing regimen and an excellent safety profile.

In addition to ORION-11, we toplined the 2 remaining pivotal trials, ORION-9 and ORION-10, in late September. Top line data for ORION-9, which is the Phase III clinical study in patients with heterozygous familial hypercholesterolemia, or HeFH, show that the study met all primary and secondary endpoints.

Inclisiran demonstrated durable and potent efficacy and was well tolerated with excellent safety that was generally well balanced between the treatment groups with no treatment-related liver or renal laboratory abnormalities. ORION-10, a Phase III clinical study in patients with ASCVD, marked the successful conclusion of the pivotal Phase III LDL-C-lowering studies of inclisiran. ORION-10 met all primary and secondary endpoints, and inclisiran demonstrated efficacy and tolerability and safety that were at least as favorable as observed in ORION-11 with no treatment-related liver or renal laboratory abnormalities. Detailed efficacy, tolerability and safety data from ORION-10 will be presented at a late-breaking science session at the American Heart Association annual meeting in Philadelphia on Saturday, November 16 at 11:06 Eastern Standard Time.

The company will also present data from the ORION-9 study in patients with HeFH at a separate late-breaking science session of the AHA congress on Monday, November 18 at 9:24 Eastern Standard Time.

With our clinical development program is also ORION-4, our cardiovascular outcomes trial. Enrollment of patients into ORION-4 is ongoing and remains on track. We expect to complete enrollment within 1 to 2 years from the beginning of enrollment. During the quarter, we also completed manufacturing validation of inclisiran and achieve commercial scale. With this validation and the completion of the pivotal Phase III studies, we are progressing rapidly towards anticipated regulatory submissions. We expect to file an NDA by the end of this year and an MAA in Europe during quarter 1 of next year. In parallel, we continue with our robust precommercialization work that reinforces the transformational profile and potential of inclisiran.

Our Phase III data reps further fuel our excitement in the product profile. This enthusiasm is matched by thought leaders and stakeholders keen to change the trajectory of cardiovascular disease. Our planning has been informed by a wealth of insight-driven analysis centered on patients, health care professionals, health systems and payers that comprise the health care ecosystem.

We've been working with industry-leading partners to conduct several rounds of qualitative and quantitative market research globally. Early feedback on the target profile for inclisiran has been very positive across stakeholders who see the game-changing potential for this first-in-class, cholesterol-lowering, small-interfering RNA therapy to deliver durable and potent lowering of LDL-cholesterol and is, thereby, ideally suited to address the risk of cumulative exposure to LDL-C. Across all stakeholders, patients, providers, health plans and health systems around the world, the feedback is remarkably consistent.

Messaging related to disease burden as well as clinical efficacy and safety for inclisiran has resonated well with decision-makers across all markets. They see how a product with inclisiran's profile can help address the overwhelming unmet needs that contribute to the world's leading cause of death. Low adherence to existing therapies is seen as a significant driver of unmet need, and inclisiran's dosing profile is viewed as a potential solution to help circumvent the challenges of treatment adherence by improving therapeutic coverage and persistence.

There is strong feedback on the possibility for inclisiran to deliver a positive treatment experience through twice-a-year dosing administered to the patient by a health care professional, which aligns with common approaches to care for patients with ASCVD, including the frequency of follow-up office visits.

Looking a little deeper into what differentiates inclisiran for payers, this important stakeholder group used twice-a-year dosing, health care professional administration and the ability to significantly lower LDL-C over a long period of time as core value drivers.

All stakeholders are also receptive to our focus on patient affordability, an attempt to create an environment that responsibly supports access to all patients who could benefit from inclisiran. These consistent and continued insights from stakeholders around the world reinforce our confidence in inclisiran as the first-in-class cholesterol-lowering siRNA that offering a vastly different value proposition compared to any other LDL-C-lowering option.

The opportunity to help patients simply and dramatically lower LDL-C and, therefore, live healthier lives and the magnitude of the unmet need and health challenges speak to the potential market opportunity for inclisiran. The number of high-risk undertreated patients requiring lipid-lowering therapies is staggering. We believe there is an opportunity for inclisiran to provide durable and potent LDL-C lowering among the more than 40 million people with ASCVD or FH across the U.S., the largest European countries, China and Japan, who are currently treated with LDL-cholesterol-lowering therapies but are not a goal.

We are confident in the promise of inclisiran as the first and only cholesterol-lowering siRNA with the potential to deliver durable and potent lowering of LDL-C levels via twice-yearly dosing that can help address the 2 critical unmet needs: additional LDL-C lowering and poor adherence to therapy.

I'll now turn the call over to our Chief Financial Officer, Chris Visioli, who will cover our financial results for the quarter. Over to you, Chris.

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Christopher J. Visioli, The Medicines Company - CFO & Treasurer [4]

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Thank you, Mark, and good morning, everyone. During the third quarter of 2019, we continue to execute to our operational and financial plan. Research and development expenses were $42.8 million, including $1.9 million in stock-based compensation expense and approximately $12 million related to the release of 3 manufacturing validation lots in the third quarter of 2019 compared to $32.7 million, including $1.4 million in stock-based compensation expense for the same period in 2018.

In addition to the manufacturing validation work, R&D expenses for the third quarter of 2019 included costs associated with the pivotal ORION Phase III clinical programs, progression of enrollment in the ORION-4 CVOT program, the continued transition of patients from the pivotal programs into the ORION-8 extension study and headcount associated with R&D. The manufacturing validation lots will be part of our NDA filing and will be used for clinical and commercial supply pending approval.

SG&A expense was $18.6 million, including $2.6 million in stock-based compensation expense in the third quarter of 2019 compared to $6.8 million, including $2.7 million in stock-based compensation expense and a $7 million gain from the sale of the company's rights to branded Angiomax in the United States to Sandoz for the same period in 2018. Our cash and cash equivalents at the end of the third quarter was $265.9 million, which we anticipate will enable us to fund operating expenses into the second half of 2020.

With that, I'll turn the call back over to Mark. Mark?

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Mark Timney, The Medicines Company - CEO & Director [5]

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Thanks, Chris. So in summary, The Medicines Company has entered an exciting period for inclisiran, which we believe is a class of one with the therapeutic profile that offers a vastly different value proposition compared to any other LDL-C-lowering option. It is a product with substantial possibility to fundamentally reshape the landscape of cardiovascular care.

Looking ahead to the rest of the year, we have a number of important upcoming catalysts that include ORION-9 and ORION-10 presentations at the AHA conference in November, publications of data from Phase III studies in peer-reviewed journals and the anticipated U.S. NDA filing in the fourth quarter. In parallel, precommercialization work is ongoing and affirms the highly competitive profile of inclisiran. The Board and the management team are fully aligned, and we're committed to unlocking the full potential of inclisiran for its shareholders and, ultimately, patients who would benefit from this unique therapy. We are more confident than ever in our belief that inclisiran could become a game-changer in cardiovascular care and help to overcome many of the existing barriers in the fight against cardiovascular disease, the world's leading cause of death.

With that, we thank you for listening, and I'll turn the call back over to Rob so that we can take some questions.

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Questions and Answers

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Operator [1]

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(Operator Instructions) Our first question comes from the line of Umer Raffat with Evercore.

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Umer Raffat, Evercore ISI Institutional Equities, Research Division - Senior MD & Senior Analyst of Equity Research [2]

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Mark, can you speak to any contracting work you guys have already been doing potentially with any government agencies, U.S. or ex-U. S.? What the size of that looks like? What the volume of that looks like? And what's the dollar pricing for that look like?

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Mark Timney, The Medicines Company - CEO & Director [3]

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Umer, thanks for the question. As you can imagine, we've been in deep discussions with payers and health systems around the world, and we have tremendous optionality as we speak to them. It's too early for me to disclose any of those conversations at this point in time.

They are ongoing. It's suffice to say that there is tremendous excitement around the possibility of treating large populations with a product -- with a profile like inclisiran. And let me leave it there, but it's very exciting times.

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Operator [4]

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Our next question is from the line of Joseph Schwartz with SVB.

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Dae Gon Ha, SVB Leerink LLC, Research Division - Associate [5]

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Congrats on all the progress. This is Dae Gon dialing in for Joe. So Mark, 2 questions on the earlier payer feedback that you commented in your prepared remarks. First question is, does the potential for inclisiran to be reimbursed via Part B, Part D or population health approaches provide you with any strategic flexibility relative to the monoclonal antibodies? What are the implications for market opportunity?

And second question kind of related to that, perhaps, more on a tangential basis is, can you share some of your market research with payers, specifically, where are you getting the most traction with them? And what does it imply, both for the potential market share of inclisiran and how inclisiran could impact the size of the overall -- the pie, if you will, of the PCSK9 market?

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Mark Timney, The Medicines Company - CEO & Director [6]

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Thanks for the question, Dae Gon. Let me answer the second one first. Obviously, payers is a very important stakeholder group for us. It's very clear in the market research that we've done that they view twice-a-year dosing, health care professional administration and the durability and the potency lowering of LDL-C as core value drivers.

For them, it's clear in the research that lower adherence to existing therapies is seen as a significant driver of the unmet need. And inclisiran's profile is really viewed as a solution to help circumvent some of those challenges of treatment adherence.

If we look a little bit deeper into some of that research, it's an important stakeholder group, but they do say that twice-a-year dosing is the critical piece for them. There is really strong feedback that there is an unprompted link to improved adherence and that leads to the possibility to deliver a differentiated treatment experience, which is very exciting for them. I think, finally, they've also been very receptive to our focus on patient affordability and our attempts to create an environment that responsibly supports access for patients.

With regards to your first question, it really is -- our opportunity is really very broad because of our differentiated product profile. We do have a unique product, and therefore, we're having very different types of discussions. It's early for us to talk about those, as I said, in greater detail, but it does leave us with optionality and great optionality and whether that's around Part B medical benefit or pharmacy benefit, we have options in both, which are very exciting for us.

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Operator [7]

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Our next question comes from the line of Jessica Fye with JPMorgan.

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Jessica Macomber Fye, JP Morgan Chase & Co, Research Division - Analyst [8]

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First, on those commercial-scale validation batches, do those now need to fit for stability? Or do you have stability data already?

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Peter Wijngaard, The Medicines Company - Executive VP & Chief Development Officer [9]

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Jessica Fye, this is Peter. We do have stability data already because that would also be part of the file, both for the API as well as for the drug product.

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Jessica Macomber Fye, JP Morgan Chase & Co, Research Division - Analyst [10]

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Okay. Great. And then separately, on the outcomes trial, which you mentioned was enrolling. I think you said it would complete enrollment in 1 to 2 years from when it started. Can you remind me when that trial started enrolling?

And then related to that, how much of the cost of the CVOT has already been incurred? And how much still remains in front of the company?

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Peter Wijngaard, The Medicines Company - Executive VP & Chief Development Officer [11]

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So we announced the first patient enrolled in ORION-4 late last year. I believe it was October. So the time frame from the 1 to 2 years has to be seen from that time point onwards.

Chris, do you want to...

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Christopher J. Visioli, The Medicines Company - CFO & Treasurer [12]

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Yes. On the cost, yes. As we stated, the total program would cost approximately $150 million and that would roll out over 4 to 5 years of the trial, and we're tracking towards that. And we set it on a fairly linear basis. So we're tracking within that range.

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Operator [13]

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The next question is from the line of Tazeen Ahmad with Bank of America.

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Tazeen Ahmad, BofA Merrill Lynch, Research Division - VP [14]

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Just a couple on a comment that you made about your financial. So you said that you have enough cash to take you through to, I think, you said around the middle of 2020. Is that assumption inclusive of having to build out a sales force? That's question one.

Question number 2 is what are your thoughts about partnering the program, at least on the ex-U. S. front? Is it your assumption that you will be partnered by the time you launch? Or do you have expectations that you will at least start the launch, ex-U. S.?

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Christopher J. Visioli, The Medicines Company - CFO & Treasurer [15]

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Yes. So -- this is Chris. On the runway, it would include -- we said that we have cash to take us into the second half of next year, and it would include the work necessary to -- the precommercialization work necessary and R&D work necessary.

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Mark Timney, The Medicines Company - CEO & Director [16]

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So that we could -- as you think about sort of the build-out of any commercial team, that wouldn't really begin until the third quarter to them. So I think you can factor that into what Chris is saying.

With regards to partnering, obviously, we're not -- if and when we have anything to announce, we'll obviously announce that at the appropriate time. All strategic optionality is in front of us, and we're excited by those options.

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Tazeen Ahmad, BofA Merrill Lynch, Research Division - VP [17]

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And then just one follow-up. Do you have a sense of how big of a commercial sales force you would need in the U.S.?

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Mark Timney, The Medicines Company - CEO & Director [18]

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Yes, it's a -- this is a common question that I do get asked. It's a little bit early for us at the moment. And the reason being is our extensive research continues and as our discussions with payers and providers alike starts to build, it goes back to some of the earlier questions about how you actually would launch a product with such a differentiated profile. So a little bit early for us to comment on that at this stage.

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Operator [19]

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The next question is from the line of Yasmeen Rahimi with Roth Capital.

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Yasmeen Rahimi, Roth Capital Partners, LLC, Research Division - MD, Senior Research Analyst & Co-Head of Biotechnology Research [20]

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I have 2 for you. The first one is for Peter. Peter, can you walk me through what type of event rate data are you planning to share with your payers to really link improved compliance to reduce event rate in the absence of CVOT results?

And then the second one, it's just a little bit detailed in regards to inclisiran packaging. Maybe you remind us, what's the [difficulty] with needle? Does it require re-suspension? What is the volume of administration itself?

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Peter Wijngaard, The Medicines Company - Executive VP & Chief Development Officer [21]

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Thanks, Yasmeen, for your questions. I'll start with the second question. So inclisiran is going to be administered as a subcutaneous injection of 1.5 ml. This will be in a prefilled syringe that has a needle gauge of 27, so it's a very fine needle.

Your first question was the type of events around adherence. Obviously, we have started inclisiran so far only in clinical trial setting. And as you probably know from the results we presented before, the adherence in clinical trial setting is extremely high. We had 95% or more of the patients in ORION-11 completing the trial and receiving the 4 doses out to the 18 months duration of study.

At that rate, of course, it will be very useful in those discussions you referred to. But ultimately, it's more important to look at the market research we're doing, how the perception is, the profile of inclisiran with twice-yearly administration and in administration by the health care provider. What I would translate into a real-world setting of adherence, which we do anticipate to be much higher in typical drugs that are administered much more frequently.

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Yasmeen Rahimi, Roth Capital Partners, LLC, Research Division - MD, Senior Research Analyst & Co-Head of Biotechnology Research [22]

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And how aware are the payers of the lack of compliance resulting in high event rate?

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Mark Timney, The Medicines Company - CEO & Director [23]

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Yes, that's coming through very strongly in our research, Yasmeen. It's clear that they understand the challenges with adherence. Many companies have tried to solve this, and many systems have tried to solve this over periods of time. We're actually coming through the research. We're starting to see health systems and how much they're actually spending on trying to solve this per patient, which is -- it's been fairly dramatic for us to see that in the lengths that they're going to, to try to change adherence because they know, obviously, it has such an impact on outcomes.

So the awareness levels are very high. And as Peter said, there's tremendous excitement around a product, which can be delivered by a health care practitioner, which basically guarantees that the drug is on board for a long period of time.

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Operator [24]

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Our next question is from the line of Paul Choi in Goldman Sachs.

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Kyuwon Choi, Goldman Sachs Group Inc., Research Division - Equity Analyst [25]

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My first question is on the regulatory side. And we were just wondering, what are the remaining steps that you have to do before filing the NDA?

And then if you could layout for us, what are your base-case expectations with regard to the timing and potential topics for our potential advisory committee meeting for inclisiran, given that it could be the first-in-class siRNA for LDL management?

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Peter Wijngaard, The Medicines Company - Executive VP & Chief Development Officer [26]

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Thanks, Paul. I'll take those questions. So where we are with the NDA, we've always had the clinical program being the driver of time lines towards the NDA, as the nonclinical and CMC part has essentially finished earlier in the year. So the widening of the NDA of that part is also very advanced.

And what drives the overall time lines in terms of the final steps towards the NDA submission is the writing up of the Phase III clinical data in the study reports and the integrated analysis. We are on track to have that completed by year-end and submission to the FDA by the same time.

And with respect to your second question about -- questions of the outcome. First of all, we don't anticipate to get an outcome at this point in time, we will be -- we have performed a LDL-C-lowering program, which is unique in one sense because of the profile of inclisiran. But on the other side, it's standard as has been for other LDL-C-lowering programs, and they're being held with the same standard. The decision is ultimately in the hands of the FDA. It would be speculative for us to make any statements on that. But from what we know today, we don't anticipate we will be having an outcome.

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Operator [27]

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Our next question is from the line of Chris Shibutani with Cowen.

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Chris Shibutani, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [28]

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A couple of questions. In terms of thinking about potential commercial partners, I think we've had a discussion previously about how the current commercializing companies with the monoclonal antibodies might have "a difficult time" getting their heads around the idea of also having within their portfolio of product like yours. Is that something that you continue to feel that way? And would you, for instance, think that there might be any antitrust-related issues if one of the existing players considered partnering or commercializing or even owning the assets?

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Mark Timney, The Medicines Company - CEO & Director [29]

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Chris, it's Mark. I'll answer that. Obviously, we can't speculate our comment on any sort of potential partners. I think you took a third-party view, I think, you'd have to say the FTC, it's -- at this point in time, it's taking quite a strict approach to these types of, let's say, close collaborations. I think it's -- it would be difficult. Certainly, I would think in my mind, but that's -- I wouldn't want to speculate.

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Chris Shibutani, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [30]

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And then when you commercialize, potentially, a group of patients would be those who are already taking the monoclonal antibodies. Can you remind us, I believe, number one, what studies you are actually doing? I think there was a study that was looking at transitioning patients. Number two, would you think that you would be needing any particular data from a regulatory standpoint to have something in the label for that, instruct physicians what to do? For instance, if you're on a monoclonal, but you need to do that initial sort of dose in 3 months and then go to 6 months.

And then finally, have you had any discussions with payers about what they think they need to know or understand in the situation where they have a patient on a monoclonal antibody and would like to transition over? So it's really clinical studies, regulatory and sort of the commercial discussions with payers for that potentially attractive subgroup of patients.

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Mark Timney, The Medicines Company - CEO & Director [31]

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Yes, let me start, and I'll ask Peter to comment on ORION-3. So we expect the inclisiran label at launch to be in combination with maximally tolerated statins in patients with ASCVD or HeFH. Frankly, we see cardiovascular disease as our competitor. We see real opportunity at the top of the funnel when you think about the number of more than 40 million people with ASCVD or FH across those major markets, including the U.S., European countries, China, Japan that -- who all need additional LDL-C lowering and are not a goal.

So it's clear to me there is a much larger opportunity out there than just a small number of patients who are actually taking the monoclonal antibodies. So we expect to source patients from all lines of therapy and that's been consistent within our research as well, whether that's been with payers, health care providers and patients.

So basically, it's -- any -- all who are in need of durable potent lowering of LDL-C and where twice-yearly dosing will improve adherence.

Peter, would you like to talk about the studies?

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Peter Wijngaard, The Medicines Company - Executive VP & Chief Development Officer [32]

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Yes, Chris. So ORION-3 study is the extension study of the Phase II ORION-1 study. We presented the data for the patients who've maintained therapy on inclisiran earlier in the year at NLA.

But the placebo patients that were in ORION-1, transitioned into ORION-3, first by a year of treatment, the evolocumab. And then they all have been switched to inclisiran in 2 different ways, by 2 different transitions modality, concomitant administration of the last dose of evolocumab combined with inclisiran or by an interval of 2 to 3 weeks, which is sort of typical dosing interval for the antibodies.

That data will be forthcoming. We will, of course, have information from that study that will provide guidance on how to switch from a monoclonal antibody to inclisiran. And obviously, at the appropriate time, we will try to have it also reflected in the label. Whether that will be possible will depend on the suitability of the data that we have and the FDA's opinion on that as well as other activators in the world. But we certainly intend to have it ultimately in the label.

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Chris Shibutani, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [33]

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Great. And then last quick detail, the previous wording in the second quarter with cash well into the second half. This quarter, you say, into the second half, am I being too specific about this? Was that a deliberate change of wording? Or...

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Christopher J. Visioli, The Medicines Company - CFO & Treasurer [34]

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No. No. Not deliberate. Yes, you're just -- you're being too specific, Chris.

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Operator [35]

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Our next question is from the line of Mayank Mamtani with B. Riley.

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Mayank Mamtani, B. Riley FBR, Inc., Research Division - Research Analyst [36]

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Congrats on the flawless execution through the quarter. Interesting to hear Amgen's management team commented last evening on inclisiran. Mark, wondering if you could comment would you or even Diane might be hearing from your industry peers? Or should I say some of them ex-colleagues in case you've had a chance to and formally review inclisiran's overall profile?

Or maybe you run into some of them at AHA, just curious. From the industry side, who -- folks committed to cardiovascular, what you're hearing there?

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Mark Timney, The Medicines Company - CEO & Director [37]

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Thanks for the question, Mayank. And obviously, I can't comment on any strategic discussions or any speculations. I will say it's well known, and we saw this at ESC, there is tremendous excitement around inclisiran. And I think that's across all stakeholder groups. It's a well-known product. I think the data speaks for themselves, and that's only built around the excitement of the product profile that is now coming to bear. So very exciting, and I don't think that's changed.

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Mayank Mamtani, B. Riley FBR, Inc., Research Division - Research Analyst [38]

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Okay. Great. If I could do a follow-up. So now you have all the data in house. And obviously, you talked about your precommercial plans, and you think about the different patient profiles that any cholesterol-lowering company considers as part of their launch plan. Maybe could you comment on what that ideal patient looks like for inclisiran until we have that longer-term safety exposure and, of course, the outcomes data just across the different patient profiles?

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Mark Timney, The Medicines Company - CEO & Director [39]

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Yes, it's remarkably consistent with what I've said. I mean we do expect the label to have at launch to be with maximally tolerated statins in patients with ASCVD or HeFH. And really, it is those patients who are struggling to get to goal, though secondary prevention, high-risk patients that will really form the basis of the patient group that will be -- what will really benefit from inclisiran at launch.

Obviously, we would have a full life-cycle management plan that will expand that patient population over time as we learn more about it. We don't -- even though we will not have outcomes, cardiovascular outcomes, at launch, we don't expect that to be a barrier for any of our major stakeholder groups.

The question that -- whenever I pose this question and whether we pose it in research, what consistently comes back to us is, well, did anybody wait for outcomes when rosuvastatin launched and the clear answer is no. PCSK9 is a well-validated target. We've got outstanding data over a long period of time. We've done some of the longest LDL-C studies in the history of cardiovascular medicine. And that all supports a very strong profile, and it will support a strong launch.

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Mayank Mamtani, B. Riley FBR, Inc., Research Division - Research Analyst [40]

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Excellent. And if I can squeeze one in for Peter. Peter, any color you could provide on emerging cardiovascular targets such as ANGPTL3, which according to some, again, early, but it could be a competitive threat to the PCSK9 class as a whole? And any thoughts there?

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Peter Wijngaard, The Medicines Company - Executive VP & Chief Development Officer [41]

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Yes. Of course, they are early programs right now. So it's hard to predict what exactly their data set will be by the end of Phase III. But the only thing I would add to that is, is that most of those opportunities do not touch the patient populations at large that we are targeting, who has ASCVD and FH with the patients of LDL-C not their target goal.

Most of those opportunities you're talking about either targets specific subpopulations like the FH or homozygous FH or patients with elevated triglycerides, which kind of come secondary to LDL-C.

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Operator [42]

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The next question is from the line of Akash Tewari with Wolfe Research.

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Akash Tewari, Wolfe Research, LLC - Director of Equity Research & Senior Research Analyst [43]

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So maybe just going a bit on the Phase IIIs that are going to get the full data. Can you compare and contrast like the baseline severity in CVD burden of the ORION-9 population versus ORION-11? And have you seen any change in the net reduction of LDL-C as patients' baseline LDL-C increases?

And it also looks like you're mentioning the Japanese and China market a bit more in your prepared comments, is it fair to assume that those are markets you'd likely look to partner? And how would you kind of characterize the size of the commercial opportunity in those markets versus, let's say, U.S.?

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Mark Timney, The Medicines Company - CEO & Director [44]

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Peter, do you want to take the first one?

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Peter Wijngaard, The Medicines Company - Executive VP & Chief Development Officer [45]

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Yes. Obviously, I can't comment on specific data points from 9 and 10 as they will be presented at AHA on Saturday for ORION-10 and on Monday for ORION-9.

But I can speak to the difference in the patient populations of those trials. So while 11 was a European and South African study in ASCVD patients and ASCVD risk equivalence, who should have the same risk of cardiovascular events and need for LDL-C lowering, the ratio between the 2 populations in ORION-11 was approximately 85% to 15% of ASCVD and risk equivalents.

ORION-10 is a U.S.-only study and only included ASCVD. So it's highly similar than ORION-11. But there are some fine differences in the exact composition of the patient population and, of course, the geography where it was discussed -- where it was conducted.

ORION-9, on the other hand, is a dedicated study in heterozygous FH patients that was conducted globally. Now heterozygous FH patient is an early manifestation of ASCVD. So patients are at risk of an early stage in life and, largely, in totality, are considered to have a high-risk of ASCVD because of that early manifestation, and it's all driven by the genetic backlogs of the mutations that they carry that causes them to have the disease of FH.

So in that context, they're at a higher risk over their life course, whether they are specifically different in the risk population in this study. We will show you the data when we get to AHA.

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Mark Timney, The Medicines Company - CEO & Director [46]

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And let me just touch on the question around Japan and China. We are receiving significant interest in the profile of inclisiran within those countries, whether that's with the payers or with the key opinion leaders. As you would well know, there is significant ASCVD in those regions of the world. And therefore, it's incumbent to all of us to ensure that there is a robust plan for how those regions would actually be accessed.

We've said and we continue to believe that if we are to do anything within Japan, we would do that with a partner, and we have regulatory pathways to what type of bridging studies would need to be conducted in both markets.

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Operator [47]

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Next question comes from the line of Madhu Kumar with Robert W. Baird.

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Madhu Sudhan Kumar, Robert W. Baird & Co. Incorporated, Research Division - Senior Research Analyst [48]

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So thinking about the MACE observation that you guys made with ORION-11 and ESC. If there weren't, I'm not saying whether they are or not, in the ORION-10 data set at AHA, would that be similarly presented in the presentation? Or like how should we think about kind of MACE observations in the U.S. ASCVD trial?

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Peter Wijngaard, The Medicines Company - Executive VP & Chief Development Officer [49]

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Thanks, Madhu. ORION-9, 10, 11, for that matter, were designed with the exact same concept of the protocol. So the endpoints we collected in 11 are the same endpoints we collected in 10 and 9. 10 is about the same size as ORION-11. So yes, we will be able to provide that data in the upcoming presentations. 9 is a much smaller study. So I would not read too much in that particular endpoint for ORION-9.

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Operator [50]

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The next question is from the line of Jay Olson with Oppenheimer.

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Jay Olson, Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst [51]

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I wanted to ask about your discussion with payers that you commented on earlier. I was wondering if you're considering any innovative approaches with payers such as performance-based reimbursement where payers may pay more or less depending on patients getting to goal?

And then as a follow-up, I just wanted to circle back on some of the comments you made about Europe, where I think you mentioned that all options are still on the table. I was wondering if that meant that you are, in fact, considering building a commercial infrastructure in Europe?

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Mark Timney, The Medicines Company - CEO & Director [52]

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Jay, thanks for the questions. With regards to the payers, as I said, the research is very clear for us, and they're very excited about the differentiated profile. It's fair to say, for us, all options are still on the table. It's very early within our research. As you say, as the data become available not only our outreach but inbound questions around inclisiran and how best to create access are leading us to really think very carefully about that.

And hence, to my earlier comment, that really has an impact on how we think about commercial planning and infrastructure going forward. That's not dissimilar to how we see it. Within Europe, it's a differentiated profile. You have an opportunity to do something very different, and all strategic options are still on the table for us.

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Operator [53]

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Our next question is from the line of Biren Amin with Jefferies.

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Biren N. Amin, Jefferies LLC, Research Division - MD and Senior Equity Research Analyst [54]

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Mark, I want to get your views on what you think continues to ail the PCSK9 class. Historically, the criticism has been that the class is priced too high at $10,000 to $13,000. But now that the price has been cut to less than $6,000, we still continue to see sales growth being flat. Yesterday, last night, for example, Amgen reported Repatha at about $80 million to $85 million, which is basically where they've been stuck at the last few quarters. So I just want to get your impression on what you think triggers the class and causes the trajectory that we've been expecting?

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Mark Timney, The Medicines Company - CEO & Director [55]

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Yes, thanks for the question. I think it's -- I think the issues of -- around pricing are well known and not for me to comment on. I think that what was a real positive, and certainly, what we see in our research in multiples is that you did hear on the call that there is increasing volume certainly coming from Repatha and Amgen. And I think that only speaks to the opportunity that we certainly see in the research.

I still keep anchoring back to the size of the treatment population that could benefit from a product like inclisiran, which as I talked about in these major markets, is around about 40 million patients. And therefore, for us, the opportunity is much larger. I think in order to take advantage of that opportunity, you have to do a number of things. You have to be able to clearly understand the research and find and define a clear patient population that ASCVD, secondary prevention population who would really benefit of getting additional LDL-C lowering but also the patient population you just struggle with adherence.

And that just increases the risk, especially around cumulative exposure to LDL-C. No other product can do the types of studies that we've been able to do around cumulative exposure. And that, for me, is -- it's a very exciting possibility. So as I do think about it, I think you've -- it's -- we obviously watch. We watch closely. It's not a competitive set that is really where we would anchor ourselves. Because we think of product profile, it's so differentiated and much more suitable to a chronic indication.

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Biren N. Amin, Jefferies LLC, Research Division - MD and Senior Equity Research Analyst [56]

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Got it. And then maybe a couple of follow-ups. I think the company has previously mentioned that you plan to target not just cardiologists, but also general practitioners. So I guess my question is, what percentage of eligible patients are treated by GPs compared to cardios? And what type of sales force would be necessary to cover GPs?

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Mark Timney, The Medicines Company - CEO & Director [57]

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It's a great question. I'll -- let me -- because I don't want to get too much into what would be a potential commercial strategy here, but it's fair to say that as you think about the management of our cardiovascular patient. The cardiovascular patient is managed within the GP setting.

There's no doubt that cardiologists have a clear and very important role to play. But that day-to-day management is clearly done through the GP side. So there's a real blend here. And I think both stakeholder groups are very, very important.

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Biren N. Amin, Jefferies LLC, Research Division - MD and Senior Equity Research Analyst [58]

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And then, I guess, on the question on the sales force size, you would need to cover the GPs?

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Mark Timney, The Medicines Company - CEO & Director [59]

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Yes, that's still -- we're still looking at that. It's very early for us to comment. I think in some way, shape or form, we will be engaging with that important stakeholder group, but how and what that looks like, it's still yet to be determined.

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Operator [60]

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The next question is from the line of Joel Beatty with Citi.

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Joel Lawrence Beatty, Citigroup Inc, Research Division - VP & Analyst [61]

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Can you go into a little more detail on which types of health care providers are most likely to be administering inclisiran? And then also, what types of settings administration is most likely to occur?

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Mark Timney, The Medicines Company - CEO & Director [62]

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Thanks for the question, Joe. We've got tremendous optionality around this. And again, it's very much part of our current work and current thinking. Obviously, a health care practitioner comes in many, many guises. I think that the setting and our focus is making the setting the one, which is most appropriate. Where obviously, we have the great benefit that a substantial amount of the patients are seeing their health care provider at least twice a year. So it's very consistent with the dosing schedule. But again, it comes back to how do we make this as simple and as accessible as possible for the patients to get it, and that's part of our planning.

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Joel Lawrence Beatty, Citigroup Inc, Research Division - VP & Analyst [63]

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And one follow-up. Can you talk about the potential timing of publications for the ORION Phase III datasets and if that could come at the same time as AHA?

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Peter Wijngaard, The Medicines Company - Executive VP & Chief Development Officer [64]

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We're working together with the principal investigators and the steering committee to get the data of all the 3 Phase III studies published as soon as we possibly can.

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Operator [65]

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We have reached the end of our question-and-answer session. And I'll turn the call over to management for closing remarks.

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Mark Timney, The Medicines Company - CEO & Director [66]

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Okay. Thank you, Rob, and thank you all for your questions. So we've successfully completed inclisiran's pivotal Phase III trials and presented exceptional safety and efficacy data for the ORION-11 study at the ESC conference in Paris. And we look forward to presenting ORION-9 and 10 studies at the AHA conference in November.

Inclisiran's highly differentiated profile and vast global market opportunity, coupled with The Medicines Company's full unencumbered commercial rights to inclisiran in all markets and market exclusivity to mid-2034 with expected extension into 2035, sets the stage for significant shareholder value creation.

And with that, I'll close the call, and wish you all a very good day. Thank you.

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Operator [67]

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This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.