Q3 2019 Earnings Call

Welcome to <unk> Corporation conference call to discuss its financial and operating results for the third quarter 2019.

Operator: Amarin Corporation's conference call to discuss its financial and operating results for the third quarter of 2019. This conference call is being recorded today, November 5th, 2019. I would like to turn the conference call over to Elizabeth Schwartz, Senior Director of Investor Relations of Amarin. Good morning.

The conference call is being recorded today November six 2019.

Well, let's turn the conference call over to Elizabeth Swartz Senior Director Investor Relations.

Good morning, please be aware that this conference call will contain forward looking statements that are intended to be covered under the safe Harbor provided by the private Securities Litigation Reform Act. Examples of such statements include but are not limited to our current expectations regarding our commercial and financial performance, including levels at the seat but.

Unknown Executive: Please be aware that this conference call will contain forward-looking statements that are intended to be covered under the safe harbor provided by the Private Securities Litigation Reform Act. Examples of such statements include, but are not limited to, our current expectations regarding our commercial and financial performance, including levels of the SEPA shipments and prescriptions, the SEPA product and licensing revenues, costs, and other commercial metrics, gross margin, expenditures, and the adequacy of our financial resources, our current expectations regarding regulatory reviews, including our expectations related to the upcoming advisory committee meeting regarding our REDUCE-IT SNDA and our expectations for the SEPA label expansion, our current expectations for scientific presentations, publications, and related timing thereof, our expectations that REDUCE-IT results could lead to a new treatment paradigm in the patient population studied, our plans in preparation for expanded promotion of the SEPA and related marketing positioning of potential, our plans to purchase additional products via the SEPA, our goals regarding the timing and scope of international expansion, and our current plans for Salesforce and other commercial expansion.

And then some prescriptions this product in licensing revenues costs and other commercial metrics gross margin expenditures adequacy ever financial resources, a current expectations regarding regulatory reviews, including our expectations related to the upcoming Advisory Committee meeting regarding our reduce it San Diego expected.

Patients for people label expansion, our current expectations for scientific presentations publications and related timing thereof, our expectations that reduce that results could lead to a new treatment paradigm and the patient population studied our plants in preparation for expanded promotion that the c., but I related marketing positioning a potential upsides to purchase additional.

I have to see our.

Our goals regarding the timing and scope with international expansion and our current plans for Salesforce. Another commercial expansion. These statements are based on information available to US today November 15, 2019, we may not actually achieve our goals carry out or plans or intentions or meet the expectation is disclosed in our forward looking statements actual results or events.

Unknown Executive: These statements are based on information available to us today, November 5, 2019. We may not actually achieve our goals, carry out our plans or intentions, or meet the expectations disclosed in our forward-looking statements. Actual results or events could differ materially, so you should not place under-reliance on these statements. We assume no obligation to update these statements as change. Our forward-looking statements do not reflect the potential impact of significant transactions we may enter into, such as mergers, acquisitions, dispositions, joint ventures, or any material agreements that we may enter into, amend, or terminate.

Could differ materially so you should should not place undue reliance any statements. We assume no obligation to update these statements that circumstances change a forward looking statements do not reflect the potential impact that significant transaction when they enter into such as mergers acquisitions dispositions joint ventures or any material agreements that we may enter into.

To amend or terminate for additional information concerning factors that could cause actual results to differ materially we see the forward looking statements section in today's press release and the risk factor section of our quarterly reports on Form 10-Q for the quarter ended September Thirtyth 2019. These documents have been filed with the FCC and our.

Unknown Executive: For additional information concerning the factors that could cause actual results to differ materially, please see the forward-looking statements section in today's press release and the risk factors section of our quarterly report on Form 10-Q for the quarter ended September 30, 2019. These documents have been filed with the SEC and are available through the Investor Relations section of our website at AmarinCorp.com. We encourage everyone to read these documents.

<unk> for the Investor Relations section of our web site at Amarin Corp. Dot com, we encourage everyone to read these documents. This call's intended for investors enamored is not intended to promote the you said the SEPA outside its approved indication. Please note that we're also providing slides to accompany this morning's call. These slides, which can be found on our website at <unk> camera.

Unknown Executive: This call is intended for investors in Amarin and is not intended to promote the use of a SIPA outside its approved indication. Please note that we are also providing slides to accompany this morning's call. These slides, which can be found on our website at AmarinCorp.com in the Investor Relations section under the subcategory Events and Presentations, summarize some of the key updates discussed on today's call. Finally, an archive of this call will be posted on the Amarin website, also in the Investor Relations section. I will now turn the call over to John Tharo, President and Chief Executive Officer of Amarin.

Dot com any investor relations section under the subcategory events and presentations summarize some of the key updates discussed on today's call. Finally, an archive of this call will be posted on the AMRAAM website also in the Investor Relations section I'll now turn the call over to John Thero, President and Chief Executive Officer Cameron.

John Tharo: Good morning. Thank you for listening to our comments today regarding Amarin's third quarter progress in this busy and exciting time. Amarin's growth was again positive in Q3. We reported record revenue levels, positive cash flow, and a strong financial position while adding to the breadth, depth, and experience of our commercial organization.

Good morning.

Thank you for listening to our comments today regarding airports third quarter progress in this busy an exciting time.

Amarins growth was again positive in Q3.

We reported record revenue levels positive cash flow and a strong financial position, while adding to the breadth depth and experience of our commercial organization.

We will comment further on such operating matters during this call.

John Tharo: We will comment further on such operating matters during this call. First, I will address our pending SNDA with the U.S. Food and Drug Administration in which we are seeking a cardiovascular risk reduction indication for Vasepa based upon the landmark results of the REDUCE-IT cardiovascular outcome study. The targeted BDUFA date for FDA action on this SNDA is December 28th, of this year. As part of its review, the FDA is planning an Advisory Committee meeting, or ADCOM, to be held on November 14. We are looking forward to the ADCOMM with cautious optimism. The EDCOM should be an opportunity to provide education and insights regarding the differentiated effects of Vasepa, the positive results to reduce it, and the potential to use Vasepa and its cardioprotective results to help millions of patients, based upon reduced results.

First I will address our pending S.N.D.A., where the U.S. food and drug administration in which we are seeking a cardiovascular risk reduction indication for Vascepa based upon the landmark results I wanted to reduce it cardiovascular outcome study.

The targeted but do for date for F.D.A. action on this at San Diego is December 20 Eightth.

This year.

As part of its review the F.D.A. is planning and Advisory Committee meeting or AD com to be held on November 14th.

We're looking forward to the I'd come with cautious optimism.

The AD com should be an opportunity to bright education.

And insights regarding the differentiated affects the placebo.

The positive results to reduce it and the potential to use but see buck and its cardio protective results to help millions of patients.

[noise] based upon reduce the results.

John Tharo: If all statin-treated patients in the United States with elevated triglyceride levels were treated with vasepa, we estimate that major adverse cardiovascular events such as stroke, heart attack, and cardiovascular death, Could an aggregate be reduced by $150,000 to $450,000 per year? We believe that this represents a tremendous potential health care improvement, not just for at-risk patients, but also for their families and society. Fewer major adverse cardiovascular events potentially translates into increased productivity and lower healthcare spending for these expensive events and subsequent patient rehabilitation.

If all started treated patients in the United States with elevated triglyceride levels were treated with the seep up we estimate that major adverse cardiovascular events, such as stroke heart attack in cardiovascular death.

Could an aggregate be reduced by 150000 to 450000 per year.

[noise], we believed that this represents a tremendous potential health care improvement not just for at risk patients, but also for their families and society.

Fewer major adverse cardiovascular events potentially translate into increased productivity and lower health care spending for these expenses events and subsequent patient rehabilitation.

As we have expressed previously it is common for the FDA, how bad columns in conjunction with first in class drug applications, such as our Sn D.A. purpose SEPA.

John Tharo: As we have expressed previously, it is common for the FDA to have ADCOMs in conjunction with first-in-class drug applications such as our SNDA for Vasepa. At the ADCOMM, we expect questions on a range of topics, including questions regarding REDUCE-IT trial design and about the demonstrated efficacy and safety of VASIPA. Some of these questions may pertain to potential labeling language. As is typical of Adcoms, we expect that some of these questions will be intentionally tough. We are a science driven company and we believe that we are ready for such potential questions, based upon our current understanding of FDA's focus and perspective. We expect the MDAC meeting to cover the following topics, among others related to our Reducit SNDA.

At the AD Com, we expect questions on a range of topics, including questions regarding reduce it trial design and at about the demonstrated efficacy and safety Opus SEPA.

Some of these questions may pertain to potential labeling language.

As is typical bad comps, we expect that some of these questions will be intentionally tough.

We are a science driven company and we believe that we're ready for such potential questions.

Based upon our current understanding of F.D. ace focus and perspectives.

We expect the M DAC meeting to cover the following topics among others related to our reduce it sndk.

John Tharo: These topics are consistent with topics typically explored at FDA Advisory Committee meetings, and cover matters consistent with Amarin's prior disclosures and available data. Review of patient population study and reduce it and how best to communicate this population to prescribers and other health care professionals, including considerations related to LDL cholesterol management on statin therapy, triglyceride levels as an identifier of cardiovascular risk, and other identifiers of high cardiovascular risk. Analysis of the degree of treatment benefit in the overall study population for the primary endpoint of the study, as well as in different reduced subgroups. For example, as previously disclosed, the established cardiovascular disease secondary prevention cohort, which, consistent with the trial design, represented approximately 70% of enrolled patients in REDUCE-IT, and had a high observed event rate, experiencing a numerically higher effect size, 27% relative risk reduction, than the high-risk diabetic primary prevention cohort, which, consistent with the trial design, represented approximately 30 percent of the enrolled patients and had a relatively lower observed event rate and experienced a 12 percent relative risk reduction in an exploratory analysis of this smaller subgroup.

These topics are consistent with topics typically explored after FDA Advisory committee meetings and cover matters consistent with Amarins prior disclosures in available data.

[noise] review, a patient population studies and reduce it and how best to communicate this population to prescribers and other health care professionals, including considerations related to LDL cholesterol management on Staten therapy, triglyceride levels isn't identifier cardiovascular risk and other identifiers of.

Hi, cardiovascular risk.

[noise] analysis of the degree of treatment benefit in the overall study population for the primary endpoint of the study as well as in different reducing subgroups. For example, as previously disclosed the established cardiovascular disease secondary prevention cohort, which consistent with the trial design.

Fine represented approximately 70% of enrolled patients and reduce it and had a high observed event rate experiencing a numerically higher effect size, 27% relative risk reduction.

Then the high risk diabetic primary prevention cohort, which consistent with the trial design represented approximately 30% of and enrolled patients and had a relatively lower observed event rate and experience a 12% relative risk reduction in exploratory analysis.

Oh, the smaller subgroup.

[noise] analysis of the degree of treatment benefit on specific study endpoints.

John Tharo: Analysis of the Degree of Treatment Benefit on Specific Studied Endpoints, in the different subgroups. For example, as previously disclosed, Beyond the primary endpoint and key secondary endpoint, seven secondary endpoints of different clinical relevance were achieved to varying degrees of impact and degrees of statistical significance in the order of sequential statistical testing within the pre-specified hierarchy, including myocardial infarction. Cardiovascular death and stroke.

In the different sub groups for example, as previously disclosed beyond the primary endpoint and key secondary end 0.7 secondary endpoints are different clinical relevance were achieved to varying degrees of impact and degrees Oh statistical significance.

In the order of sequential statistical testing within the pre specified hierarchy, including myocardial infarction.

Cardiovascular death and stroke.

[noise] analysis related to study conduct and data robust us.

John Tharo: Analysis related to study conduct and data robustness. For example, as previously disclosed, REDUCE-IT was a single clinical trial conducted based upon a special protocol assessment agreement, with the FDA and as is typical of all cardiovascular outcome studies. Related analysis are expected on the overall strength and limitations of the study data to support the indications sought, as described above, considering factors including, but not limited to, the use of mineral oil used in the study and questions explored in past FDA reviews and raised publicly since then over the plausibility of an interaction of the placebo with statin that some have argued could have led to reduced absorption of statin medication. We do not believe such an interaction occurred for reasons previously disclosed, among others.

Quality integrity and consistency.

For example, as previously disclosed reduce it was a single clinical trial conducted based upon a special protocol assessment agreement.

With the FDA and.

As is typical of all cardiovascular outcome studies related analysis are expected on the overall strength and limitations of the study data to support the indication sought as described above considering factors, including but not limited to the use of mineral oil.

Using the study and questions explored in past F.D.A. reviews, and raise publicly since then over the plausibility of an interaction of the placebo, which Dan. That's some have argued could have led to reduced absorption of staton medications.

We do not believe such an interaction occurred for reasons previously disclosed among others.

John Tharo: Consistent with the publication of reduced results in the New England Journal of Medicine. We believe FDA has assessed that even if plausible based upon indirect evidence of potential effect, That exploratory analysis.., indicates the effect, if any, of mineral oil on biomarker values such as LDL cholesterol values on the time to the primary endpoint is numerically small and unlikely to change the overall conclusion of treatment benefits. We also expect analysis on safety data and related risk-benefit considerations in light of the above.

Consistent with the publication of reduced results in the New England Journal of Medicine.

We believe F.D.A. has assessed that even if plausible based upon indirect evidence of potential effect.

That exploratory analysis indicates the affect your Fannie of mineral oil on biomarker values, such as LDL cholesterol values on the time to the primary endpoint is numerically small and unlikely to change the overall conclusion of treat.

And benefit.

We also expect analysis on safety data and related risk benefit considerations in light of via both for example, as previously disclosed overall safety findings and reduce it were generally consistent with product labeling and available data on the Omega three class.

John Tharo: For example, as previously disclosed, overall safety findings in REDUCIT were generally consistent with product labeling and available data on the Omega-3 class. More patients in the VACIPA group experienced an adjudicated event of atrial fibrillation or atrial flutter requiring hospitalization 24 hours or greater compared with patients in the placebo group. 3.1% versus 2.1%, and more patients experience any treatment emergent adverse event of atrial fibrillation or atrial flutter in the vasepa arm versus placebo. The incidence of fibrillation in atrial flutter was greater in the subset of patients with a previous history of atrial fibrillation or flutter, and the relative imbalance was numerically greater between arms in this subgroup compared with the imbalance in those patients without a previous history.

More patience and have a SEPA group experienced in adjudicated event of ATRIO fibrillation re drill flutter, requiring hospitalization 24 hours or greater compared with patients and the placebo group.

3.1% versus 2.1% in.

And more patients experienced any treatment emergent adverse event of ATRIO fibrillation right you have water in the SEPA arm versus placebo.

The incidence of fibrillation NHL flutter was greater in the subset of patients with the previous history or they drill fibrillation or flutter.

And the relative imbalance was numerically greater between arms in the subgroup compared with the imbalance in those patients without a previous history.

Additionally, more patients, but supergroup experienced an adverse event, a bleeding compared with patients in the placebo group.

John Tharo: Additionally, more patients in the placebo group experience an adverse event of bleeding compared with patients in the placebo group. Excluding hemorrhagic stroke, which was an adjudicated efficacy event. 482 patients, 11.8 percent, in the vasepa treatment arm experienced bleeding events compared to 404 patients, 9.9 percent, in the placebo treatment arm, in each case consistent with prior disclosure.

Excluding hematologic stroke, which was an adjudicated efficacy event.

482 patients, 11.8% Indevus SEPA treatment arm experience bleeding events compared to 404 patients 9.9% in the placebo treatment arm.

In each case consistent with prior disclosures.

So much discussion is likely to include consideration of disclosure of safety information to prescribers and patients.

John Tharo: Such discussion is likely to include consideration of disclosure of safety information to prescribers and patients, and also to consider the downstream effects typically associated with these adverse events, which in the case of atrial fibrillation and atrial flutter were generally lower on the placebo arm than the placebo arm with consideration of relative benefit risk. We cannot be sure that the same content, or more or less, will be presented or discussed as key topics at the MDAC meeting, in preparing for the FDA's EDCOM. We have held a series of mock adcoms in which we invited leading physicians and statisticians to challenge us and our advisors with questions, which the invited professionals believe could or should be asked at the actual EdCom. We believe we are ready for a successful ADCOM. Regarding potential labeling of a SEPA, Some panelists at the mock-ed comms have suggested that the language of the label should be relatively broad reflecting that educated healthcare professionals know their patients best and don't need a label to be unnecessarily prescriptive or restrictive. Other panelists have expressed a preference for having more detail in a label.

And also to consider the downstream affects typically associated with these adverse events, which in the case of atrial fibrillation nature of water, we're generally lower.

On the let's see bar than the placebo arm with consideration of relative benefit risk.

[noise], we cannot be sure that the same content or more or less will be presented or discussed as key topics at the m. DAC meeting.

And preparing for the F.D. is AD com [noise].

We have held a series of mock add comps in which we invited leading physicians and statisticians to challenge us in our advisors with questions.

Which they invited professionals believe could or should be asked at the actual ad com.

We believe we're ready for a successful ad com.

[noise] regarding potential labeling of a SEPA.

Some panelists that the mock add gums have suggested that the language the label should be relatively broad, reflecting that educated health care professionals no their patients best and don't need a label to be unnecessarily prescriptive or restrictive.

Other panelists have expressed a preference for having more detail in a label.

John Tharo: Some of this discussion has involved, for example, the degree to which reference to patient characteristics, patient age, cholesterol levels, and triglyceride levels should be in the label, and for the primary prevention patient. Some of the discussion has involved the degree to which patients need to have diabetes and to what other risk factors should be considered when selecting patients who might benefit from use of the drug, while opinions have varied regarding the levels of such details. The overall perspective of these mock adcoms has been that there is a meaningful cardiovascular risk reduction indication, which is applicable for vesipa. Again, we cannot be assured that the EDCOM on November 14th will parallel what we have heard at the mock EDCOMs regarding questions, feedback, or general support for the CEPA label expansion. And, as is typical, we don't yet know the identities of the panelists whom the FDA has selected for the EDCOM.

Some of this discussion has involved for example, the degree to which reference to patient characteristics patient age cholesterol levels and triglyceride levels should be in the label.

And for the primary prevention patients some of the discussion has involved the degree to which patients need to have diabetes into what other risk factors should be considered when selecting patients who might benefit from used to the drug.

While opinions have varied regarding the levels from such details.

The overall perspective of these mock Ed comps has been that there is a meaningful cardiovascular risk reduction indication, which is applicable for office depot.

Again, we cannot be assured the de Ed common November 14th well parallel while we have heard at the MCAD coms regarding questions feedback or general support for the SEPA label expansion.

And as is typical we don't yet know the identities of the panelist, whom the F.D.A. has selected for the AD com.

John Tharo: The team leading the presentation for Amarin will include the study's principal investigator, Dr. Deepak Bhat. In preparations for ADCOMS, there are briefing books prepared, first by the drug sponsor, in this case Amarin, and then by the FDA. After these briefing books are drafted, they go through a quality review process at the FDA, which includes, amongst other matters, redaction of any patient-specific information. Following this quality review process, an appropriate redaction of personal information.

The team leading the presentation for Amarin will include the studies principal investigator Dr. de park, but.

[noise] in preparations for Ed comps there are briefing books prepared first by the drugs sponsor in this case Amarin and then by the FDA.

After these briefing books are drafted they go through a quality review process at the FDA, which includes amongst other matters redaction of any patient specific information.

Following this quality review process inappropriate redaction, a personal information the F.D.A. makes the briefing books public.

John Tharo: The FDA makes the briefing books public. It is up to the FDA and not Amarin to make the briefing books public. Making the briefing books public typically occurs two days before the commencement of the EdConf.

It is up to the FDA and knotty amarin to make the briefing books public.

Making the briefing books public typically occurs two days before the commencement of the AD com.

We expect this process to be no different for the upcoming AD com for Vascepa.

John Tharo: We expect this process to be no different for the upcoming ADCOMM for VISIPA. As is typical, panelists at the EDCOM will be supplied the briefing book, and they may ask their own questions regardless of whether such questions are covered in the briefing books or not. In addition to the briefing books, both the sponsor and FDA will prepare slides to present to the invited panelists at the EDCOM. As is typical, Amarin will not see the FDA slides prior to their presentation at the EDCOM. In our mock ad comms, we have attempted to prepare for a range of potential questions beyond those which we most anticipate will be asked.

As is typical panelist at the AD com will be supply the briefing books.

And they may ask their own questions, regardless of whether such questions are covered in the briefing books or not.

In addition to the briefing books, both the sponsor and F.D.A. will prepare slides to present to the invited panelist at the AD com.

As is typical amarin will not see the F.D. slides prior to their presentation at the AD com.

In our mock add coms, we've attempted to prepare for a range of potential questions beyond those which we most anticipate will be asked.

[noise] recall that the reduce this study was designed under a special protocol assessment agreement with the FDA [noise].

John Tharo: Recall that the REDUCE-IT study was designed under a special protocol assessment agreement with the FDA. Further, before this important study was completed and unblinded. Amarin reached agreement with the FDA regarding the details of the Statistical Analysis Plan and the definitions of the clinical endpoint. These factors, combined with Amarin having collected final vital data on 99.8% of the patients studied, should, we believe, help mitigate some of the types of concerns often heard at adcoms pertaining to quality of data or differing views on methods of data analysis. While it is possible that FDA may ask Amarin additional questions in conjunction with its review of Amarin's SNDA. We have thus far responded to all of the FDA's questions and data requests.

Further before this important study was completed in unblinded.

Amarin reached agreement with the FDA regarding the details of the statistical analysis plan and the definitions of the clinical endpoints.

These factors combined with hammering, having collected final vital data I, 99.8% or the patient studied should we believe helped mitigate some of the types of concerns often heard at Ed coms pertaining to quality of data or differing views.

On methods of data analysis.

[noise], while it is possible that F.D. I may ask Cameron additional questions in conjunction with its review of Amarins Sndk.

We have thus far responded to all of the F.D. as questions and data requests.

John Tharo: As you know, it would not be constructive to our interactions with the FDA for us to disclose the details of all such interactions. And, during this review, all Amarin personnel with knowledge of such interactions have been in a closed-window period regarding public trading and shares of Amarin, and, of course, We have taken extensive steps to safeguard sensitive information. The outpouring of support Amarin has received from healthcare professionals, patients, investors, and other stakeholders has been overwhelming and gratifying. Approximately a hundred comments have been written to FDA Expressing their reasons for why basipa should be approved promptly for cardiovascular risk reduction, And, many doctors and patient advocacy groups have volunteered to help Amarin with the ADCOM. Reading these letters, many of which reflect personal experiences, is inspiring.

As you know it would not be constructive to our interactions with the FDA for us to disclose the details of all such interactions.

And during this review all amarin personnel with knowledge of such interactions have been in a close window period regarding public trading in shares of Amarin and of course.

We have taken extensive steps to safeguard sensitive information.

The outpouring of support Ameren has received from health care professionals patients investors and other stakeholders has been overwhelming and gratifying.

Approximately 100 comments have been written to F.D.A. expressing their reasons for why but SEPA should be approved promptly for cardiovascular risk reduction.

And many doctors and patient advocacy groups have volunteered to help amarin with the AD com.

Reading these letters many of which reflect personal experiences is inspiring.

John Tharo: If you are interested in reading them, they are publicly available at bit.li forward slash, 36YPKEV, As you know, various medical societies have already, in advance of FDA approval, changed their treatment guidelines or otherwise provided notice recognizing the cardioprotective effects of Ococibuntethyl, the brand name of which is Visepa, beyond statin treatment in patients with triglyceride levels of 135 mg per deciliter or greater. These are leading organizations in cardiology, endocrinology, and lipidology, including ADA, ESC, EAS, AHA, and NLA. It is notably inspiring to see ESE, which is the European Society of Cardiology, and EAS, which is the European Atherosclerosis Society, recognize the value of vasepa in their guidelines, as vasepa is not yet available in Europe. And we appreciate getting the support of NLA, the National Lipid Association, as the multifactorial effects of Vasepa extend beyond lipid management. Each of these medical societies recognizes the significant cardiovascular risk which exists beyond current standards of care for cardiovascular risk management, including cholesterol management.

[noise], if you're interested in reading them. They are publicly available at bit dot ally forward Slash three six why P.T.K. E V.

[noise] as you know various medical societies have already in advance of FTC approval change their treatment guidelines or otherwise provided notice recognizing the cardio protective effects of of course, a bunch Ethel the brand name, which is the SEPA beyond.

Stat and treatment in patients with triglyceride levels of 135, megs per deciliter or greater.

These are leading organizations in cardiology, endocrinology, and Lipidology, including 80, A.S.C., Yeah, Yes ha and Mandalay.

It is notably inspiring to see E. S C, which is the European Society of Cardiology and here, Yes, which is a European atherosclerosis society recognize the value of a SEPA in their guidelines as of a SEPA is not yet available in Europe .

And we appreciate getting the support of Emily the National Lippitt Association.

As the multi factorial effects of a SEPA extend beyond lippitt management.

Each of these medical societies recognizes the significant cardiovascular risk, which exists beyond current standards of care for cardiovascular risk management, including cholesterol management.

Because the AD com will be conducted during the trading day on November 14th.

John Tharo: Because the ADCOM will be conducted during the trading day on November 14th, for reasons which I hope are obvious. We intend to ask NASDAQ to halt trading in Amarin shares until the EDCOM is complete and its results are communicated by us. Please do not read anything positive or negative into such trading halts, other than our desire to ensure a level playing field.

For reasons, which I hope are obvious.

We intend to ask NASDAQ to halt trading and amarin shares until the AD com is complete and its results are communicated by us.

Please do not read anything positive or negative into such trading halt other than our desire to ensure a level playing field.

John Tharo: The FDA makes a live broadcast of its ADCOMS available. In addition to pursuing U.S. regulatory approval of Visepa for cardiovascular risk reduction. Our international initiatives remain on track.

The FDA makes a live broadcast of it's Ed comes available.

In addition to pursuing U.S. regulatory approval of the SEPA for cardiovascular risk reduction.

Our international initiatives remain on track.

John Tharo: For Europe, we plan before the end of this year to submit an application seeking approval of VASIPA for the first therapy in Europe to address the substantial residual cardiovascular risk that persists beyond cholesterol management as studied in reduced... In Canada, it is our understanding that Health Canada is progressing on its review. In the Middle East, we continue to anticipate further approvals of the CEPA.

For Europe , we plan before the end of this year to submit an application seeking approval of a c., but for the first therapy in Europe to address the substantial residual cardiovascular risk that persists beyond cholesterol management as studied in reduce it.

In Canada. It is our understanding that health, Canada is progressing on its review.

In the Middle East, we continue to anticipate further approvals of a SEPA.

John Tharo: In China, in the clinical study of Visepa being conducted by our partner, the pace of patient enrollment has been increasing, positioning that biomarker-focused study for potential completion in 2020. Coincidentally, starting on the weekend following the ADCOMM for Visepa, the American Heart Association, or AHA, is holding its annual scientific session. At that meeting, which this year will be in Philadelphia, there were seven known presentations which pertain to VASIPA. We are pleased to support these scientific presentations. We believe that these presentations include valuable insight. However, in our view, none of the data being presented is needed for the review of the SNDA we have submitted to the FDA.

In China in the clinical study of asleep of being conducted by our partner the pace of patient enrollment has been increasing positioning that biomarker focused study for potential completion in 2020.

Okay.

Coincidentally, starting on the weekend following the AD Com pharmacy bump the American Heart Association or AJ, it's holding its annual scientific sessions.

At that meeting, which this year will be in Philadelphia, there were seven known presentations with pertained to the SEPA.

We are pleased to support these scientific presentations, we believe that these presentations include valuable insights.

However, in our view none of the data being presented is needed for the review of the S.N.D.A., we have submitted to the FDA.

Because not everyone can attend AJ at the end of their program Amarin intends to conduct a webcast in which leading physicians will summarize information presented at the AJ conference, which they believe are potentially applicable to have a SEPA and the patient population we seek to it.

Mike Cobb: Because not everyone can attend AHA, at the end of their program, Amarin intends to conduct a webcast in which leading physicians will summarize information presented at the AHA conference, which they believe are potentially applicable to VASIPA and the patient population we seek to address. I now hand the discussion over to Mike Cobb, our CFO, to cover Amarin's recent financial results. When he is done, I will add a few comments for further perspective, and then, with the time remaining, we will respond to some questions. Thanks, John.

Address.

I now hand, the discussion over to Mike called our CFO to cover Amarins recent financial results.

When he is done I will add a few comments for further perspective, and then where the time remaining we will respond to some questions Mike.

Thanks, John as mentioned that the start of this call both our Form 10-Q , and our press release issued today discussing Amarins Q3 results can be found on Amarins website.

Mike Cobb: As mentioned at the start of this call, both our Form 10-Q and our press release issued today discussing Amarin's Q3 results can be found on Amarin's website. They include details which go beyond the highlights we will cover in this morning's call. Our third quarter total revenue was $112.4 million. This was a record high for Amarin and an increase of 103% over the same period in 2018. We recorded total revenue of $286.5 million for the nine months ended September 30th, 2019. This also was a record high for Amarin and an increase of 89% over the same period in 2018. This nine-month revenue also well exceeds the 12-month total for 2018. As expected, nearly all of our total revenue consisted of product revenue from Visepa sales in the United States. The increase in net product revenue was nearly all attributable to increases in new and recurring prescriptions of Azepa. Such prescription levels reached record highs for Visepa during the reported three and nine month periods of 2019.

They include details, which go beyond the highlights we will cover in this morning's call.

Our third quarter total revenue was $112.4 million.

This was a record high for Amarin, and an increase of 103% over the same period in 2018.

We recorded total revenue of $286.5 million for the nine months ended September Thirtyth 2019.

There's also was a record high for Amarin and an increase of 89% over the same period in 2018.

This nine month revenue also well exceeds the 12 month total for 2018.

As expected nearly all of our total revenue consisted of product revenue from the super cells in the United States.

The increase in that product revenue was nearly all attributable to increases in new and recurring prescriptions of SEPA.

Such prescription levels reached record highs for C., but during the reported three and nine month periods of 2019.

Mike Cobb: The net selling price of this Vipa varies modestly from quarter to quarter and was slightly higher in Q3 2019 than the same quarter of 2018 but remained relatively unchanged for the nine months ended September 30, 2019 as compared to the same period in 2018. The estimated number of normalized total Visepa prescriptions, based on data from Symphony Health and IQVIA, for the three months ended September 30, 2019, were approximately 865,000 and 787,000, respectively, compared to 458,000 and 417,000, respectively, in the three months ended September 30, 2018. These estimates reflect increases of 89% in the third quarter of 2019 over the same period of 2008. As a reminder, Amarin recognizes product revenue based on sales to regional wholesalers and specialty pharmacy providers in the United States, or collectively, its distributors or its customers, and not based on prescription levels estimated by Symfony Health or IQVIA.

The net selling price of a SEPA various modestly from quarter to quarter and was slightly higher in Q3 2019, then the same quarter of 2018, but remained relatively unchanged for the nine months ended September 32019, as compared to the same period in 2018.

The estimated number of normalize total to see prescriptions based on data from Symphony Health and I QVC.

Three months ended September Thirtyth 2019 were approximately 865007 hundred 87000, respectively compared to 458400 17000, respectively and the three months ended September Thirtyth 2018.

These estimates reflect increases of 89% in the third quarter of 2019 over the same period of 2018.

As a reminder, amarin recognizes product revenue based on sales to regional wholesalers and specialty pharmacy providers in the United States or collectively it's distributors or its customers and not based on prescription levels estimated by Symphony health or Acuvue.

Mike Cobb: We reference the data from Symfony Health and IQVIA in response to requests for such information from investors. Channel inventory, meaning the amount of a SEPA held at independent distributors, varies from quarter to quarter based on the ordinary course of business. At the end of September, it was estimated to be within the normal business range of approximately two to three weeks of a SEPA supply on-handed distributors. Such channel inventory is separate from inventory held by Amarin.

We referenced the data from Symphony Health and I to via in response to request for such information from investors.

[noise] channel inventory, meaning the amount of a c., but how did independent distributors varies from quarter to quarter based on the ordinary course of business.

At the end of September it was estimated to be within the normal business French of approximately two to three weeks of a super supply on hand at distributors such channel inventories separate from inventory held by Amarin.

Mike Cobb: In addition to net product revenue, licensing revenue recognized by the company were $1.1 million and $600,000 in the nine months ended September 30, 2019 and 2018, respectively, related to the amortization of milestone payments and other factors impacting revenue recognition for licensing fees under agreements for the commercialization of Vizipa outside the United States. Amarin's guidance for 2019 total revenue remains unchanged. For 2019, we anticipate reaching between $380 million and $420 million in total revenue. We do not intend to provide quantified guidance for 2020 until Visepa's label is known and our launch of Visepa for cardiovascular risk reduction has commenced. John will in a moment discuss our preparations for that lunch.

In addition to net product revenue licensing revenue recognized by the company were $1.1 million.

And $600000 and the nine months ended September 32019, and 2018, respectively related to the amortization of milestone payments and other factors impacting revenue recognition for licensing fees under agreements for the commercialization of asleep outside the United States.

[noise] Amarins guidance for 2019 total revenue remains unchanged for 2019, we anticipate reaching between $380 million and $420 million in total revenue, we do not intend to provide quantified guidance for 2020 until the Seapass label is known and our launch of to see if for Cardiome.

Ask your risk reduction has commenced John well in a moment discuss our preparations for that lunch.

Mike Cobb: Our gross margin on product sales for the 9 months ended September 30, 2019 was 77%, up from 76% in the same period of 2018. Our spending levels have also increased, but at growth rates which are considerably slower than our revenue growth. Selling General and Administrative, or SG&A, expense for the nine months ended September 30, 2019 were $227.6 million, an increase of 55 percent over the same nine-month period in 2018. This increase is due primarily to increased commercial and other promotional spend for expansion following successful reduce-it results, which were announced on September 24, 2018, including costs for expanding of the Amarin sales team to 400 sales representatives at the beginning of 2019 and some recent further expansion to support the assumed launch of the SEPA for a cardiovascular risk reduction indication after the December 28th, 2019 PDUFA date.

Our gross margin on product sales for the nine months ended September 32019 was 77% up from 76% in the same period of 2018.

Our spending levels have also increased but a growth rates, which are considerably slower than our revenue growth.

Selling general and administrative or SGN <unk> expense for the nine months ended September Thirtyth 2019 were $227.6 million, an increase of 55% over the same nine month period in 2018.

This increase is due primarily to increased commercial and other promotional spend for expansion following successful reduce it results.

Try announced on September 24th 2018.

Including cost for expanding of the Amarin sales team to 400 sales representatives at the beginning of 2019 and some recent further expansion to support the assumed launch of the shape of for cardiovascular risk reduction indication.

After the December 28, 2019 PDUFA date.

We anticipate that extra day spending will increase further as we further prepare for and then assuming FDA approval launch for C., but for the cardiovascular risk reduction indication currently under review by the FDA.

Mike Cobb: We anticipate that SG&A spending will increase further as we further prepare for and then, assuming FDA approval, launch the SEPA for the cardiovascular reduction indication currently under review by the FDA. Research and Development, or R&D, expense for the 9 months ended September 30, 2019 was $23.3 million, a decrease of 47% compared to the same period in 2018. This decrease is primarily due to timing of completion of the reduced cardiovascular outcome study and related costs. Under U.S. GAAP, Amarin reported a net loss of $3.5 million in Q3 2019, or a basic and diluted loss per share of $0.01. This net loss included $8 million in non-cash, stock-based compensation expense. Amarin reported a net loss of $24.5 million in the third quarter of 2018, or basic and diluted loss per share of $0.08. This net loss included $6.7 million in non-cash, stock-based compensation expenses.

Research and development or R&D expense for the nine months ended September Thirtyth 2019 was $23.3 million a decrease of 47% compared to the same period in 2018.

This decrease is primarily due to timing of completion of the reducing cardiovascular outcome study and related costs.

[noise] under U.S. gap Amarin reported a net loss of $3.5 million in the third quarter of 2019 or basic and diluted loss per share of one cents.

This net loss included $8 million and noncash stock based compensation expense.

Amarin reported a net loss of $24.5 million in the third quarter of 2018 or basic and diluted loss per share of eight cents. This.

This net loss included $6.7 million and noncash stock based compensation expense.

Excluding noncash gains or losses for stock based compensation non-GAAP . Adjusted net income was $4.5 million for the third quarter of 2019 or non-GAAP adjusted basic and diluted earnings per share of one cents compared to non-GAAP adjusted net loss of 17 point.

Mike Cobb: Excluding non-cash gains or losses for stock-based compensation, non-GAAP-adjusted net income was $4.5 million for the third quarter of 2019, or non-GAAP-adjusted basic and diluted earnings per share of $0.01 compared to non-GAAP-adjusted net loss of $17.8 million for the third quarter of 2018, or non-GAAP-adjusted basic and diluted loss per share of $0.06. As of September 30, 2019, we had cash and cash equivalents and restricted cash of $677.1 million, an increase of $426.4 million from December 31, 2018. As of September 30, 2019, we also had accounts receivable net of $103.6 million, all of which was current, and inventory of $54.6 million. The increase in our reported cash at September 30th, 2019 includes both the results of our previously announced equity financing and cash flow positive operations for the quarter. Based on our current plans, we believe that our cash resources are sufficient to support the requirements for a successful launch of a SEPA without the need for additional funding. For the three months ended, September 30th, 2019, excluding cash inflow from financing.

$8 million for the third quarter of 2018, or net non-GAAP adjusted basic and diluted loss per share of six cents.

As of September Thirtyth, 2019, we had cash and cash equivalents unrestricted cash of $677.1 million, an increase of $426.4 million from December 31st 2018.

As of September Thirtyth 2019, we also had accounts receivable net of $103.6 million, all of which was current and inventory of $54.6 million.

The increase in our reported cash at September Thirtyth 2019 includes both the results of our previously announced equity financing and cash flow positive operations for the quarter.

Based on our current plans, we believe that our cash resources are sufficient to support the requirements pretty successful launch of a seat, but without the need for additional funding.

For the three months ended September Thirtyth 2019, excluding cash inflow from financing Amarin was cash flow positive, reflecting growing and revenue levels.

Mike Cobb: Amarin was cash flow positive reflecting growing in revenue levels. Expense Management and the Timing of Inventory Purchases, For the nine-month period ended September 30, 2019, further excluding cash flow associated with all forms of financing and R&D payments, most of which relate to the REDUCIT study and associated regulatory affairs activities, and excluding payments made in preparation for expansion upon positive REDUCIT results, such as increasing Visepa inventory levels. The company was $27.6 million net cash flow positive.

<unk> expense management, and the timing of inventory purchases.

For the nine month period ended September Thirtyth 2019, further excluding cash flow associated with all forms of financing in R&D payments, most of which relate to the reduce it study and associated regulatory affairs activities and excluding payments made in preparation for expansion upon positive.

Reduce it results such as increasing the seep inventory levels. The company was $27.6 million net cash flow positive.

[noise] Amarin anticipates, increasing its cash outflows in the fourth quarter of 2019 and in 2020 to prepare for enlarged for sleep in the U.S. for the cardiovascular risk reduction indication we are seeking.

Mike Cobb: Amarin anticipates increasing its cash outflows in the fourth quarter of 2019 and in 2020 to prepare for and launch for SEPA in the U.S. for the cardiovascular risk reduction indication we are seeking. Such added cash outflows will, in addition to expanding Amarin's sales force size and promotional initiatives, also include spending for further medical education and investment in the growth of ASEPA inventory levels. At the start of 2019, Amarin projected that it could spend $50 to $75 million more in 2019 for building inventory levels and testing the capacity of our suppliers than would be needed to support our then current revenue forecast. While some of these increased purchases have been used to support higher-than-initially-guided revenue levels, some of these incremental orders for inventory growth are anticipated to be delivered in late 2019 for payment either late this year or early next year such that cash flow from operations may be negative in Q4 2019 despite anticipated higher revenue levels.

Such added cash outflows well in addition to expanding amarin sales for size and promotional initiatives also include spending for further medical education and investment in the growth of a c., but inventory levels.

At the start of 2019, amarin projected that it could spend $50 million to $75 million more in 2019 for building inventory levels and testing the capacity of our suppliers then would be needed to support our then current revenue forecast.

Some of these increased purchases have been used to support higher than initially guided revenue levels.

Some of these incremental orders for inventory growth are anticipated to be delivered in late 2019 prepayment either late this year or early next year, such that cash flow from operations, maybe negative in Q4 2019, despite anticipated higher revenue levels.

As of September Thirtyth, 2019, Amarin had approximately 357.2 million American depository shares or adss and ordinary shares outstanding 28.9 million common share equivalents of series a convertible preferred shares outstanding and approach.

Mike Cobb: As of September 30th, 2019, Amarin had approximately 357.2 million American Depository Shares, or ADSs, and Ordinary Shares Outstanding, 28.9 million Common Share Equivalents of Series A Convertible Preferred Shares Outstanding, and approximately 16.3 million Equivalent Shares Underlying Stock Options at a Weighted Average Exercise Price of $6.21, as well as 9.4 million equivalent shares underlying restricted or deferred stock units. I will now turn the call back over to John for closing remarks. Thank you, Mike.

It's probably 16.3 million equivalent shares underlying stock options at a weighted average exercise price of $6.21.

Well, it's 9.4 million equivalent shares underlying restricted or deferred stock units.

I will now turn the call back over to John for closing remarks, John .

Thank you Mike.

John Tharo: We are planning for success regarding an expanded label for Visepa. As previously expressed, We intend to increase the size of Amarin's U.S. sales force from 400 to 800 sales representatives for the launch of Vaseepa for cardiovascular risk reduction, assuming FDA approval. In Q3 2019, we hired or internally promoted nearly all of the sales management team needed to support this growth. Included in this expansion is the addition of Joe Balzer as Senior Vice President of National Sales. Joe is very experienced with a track record of success in leading teams which are much larger than what we are growing to initially.

We are planning for success regarding an expanded label for office depot.

As previously expressed.

We intend to increase the size of Amarins U.S. Salesforce from 400 to 800 sales representatives for the launch of us see buffer cardiovascular risk reduction assuming FDA approval.

In Q3, 2019, we hired or internally promoted nearly all of the sales management team needed to support this growth.

Included in this expansion is the addition of Joe balls are as senior Vice President of National sales.

Joe is very experienced with a track record of success and leading teams which are much larger than what we are growing to initially.

He has surrounded himself with good people, including retention of the sales leadership team responsible for getting us to this stage and who will now manage sales for significant portions of the U.S. under Joe's overall responsibility.

John Tharo: He has surrounded himself with good people, including retention of the sales leadership team responsible for getting us to this stage, and who will now manage sales for significant portions of the U.S. under Joe's overall responsibility. In Q3, we continued to witness increased prescription rates, from physicians called on by our veteran Visepa sales representatives and by our newest sales representatives. The sales representatives we added near the beginning of this year continue to contribute faster than we initially anticipated. Their progress adds to our confidence as we move to hire and train additional waves of new sales representatives. In recent months, we received over 10,000 job applications for the sales positions we are seeking to hire.

In Q3, we continued to witness increased prescription rates.

From physicians called on by or better in the SEPA sales representatives and by our newest sales representatives.

The sales Representatives, we added near the beginning of this year continued to contribute faster than we initially anticipated.

Their progress adds to our confidence as we move to hire and train additional waves of new sales representatives.

[noise] in recent months, we received over 10000 job applications for the sales positions, we're seeking to higher.

We recently added some of these incremental sales representatives.

John Tharo: We recently added some of these incremental sales representatives. Many of our recent hires are referrals from our existing sales representatives. We are confident that we will be able to recruit and train qualified people to support our planned expansion for launch of VACIPA in early 2020 based upon the cardiovascular risk indication we are seeking and assumed approval of VACIPA on or before the December 28th PDUFA date. Other preparations for this launch beyond Salesforce expansion are also progressing, including Managed Care Outreach and Education. While Managed Care has generally viewed Vestipa to be reasonably priced, Recently presented third-party analysis showing that Facepa is cost-effective will aid our activities to ensure that Facepa is available and reimbursed when prescribed to help at-risk patients.

Many of our recent hires are referrals from our existing sales representatives.

We are confident that we will be able to recruit and train qualified people to support our planned expansion for launch of a SEPA in early 2020 based upon the cardiovascular risk indication, we are seeking and assumed approval of a SEPA on or before the December 28 <unk>.

Good day.

[noise] other preparations for this launch beyond Salesforce expansion are also progressing including managed care outreach and education.

Well I imagine care has generally viewed the c., but to be reasonably priced.

Recently presented third party analysis, showing that SEPA is cost effective will aid our activities to ensure that we'll see but is available and reimbursed when prescribed to help at risk patients.

We look forward to potentially more comprehensive analysis regarding the cost effectiveness of a c., but to be presented later this month at the scientific sessions of AJ.

John Tharo: We look forward to potentially more comprehensive analysis regarding the cost effectiveness of this, to be presented later this month at the scientific sessions of AHA. Before beginning the Q&A portion. I will also touch upon the summary judgment ruling issued by the court hearing our ANDA litigation in Nevada on October 29. The litigation is proceeding towards the previously announced trial date of January 3rd. If this litigation goes to trial... It will be a trial held by a judge, not a jury trial. We are quite pleased with the court's summary judgment ruling. Seeking summary judgment at this stage and end of patent litigation is a common approach for generics to seek an early end to litigation, and for both parties. Seek to limit the scope of issues at trial.

Before beginning in the queue in a portion of the school I will also touch upon the summary judgment ruling issued by the court hearing our Anda litigation in Nevada on October 29.

The litigation is proceeding towards the previously announced trial date of January 13th.

If this litigation goes the trial.

It will be a trial held by a judge not a jury trial.

We are quite pleased with the courts summary judgment rolling.

Seeking summary judgment at this stage and end up patent litigation is a common approach for generics to seek an early into litigation.

And for both parties to seek to limit the scope of issues that trial.

The judge ruled against the into Filers summary judgment motion that sought to end the case at this early stage in their favor.

John Tharo: The judge ruled against the Indefilers summary judgment motion that sought to end the case at this early stage in their favor, and ruled more in Amarin's favor to limit the scope of issues that remain for trial. See this ruling as strengthening our position in the litigation, by eliminating from the case several potential lines of generic argument. As such, The ruling strengthens Amarin's position should it be determined that case settlement is in the company's best interest. We look forward to litigation progressing. Due to the complex nature of patent litigation, we refer investors to the court's order and other court documents for further detail, which can be located through the FAQ section of our Investor Relations website. We also refer investors to the Risk Factors section. Today's Form 10-Q for detail. We intend to continue to vigorously defend our patents, but don't intend to go into more detail on that today. With that, we conclude our prepared comments and would like to open the line to some questions. Operator?

And rule more in amarins favor to limit the scope of issues that remain for trial.

[noise], we see this ruling as strengthening our position in the litigation.

By eliminating from the case several potential lines of generic argument.

As such the ruling strengthens amarins position should it be determine that case settlement isn't the company's best interest.

We look forward to litigation progressing.

Due to the complex nature of patent litigation, we refer investors to the courts order and other court documents for further detail.

Which can be located through the F. Q section of our Investor Relations website.

We also refer investors to the risk factor section in today's Form 10-Q for detail.

We intend to continue to vigorously defend our pads, but don't intend to go into more detail on that today.

With that we conclude our prepared comments and we'd like to open the line to some questions operator.

Operator: At this time, we'll be conducting a question and answer session. If you'd like to ask a question, please press star 1 from your telephone keypad, and a confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key.

Thank you.

At this time will be conducting a question answer session. If you like to ask a question. Please press star one from your telephone keypad and a confirmation telling when indicate your line is in the question Q.

You mean press star too late to move your question from here.

Presenting speaker equipment, and maybe necessary to pick up your handset before pressing the star here.

One moment, please hold the poll for questions.

Operator: One moment please while we poll for questions. Thank you. The first question today comes from the line of Yasmeen Rahimi with Roth Capital Partners. Please proceed with your question. Hi, team.

Thank you first question today comes from the line of Yasmeen Rahimi with Roth Capital Partners. Please proceed with your.

Hi team. Thank you John Yeah, well prepared remark.

Yasmeen Rahimi: Thank you, John, for your thoughtful, prepared remarks in regards to outcome procedure and topics. You mentioned in your prepared remarks that some of the questions might be tough versus others. I would love to hear your thoughts on which of the topics you could consider more tough. And then the second question is in regards to Evaporate, we're excited to look at the data at AHA. Maybe you can tell us what percentage progressionally you expect to see and what is the purpose of this study? Is it just helping us mechanistically support the SIPA, or do you plan to utilize this data into the label? And thank you again for taking my question.

I'm procedure and topic.

You mentioned in your prepared remarks, the question might be <unk> other I'd love to hear your thought.

What's at the topic, you could consider well what Tom <unk> second question in regards to operate like that it to look at the date I eat say, maybe you can tell us what person is progressing nicely.

You back to see what is the purpose of this study is that just helping your typically support deep out or do you where you utilize.

The label and thank you again, you can request.

Yeah.

John Tharo: I mean, thanks for the questions. Good morning.

The questions a good morning.

John Tharo: With respect to adcom questions, the nature of an adcom is to bring in advisors to the FDA, and these are smart people and they all want to be heard, so there is sort of a natural adversarial tone that goes into those questions. You can see in adcoms for other products that people often ask tough questions and at the end they may have more different views than the questions that they ask, but they ask pointed questions and try to get to answers on topics. I think we have good responses, I think there are very good responses to what we think will be the likely question at the meeting, but my purpose of mentioning that there are likely to be tough questions is to, in some respects, state the obvious, and for those who are potentially attending or listening to the adcom, not to take out of context difficult questions, that's the nature and purpose of an adcom is to be challenged on the data.

With respect to AD com is ER and the nature of an AD com.

He is to bring in advisers to the FDA leaders smart people and they all want to be heard. So you know there is a natural adversarial tone that goes into you know those questions. You can see that allows for other products people often ask questions at the end they may have more different.

And then the question that they asked but are you know what they've got pointed questions try to get to answered on topic.

I think we have good responses I feel very good responses do what we think will be the likely question at the meeting, but I like the purpose of mentioning that are likely to be tough questions is too.

In some respects state the obvious into <unk>.

So are those who are potentially attending or listening to the yet.

Not to take out of context difficult question. That's the major urban purpose of that is to be challenged on the data. We think we've been challenged data.

John Tharo: We think we've been challenged on the data in various medical conferences, we think we've been challenged on the data in reviews by publications like the New England Journal of Medicine and Journal of American College of Cardiology, and I believe and we've seen that the deeper people dig into the data, the stronger the data gets. So, you know, tough questions, in reference to tough questions, is really just a contextual piece, but there's nothing that we're walking into the adcom fearing as being a, you know, real gotcha that we're not prepared, you know, to answer.

Sorry medical conferences.

On the data and reviews by publications like the knowing what girl of medicine under over Cardiology, and I believe and we've seen a deeper people dig into that was probably the data can get so a couple questions as referenced don't questions. It really is in technical piece.

There's nothing that we're walking into that I'm hearing anything it yeah.

GAAP here that we were not prepared to answer.

John Tharo: With respect to Evaporate, that's an investigator-initiated study. You know, the mechanism of action of MOSFETA is multifactorial. As you may recall, there was a study done in Japan called the CHERI study. In the CHERI study, you use cosplenoic acid on top of statins compared to statin alone. And, you know, in that study, which was a, you know, decent size, only used about 200 patient, you know, study, it showed that the use of EPA, cosplenoic acid, on top of statin versus statin alone, essentially doubled the.., prevalence of plaque regression, you know, versus not having the EPA at it. Techniques for assessing, you know, plaque have continued to improve. They're not perfect, but they've continued to improve.

With respect to evaporate, that's the investigator initiated study.

You know the mechanism of action.

It was even though it's multifactorial as you may recall it was study done a Japan called Cherish study and the Terry So they use.

Yes.

On top of stands compared to stand alone and getting that study.

So I know you about 200 patients to go study showed that the use of Ah EPA.

On top of standard stand alone essentially.

Don't doubled the.

So prevalent plaque regression, you know versus not having the EPA added.

Techniques for assessing.

You know class and continue to improve their not for their contagion through.

John Tharo: We've got a number of investigators who are very interested in looking at, you know, plaque and trying to better understand the, you know, plaque regression that may be occurring with EPA. And so we're looking forward to all seven presentations at AHA, including the one relative to evaporate. That being said, the SNDA has been submitted. The SNDA includes all the data that we believe is necessary to support the approval of our drug. And, you know, as is the case for many breakthrough therapies, I'm sure that the data that we have generated with VASIPA will generate or encourage research in lots of different areas, you know, going forward as people try to dissect and further understand, you know, different mechanisms. That type of scientific research is terrific, but we don't believe that the evaporate results, as interesting as they may be, are necessary for the approval of the drug.

A number of investigators who are very interested and looking at Oh plaque and trying to better understand.

Plaque regression that maybe occurring with EPA and so we're looking forward to the all seven presentations that AJ, including the one relative to Oh evaporate.

That being said the San Diego has been submitted Ah, yes, since you and D.A. with all the data we believe is necessary.

To support the approval of our dog and you know as is the case for many breakthrough therapy. So I'm sure that the data that we have generated when the season will generate are encouraged research and lots of different areas, you're going forward as people try to.

Sac and further understand a in a different mechanisms.

That type of scientific research is it cryptic, but we don't believe that they've got great result, so interesting is that may be are necessary or the approval.

Thank you team and best of luck to me not that you need.

Yasmeen Rahimi: Thank you, team, and best of luck next week. Not that you need it.

John Tharo: Thank you. I believe in science but I'll always take luck. Thank you.

Thank you.

I believe in science to always take lot. Thank you.

Michael Yee: The next question is coming from the line of Michael Yee with Jefferies. Please proceed with your question. Hey, John, congrats on a good quarter and progress so far.

The next question, it's coming from the line of Michael Yee with Jefferies. Please proceed with your question.

Hey, John Congrats on a good quarter in progress so far two questions for you one was related to a <unk> commentary around <unk>.

John Tharo: Two questions for you. One was related to the commentary around the ADCOM and how you think about a label. It does seem that a lot of the discussion questions you mentioned are perhaps around labeling and population. So, could you just level set our expectations as to what you expect for what a broad population or broad label is? Is that something like PCSK9 or would you expect that it's possible commentaries around primary and secondary prevention or even TRIG levels? And then, as it relates to the second question, can I confirm that you did get a preview briefing document in advance already and that you've gone through that? And that the comments you've made are many of the topics that are in that briefing document, including your comments around mineral oil. Thanks so much.

And how you think about a label it does seem that a lot of discussion questions. You mentioned are perhaps around labeling and population. So could you just almost that our expectations as to.

Then one.

Back for what he brought population are broad label is is that something like PCSK nine or would you expect.

That it's possible commentaries around primary and secondary prevention or even trick levels and then as it relates to.

Second question can I confirm that you did get a preview briefing document it didn't Bam ceridian that you've gone through that not the comments you made are many of the topics that are in that briefing document, including your comments around mineral oil. Thanks, so much.

Michael Yee: Michael, good morning. Thanks for the questions. With regard to documentation that we've seen, we've had numerous questions from the agency, as you might expect in an FDA review, over the multiple months since it was submitted in March. We've had various other forms of communication. Briefing books at this point in time are not final, and I think we've got a pretty good sense of what might be in it from a draft perspective, but they're not final, and I wouldn't want to put a stronger period after something that's not a final document at this stage.

Good morning, Thanks for your questions.

With regard to a in documentation that we've seen.

We had a numerous questions from the agency as you might expect a net gain review.

Oh, yeah multiple months since it was submitted and in March.

Yeah, we've had various other forms of communication.

You know briefing books at this point in time or not.

[noise] vinyl and.

Got it.

Pretty good sense, what might be in it from a graph perspective, but they're not final and Oh I wouldn't while.

[laughter] stronger.

[noise] period after something that's not a a final document so is at this stage.

With regard to the AD com.

John Tharo: With regard to the ADCOM and questions, I do think that there are likely to be a number of questions which could be interpreted as questions that would pertain to labeling. That being said, that doesn't mean that those will be the only questions. As it pertains to labeling, from a macro perspective, the studies were statin-treated patients with elevated triglycerides and other cardiovascular risk factors. How that is best described to physicians and patients, there are varying opinions on, and those varying opinions get into does it make sense to quantify LDL, does it make sense to quantify triglyceride levels, does it make sense in the label to get into definitions of established cardiovascular disease and diabetes and other risk factors. Does age matter?

And questions I I do think that there are likely to be a number of questions, which.

You could be interpreted as questions that would pertain to labeling.

That being said that doesn't mean that those will be the only questions and you know as it pertains to labeling you know on on a go from a macro perspective, what we study were stat treated patients Oh, we had elevated triglycerides another cardiovascular risk factors.

You know how that is best describe to physicians and patients are you know there are varying opinions on and Oh, there's varying opinions.

In June .

And does it make sense to quantify.

LDL, they make sense quantified triglyceride levels.

Makes sense the label to go get engine definitions of establish cardiovascular disease and diabetes and other other risks factors.

And does does age does age matter.

There's the Oh, a long list of entry criteria, that's a use for a.

Amin Fadia: There's a long list of entry criteria that's used for a... Clinical Outcome Study, and you use those in outcome studies to ensure a consistent result across both arms of the study. And then, you know, this is not a unique topic. You get into the FBA considerations as to how is that information from an outcome study, you know, best communicated to physicians and patients. And there are always varying views on that. Some folks would prefer to have it be really left to the judgment of physicians and knowing that physicians understand their patients the best. And if you describe, you know, patients being at risk, the docs will know who that is. And others think that maybe an indication ought to be, you know, more detailed than that.

Clinical outcome study and Ah you, though that outcome studies to ensure a consistent results across all of the study and then or.

This is not a unique topic you get into the that's got to be a considerations as to how is that information from an outcome study you know best communicated to physicians and patients.

And there are always varying views on that Oh, I prefer to have it to be really left to the judgment of physicians and.

Knowing that physicians understand the agents the best and if you describe you know it's being at risk ER Docs will know that is and.

Others things that maybe a an indication ought to be more detail than that or we've not entered into labeling. It was just for voice data, we not entered into labeling discussions with the FDA is no. It is difficult not enter engines.

Amin Fadia: We've not entered into labeling, you know, this is for avoidance of doubt, we've not entered into labeling discussions with the FDA. It is difficult to not enter into those labeling discussions after an outcome is complete, you know, but, you know, it's somewhat inescapable, you know, during an outcome for views not to be shared on topics that could inform FDA's thinking relative to, you know, labeling considerations, whether the FDA chooses to follow those, the advice of the committee or not in those matters, you know, is, you know, always remains to be seen.

Those labeling discussions after till after that.

It's complete.

But it's somewhat inescapable you know during an AD com or views not to be shared on topics that.

And for F.D.A. thinking relative to labeling.

Considerations, whether the FDIC chooses to fall those are invited these bites of the committee or not and those matters.

Is there always remains busy.

Got it Oh, yes.

John Tharo: Got it, thanks. Our next question comes from the line of Amin Fadia with SBB Larrick. Please proceed with your question. Hi, good morning. Congrats on the nice quarter.

Our next question comes from the line of I mean, I'd, yet with SPV. Larry. Please proceed with your question.

Hi, good morning, rats, and the nice quarter.

I had to questions regarding the topic that you mentioned John the dots to you know what might come up at the outcome.

Amin Fadia: I had two questions regarding some of the topics you mentioned, John, with regards to you know what might come up at the ad comp. Firstly, with regards to the patient population, can you talk to the minimum TG level of patients that were enrolled in the REDUCES study? I believe that the SBA was for 200 TG level, but you enroll patients all the way from 135.

Firstly with regards to the patient population can you talk to be the minimum P.G. level of patients that wasn't going to give us a study I believe the DSP was for 200 TV lever, but do you enjoy patients all the way from 135.

Can you talk to sort of some of the considerations that me be involved and thinking about.

John Tharo: Can you talk to sort of some of the considerations that may be involved in thinking about, What patients the SEPA would be prescribed for from a labeling perspective and also what percent of patients in the trial were in that 135 to 200 range. And then separately, you know, regarding the interaction between mineral oil and statin. [inaudible] You know, you've sort of expressed some of your views on the company website, but I also wanted to understand, do you believe that, It is possible to do some sort of a drug-drug interaction study between mineral and statins. And then do you think it would be informative in, you know, clarifying that interaction? and you know what type of time and resources may be required to do something like this. Thank you.

What patients the female would be upside for from a labeling perspective, and how it so what percent of patients the trial well in that 135 to 200 range.

And then separately you know regarding the.

Interaction between mineral oil in Stockton.

You do you sort of expect some of your views.

Oh on the company website, but I also wanted to understand do you believe that.

It is possible to do some sort of food drug drug interaction study between them at all in Stockton.

And then do you think it would be in for made as a in you know clarifying that interaction and you know what type of time. Indeed, this is maybe to glad to do something like that.

Thank you.

Oh my time for the questions.

John Tharo: Thanks Amin for the questions. With respect to the patient's population, THE END, The study was designed to use triglycerides as an identifier risk, and this gets a little bit tricky, and I think you know this, but just for the benefit of others, we were not trying to demonstrate that lowering triglycerides alone provides all the benefit from the study. So we've got triglycerides, which I think are really pretty well established as a marker of risk, but as a modifiable risk factor, you know, still known in the CFA as multifactorial effects of which one is triglyceride lowering. When we went into the study, reduce it, we went into the study with a, statistical plan and analysis that assumed, you know, lots of different things. We assumed that obviously all the patients were going to be on statins, all the patients had elevated triglycerides. We assumed things like, you know, 70% of them were going to be secondary prevention, 30% are going to be primary prevention.

With respect to the patient population.

The.

The study was designed to use triglyceride and identifier risk and though this gets a little bit tricky and I think you know is for the benefit of others. Oh, we were not trying to demonstrate that lowering triglycerides alone or revise all the benefit.

Oh from the study so we've got a Ah triglyceride I think are really well established as a marker of risk but.

The modifiable risk factor.

Still unknown in the <unk>.

As multifactorial effect with one is triglyceride lowering.

When we went into the study.

Reduce it when you went into the study with a.

Statistical plan analysis that assumed lots of different things. We assume that are obviously all of these are really understands all these elevated triglycerides, assuming things like you know 70% of them, we're going to be a secondary prevention, 30% Itll be primary prevention. We also had assumptions are modeling.

Or the.

The sort of number of patients are the balance of patients who might have triglyceride at different levels, but we try to get ER, we try to try to get a spectrum of data based on different triglyceride levels.

John Tharo: We also had assumptions in our modeling for the sort of number of patients or the balance of patients who might have triglycerides at different levels so that we would try to get a spectrum of data, you know, based upon different triglyceride levels. When we began the study, the, threshold was triglycerides 115 above with a 10% allowance. So the the lower boundary was effectively 135.

We are again the study or the.

Threshold was triglycerides Ah 115 about with a 10% allowance so they are.

Let me.

<unk> boundary was effectively 135 or when you enroll patients in this study there's a.

John Tharo: When you enroll patients in the study, there's a marker that people have at the beginning of the study when they get enrolled, you know, then they go through a washout and randomization period, and then there's another marker at the measure of their triglycerides at the end of that, and, you know, where they're actually beginning to receive, you know, placebo therapy or placebo, and, you know, during that phase, some patients had triglycerides that went up and some down, like if we had some patients who had trigs at the beginning of the study in the, you know, around the low 80s in terms of, you know, triglyceride levels. During the conduct of the study, we found that early on, sort of at the midway of enrollment, we found that a greater proportion of the patients enrolled in the study than what we had been targeting, you know, had triglyceride levels below 200 mg per deciliter, such that as we looked at our enrollment, we sort of got to the stratification that we wanted of patients with trigs below 200 fairly early on and didn't have enough patients, in our view, against what we had originally forecast of patients with trigs above 200, and at that point in time, we switched to enrolling only patients with trigs above 200, but of course continuing to treat and monitor those patients, you know, with trigs, you know, below 200.

Marker that people have or beginning of the study when they get a enrolled and then they go through a.

Wash out and randomization period, and then there is a.

No there marker of the marriage measure their triglyceride the end of that and Ah you know, where they're actually beginning to receive a super therapy or.

Well see ball and during that phase some patients had triglycerides well some down like that we had some patients who I've tried pretty big is study.

The Oh and around the low eightys in terms of Ah triglyceride levels.

During the conduct of the study.

We found that early on.

Midway enrollment we found that are a greater proportion of the patients enrolled in this study than what we had been targeting high triglyceride level below 200 begun front desk leaders such that as we looked at our enrollment we sort of got to the stratification that we wanted to patients betrayed low to watch.

And.

Fairly early on and it didn't have enough patients in our view against what we had originally.

Forecast of patients they trade above 200 and at that point in time, we switched to enrolling only patients. So we trade above 200, but of course, continuing trees and monitor those patients.

Weve Trxs Ah you know below 200 at the end it probably doesn't really matter because the results were consistent across the triglyceride.

John Tharo: At the end, it probably didn't really matter because the results were consistent across the triglyceride levels, and there's been some data out there which shows, you know, cardiovascular risk as it relates to triglyceride levels, which shows that, your cardiovascular risk really begins to increase, you know, with trig levels, sort of in that 70 to 80, you know, mgs per deciliter range, and then goes up. And, you know, doesn't go down, but sort of plateaus between the 150 and 200 mgs per deciliter range.

Levels and there's been some data out there, which shows a cardiovascular risk as it relates to triglyceride levels, which shows that you're cardiovascular risks really begins to increase I O. We treat levels are going 70 to 80 Megs per deciliter range, and then goes up and Ah you know.

Does it go down but sort of plateaus between the 150 in 200 Megs per deciliter range. So essentially a you know all patients or whether it's 135 Mboe a day or you know 115 above EUR 200 above all had elevated triglycerides and elevated a cardiovascular risk.

John Tharo: So, essentially, you know, all the patients, whether it's 135 and above, or 150 and above, or 200 and above, all had elevated triglycerides and elevated, you know, cardiovascular risk. And, you know, based upon this other data that I'm referring to, you know, the elevation of risk isn't all too different for patients who are, say, at 150 versus 200, because the risk is high for both, but has plateaued a bit. There were, About 10% of the patients in the study who had triglycerides between the The 135 and 150 range, the number, you know, after treatment with VASIPA, you know, below 150 increased. But in terms of at the beginning of the study, that's about what it was. And I forget the exact split above and below 200, but I think it's somewhere around 50-50.

Based upon this other data I'm, referring to you know the elevation or rescue isn't all two different for patients who were saying I want to see versus 200.

The rest is high for both but has a has plateaued of it there were Ah.

About 10% of the patients in the study who had triglyceride or between they.

Or 135, and 150 a range number after treatment with the seep Ah you know below 150 increase but in terms of at the beginning in the study about what it was and I forget the exact what above and below 200, but I think it's somewhere.

Sure.

The but that's a you know that in the I actually actually maybe closer to 60% or the a about 200 a group, but again the results were.

John Tharo: But that's, you know, that's in the, actually, maybe closer to 60% for the above 200 group. But again, the results were, you know, consistent across the 150 to, excuse me, the 135 to 150, the 150 to 200, and the 200 and above. You know, and that, you know, and that brings people into the focus in on the multifactorial effects of VASIPA, you know, which, you know, includes. Lots of things that we've talked about in the past, and it brings up the earlier question on evaporate, which is studying one of those multiple mechanisms related to potential plaque regression, which goes beyond plaque stability, et cetera. With respect to mineral oil, You're right, we have a Frequently Asked Questions section on our website.

You know consistent across the 152.

You know what 35 to 150 the ER maybe.

The one that you do wider than the a and the 200 and above you know and that you know that brings people into the August and on the multi factorial back Susie.

Yeah, which you know includes.

And I'm talking about in the in the path and brings up the earlier question on evaporated just studying one of those multiple mechanisms so related to.

Ration.

Goes beyond you know plaque stability and Ah I cetera, with respect to mineral mineral oil you're right. We haven't frequently asked question section on our website I will remind people that the.

John Tharo: I will remind people that the controversies that some third parties have tried to create on this particular area are driven off of biomarker changes. And those biomarkers at the beginning of the study were intentionally not primary or secondary endpoints of the study, including, you know, that all the patients enrolled in the study, you know, needed to have LDLs, you know, below 100, in our case, you know, had the mean LDL levels of 75, that, you know, regression, the mean was to be expected on certain of those biomarkers.

The controversies that's a sales from third parties have a you know trying to create on this particular area are driven a lot of biomarker changes and Ah you know those biomarkers at the beginning of this study we're intentionally not primary or secondary endpoints in the study.

We they were we'd already done biomarker based study, but you know based upon the design of the study.

Including a you know that all the patients or.

Enrolled in this study I'm pleased to have LDL. So you know below 100 in our case, a young and ER beat me to LDL levels 75 that you know regression to the mean was to be expected on certain of those biomarkers.

John Tharo: And throughout the course of the study, the data monitoring committee had access to data relative to the placebo arms of other studies, not using mineral oil, and in high risk patient populations were able to observe the, LDL changes and distributions of those changes in those other studies, at least in our view, and the data monitoring committee didn't raise issue with it either, the results in our placebo arm were very consistent with what we saw in those other studies. You know, at this point in time, you know, doing an additional drug-drug interaction study, we did a bunch of those as part of this, you know, clinical program that's been going on now for over a decade, you know, with the FDA relative to, you know, interaction with the placebo and lots of different drugs.

And Ah you know throughout the course of this study the data monitoring committee had access to data relative to the placebo arms of other studies done not using mineral oil and in high risk patient populations were you able to observe.

The.

LDL changes and distributions of those changes in those other studies and or at least in our view and the data monitoring.

He didnt raise their short with either a the results in our policy warm are very consistent with what we saw and those are all their studies you know at this point in time.

Doing a additional drug drug interaction study, we did a bunch of those as part of this you know when they go forward rather than going on now or over a decade or you know with yeah, Jay relative to your interaction to the simple and lots of different drugs at this point in time, Yeah, we have outcomes data the.

Outcomes data data is filing or Boston.

John Tharo: At this point in time, you know, we have outcomes data. The outcomes data is fairly robust. The inconsistent and going off and doing some form of other study in animals or trying to be predictive, we don't think would end up providing any meaningful added value to what we're doing. This has been looked at in lots of different ways and while we don't think that the mineral oil has any impact, I think a lot of people have concluded and we believe, as I stated, that analysis from the FDA, to the extent we're aware of it, has concluded similarly that if it has any effect, that that effect is very small.

The inconsistent and going off and doing a you know some warmer weather.

So study.

In animal or probably running predictive, we don't think and providing any meaningful added value to what were what we're doing you know this has been looked at and lots of different ways and why we don't think Meanwhile has any impact.

I think a lot of people have a who didn't we believe as I stated that the analysis from the FDA I guess do so we're aware of it. This concludes generally that Ah Ah. If it has any effect that effect is is very small I know, we're sort of time I, we didnt get some questions from investors are.

John Tharo: I know we're sort of out of time. We did get some questions in from investors. I think we've answered most of the one that we didn't was about other research and development beyond the SIPA. You know, we're going to get approval in the U.S. here hopefully first. That's our focus with the timelines that we've laid out. We're going to have the European submission in. Hopefully, we'll make advancements in Canada and elsewhere.

He asked most in the one that we Didnt was about other research and development or beyond but SEPA, you know where I get approval in the U.S. here hopefully earth, that's our focus or with the timelines or that we've laid out over another European Commission and we a woman.

Investments in the Cana and elsewhere.

After we get through the approval in the U.S., we've got a very talented R&D team, who will reserve for some of the idea that they've up or the that I halted in the path then we'll come back with some indication as to what we're going to be you're working on that but right now there's.

John Tharo: After we get through the approval in the U.S., we've got a very talented R&D team who will resurface some of the ideas that they've, that I've halted in the past, and we'll come back with some communication as to what we're going to be, you know, working on next. But right now, there's nothing larger that we could be working on than what we're doing with VISIPA, and we want to ensure that we provide that's the appropriate focus. So we'll get back to you in the future relative to what we might be working on, you know, beyond VISIPA. But VISIPA's pretty big, so let's get that right.

Nothing larger that we could be working on than what we're doing with the FIFA and we want to ensure that we provide the pro rate.

Okay, so well get back to you a in the future relative to what we might be working on your beyond a disease.

Pretty big so, let's let's get that right.

John Tharo: With that, I think we've usurped the time that we had set out for this meeting. I know others wanted to ask questions, but you also have to get on to other matters as well. So, again, thank you for your interest. Look forward to providing additional updates, and hopefully we'll have, you know, some celebration, not just after Vietnam, but particularly, you know, on or around the PDUFA date as we are looking for a way that will not just help Samaritan, but in particular will lead to the use of VISIPA to help hopefully, you know, millions of patients. Thank you.

With that I think we bought a insert the time that we had set up is being I know what they wanted to ask questions. But are you also have to get on to other matters as well. So I. Thank you for your interest.

Forward and providing additional updates.

We will have a you know some celebration not just haven't yet on the particularly hotter around the up the date or we are looking for a label that are just help Sam right, but in particular will lead to the use of the people to help us hopefully millions of patients. So thank you.

Thank you [laughter] today's call has concluded. Thank you for your participation you may now disconnect your lines at this time.

Operator: Thank you. Today's call has concluded. Thank you for your participation. You may now disconnect your lines at this time.