Ionis Pharmaceuticals Inc (IONS) 2010 Q2 法說會逐字稿

Welcome to Isis Pharmaceuticals second-quarter financial results conference call.

Leading the call today from Isis is Dr.

Stan Crooke, Isis Chairman and CEO.

Dr.

Crooke, please begin.

First of all, apologies, everyone.

There seems to have been some trouble with the phone connection.

I just need to make sure that Lynne is on the call.

Lynne?

Madge, can you try to make sure that there are other speakers on the call?

Stan, I'm here.

Thank you.

Well, again, I apologize for the problems with the call.

Good morning, and thank you, everyone, for joining us on today's call to discuss our second-quarter financial results.

Joining us on today's call are Lynne Parshall, COO and CFO; Beth Hougen, Vice President of Finance; Kristina Lemondtis, Director of Corporate Communications.

Kris, will you read the forward-looking statement?

Sure, Stan.

Good morning, everyone.

A reminder to everyone that this webcast includes forward-looking statements regarding Isis's business, the financial outlook for Isis as well as Regulus, its majority owned subsidiary, and the therapeutic and commercial potential of Isis' technologies and products in development.

Any statement describing Isis' goals, expectations, financial, or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement.

Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and the endeavor of building a business around such drugs.

Isis' forward-looking statements also involve assumptions that if never materialized or proved correct could cause its results to differ materially from those expressed or implied by such forward-looking statements.

Although Isis' forward-looking statements reflect the good-faith judgment of its management, these statements are based only on facts and factors currently known by Isis.

As a result, you are cautioned not to rely on these forward-looking statements.

These and other risks concerning Isis' programs are described in additional detail in Isis' annual report on Form 10-K for the year ended December 31, 2009, and its most recent quarterly report on Form 10-Q, which are on file with the SEC.

Copies of these and other documents are available from the Company.

And with that, I will turn the call over to Lynne to review our financial results.

Thanks, Kris.

We continue to make progress for the first half of 2010, highlighted by our announcement last week of additional positive data on mipomersen.

We're now on track to file an NDA early next year to bring mipomersen to our first patient population.

These are patients with severe risk who have no therapeutic alternatives.

We hope that mipomersen will be the therapeutic alternative that will help them lead longer, healthier lives.

As usual, I will assume that you've read the details of our second-quarter financial release in our press release, but I would like to cover a few of the highlights now.

Of course, I will be happy to take questions at the end of the call.

We had a pro forma net operating loss of $17.1 million for the first half of 2010.

This result reflects a slight decrease in revenue and an increase in expenses compared to the same period last year.

We expected the reduction in revenue, as it comes from the end of amortization periods for collaborations that were ending in accordance with their terms.

The higher expenses in the first half of the year were also anticipated, and mostly due to an increase in activities related to the ongoing mipomersen Phase 3 program, including work to complete the Phase 3 study, NDA preparation, and preparation to manufacture for mipomersen launch.

We expect our mipomersen expenses to continue at this level in the second half of the year as we continue to progress towards our initial regulatory filings for mipomersen and continue clinical activities to support our next filings, as well as product enhancements.

In addition to our mipomersen progress, the second highlight of 2010 so far was the initiation of our new collaborative relationship with GlaxoSmithKline.

We are extremely pleased that so early in the relationship, we've achieved our first milestone in the collaboration, resulting not only in the new development candidate added to our pipeline, but also a $5 million milestone payment.

When we completed this transaction, we told you that it represented upside to our guidance.

As promised, we're now formally amending our 2010 financial guidance to reflect the positive financial impact of this new partnership.

Our previously announced financial guidance not only included predicted revenue from existing partnership.

Our updated guidance reflects revenue and expenses associated with our new relationship with GSK, and the $1.9 million from Regulus resulting from their recent deal with sanofi-aventis.

Our new guidance for 2010 of a pro forma net operating loss in the mid to high $40 million range represents a 10% to 20% improvement over our initial NOL projection.

Additionally, we've improved our year-end cash guidance by $25 million and now expect to end the year with over $450 million in cash.

So let me just solidify the business picture in the first half of the year and its consequences.

We added GSK as a new partner and received $35 million in upfront fees that we will amortize into revenue over five years.

We've earned our first milestone payment under the collaboration of $5 million that we will recognize in the third quarter.

BMS advanced their PCSK9 inhibitor into clinical trials, from which we earned a $6 million milestone payment in the first quarter, and we extended our collaboration with BMS for an additional two years to continue to build the PCSK9 franchise with follow-on products.

Our partners at Regulus completed a very attractive transaction with sanofi-aventis, which further strengthens Regulus' cash position and ensures that Regulus is fully financed.

We also earned $1.9 million in sublicensing revenue in the second quarter from this transaction.

Our partners at Achaogen initiated Phase 2 clinical trials with their novel aminoglycoside antibiotics, from which we earned a $2 million milestone payment in the second quarter.

Achaogen will pay us half of this milestone in equity.

While we don't book revenue for equity in private companies, historically, this has been an attractive source of financial upside for us as our satellite companies continue to succeed.

As you can see, the breadth and depth of our technology platform and our relationships result in a fairly steady stream of opportunities for financial benefit.

This is the value of our unique asset base and our unique business strategy.

With that, I will now turn the call back over to Stan.

Thanks, Lynne.

As Lynne outlined, we've made significant advances throughout our pipeline in the first half of this year.

The most recent and the most important advance is the completion of the Phase 3 program for mipomersen.

That program will support our applications for first marketing approval.

Last Wednesday, we announced that we had completed the Phase 3 program for that initial filing.

All four Phase 3 trials have been completed.

All four Phase 3 trials were positive.

The results of all four trials showed significant reductions in all forms of bad cholesterol.

And the safety profile was consistent in each trial, and the side effects are easy to monitor and straightforward to manage.

I'm going to divide my comments on mipomersen in two parts.

First, I'm going to describe the immediate future for mipomersen.

Obviously, this is the most important thing to focus on, and then I will discuss the work that we're doing to enhance mipomersen's profile and expand the market over time.

Our first priority is to bring mipomersen to patients who desperately need it.

These are patients with severely high levels of bad cholesterol despite all that medicine has to offer today.

They are at extremely high cardiovascular risk.

In just the USA and Europe, Genzyme estimates that there are about 30,000 of these patients.

When we talk about these patients, we frequently divide them into two groups -- homozygous familial hypercholesterolemia, or homozygous FH, and severe.

But in truth, they all have the same profile.

Most have already had a cardiovascular event, and they are all doing everything they can to get their bad cholesterol down.

These patients are young.

The average age, for example, in the severe trial that we reported last Wednesday was 51 years old, and most of the patients have had multiple cardiovascular events.

These patients all know that they are likely to die because of a heart attack or stroke or some other cardiovascular event.

These patients have two options.

They can get apheresis, a time-consuming and uncomfortable process, much like dialysis, that mechanically removes cholesterol from their blood, and that costs approximately $100,000 a year.

Their other option is to wait for their next heart attack or other cardiovascular event.

In the two Phase 3 trials we conducted in these very sick patients, mipomersen reduced their LDL cholesterol on average more than 100 milligrams per deciliter.

That could translate into a greater than 50% reduction in their cardiovascular risk.

These are the patients we plan to treat first with mipomersen.

We've also shown that mipomersen has a consistent safety profile.

Side effects are now well characterized, easy to identify and straightforward to manage.

These patients are mostly taken care of by a group of very sophisticated and specialized physicians called lipidologists.

As you heard from Dr.

Cromwell at our annual meeting, the doctors who are treating these patients recognize the clear need for mipomersen and are truly excited to offer mipomersen treatment to their patients.

They feel that management of the mipomersen safety profile is consistent with the management of many other therapies that these patients undergo.

The data and the treating physicians tell us that in this patient population, the benefit to mipomersen far outweigh the risks.

Just to recapitulate, we've identified a needy patient population.

We've identified the sophisticated and focused treating physician group, and we've developed a drug that meets their needs.

Now let's talk about the long-term opportunities for mipomersen.

The first step is to bring mipomersen to the patients who need the drug the most.

The rest of the plan that we conceived years ago and are now well along in implementing, is to expand our experience with mipomersen and continue to enhance its ease of use, so that we can expand the types of patients to whom it's offered.

We're making great progress in these plans.

And we believe that these efforts will have immediate and long-term benefits in all the patient populations we're talking about.

Now that work includes doing a better job of training doctors, nurses, and patients about how to administer a subcutaneous drug and what to expect.

It includes allowing patients to dose themselves and to select a preferred site for injection.

It includes giving patients a choice to dose themselves and about where they dose.

We've already developed simple measures to reduce injection-site reactions like cold or hot compresses.

We're also allowing doses to be reduced in the patients who have rapid and profound responses to mipomersen.

Finally, moving along with our plan to provide patients the choice of daily dosing, so we're moving toward daily dosing or three times a week dosing, or, of course, once a week.

Our goal is to provide patients as many options as possible so physicians can individualize mipomersen treatment for patients.

So by the time of the first launch, we will already have a number of approaches available that will enhance long-term compliance.

So in summary, we have a new medicine that consistently brings significant benefit to very sick patients.

Mipomersen lowers all forms of bag cholesterol, not just LDL.

We're focused initially on treating the very needy patients who have no other options.

Those patients are being treated by a specialized group of physicians, many of whom have participated in mipomersen trials and know it well.

Mipomersen has a consistent and manageable side effect profile.

The bottom line is we know that mipomersen is a great option for these patients.

Furthermore, we have a plan, and we know what we need to do to enhance mipomersen and expand into additional market opportunities in the long term.

And we're on track, we're on track, for our first filings in the first half of 2011.

Before I leave mipomersen, just a brief reminder.

We look forward to the full presentation of the heterozygous FH Phase 3 study at the European Society of cardiovascular Medicine, or Cardiology, in Stockholm, in a few weeks, in fact, on September 1.

Of course, our success goes beyond mipomersen and our cardiovascular franchise.

We and BMS initiated a Phase 1 study on our other lipid lowering drug, PCSK9.

We're also pleased with the progress that we have made with BMS and are happy to be extending the collaboration another two years as we continue to work collaboratively on a follow-on compound to extend the longevity of what we hope will be an exciting commercial franchise.

Additionally, we are completing Phase 1 studies on our CRP inhibitor and preparing to initiate Phase 2 studies.

We added a selective triglyceride-lowering drug with a drug that targets APOCIII, and our first clotting drug, targeting Factor XI to our pipeline.

Both of these drugs are progressing nicely toward clinical trials.

So, we continue to be -- significant progress on the drugs in our cardiovascular pipeline, and we believe this will yield important advances for patients and generate great value for our shareholders.

Our metabolic franchises had significant interest from the scientific community, as evidenced by our presence at the ADA this year, where we represented the Phase 2 data of our PDB1b drug, and the Phase 1 data from our glucagon receptor drug.

In addition, we and our partners presented data from five other programs, demonstrating that antisense drugs can approach novel targets to treat metabolic diseases, including obesity.

We made progress on our other key therapeutic areas, neurodegenerative rare diseases and cancer.

In our neural program, we initiated Phase 1 studies on our SOD1 drug for the treatment of amyotrophic lateral sclerosis, or ALS.

This study is the first step in demonstrating the applicability of antisense drugs to treat severe neurodegenerative diseases.

We've initiated the development of our first new drug to treat a severe rare disease with our partner, GSK, expanding the breadth of this therapeutic area.

This event also marked the successful achievement of our first milestone associated with this preferred partner relationship.

And in cancer, OncoGenex and Teva initiated the first study in a broad Phase 3 program for OGX-011 in patients with prostate cancer.

OncoGenex also reported promising Phase 1 data for the study evaluating OGX-427 in patients with cancer at the ASCO meeting this summer.

We look forward to the advancement of this drug into Phase 2 studies later this year, and we're also close to initiating the first Phase 2 study of eIF-4E drug.

Our plan is to add another exciting cancer drug to the pipeline this year, which would bring our cancer pipeline to five.

In addition, our partners at Excaliard recently completed and reported the first of their Phase 2 studies evaluating EXC 001 in patients with elective abdominal surgery.

Using multiple measurements of wound healing and scarring, they reported that treatment with EXC 001 shows statistically significant reductions in scarring.

With a large and expanding pipeline, we spent some time the first half of this year outlining the strategic context for our drugs that are in development through a series of pipeline calls.

We hope that you found those calls beneficial.

We did receive a lot of positive feedback, and the transcripts of those calls are still accessible on our website in our current advances page.

In conclusion, I just want to reiterate some of the exciting near-term activities to look forward to.

We and Genzyme continue to advance mipomersen for a diverse market in patients with severe high cholesterol and extreme cardiovascular risk.

Clearly, as we progress, we will keep you informed.

We'll also report the full data from the heterozygous FH Phase 3 study of mipomersen on September 1 at ESC.

We'll report the two most recent trials at medical meetings and we'll be determining where that will happen in the next little bit.

We plan to initiate Phase 2 programs on our CRP and eIF-4E drugs.

Excaliard expects to complete and report the remaining two Phase 2 studies on EXC 001.

iCo announced that they have clearance to begin a Phase 2 study in patients with diffuse diabetic macular edema, and we hope that begins soon.

And finally, we plan to add two to three new drugs to our pipeline in core therapeutic areas before the end of the year.

Now I want to thank all of you for joining us today, and we will open up the call for questions.

Madge, if you can set us up, please.

(Operator Instructions).

Salveen Kochnover, Collins Stewart.

Thanks for taking my question.

In terms of mipomersen, how confident are you that you will be able to file for the severe indication in the first half of next year?

And if this does not occur, is your regulatory strategy in terms of timelines for the outcome study going to change?

We're absolutely confident.

We have four positive Phase 3 trials, and we're working hard on the registrations.

Great.

And then just timelines for initiation of the outcome study?

We're getting -- the outcome study will -- has -- there's a lot more work to do on getting ready for the outcome study.

The next step is to initiate our long-term or longer-term trials that provide the safety database for our heterozygous FH filing, which we hope to have take place in Europe as the next filing.

Lynne, do you want to add anything to that?

No.

Thank you.

Ted Tenthoff, Piper Jaffray.

Great.

Thank you very much for taking my question.

Lynne, if I may just spend a little bit more time on the R&D side.

We did see that big bump up in 2Q, and I think you said this was mipo related.

And you gave some new guidance with respect to operating expenses and where the loss would come in.

Was there anything special in this quarter that I missed?

And is this kind of the level you expected to be at for the rest of the year, as you said?

Yes, the R&D expenses are, Ted, at about the level we would expect them to be at.

And actually, while there is what looks like a significant bump-up between this quarter last year and this quarter for 2010, those expenses have been increasing gradually as the Phase 3 program has expanded and as we are preparing other things that are necessary to launch mipomersen, for example, getting ready for commercial manufacturing.

Okay, great.

That's very helpful.

Thank you.

Eun Yang, Jefferies.

Thanks very much.

From the last weeks, the two Phase 3 data, one is in severe, the other is in high risk -- comparing the data from the last weeks of data versus previous homozygous and heterozygous, can you comment on why the persistent ALT elevation was higher with severe and high-risk patients compared to homozygous and heterozygous?

Well, what we said on the call, and it's what we believe, is that in the homozygous FH patient population, the median reduction in LDL was 25% at 28 weeks.

And in the study that we reported, the median reduction and intent-to-treat analysis in the severe was 37 -- 36%.

And, we saw -- so in that older, less drug-resistant patient population, of course, homozygous FH patients are more drug-resistant, we did see more rapid and more profound APOB reductions.

And, we look at these ALTs as really manifestations of the basic activity of the drug and altering lipid.

And so we had people who had 70%, 80%, 90% reductions in LDL in a very short period of time, and we think that's the explanation for the differences in numbers.

The other thing I would say to folks is that we are still dealing with pretty small numbers -- 54 patients in one study, 58 patients in another.

And I think you can get some variations in response and other measurements that really smooth out as you get a larger patient experience.

But, in sum, we think that there was a slightly higher incidence of ALT elevations in the severe because we got a fairly significantly greater reduction in LDL.

Okay.

And then the second question is that you mentioned that this alternately reducing study at 30 milligrams daily or 70 milligrams 3 times weekly -- patients on those alternately reducing -- did you see lower dropout rates than 200 milligram weekly dosing?

We've only done the initial study, which was a three-week study.

You remember in our Phase 2 experience, we had very few dropouts at five and 13 weeks.

The challenge is six months and 12-month studies.

So we can't comment on a dropout rate.

What I think is important is that our intention is, over time, to provide better patient physician and nurse education.

We're starting to do that.

We've started to do it over the last few months, that we are going to offer patients the opportunity to dose themselves, not just in open-label studies, but in all studies.

We're going to allow patients to select their site and we're going to give patients, eventually, a choice of whether they like to give themselves an injection once a day, 3 times a week, or once a week.

I don't think it's possible to predict which dose -- type of dosing is going to be preferred by the largest group of people.

What's important is that people are different, and some people would rather give themselves a dose daily that's very small.

Some people would rather just get it over with and do it on a Sunday night.

And so our whole strategy is and has been to educate more and offer better options or more options to patients so that they can select the thing -- the approach that they like best.

And then I want to ask you the question differently.

So, in terms of then injection-site reactions, was the 30-mg daily or 70-mg 3 times weekly milder than 200-mg weekly dosing?

Yes, probably.

Again, we have a lot more work to do, and what we need is experienced dosing for six months or a year before we can draw firm conclusions.

That's the point of the next study is to figure out what -- how people feel about giving themselves daily doses versus every week doses.

And we need longer-term experience before we know what the overall behavior of injection site reactions is and the function of dose and frequency of dosing.

Thank you.

Mark Monane, Needham & Company.

Thank you.

Good morning for taking my call.

You presented quite a lot of data on the Phase 3 trials in terms of LDL reduction absolute, LDL reduction percent, LDL levels less than 100, LDL levels less than 70.

When you and Genzyme as a team think about the data, how do you position these different data points which you pointed out, in terms of both regulatory and commercial?

Are there any Stan or Genzyme favorites here?

No.

There are cardiovascular community favorites.

And it all depends on the patient type.

In the first group of patients that we're going to be treating, of course, percent reduction matters, but what really I think matters the most is the absolute reduction in LDL and other atherogenic lipids.

And so for those patients, that's why we tried to show the 100-mg per deciliter average drop.

That's terribly important because that's tied directly to reductions in cardiovascular risk.

So the absolute reduction in all these atherogenic lipids will be important to everyone, but obviously, if you come in with an LDL of 400, getting your LDL down to any reasonable level is a giant step forward.

Then, there are standards based on cardiovascular risk that people would like to achieve.

And, for people at -- who already have pre-existing cardiovascular disease, in a perfect world, cardiologists would like to get their LDL down to 70.

And so we talk about a below 70 because 70 is the number at which cardiovascular lesions are -- pre-existing cardiovascular lesions are thought to begin to resolve.

And, for somewhat lower risk people, getting to below 100; and then for the very, very high risk people, getting to the level where you don't need a apheresis.

So all of these things matter, and we try -- to the physicians who are treating these patients and these patients, and they matter differently depending on the patient.

And so we try to present as much information as possible, in the vernacular that's used by the physicians who treat these patients.

(technical difficulty) Does that help?

Yes, that definitely helps.

The (technical difficulty) is somewhat in the eye of the beholder, and you've been very straightforward (technical difficulty) parameter.

So that's been helpful.

Can I ask a follow-up question?

In terms of the key milestones, what's noticeable is that you have a number of different organizations that are using antisense in different delivery technologies in terms of injections into the eye, which I know you've started with Vitravene a while ago; but also aerosolized products, topical products.

Can you talk about how do you match the disease and the drug in terms of thinking about the Isis pipeline; and the disease, the drug and the delivery method in terms of the Isis pipeline?

Well, I'm just going to recapitulate the basic themes of the pipeline calls, Mark.

We use systemic delivery for targets that we believe are attractive by systemic delivery.

These are targets in the organs of major accumulation of these drugs -- liver, kidney, bone marrow, fat cells, spleen, and cancer and sites of inflammation.

We also balance our portfolio with drugs that aren't administered systemically because clearly a drug that's not administered systemically has a different kind of safety profile.

And we use local delivery when there are targets that are sensible, used locally.

So in the eye, clearly macular edema is a local disease.

And we also know that administered systemically, antisense drugs don't get in the eye.

In the brain, we know that we don't cross the blood/brain barrier, but, we know that we can give these drugs intrathecally, or directly injected into the fluid around the spinal column.

So that's how we treat severe neurodegenerative diseases.

And again, the opportunities and risks with the severe neurodegenerative diseases are quite different from the opportunities and risks associated with lowering cholesterol.

And our drugs can work topically, and there are opportunities to improve wound healing, so our partners at Excaliard are doing that.

And finally, our drugs can be administered by aerosol administration quite nicely, and they are administered that way for long targets, where we don't really want a lot of systemic delivery.

All of that then balances our portfolio in terms of opportunity and types of risk.

And we think it adds to the attractiveness of the technology and the overall portfolio that we can do all those things.

That was helpful.

And then lastly, I was unclear, and I apologize if this has been asked already -- the data that we just heard about from you and partner, Genzyme, in terms of the patients at high risk and the severe hypercholesterolemia patients, the data they presented last week, at [top line], when will we see that data so we can evaluate the entire data package?

Well, we can't tell you.

We're still analyzing the data.

And, as you know, the analysis of two Phase 3 trials like this takes time.

And then, you have to put together submissions for scientific meetings, and typically those submissions are many, many months ahead of the meeting, so we don't know yet.

As soon as we do know, we will let everyone know when we are doing it.

But, you know very well that typically is a lag of a good many months.

That's fair.

That's fair.

Thank you very much for the added information.

Pamela Bassett, Cantor Fitzgerald.

Thank you.

Good morning, everyone.

I would like to know whether the follow-on drug to BMS PCSK9 will involve 2.5 chemistry, and to what extent the advanced chemistry factor into the relationship?

In fact, the goal of the follow-on program with BMS is principally a generation 2 goal.

We expect the follow-on compound to be a generation 2 compound.

Remember that we are not quite ready to select a generation 2.5 chemistry.

We will do that before the end of the year.

But, even with the very potent generation 2 drugs that we have, with additional screening and additional work, we usually can find a drug that's 3 to 5 times more potent than the compound that we've selected some years ago.

So that's what we're doing with BMS.

Do you want to add anything to that, Lynne?

No.

Thank you.

Carol Werther, Summer Street.

Thank you.

Stan, how do you think the label might read when mipomersen is approved?

Do you think it will be more a label for saying something like homozygous plus severe?

Or do you think there will be levels of LDL?

Do you have any thoughts on that at this point?

You know, we've been -- we're working with Genzyme, and we have a lot of thoughts about it.

Lynne, do you want to respond to that question?

I think the most important thing is that we believe that it will be written to cover both of those patient populations, and I think I would defer that question with time and to our colleagues at Genzyme, who are taking the lead in that regulatory strategy.

Okay.

And do you think you will have any of the data on the 3 times a week or daily dosing in the filing?

Those are -- the studies will be still in progress I think or going on.

We have always contemplated those as supplemental NDAs -- being submitted in supplemental NDAs.

Of course, we will have some data because the studies will be in progress.

But we think of those as supplemental NDAs.

And then with the Bristol PCSK9 product, are you -- are they seeing skin reactions with that product also?

Oh, sure.

We see injection-site reactions -- I mean you see injection-site reactions with all sub-q drugs.

You see it with saline.

And the injection-site reactions with these second-generation antisense drugs were all fairly similar.

And, of course, we benefit with regard to all of our programs based on the experience that we've had in Phase 3 with mipomersen, and that informs how we handle and what we do with all of our drugs.

Clearly, people who have LDL problems being treated with PCSK9 are going to be similar kinds of patients to what we're treating with mipomersen, and so all these learnings are applied across the pipeline.

And my last question has to do with titrating mipomersen, and with the thought of, can you individualize care?

Because some patients seem to respond really well to the 200-mg dose, and some less well.

Can you comment on that, please?

Yes.

In all the trials that we have conducted in Phase 3, we have had a rigid requirement that all patients be treated with 200 milligrams a week full stop; no dosage estimates up, no dosage estimates down.

We do know that there is a range of responses to mipomersen, like every other drug.

Actually, I think one of the more remarkable things about mipomersen is how consistently it works in virtually everybody, but it's a drug.

So there will be people who are more responsive and people who are less responsive.

The first step that we are taking to get to the place where the drug is used more like the real practice of medicine is an open-label studies, we're allowing dosage estimates downward if someone is responding with a dramatic reduction in LDL or they have an issue.

And as we progress, we will get a lot more experience with individualizing dosing.

Those things happen not in Phase 3 typically or certainly not in your first Phase 3 studies; they happen as you get experience with the drug and physicians become more comfortable with it and look at ways to use the drug better.

And I look at it as entirely analogous to what people -- what physicians do with statins.

They don't, as you probably heard at our annual meeting -- they don't think about doses in a fixed way.

They look at the patient; they adjust the dose.

And there are patients who respond very promptly and resoundingly to a 20 milligram dose of Lipitor and there are others that don't.

And they use the dose that seems to make the most sense.

That's a product of experience over what -- how long have statins been on the market?

30 years or something like that.

We're at the beginning.

And all of that is going to take place over time.

I think it's very difficult to predict exactly how it will work out, but my prediction would be that individualizing doses will be the way people are treated, but the label will be 200 milligrams a week as our initial label.

Thank you.

Yes, you bet.

And there are no more questions in the queue.

And I would now like to turn the call back over to Dr.

Crooke for closing remarks.

Thank you.

In summary, I think the most important things that we said today is that we are on track for our initial filing for mipomersen in this initial group of desperately needy patients, these people with severe high cholesterol and extremely high cardiovascular risk; that we believe these patients -- that the therapeutic benefit of mipomersen in these patients is obvious.

We know the physicians who treat these patients.

Many of them have participated in the trials.

And we are confident that they are excited and looking forward to the drug.

We have a long-term plan to improve the performance of mipomersen, as we should.

And that progress is getting underway in a nice way, and we've already made significant progress.

I think we should look forward to a continuing evolution of the performance of mipomersen over the long haul.

Thank you very much.

Ladies and gentlemen, that concludes today's conference.

Thank you for your participation.

You may now disconnect.

Have a great day.