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Isis Pharmaceuticals, Inc. (NASDAQ:ISIS)

Q2 2010 Earnings Call Transcript

August 9, 2010 8:30 am ET

Executives

Stan Crooke – Chairman and CEO

Kristina Lemonidis – Director, IR

Lynne Parshall – COO and CFO

Analysts

Salveen Richter – Collins Stewart

Ted Tenthoff – Piper Jaffray

Eun Yang – Jefferies

Mark Monane – Needham & Company

Pamela Bassett – Cantor Fitzgerald

Carol Werther – Summer Street

Operator

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.

Stan Crooke

Thank you. Well, again, apologies for the problems with the call. Good morning and thank you, everyone, for joining us on today’s conference 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; and Kristina Lemonidis, Director of Corporate Communication. Kris, will you read the forward-looking statements?

Kristina Lemonidis

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 and 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 in 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’s 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’ll turn the call over to Lynne to review our financial results.

Lynne Parshall

Thanks, Kris. We continue to make progress in the first half of 2010, highlighted by our announcement last week of additional positive data on mipomersen. We are 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 alternative. We hope that mipomersen would be the therapeutic alternative that we will help them lead longer, healthier lives.

As usual, I’ll 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’d 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 with the same period last year. We expect a reduction in revenue, as it comes from the end of amortization period for collaborations that we are 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 studies, 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 are 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 partnerships. Our updated guidance reflects revenue on 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 form 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 about $450 million in cash.

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 in the clinical trial, from which we are in the $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 to 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 with sub-licensing 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 breadths and depths of our technology platform in our relationship result in a fairly steady stream of opportunities for financial benefits. This is the value of our unique asset base and our unique business strategy.

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

Stan Crooke

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 was 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 have 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 straight-forward to manage.

I want 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’ll discuss the work that we are 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 the medicines has to offer a day. They are at extremely high cardiovascular risk.

In just the US and Europe, Genzyme estimates that there are about 30,000 of these patients. When we talk about these patients, we’ve frequently divided 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’ve 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 from their blood and that costs approximately $100,000 a year. Another 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 [ph] are well characterized, easy to identify, and straight forward to manage. These patients are mostly taken care of by a group of very sophisticated and specialized physicians called lipidologists.

As you’ve heard from Dr. Caldwell at their annual meeting, the doctors who are treating these patients recognize the clear need from 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 benefits of 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 can see years ago and are now well along on 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 is offered. We are making great progress in these plans. And we believe that these efforts will have immediate and long-term benefits with all the patient populations we are talking about.

Now that work concludes 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 side reactions like cold or hot compresses. We are 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 are moving towards 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 bad cholesterol, not just LDL. We are focused initially on treating 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 trial and know it well.

Mipomersen has the consistent and manageable side-effect profile. The bottom line is we know that mipomersen is 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 are 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 1st. Of course, our success goes beyond mipomersen.

On a cardiovascular franchise, we and BMS initiated a Phase 1 study on our other lipid-lowering drug, PCSK9. We are also pleased with the progress that we’ve made with BMS and are happy to be extending the collaboration in other 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 ApoC-III and our first clotting drug targeting Factor XI to our pipeline. Both of these drugs are progressing nicely for the clinical trials. So there will continue to be significant progress in 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. We represented the Phase 2 data of our PDB1b [ph] 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 in our other key therapeutic areas, neurodegenerative rare diseases in cancer. In our neuro 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 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 this 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 are also close to initiating the first Phase 2 study of our eIF-4E drug. Our plan is to add another exciting cancer drug to the pipeline this year, which will bring our cancer pipeline to five.

In addition, our partner Excaliard recently completed the report of the first of their Phase 2 studies evaluating EXC-001 in patients with elective abdominal surgery. Using multiple measurements of wound healing and scaring, they reported that treatment with EXC-001 shows statistically significant reductions in scar.

For the large and expanding pipeline we spent sometime in the first half of this year outlining the strategic context of 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 we forward to. We and Genzyme continue to advance mipomersen toward the first market in patients with severe, high cholesterol and extreme cardiovascular risk. Clearly, as we progress, we will keep you informed. We will also report the full data from the heterozygous FH Phase 3 study of mipomersen on September 1st at ESC.

When we report the two most recent files at medical meetings, we will 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 trial studies on EXC-001. iCo announced that they have plans to begin a Phase 2 study in patients with diffusement of diabetic macular edema. And we hope that begins soon. And finally, we plan to add two to three new drugs for 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 question. Madge, if you can set us up, please?

Question-and-Answer Session

Operator

Thank you, sir. (Operator instructions) And your first question comes from the line of Salveen Richter from Collins Stewart. Please proceed.

Salveen Richter – Collins Stewart

Good morning. 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?

Stan Crooke

We’re absolutely confident. We have four positive Phase 3 trials, and we are working hard on the registrations.

Salveen Richter – Collins Stewart

Great. And then just timelines for initiation of the outcome study?

Stan Crooke

We are getting – the outcome study will have – there is a lot more work to do in getting ready for the outcome study. The next step is to initiate our long-term – 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?

Lynne Parshall

No.

Salveen Richter – Collins Stewart

Thank you.

Operator

And your next question comes from the line of Ted Tenthoff from Piper Jaffray. Please proceed.

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 on 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?

Lynne Parshall

Yes. The R&D expenses are at about the level we would expect them to be at. And actually, while there is – it 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 right to commercial manufacturing.

Ted Tenthoff – Piper Jaffray

Okay, great. That’s very helpful. Thank you.

Operator

And your next question comes from the line of Eun Yang from Jefferies. Please proceed.

Eun Yang – Jefferies

Thanks very much. From the last week’s the two Phase 3 data, one is in severe, the other is in high risk – comparing the data from the last week’s 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?

Stan Crooke

Well, what we said on the call and what we believe is that in the homozygous FH patient population, median reduction and LDL was 25% at 28 weeks. And in the study that we reported, the median reduction and an intent to treat analysis in the severe was 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 ALT 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 the 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 to 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 severe because we’ve got a fairly significantly greater reduction in LDL.

Eun Yang – Jefferies

Okay. And then the second question is that you mentioned that this alternative dosing study at 30 milligram daily or 70 milligrams three times weekly, patients on those alternative dosing, did you see low dropout rates than 200 milligram weekly dosing?

Stan Crooke

We’ve only done the initial study, which is the three-week study. You remember, in our Phase 2 experience, we had very few dropouts at the 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 are 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 are 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, three times a week, or once a week. I don’t think it’s possible to predict which 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 that – the approach that they like best.

Eun Yang – Jefferies

And then I want to ask you the question differently. So in terms of the injection side reactions, was the 30 mg daily or 70 mg three times a weekly milder than 200 mg weekly dosing?

Stan Crooke

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 a firm conclusion. 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 side-reactions is and the function of dose and frequency of dosing.

Eun Yang – Jefferies

Thank you.

Stan Crooke

You bet.

Operator

And your next question comes from the line of Mark Monane from Needham & Company. Please proceed.

Mark Monane – Needham & Company

Thank you – good morning – for taking my call. You’ve presented quite a lot of data on the Phase 3 trials in terms of LDL reduction absolute, LDL reduction present, LDL levels less than 100, LDL levels less than 70. When you and Genzyme and your teams think about the data, how do you position these different data points that you’ve pointed out in terms of both the regulatory and commercial? Are there any Stan or Genzyme favorites here?

Stan Crooke

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’ve tried to show the 100 milligram 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 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 below-70 because 70 is the number at which cardiovascular lesions – pre-existing cardiovascular lesions are thought to begin the result; 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 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. Does that help?

Mark Monane – Needham & Company

Yes, that definitely helps. The (inaudible) is somewhat in the eye of the beholder, and you've been very straightforward (inaudible) parameter. So that's been helpful. Can I ask a follow-up question?

Stan Crooke

Sure.

Mark Monane – Needham & Company

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?

Stan Crooke

Well, I’m just going to recapitulate the basic scenes of the pipeline called, Mark. We use systemic delivery for targets that we believe are attracted 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 sensible to use locally. So in the eye, clearly macular edema is a local disease. And we also know that administered systemically antisense drug 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 canal, but that’s how we treat severe neurodegenerative diseases.

And again, the opportunities in the US for the severe neurodegenerative diseases are quite different from the opportunities in 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 lung targets where we don’t really want a lot of systemic delivery. And 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.

Mark Monane – Needham & Company

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?

Stan Crooke

We can’t tell you. We’re still analyzing the data. And so the analysis of two Phase 3 trials like this takes time, and then we 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 I mean, you know very well that typically is a lag of good many months.

Mark Monane – Needham & Company

Right now, that's fair. That's fair. Thank you very much for the added information.

Stan Crooke

Sure.

Operator

And your next question comes from the line of Pamela Bassett from Cantor Fitzgerald. Please proceed.

Pamela Bassett – Cantor Fitzgerald

Thank you. Good morning, everyone. I’d like to know whether the follow-on drug to BMS’ PCSK9 will involve 2.5 chemistry and to what extent does the advanced chemistry factor into the relationship.

Stan Crooke

In fact, the goal of the follow-on program with BMS is principally a generation-two goal. We expect the follow-on compound to be a generation-two compound. Remember that we are not quite ready to select the generation-2.5 chemistry. We’ll do that before the end of the year. But even with the very potent generation-two drugs that we have, with additional screening and additional work, we usually can find a drug. That’s three to five times more potent than the compound that we’ve selected some years ago. And that’s what we are doing with BMS.

Pamela Bassett – Cantor Fitzgerald

Okay. Thanks.

Stan Crooke

Do you want to add anything to that, Lynne?

Lynne Parshall

No.

Pamela Bassett – Cantor Fitzgerald

Thank you.

Operator

And your next question comes from the line of Carol Werther with Summer Street. Please proceed.

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 label for, say, something like homozygous plus severe, or do you think there would be levels of LDL? Do you have any thoughts on that at this point?

Stan Crooke

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?

Lynne Parshall

No. I think the most important point 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 a lead in that regulatory strategy.

Carol Werther – Summer Street

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

Stan Crooke

Those are – the studies will be still in progress, I think, going on. We’ve always contemplated those as supplemental NDAs – being submitted in supplemental NDAs. Of course, we’ll have some data because the studies will be in progress that we think of those as supplemental NDAs.

Carol Werther – Summer Street

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

Stan Crooke

Sure. We see injection side reactions – I mean, you see injection side-reactions with all subcu drugs. You see it with (inaudible). And the injection side-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 are treating with mipomersen. And so all these learnings are applied across the pipeline.

Carol Werther – Summer Street

And my last question has to do with titrating t1. And with the thought of – can you individualize care? Because some patients seem to respond really well to the 200 milligram dose and some less well. Can you comment on that, please?

Stan Crooke

Yes. In all the trials that we have conducted in Phase 3, we’ve had a rigid requirement that all patients be treated with 200 milligrams a week, full stop. No dose adjustments up, no dose adjustments 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. It works with 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 in open-label studies. We’re allowing dose adjustments downward if someone is responding with the 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 three 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 look at 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 patients, they adjust the dose, and there are patients who respond very promptly and resoundingly [ph] to a 20 milligram dose of Lipitor and there are others that don’t. And they use the dose that seems to make more sense. That’s a product that we experience over what? How long the statin has been in 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. My prediction would be that individualizing doses would be the way people are treated, but the label will be 200 milligrams a week as our initial label.

Carol Werther – Summer Street

Thank you.

Stan Crooke

You bet.

Operator

And there are no more questions in the queue. And I’d now like to turn the call back over to Dr. Crooke for closing remarks.

Stan Crooke

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.

Operator

Ladies and gentlemen, that concludes today’s conference. Thank you for your participation. You may now disconnect. Have a great day.

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Source: Isis Pharmaceuticals, Inc. Q2 2010 Earnings Call Transcript

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