Ionis Pharmaceuticals Inc (IONS) 2014 Q2 法說會逐字稿

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

Please note this event is being recorded.

Leading the call today from Isis is Dr. Stan Crooke, Isis' Chairman and CEO.

Dr. Crooke, please begin, sir.

Thank you and good morning, everyone.

Thanks for joining us on today's call to discuss our second quarter financial results.

On the call today, Beth will walk you through the financials and then Lynne will highlight recent news.

After that, I'll focus on a few of our upcoming events.

Joining me on today's call are Lynne Parshall, Chief Operating Officer; Beth Hougen, Chief Financial Officer; and Wade Walke, Vice President of Corporate Communications and Investor Relations.

And now, Wade, will you read our forward-looking language statement please?

Yes.

Thanks, Stan.

A reminder to everyone that this webcast includes forward-looking statements regarding the financial outlook for Isis, Isis' business 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, including the commercial potential of KYNAMRO, 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 they never materialize or prove 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, 2013, 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.

Now I'd like to turn the call over to Beth.

Thank you, Wade.

Good morning, everyone, and thanks for joining us.

I'm pleased to report that we ended the second quarter with pro forma operating profit of $1.1 million.

In addition, we maintained our strong cash position with more than $590 million.

Our pro forma profitability in the second quarter exemplifies the effectiveness and success of our business strategy, which provides us with a steady stream of cash and revenue.

Because of the success of our drugs and our partnerships, we have generated nearly $75 million in payments from our partners so far this year, including $48 million in the second quarter alone.

And we've continued this momentum into the third quarter.

Through the successful execution of our business strategy and as our drugs advance, we generate payments from our partners.

These payments come in the form of up-front payments when we initiate a collaboration or expand the scope of an existing collaboration, milestone payments as our drugs advance through research and development, payments when our partners license our technology to their partners, and payments for the drug we manufacture for our partners.

All of these payments result in revenue to us.

We recognize some of those payments immediately as revenue and amortize others into revenue over time as we perform work for our partners.

In the first six months of this year we earned $85 million in revenue, which includes revenue from all of these types of payments as well as amortization from payments we received in prior years.

Milestone payments not only bolster our financial results but also signify significant pipeline and partnering successes.

For example, let me focus on our partner Biogen Idec for a moment.

We earned a $14 million milestone payment from Biogen Idec for initiating a Phase I study on ISIS-DMPKRx.

This is our second drug to advance into clinical studies in our Biogen Idec collaboration.

Another component of our Biogen Idec collaboration is the discovery and validation of new targets for neurological diseases.

Here, again, we've made great progress, as demonstrated by a $10 million milestone payment that we earned for the validation of a neurological disease target.

And then finally, together with Biogen Idec, we continued to advance our SMA drug.

To date we have earned $48 million as ISIS-SMNRx has advanced.

Additionally, last week we initiated the ENDEAR Phase III study in infants with SMA.

When we dose the first infant, we'll earn an $18 million milestone payment.

And later this year, we plan to earn a $27 million milestone payment when we dose the first patient in the Phase III study in children with SMA.

Our partnership with GSK also continues to be very successful.

We are evaluating ISIS-TTRRx, the most advanced drug in this collaboration, in a Phase III study in patients with familial amyloid polyneuropathy.

To date, we have earned $27 million as ISIS-TTRRx has advanced and we have the opportunity to earn an additional $43 million as we complete the Phase III study.

As this program and others in our GSK collaboration proceed, we have the potential to earn hundreds of millions of dollars.

We also made significant progress in our AstraZeneca collaboration.

In addition to the two Phase II studies now going for ISIS-STAT3Rx, we have advanced into clinical trials our second drug in this collaboration, ISIS-ARRx.

Because of that, we earned a $15 million milestone payment.

And of course, we have the opportunity to earn significant additional milestone payments as both of these drugs progress.

With numerous successful partnerships encompassing multiple drugs, we have continuing opportunities to earn additional milestone payments from our partners throughout the year.

These successes place us on track to meet our guidance of $110 million in revenue from milestone payments this year.

When we amortize payments from our partners, we do so over the period of time we perform work for them.

This creates a large and predictable stream of revenue for us.

Through the first half of this year, we have earned $32 million in revenue from amortized payments, which puts us on track to exceed our guidance of $45 million.

Together with our other sources of revenue, most significantly milestone payments, we have earned more than $85 million so far this year and we are on track to meet our guidance of more than $160 million in total revenue for this year.

We're very pleased with this financial performance and it's noteworthy that our revenue has steadily increased year over year, which we believe exemplifies the success of our business model, the excitement about our technology and the successful progress of our large and diverse pipeline of drugs.

Of course, as our pipeline of drugs for which we are conducting studies matures, those studies become larger and longer.

By the end of the year, we plan to be conducting multiple Phase III studies, including our Phase III study of ISIS-TTRRx, our recently initiated Phase III program for ISIS-SMNRx, and our planned Phase III program for ISIS-APOCIIIRx.

We also plan to be evaluating numerous drugs in Phase II clinical studies and we are advancing our earlier stage drugs as evidenced by the three Phase I studies we initiated in the second quarter.

All of these activities reflect the significant maturation of our pipeline and ensure that we have a large pipeline of important late-stage drugs for the future.

We expect to conduct all of these activities while keeping our spending increases consistent with our guidance for this year.

It's important to note that development programs conducted by our partners do not add to our expenses.

For example, we do not incur any of the clinical costs associated with the liver cancer study AstraZeneca is conducting on ISIS-STAT3Rx or the Phase I study of ISIS-ARRx but we have the potential to benefit financially from this work through milestone payments and future royalties as ISIS-STAT3Rx and ISIS-ARRx advance.

So as you can see, the first half of the year has been very successful for us.

We ended the quarter with pro forma operating profit and maintained our strong cash position.

And we remain on track to meet our financial guidance of a pro forma net operating loss in the low $50 million range and a year-end cash balance of more than $575 million.

And now I'll turn the call over to Lynne.

Thanks, Beth.

Good morning, everyone, and thank you for joining us.

We predicted that 2014 would be an important year with multiple pipeline events that would continue to enhance value.

The year is shaping up to be just that.

Over the past several years our pipeline of novel drugs has matured from earlier stage drugs into a pipeline of later stage drugs with significant commercial potential.

By the end of this quarter, we plan to have 5 drugs in Phase III development, over a dozen drugs in Phase II development, and a number of promising earlier stage drugs designed to treat patients with a broad range of diseases.

With this many drugs in development, we have numerous opportunities to report pipeline progress.

Just last week we initiated the Phase III program for ISIS-SMNRx, the first Phase III study named ENDEAR will evaluate ISIS-SMNRx in infants with spinal muscular atrophy and we remain on track to initiate the second Phase III study in treat children with SMA later this year.

Both of these studies are registration directed studies designed to provide us with sufficient data on activity and safety to file for marketing approval in the US and abroad for both infants and children with SMA.

We and Biogen Idec are also planning to conduct controlled studies in additional patient populations and we'll be providing more detail on these studies in the near future.

We're pleased that this program has quickly progressed from pre-clinical studies into Phase III studies in under three years.

Our clinical experience to date has provided early, but encouraging, results that support the continued development of this drug for patients with SMA.

We and our partner Biogen Idec have a deep commitment to patients with spinal muscular atrophy and their families.

We and Biogen Idec have been working extensively with the SMA patient advocacy groups and we've gotten to know many families living with spinal muscular atrophy and have been deeply affected by their experiences.

This fuels our commitment to developing ISIS-SMNRx with the hope of making it available to the entire SMA community as quickly as possible.

Our Phase III study with ISIS-TTRRx in patients with the polyneuropathy form of TTR amyloidosis is going well and enrolling on schedule.

We now have patients who have completed 15 months of treatment and are rolling over into our open label extension study, which is designed to provide patients with continued access to ISIS-TTRRx.

We also benefit financially from our partnership with GSK and, just this year, we've already earned three milestone payments from GSK related to the progress in the ongoing Phase III studies.

TTR amyloidosis is a fatal disease and patients with the familial amyloid polyneuropathy form have TTR protein buildup in their peripheral nerves and experience a loss of motor functions, such as walking.

This is a disease of relatively young people, the diagnosis of which predicts not only a rapid decline in function, but also pending death.

We designed ISIS-TTRRx to block the production of TTR protein, which should prevent further TTR protein accumulation in the nerves.

In our Phase I studies we observed significant reductions of greater than 80% in TTR protein.

Based on these data, we believe that ISIS-TTRRx can provide significant benefit to these patients and we look forward to advancing this drug to the market.

We're on the brink of initiating the first study of the Phase III program on our novel triglyceride lowering drug ISIS-APOCIIIRx.

This registration directed study will evaluate ISIS-APOCIIIRx in patients with familial chylomicronemia syndrome, or FCS, a rare orphan disease in which patients can have triglyceride levels of greater than 2,000 milligrams per deciliter.

Because of their extremely high triglyceride levels, FCS patients are also at significant risk of acute pancreatitis.

In this study, we'll be evaluating the effects of ISIS-APOCIIIRx in lowering triglycerides, apoC-III and other lipid parameters.

Evidence suggests that lowering triglycerides and apoC-III should reduce the incidences and severity of pancreatitis in these patients.

Later this year we plan to initiate the next of the Phase III studies in patients with triglycerides greater than 880 milligrams per deciliter.

ISIS-APOCIIIRx reduces the production of apoC-III, a gene target that was the focus of two New England Journal of Medicine articles published this June.

In these independent studies, researchers concluded that there is a significant cardiovascular benefit to reducing apoC-III levels and that lowering triglycerides by lowering apoC-III could have a dramatic effect on the risk of cardiovascular disease.

Like many of the drugs in our cardiovascular franchise, ISIS-APOCIIIRx not only reduces its target, apoC-III, but has also been shown to reduce other lipid parameters including triglycerides and non-HDL cholesterol and to increase HDL cholesterol.

In patients with type 2 diabetes, ISIS-APOCIIIRx produced significant reductions in HbA1c and other measures of glucose control, suggesting that ISIS-APOCIIIRx could provide benefit beyond lipid lowering, particularly in patients who have severely elevated triglycerides and type 2 diabetes, or metabolic syndrome.

This profile could translate into significant therapeutic benefit for the patients we plan to treat.

The tolerability profile we've observed so far is attractive.

The injection site reactions that we've observed have been infrequent and mild and we've not observed any flu-like symptoms.

We're also looking forward to the completion of the FOCUS FH study for KYNAMRO.

This study was fully enrolled late last year and Genzyme plans to have data from the study in early 2015.

We were pleased to announce that, together with Genzyme, we were awarded the 2014 Partners in Progress corporate award for our work in bringing KYNAMRO to the market for patients with an orphan disease.

This award from the National Organization for Rare Disorders, or NORD, highlights the considerable unmet needs that still exist for patients who have rare diseases like homozygous familial hypercholesterolemia.

In addition to these us exciting late-stage products, we have a robust and broad pipeline of more than a dozen Phase II drugs.

We reported top line results from our Phase II study of ISIS Factor XIRx.

In this study we showed for the first time that reducing levels of factor XI in patients who are undergoing total knee replacement surgery significantly lowered these patients' incidence of venous thromboembolical events without increasing the rate of bleeding events.

In fact, patients treated with ISIS Factor XIRx experienced numerically fewer bleeding events compared to patients treated with enoxaparin.

Moreover, we have a very clear idea now of where ISIS Factor XIRx should fit in the treatment and prevention of thromboembolic events, with a development plan focused on the right therapeutic opportunities for this important new drug.

We plan to import the full data from this study at an upcoming medical meeting.

We also reported positive Phase II results from our glucagon receptor targeting drug, ISIS-GCGRRx, to treat patients with type 2 diabetes.

In this 13 week study we reported statistically significant reductions in multiple measures of glucose control, including an HbA1c reduction of greater than 2 percentage points.

Given the robust glucose lowering we observed in this short study, we plan to conduct additional studies to identify the optimal dose and schedule to achieve glucose control with manageable glucagon receptor-related liver enzyme elevations.

We believe these activities will significantly enhance the profile of this drug.

Today we reported results from a Phase II study ISIS-CRPRx in patients with atrial fibrillation.

We conducted the Phase II study at a single trial site in seven patients with severe enough atrial fibrillation that they required the implantation of a pacemaker.

The pacemaker allowed us to follow minute-by-minute each patient's cardiac rhythms over several months.

Prior to treatment in the first month of the study, patients were withdrawing from their antiarrhythmic treatments.

In the second month of the study they were treated either with placebo or drug.

In the third month of the study they were crossed over and treated for another month.

They were followed for a fourth month after that.

Thus, even though the number of patients in this study is small, we have minute-by-minute data for several months in each of these patients that allow us to calculate their atrial fibrillation burden, or the fraction of time during which they're in atrial fibrillation, despite having a pacemaker.

In this study, ISIS-CRPRx did exactly what we designed it to do.

We observed statistically significant mean reductions of CRP of 65%, with reductions as great as 84%.

All patients experienced a significant reduction in CRP and a majority of these patients experienced a decrease in AF burden while they were on treatment.

Two of these patients entered the study with CRP levels greater than 5 milligrams per liter, which is considered a significant chronic elevation of CRP.

In both of these patients we observed a reduction of CRP that was associated with a decline to zero in their atrial fibrillation burden while on treatment.

Once treatment was completed, the AF burden in both of these patients returned to approximately pretreatment levels.

While these data suggest that reducing CRP might be of value in patients with AF and significantly elevated CRP, given the challenges of performing studies of this type we do not plan to pursue this indication.

Because CRP is strongly associated with the presence and severity of many diseases, including numerous inflammatory and cardiovascular diseases, there is significant interest in academia and we expect that there may be additional investigator initiated studies with ISIS-CRPRx in the future.

In addition to the positive Phase II data we've reported this quarter, we've advanced a number of drugs in our pipeline.

We recently initiated a Phase II study for ISIS-APO(a)Rx, our novel drug to lower Lp(a).

Lp(a) is a unique cardiovascular risk factor in that elevated levels of Lp(a) are genetically determined.

This means that diet and lifestyle changes cannot reduce Lp(a) levels from patients who have high Lp(a) and are at risk for cardiovascular disease.

Unfortunately for these patients, there are no marketed therapies that are approved to lower Lp(a) levels.

We look forward to results from our ongoing Phase II study in which we're treating patients with elevated Lp(a).

We also began clinical development on two drugs from our severe and rare disease franchise, ISIS-PKKRx and ISIS-DMPKRx, and we advanced ISIS-HTTRX into development for the treatment of Huntington's disease.

Because of our business strategy, many of our pipeline achievements go hand-in-hand with our successful financial results that Beth summarized.

So as you can see, it's already been a very productive and busy year.

We look forward to continuing this momentum throughout the second half of 2014 and into next year.

With that, I'll turn the call over to Stan.

Thanks, Lynne.

As our pipeline of novel and first or best-in-class drugs continues to advance in clinical development, we expect a number of pipeline events in the remaining half of the year.

Of course, we'll be dosing our first infant in our Phase III SMA study shortly.

This will be the first controlled study that we will conduct with ISIS-SMNRx and will allow us to define the benefit that we can bring to these sick babies.

We and Biogen Idec remain very committed to advancing this drug as rapidly as possible and plan to follow the initiation of the infant study with the initiation of a study in children with SMA later this year.

And we're also planning additional studies as part of a comprehensive clinical program that will evaluate ISIS-SMNRx.

In the fall at a medical conference, we plan to provide an update of our open label Phase II studies on ISIS-SMNRx.

We hope to see, at that time, results that are consistent with our earlier encouraging observations.

Next we'll begin dosing in the first of our Phase III studies on ISIS-APOCIIIRx.

The first study to begin will evaluate ISIS-APOCIIIRx in patients with FCS.

And then we plan to conduct Phase III studies in patients with triglycerides greater than 880 milligrams per deciliter.

In these studies we'll evaluate our drug as a single agent and in combination with fibrates.

We plan to conduct all of these Phase III studies in parallel.

Moreover, in support of the two indications we are pursuing, we'll be fleshing out the profile of ISIS-APOCIIIRx.

For example, we'll determine if we can replicate the exciting results that we saw in patients with type 2 diabetes.

If positive, this would represent a substantial addition to the profile of ISIS-APOCIIIRx.

Third, near the end of the year or early next year, we plan to report Phase II data from our ISIS-PTP1BRx, our novel insulin sensitizer and ISIS-GCCRRx, our glucocorticoid receptor drug in patients with type 2 diabetes.

These drugs, along with our glucagon receptor drug, are part of our substantial portfolio of drugs to treat metabolic disorders, including type 2 diabetes.

We designed each of these drugs to address a significant unmet medical need in specific segments of the diabetes population.

We plan to report the full data from our novel anti-thrombotic drug, ISIS-FXIRx later this year at a medical meeting.

Our top line Phase II results were certainly very encouraging.

And finally, we'll continue to mature our pipeline, advancing drugs into Phase I and Phase II clinical trials and adding new drugs to the pipeline.

And with that then, I'll open up the call for questions.

Maureen, if you can set us up please?

Thank you.

(Operator Instructions) Alethia Young, Deutsche Bank.

Congrats on the clinical and revenue success over the year.

Just one: I wanted to get your thoughts on the natural history study that just came out from Dr. Finkel, and how it ties to the Phase III study.

And I have a follow-up.

Well, this is the publication of the study that we've referred to a number of times.

And we think that this study is the ideal study to use to compare the results that we have in infants with ISIS-SMNRx because it's contemporaneous.

It's performed by many of the investigators that are in our study.

And the standard of care is similar.

We worked with Dr. Finkel and others to assure that our inclusion/exclusion criteria were matched.

And as we look at the demographics, we certainly think that the demographics of our patients are similar to the patients that contribute to the 10.5-month survival median endpoint.

So, it's the study that we believe is most comparable.

It's the study that we will refer to, in the fall, when we present the rest of the data.

And we're pleased, of course, that it's now published and available for full scrutiny.

Great.

And just as a follow-up, I'm just wondering if you can walk us through the other potential milestone payments over the second half of the year from each of your collaborators, Elizabeth.

It's Beth.

Good morning.

So, the two most recent ones that you can anticipate are obviously the ones for SMN, the infant study, which is $18 million, and then the childhood study for SMN that's $27 million.

We mentioned those in the call.

We then have other opportunities as we advance TTRRx to earn milestone payments as the drugs under that collaboration, in addition to TTRRx, advance their milestone payments associated with those.

And there are also milestone payments associated with the advancement of ISIS-STAT3Rx.

So, those are the ones that I think are probably most -- to keep your eye on those.

We also have milestones that come from the target validation and drug discovery processes with Biogen Idec, and other activities with AstraZeneca and GSK.

That, of course, is research so you can't absolutely predict exactly when, but certainly there will be contributions from those areas as well.

Great, thanks.

Stephen Willey, Stifel.

This is Prakhar Verma for Steve.

So, just two questions.

One regarding the apoC-III program.

Have you completed your discussions with FDA regarding the Phase III design?

And where are you in the process?

And second question: On the STAT3 program, do you have any update on the Phase II expansion study and the ACC patients?

Thank you.

The answer to the first question is, yes, we've completed our discussions with the FDA and the European regulatory authorities.

Those discussions contributed to the design of the Phase III program.

And based on those discussions, we're moving forward aggressively and optimistically that the package we'll put together will be approvaled.

So, all is going very well with that drug.

And then the next question is on STAT3.

We think there will be an opportunity to update the STAT3 program later in the year.

And our hope is that we'll be able to update both the lymphoma in general and expansion cohort, as well as the liver cancer results from the study that AstraZeneca is conducting.

Thank you.

Nicholas Abbott, BMO Capital Markets.

Congrats on the progress.

I just want to step back a little bit and ask: As you consider which areas to invest, in terms of research, given your ability to exquisically interrogate these pathways, are you swayed by, for example, the massive amount of interest all of a sudden in NASH, and then immuno-oncology over the last 12, 18 months in terms of directing effort to research, that you perhaps can come up with a set of programs that's going to be more comprehensive than pretty much anybody else out there?

Thanks.

Well, we look at all kinds of factors as we decide where to focus our research: unmet need, feasibility of antisense, organ in which the target is expressed, and places where we think antisense can uniquely bring value.

We've been interested in NASH for quite some time.

And we're much more encouraged about the opportunity in NASH today, more from our own experience than from the enthusiasm around the rest of the world -- although that's nice, too.

And the experience that was most informative to us was the MRI study that we did on KYNAMRO, which proved to our satisfaction that it's possible, in a cost-effective way, to evaluate changes in liver fat, and define a positive effect.

So, we're keenly interested in NASH.

We've got -- have a number of targets that we've demonstrated that appear to reduce liver fat.

And so, it's an exciting area for us, and we now think that a Phase II study is really quite feasible that would show -- would be proof of concept.

With regard to cancer -- of course, cancer is an interesting spot and an interesting space and a very complicated space.

The things that we've learned over the recent past that are most exciting to us is how much activity we have in stromal cells, the cells that feed cancer cells.

And as we've learned more about that, we've increased our interest in targeting that space, as well as the cancer cells themselves.

And you'll, of course, know that the stromal cells include parenchymal cells in the organs where the cancer is found, as well as cells that appear to be inflammatory cells that have migrated to the site.

So, we have a very keen interest there.

And the final point on that is that if you look at what's going on in both the tumor and the stromal cell that is responding to the cancer, a lot of those changes are driven by changes in non-coding RNA.

And of course, the ability to target non-coding RNAs is very much in our sweet spot.

So, the answer to both your questions, Nick, is a resounding yes.

Okay.

Thank you.

Chad Messer, Needham and Company.

I have just a couple: If I may start out with a clarifying question on milestone payments?

In the release, it says that you ended the quarter with around $591 million in cash, not including $41 million received after the quarter ended.

Was that all or partially recognized during the quarter, or is that $41 million milestones earned in third quarter?

Hi, Chad, it's Beth.

Those were all revenues that we earned in the second quarter, but because of the payment terms, the cash just didn't come in until the third quarter.

So, we've received all that cash at this point, and then it'll be in our balance in the third quarter.

Great.

Thank you.

That's very helpful.

And then I had a question on KYNAMRO revenues.

We haven't seen any reported, and I know that's because it's a profit share, and that won't happen till the franchise is profitable.

But is there anything you could share with us qualitatively how things are going, now that we're several quarters into the launch here?

I'll answer that briefly, and then Lynne can amplify.

We continue to see encouraging signs.

Sales are continuing to grow.

Genzyme continues to invest significantly in KYNAMRO.

And so, we remain optimistic that KYNAMRO will be a meaningful contributor to our revenues in the coming years.

We also continue to see just good data coming, and FOCUS FH we'll be excited to look at.

And then there are other data events that we think are important that could be exciting as well.

So, we're encouraged.

We wish we could share more information with you, but that's what we can share today.

Lynne, do you want to add anything to that?

No, you said everything.

Great.

Thanks.

And then one more, if I may.

TTR -- you're enrolling your Phase III study in the polyneuropathy patients.

If I'm remembering correctly, that's actually a smaller cut than the cardiomyopathy patients.

What are the plans to potentially expand?

And I can't remember if we ever discussed this before -- what was the rationale for starting with polyneuropathy?

Let me answer the second question, first.

The rationale was that the polyneuropathy patients have fewer cardiovascular -- they do have some cardiovascular risk -- but they have fewer cardiovascular risks.

And we felt that those cardiovascular risks were something that we wanted to get a real meaningful experience in.

And we also thought that the endpoints for evaluating the polyneuropathy have been well worked out.

And so, we just felt that polyneuropathy was the best first bet -- or the better first bet, I guess.

And as I may have mentioned, the decision to begin a study in cardiomyopathy patients is a decision that GSK will make.

And we're in the process of developing our plans for that now.

And when we can discuss those, we certainly will.

All right.

Great.

Thanks for the added input.

Cory Kasimov, JPMorgan.

This is Whitney on for Cory.

First question is: I realize you probably won't say what conference you're expecting to provide an SMN update, but can you outline maybe some of the potential conferences or highlight some of the major neurology conferences in the second half?

I don't think I should do that.

There are a couple of conferences in the fall that we're paying attention to.

They are large conferences, and we'll present at one of them.

You'll get a thorough update of the Phase II program, both in infants and in children, and we're very excited about what we'll be able to tell you then.

Whitney, when we have an accepted abstract, we won't keep you in the dark.

We'll let you know where the data will be presented.

Got it.

Okay.

And then next question is just on ISIS-PKK: I'm not seeing it on Clin Trials, so can you maybe tell us what doses you're evaluating or how frequently you're dosing that product?

It's weekly dosing.

And it's our standard dose -- initial patient dose regimens -- 100-, 200-, 300-milligram dose escalation kind of thing.

This drug works just like the other generation 2 antisense drugs, and the doses will be very similar.

Got it.

Thanks for taking the questions.

Eric Schmidt, Cowen & Company.

Just a quick one on the various Phase I studies that have started up: the PKK, the AR and the DMPK.

Are those being studied in patients or volunteers?

Let's see -- let's start with angiopoietin-like 3.

Androgen receptor was what --

I know, but let's start with angiopoietin-like 3. You didn't ask it, but angiopoietin-like 3 is being studied in normal volunteers.

And that study is fairly advanced now.

And then PKK -- I can't remember -- is it normal volunteers?

I think first normal volunteers, and then quickly into patients.

SMN is --

DMPK.

DMPK --

It is the same.

It's a short study in normal volunteers, and then quickly into patients.

And what was the other one you asked?

Androgen receptors.

Androgen receptors in patients -- in patients with prostate cancer.

And then on the new candidate -- the Roche Huntington's program -- when might be a reasonable time frame for an IND?

Sometime in the next 6 to 12 months, I would say.

So, next year?

Yes, I think early next year.

Now, again, that will be another intrathecally delivered antisense drug.

So, that would go into patients?

It will.

Thank you.

(Operator Instructions) Navdeep Singh, Goldman Sachs.

This is Lisa in for Navdeep.

Just on SMNRx, would it be possible to specify how long the follow-up will be?

And then, how many patients when you present the updated data at a medical meeting?

We'll tell you all about it when we present the data.

Okay.

And then, a follow-up on TTRRx -- can you just provide us some color around the safety profile?

Because I understand TTRRx is derived from the same version platform technology as KYNAMRO.

So, do you anticipate similar safety issues that you saw with KYNAMRO to also arise with TTRRx?

I think in healthy volunteers, we saw some injection site reactions, although they were mild.

No, we don't expect the same profile as KYNAMRO.

Remember, KYNAMRO had a number of liver effects that were tied to the reduction of apoB-100.

So, in addition to its platform effects, the effects on the liver were tied to the target.

Second, as we've said quite a number of times, advances in screening methodology have supported quite significant improvements in tolerability and potency of generation two ASOs that are later vintage than KYNAMRO.

We're seeing about double the potency.

We're seeing fewer and very minimal injection site reactions with all of these agents.

And we're not seeing flu-like syndromes -- we're rarely, if ever, seeing a flu-like syndrome these days.

With regard to that trial, the safety and tolerability of the drug has continued to be, I think, very attractive.

We, of course, are blinded.

The data -- the Drug Safety Monitoring Board watches the information.

And we are quite encouraged by the performance of the drug so far.

Okay, great.

And then lastly, as you're enrolling these patients into your -- that trial, what stage of patients are you seeing come on the trial?

Thank you.

You're asking about TTRRx?

Yes, exactly.

Well, these are patients who have quite significant disease.

And so, they're relatively advanced patients.

I don't know if there's a specific item that you're asking.

Maybe Lynne -- ?

The patients are late stage-one patients and stage-two patients.

Thanks so much.

Having no further questions, this concludes our question-and-answer session.

I would like to turn the conference back to Dr. Crooke for any closing remarks.

Thanks, everyone, for joining us.

I think we've had an important and successful first half of the year.

And I think the second half of the year is going to be pretty full of important pipeline events of various sorts, and we look forward to sharing that information with you as we progress.

The conference is now concluded.

Thank you for attending today's presentation.

You may now disconnect.