Ionis Pharmaceuticals Inc (IONS) 2007 Q2 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Isis Pharmaceuticals Second Quarter Financial Results Conference Call.

One note, today's call is being recorded.

Leading he call today from Isis is Dr.

Stan Crooke, Isis Chairman and CEO.

Dr.

Crooke, please go ahead.

Good afternoon everyone and thank you for joining us on today's conference call to discuss the financial results and highlights for the second quarter of 2007.

Presenting with me today are Lynne Parshall, Executive Vice President and CFO, [Christina Lemonitas], Our Associate Director of Investor Relations.

Also sitting in with us are Kate Corcoran, our Vice President of Corporate Development and Beth Halgren, our Vice President of Finance and Chief Accounting Officer.

In our last earnings call we talked about our BMS collaboration and about how the agreement further validated both our antisense drug platform and the strength of our business model.

We also provided detail on the development plan for Isis 301012, our Phase 2 lipid lowering drug that is the key asset in our cardiovascular program.

Today Lynne will talk further about the business model focusing on how our recent partnership activities fit in with our strategic plan.

She will also comment on the financial impact of our licensing activities and go over our updated guidance.

I will then take the opportunity to call your attention to our metabolic disease program and to provide you with an early glimpse of some of our potential future pipeline drugs.

At the end of our prepared remarks, of course, we'll be happy to answer any questions that you might have.

But before we begin first let me turn the call over to Christina to review our forward-looking policy statement.

I'd like to add my welcome to everyone listening in.

A reminder to everyone that this webcast includes forward-looking statements regarding our business, the financial outlook for Isis Pharmaceuticals and Ibis Biosciences and the therapeutic and commercial potential of Isis technology and products in development.

Any statement describing Isis' goals, expectations, financial or other projection, intentions or beliefs is a forward-looking statements and should be considered an at risk statement including those statements that are described as Isis goals or projections.

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

Isis' forward-looking statements also provide-- also involve assumptions and if they never materialize or prove could cause its results to differ materially from those expressed or implied by such forward-looking statements.

Although Isis' forward-looking statements reflect 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 ending December 31st, 2006 and its quarterly report on Form 10-Q for the quarter ending March 31st, 2007, which are on file with the S.E.C.

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

And now I'll turn it over to Lynne.

Our partnerships with BMS, Ainylam and Archemix continue to reinforce the value of our intellectual property estate and further validate the sustainability and power of our business model.

We have built this model around leverage and our innovation and our antisense platform technology to discover new drugs, then out license these drugs at value inflection points creating in the process a growing stream of annuity revenue from milestones and royalties.

In parallel we allow others access to our IP for technology development in exchange for sharing financially in their successes.

Our BMS collaboration is an example of our drug discovery and licensing strategy at work.

As we have often said, we discover many more drugs than we can expect to develop ourselves.

Selectively we license our drugs to partners with complementary expertise and a clear commitment to developing them.

We benefit from our research collaborations with these partners as together we advance the drugs and the underlying technology.

Of course, we also benefit financially through milestone payments and royalties as our drugs are advanced by our partners.

At the same time, this strategy allows us to bring new drugs forward from our research pool and into our development pipeline.

We have seen the exciting performance of Isis 301012 in the clinic, which offers validation for the platform as a whole and antisense drugs for chronic diseases in particular.

As a result, we have had substantial interest from perspective partners in our research programs as well as in our drugs in development.

For example, BMS licensed our PCSK9 program for $15 million up front and nearly $200 million overall plus royalties while the program was still in research before identification of the development candidate.

While fitting with our strategy, the deal was nevertheless opportunistic.

We have not been actively seeking to license this program but following the publication of our research studies with pcsk9 antisense inhibitors we were approached by multiple interested partners offering very attractive terms.

We showed that with antisense drugs we could effectively inhibit this target and produce anticipated lipid lowering effects that were the reason or so much enthusiasm among drug developers for pcsk9 as a target.

So we opted to take advantage of the pharma appetite for antisense drugs that inhibit production of pcsk9.

With BMS we selected a partner, which is a leader in cardiovascular disease therapeutics and which clearly has the resources and the motivation to make our drug a key component of its pipeline.

BMS is not only licensing our pcsk9 program but also funding a research collaboration with us through which we expect to continue to contribute to the future success of our pcsk9 program.

Another drug development partner, OncoGenex, is also reaching important milestones in the development of our drugs.

OncoGenex has announced encouraging data for its lead cancer drug, OGX-011, in several Phase 2 studies.

The results in combination with those with [Taxol] in both first line and second line advanced prostate cancer are supporting OncoGenex plan to proceed with the pivotal Phase 3 study of this combination in prostate cancer.

OGX011 is our antisense drug targeting clusterin and we own 35% of that drug.

OncoGenex also announced that it has begun its Phase 1 clinical trial of OGX427, antisense drug targeting Hsp27 for cancer.

OGX427 is the subject of a more traditional drug licensing deal we have with OncoGenex and we will receive milestones and royalties on this drug as it moves forward.

These are just a few examples of some of our drug licensing activities and you can see how the value of our strategy grows as development of antisense drugs advance and as momentum grows for the antisense drug platform as a whole.

In addition to discovering and developing and licensing drugs, we also continue to invest in innovation to expand our technology platform.

Strategically and selectively we also engage in technology collaborations in which we enable partners to develop related technologies by allowing access to our patents.

We have an extensive intellectual properties stake covering most aspects of messenger RNA targeting mechanisms as well as oligonucleotide medicinal chemistry.

Our siRNA partner, for example, is Ainylam Pharmaceuticals.

In 2004 we licensed to Ainylam the use of our patent estate for development of double-stranded siRNA drugs and, as a result, Isis receives a portion of the up front feel Ainylam receives for deals involving sublicensing our patents as well as milestones and royalties on Ainylam's and its partners' products enabled by our technology.

You can see the value of this aspect of our partnering strategy quite concretely with the $2.6 million we'll be receiving from Ainylam related to its Roche alliance-- sorry, that was $26.5 million.

I am the CFO.

I should be able to read numbers-- related to its Roche alliance once the transaction receives Hart-Scott Rodino clearance, which we expect this quarter.

Along similar lines we recently completed a technology enabling license transaction with Archemix.

Archemix is developing aptamer drugs that take advantage of the three-dimensional structure of oligonucleotides to bind proteins rather than messenger RNA targeting aspects that antisense mechanisms including siRNA exploit.

Companies such as Archemix, which are trying to turn oligonucleotides into drugs almost inevitably find that they need access to our medicinal chemistry.

We hope Archemix will be successful so that we will be able to share in its successes in the same way we share in Ainylam's and other partners' successes.

I'll now turn to our second quarter results and the impact of our recent activities on our financial projections for 2007.

As usual, I am assuming that you have all had the opportunity to read the Press Release we issued earlier this afternoon so I will not reiterate what's the detailed in the Release but please feel free to ask any questions at the end on any points from the Release that you need clarification on.

Looking ahead our partnership successes are resulting in a significantly improved financial position as we proceed into the second half of 2007.

The amortized revenue from our $15 million up front payment from BMS, the research funding associated with our BMS deal and the $26.5 million payment we will receive from Ainylam after this Roche transaction receives regulatory clearance significantly improve our operating projections.

As a result, we are reducing our estimated pro forma operating loss guidance for 2007 by approximately $20 million to a net operating loss in the mid to high $40 million range.

This represents a reduction of over 30% in our estimated pro forma NOL for the year.

Additionally, the BMS and Ainylam payments will provide us with over $40 million of additional cash further strengthening our balance sheet.

As a result, we're extending our previous cash guidance and now believe based on reasonable assumptions for new sources of revenue and cash that we have sufficient resources to meet our anticipated funding requirements at least through the end of 2010.

We are pleased with the improvements in our financial projections that our recent licensing activities have enabled.

We expect to continue to invest our cash in clinical development our key drugs as well as in further advancing our technology platform and expanding our intellectual property estate so that we can continue to profit from our innovations through licensing opportunities.

So now I'll turn the call over to Stan.

As Lynne mentioned, our internal development efforts are primarily focused on cardiovascular and metabolic disease and our focus during the early part of this year has been appropriately on Isis 301012 but in the next few minutes I want to focus on the other part of that pipeline, the metabolic disease opportunities.

In June we had the opportunity with scientific presentations at the American Diabetes Association meeting to share some of our research on new targets for diabetes and for obesity, which we think is an important opportunity for us in the near future.

These presentations demonstrated the power of our antisense technology platform as a drug discovery engine.

We are able to systematically evaluate many potential target genes in relevant animal models and then based on the data from those animal models select the most promising among them for further study and potential development.

This is especially advantageous in such complicated multi-factorial diseases as diabetes and obesity.

In fact, we've examined over 120 target genes in animal models of diabetes and obesity and, as a result, we have a rich pool of research data diabetes and obesity drug candidates just waiting for investment to advance in the development.

At the ADA we presented research on four new targets, SGLT2 and PKC-delta for diabetes and JNK1 and mDIC for obesity.

I'm not going to go into detail about each of these and I'm not even going to define what each of those targets are for you but I will spend a minute on SGLT2 because I think it is an interesting target and an interesting step forward for antisense.

SGLT2, or sodium dependent glucose transporter type 2, is expressed in the kidney and contributes to glucose reuptakes back into the bloodstream following filtration by the kidney.

So inhibiting SGLT2 function promotes glucose excretion into urine and that is expected to help reduce blood sugar level, making it of course an attractive target for diabetes that's highly complementary to the other mechanisms to treat diabetes that are being explored and exploited.

Now I've told you before that our antisense drugs, our second generation antisense drugs, dissolve simply in saline and administered subcutaneously at low doses distribute to the liver, kidney, bone marrow, fat cells, bone and spleen.

Our diabetes drugs targeting PTB1B, glucagon receptor and glucocorticoid receptor, all primarily affect liver targets and to some extent fat.

With SGLT2 we are taking now for the first time advantage of the distribution of these drugs to the kidney.

In a study presented at the ADA data from several animal species demonstrated that antisense inhibitors of SGLT2 effectively reduced target messenger RNA levels, increased glucose excretion into urine and consequently lowered blood glucose level without causing hypoglycemia or dangerously low blood sugar.

The reported data included studies conducted in dogs and rats with different treatment periods ranging from 6 to 20 weeks.

In genetically diabetic rats weekly treatment with a low dose of the antisense drug to inhibit SGLT produced a sustained and significant 40% decrease in plasma glucose levels and a decrease in HBA1C of greater than 4 percentage points compared to untreated or control treated groups.

Further, our antisense drugs effectively and specifically inhibit the production of SGLT2 in the kidney without having any effect on related gene products such as SGLT1 or SGLT3 and having no effects on SGLT expression in other tissues as well.

Interestingly, with this particular target, at least in animals, the optimal antisense drug is only 12 nucleotides long rather than our usual 20 and it is extremely potent.

It is by far the most potent antisense drug we've identified to any target.

Moreover, in the ADA presentation we also reported comparable activity in rats comparing subcutaneous and [interal] delivery, that is delivery orally through a tube put into the intestine.

The effective intestinal absorption and distribution to the kidney along with the high potency and shorter length of the SGLT2 drugs mean that oral delivery should be very peaceable with this drug.

So antisense drugs targeting SGLT2 may offer an attractive therapeutic opportunity for diabetes that exploits a mechanism that's quite distinct from those of other diabetes medicines on the market and also distinct from the three diabetes drugs that we have in development today.

Our antisense drugs are potent.

They're selective.

They have significant potential for oral delivery in the long term and we are in the process of making a decision about what our plans to pursue the development of an SGLT2 drug may prove to be.

On the other hand, our obesity discovery research exploits a different property of antisense drugs.

It exploits the fact that these drugs distribute to fat cells and liver.

Remember that our drugs go primarily to liver, kidney, fat cells, bone marrow and bone and they do not cross an intact blood brain barrier so they are not associated with central nervous system side effects.

Thus, we're able to discover drugs that affect body weight purely by effects on metabolic tissues in the periphery, not in the central nervous system.

And, as a consequence, we believe these drugs have the potential to be significantly safer and of course they would complement centrally active anti-obesity drugs that may come to the market.

Again, since we evaluate so many potential targets in animal models of obesity, both genetic and diet induced, this provides us with a very good sense of which targets really show promise for development as targets as peripherally acting anti obesity drugs and from that list of targets that we have evaluated we can pick the best looking.

We presented data on two such targets at the ADA, JNK1 and mDIC.

Antisense inhibition of each of these targets in mice reduced body weight and body fat content without affecting food intake and with no evidence of central nervous system toxicities or any other significant toxicities for that matter.

There were also favorable effects on insulin sensitivity and metabolic rate and other parameters so we have a rich supply of candidates that work in unique and complementary ways to potentially treat metabolic diseases from which to choose to expand our pipeline.

So you should expect in the coming years that both our cardiovascular and our metabolic pipeline will expand and that we will have drugs with a variety of mechanisms working in a variety of tissues that complement each other and complement existing drugs that are on the market.

We're excited about it.

Before taking your questions I want to preempt some of those questions that I know are on your mind by giving you a brief update on Isis 301012, our lipid lowering drug targeting [HoV] 100 in the liver.

As we told you last quarter, we selected 200 milligrams a week as our registration dose.

We think this is a very prudent choice.

It's in the middle of the dose response curve.

We know it's well tolerated.

It simplifies the dose schedule and makes the clinical trials themselves simpler as well.

We remain on track to announce our heterozygous FH data later this year as well as the results of our 3-month add on to statin therapy cohort patients with routine high cholesterol.

We'll also be conducting our end of Phase 2 meeting with the FDA shortly and our initiating pivotal trials of homozygous-- for homozygous and heterozygous FH.

Whether a single pivotal trial will be sufficient for registration in heterozygous FH remains a question that we expect to answer in our discussion with the Agency.

So we'll have more to tell you about all that later this year.

Finally, we'll also be starting our longer term Phase 2 study in routine high cholesterol patients.

We'll be treating at 200 milligrams a week for six months and then following these patients in an open label extension arm of the study to bring patient exposure out to at least a year.

All of these new studies, as I mentioned, will be with the simple dose schedule of 200 milligrams a week from start to finish.

Of course, we're in the process of selecting a partner to complete the development and advance Isis 301012 to the market.

I will simply say that the process is going very, very well.

We really can't give you any more insight into the timing of the deal than we have other than to say it is-- it remains our goal to have a partner before initiating, well before initiating Phase 3 trials for routine high cholesterol population, which we expect to begin next year in the middle of the year or so.

To conclude, it's been a great quarter for Isis and we think we're executing across the board.

We are especially pleased with the success of our business strategy.

Several of our older partnerships are maturing and generating interest and value and new partners are joining their ranks with increasingly attractive deal terms.

Antisense research and discovery activities have been very productive and we are experiencing more significant interest than ever from would be partners wanting to add antisense drugs to their pipelines.

Our preclinical and clinical development teams continue to make outstanding progress.

We are on track with every one of our drugs and we look forward to sharing new clinical trial data with you as they are generated from the drugs in our internal pipeline.

And with that, I am going to end and we'll now entertain your questions so, Sarah, if you can set us up please to deal with the questions.

(Operator Instructions) We'll go first from Piper Jaffray, Edward Tenthoff.

Congrats on the quarter.

I guess my first question really had to do with respect to whether or not you can give us a little bit more clarity on the timing of the three month statin data as well as is the end of Phase 2 meeting with the FDA scheduled yet?

And do you have any comments just on the Ibis business and how that's proceeding?

Why don't I take them in reverse order.

Thanks, Ed.

The Ibis business is moving along nicely.

We are on track to meet our guidance for placement of instruments and the beginning of sales of kits.

Our contract revenue continues to grow and do well and our revenue from our service business is continuing to do well, so overall we're extremely pleased with where Ibis stands today and very encouraged by the level of interest in the platform.

We have chosen to delay financing a bit because we've been busy with other things but we're very confident when we choose to finance we'll be able to choose-- we'll be able to finance on effective terms.

Now the next question is the end of Phase 2 meeting with the FDA, it is scheduled and we will be proceeding with that meeting at the opportunity that the FDA presented.

With regard to the next round of data from 301012, both the heterozygous study, which remember is a randomized double blind placebo controlled trial with doses of 50, 100, 200 and 300 milligrams a week involving about 45 patients and the 200 milligram 13 week statin combination data will be presented later this year at a scientific meeting.

Remember also that at the ACC we presented blinded safety data on all the studies that we had and so we would expect to provide an overall safety summary of the drug that would involve all the studies at that time.

We expect no surprises.

Alan Carr with Needham.

I guess can you tell us a little bit more about your partnering discussions with 301012, maybe if there's any trends or also any preferences emerging in terms of type of partners?

I think the only thing I can really tell you is that we are on track.

It's moving exactly as we hoped and we expect to achieve a very attractive partnership.

And can you go over the scheduling again for when you'd like to start the Phase 3 trial and the larger Phase 2B trial?

Were those both in the fourth quarter?

Well, I think the guidance that we've given is later this year.

Suffice it to say that those trials are moving along very aggressively.

Planning for those trials and initiation of those trials is in that whole process, which as you know, takes a while, is very aggressively in progress now.

Okay and then just one last question about the Archemix deal, was this a two way deal where IP was going both ways?

No.

Can you say-- was that a yes or a no?

No.

Oh okay so it was just a license in that direction okay.

That's right.

It really boils down to our medicinal chemistry.

If you think about oligonucleotides, the building blocks for oligonucleotides or the various modifications that we've made and if you want to make an oligonucleotide based drug at some point you'll want access to our chemistry just as [Makigen] used some of our chemistry and that's why we ended up with the royalties on Makigen.

Similarly with Archemix working in aptamers of various types, they wanted access to our chemistry to make their oligonucleotide based drugs and we're very pleased to give them that access because it just increases our opportunities for success.

Okay I seem to recall though there was some story you were getting access to their [Celex] technology too but I must have been mistaken.

No.

And from our perspective we're not an aptamer company and so we leave the aptamer business to Archemix.

Carol Werther from Summer Street Research.

I was wondering on the homozygote trial that you're going to start later this year if you could just go over how large you think that might be and how long it might take?

I'll just repeat the guidance that we've given, Carol.

We expect it to be about 45 patients.

We expect the dose to be 200 milligrams a week.

We expect the duration of dosing before we measure the end point is 26 weeks and we expect the patients to be rolled over into an open label extension.

I do want to caution you that, of course, there may be changes after we speak with the FDA but that's based on earlier conversations that we had with the FDA.

We believe this trial design will be sufficient.

For registration?

Yes.

Okay and then you showed us some of the homozygote data at ACC.

Will we see more data second half this year from the homozygote?

You'll see more data on the heterozygote.

The lower doses in the homozygote study were not very revealing because in the lower doses we had a lot of patients on Apheresis and it made analysis of the drug effects complex so I think you've see the important information out of the homozygous trial and you will see, of course, much more important because it's a larger trial and randomized and placebo controlled set of data in similar patients, the heterozygotes, and the heterozygotes that we're studying are obviously heterozygotes that have severe form of heterozygote FH and cardiovascular disease so they are much more akin to the homozygous patients than they are to just the run of the mill high cholesterol patient.

And will that registration plan be in parallel to the homozygotes?

I'd like to defer answering that question if I may until after we've had further conversations with the FDA.

So the data we'll see later this year it will be 5 week or 3 month data for the heterozygous?

Both.

Both okay.

That's what I thought.

Thanks very much.

Hamed Khorsand from BWS Financial.

My question was regarding your cash guidance.

Are you basically taking into consideration that you will have a partner for 301012 or is that with the development of 301012 being in house for Phase 3?

That did not assume a partnership for 301012.

Eric Schmidt from Cowen and Company.

Just on the Archemix relationship, were there any monies that changed hands up front and, if so, when will we start to see those through your P&L?

We received equity consideration up front in that transaction.

And we do see-- we will-- we expect to see a fraction of any up front funding that they receive out of deals that they might do that involve our technology, just as we do from other companies that we've worked with.

And then on the Ibis side, are we still tracking to meet the guidance for placements in 2007?

Yes we are.

Geraldine O'Keefe with Fortis Bank.

Stan, I was a little late so sorry if you discussed this already but the Symphony deal, is your plan to take that out sooner rather than later and do you need to take that deal out before a partnership or is it [lost] crystal at this point?

Well, we have filed for Hart-Scott Rodino approval to repurchase the Symphony transaction.

I suppose that signals some intention.

I want to remind you that there are three drugs in the partnership, Isis 301012 and two diabetes drugs so there could be many stimuli other than a license of 301012 to reacquire the partnership early.

They could be nothing more than the stock price being attractive.

It could be another deal involving some of the other drugs in the partnership or it could be other deals in other parts of the Company.

After all the money is fungible and we're-- and it's very much in our interest to reacquire Symphony as early as we think is practical and save some of that interest.

Then I was just wondering if there's a sticking point to some of your partnering discussions for 301012?

Not a bit.

The deal is absolutely crystal clear and our partners understand fully that it's not an impediment to any partnering activities, our potential partners.

And just one maybe follow-up question if I may, a more general question, in your introduction there you said that you have several targets now in the whole metabolic and cardiovascular area and then presumably with your research you're going to get more and more of these kind of targets.

What's your general strategy now?

Is it still to keep your targets until they're in safety and you have proof of concept or should we expect to see you licensing out more likely as somebody did earlier this license out some of the targets at the pre-clinical stage?

Well, it absolutely is true that it's a cost of money.

It's first a cost of money equation and the lower our cost of money, the more willing that we-- and more able we'll be able to develop drugs further but we look at each one of these drugs individually and ask what is the most opportune moment to partner them?

When are they at a local value inflection point and so I think what you'll see out of us is a tendency toward keeping our drugs, more of our drugs longer, but very being-- but considering each drug and each licensing opportunity entirely individually and in the context of our portfolio of activity.

[Ash Gobendef] from [Moony's].

I wanted to specifically ask what the Ainylam collaboration quick patents in relation to the chemistry involved in oligonucleotides and what I am trying to get at is are these patent, intellectual properties surrounding this area, will other RNAI based technologies need your patents maybe regarding the chemistry because I know you made a lot of headway with chemistry with your programs.

Is it dealing with the actual delivery or chemistry as well as in increases of absorption?

Can you talk a little bit about that?

Well, our chemistry patents control virtually, not entirely, but virtually the entire chemical space that's available for making oligonucleotides and, of course, siRNAs are oligonucleotides so we do believe that anyone who is making and siRNA that's modified to make it a better drug almost certainly is going to need a license from us at some point prior to commercializing the drug.

So the chemistry is universal as chemistry tends to be.

The Crooke patents cover the design of siRNA molecules to take advantage of the risk mechanism and so they are also very broad and mechanistic in their coverage so again, we think the vast majority of siRNAs that are likely to be developed are chemically modified and if they're chemically modified then by and large most of those will require access to the Crooke patents.

And so I guess the final part of the question is yes we believe that other practitioners of siRNA will require licenses from us before they're able to commercialize drugs based on siRNA technology, that is most of them.

We don't believe that our patents cover just straight naked siRNA but they-- but modified oligonucleotides for siRNA are covered by and large.

Lynne, you want to add or subtract anything from that?

No.

So any chemical modification to an oligo that would increase say its absorption or enhance its PKPD profile would have to go through your license?

We think so.

I wouldn't-- I would say virtually any.

There are some chemistries.

There are a couple, three chemistries that lie outside our patent estate there but then if those modifications were employed we think they would encounter the Crooke patents and other patents that we have so we believe and our partner Ainylam believes and others who have looked at this believe that our control of that mechanism of antisense is very substantial.

Then I had a (inaudible) question then, on the BMY up front payment of the amortized where the Ainylam payment will be recognized as a one-time third quarter once clearance?

That's correct.

That's right.

Because the research collaboration-- there is a research collaboration with BMY.

Right so and you get reimbursed R&D expenses as well.

That's right but the $15 million is amortized over the period of the collaboration.

And then R&D is reimbursed quarterly?

Yes.

That's right.

(Operator Instructions) Aaron Reames with A.G.

Edwards.

I was wondering if you could provide us with a quick update on alicaforsen and how close Atlantic is to starting Phase 3 trials with that compound?

Atlantic is busy getting the-- planning the trials and getting them underway.

I haven't spoken with Atlantic for a while so I can't be much more precise than that, Aaron.

Sorry.

Sometime in the next little bit, that's all I know.

No problem.

Okay and then do you have any update on the Lilly compounds?

Yes they're progressing and what is gratifying to us is that at the very high doses being employed they appear to be very nicely tolerated.

Lilly intends to move the Phase 2 program and surviving along and the Phase 1 program is moving along as well.

I can't be more precise than that obviously.

That's our-- those are partnered drugs and it's up to Lilly to be--

Sure okay.

And then I was wondering if you had any additional visibility on when we might expect data on 3715?

Nothing more than we've said, late this year or early next year [Inmoma] continues to go along nicely and so I think we're on track for if I were to guess it would be next year, not this year and obviously we need to see if we get it done in the right time so we can submit to the ADA and if we do that then-- so it's I know when we're going to know the data.

I don't know at the moment exactly when we're going to be able to make it public.

It will depend on what meeting we try to submit the data for.

[Ajem Tembuly], Lehman Brothers.

With your guidance for extended cash reserves through the end of 2010 I was hoping you could guide us as best as possible through what new clinical trial initiations and anticipated collaborative revenues that includes.

Well, obviously we have a large pipeline of drugs and we do make reasonable assumptions about moving those drugs forward.

You also know that our strategy is to partner drugs at key value inflection points so we make reasonable assumptions about new sources of revenue from partnerships and obviously when you do partnerships like that you both get revenue and can reduce expenses as you turn things over but, as Stan said earlier, we have not assumed in those projections that we do a large corporate partnership for 301012.

That would obviously have a profound impact on our projections.

At least we hope it would and so we have not added that assumption into the projections that we've given you.

But the projections do include the initiation and pursuit of glucagon and glucocorticoid drugs into clinical development, the initiation and pursuit of our IL4 receptor alpha aerosol drug for asthma, the continuation of the studies that we've outlined for Isis 301012 and the completion of the work that we're doing on Isis 113715 and bringing the CRP inhibitor forward into the clinic.

All of those things are in the projections.

And then how would the Symphony Genisis deal play into the guidance as well as anything with the Ibis division?

We have made I think very conservative but reason-- and very reasonable assumptions about growth in the Ibis business as well.

And with regard to Symphony, we've--

Sorry, with regard to Symphony because we haven't assumed a licensing transaction for Isis 301012, conversely we haven't assumed the cash to buy back Symphony transaction.

Carol Werther.

I was just wondering if you had completed the 12-month primate toxicity study with 301012?

Yes we have.

We had essentially completed that at the time of the ACC and I think we reported at least in general terms the results.

They certainly confirm the lack of [cyatosis] even at high doses for one year in the monkey and they support and argue continuing the development of 301012 and chronic dosing and provide an excellent therapeutic index.

(Operator Instructions) Brent Kelly with Jeffries & Co.

This Brent in for [Selvine Customer].

I was just wondering if you guys can give a little bit more granularity on what medical meetings specifically we can look for 301012?

Are we looking for a large medical meeting or a more smaller, more specific?

We expect to present 301012 data in a large medical meeting in the-- in later this year.

And there are no further questions at this time, Dr.

Crooke.

If there are no further questions I want to thank everyone for your attention and support and excellent questions, and we'll sign off now and stay tuned for continued progress.

Thank you.

Ladies and gentlemen, that does conclude our conference today.

We thank you for your participation.

Have a great rest of your day.