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Eli Lilly and Company (NYSE:LLY)

Ixekizumab Phase II Psoriasis Data Conference Call

April 10, 2012 10:00 am ET

Executives

Philip Johnson -

Eiry Roberts -

Subhashis Banerjee -

Michael Overdorf -

Analysts

Salim Syed - ISI Group Inc., Research Division

Gregory B. Gilbert - BofA Merrill Lynch, Research Division

Kyle Rasbach

David Risinger - Morgan Stanley, Research Division

Seamus Fernandez - Leerink Swann LLC, Research Division

Alison Yang - Barclays Capital, Research Division

Catherine J. Arnold - Crédit Suisse AG, Research Division

Operator

Ladies and gentlemen, thank you for standing by. Welcome to the Ixekizumab Phase II Psoriasis Data Conference Call. [Operator Instructions] And as a reminder, this conference is being recorded. I would now like to turn the conference over to our host, Vice President of Investor Relations, Mr. Philip Johnson. Please go ahead.

Philip Johnson

Thank you, Connie. Good morning. Thanks for taking the time and join us for today's call. I'm Phil Johnson, Vice President of Investor Relations.

As you know, the New England Journal of Medicine recently published an article detailing Phase II results in patients with chronic plaque psoriasis treated with our anti-IL-17 monoclonal antibody, ixekizumab. Joining me today to discuss these results and to answer your questions are Dr. Eiry Roberts, Vice President of Product Development in our Bio-Medicines business with responsibility for our Autoimmune portfolio, our Bone-Muscle-Joint portfolio and Liprotamase; Dr. Subhashis Banerjee, Senior Medical Director of our Autoimmune platform and the senior author of ixekizumab NEJM article; Michael Overdorf, Global Brand Development Leader for Autoimmune biologic portfolio; and Ilissa Rassner and Travis Coy from the Investor Relations team.

Ixekizumab is one of the 12 potential new medicines that we currently have in Phase III testing. Nine of these 12 have come from our own research labs, with 2 from ImClone and 1 from Boehringer Ingelheim. Ixekizumab is also one of the 2 Phase III assets in an emerging area of focus for Lilly, autoimmune diseases. The other is our anti-BAFF monoclonal antibody, Tabalumab, which is being studied in Phase III for rheumatoid arthritis and lupus.

The remaining 10 potential new medicines in Phase III come from our traditional areas of focus: Diabetes, with our GLP-1 dulaglutide, our 2 basal insulins and the SGL T-2 inhibitor from Boehringer Ingelheim, empagliflozin; neuroscience, with solanezumab for Alzheimer's disease; pomaglumetad methionil for schizophrenia; and edivoxetine for depression; and oncology, with ramucirumab in various solid tumors; necitumumab in squamous non-small cell lung cancer; and enzastaurin in diffused large B-cell lymphoma.

The lifeblood of any pharmaceutical company is launching innovative medicines that deliver clear value for patients, physicians and payers. We're pleased with the progress we've made building a robust mid- and late-stage pipeline, predominantly, from our own internal research efforts. And we believe this pipeline positions us to drive growth post-2014. As we're doing today, we'll continue to look for opportunities to share information with you in a timely manner on the data we generate on our pipeline assets.

Now during this conference call, we anticipate making projections and forward-looking statements based on our current expectations. Our actual results could differ materially due to a number of factors, including those listed on Slide 2 and as outlined in our latest Forms 10-K and 10-Q filed with the Securities and Exchange Commission. The information we provide about our products and pipeline is for the benefit of the investment community. This discussion is not intended to be promotional in nature. Ixekizumab has not yet been submitted to regulatory agencies for potential approval and is still being evaluated for safety and efficacy.

Now I'll turn the call over to Dr. Eiry Roberts. Eiry?

Eiry Roberts

Thanks, Bill. It's a pleasure to have the opportunity to discuss ixekizumab with you today. Our team is encouraged about the data we have generated to date with this molecule, and we're motivated by the prospect of helping provide a new treatment option for patients with psoriasis.

First, I'll provide a brief overview of psoriasis and the role IL-17 may play in the disease, then some highlights on ixekizumab and an overview of the design of our Phase II psoriasis trial. Then Dr. Subhashis Banerjee will review the safety and efficacy findings from the Phase II study, and Michael Overdorf will conclude our prepared remarks with a brief overview of our development plan.

As you may know, psoriasis is thought to be an autoimmune disease, in which immune cells in the body incorrectly identify skin cells as pathogens and become activated. This process leads to production of inflammatory mediators by the immune cells and abnormal accumulation of skin cells. It is estimated that psoriasis affects roughly 7.5 million people in the U.S. alone, making it the most prevalent chronic autoimmune disorder.

Plaque psoriasis is the most common form of psoriasis. It often appears as raised red patches covered with a silvery white buildup of dead skin cells and can affect the skin on any part of the body. The National Psoriasis Foundation has estimated that about 17% of patients with psoriasis have moderate to severe plaque psoriasis, which requires treatment with systemic agents. This is the patient population studied in our Phase II trial.

From a mechanistic perspective, the underlying pathology or cause of psoriasis is not fully known. Psoriasis is characterized by inflammation, which, as I alluded to earlier, is thought to be the consequence of activation of immune cells, particularly T cells. Specific T cells called type 17 helper T cells, as well as gamma delta T cells and other immune cell types, secrete interleukin-17A or IL-17, which is a pro-inflammatory cytokine. IL-17 is found in elevated levels in lesional psoriatic skin. In summary, therefore, this is the basis for targeting and neutralizing IL-17 as an approach to treat psoriasis. Lilly is currently one of several biopharmaceutical companies actively pursuing this target in clinical testing.

Our molecule, ixekizumab, is a humanized IgG4 monoclonal antibody that binds to and neutralizes the pro-inflammatory cytokine, interleukin-17A, or IL-17, with high affinity and high specificity. Ixekizumab is administered via subcutaneous injection.

Our Phase II study was conducted in patients who had experienced moderate to severe chronic plaque psoriasis for at least 6 months prior to enrollment in the study. A total of 142 patients were enrolled in the U.S. and Denmark. The trial was a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study. Patients were randomized into 1 of 5 arms: Placebo and ixekizumab dosed at either 10, 25, 75 or 150 milligrams. Subcutaneous injections were administered at 0, 2, 4, 8, 12 and 16 weeks, and patients were followed to week 20. The trial began enrollment in April 2010, and while this trial is no longer enrolling patients, patients already enrolled may still continue in the trial for up to 264 weeks.

The primary endpoint of the study was the proportion of patients at week 12 achieving a PASI 75 response, which represents at least a 75% reduction in a measure of skin disease severity, called the Psoriasis Area and Severity Index or PASI. There were also a host of secondary endpoints including PASI 90 and PASI 100 responses at 12 weeks. The PASI 90 represents at least a 90% reduction in the PASI score, while PASI 100 represents a 100% reduction in the PASI score.

Another measure of skin severity, namely the static Physician Global Assessments or sPGA scores, with a particular focus on scores of 0, or 0 or 1 at 12 weeks was also included as an endpoint. An sPGA score of 0 represents skin clear of disease, while a score of 1 represents minimal remaining disease.

Slide 7 summarizes the baseline characteristics of this study population. I'll highlight here that the average age of patients in the trial was in the mid-40s; over half of these patients were male; the average duration of psoriasis was greater than 13 years; the average PASI score was in the high teens; and the average sPGA score was approximately 3.3, with a range from 3 being moderate to 5 being severe. With this background, Dr. Banerjee will now review the efficacy and safety results seen in this Phase II psoriasis study.

Subhashis Banerjee

Thank you, Eiry. I'll start by covering highlights of the efficacy results from our Phase II study, and then will review key safety findings.

As Eiry mentioned earlier, the primary endpoint was PASI 75 at 12 weeks. As you can see on Slide 8, we observed statistically significant reductions at 12 weeks with the 25-, 75- and 150-milligram doses of ixekizumab. Specifically, the percent of ixekizumab patients achieving PASI 75 was 82%, with the 150-milligram dose, 83% with the 75-milligram dose and 77% with the 25-milligram dose compared to 8% in the placebo-treated patients. The P value for each of the differences was less than 0.001. There was a rapid onset of action, as seen by significantly higher PASI 75 responses as early as week 2 at the 150-milligram dose, and by 4 weeks, at the 25-milligram and 75-milligram doses compared to placebo.

The next slide shows the secondary endpoint of PASI 90 responses at 12 weeks where again, statistically significant reductions were seen at 12 weeks with the 25-, 75- and 150-milligram doses of ixekizumab compared to placebo. Percent of ixekizumab patients achieving PASI 90 was 71% with the 150-milligram dose, 59% with the 75-milligram dose and 50% with the 25-milligram dose compared to 0% in placebo-treated patients. Again, the P value for each of the differences were less than 0.001.

Another secondary endpoint, the PASI 100 response. This represents complete skin clearance at 12 weeks, is shown on Slide 10. In this case, the 2 highest doses of ixekizumab, 75 and 150 milligrams, demonstrated statistically significant differences from placebo at 12 weeks, with 39% of the 150-milligram dose and 38% of the 75-milligram dose achieving PASI 100 compared with 0% of placebo-treated patients. Once again, these P values were less than 0.001.

Next, let's look at the results of the secondary endpoint of sPGA score of 0, which is another measure of complete skin clearance at 12 weeks. As you can see on Slide 11, a significantly higher percent of patients on the 25-, 75- and 150-milligram doses of ixekizumab achieved an sPGA score of 0 compared to placebo-treated patients. Specifically, 46% of those receiving the 150-milligram dose, 38% of those receiving the 75-milligram dose and 20% of those receiving the 25-milligram dose achieved an sPGA score of 0 compared to 0% of placebo treated patients. In this case, the P values range from less than 0.001 to less than 0.05.

While not shown here, patients are also evaluated on achieving an sPGA score of 0 or 1, which indicates clear or minimal psoriasis. At the 25-milligram, 75-milligram and 150-milligram doses of ixekizumab, approximately 70% of patients achieved such a score at 12 weeks, which is statistically higher than the 8% response rate observed in patients treated with placebo.

In patients of psoriasis, the disease in fingernails and toenails as well as in the scalp can be particularly hard to treat. As shown on Slide 12, among patients with nail psoriasis, those taking the 75-milligram and 150-milligram doses of ixekizumab experienced statistically significant reductions compared to placebo in the Nail Psoriasis Severity Index or NAPSI scores at 12 weeks. The mean decrease from baseline was approximately 50% in patients receiving the 75- and 150-milligram doses compared to an approximate 7% increase in placebo-treated patients.

Slide 13 shows the mean change in Psoriasis Scalp Severity Index or PSSI scores in those patients with scalp psoriasis in the trial. Patients receiving the 25-milligram, 75-milligram and 150-milligram doses of ixekizumab experienced statistically significant reductions in PSSI score at 12 weeks. On this measure, the mean decrease from baseline was 85% or greater in the patients receiving these doses compared to approximately 30% in placebo-treated patients.

In summary, we saw statistically significant improvement between ixekizumab and placebo on the primary efficacy endpoint of PASI 75. At the higher-dose regimens, statistically significant improvements were observed across the various secondary efficacy endpoints. Statistically significant differences from placebo in PASI 75 responses, as well as in sPGA 0 or 1 scores, were observed as early as week 2 at the highest-dosing regimen of ixekizumab. And while not shown, but reported in the NEJM article, significant differences from placebo in PASI scores were seen as early as 1 week at the 2 highest-dose groups. Moreover, differences in these clinical measures were all sustained through 20 weeks.

Now let's review the safety finding from the study. No serious adverse events were reported in any of the study arms. The frequency adverse events in the combined ixekizumab groups, as well as in the placebo group was 63%.

As shown in the table on Slide 14, the most common adverse events observed were nasopharyngitis, upper respiratory infection, injection site reaction and headache. In total, infections occurred in 33% of patients receiving ixekizumab and 26% of patients receiving placebo. We did not see any dose-related trends in infections or other adverse events.

In terms of discontinuations, 1 patient in the placebo group, 2 in the 10-milligram ixekizumab group and 1 in the 25-milligram ixekizumab group discontinued the study due to adverse events. Due to the known effect of IL-17 on neutrophil recruitment, we monitored neutrophil counts. In this study, we observed no significant change in mean neutrophil counts when ixekizumab treatment was given. And there were no cases of clinically significant, and by that I mean grade 3 or 4 neutropenia was observed in the ixekizumab arms.

In one ixekizumab patient, with a prior history of treated basal-cell carcinoma, 2 new basal-cell carcinomas were detected during the treatment period. No other cancers were reported in the trial. While the safety profile observed in the safety trial is encouraging, the trial itself was relatively short and involved a relatively small number of patients. Larger and longer-term studies are required to fully characterize the safety profile of ixekizumab. Michael?

Michael Overdorf

Thank you, Dr. Banerjee. I'll conclude our prepared remarks with a brief discussion of our development plans. Based on the encouraging data generated in our Phase II trial, we initiated our Phase III trial program in psoriasis in December of last year. Our first Phase III trial is a randomized, double-blind, placebo-controlled study in patients with chronic, moderate-to-severe plaque psoriasis. This study is being conducted in the U.S., Canada, Europe, Japan and Australia and is expected to enroll approximately 1,300 patients.

Patients are randomized initially into 1 of 3 arms: 2 arms with different dosing schedules of ixekizumab and 1 arm with placebo. At 12 weeks, responder patients will then be re-randomized to 2 different ixekizumab dosing schedules or placebo during the maintenance period and will then be followed on these dosing schedules through 60 weeks.

The primary endpoints for the study are sPGA 0 or 1, as well as PASI 75 at 12 weeks. There are a number of secondary endpoints including these same 2 measures, as well as patient-reported outcomes, which will be evaluated during the blinded maintenance dosing period up to 60 weeks. We expect to initiate 2 additional Phase III psoriasis trials within the next few months. Our overall program is intended to generate data sufficient for global regulatory submissions. Beyond psoriasis, we're also evaluating options to study ixekizumab as a potential treatment for other autoimmune conditions, such as psoriatic arthritis, ankylosing spondylitis and rheumatoid arthritis.

This concludes our prepared remarks. Now we're happy to address your questions. Operator, first caller please.

Question-and-Answer Session

Operator

Our first question comes from the line of Mark Schoenebaum from ISI.

Salim Syed - ISI Group Inc., Research Division

This is Salim stepping in for Mark. Just a question, comparing it to brodalumab, what are you sort of looking at in terms of advantages with ixe? And then what are your areas of concern?

Philip Johnson

Salim, thank you very much for the question. Thanks for joining the call. I believe -- maybe have Eiry answer the question, and then Michael or Subhashis feel free to chime in as well.

Eiry Roberts

I think, first -- the first point I would make is that both of the articles and both of the molecules that were described in the articles really provide encouraging validation for the role of IL-17 in psoriasis. In particular, we're very encouraged in our own data by the ability to see the type of efficacies that we saw by blocking, specifically, the IL-17A cytokine. We specifically engineered our monoclonal antibody to be specific to that target. We do understand and know that Amgen as a receptor antagonist, has a much broader impact in terms of the cytokines that impacts this [ph]. It's actually very encouraging to see that the PASI scores for our own molecule are in a similar range. Obviously, you don't have direct, head-to-head comparison here, so it's impossible for us to say whether they're the same or not. Theoretically, by being more specific in blocking a single cytokine, it may translate into an improved tolerability profile. We are encouraged by the tolerability profile we saw in our Phase II study. But obviously, it's going to require larger scale clinical trials to truly understand that.

Salim Syed - ISI Group Inc., Research Division

Any concerns?

Eiry Roberts

Again, we're very encouraged by the data that we've seen to date. I think that Dr. Banerjee went through the efficacy and safety data in some detail. I would very much agree with his comment though, this is a relatively small Phase II study still. And we're now, obviously, undertaking a larger-scale Phase III program to understand the overall benefit-risk for patients in this disease setting.

Philip Johnson

Salim, we are pleased that both our sort of Phase Ib proof-of-concept study as well as this Phase II did produce consistent results as well. So again, very excited about the opportunity. But again, we'll need to generate the data in the larger Phase III programs to fully characterize the safety and the benefits that could be offered by the drug in psoriasis.

Operator

[Operator Instructions] And our next question comes from the line of Greg Gilbert with Bank of America Merrill Lynch.

Gregory B. Gilbert - BofA Merrill Lynch, Research Division

I have 2. Looks like Amgen's product has a neutropenia signal. Aside from the data you just covered, is there anything you could point us to that would give us some comfort that this is less likely to occur with your product over longer treatment durations? Is it just about that selectively you just discussed? And secondly, do you expect to have all Phase III trials in hand to file the product?

Philip Johnson

Thanks, Greg, for the questions. We'll have Subhashis to answer your first question, and then Michael to handle the second one. Subhashis?

Subhashis Banerjee

Yes. It's very difficult to speculate on cause of neutropenia, but what we have seen and what Amgen has seen with their antibody. And all we know is that our antibody is very specific for one particular cytokine IL-17A, whereas what's publicly known is, as Eiry pointed out, is their antibody receptor blocks multiple cytokines. Whether that plays a role in eventually seeing different grades of neutropenia remains to be seen in the larger Phase III studies and the longer-term trials. So it's -- at this point, it's difficult to speculate on that.

Eiry Roberts

The only thing I would add, Greg, is that as Subhashis said, we've monitored neutrophils very closely in this Phase II study. We did not see any cases of grades 3 or 4, which would be considered clinically significant and no correlation between the neutrophils and infections. And so that's very relevant, we believe, for this molecule as it moves forward.

Subhashis Banerjee

And not only that, as I mentioned earlier, we did not see any change in mean neutrophil count with treatment. That's the first question. Second question is we expect all of -- all 3 of the Phase III trials to be ready by submission time.

Michael Overdorf

Yes. All 3 trials are global studies, and we expect the data from all 3 of those trials to support a global regulatory submission.

Operator

Our next question comes from the line of Kyle Rasbach with Cowen and Company.

Kyle Rasbach

This is Kyle Rasbach at Cowen & Company. If you could maybe just give us some idea about the market, what number – or what percentage of patients with psoriasis are currently treated with biologics? Maybe what you see as the largest barrier to starting a patient on a biologic for psoriasis? And how you believe that IL-17 paradigm can fit in? Maybe how you see this position.

Michael Overdorf

Yes, thanks for that question. In terms of the market size, about 7.5 million patients have psoriasis. And of that, 17% of those patients have the moderate-to-severe plaque psoriasis that we're targeting. In terms of patients who are currently treated with biologic, that number varies a little bit based on the market research that you look at. But on average, it's around 18% to 20% of patients currently with psoriasis are treated with biologic agents. And I think some of that percentage, we're seeing that increase over time with the introduction of newer agents that are able to deliver higher response rates. And I think there's a growing comfort on the part of the prescribing dermatologist physician with the use of these biologic agents. And so I think the more they're able to see the data and see what these agents are able to deliver in terms of efficacy as well as the balancing of the safety, we're seeing and are encouraged by the increased percentage of patients who are being treated with the biologic agents.

Eiry Roberts

Yes. So I think, as Michael mentioned, our trials are focused on the indication of moderate-to-severe plaque psoriasis, and that's where we believe and intend that if we're successful in Phase IIII that the therapy would be used. Clearly, and similar to several other autoimmune diseases, psoriasis is a long-term, chronic disease, although some patients get a very significant response to the currently available therapies such as the anti-TNFs or the 12/23 monoclonal antibody. There's still a lot of patients that flare on those therapies and/or lose response for many reasons. And so we believe there is still significant unmet need in this patient population that will be addressed by the anti-IL-17 monoclonal antibody. I think the other thing I would say in that regard is that our Phase III program is designed to, we believe, give us best chance of optimally addressing the benefit-risk scenario here for patients of this treatment. We understand that some of the reluctance that dermatologists have to start biologics is associated with their long-term question about safety and tolerability. And so as Michael described, our program is designed with an initial dosing phase, followed by a maintenance phase of treatment. And we have designed that specifically in order to address a key amount of the feedback that we received from dermatologists about how to treat patients to a remission or full-skin clearance early and then maintain their treatment in a -- such a fashion that optimizes benefit-risk.

Michael Overdorf

Yes. The only other thing I would add is, typically, with the treatment of diseases, the goal is to return a patient to a normal or a disease-free state. At this point, PASI 75 has been the best that agents have been able to deliver upon. And I think that leaves some patients -- some psoriasis patients with some frustration, because they're not able to achieve complete skin clearance, so the sPGA 0 or PASI 90 or 100 stores. And so I think that's where the unmet need and the opportunity really lies with newer agents to be able to deliver more for these patients, who aren't satisfied with what current treatments are able to provide for them.

Operator

Our next question comes from the line of David Risinger with Morgan Stanley.

David Risinger - Morgan Stanley, Research Division

With respect to the future development, it's clear on this call that the study that's been discussed is a relatively small study. And you're encouraged by the safety profile that you've seen, but you need to do more work. So can you provide a little bit more color on the timeline for Phase III results, including how long the maintenance phase would be so that we can understand when we're going to get more clarity on the safety profile and also how big Phase III will be? And then second, with respect to where this drug will fit in the treatment paradigm, I guess, obviously, the profile will dictate that, but maybe you could talk more specifically about whether, for example, you see this as a potential head-to-head competitor with Humira or as a treatment for Humira failures?

Philip Johnson

Great. Dave, thanks for the questions. We'll have Michael start off and then maybe have Eiry comment as well.

Michael Overdorf

Dave, thanks for your question. In terms of the overall program, the timing of the program, what we have shared, and it's still consistent based on the fact that we're early into the Phase III program, just having started in December, is that we anticipate in April of 2014 the primary completion timing of the Phase III program. And again, that's consistent based on what we're seeing in these early stages. The maintenance period of this that we're looking at, are 60 weeks, is the maintenance period of each of these studies that we're evaluating. And the overall size of the study, we've disclosed the first study so far, which is about 1,300 patients. As we start our next 2 trials, we'll be disclosing on clinicaltrials.gov the size of those programs and the treatment duration and things like that. We're not in a position today to reveal any more information about that. But the size of the program will be consistent based on the regulatory guidance we've received and the regulatory guidance of other agents going forward. The treatment paradigm that we see with this, obviously, all depends on the Phase III data and what we see in Phase III. But there always, I think, will be the paradigm where dermatologists, starting with some phototherapy, topical agents before they're considering some of the biologic agents. But based on the data that we see, we would anticipate an agent that were to deliver similar Phase III results would be considered as an initial biologic agent. It wouldn't be something that would be reserved for biologic failures, particularly if the agent were able to deliver upon the enhanced clearance that patients so desperately need. So again, those sPGA 0 or the PASI 90 or 100 scores, I think would position that agent well in terms of its use as a first-line biologic agent.

Operator

Our next question comes from the line of Seamus Fernandez with Leerink.

Seamus Fernandez - Leerink Swann LLC, Research Division

I have several questions. First off -- and again thanks for doing the call, Phil, very impressive elocution of the different names of the pipeline products. So as we kind of get to the questions, can we just maybe go through your willingness to perhaps evaluate patients? I mean, it seems like obviously, efficacy in the nails and the scalp is very impressive. It was called out in the discussion in the article and also called out in the editorial in The New England Journal. But it seems to me like going head-to-head versus etanercept as your competitors are doing. So you see ustekinumab, the IL-12/23, doing a study versus Enbrel. We've got a study from Novartis with their own anti-IL-17 going head-to-head as well, with their trials poised to complete in 2013. So I'm just trying to get a better sense of how you really differentiate. And it seems like safety might be the way to go. Would you be willing to enroll patients with prior TB exposure? Do you have plans to go head-to-head versus one of the TNFs? If so, which one? You have a JAK1, 2 in development. Pfizer is developing tofacitinib in psoriasis as well. Would you envision your JAK1, 2 going after the market or after this market as well? And then from a marketing perspective, you really don't have -- and correct me if I'm wrong, but there's isn't much of a presence at Eli Lilly in dermatology. Why not partner this compound with an expert in dermatology to really kind of more quickly penetrate and perhaps get a leg-up on some of the competitors that might come to market a little bit earlier? The last question is diagnostic component, if there is one, do you see a way to drive better treatment selection and patient selection as you move forward in potentially psoriatic arthritis and rheumatoid arthritis?

Philip Johnson

Let me just try to make sure that I've captured these questions. So basically, in terms of the future development for the molecule, would we consider a head-to-head versus one of the TNFs, for example? Will we consider enrolling patients with prior TB exposure? I heard, could we – sort of what's the bother of developing the JAK1/JAK2 in psoriasis as in how it might fit into the treatment? We don't have much of a presence in this area currently, why wouldn't we go ahead and partner? And the last one, is there a diagnostic component to this to potentially drive patient selection or treatment?

Seamus Fernandez - Leerink Swann LLC, Research Division

You got it. It's almost as impressive as the names, Phil.

Philip Johnson

I think I'm going to be getting a call later asking for something. I'm getting passed. Eiry, would you like to?

Eiry Roberts

Yes, I'd be happy to start and then have my colleagues join me. I'm actually going to start at the end and work forwards because I think some of the core questions about the Phase III plan and our strategy for this molecule, Subhashis and Michael can address directly. I think we had mentioned when we'd spoken in a previous investor call that we are always willing and interested in considering opportunities for partnership and collaboration and Lilly overall as an organization has a strong history of doing that. I think we also believe that given the nature of these data and our commitment that we're making to the area of immunology and autoimmunity that Lilly can build the presence to be successful in this market in very much the same way that we have done in previous markets with medicines like Cialis or even in the newer science area when we entered that arena initially. So we're not nervous about the opportunity; if the data hold up in the way they are we are very encouraged by the opportunity to do that. But certainly, we continue to consider potential for collaborations as we have done on the, inside JAK1, 2. Obviously, that is a collaboration and partnership right now. Moving then to the question around the JAK1, 2. And you're correct, we do have our own Phase II psoriasis program ongoing now with our JAK1, 2 in development and that study is proceeding very well and enrolling to plan. As we look, however, at the data that have been generated for tofacitinib and apremilast and other orals in the psoriasis space, it's clear that the degree of PASI 75 clearance that is being achieved is less, although obviously, not a direct head comparison than we believe could be achieved with these -- with our own ixekizumab. I mean, if you look at -- I think for tofacitinib at its highest dose, it was a PASI 75 of around 60% to 70%, but we know that's not the dose that's being tested in Phase III. And so I think we believe strongly that there is room for both orals and new and improved biologics in the psoriasis space. And that in reality, some of the orals provided the tolerability and safety profile plays out effectively for the benefit-risk ratio, could be positioned bringing more patients into biologic-type treatment earlier in the treatment paradigm. And so we will clearly be looking at that as we develop our overall strategy for treatment of psoriasis with our JAK1, 2 and ixekizumab providing our Phase II data play out for the JAK1, 2 molecule obviously. So I think there certainly is room for both; different patient populations, in our opinion. And certainly for the ixekizumab anti-IL-17, our goal with our Phase III program, and I'll hand over to my colleagues then in that regard, given the magnitude and the degree of efficacy that we believe we've seen in this initial study, would be to have that -- generate a plan that allows that to have the potential to become a best-in-disease biologic treatment for patients with psoriasis. One comment about the diagnostics. I think obviously, there is huge interest in this arena, in the autoimmune diseases as a whole in using biomarkers or diagnostics wherever appropriate and possible to identify who's the right patient to treat with each intervention. It's, as you know, been extremely challenging, very, very difficult to repeat any of the initial findings that have emerged in this area, particularly in the field of RA. But we, like others, continue to invest in this arena, and we'll continue to do that in parallel with our programs to identify any markers that are possible moving forward.

Michael Overdorf

In terms of your question around the head-to-head analysis versus Enbrel, it's something clearly that we're evaluating. We are aware of the publicly available information from our competitors that are considering studying that and is something, different parts of the world, most specifically in Europe, where it is important to have that head-to-head data if you want to be registered. We're, unfortunately, right now, not in the position to share the remaining 2 studies that we're going to be conducting in psoriasis. But we are positioning those studies in such a way that we don't only want to be competitive, but actually differentiate this molecule in the marketplace. And so we'll be disclosing publicly the study design and trial design of those very soon within the next couple of months, and then we'll be more in a position to be able to share our total strategy for the development of this molecule at that point.

Subhashis Banerjee

Regarding your other question, regarding enrolling patients with prior TB exposure, we are enrolling patients who have had prior TB exposure, provided they've had appropriate treatment for their TB, especially for latent TB. I must point out here that unlike TNF, where in both animal studies and in humans -- in human and patients, there's increased risk of TB, or even with the entire 12/23 pathway where there is a increased risk of mycobacterial infections. There is no evidence so far in the literature suggesting the role of IL-17A in relation [ph] to TB, either in animal models or in patients who have mutations in the pathway. So we are fairly comfortable that TB is not a risk that we may see with our drug. However, we need to be precautionary -- take a precautionary attitude to this because this is a biologic. There are still unknowns there. We haven't taken enough number of patients to know whether it's a risk or not. So we are -- on the safe side, we are doing our TB screening of our patients enrolling the study and making sure that they've had adequate treatment of TB if they've been exposed to TB prior to enrolling in the study.

Operator

Our next question comes from the line of Tony Butler with Barclays.

Alison Yang - Barclays Capital, Research Division

My name is Alison Yang. I'm calling on behalf of Tony Butler. Two quick questions. Question number one, could either of the 3 speakers give a little more detail on the case of basal-cell carcinoma. I realize this is a very benign and rather common cancer. But if you can give some indication on, have there been situations where this could be a transformational signal towards other malignancies and how were these cases resolved? And number two is on the ease-of-use in dosing. There if you were to look at some of the comparator trials that have been done like ACCEPT comparing STELARA and Enbrel, there's been incidences where monthly subcu drugs can get very good tachy scores. So how is -- are there attempts within Lilly to make your IL-17 less frequent of a dose? Or do you think that the current dose is competitive from the patient median stand [ph] point of view?

Philip Johnson

Thanks, Alison. We're going to have Subhashis take your first question on the case of basal-cell carcinoma and then, Michael, the question on dosing frequency.

Subhashis Banerjee

Basal-cell carcinoma is not infrequent in patient psoriasis, amongst the reasons, partly due to the fact that they've had prior phototherapy. And this is not increasingly observed in the trials in psoriasis. Now what is known is that the addition of squamous cell carcinoma is very rare in these patients, mostly basal-cell carcinoma. The one patient who developed recurrent lesions of the basal-cell carcinoma had a prior treated basal-cell carcinoma. So whether it's inherent in that patient and now we don't know whether it's sort of come up with any drug or spontaneously. It's difficult to speculate. Only larger trials can answer the question. But if you'll notice from all the Phase III trials, our view in anti-TNF agents, there basal-cell carcinomas have been reported, but usually a higher proportion than squamous cell carcinomas. To gel sort of numbers quoted by the key opinion leaders are 3s to 1. There are more basal-cell cancers than squamous cell cancers. Again, as I said, mainly because of the prior exposure to phototherapy.

Michael Overdorf

Yes. And good question around the dosing schedules. As we are understanding the journey that patients take with the psoriasis disease, obviously, the frequency of injection is something that's of concern to them and a monthly injection is obviously a frustration for these patients. And so as we evaluated the different dosing schedules that we're using in our maintenance, we are exploring different dosing schedule options, primarily driven by the duration of response that we saw in Phase II, but also by the understanding that patients are desiring less frequent dosing as they go -- as they move on that journey with the psoriasis. But also the device, as well, is an important interaction for them. And so that's something that we're exploring as well is to bring improved device to patients with this disease.

Philip Johnson

Thanks, Michael. Even though we're past the initial allotted time, we do have at least one additional caller in the queue. We will continue to take questions as they come in up until the top of the hour. So Connie, if we could have the next caller, please.

Operator

[Operator Instructions] Our next question comes from the line of Catherine Arnold with Crédit Suisse.

Catherine J. Arnold - Crédit Suisse AG, Research Division

So the STELARA label, it indicates that the drug should be administered by a health care provider. I can't recall whether you said, whether the subcutaneous injection is administered by a health care provider or can be administered by the patient. So if you could clarify that. And then I also wanted to know if you had any specific markers that were included in your Phase II trial to the prior conversation regarding looking for patient characteristics for therapeutic stratification. And then my last question is, where is your interest in terms of business development in the dermatology space as you move this into Phase III and want to, obviously, enhance your relationships with that physician prescribing audience?

Michael Overdorf

Yes, great. I'll take the first question in terms of the dosing. Our Phase III studies are designed such that the initial dose is administered by the health care professional and then subsequent doses are patient administered in the home with the anticipation that, that's what -- if the molecule were on the market, that patients would be self-administering this medication.

Philip Johnson

Then Subhashis, on the markers included in Phase II?

Subhashis Banerjee

Yes. So we have done a study in collaboration with Dr. Jim Krueger and Rockefeller University using -- looking at the biomarkers in Phase I and Phase II. And we have found – there were some promising markers which we have submitted an abstract for a presentation later this year, which may suggest markers there which may be predictable for a response or treatment. But again, this needs to be validated in longer-term and larger studies.

Eiry Roberts

Yes, I'd just add one comment to Subhashis' comment. I mean, I think given the magnitude of the efficacy signal that we saw in the general population in the psoriasis study, our belief is that the value of a diagnostic marker in that psoriasis setting for this therapy may be less than it may be in other areas such as in RA. And so one of the other key questions that we are seeking to address given the investment that we've made in the biomarker arena with Dr. Krueger and in the context of some of our RA Phase II program is to understand the transferability of some of that learning from one disease state to another since many of the markers are focused on understanding the pathway. With respect to the business development discussion, I think we're in the very early stages of thinking about this. I don't think we have a core strategy, and indeed as I mentioned earlier, our goal is to move ahead alone in this setting, and we believe that we can be highly successful in doing that, provided the therapy performs in Phase III in terms of efficacy and safety obviously. But -- and so it was a more general comment really rather than a reflection of a core strategy that we have right now.

Operator

Yes, we have a follow-up question from the line of Mark Schoenebaum with ISI.

Salim Syed - ISI Group Inc., Research Division

It's Salim again. Just on quality of life, I apologize if I missed this in the paper. Were there any measures taken on the quality of life and also psychological impact?

Subhashis Banerjee

Yes. The measure called DLQI is a measure of quality of life, and the ixekizumab at the highest doses, 2 highest doses significantly reduced the [indiscernible], meaning that the patients felt much better with treatment. So yes, that was certainly examined in the study. We also looked at symptoms caused, such as depression, and there was -- in those cause there was some reduction of treatment with therapy. But having said that, the patients who came into the study did not have high scores to begin within those indices. Whereas the DLQI scores, they are much higher, meaning they had a very worse quality of life and ixekizumab did decrease DLQI scores, meaning that the patients felt much better after treatment.

Operator

That is the last question. Please continue.

Philip Johnson

Great. Well, we thank you all for joining us today. We hope you found this type of information session around the data that was generated with ixekizumab Phase II psoriasis trial to be helpful and look forward to having some similar discussions on other molecules in the future. If you have additional questions during the day, the IR team would be available for your question. Have a great day, and thanks for the call, or thanks for participating in the call.

Operator

Ladies and gentlemen, this conference will be available for replay after 12 p.m. Eastern today through April 17, 2012 at midnight. You may access the AT&T Teleconference replay system at any time by dialing 1 (800) 475-6701 and entering access code 243508. International participants can dial (320) 365-3844 and entering access code 243508. That does conclude our conference for today. We thank you for your participation, and for using AT&T executive teleconference. You may now disconnect.

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