Bristol-Myers Squibb Company

Bristol-Myers Squibb Company

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Bristol-Myers Squibb Company (BMY) Q2 2008 Earnings Call Transcript

Published at 2008-07-21 23:20:29
Executives
Michael York - Senior Director, IR Daniel M. Bradbury - President and CEO Mark G. Foletta - Sr. VP, Finance and CFO
Analysts
Thomas Wei - Piper Jaffray Margaret Malloy - Goldman Sachs Research William Ho - Bank of America Securities Matthew Osborne - Lazard Capital Markets Biren Amin - Stanford Group. Phil Nadeau - Cowen & Company Tom Russo - Baird
Operator
Good day ladies and gentlemen and welcome to your Amylin Pharmaceuticals Second Quarter Earnings Call. At this point, all attendees are in a listen-only mode. Later we will conduct a question-and-answer session and instructions will follow at that time. I would now like to turn the call over to Michael York, Senior Director of Finance. Sir, you may begin. Michael York - Senior Director, Investor Relations: Good afternoon. Welcome to Amylin Pharmaceuticals quarterly update conference call. Today's discussion will contain forward-looking statements that involve risk and uncertainties. These risks and uncertainties are outlined in today's press release and in our recent filings with the Securities and Exchange Commission. Our actual results could differ materially from what is discussed on today's call. Let me introduce the other members of the Amylin management team here today, Daniel Bradbury, President and Chief Executive Officer; Mark Foletta, Senior Vice President, Finance and Chief Financial Officer. I will now turn the call over to Dan Bradbury. Daniel M. Bradbury - President and Chief Executive Officer: Thanks, Michael. Good afternoon and thank you for joining us today. We made steady progress in the second quarter of 2008 across our near, mid, and long-term opportunities, executing against the strategy to build Amylin's diabetes portfolio and establish our presence in the obesity field. This strategy is consistent with our goal of creating a company that can increase shareholder value over time by producing sustainable growth. The importance of our focus on diabetes was once again highlighted this month when the Centers for Disease Control announced their latest estimate for the number of patients with diabetes in the United States. Clearly, the diabetes pandemic is growing at a faster rate than the overall population as the CDC updated the number of patients with diabetes in the US in 2007 to 23.6 million from 20.8 million in 2005, an increase of 13% over just two years. Also, one of the key takeaways from this year's American Diabetes Association meeting was that not only is glucose control important in managing diabetes; but how you manage it is critical too. A medicine such as BYETTA, which provides powerful durable glucose control with progressive weight loss and other benefits is uniquely poised to take advantage of the growing market. It was certainly an exciting ADA meeting for Amylin. We had more than 30 abstracts with eight oral presentations, including two of the five in the prestigious late breaking session. This demonstrates the breadth and depth of Amylin's scientific and clinical programs for both diabetes and obesity and reflects the tremendous interest among the medical community to our novel approach for developing first-in-class medicines. We're poised to take advantage of this interest, as starting earlier this year we undertook a number of initiatives to drive BYETTA revenue and we expect to see the impact of these changes in the second half of the year. SYMLIN continued to show steady growth in the second quarter with total prescriptions growing more than 5% quarter-over-quarter. Now, as you are fully aware, our mid-term plans focused on the exenatide once weekly program. Recently, commercial scale material from our Ohio facility has been produced and shipped for use in ongoing and planned clinical trials in the coming weeks. And I am also pleased to report that we had our pre-NDA meeting with FDA in the second quarter to discuss the open items for our regulatory submission. The meeting went well, and I'll discuss our regulatory path forward in a moment. Additionally, we are continuing to execute DURATION, the strong clinical superiority program designed to position exenatide once weekly for market dominance. For the long-term, we continue to make prudent investment decisions based on strong clinical data to advance our obesity program, and we'll continue to manage our expenses appropriately leveraging our assets to increase efficiency and assessing financing or partnership alternatives to offset expenses. I'll now turn things over to Mark Foletta to review our financial results. Mark G. Foletta - Senior Vice President, Finance and Chief Financial Officer: Thank you, Dan, and good afternoon. Earlier this afternoon, we announced our financial results for the quarter ended June 30, 2008. We reported total revenue of $222 million for the second quarter, which includes net product sales of $200.3 million. Product sales are made up of $177.5 million for BYETTA and $22.8 million for SYMLIN, resulting in second quarter growth in product sales of nearly 20% compared to the second quarter of 2007, and an increase of 12% from the first quarter of 2008. As a reminder, BYETTA sales last quarter were impacted due to the reversal of wholesaler stocking that occurred in the fourth quarter of 2007. We believe that product revenues in the second quarter reflect patient demand and the channel inventory levels are comparable with where they were at the end of the first quarter. Our revenue under collaborative agreements was $21.7 million compared to $29.6 million for the same period in 2007. Collaborative revenues for the second quarter consists primarily of cost sharing payments from Eli Lilly and Company for development expenses associated with the exenatide franchise. As a reminder, collaborative revenues for the second quarter of 2007 included a $15 million milestone payment associated with Lilly's launch of BYETTA in the European Union. Cost of goods sold was $24.7 million reflecting a gross margin of approximately 88%. This compares to cost of goods sold of $14.4 million for the second quarter of 2007 and a gross margin of approximately 91%. Gross margin decreased year-over-year primarily because of increased discounting, higher production cost for BYETTA and our product mix including the introduction of the SymlinPen, which has a higher cost of goods sold in the vial presentation. Selling general and administrative expenses for the second quarter of 2008 were $111.1 million compared to $93.1 million for the same period in 2007. The increase primarily reflects sales and marketing expenses including expenses associated with the recent expansion of our field force, promotional expenses for BYETTA and SYMLIN, expenses associated with exenatide once weekly market development and modest increases in business infrastructure to support growth. Research and development expenses were $75.4 million for the second quarter of 2008 compared to $71.7 million for the same period in 2007. The increase primarily reflects higher development expenses for exenatide once weekly and to a lesser extent growth in our research capabilities. Research and development expenses net of cost sharing payments from Lilly on the exenatide portfolio decreased of $54.8 million for the second quarter compared to $58.2 million for the same period in 2007. As a reminder, we are reimbursed by Lilly to share exenatide development cost and we believe that this net R&D number is a better indicator of R&D activities at Amylin. Lilly's share of the gross margin for BYETTA, which we refer to as collaborative profit sharing was $79 million for the second quarter of 2008 compared to $70.4 million for the same period in 2007. We reported a net loss of $64.8 million or $0.47 per share for the quarter ended June 30th, 2008 compared to a net loss of $45 million or $0.34 per share for the same period in 2007. At the end of the second quarter, we held approximately $890 million of cash, cash equivalents and short-term investments. I will now quickly review top and bottom line results for the six months ended June 30th, 2008. Total revenue was $419.3 million dollars consisting of product sales of $379.1 million, which grew 15% over the prior year and revenue under collaborative agreements of $40.2 million. This compares to total revenue of $368.9 million and product sales of $329.3 million in 2007. Net product sales for 2008 consist of $336 million for BYETTA and $43.1 million for SYMLIN. Our net loss for the six months ended June 30, 2008 was $133.6 million, or $0.98 per share compared to $94.4 million, or $0.72 per share for the same period in 2007. I'd now like to highlight some information regarding key trends and assumptions for the remainder of 2008. We have included in these numbers non-cash stock based compensation expense, an estimated $85 million in aggregate, covering expenses for both stock options and our employee stock ownership plan. Our previous guidance for total revenues in 2008 of $900 million to $950 million included collaborative revenue of $100 million to $125 million. Our expectations for product revenue remain unchanged. And we now expect the collaborative revenue will be at the bottom of the range, consistent with expected decreases in research and development expenses, which I will discuss in a moment. Based on our assessment of gross margins in the first half of the year, we believe that we will maintain gross margins of approximately 88% for the remainder of the year. We continue to expect that our selling, general and administrative expenses for 2008 will be towards the lower end of our previous range of $425 million to $475 million. This range reflects costs associated with continued investment in commercial activities for BYETTA and SYMLIN, investments in pre-launch education activities for exenatide once weekly and appropriate investments in infrastructure to support our growing business. Our SG&A expense guidance also includes approximately $50 million of stock-based compensation expense. Consistent with our lowered expectation of collaborative revenue discussed previously, we now expect that our research and development expenses for 2008 will also be towards the lower end of our previous range of $325 million to $375 million. This includes approximately $35 million of stock-based compensation expense. Furthermore, we are pursuing options to offset the R&D expense associated with our obesity and early stage programs through potential partnerships and/or project financing. Finally, I would like to reaffirm our net interest income guidance of approximately $5 million in 2008. I'll be available at the end of the call to answer to any questions, and I will now turn the call back to Dan for an update on recent business activities. Daniel M. Bradbury - President and Chief Executive Officer: Thanks, Mark. First, I will provide a commercial update on BYETTA, the first and only FDA approved incretin mimetic, a new class of drug that mimics the action of the human hormone glucagon-like peptide-1. We have marketed BYETTA for more than three years and has been used by approximately 1 million patients. Importantly, BYETTA is the only medicine currently available that addresses the significant unmet need for the Type 2 diabetes treatment that achieves powerful, durable glucose control with progressive weight loss and a favorable safety profile. In the second quarter, we maintained a steady level of BYETTA prescriptions compared to the first quarter. Today, I am going to report on key market accelerators, our enhanced marketing approach, and our more closely aligned sales organization. Together we believe these factors will drive BYETTA sales and ensure we can effectively launch once weekly exenatide when approved. We got a tremendous assist in the second quarter towards building momentum for BYETTA and for exenatide once weekly. New market accelerators were prominent at the American Diabetes Association meeting in June. Simply put, exenatide was the news of ADA 2008. First, this year, we saw more scientific presentations about exenatide and the class to ADA than ever before. As these topics were featured in more than 159 independent and company-scientific presentations. Second, the influential Banting Lecture put BYETTA firmly in the spotlight. The 2008 Banting Medal recipient Dr. Ralph DeFronzo advocated for a new paradigm in the treatment of Type 2 diabetes and called for a change to the ADA treatment algorithm. His recommendations included in A1C target of less than 6% achieved by lifestyle modifications along with a triple combination therapy of metformin, PCDs and exenatide as early initial therapy to correct known pathophysiologic defects in Type 2 diabetes patients. The ADA is now funding a research study by Dr. DeFronzo to compare his proposed algorithm with the existing ADA algorithm in respect to long-term health benefits. Third, shortly as discussed and generally consented because it matters how doctors achieved tight glycemic control for patients with Type 2 diabetes. These discussions are an outcome from the seemingly contradictory findings of large scale trials including the ACCORD trial, Advanced trial and the veterans administration diabetes trial. These studies show the aggressive treatment of diabetes with older therapies can come with a price such as the risk of hyperglycaemia, weight gain or increased cardiovascular risk. We believe doctors are now more center typed to these issues and are looking at BYETTA and other treatment approaches that did not incur these risks. In fact, data presented from the ACCORD trial suggest that the mortality hazard ratio was reduced only for patients on BYETTA, which is confirmed is indicative of a strong trend towards decreased cardiovascular events for the medicine. Now, while the ACCORD study was not powered to look at this end point, many in the medical community have commented that this further supports the benefits of BYETTA. These events are notable because for the first time, it is the medical community and not Amylin or Lilly driving the conversation about the shifts that are needed in the treatment of type 2 diabetes and the potential of the class and the benefits of BYETTA. Specifically, we are starting to see that physicians, patients and payers are beginning to advocate for a new definition of efficacy, glucose control with weight loss and safety in the type 2 diabetes medicine. For safety, there is a new emphasis on medicines showing a low risk of hypoglycemia and low potential for exacerbating cardiovascular risk factors. Amylin is in an enviable position as we have the only available medicines that meet these criteria. We are in a position to leverage this emerging tide of support from the medical community and to translate it into BYETTA sales. In the second quarter, we executed a range of marketing and sales initiatives to better communicate with doctors and patients. First, during the quarter, we implemented the expanded and more closely aligned sales organization with our partner Lilly. As part of that execution, we initiated the BYETTA-CIALIS co-promotion at the end of the quarter. Second, we introduced an expanded program to communicate with primary care physicians about the benefits of BYETTA. Let me first discuss the expanded and more closely aligned sales organization. We optimized the sales force in concert with Lilly by expanding the overall number of representatives by 40% through the BYETTA-CIALIS co-promotion agreement. Concurrently, we expanded our primary care field force by 15% to allow alignment of our territories with Lilly to improve the reach and frequency of code on high prescribing primary care physicians. We also rolled out expanded physician and patient support programs for the primary care market. These programs are designed to better support patient new starts and to improve the long-term patient adherence. Further we are recruiting sales representatives with a targeted access education program for primary care physicians that reinforces the over 85% of access for BYETTA across commercial managed care providers. Next, I will discuss the messages to primary care physicians. The messages complement our expanded and more closely aligned sales force and will continue to evolve as we gain additional insights into what impact prescribing behaviors. In the first quarter, we began to emphasize that BYETTA provides powerful glucose control along with the products known weight benefits. We track key metrics and so about that message began to resonate early in the second quarter. These metrics included improved primary care physician recall of BYETTA brand messages. Looking closely for a recall of glycaemic control as the number one message followed by weight. Improved primary care physician comfort with prescribing BYETTA, which correlates to a greater understanding of what to expect from the medicine. Our research shows that doctors who have clearer expectations of BYETTA prescribed more. As we were raising the awareness about the potential for powerful glucose control with BYETTA, we learnt something rather surprising. Weight as a clinical parameter in the treatment of type 2 diabetes is undervalued by primary care physicians. To address this we evolved BYETTA messages and marketing tools to include education on the importance of weight as a clinical parameter in the treatment of type 2 diabetes. This complements the data demonstrating that BYETTA is a unique solution with opposite vantages of a reduction in A1C and a reduction in weight. We expect to start to see the impact of this latest message evolution during the second half of this year. In order to determine we are on the right track towards increased prescription, we will be watching for one, an increased understanding of the importance of treating both A1C and weight in the treatment of type 2 diabetes. Two, increased record of BYETTA's core messages and three, increased new patient stocks on BYETTA. To be clear we look forward to seeing the results of the market accelerated and our enhanced marketing and sales efforts in the second half of 2008. Now lets move on to SYMLIN. A synthetic analog of human Amylin and naturally occurring hormone that is made in the beta cells of the pancreas. The same cells that make Insulin. Symlin is the first and only Amylin mimetic. Its key benefits are that it provides mealtime glucose control and weight loss to patients who use mealtime insulin. Symlin continued to show steady growth, with total prescriptions growing 5% for the second quarter over the first quarter. In the second quarter, Symlin Pen accounted to nearly 60% of new Symlin prescriptions and 40% of total Symlin prescriptions. Total sales for Symlin grows 13% quarter-over-quarter. In the same pain of improving the BYETTA patient experience we've continued to Symlin's support program. We have the live telephone support from medical professional is to aid new SYMLIN patients in the first few weeks of therapy and beyond. We are also pleased to report that within six months of the SymlinPen launch, we already have nearly 80% open access for SymlinPen with over 60% of covered lifes at Tier 2. Now I want to share with you the latest developments regarding exenatide once weekly, the next planned medicine in our pipeline. This product candidate is poised to become the first once weekly therapy to treat type 2 diabetes with unprecedented duel efficacy defined as powerful glycaemic control and sustained weight loss. This is durable control that is offered in just one dose per week, a break through in convenience. In the second quarter, we had our pre-NDA meeting with the FDA and continue to plan on submitting an NDA before the end of the first half of 2009. However, I want to underscore that Amylin and our partners are focused on moving the submission date forward. To that end, we have made great progress by finalizing the commercial scale manufacturing process at our Ohio facility. Indeed, we've already produced and shipped commercial scale material, which we will use in ongoing and planned clinical trials in the coming weeks. As I've already mentioned, we met with the agency in the second quarter to discuss the open items for our regulatory submission. I'm pleased to say that following these discussions, we believe that the DURATION-1 study we reported last year provides the necessary safety and efficacy data for a submission. As a reminder, exenatide once weekly is a line extension product and the DURATION-1 study was designed in consultation with the FDA. Our regulatory strategy is based on leveraging the existing safety database for BYETTA. The rate limiting step to a regulatory submission is showing comparability between the material manufactured and our facility in Ohio and the intermediate scale material used in clinical studies to date. During our pre-NDA meeting, we received more clarity on our strategy for showing comparability. We continue to execute this strategy and data from our in vitro-in vivo correlation or IVIVC studies will be reviewed in the next few months. If this stays as accepted, we can accelerate the submission. However, as we've said in the past, this is a data driven process and until we are able to demonstrate to the FDA that this data is sufficient to show comparability, we are reiterating our previous guidance on timing of a submission. We have discussed the other parts of the strategy to demonstrate comparability, one, the crossover of patients from the extension of our pivotal study and, two, a new pharmacodynamic bridging study with a clinical endpoint. These studies are moving forward. To be clear, our guidance on the timing of an NDA submission is based on the conservative path of completing the latter study. Now I should understand there are specifics of our interactions with the FDA and elements of the pre-NDA meeting that we are not able to share with you at this time. This is consistent with ensuring that we meet the requirements of the agency. We will not speculate on potential FDA action regarding the date of dependent nature of our regulatory path going forward. Now, moving on to clinical data, DURATION-1 findings, both the 30-week pivotal study and the 52-week extension study were presented at ADA 2008. The data showed the continuous steady state levels of exenatide on board 24 hours a day, seven days a week provides durable glycemic control with weight loss. I will quickly summarize the findings of this landmark study. At ADA, we provided detail that in the 30 week study Type 2 diabetes patients treated with exenatide once weekly showed statistically significant improvements in A1C and fasting plasma glucose from baseline compared with BYETTA. Patients in both treatment groups also reported significant weight loss averaging 8 pounds and 77% of patients treated with exenatide once weekly achieved an A1C at 7% or less. After one year of treatment, patients taking exenatide once weekly sustained improvements in glycemic control and weight. Additionally, improved glucose control was seen in patients switching after 30 weeks to exenatide once weekly from exenatide taking twice a day. Specifically, patients in both treatment groups experienced an average A1C decline of 2.0%. This level of A1C decline is unprecedented in a study of this type in patients with a mean baseline A1C of 8.3%. 74% of all patients achieved an endpoint A1C of 7% or less at 52 weeks. Furthermore, patients in both treatment groups reported a sustained average weight loss of 9.5 pounds over 52 weeks. Based on our confidence from these data, we put in place an aggressive clinically relevant program that compares exenatide once weekly against competing products that demonstrates superiority. The objective of these studies is to support the launch and demonstrate the transformational nature of exenatide once weekly therapy. These trials are on track. DURATION-2 comparing exenatide once weekly against the TCP and DPP-4 inhibitor on a background of metformin therapy and DURATION-3 continued exenatide once weekly against insulin glargine on a background of oral agent therapy are currently in rolling patients. We look forward to reporting results of those studies in the first half of 2009. DURATION-4, looking at exenatide and as a standalone therapy against either metformin, TZD or DPP-4 inhibitor will begin later this year. Additionally, given the positive effect from cardiovascular surrogate outcomes seen with exenatide, the encouraging data seen in the ACCORD trial and the current regulatory interest in cardiovascular outcomes, we have initiated discussions with outside experts to help design a robust post-marketing cardiovascular outcomes trial. Clearly, we are actively positioning the exenatide franchise for near and long-term success with an eye to addressing the potential entrants of competitors in our class. The powerful durable results from the exenatide trial, the three years of BYETTA's experience in the market and the stellar results from DURATION 1 trial are compelling proof to exenatide is the best molecule in a class as a twice a day product now and as a once week product in the future. Also I would note that given exenatide's potency, we are continuing to study with our partners the potential for less frequent dosing regimens as well as non-invasive dosing forms. Transitioning now to the broader regulatory environment, I will comment quickly regarding our perspective on the impact of the recent FDA Advisory Committee meeting focused on safety issues in developing medicines for the treatment of diabetes. We are pleased that the FDA is considering the importance of cardiovascular health in the treatment of type 2 diabetes. We do not see the potential new guidance as having an impact on the commercialization timeline for exenatide once weekly. The draft guidance is designed to address new chemical entities, while the regulatory strategy for exenatide once weekly is a line extension referencing the BYETTA label. We do believe, however, that the guidelines may create a higher hurdle for new entrants into the market. Now I will move on to describe our significant opportunities in obesity. We believe peptide hormones provide a unique opportunity to create a meaningful product that produces clinically important weight loss safely. We previously announced our commitment to pursue a medicine for obesity that is a combination of pramlintide, an analog of human amylin and metreleptin, an analog of human leptin. This commitment is based on impressive study results, 12.7% reduction in body weight over 24 weeks when pramlintide and metreleptin were used together. In the second quarter, we initiated a Phase 2b study to evaluate different dosing combinations of pramlintide and metreleptin. This is a six month multi-arm study that will enroll approximately 600 patients and will take about a year to complete. We believe this product candidate has the promise to meet the unmet medical need for a highly effective and safe weight loss therapy. Additionally, we look forward to having a significant presence as the Obesity Society's Annual Scientific Meeting in the beginning of October. And as Mark mentioned earlier, we are actively pursuing options to offset the R&D expenses associated with our [inaudible] early stage programs through potential partnerships and/or project financing. Now, I'll add a few more comments before we close. As a member of Pharma, we are proud to support the newly revised pharma guidelines on interactions with health care professionals, which demonstrates our industry's commitment to high ethical standards and transparency. I'm also pleased to announce that consistent with our mission of putting the patient first. In the second quarter, we submitted a treatment IND for leptin, as a treatment for severe lipodystrophy, which is a rare, but very serious disorder and we're pleased to be able to make leptin available to these patients. It is an exciting time here at Amylin as we position the company for sustained value creation and growth. I want to make it clear, that this year we are focused on one driving BYETTA and SYMLIN growth. And I would emphasize that our expectations for product revenue in 2008 remains unchanged. And two, accelerating the NDA submission for exenatide once weekly. With that I'll conclude the formal portion of today's call and turn things back over to the operator for your questions. Question and Answer
Operator
[Operator Instructions]. Our first question comes from Thomas Wei with Piper Jaffray. Your line is open. Thomas Wei - Piper Jaffray: Hi, thanks very much. I had a couple of questions, just first on the pre-NDA meeting, you mentioned that it was actually in the second quarter, have you had a chance to talk to the FDA, since the panel vote to just confirm the adequacy of Duration One, in light of how [inaudible] there? Daniel M. Bradbury - President and Chief Executive Officer: Hi, Thomas yes , thanks for the question. You're right, we didn't say within the second quarter, and that the FDA panel meeting was actually subsequent to that. I'd make a note that, Thomas, you know... the FDA panel meeting was really focused on cardiovascular risk associated with new chemical entities and that's what the major difference is here, that I think, I emphasized in the call and I'd re-emphasize to you again. The exenatide once weekly strategy is a line extension regulatory strategy and it really takes into account, the entire safety database that we have with Exenatide. BYETTA has been on the market now for over three years, we have over a million people have been exposed to it and met clearly the strategy that the agency is undertaking. I'd also further emphasize, Thomas, as you think about the profile that we have with exenatide, this is a compound which lowers body weight, has a low risk of hypoglycemia and most importantly I think as you noted in one of your writings earlier this year, we look at cardiovascular surrogate endpoint, all of those are going in the right direction, blood pressure goes down, triglycerides goes down, LDL goes down, HDL goes up. So in terms of cardiovascular risk, we are actually in a strong position as a company and therefore I think the agency was fully cognizant of that at the time that we had the meeting with them in June. Thomas Wei - Piper Jaffray: And also in the pre-NDA meeting, when you talk to FDA about the IVIVC studies and the crossover strategy is kind of unconventional alternative to bioequivalence, what did they actually say? In theory, if you have good data, do they endorse either one or both of those approaches? Daniel M. Bradbury - President and Chief Executive Officer: As I mentioned, certainly I would just leave you with the thought that if we are able to provide the data in the format and to meet the requirements of the agency with regard to the IVIVC and/or the crossover study from DURATION-1 extension, we will be able to accelerate the submission time line. One thing I did mention on the call that there are specifics of the interactions that we had with the agency and elements of the pre-NDA meeting that we are not able to share with you in this time. And that's really making sure that we don't get ahead of ourselves and making sure that we don't speculate on potential FDA reaction to the data that we are going to generate from those studies going forward. Thomas Wei - Piper Jaffray: Thank you. Daniel M. Bradbury - President and Chief Executive Officer: Thanks, Thomas.
Operator
Our next question comes from Meg Malloy with Goldman Sachs. Margaret Malloy - Goldman Sachs Research: Thanks very much. I'd like to follow up on Thomas' question, in terms of... if a de novo study were required, did you talk about what the requirements there might be, so could it be something like a 100 patients and you could look at... I don't know if you need to look at HbA1c or if there would be maybe a shorter metric that might be considered, have you hammered that out at all? Daniel M. Bradbury - President and Chief Executive Officer: You know, Meg, I'd just sort of go back to my previous statement. We certainly did have conversation with the agency as I mentioned in my prepared remarks about a new pharmacodynamic bridging study with a clinical endpoint. However... and I think it's fair to say that we do have pretty clear view in terms of what would be required going forward. However, because we also have other strategies that potentially would meet the agency's requirement to meet comparability that we are continuing to pursue those as well and they may or may not meet the need without the initiation of that study. So at this point what I would say is we do have a very clear idea however whether or not we will need to do that or not is yet to be determined based on the data coming up from our existing efforts in terms of showing comparability. What I would say is that we are confident that the guidance that we've given that submission by the end of the first half of 2009 is consistent with any particular I should say any specific requirements that the agency would have for a new pharmacodynamic [inaudible] study. Mark G. Foletta - Senior Vice President, Finance and Chief Financial Officer: Yeah, yeah hi Meg, how are you? Margaret Malloy - Goldman Sachs Research: Thanks so much. And if could ask an additional question maybe for Mark. Could you comment on actual inventory levels that it, was the inventory level normalized for the Q4 stocking and Q1 draw down, can you give us a sense of what you consider it to be normalized? Mark G. Foletta - Senior Vice President, Finance and Chief Financial Officer: Hi, Mag how are you? Thanks, for the question. We believe as I stated in the prepared remarks I'll reiterate that inventory levels at the end of the second quarter were comparable to where they were at the end of the first quarter and that actual shipments in the second quarter reflect patient demand, obviously there is a range of the inventory levels that's based upon our visibility to the channel varies though we think it's certainly well within that range and we would expect script date [ph] in future kind of like we said at the last call to be productivity [ph] well of revenue that we record in future quarters. Margaret Malloy - Goldman Sachs Research: There wasn't really a work down in Q2 then? Mark G. Foletta - Senior Vice President, Finance and Chief Financial Officer: No, we really think that it was... it was relatively at the same levels as we were at the end of Q1. Margaret Malloy - Goldman Sachs Research: Okay. And if I could just ask one final question, could you elaborate on what you are thinking about in terms of the obesity program you mentioned possible partnerships or strategic financing and not using your exact [inaudible] I was wondering if you could share your thought process around that, Dan or Mark? Daniel M. Bradbury - President and Chief Executive Officer: Yeah. Hi Meg. Yeah Meg I will take that one. I mean, one of the things we are looking at going forward is how best to advance those programs going forward and also maximize the value of the programs to our shareholders. Those programs are global development programs and so we have this range of different options that are available to us, whether it be just looking to have just a financing partners that enables us to advance the program without incurring the income statement's cost associated with the program or whether it be strategic commercial partner and development partner who could actually enable us to... which would bring new capabilities that would enable us to advance the program more efficiently going forward. I would say that our thinking in this area is highly dependent on our commercial success that we see going forward with regards to exenatide and SYMLIN... sorry, BYETTA and SYMLIN, both in terms of revenues, as well as some of the technical success that we have on an ongoing basis. So, it's both revenue and as well technical success basis for going forward. Margaret Malloy - Goldman Sachs Research: Okay. Thanks, Mike. Daniel M. Bradbury - President and Chief Executive Officer: Thanks, Mag.
Operator
Our next question comes from William Ho with Bank of America Securities. Daniel M. Bradbury - President and Chief Executive Officer: Hi, William.
Operator
William, please check your mute button. William Ho - Bank of America Securities: Hello, can you hear me? Daniel M. Bradbury - President and Chief Executive Officer: Hi, William. Yes. William Ho - Bank of America Securities: Hi. Just want to see if you could discuss a little bit more about the progress you've been making with the expanded sales force. It appears that SG&A may be increasing, but we've seen... we haven't seen a strong uptick in sales as a prescription number thus far. And in order to get to your, I guess, your revenue guidance, it looks likes we need to see a strong uptick in sales. How long does it generally take for each new rep to ramp up and what kind of progress are you making there? Daniel M. Bradbury - President and Chief Executive Officer: Hi. William, I will make a comment about the sales force and then ask Mark to comment about SG&A levels. So basically, we announced at the end of... in our previous quarterly call that during the second quarter we would be ramping our sales force and indeed also completing initiating I should say the BYETTA-CIALIS co-promotion agreement. All of that was done in the later part of the second quarter, and indeed the BYETTA-CIALIS co-promotion agreement did not commence until the first of July. So we wouldn't expect at this point to have seen anything from our adjustments and that would be... as I mentioned on the call, we would be expecting to see benefit from those sales force efforts appearing in the second half of this year. Now a lot of this was anticipated in our previous guidance, but may be Mark you could add to that. Mark G. Foletta - Senior Vice President, Finance and Chief Financial Officer: Yeah, Will. Thanks for the question. I think you should think of the majority of the cost certainly being in the 2Q numbers and the guidance that we have given really at the lower end of the range of 425 million to 475 million for SG&A for the year. If you just annualize -- if you semi-annualize the second quarter number, I think, you will find that, that's exactly where you will be. So we see essentially the costs are in place and executing in terms of driving BYETTA and SYMLIN sales during the second half of the year. William Ho - Bank of America Securities: Okay, great. Thank you. Daniel M. Bradbury - President and Chief Executive Officer: Thanks, William.
Operator
Our next question comes from Matt Osborne with Lazard. Matthew Osborne - Lazard Capital Markets: Hi, and thank you for taking the questions. Just had a few on the cardiovascular outcome trials you mentioned, would you contemplate starting these at the time that the exenatide LAR filing is under review or truly post...post approval? Daniel M. Bradbury - President and Chief Executive Officer: It's a great question, Matt. Thanks for question. Actually, it's really dependent, I think on the advice that we are getting from our experts at the moment. I expect to... that we will be in a position by the end of this year to finalize the study design on cardiovascular outcome study and of course the... so the timing relative to submission will depend on how successful or not we have been enable to accelerate the submission of exenatide once-weekly. I don't think we hold back on initiating the study prior to the submission. Matthew Osborne - Lazard Capital Markets: Okay. And will you be able to provide data from BYETTA patients from real world experience, in terms of high-risk patients, who are on BYETTA now. It's kind of a data package that would precisely update in terms of showing and CD benefit? Daniel M. Bradbury - President and Chief Executive Officer: So we have very expensive data are actually, already on BYETTA in terms of cardiovascular surrogate endpoints. There is a... actually at the American Diabetes Association this year we showed both with BYETTA and with exenatide once weekly benefits in terms of lowering triglyceride, lowering LDL, increasing HDL and I think most impressively the affects that we are seeing on blood pressure. I am seeing very significant reductions in blood pressure particularly with exenatide once-weekly. So, when you think back about... particularly about the panel discussion, the co-fo [ph] additional studies was really directed when there was some kind of signal in that suggested that there might be an issue with regards to cardiovascular risk. In our case, what you're seeing is a compound, where the cardiovascular risk factors, I should say, surrogate endpoints all actually going in the right direction and that of courses is further reinforced with the benefits in terms of decreased bodyweight. I also don't think by the way the preliminary outcome analysis from the ACCORD study harms us in any regard in that results... in that regard as well. I mean, the fact that a major independent study is completed and the only compound that was actually shown to reduce the acid ratio with regards to cardiovascular outcome with exenatide, I think certainly helps us. Matthew Osborne - Lazard Capital Markets: Again, last question actually for Mark. Can you remind us on the cost-sharing agreement with Lilly would that CB Outcome trial be split with Lilly? Mark G. Foletta - Senior Vice President, Finance and Chief Financial Officer: Yes, absolutely, it would be. Matthew Osborne - Lazard Capital Markets: Okay. Thank you. Daniel M. Bradbury - President and Chief Executive Officer: Thanks very much.
Operator
Our next question comes from Biren Amin with Stanford Group. Biren Amin - Stanford Group: Yeah, hi and thanks for taking my questions. Could we expect to hear by the Q3 call regarding IV, IVC and cross over on direction... [inaudible ] when expansion and whether they are not profiling? Daniel M. Bradbury - President and Chief Executive Officer: Hi, Biren. Yeah, I think it's going to depend very much on how this data comes out. I said in the call... I think so I've mentioned it. It would be in the coming months we'd be getting the data and just to say that I wouldn't like to give a specific time point to that because until we see the data and until such time that we also know... and have the opportunity to have further discussions with the agency, I think it would be an appropriate for me to give you a specific date upon which that we would be providing an update. Biren Amin - Stanford Group: Okay. And a follow up question, would you also give us an update regarding the needle gauge where we are? Do you plan to file on the 23 gauge needle? Daniel M. Bradbury - President and Chief Executive Officer: Biren, I guess the way I would answered that question is to say, we are really committed to ensuring that we have the most patient convenient product form available at the time of launch that is possible, and we're continuing to look for opportunities to refine that product offering. That includes the instructions that we'd be giving the patient, the needle dimensions, both in terms of length and gauge, et cetera, but also in terms of how the patient actually has to handle the product. I would say, I mean just to sort of pick up on your question, well, I think now where you're going here is there has been some concerns in the, I should say investment community that needle gauge is going to be an issue. And I'd point you to the data that we presented at the American Diabetes Association which showed extremely high patient satisfaction scores with the presentation that was used in the study and we of course intend to improve upon that patient... on that product offering. Biren Amin - Stanford Group: Great, thanks. Daniel M. Bradbury - President and Chief Executive Officer: Thanks, Biren.
Operator
Our next question comes from Phil Nadeau with Cowen & Company. Phil Nadeau - Cowen & Company: Good afternoon. Thanks for taking my question. Two questions, first just housekeeping item, Mark, could you tell us how much stock comp expense was in the R&D and SG&A line? Mark G. Foletta - Senior Vice President, Finance and Chief Financial Officer: Yeah, one second. Let me pull that up. Hi, Phil. In the quarter there was $20 million of stock comp, $12 million in SG&A, and $8 million in R&D. And the year-to-date period would be $23 million in SG&A and $16.5 million in R&D. Phil Nadeau - Cowen & Company: Okay, great. That's really helpful. And my second question is on really the... wanted to take it to the [ph] earlier files, and it seems one of the things that's missing from your three-part strategy is just a simple PK study. So, a PK study with a PK end point. Can you talk a little bit more about why that's not one of your options and whether that is something that Amount [ph] itself has decided probably wouldn't work or did those come from the FDA? Daniel M. Bradbury - President and Chief Executive Officer: Yes, great question Phil. So, I guess we're kind of addressing it when you're thinking of a simple PK, I think what you're thinking is a single dose study, right. And when you give a single dose of exenatide once weekly produced at intermediate scale and one was given [inaudible] using material produced at commercial scale. Am I right in terms of thinking that's what you are thinking of as a simple PK case study? Phil Nadeau - Cowen & Company: Yeah, or something may be you give a couple of weeks worth of LAR and you just look at pulse [ph] levels? Daniel M. Bradbury - President and Chief Executive Officer: Yeah. Well, so... certainly, we will be looking at either in the crossover from the extension study and/or if we do a new pharmacodynamic bridging study, we would be looking at PK. However, one of the key things here is that when you look at the PK, you can actually have pretty significant variability and so have the same level of effect on blood glucose, and that's mainly because the therapeutic index of exenatide is so wide. And so in terms of comparability, what the agency is really trying to show here is... and that is not necessarily the case by the way with every medicine. I mean, with medicines that have narrower therapeutic indexes, it is more important to have a more precise comparability with regards to PK. And I am not so sure you are aware, Phil, when you look at subcutaneous injections, you have very high variability in PK anyhow both intra and inter patients as well. So that's particularly the case when it comes to you looking at long acting release versions and particularly long acting release versions where a single injection is released over two to three-month period, but dosed on a weekly basis. So the PK from a single injection is not necessarily indicative of the PK that you would get from a series of injections and that's why the studies that we are looking at are little bit more complicated than this simple PK study. Phil Nadeau - Cowen & Company: That's very helpful. Thank you Daniel M. Bradbury - President and Chief Executive Officer: Thank you, Phil.
Operator
Ladies and gentlemen, due to time constraints we only have time for one more question. Our final question comes from Tom Russo with Baird. Tom Russo - Baird: Hi, thanks for taking my question. Dan, could you comment if the antibodies issue came up at all in your FDA meeting? I know some have looked at the level in the once weekly formulation versus the twice-daily? Daniel M. Bradbury - President and Chief Executive Officer: Yeah. Hi, Tom. Well, as I said previously, we haven't given specifics. We just say we don't believe that's a constraint for our submission going forward. And I would comment by the way that this is an area again, where I think has been, I guess an inappropriate level of interest relative to what the concerns are here, because if people spent enough time actually looking at the data, what we'd see is that antibody levels associated with the exenatide once weekly returns to the levels that we see with exenatide when given twice a day in the form of BYETTA after about one years worth of use. And so consequently, we don't see that this is a real challenge from the agency standpoint. Certainly, what we absolutely can confirm is that there is no major safety issues associated with those antibodies which is of course the primary concern that most people have when considering antibodies associated with protein or peptide based drugs. Tom Russo - Baird: And then real quick one follow up. The ACCORD data, the cuts that were presented on the last day of ADA, do you anticipate that those might be published at some point in the future and provide you an opportunity to maybe leverage those commercially or in medical education effort? Daniel M. Bradbury - President and Chief Executive Officer: Yes, terrific question. We're certainly very hopeful they will be published. It is our understanding that they are. The slides from the presentation actually are available on the Web now, and so that data I mean has been made available publicly. So I would expect that it would be subject to peer review going forward. And the extent that we can leverage it from a commercial standpoint, I think depends very much on exactly what is published and what statements are made around it. Tom Russo - Baird: Okay. Thanks very much. Daniel M. Bradbury - President and Chief Executive Officer: Thank you very much, Tom. Okay, well thanks. Just a few final remarks to say thank you to everybody for being on the call today. We appreciate your time and as always your interest in our company. If there are any additional questions, please contact Michael York in Investor Relations and we will get back to you. I would finish by stating that Amylin, we are focused on driving further BYETTA and SYMLIN growth and accelerating the NDA submission for exenatide once weekly. Thank you again for your interest.
Operator
Once again ladies and gentlemen, thank you for participating in today's conference. This does conclude our program for today. You may all disconnect and have a wonderful day.