Curis, Inc. (CRIS) Q4 2011 Earnings Report, Transcript and Summary

Good morning, ladies and gentlemen, and welcome to the Fourth Quarter and Year End 2011 Curis Earnings Conference Call. [Operator Instructions] As a reminder, this conference call is being recorded for replay purposes. I would now turn the call over to Mike Gray, Curis' Chief Financial Officer. Please proceed.

Okay, thanks, Ben. Good morning, everyone and thanks, as always, for joining us today. During the call, we'll provide you with an update on our corporate developments and also discuss our fourth quarter and year-end 2011 financial results. Before we begin, I'd like to advise you that this conference call contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including without limitations, statements relating to expectations concerning the further development and commercialization of Erivedge, plans and prospects for progressing the development of CUDC-101, CUDC-907 and Debio 0932 and estimates with respect to our 2012 expenses, year-end cash position and other operating results. Actual results may differ materially from those indicated by forward-looking statements in this conference call as a result of various important factors including the Genentech and Roche may experience delays or failures in the further development, manufacture and commercial launch of Erivedge, we and/or Debiopharm may experience adverse results, delays and/or failures in our drug development programs. We may experience difficulties with maintaining intellectual property protections, maintaining key collaborations, managing competition and obtaining the substantial additional funding required to conduct our business. So we may experience unplanned cash requirements, may not receive additional anticipated payments under our collaborations, any of which would shorten the estimated period in which we expect to have cash to fund our operations. We also face other risk factors described in our quarterly report on Form 10-Q for the quarter ended September 30, 2011, and in other filings that we periodically make with the SEC. We caution you that we are making these forward-looking statements as of today, and that we may not update any of these statements even if events and developments subsequent to the date of this call cause these estimates and expectations to change. I'd now like to introduce Dan Passeri, Curis' President and CEO, who will discuss our corporate highlights and will also provide an update on our pipeline. Following Dan's remarks, I'll return with -- provide an overview of our financial results for 2011 and then we'll open the call up for questions. Dan?

Okay. Thanks, Mike. Good morning, everyone, and thanks for joining us today. 2011 was a highly important and critical year for us, one in which our execution in clinical development progress set the stage for important milestones and corporate development growth of 2012. Already, of course, the beginning of 2012 has been transformative following the recent FDA approval of our collaborative Genentech's NDA submission of Erivedge, as the first and only FDA approved medicine for patients with advanced BCC, which is a type of basal cell carcinoma that has spread to other parts of the body or that has come back after surgery or healthcare provider decides cannot be treated with surgery or radiation. This is Curis' first drug approval and Erivedge is also the first in class Hedgehog inhibitor to reach commercialization. As such, it's truly a landmark event for Curis and our shareholders, we look forward to further value-creating advances through 2012 and look forward to providing you with ongoing updates. Erivedge is being developed and will be commercialized by our partner, Genentech and Roche, under our collaboration agreement. At this time, I'd like to remind everyone that although this approval represents a watermark event for Curis and its shareholders, the Erivedge approval is more importantly a breakthrough for patients suffering from advanced BCC. And just to give you a context, BCC is the most common form of cancer in the United States and the most common type of skin cancer accounting for approximately 2 million new cases annually. While the disease is generally considered curable when restricted to a small area of the skin, a small percentage of this population may have the cancer advance further into the skin, bones or other tissue or spread to other parts of the body. In these cases, the disease is difficult to treat and often life threatening. Erivedge is now the only approved treatment for this advanced form of the disease. Prior to Erivedge's approval, there was no approved therapy for this disease. Advanced BCC often results in severe deformity or impaired function of the affected organs, and patients, historically, have typically received one or more interventions including surgery, radiation and various chemotherapies, none of which are effective therapies for advanced BCC. So the FDA approval of Erivedge is based on results from the ERIVANCE BCC trial, which was a pivotal international single-arm multicenter, 2-cohort, open-label, Phase II study that enrolled 104 patients with advanced BCC. This included 71 patients with locally advanced BCC and 33 patients with metastatic BCC. Patients with locally advanced BCC had lesions that recurred after surgery, or were not candidates for surgery because the lesions were considered inoperable or for whom surgery would result in substantial deformity or the lesions had recurred after radiotherapy, or were not candidates for radiotherapy. Study participants received 150 milligrams of Erivedge orally, once daily, until disease progression or unacceptable toxicities. The primary endpoint of the study was objective response rate as assessed by an independent review. The study showed Erivedge shrank lesions in 43% of patients with locally advanced BCC and 30% of patients with metastatic BCC. The median duration of response was 7.6 months and the median duration of treatment was just over 10 months. The most common adverse events observed in the study, which include those observed in greater than 20% of patients, included muscle spasms, hair loss, altered taste sensation, some weight loss, fatigue, nausea, decreased appetite and diarrhea. 4 patients, which was approximately 4%, had serious adverse events that will continue to be possibly related to Erivedge. Fatal events were reported in 7 -- 7% or 7 patients, one -- none of which were considered by the investigators to be related to Erivedge. In all these fatalities, pre-existing risk factors and co-morbid conditions were present. In addition to offering an important new treatment for patients, we believe that this approval has important immediate and potential long-term financial implications for Curis and its shareholders. Following the approval, Curis has earned a $10 million milestone payment from Genentech, and we expect Erivedge to provide Curis with potentially significant future revenues from our royalties on Genentech's net sales of Erivedge in the U.S. market with sales beginning eminently at a price of $7,500 per month per patient. Genentech and Roche are working to closely identify the exact patient population as they begin to launch this new drug. Importantly, though, Roche recently communicated that they estimate the market for advanced BCC in the U.S. alone to be approximately 14,000 patients. It's important to note, this number is an estimate, as there is no published epidemiological data on advanced BCC. In addition, we would receive potential additional milestone payments and royalties for development and regulatory approvals of Erivedge in advanced BCC in territories outside the U.S. market. For example, Erivedge is currently under review by the European Medicines Agency, the EMA, which if approved, will result in patient access within Europe. Roche has indicated that it currently anticipates possible approval by the EMA in either late 2012 or early 2013. Genentech is also currently conducting a Phase II clinical trial of Erivedge in patients with operable nodular basal cell carcinoma, which is a less severe form of the disease and accounts for a significant percentage of the approximately 2 million BCC's diagnosed annually in the United States. The study was initiated by Genentech in October 2010 to test Erivedge as a single agent therapy in approximately 50 patients with operable nodular BCC and a U.S.-based open-label, 2-cohort clinical trial. All patients received 150 milligrams daily oral dose of Erivedge for 12 weeks. The primary outcome measure for the first cohort is the rate of complete histological clearance of target nodular BCC lesions at the time of tumor excision, which may occur up to 12 weeks following initiation of treatment. While the primary outcome measure for the second cohort is the rate of durable complete clearance of target nodular BCC lesions at the time of excision, which may occur up to 36 weeks following treatment, initiation of treatment. Genentech has completed enrollment and data evaluation for patients treated in the first cohort of the study and has submitted data for this cohort for presentation at a medical conference during the first half of 2012. Genentech has informed Curis that further study and analysis of Erivedge inoperable BCC is required to determine a potential future development plan including completing ongoing patient enrollment and treatment in the second cohort, and we currently anticipate that the study will be completed during early 2013. We look forward to giving you updates as they become available. In addition to the operable BCC study being conducted by Genentech, multiple trials in other cancer types are ongoing by third-party investigators, including exploring Erivedge in basal cell nevus syndrome, which is also called Gorlin Syndrome, medulloblastoma, which is a pediatric brain cancer. It's approximately 30% to 40% have a Hedgehog involvement. Sarcoma, glioblastoma multiforme, as well as in pancreatic small cell lung, gastroesophageal junction, gastric, breast, prostate cancers, among others. We expect that some of these studies should yield data during 2012, and we look forward to providing additional updates on the Erivedge program as data becomes available on an ongoing basis. Not only does the Erivedge approval have significant financial implications for Curis but we believe that it also demonstrates the real potential of our pipeline of innovative, multi-targeted small molecule inhibitors, all of which are designed to achieve a more durable suppression of cancer networks with the potential to address the resistance that often develops with most targeted therapies. Curis was a pioneer in the basic discovery research around the Hedgehog pathway and we began our collaboration with Genentech in 2003 to continue research and development around the discovery and development of cancer therapeutics that are designed to inhibit this important pathway. Our scientists were actively involved in the preclinical research and development of Erivedge until its clinical testing began, at which point Genentech and Roche drove further development of this molecule. Our relationship with Genentech has been extremely important to Curis and our experience working with a world-class research and development organization has truly helped us develop highly capable core competencies and to shape Curis' strategic focus on internal discovery and development of next-generation targeted small molecule drug candidates for treating cancer. As a result of this strategic focus, Curis has discovered a number of highly promising drug candidates, including CUDC-101, which is our first-in-class proprietary potent and selective multi-target EGFR, Her2 and HDAC inhibitor, which we are developing and control ourselves as a key assets of company and I'd like to underscore that it's exemplary of our multi-target cancer network disruption approach. Also, Debio 0932, which is an orally available, wholly synthetic, non-geldanamycin Hsp90 inhibitor, licensed to Debiopharm, CUDC-907 is also a multi-class, multi-target inhibitor which is a first-in-class orally available small molecule, dual inhibitor of PI3 kinase and HDAC that we're advancing towards an anticipated IND filing later this year and I'll provide further updates on these programs momentarily. As we look ahead for the rest of 2012, the Erivedge approval is just a first of what we expect will be many key milestones for each of our 4 programs, which I'll outline for you now in more detail beginning with proprietary program CUDC-101. I'll now provide an update on 101 in terms of its clinical progress and also the development of a potential oral form. 101 is our lead proprietary drug candidate from our cancer-targeted network disruption programs. We believe that CUDC-101 is exemplary of our overall approach to designing novel drug candidates in which we aim to enhance the therapeutic effect and durability of clinical response by designing molecules that attack cancer cells at multiple complementary and potentially synergistic points of intervention. We refer to this approach as cancer network disruption. Very good, everyone is familiar with the limitations of single-targeted agents, to which the cancer typically adapts resistance to work around a single point of blockade. So our approach is to disrupt more than one point and the objectives of disrupting the networks that the cancer has access to. During the fourth quarter, we completed enrollment of the first cohort in our ongoing Phase I clinical trial of CUDC-101 and patients with human papillomavirus or HPV negative, locally advanced head and neck cancer, in combination with radiation in cisplatin. Just to remind everyone, HPV positive head and neck cancer is about 1/3 of the total number. The total number is about 45,000 patients annually, so there's about 30,000 patients that are HPV negative. The practical implications of that are that the virus is not driving the cancer and radiation in cisplatin have proven very effective against the virally -- the virus-driven cancer. We're focusing on the non-HPV EGFR and Her2 driven cancer. So the primary objective of this study is to evaluate the safety and tolerability of CUDC-101 when administered in combination with the current standard of care, which is radiation in intermittent cisplatin, which is a chemotherapeutic drug. Patients in the first cohort show no obvious toxicities beyond those related to the concomitant dosing that are generally observed with radiation and intermittent cisplatin. And appear to be benefiting from the drug combination, albeit it's still too early for conclusive statements. We are, however, highly encouraged by the early data as in these patients that we're observing and we look forward to providing you with further details as more detailed data emerges. Assuming that the last 2 patients remain on the study, without the occurrence of a dose-limiting toxicity, we anticipate that we can begin treating the first patient in the second cohort of this study later this month. We're currently recruiting patients at 4 study centers in the U.S. and plan to expand enrollment to additional sites. Importantly, our initial dose of CUDC-101 began at 225 milligrams per meter squared in this study and we're hopeful that we will only need to dose escalate one time, as we plan to dose the next cohort at our Phase Ia maximum tolerated dose of 275 milligrams per meter squared. I'll remind everyone that the starting dose of 225 is within the range that we believe is a therapeutic window where in earlier studies, we did see response at 150 milligrams. So we feel confident that we're within the therapeutic window starting at 225 and are optimistic that we'll be able to achieve the MPD in combination. Barring any occurrence of dose-limiting toxicity, in any of the patients treated at 275 milligrams per meter squared, our goal is to complete the dose escalation portion of this study in mid-2012 and then to treat up to 10 additional patients at that dose. Assuming the successful outcome of the study, we plan to progress CUDC-101 into a randomized Phase II study comparing the safety and efficacy of radiation and intermittent cisplatin therapy plus or minus CUDC-101 to begin in 2013. We view the head/neck cancer indication to be an ideal initial -- a commercial path indication with our current IV formulation of CUDC-101, as the drug targets the primary driving mechanisms of HPV negative head and neck cancers. It's also been synergy reported with the use of HDAC inhibitors with radiation and our scientists have demonstrated with preclinical data that CUDC-101 appears to synergize with intermittent cisplatin. Also, the IV-dosing schedule aligns well with the current standard of care where patients must present to the clinic every weekday for 7 straight weeks to receive radiation. So we're also continuing to progress, as I stated earlier, a possible oral formulation of CUDC-101 and currently expect that we'll file an IND during 2012. We're confident by the data that we have generated to date and optimistic that we'll be successful with this objective. Importantly, the oral formulation would allow us to expand potential clinical indications and take advantage of what we've observed and learned from the Phase I expansion cohort with the IV formulation. We're currently in the process of finalizing data and study close out of our Phase I expansion study with CUDC-101, and we anticipate that we'll present observations of the full data from this study at a medical conference during 2012. I'd now like to turn to CUDC-907 -- excuse me, which is an orally available synthetic small molecule dual inhibitor of PI3 kinase and HDAC. We believe that we received important external validation for this molecule during the fourth quarter of 2011 when we entered into an agreement, under which The Leukemia & Lymphoma Society, or the LLS, will support our ongoing development of CUDC-907 for patients with B-cell lymphoma and multiple myeloma. I'd like to just briefly touch upon, mechanistically, the advantages we believe 907 has. First, it's orally available. And we've demonstrated preclinically that it is potently and selectively blocking PI3 kinase phosphorylation and importantly, the HDAC component appears to block the compensatory bypass mechanism of MEK. And if you look at the clinical trials ongoing with large pharma companies that have PI3 kinase inhibitors, most of them have had to go back into Phase I studies combining it with a MEK inhibitor because that's the resistance pathway that's up regulated, and we believe the real advantage of the 907 is that it concurrently blocks 907 and prevents this resistant mechanism from being acceptable. So the agreement with, as part of the LLS therapy acceleration program, was a strategic initiative to speed up the development of therapies that have a potential to change standard of care for patients with hematological cancers, especially in areas of high met -- high-unmet medical need. And under the agreement, LLS will fund approximately 50% of the direct cause of the development of CUDC-907, which is up to $4 million. We're currently conducting preclinical studies of CUDC-907, and we have a solid body of data demonstrating, mechanistically, that 907 should have therapeutic effect on lymphoma, because we've seen that's the principal target mechanism of 907 where we're seeing really impressive targeting of lymphocytes. We expect to file an IND and then we'll start patient enrollment in a Phase Ia dose escalation clinical trial in the second half of 2012 in patients with B cell lymphoma and multiple myeloma. Again, underscoring the specific mechanism that we've observed preclinically in the study. If it's successful, LLS has agreed to support our subsequent Phase 1b or Phase IIa study in one or more specific indications, as well as our ongoing investigation of biomarkers for CUDC-907 in these diseases. We're very pleased with the opportunity to collaborate with LLS on the development of CUDC-907, and we are presently completing the required IND enabling studies for the CUDC-907, which again is an oral form, and we're also working on the final formulation of this drug candidate. Assuming favorable outcomes of these ongoing efforts, we plan to file an IND application for this compound in the third quarter of 2012. We look forward to providing further updates on CUDC-907 as this molecule advances towards the IND filing and Phase I initiation. I'll now turn to our Hsp90 program which is being developed by our licensee, Debiopharm. The lead candidate under this agreement is designated Debio 0932, which is a synthetic, non-geldanamycin, orally available small molecule Hsp90 inhibitor. In April 2010, Debiopharm treated the first patient in the Phase I clinical trial to evaluate the safety of Debio 0932 in patients suffering from advanced solid tumors. In 2011, Debio 0932 successfully advanced to the dose escalation portion of the Phase I study and the clinical results observed include single-agent responses in certain cancers and what appears to be a highly favorable safety profile. Debio has indicated that it expects to present results of this Phase I study at a medical conference during the first half of 2012. And just to remind everyone, the fact that we appear to have a highly favorable safety profile is already a differentiating competitive factor in positioning the drug where a number of Hsp90 inhibitors have demonstrated toxicities that have prevented their progressing further. So we're very pleased with the data generated to date. Debio is screening patients to initiate a Phase Ib study of Debio 0932 and we expect that a Phase I/II study of Debio 0932 in small cell lung cancer patients will be initiated in the second quarter of this year. The objective of this Phase 1b study and expansion cohort of certain solid tumor patients will be to further assess the safety profile, pharmacokinetics and pharmacodynamics of Debio 0932 at a potential Phase II dose level and to make a preliminary assessment of antitumor activity in patients with advanced solid tumors. We will be eligible for our next milestone under this agreement if and when Debio treats its fifth patient in a Phase II clinical trial, assuming that Debio advances, Debio 0932 into Phase II clinical testing. We currently anticipate that Phase II testing could initiate in the first half of 2013. Before turning the call back to Mike to review our fourth quarter and year-end 2011 financial results, I'd also like to note that the Head of Research, Chang Qian, will be departing Curis in the near future to pursue other opportunities, including the prospect of establishing a company in China to conduct preclinical and clinical development for the China market. Chang has been a valued colleague at Curis, has been instrumental in leading our research group that discovered CUDC-101, Debio 0932 as well as 907, since we began focusing several years ago on the discovery and further development of targeted small molecules for cancer indications. I'd like to personally acknowledge and thank Chang for his important contributions and wish him continued success in his future endeavors. Although Curis intends to continue to further develop selected discovery stage programs, our principal focus moving forward will be directed to continuing to enhance our capabilities and capacities for clinical development for our next-generation targeted cancer therapies including our proprietary asset CUDC-101 and 907. We've been transitioning our internal research team over the past year to focus upon translational research studies in support of our ongoing clinical studies of CUDC-101 and we expect that this will continue in the future for both CUDC-101 and 907. Going forward, all discovery and translational research activities will be conducted under Dr. Maurizio Voi, who has recently joined Curis as our Chief Medical and Development Officer and joined Curis in November of last year from Pfizer. As such, we currently have no plans to -- or we believe requirements to fill Chang's position. Again, I'd like to thank Chang for his contributions to Curis over the past several years and we certainly wish him success in his future endeavors. I'd like to now turn the call over to Mike for financial discussions and the following Mike's remarks, we'll open the call up for questions. Thank you.

Okay. Thanks, Dan. I'll now briefly run through our full year 2011 financial results. For more details on this and on our quarter results, please refer to this morning's press release. For the year ended December 31, 2011, we reported a net loss of $9.9 million or $0.13 per basic and fully diluted share as compared with a net loss of $4.4 million or $0.06 per basic and fully diluted share for the year ended December 31, 2010. Revenues for 2011 were $14.8 million as compared to $16 million in 2010. Operating expenses were $22 million for the year ended December 31, 2011, as compared to $21.6 million in 2010, with R&D expenses at $13.7 million for 2011 versus $11.4 million in 2010 and G&A expenses of $8.3 million for 2011 as compared to $10.3 million in 2010. Other expenses $2.7 million in 2011 as compared to $1.2 million in 2010. And as of December 31, 2011, our cash, cash equivalents and marketable securities totaled $37.7 million and there were 77.1 million shares of our common stock outstanding. Looking forward into 2012, we expect that we'll end 2012 with cash, cash equivalents and marketable securities of $23 million to $27 million, importantly, this excludes royalty revenues that we expect to receive from Genentech on its net sales of Erivedge. And this expectation also excludes any future milestone payments from existing or new collaborators that we may receive later in 2012. We expect our 2012 R&D expense to be between $16 million and $20 million and G&A expense to be between $10 million and $12 million. These expense expectations include approximately $800,000 and $2.5 million of stock-based compensation expense in R&D and G&A expense, respectively. And just in closing, as Dan mentioned, we anticipate 2012 will be a transformational year for Curis. I'd just like to wrap up quickly by bulleting through some of the key catalysts in each of our 4 significant programs. For Erivedge, Genentech is selling the drug either now or in the imminent future and we'll begin earning important royalty revenue on Genentech's net sales of Erivedge this quarter. Additionally, Roche could receive potential approval of its marketing authorization application from the EMA in late 2012 or early 2013, triggering an additional milestone payment to Curis and expanding the global commercial opportunity of Erivedge. We expect also that we'll receive additional updates from the ongoing Phase II operable BCC trial and that we'll receive additional data from multiple ongoing trials being conducted by third parties on Erivedge. For CUDC-101, we expect to begin dosing the second cohort in the Phase I HPV negative head and neck cancer trial in February, and complete the dose-escalation portion in mid-2012, followed by an additional approximately 10 patients using the same dose prior to advancing to a randomized Phase II study next year. We expect that we'll present data from our Phase 1b expansion study at a medical conference in the first half of 2012, and we plan to file an IND and begin testing of an oral form of CUDC-101 in the second half of this year. For CUDC-907, we expect that we'll file an IND and begin Phase I testing of this molecule in the second half of 2012 as well. Importantly, on that end, we'll also begin receiving LLS funding for development around the same time in the second half of 2012. For Debio 0932, Debiopharm is screening patients for the initiation of a Phase 1b study of this molecule and we expect also that Debiopharm will begin a separate Phase I/II study of Debio 0932 in non-small cell lung cancer patients in the second quarter. Followed by potential Phase II testing in non-small cell lung cancer patients in the first half of 2013, which will trigger a milestone to Curis. In addition, Debiopharm will present Phase I study results at a medical conference during the first half of the year. So in summary, 2012 promises to be a really productive period for Curis, really a very significant catalyst across all of our development programs. So with that, we'll open the call up to questions. Operator?

[Operator Instructions] Our first question today comes from the line of Ren Benjamin.

A couple of questions before I jump in the queue. Can you talk a little bit about, is there anything you can tell us regarding the sales and marketing strategy that Genentech will employ here in the U.S.?

Yes, so the general sort of reaction to that is we've seen their-- some of their marketing material. I mean they're clearly focusing on this patient population that has no therapeutic alternative, they've put together an extremely professional sort of proactive strategy ready to launch. So we've been impressed by how prepared they are for the prospect of approval and now that we have approval, they're really well-established to hit the ground running and to educate the end users, the prescribers, as with the benefits of this drug. We're really encouraged by their support of this program, their commitment to it, the importance of this drug for this indication and we haven't really talked to them about forecast from a revenue generating standpoint. And that will clarify over each quarter. But the short answer is, Ren, we saw some of their material, and we're very impressed with sort of how dedicated they are to this program and how prepared they are to launch.

And just regarding the status of the operable study. You mentioned that the study would complete in -- at least as of now, you think the study will compete in early 2013. And if that is correct, it seems to be a push-out in terms of the timetable what we've previously thought. Can you give us any sort of a sense as to why that is? Is it Genentech Roche is going to be spending a little bit more time looking at the first cohort data? Are they seeing anything from the data that might make them modify the trial going forward or is this just the normal phase?

They've made some observations that clearly, they're seeing activity and it's really trying to clarify the activity that they're seeing, the best prospective use of the drug in this indication, bearing in mind that there are adverse events with the drug. So it's trying to better understand if they can position it in this market, how to position it and looking at sort of different scenarios and to better understand the data that's been generated with a very small group so far. So I think what they want to do is take a closer look at this data and generate additional data to clarify what the best strategy forward is.

Okay. And just switching gears real quick to 101, you had mentioned that the status in the head and neck cancer study, that also, it seems like the randomized study would start in 2013. It suggests to me that you think that the dosing portion of the study could go longer than what you thought based on the data that you're seeing. Can you give us any sort of clarity or color around what's happened with the first 3 patients in the cohort, are you seeing any sort of what would be better-than-expected responses or better-than-expected side effect profile?

Yes. Thanks, Ren. So first, we're not actually having to push the data, this is actually right on target with what we were expecting based on the enrollment rate. We're not allowed to start the second cohort until we finish the first. So a couple of comments. First, I'd like to just add that with Dr. Maurizio Voi's addition to our team, the dialogue with the PI's has really improved dramatically, so we're really getting good quality input from the physicians. They're very encouraged by the prospects of this drug for targeting this patient population. In the first cohort, it's certainly too early to make any conclusive statements. We have seen activity, very encouraging activity with the first patients, second and third are starting to emerge with some encouraging signs, but it's too early to make any public conclusive statements. But suffice to say that we're highly encouraged and we're looking forward to completing the dose escalation with the prospects of starting the Phase II on schedule, which we anticipated to be, I think, we've always stated end of 2012, beginning of 2013.

Okay. And in the past, when we've been on these calls, we've gotten probably additional data updates from the expansion study and I know that you'll be presenting the full data later this year at our scientific meeting, but is there anything as far as an update or additional color you can tell us, especially maybe with the liver cancer responders who were showing some pretty impressive data. Can you give us any sort of an update as to what's going on with the study?

Yes, we're completing the analysis of the full data and I think our conclusions are consistent with what we've stated in the past. With the IV, recognizing it was not practical for broad application, but we surveyed different groups of patients to ascertain mechanistic activity of the drug and in those cancers where there was good published mechanism of action, support for the drug's application as well as our preclinical observation, so we surveyed 5 tumor types. And what was encouraging is we saw some long-term stable disease with a more convenient dosing schedule of every other day, particularly in liver, we saw several advanced refractory liver patients that have quite long-term stable disease. We had a breast cancer long-term stable disease as well, as well as head and neck. What we've ascertained is we're encouraged by the biomarker data that we've been able to call together and we're encouraged by the clinical benefits that we've seen but we've also concluded that, as an IV, a, it's not practical; and b, the every other day dosing, we're probably not getting enough exposure. So the oral is really important for exploiting these observations in a more robust manner. So Maurizio and his team are going through the final data set and plan on reporting on that data at an upcoming conference. But we're encouraged by what we're seeing and it really supports the premise that if we're successful with the oral formulation and which currently we're very optimistic we should be able to proceed, that with the oral we can dose every day, possibly even twice daily, to maximize the exposure to exploit these observations we've made with the IV.

And is the window study still on schedule, or is that something that's being reviewed?

It's still being reviewed and still on schedule if we end up executing that, so that's an important study from a mechanistic observation. And just to remind everyone, that window study would be a survey using the drug in patients not as a therapeutic but just as a biomarker study to be able to assess exposure in the drug's activity with various time points of exposure to show suppression of targets.

Our next question comes from the line of Simos Simeonidis from Cowen and Company.

Dan, I have a question for you on the label. I'd love to get your thoughts on the following: the label reads that the drug is indicated for adults. I see 3 patient populations here, it says adults with metastatic basal carcinoma, that's one, or with locally advanced basal cell carcinoma that has recurred following surgery, that's two. Then I see this third-- the last of the label that says, or who are not candidates for surgery and who are not candidates for radiation. That seems to me -- and that's what I want to get your thoughts on, that it potentially leaves the door open to detail this drug into a little outside of the narrow window of metastatic and locally advanced. Am I seeing this correctly or what are your thoughts?

Well, my thoughts are -- well, relying with your question-- is it remains to be clarified over time, but it does potentially, I think, first, just to comment, we're extremely pleased with the label that Genentech was able to acquire. And I think, it leaves the prospect of through education and marketing, it does leave the prospect of it being applicable beyond just that narrow application. So I think, that's an important reading and something that we're waiting for clarification as the drug is launched and we get clarity from Genentech.

So when you say you're pleased with the label, why exactly are you pleased?

Well, the label could have been more narrowly construed. And I think it's reflective of the quality of the data and the clinical benefit that FDA saw patients derive from this drug. And an important indication where they really don't have much therapeutic alternative other than debilitating surgery in many cases, so we're pleased with the language that was used.

Okay. The other question I want to ask was, a week or 2 ago, we saw Infinity's Hedgehog inhibitor fail in pancreatic. And I know there are some mechanistic differences, and that signaling differences in the way that the 2 molecules act. So I wanted to get your thoughts on that, either any read-through for Erivedge from that failure or is there something, in terms of the difference in the way the two pathways, the way the drugs act that's different that would make you think not necessarily?

Yes, thanks. I think that's a very important question. So the short response to that is not necessarily and I'll elaborate why. First of all, it was one study under one set of conditions. Genentech has used more of a broad-survey approach in these NCI collaborations, so they're surveying pancreatic cancer and at least 5 clinical trials under different treatment scenarios, treatment dosing sequence scenarios, that's one difference. The other difference is there's also possible mechanistic differences in the compounds. Infinity's compound is a derivative of a natural product called cyclopamine and it's a very large complex molecule, different characteristics from small molecules. Also, there's evidence in the published literature, Andy McMahon published, I think, about a year and a half ago, studying hedgehog activation and noting that when the Hedgehog pathway is activated, this path disassociates from another membrane protein called Smoothened. As a result of that, Smoothened then aggregates into microcilia and that is where it signals. In this publication, he found that Hedgehog antagonists behave differently in that the cyclopamine form of antagonist did not prevent the aggregation of Smoothened in the microcilia, where the small molecules did. So there are some mechanistic possibilities as well. So I think it remains to be seen with data, but we don't think it is a direct corollary to the ongoing studies.

Okay. Quickly on 101, have you submitted anything for ASCO this year?

Yes, we have.

Yes, okay. And final question for Mike before I jump back in the queue. Mike, the guidance you gave us for cash of $23 million to $27 million by year end this year includes the $10 million received on approval, correct?

Correct.

Okay. And then the $10 million, you're going to recognize immediately when received same as the $14 million you got last quarter?

That's right. It will all be Q1.

Our next question is from the line of Brian Skorney from Brean Murray.

I guess my only question, I was just wondering if you can kind of provide us with some of the details on the oral formulation switch to CUDC-101. Could you kind of detail how exactly this was being reformulated or what technology is being applied and what sort of confidence do you guys have at this point that oral viability at a regular dose will provide similar levels of drug that the IV-formulation does?

Okay, sure. So several components to the question. I'll start just by giving a description of when a drug is insoluble, it doesn't like to associate with water or its surroundings, it aggregates with itself and it forms crystals, and that's the case with 101, so it's primarily an insoluble drug. So the challenge there is finding a formulation where you're basically suspending the active chemical component in some carrier that will keep the molecule from aggregating with itself. So it has to associate with the carrier and has to associate in such a ratio that you have an adequate carrying capacity as you got a certain limitation of how much -- how large the pill can be and you got to be able to deliver so much active ingredient. So those are kind of the -- and then you have to demonstrate that you're able to get all of oral absorption once you get it through into the GI tract. So those are the key parameters. So we've done a very systematic review. First, starting with the premise that 101 has similar attributes to other HDAC inhibitors that also have shown preclinically to be insoluble and not orally available but clinically, SAHR [ph], an example of Merck's drug, clinically showed good oral absorption in humans. So we have demonstrated with some formulations that we've been investigating -- that we are getting some oral absorption in preclinical animals, then extrapolating, we should have a better oral absorption in humans. We're optimistic right now that we'll have an oral form to proceed with based on our preclinical studies. We're looking presently at several formulations in parallel and based on the balance of these various attributes that we need to address, we'll be selecting the lead formulation and going forward with that. So we're presently, actually quite optimistic, Brian, that we'll be successful with the ability to file an IND with an oral form. And then the dosing requirements are going to be -- and that's where the IV actually has given us a lot of insight. We know what the exposure requirements are overall and if we could do dosing twice a day, their real exposure advantage where we may be able to keep an exposure amount of the drug in plasma circulating and in concentrating in tumor that's even more attractive. So a number of issues still need to be delineated, but we're very encouraged right now.

Our next question comes from the line of Mani Mohindru from ThinkEquity.

A couple of questions on the pipeline, maybe I'll begin with the Hsp90 program, Debio 0932. So you mentioned that Debio had seen some single-agent responses. I just wanted to make -- get clarity on what kind of best responses were they -- if it disclosed table disease or partial response? And also, what will the Phase 1b study entail, how will it be different from Phase I that they've already conducted and a related one if I might throw in there is the Phase I/II is it non-small cell lung cancer that you indicated study? Why would that not qualify as a Phase II study for you to get a milestone and why would they run that and another Phase II in 2013 if I got that correctly? And I'll take another follow-on question.

Sure. So a multitiered question, so if I can recall all of it. So the first part of it was, what type of response and clinical benefits do they see. They saw both stable disease and PR in the single-agent, which is encouraging. And I think it's also important to again underscore that the drug appears to be extremely well tolerated. The reason they're doing a Phase 1b expansion is to further study a single-agent activity in more of a controlled focused setting. As you know, the dose escalation is basically all-comers. It's not -- it's tightly controlled. So they're looking at getting the better understanding of the drug's activity in what patient groups may show a better response as a single agent and then to gain some insights on what combinations they may want to pursue. And then the difference in the Phase I and Phase II, it's not a formal Phase II until they launch it. And again, what they're trying to delineate out is looking at this cohort of patients non-small cell lung and trying to get further insight on what subgroups may benefit from Hsp90 inhibition as a single agent versus in combination. So it's really just to learn with further detail, mechanistically, how to apply the drug with a higher probability of success going forward.

Okay. So that pushes your milestone into 2013 for the...

We're saying that conservatively.

Okay, okay. And just maybe quickly on CUDC-907, you mentioned that you will be looking into B-cell lymphomas as well as multiple myelomas. So just to maybe drill down on the B-cell lymphoma part, it's obviously a big space with a lot of subsets and some of them are crowded. What sort of are you thinking and I know it's early-stage but I'm sure based on preclinical data, are you going to go in for All-Comers in the beginning or are you going to have a focus from the get-go like a smaller or more difficult to drink subset like follicular or something like that? Or the field, sorry, not follicular, the field's large B-cell versus follicular or mantle cell, so just to get a sense of your strategy there.

So it's predicated on the quality of our observations of preclinical data mechanistically. What we've seen is really profound synergy on the PI3 HDAC front with a particular cell type, and it's lymphocytes. We see very impressive lymphopenia with 907. And we believe mechanistically this is an ideal drug for lymphoma, based on the fact that the cancer is derived from uncontrollable proliferation in differentiated B and sometimes T-cell lymphocytes. So that's the objective of focusing. I think initially, we're not going to narrow it down into a subgroup. We want to do a survey in the Phase I. But it's really predicated on very robust synergy that we've seen in pre-clinical data and through discussions with hematological cancer experts.

Our next question comes from the line of Joe Pantginis from Roth Capital Partners.

I got a strategy question for you. Obviously, part of my question is answered in your burn guidance, but I was just looking towards 2012 and even potentially beyond here. With the potential cash flow impact that we're looking at here from milestones and potential Erivedge royalties, I just wanted to look at what is the impact on potentially accelerating your current programs and also importantly, building the breadth of your pipeline opportunities. And obviously, that sort of links to the partnering question, that it-- well, this cash flow could also give you the opportunity to hold on to your products potentially longer.

Thanks for the question, Joe. It's a really important point to emphasize. So when we say that Erivedge approval is transformative, this is really what we're underscoring in the fact that it de-risks the model, it gives us access to potentially a reliable and growing source of revenue of which we can further build our depth and capabilities and build out our clinical trial surveys. We're really confident right now that we're very well positioned and primed for continuing to grow the company and create further value through exploiting the assets we have as well as preclinical assets that we've focused on. We still have a couple of preclinical assets that we're not talking about quite yet until we get further data that look very encouraging. So we've got a very deep pipeline, competitive positioning with a network disruption approach that this concept has really taking route in the oncology space, and we think that this revenue source really allows us to stay the course, further build out competencies in the translational medicine space, which I'll underscore is the reason we hired someone of the quality of Maurizio Voi from Pfizer and to really just build our positioning and to continue positioning the company with the pipeline that we have and to shore up the data set. It allows us to stay the course without having to partner as a requirement for capital access. So I think we're very well poised to execute on the strategy that we have put into place and that is the reason we call it transforming.

Our next question comes from the line of Jason Kantor from RBC Capital Markets.

I'm just wondering, just looking at some of the expansion indications for Erivedge. I mean, where do you guys see the most likely opportunity for success given the failures we've seen from-- already for your drug and also from Infinity and could we see data at ASCO this year at all from any of these studies that are ongoing or is it further out?

Thanks, Jason. So first, in terms of where we'll see success, I just want to remind everyone that I think we've already just achieved quite a significant success with approval and with the label that we have and we think that that's a very significant market potential, just even based on the estimate that Roche has stated publicly and then if we end up with European approval that's -- I think they've stated publicly, that's north of 20,000 and then with the pricing. So we think just that is a success in growth story for Curis. And then expanding beyond that with the survey of over 20 clinical trials through the NCI collaboration. There's a large amount of data that's been published on a number of these solid tumors over-expressing Hedgehog. Tumors don't expend very valuable metabolic energy on producing protein unless it is playing a role in the tumor's ability to proliferate and survived. So the key here is this broad swath survey that they are able to achieve with this collaboration should shed some light on what indication and under what dosing scenario we may be seeing some positive responses that we can then further understand and possibly exploit in other indications. So I don't think the Infinity data really is indicative of failure of the mechanism in that tumor type and it's pretty premature to conclude anything right now. It's known that pancreatic cancer, for instance, expresses high levels of the Hedgehog protein and we still remain optimistic based on this broad survey. A number of tumor types should read out in 2012 and we believe there will be some data released at ASCO on some of these tumor types. So it remains to be seen what the data reveals, Jason, but we continue to be optimistic that there is a prospect of further expansion of application of pathway inhibition.

And then just in terms of how you guys are thinking about or how Genentech might be thinking about, how the drug is used in BCC. What's the average duration that one might expect somebody to be on this drug? And do you expect that this is going to be a drug that's used to get -- to shrink tumors enough and then get them to some sort of surgical size that they can then be removed? Or is this something where these patients are essentially going to be on drugs for the rest of their life?

I think it's still too early to come up with any conclusive statements on your question. The second part of the question, on the duration, what we saw was the average was about 10 months. So we expect that to be at least the case and it may end up expanding over time. I think as they get more experience with the drug, it's possible that physicians will prescribe the drug, see a good therapeutic response and control, may take the patient off of that daily dose for managing the AEs a bit and put them back on, we just don't have enough clarity yet, so as the drug gets more experience and we see benefits from various strategies, I think it will clarify over time, but we're encouraged by what we've seen and we -- just extrapolating, we expect that it will be at least 10 months plus. And then, in terms of the second part of that question, certainly, that's a logical and rational extrapolation that we could end up seeing this drug being used to shrink lesions for better cosmetic outcomes, et cetera. And again, I think all of that needs to be clarified with experience and observations in clinical setting.

Our next question comes from the line of Boris Peaker from Oppenheimer.

I'd like to go a little further on Jason's question, specifically in terms of duration of usage. We saw that the duration of response was roughly about 7.5 months in the study while the duration of treatment was about 10 months. So could you comment on what was the motivator for patient to remain on drugs past the disease progression and how do you think that this can actually play out in the marketplace with physicians-- would they be willing to continue the drug after the disease returns? Or what are your thoughts there?

So I think physician's judgment is that patients were still benefiting from the drug, which is why they continued to prescribe it.

I think also there's a period of time that it takes to achieve the response. So if there's a couple of months to achieve a partial response to confirm PR and then you're on drugs for the 7.5 months, I guess, median duration of that response, total median duration on therapy or treatment is 10-plus months in the pivotal Phase II. So that study was designed so that when there was disease progression or intolerable toxicity, patients came off study.

Okay. From the -- has Genentech made any comments in terms of insurance reimbursement and do they have any constraints on post progression?

They have not provided any guidance or clearance on that to date, and I'm sure that will be forthcoming.

Okay, that would be helpful. In terms of the medical meetings, there seems to be a lot of data to be presented in the near future, specifically on the operable data, do you know which medical meeting Genentech may be targeting to discuss the initial results?

It's decided, Investigative dermatology, we believe, assuming it's submitted. And that's in April.

Okay, great. And one other question I just had in general and I guess more to pipeline and strategic development. In the press release, you mentioned that Dr. Maurizio Voi also will be focusing on translational medicine and biomarker discovery. Could you comment on what if any biomarker discovery is ongoing internally and you mentioned the windows study. Is there anything else that you're focusing in terms of discovery in biomarkers?

Yes, so this is an important area. I think it's clear, when you look at the oncology sector, it's been going through a significant transition over the past several years and what's clearly emerged is an understanding of the underlying molecular aberrations that are driving cancer and then to try to match targeted therapies, accordingly. So calling cancer, for instance, non-small cell lung cancer or prostate cancer, is really an antiquated nomenclature. Going forward, it's going to be more descriptive on a molecular basis and understanding the particular aberrations that are driving tumorgenicity and what drugs or combinations of drugs will provide blockade of the central driving mechanisms and the adaptive bypass mechanisms. So that's the reason we looked for someone with Maurizio's skills and why Maurizio decided to join Curis is, it gave him the latitude and flexibility to really execute on this vision which is clearly, where the oncology space is moving. And I think our network disrupting approach, combined with biomarker identification and analysis, both for PD observations, but also patient stratification and selection going forward is really going to prove to be a value driver in this sector. So we're just starting to build out this competencies and focus on these efforts, we're going to be collaborating with some key opinion leaders going forward with each drug according to the targets that it's focused on.

Our next question comes from the line of Ed Arce from MLV & Co.

I just have a few questions, some of the compound questions have already been asked. But one, are you modeling any further milestones or U.S. sales royalties given that your 2012 year-end cash balance guidance is between $23 million and $27 million. Is that included in that?

No, it's not -- that's an important distinction. It's not including -- other than the $10 million that we've learned from the Erivedge approval, no milestones, no royalties are included in that number. So we expect that the year-end cash will be significantly higher than what we've projected. We just need to-- we're working on guidance.

Okay. And I know this question is sort of in a different form than asked. Are there any -- have there been any details forthcoming from Genentech on the upcoming launch, I guess with regards specifically to the kind of sales or marketing strategy. I mean, is this really targeting dermatological oncologists or is there a more broader area?

For the most part, it's targeting dermatologic surgeons. For locally advanced, they're mostly treated by those stations from the -- or those doctors in the U.S. and Dermato-Oncologists in the EU. For metastatic BCC, it's the medical oncologists target market. So those are the 2 sets of physicians that they'll be targeting.

Okay. And on Debio 0932, I know that you've outlined that it's the upcoming Phase 1b will be really more of a survey of lymphoma. And I'm just wondering, have you been able to identify or disclose any of the key markers, key biomarkers that you're utilizing or have discovered in that process?

So first to clarify, the Hsp90 inhibitor is not focusing on lymphoma, that's our PI3 kinase HDAC inhibitor. The Debio Hsp90 inhibitor in the Ib is serving several tumor types, amongst which is non-small cell lung and in the literature, if you look at what's been reported with Hsp90s, I mean out in K-RAS, EGFR mutant, I mean this are clear mechanisms that increase the susceptibility and sensitivity of the tumors where the Hedgehog protein must be playing a role in stabilizing some of these destabilized proteins based on mutations and over activation. So we're delineating out these -- again, this what has to do with the biomarker question. It's really important going forward in how files are designed. So we're having ongoing discussions with Debio on these fronts and there are important issues that we continue to evaluate over time for patient selection and a clinical trial design.

Okay, great. One last question, on the $14 million revenue in the fourth quarter, could you just remind us again what was the breakdown between the U.S. and EU?

$8 million was attributed to acceptance of the NDA in the U.S. and $6 million in the EU.

Right. Okay, and do you expect your -- when do you expect your 10-Q release?

K, by the end of the month.

I'm sorry, the K. Right.

Last week of the month. That's what our current plan is.

Our next question comes from the line of Ted Tenthhoff from Piper Jaffray.

Two quick questions, mostly everything has been focused on. When it comes to the operable activity, is there anything that either you're aware of or that Genentech has discussed with you in terms of staging or classification of operable BCC that may be able to kind of -- not enrich the study, but really focus on those later-stage patients where either AEs will be more tolerable because of the severity of the disease or you may have a more pronounced signal of activity?

Yes, real important issue and question. So in the study itself, they're not looking at more aggressive or more advanced stages. They're looking at the activity of the drug and mechanistically in the robustness of clearance and durability of clearance, those are the primary metrics that they are looking at in the operable survey. From that data, understanding histological clearance, durability, et cetera, they will then try to formulate a strategy on where-- if it could go forward for operable, where it would be applied and I think your comments on the question are absolutely appropriate. I think that's likely to be how they would try to position it, is looking at those patients that although operable, it's suboptimal. Would a physician have the alternative of using a drug to either eliminate the lesion or even shrink it for a better outcome and if that's a possibility, based on the support of the data, that would be the likely strategy at least in the initial stages of penetrating that market.

Just one clarifying remark, Ted, is that they are -- this trial is focused in nodular basal cell, so it's not the general -- severe form which is superficial type basal cell. So it is about the top half of severity outside of locally advanced, metastatic BCC to begin with. And then obviously, the limited treatment period does help with the AE profile.

Our next question comes from the line of Robin Davison from Edison Investment.

First of all, I just want to quickly return to the issue of pancreatic cancer, I want to see do you know if the NPI study, I think it's at the University of Chicago, has completed recruitment yet? And also, do you know if there's any analysis has been triggered by the outcome of the Infinity study or on the new pancreatic studies that are underway?

So I'm not sure if recruitment has been completed. However, on the Infinity question, I mean it's really a completely distinct study. So I think the general consensus is that it has no relevance to the ERIVANCE survey with pancreatic. Completely different compound, different properties. And again, we're looking at multiple strategic alternatives with dosing combinations and scheduling. So I think the consensus is just wait until the data emerges. And I don't think the failure in the Infinity trial sheds any light on the ongoing pancreatic trials with Erivedge.

Okay, right. Just one other one really, it occurred to me that with the approval and the sort of -- the thought of -- if you like, the sort of financial situation of the company now, you might be able to design a more robust study for CUDC-101 in the head and neck indication, the Phase II that you're planning. Is that the case? Is there anything changed with the sort of the size and scope of that study?

No, because -- we actually designed it initially to be quite robust. Based on what we've seen both preclinically and our clinical observations where we saw regressions at PRs as a single agent in highly refractory and resistant patients, very advanced head and neck, plus the synergies we've observed with the compound. We went in this with the thought process that we have a prospective path forward for a commercial registration path with the combination. So we designed the Phase II to be very robust and meaningful.

Our next question comes from the line of Dori Steinberg [ph] from Anson Group.

I just had one question that I have probably missed. Do you expect potential proof of concept data for 0449 and operable BCC sometime in the first quarter, is that reasonable?

First data presentation would be second quarter and then full study data would be early next year.

Okay. And when you say the first available data would be in the second quarter, what would be the size of the cohort or whatever?

It's the data from the first cohort, which are the patients that were treated for 12 weeks with this molecule, but then tumor cycle was excised immediately following the 12 weeks of treatment, so it's about 25 patients was the first cohort.

And the final -- and the total patient enrollment is what?

It would be 50 to 25 patient cohorts.

And with no further questions, I'd like to turn the conference back over to management for any closing remarks.

Again, we want to thank everyone for your attention and support. We look forward to giving you updates on an ongoing basis. And just to summarize, we're really pleased with where we are right now and this really has been a watermark milestone for the company and we're very well primed for further value creation in 2012 and look forward to further updates. Thank you very much.

Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program and you may all disconnect. Have a great rest of the day.