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Curis (NASDAQ:CRIS)

Q1 2013 Earnings Call

April 30, 2013 9:00 am ET

Executives

Michael P. Gray - Chief Financial Officer, Principal Accounting Officer and Secretary

Daniel R. Passeri - Chief Executive Officer and Director

Ali Fattaey - President and Chief Operating Officer

Analysts

Simos Simeonidis - Cowen and Company, LLC, Research Division

Edward A. Tenthoff - Piper Jaffray Companies, Research Division

Nicholas Abbott - BMO Capital Markets U.S.

Joseph Pantginis - Roth Capital Partners, LLC, Research Division

Brian Klein - Stifel, Nicolaus & Co., Inc., Research Division

Boris Peaker - Oppenheimer & Co. Inc., Research Division

Adnan S. Butt - RBC Capital Markets, LLC, Research Division

Gene Mack - Brean Capital LLC, Research Division

Ed Arce - MLV & Co LLC, Research Division

Reni J. Benjamin - Burrill & Company, Research Division

Operator

Good morning, ladies and gentlemen, and welcome to the First Quarter 2013 Curis Earnings Conference Call. [Operator Instructions] As a reminder, this conference call is being recorded for replay purposes. I will now turn the call over to Mike Gray, Curis' Chief Financial Officer. Please proceed.

Michael P. Gray

Okay. Thanks, Kate. Good morning, and as always, thanks for joining us. During today's call, we'll provide you with an update on corporate plans and developments and also discuss our first quarter 2013 financial results.

Before we begin, I'd like to advice you that this conference call contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 including, without limitation, statements relating to our collaborator Genentech's expectations concerning the commercialization of market opportunity for Erivedge; the timing and outcome of ongoing regulatory reviews for Erivedge; and the timing and potential outcome of ongoing clinical studies of Erivedge; our plans and expectations for advancing the CUDC-907 and CUDC-427 in the clinic; and the potential therapeutic benefits of these development candidates; and our collaborator Debiopharm's expectations regarding the advancement of Debio 0932 in presently ongoing clinical trials as well as into different clinical trials in the future. Actual results may differ materially from those indicated by the forward-looking statements in this conference call as a result of various important factors, including those risk factors described in our annual report on Form 10-K for the year ended December 31, 2012, and in other filings that we periodically make with the SEC. And we encourage you to review these risk factors carefully. We caution you that we're making these forward-looking statements only 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. Okay.

With that, I'd like to now introduce Dan Passeri, Curis' CEO, who will provide brief introductory remarks. Following Dan's remarks, Ali Fattaey, our President and Chief Operating Officer, and Dan will update our pipeline. I'll then return to review our financial results for the first quarter 2013, and then we'll open the call for questions at that time. [Operator Instructions] All right. Dan?

Daniel R. Passeri

Yes, thanks, Mike. Good morning, everyone, and thank you for joining us today. So far, our 2013 has been a highly productive period for Curis marked by several key achievements and continued progress with our proprietary and targeted cancer drug candidates. These include the initiation of Phase I clinical testing of our dual PI3 kinase and HDAC inhibitor, our designated CUDC-907 and progress towards Phase II testing of our antagonist of IAP proteins designated CUDC-427 expected to begin later this year. And as Mike stated, I will give you further details on those 2 programs momentarily. The end of the first quarter of 2013 also marked 1 year of Erivedge sales in the U.S. Our collaborator, Genentech Roche, has accomplished steady and continued growth each quarter, including approximately 20% quarterly growth in sequential net sales in the first quarter of 2013 as compared to the fourth quarter 2012, which is the second straight quarter of approximately 20% sequential growth.

In addition, Genentech and Roche have demonstrated their commitment to make Erivedge available to basal cell carcinoma patients globally. Having recently secured marketing approvals in Israel, Mexico and South Korea and receiving a positive opinion from the committee for medicinal products for human use, or CHMP, for conditional approval of Erivedge in Europe. We expect Erivedge marketing approval decisions in Europe and Australia in the coming months. And Genentech Roche are actively pursuing approvals in many other territories globally. Strategically, we are focusing on the clinical development of CUDC-907 and CUDC-427 and believe that our capital position as of March 31, 2013, with approximately $54 million in cash, provides us with ample runway to fund our operating plans into mid-2015. On top of that, we expect that our financial position will be further bolstered by a potential milestone in 2013 and '14, including those with the potential Erivedge approvals in Europe and Australia in the coming months, as well as the initiation of Phase II clinical trials with Debio 0932 are estimated to occur next year.

I will now turn the call over to Ali Fattaey, who joined Curis earlier this year as our President and Chief Operating Officer to provide more details on the internal drug candidates and I'll come back and give you an overview of our pipeline programs. Ali?

Ali Fattaey

Thank you, Dan, and good morning, everyone. I'd like to begin by providing an update on our proprietary drug candidate, CUDC-907. By its nature, CUDC-907 has a number of different properties and we believe these are very advantageous properties for the drug. Let me begin by reviewing briefly how we expect these properties to translate into activity in patients in the chronic stage. CUDC-907 is designed as a targeted agent with potent PI3 kinase and HDAC inhibitory activities, both of which have been shown to be effective at killing cancer cells. As a PI3 kinase targeted agent, CUDC-907 potently inhibits PI3 kinase alpha and delta isoforms and to a lesser extent PI3 kinase beta and spares PI3 kinase gamma inhibitions. This is an attractive target profile since PI3 kinase delta inhibitors have recently shown good clinical activity against lymphomas and PI3 kinase alpha has recently been shown to also play an important role in several hematologic cancers.

We believe that targeting both the delta and alpha isoforms of PI3 kinase should result in improved clinical benefit. For example, as recently reported in mantle cell lymphoma patient samples especially after the first relapse, PI3 kinase alpha expressions and signaling may provide a resistance mechanism to PI3 kinase delta inhibition. Therefore, by inhibiting both PI3 kinase alpha and delta isoforms, treatment with CUDC-907 may overcome this type of potential resistance mechanism. Beyond that inhibition of PI3 kinase alpha and delta may extend the activity of CUDC-907 to other cancer types such as multiple myeloma or both PI3 kinase delta and alpha isoforms are shown to be important for the survival of multiple myeloma cells. Our current Phase I clinical trial ongoing is enrolling both lymphoma and multiple myeloma patients, and we look forward to the results of these drugs in this patient population. Next as an HDAC targeted agent, CUDC-907 potently inhibits the HDAC enzymes designated HDAC 1, 2, 3, 6 and 10.

Currently, HDAC inhibitors are approved for the treatment of specifically T-cell lymphomas and next generation inhibitors of HDAC are in clinical development for the treatment of multiple myeloma. We believe that the combined inhibition of PI3 kinase alpha and delta concurrent with HDAC inhibition provides additional cell killing potential and should extend the effective use of CUDC-907 in additional hematologic cancer patient population such as multiple myeloma. Now as Dan indicated earlier, we began the Phase I clinical testing for CUDC-907 in advanced lymphoma and multiple myeloma patients in January of this year. This Phase I clinical trial is designed as a standard dose escalation study where CUDC-907 is orally administrated in patients on a once daily dosing schedule on a continuous basis.

The trial is currently recruiting patients at the Sarah Cannon Cancer Center and at the Memorial Sloan-Kettering Cancer Center with M.D. Anderson Cancer Center expected to begin patient recruitment in May of this year. Now, enrollment in the 30 milligram dose initial cohort is now complete with 3 patients. 2 multiple myeloma patients and 1 lymphoma patient was enrolled in the first cohort and all 3 patients received 2 cycles of treatment and continued to cycle 3 assessment of their disease.

Patients are continuing in this current cohort with treatment of CUDC-907. We are tracking CUDC-907's exposure in pharmacokinetic properties in our Phase I trial as well and we are pleased to see a similar pattern as what we observed in preclinical animal model observation emerging from analysis of patient plasma samples in that the dual PI3 kinase in HDAC active CUDC-907 drug is metabolized to have formed the retained PI3 kinase activity. We have characterized this metabolic life form of CUDC-907 and appears to have a similar PI3 kinase isoform selectivity and potency, and a similar potency as the parent CUDC-907 drug. This metabolite also appears to be relatively long-lived in animals and in patient plasma samples, and we view this as an attractive profile for the drug since sustained suppression of PI3 kinase seems to be important for activity while HDAC inhibitory activity can be administered with short-term exposure and based upon the analysis of the currently available clinical data, we are encouraged by the initial PK results observed. Also we note that the adverse events observed in this first cohort of patients are consistent with the expected target related side effects in these patients. Although still anecdotal and very early, these observations may represent encouraging evidence of target engagement activity by the drug in patients. I would just like to caution here that these clinical results are from the first cohort of 3 patients only and although similar in the 3 patients, they require much further analysis and we look forward to disclosing and describing those for you in the coming months. CUDC-907 is being developed in collaboration with the Leukemia & Lymphoma Society or LLS, under which, LLS will support our ongoing clinical development of CUDC-907. Under the agreement, LLS will fund approximately 50% of our direct clinical cost of the development of CUDC-907 through Phase Ib or Phase IIa clinical testing stage for a total potential funding of up to $4 million.

To date, we have recognized $1.1 million in milestone payments from LLS in recent months as a result of advancing CUDC-907 2 IND filing and beginning the Phase I clinical trial. This represents important capital to support our continued development of this molecule and we thank the Leukemia & Lymphoma Society for this commitment to this drug candidate.

Finally, we are planning to pay for a trial in which we will examine the use of CUDC-907 in solid tumor patients. We expect to initiate this trial in the second half of this year, and we look forward to providing updates on the current Phase I trial and plans for further testing of CUDC-907 in patients in the coming months. I now would like to turn to our fully owned IP EBT inhibitor CUDC-427 designation, which target mechanism of evasion from apoptosis. CUDC-427 does this by an agonizing inhibitors of apoptosis or IAP protein, which functions to regulate intercellular signals for apoptosis induction. In addition, some of the IAP proteins are also components of extracellular pathway signaling of the tumor necrosis factor or TNF found in receptors. CUDC-427 in effect switches prosurvival TNF signaling into a potent pro-apoptotic pathway. In this respect, CUDC-427 is an attractive drug candidate, particularly in combination with other anti-cancer agents that have been shown to stimulate TNF expression such as gemcitabine and taxing drugs. As a reminder, in 2012, Genentech completed the Phase I clinical trial in which 42 patients received daily dose -- daily oral doses of CUDC-427 at a single agent for the first 2 weeks in a 21 day cycle. The results of this Phase I study will be presented next month at ASCO but overall, CUDC-427 was well tolerated and single agent clinical benefit was observed for some patients in this study. We are currently working on a Phase II clinical study designed to administer CUDC-427 in combination with some of the -- in metastatic cancer patients. Preclinical studies have shown that low doses of CUDC-427 synergize well with the standard doses of Xeloda and Five-FU in breast cancer xenograft preclinical models in the projected clinical trial, we look to determine the optimal and safe dose of CUDC-427 to administer with Xeloda in this patient population, as well as to determine the level of clinical benefit that CUDC-427 can provide beyond Xeloda alone in this breast cancer population. We're also planning to initiate at least 1 additional trial in the second -- in the second cancer indication later this year. Now in addition to these combination studies, we are actively exploring treatment of distinct patient populations whose tumors may have genetic alterations that rendered them responsive to single agent CUDC-427 and we expect to make a determination on a single agent development path in the coming months for this drug as well. All of our trials with CUDC-427 will incorporate plans to evaluate each patient that is enrolled in the study to help us identify subpopulations that may be particularly sensitive to CUDC-427 effects. We look forward to providing updates to our study, design and trial start date close to the time that the results of the Genentech Cancer Phase I study will be disclosed by ASCO. Lastly, regarding our ETFR and HDAC inhibitor program CUDC-101, we have determined that IV administration of the drug is impractical and have therefore discontinued enrolling patients in the Phase I IV trial in head and neck cancer patients. We are directing our resources to the preclinical testing of oral formulation of CUDC-101 and importantly to further development of our proprietary drug candidates CUDC-907 and CUDC-427. I'd like now to turn the call back to Dan, to provide an update on our partner program.

Daniel R. Passeri

Yes. Thanks, Ali. I'd like to turn next to our partner programs beginning with discussing Erivedge, which as everyone is aware is an approved drug from our Hedgehog pathway collaboration with Genentech, which is a commercial stage product for the treatment of advanced basal cell carcinoma. Erivedge is a first-in-class Hedgehog Pathway Inhibitor, which received FDA for approval during the first quarter of 2012 for the treatment of adults with advanced BCC. Under our collaboration agreement with Genentech Roche, we're commercializing Erivedge worldwide and are also working on continued clinical development. As reflected by the continued monthly and quarterly growth in sales of Erivedge since the U.S. launch in February of 2012, the uptake of Erivedge by physicians has been very positive. Roche recorded net sales of approximately SWF 28.8 million or approximately USD 30.6 million during 2012.

During the first quarter of 2013, Erivedge net sales were approximately $14 million, representing a quarter-over-quarter increase of approximately 20% of net sales. Based on the early market launch metrics and Roche's estimates of a potential target population of approximately 28,000 patients in the U.S. with an additional 12,000 patient potential in the top 5 EU countries, we continue to expect that the advanced BCC market represents significant value for our shareholders and anticipate Erivedge's continued growth in 2013. Genentech and Roche are also working to secure approval of Erivedge in many other territories including Europe and Australia, among others and last week, the committee for medicinal products for human use of the European Medicines Agency, issued a positive recommendation for the conditional European marketing authorization of Erivedge for the treatment of advanced basal cell carcinoma.

We're obviously very pleased with the CHMP recommendation and we hope that this important medicine will soon be commercially available for patients in Europe. The European commission which is authority to approve medicines for use in the European union, generally delivers its final decision within 3 months of CHMP recommendation, and the decision will be applicable to all 27 EU member states. Approvals in the EU and Australia would result in our receiving additional milestone payments as well as royalty revenues from Genentech and Roche. Roche has also secured approvals of Erivedge in Israel, Mexico and South Korea over the past several months and has begun a global process seeking regulatory approvals for submitting filings for approval of Erivedge in a large number of other territories, including the Americas beyond the U.S., Asia and other European countries.

We expect several additional filings in the future and believe that this continues to be demonstrate both Roche's strength as a global partner and it's serious commitment to the commercialization of Erivedge. Genentech is also conducting a separate Phase II clinical trial of Erivedge in patients with operable modular BCC, which is a less severe form of the disease than advanced BCC. We believe positive data from this ongoing Phase II study will allow expansion of the potential market for use in those cases where a patient would benefit from using Erivedge prior to surgery to improve the therapeutic outcome. It's believed that this category represents approximately an additional 2% of the total BCC patient population or approximately an additional 40,000 patients annually in the U.S. alone. As such, we believe that this ongoing study represents a very significant market expansion potential for Erivedge and we look forward to providing you updates on this study when they become available.

I'm now going to turn to Debio 0932 which is an orally available small molecule Hsp90 inhibitor which is partnered with Debiopharm being developed for the treatment of non-small cell lung cancer. Debiopharm completed the dose escalation portion of the Phase I clinical trial of Debio 0932 in late 2011 and presented data from this study at the ASCO meeting last year. Debio 0932 was tested in 50 patients in the phase I study including 22 patients who received 0932 every other day and 28 patients who received daily dosing of 0932. Debio 0932 was generally well tolerated in the study with the most adverse events classified as grade 1 or 2, which is designated mild or moderate, with no apparent dose or scheduled relationship.

In addition, no ocular or cardiac toxicity were observed and no consistent changes in hematology or biochemistry parameters were seen. The most common adverse events included asthenia, constipation, decreased appetite, diarrhea, nausea and vomiting. Antitumor activity was assessed in 45 of 50 patients enrolled in the study including a -- which included a partial response observed in the patients with K-RAS mutant lung cancer and in one patient with breast cancer. Stable disease was observed in 12 patients and disease progression was observed in the remaining 31 patients evaluable for efficacy valuation. And I remind everyone that this was a single agent survey.

In August of 2012, Debiopharm initiated a Phase I/II clinical trial for Debio 0932 in combination with chemotherapy regimens in patients with advanced non-small cell lung cancer referred to as the HALO study, HALO. This trial is treating stage 3B or 4 non-small cell lung cancer patients with disease that is characterized as wild type EVFR. Debio 0932 is administered in the study in combination with cisplatin/pemetrexed or cisplatin/gemcitabine in treatment naïve patients and with docetaxel in previously treated patients. Once a recommended Phase II dose of 0932 in combination with each of these 3 chemotherapy regimens has been identified, the randomized double-blind placebo-controlled Phase II portion of the study is expected to then be initiated. In that portion of the trial, approximately 140 eligible patients will be randomized to receive chemotherapy with either placebo or Debio 0932. The primary objective of the study will be to determine the efficacy of Debio 0932 in combination with chemotherapy.

Just to remind everyone, we're eligible for our next milestone payment under our license agreement with Debiopharm, when Debiopharm treats the fifth patient in this Phase II clinical trial, which we expect will commence in 2014. In addition to the study, Debiopharm has completed a Phase Ib study of the Debio 0932 in 30 patients including patients with non-small cell lung cancer and will present this data at the medical conference in the second half of 2013. Finally, as Debiopharm is expanding its development efforts around this molecule by planning to initiate a Phase I study and patients with renal cell carcinoma in the second half of 2013. And we're obviously pleased with this development and continued development of the drug.

And so to conclude, we believe Curis represents a highly attractive investment opportunity, providing investors with significant upside potential from our fully-owned highly promising clinical stage cancer drug candidates CUDC-907 and CUDC-427 while benefiting from the growing value prospects in Erivedge, as well as from the continued progress of Debio 0932, product of Debiopharm. We view our ability to extract the full potential of CUDC-907 and CUDC-427 in the clinic as an important driver to significantly increase the value of Curis and we believe we're now very well situated to focus upon the realization of that value.

I'd like to now turn the call over to Mike for discussion of our financial results. And then I'll come back for Q&A session.

Michael P. Gray

Okay thanks, Dan. Briefly we reported a net loss of $5 million or $0.06 per share on both the basic and fully diluted basis for the first quarter of 2013 as compared to net income of $2.2 million or $0.03 per share on both basic and fully diluted basis for the first quarter of 2012. Revenues in the first quarter of 2013 were $900,000 as compared to $10.4 million for the same period in 2012. This decrease in revenue is primarily the result of $10 million in license fee revenue that we recognized upon Genentech's FDA approval of Erivedge in the first quarter last year.

Net sales of Erivedge during the first quarter of 2013 were $13.3 million which resulted in royalty revenues to us of $664,000. Cost of royalty revenues, which again are comprised of amounts due to third party University licensors in connection with Genentech and Roche Erivedge. Net sales were $33,000 and $114,000 during the first quarters of 2013 and 2012, respectively. The first quarter of 2012 included a onetime charge of $100,000 on the first commercial sale of Erivedge last year.

Operating expenses for the first quarter of 2013 were $5.2 million as compared to $8.2 million for the same period in 2012. Research and development expenses were $2.6 million for the first quarter of 2013 as compared to $5.2 million for the same period in 2012. The decrease in R&D expense was primarily due to $1.5 million dollars in expenses that we incurred in the first quarter of 2012 related to amounts due to various University licenses -- licensors in connection with the FDA approval of Erivedge.

In the first quarter of 2013, we also shifted our development program spending mix by decreasing spending on CUDC-101, as well as discovery research to $700,000 from $2.4 million in Q1 2012, and increasing our spending on CUDC-427 and CUDC-907 by $800,000 -- most of that increase, $700,000, related to expense related to CUDC-427. G&A expenses were $2.6 million for the first quarter of 2013 as compared to $2.8 million for the first quarter of 2012. Other expenses, $600,000 for the first quarter of 2013, an increase compared to other income of $30,000 for the same period in 2012, primarily due to $900,000 in interest expense related to a $30 million royalty secured debt transaction of the completed last December. Partially offset by $300,000 and other income recorded during the first quarter of 2013. As of March 31, 2013, our cash, cash equivalents, marketable securities and investments total $54.1 million and there were approximately 80 million shares of our common salsa.

That was our prepared remarks and now let's open the call for questions. Operator?

Question-and-Answer Session

Operator

[Operator Instructions] Our first question comes from the line of Simos Simeonidis with Cowen and Company.

Simos Simeonidis - Cowen and Company, LLC, Research Division

So my question is on Erivedge. First of all, if you can remind us the timing of the additional data on BCNS or Gorlin Syndrome. And secondly, if you can talk about the European opportunity with the approval expected in a couple of months? I know the treatment paradigm is slightly different and the Roche sales force has continued to make progress in the U.S. quarter-over-quarter. Can you tell us how these patients are treated differently? And thus, how are they going to be targeting different patients in Europe?

Daniel R. Passeri

Yes, Simos. So first question, a couple of questions in there. The first one has to do with the strategy around Gorlin's patients. Our belief is that, that subset of patients is an ongoing survey with a number of principal investigators such as Irv Epstein at Stanford. And that category is likely to be covered by the existing label. So I don't think we have a separate study or a survey under that but I think we'll probably be seeing Gorlin's patients coming into the market realization of the drug over time based on publications. So I think those patients are already been treated under the existing label continue to be so.

Michael P. Gray

I was just going to add, this is Mike, that radiation is contraindicated in that patient population so they fall on label.

Simos Simeonidis - Cowen and Company, LLC, Research Division

Okay, okay.

Daniel R. Passeri

Okay. And then regarding the EU opportunity, Simos, I don't believe that they are treated therapeutically any differently than they are here in the states. So we believe that is just a continual market expansion and opportunity. And I believe there are about -- estimated to be 12,000 additional patients in the EU, which is the top 5 countries. So I would think their approval will basically just be a continuation of the current strategy.

Michael P. Gray

The one add that I would have is that Roche has recently commented that the difference, and maybe this is what you're alluding to, Simos, is that the target -- the physician target is 1 group called dermato-oncologists so Roche has made some statements that the patients may be more concentrated within this physician group whereas in the U.S., they're targeting surgeons, dermatologists and in very severe cases oncologists as well. So it could help the European rollout but that obviously remains to be seen.

Simos Simeonidis - Cowen and Company, LLC, Research Division

That was my point, that there are now -- it's a much more -- it's kind of a smaller FISH group in Europe that treats the BCC patients.

Michael P. Gray

Yes.

Operator

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

Edward A. Tenthoff - Piper Jaffray Companies, Research Division

My question has to do with 907 and the Phase I, appreciate the update there. With respect to enrolling from here, we're going into the third cycle, what will be the next dose cohort and how quickly do you think you can enroll those patients? And is there anything from the preclinical data that gives you a sense of where we should start to see activity? And maybe where we should just start to see toxicity.

Daniel R. Passeri

So I think the updates that we had with respect to 907 was that the first 3 patients obviously have gone on to beyond cycle 2 which is their initial assessment of disease and gone into cycle 3 of treatment. With respect to the next cohort -- I'm sorry, and the first cohort was an initial 30 milligram dose. The next cohort that is open now and the patients are in screening for is the 60 milligram dose so we've doubled the dose from the initial cohort going into this. In terms of dose escalation and findings for the numbers of cohorts that we would enroll, we would expect that we can double the dose until we see some adverse events and then we would have to potentially increase at a slower pace going forward. From based on what we see currently in the clinical setting and trying to extrapolate or interpolate from the preclinical data, our assumptions are that by the approximately fourth escalation cohort is when we would be at similar doses to where we are seeing efficacy in animal models, good efficacy in animal models. In terms of side effects, we know what the potential expected side effects of these drugs are based on the mechanism and we're keeping close eye on the side effect profile and the adverse event profile. I don't -- I couldn't comment on when we would expect to see any adverse events that may be limiting to kick in but at least with respect to efficacy, we would expect those by the fourth cohort or so in terms of the dose escalation.

Edward A. Tenthoff - Piper Jaffray Companies, Research Division

Excellent, that's very helpful. And will you submit data for hematology in December?

Ali Fattaey

We are expecting to have sufficient data and sufficient patients enrolled for us to be able to discuss and present at the ASH conference later into the year as well yes.

Operator

Our next question comes from the line of Jim Birchenough from BMO Capital.

Nicholas Abbott - BMO Capital Markets U.S.

It's Nick standing in for Jim this morning. Just going off from Ted's question. I just want to clarify. I think you said you would double the dose and you might need to proceed a little more slowly. So that suggests you need to 180 milligrams before you think you would expect to see efficacy?

Ali Fattaey

Again, these is interpolations from preclinical based on the amount of exposure we get in preclinical and the profile of the drugs there. So far, we're pleased that we see a similar pattern in the first 3 patients again, mind you, that we're seeing a similar pattern. Our expectations are that by the fourth cohort, we should be at similar levels of exposure for patients and what we're used to seeing clinical -- preclinical activity of the drug and animal model. I don't think the expectation here is that we have to get there before we see activity. This is an interpolation from animal data by the fourth quarter or so, if you indicated, we would be expecting to see approximately similar levels and similar activity.

Nicholas Abbott - BMO Capital Markets U.S.

Okay. And then my follow up really relates to you described some -- what sounds like some fairly elegant and intricate deflection of PI3 activity and the metabolite. In terms of the HDAC activity, can you characterize that to what is known about HDAC metabolism in approved indications?

Ali Fattaey

I can describe -- so for our drug, I think what I described is the fact that we are identifying the same metabolites as what we've seen with animal experiments and we're pleased with that. What we do find is the dual active drug which has both the PI3 kinase in HDAC activity is metabolized and we identify them as metabolites that have full PI3 kinase activity and no longer HDAC activity. So that's what we see. I think a similar type of assessment has been done for other HDAC drugs where the way those drug are metabolized is likely similar to what we find for our drug. With the prolonged TV.

Operator

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

Joseph Pantginis - Roth Capital Partners, LLC, Research Division

Was wondering if you can dive a little more into the market opportunity. Obviously, you put out some numbers for Erivedge, about 28,000 patients in the U.S. and the 12,000 in the top 5 EU. Just curious now with Roche having boots on the ground, how those numbers might have been tweaked as of late or how they might be tweaked in future based on patient identification now that they're actually detailing physicians?

Ali Fattaey

I think this market has always been a little bit uncertain. They're -- basal cell, unlike other cancers, doesn't have a patient registry so the market size is an estimate from Roche. I think the market size is, at 20,000 and 12,000, is conservative. And what we can say on the U.S. side is that Roche is has been pretty aggressive in increasing their marketing efforts. They've increased the sales force recently late last year to a very Erivedge specific sales force. So I think right now our comment's really going to be limited to we're optimistic that the drug's going to continue growing. An interesting observation that we've had is that getting that first prescription is the key sales goal for Genentech sales team. So once they get the first prescription, you see a second prescription and a third and there's a snowball effect and I think we're kind of seeing this in the weekly prescription trends as well as the early in the year last year we were at a certain level or Genentech was at a certain level, midyear plateau was at another level, Q4 was at a different level and now you are at a higher level, still. So while overall absolute sales are still reasonably modest, the sales growth 25% last quarter, about 20% this quarter continues to be positive and we expect that to continue.

Joseph Pantginis - Roth Capital Partners, LLC, Research Division

So that's helpful. And maybe just a quick follow-up, if you don't mind. Ali, you made a comment regarding 427, obviously the main thrust or the main premise of this drug is in combination with other therapies but you did talk about the potential of monotherapy based on certain mutations. Are you in a position to discuss these types of mutations? And are these things that would have a diagnostic available? Or would you need to develop a diagnostic from the start?

Ali Fattaey

That's a good question, and I think if we look into it, there sort of, there are certain patient that have translocations, they're alterations genetically of components of IAPs and in particular the cIAP. And we're looking very closely to see if we can potentially do a clinical study enrolling those patients and it would be with a potential genetic alteration that we can identify diagnostically.

Operator

Our next question comes from the line of Brian Klein with Stifel.

Brian Klein - Stifel, Nicolaus & Co., Inc., Research Division

Just briefly on the operable nodular indication, can you give us an update on timing for that data?

Daniel R. Passeri

Yes, our estimate now is going to be late Q2 into Q3. That's the best of our guesstimate at this point from communications.

Michael P. Gray

Q3. Q3.

Brian Klein - Stifel, Nicolaus & Co., Inc., Research Division

Great. And just on the financials side, do you guys anticipate booking a milestone payment for EU formal approval in the second quarter or third quarter?

Daniel R. Passeri

It's -- again what we've been given in past experiences is that it's 2 to 3 months time to approval so it could straddle either way. It's going to be right around the end of the second quarter or early third. That's the best I can offer.

Operator

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

Boris Peaker - Oppenheimer & Co. Inc., Research Division

I just wanted to probe a little on the Erivedge numbers that the target patient populations that you guys mentioned, specifically 28,000 in U.S. and 12,000 in the top 5 EU. Could you tell us why such a discrepancy? I mean, the type 5 EU countries probably have roughly 80% of the U.S. population, but it seems like their advanced BCC patient numbers are certainly less than half.

Daniel R. Passeri

I mean, the published incidence rate -- which I apologize I don't have off the top of my head -- is lower, and I think it's really just a math problem. And, I mean, these are again estimates as there is no real registry for these patients so the actual patient population I think will sort of emerge as the drug is commercialized, but really it's a relative incidence rate.

Boris Peaker - Oppenheimer & Co. Inc., Research Division

I see. And on the 40,000 in the operable BCC that you mentioned in U.S., could you comment in terms of specific criteria that you used to kind of define these target patients?

Daniel R. Passeri

Well this comes from a Roche estimate where they have a presentation and they conveyed that there was a subgroup of patients that although designated operable so fall outside of the current advanced label, it's clearly a group that's suboptimal, and they estimated that this group is approximately 2% of the total. That's as simple as the math calculation it comes from. Estimating that there's an additional 2% of patients that are deemed operable but if physicians had an alternative to treat them -- potentially, for instance, with a neoadjuvant prior to surgery to improve outcomes, they would use it.

Boris Peaker - Oppenheimer & Co. Inc., Research Division

I see. And my last question on just Erivedge epidemiology with Australian approval probably not that far off, I'm curious that Roche commented on the market opportunity there. I mean, even though the overall operation is much lower in Australia compared to European countries and U.S., the incidence of skin cancer is substantially higher so I'm just curious how significant is that market for BCC.

Daniel R. Passeri

Yes, it's a different one -- difficult one to ascertain, Boris, simply because in Australia, as you stated, the incidence is much higher. As a result of that, first of all, the majority of the population is along the coastal regions so more concentrated and they have a much greater awareness. They have a very significant educational campaign in the school systems, doing continual checks. So the percentage of the population that is categorized as advanced, or operable/suboptimal, I don't think is going to be as significant as the incidence rate, just because of practice, protocols.

Operator

Our next question comes from the line of Adnan Butt with RBC Capital Markets.

Adnan S. Butt - RBC Capital Markets, LLC, Research Division

Again on 907, as for this trial that's ongoing, is there a planned balance between lymphoma and myeloma? And why the myeloma indication? And secondly, can you estimate how many patients worth of data the company might have for ASH?

Ali Fattaey

Sure; it's not a balance between multiple myeloma and lymphoma; it's open for enrollment of both patient populations and as slots become open. It depends on the patient that's available and we come into it, so it's not balanced. In the -- in terms of patient data, obviously, with having 2 types now enrolling and a third type coming on shortly we believe will have ample numbers of patients enrolled by the time the ASH abstracts are going to be due for us to submit it, and so we should have a very good idea about -- both from a good number of patients in terms of the benefits in the PK in PD profile of the drug in that regard. I think you asked a question. That middle questions was, "why multiple myeloma?"? This is based on the target profile of our drug, targeting both PI3 kinase delta and alpha as well as the HDAC inhibition. And some of our preclinical work in model is showing that we have very good activity in multiple myeloma clinical there was the reason of the enrollment of the spacious in addition to the lymphoma patients.

Operator

Our next question comes from the line of Gene Mack with Brean Capital.

Gene Mack - Brean Capital LLC, Research Division

Can you just clarify? Earlier I think you mentioned that during the 907 trial, there was a disease assessment -- I know that it was only after I guess 2 cycles but can you just give us an idea if there was any stopping criteria for patients? The point is there was a certain amount of disease progression at that point or if they were still allowed to get dose escalation going because there was no toxicity and then I just have a quick follow-up.

Ali Fattaey

In the first cohort, we did not observe dose limiting toxicity as defined in the protocol. And also, per our protocol, investigators do the assessments and make the determination if the patients have seen sufficient benefit and at the same time, lack of progression of their disease to merit continuing on the treatment into cycle 3. So it's based on physician's discretion and assessment of the disease at the of cycle 2. And we did not see dose-limiting toxicity in the first cohort.

Gene Mack - Brean Capital LLC, Research Division

Is a safe to assume though that if one of the patients had blown through the treatment, that they would've probably been moved on to something else?

Ali Fattaey

Correct.

Gene Mack - Brean Capital LLC, Research Division

Okay, great. And then I think you guys mentioned in the past there was an inflammatory pathway defined for 907. Is there any more clarity on that? And I'm sorry if you already mentioned it. I got on the call late.

Daniel R. Passeri

Yes. So, Gene, that was actually quite a while when we were talking about the prospects of it being immunomodulatory, and that was all hypothetical based on the role of PI3s. We have not investigated any further to date because obviously the primary focus is oncology and we want to see its performance from a PKPD standpoint and define the safety profile. That's something that we will revisit downstream, if the data continues to world. But right now our focus is solely on oncology space.

Operator

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

Ed Arce - MLV & Co LLC, Research Division

I just have a couple -- actually one was actually asked business I just wanted to get the sense for your expectations for data releases at ASCO, in particular with 427?

Ali Fattaey

Yes, so the investigators, the primary and principal investigator of the CUDC-427 Phase I trial will be presented at the ad ASCO. Obviously, the goal of that study was to determine the safety and tolerability and PK PD parameters, as well as any benefits from the study. What we can tell you is that the safety profile, tolerability and clinical benefits observed in the Phase I will be presented at ASCO.

Operator

Our next question comes from the line of Reni Benjamin from Burrill & Company.

Reni J. Benjamin - Burrill & Company, Research Division

Just going back to 907 and the activity that you're seeing in the earliest cohort. Can you just help us or provide a little bit of color regarding the patient or the patient history or the characteristics of the patients? How many treatments have they had beforehand? Have they -- how well did they respond to their previous therapies? And when you talk about their starting the third cycle, does that mean that they've been at least stable for 3 months?

Ali Fattaey

I think in terms of the patients that are getting enrolled, these are Phase I centers and therefore classic Phase I patients have had other relative treatments, especially being lymphoma and multiple myeloma patients, and they would have been having to progress on those treatments prior to coming on to our Phase I trial. In terms of prior therapy, I don't think -- on top of my head, I wouldn't know it but I've had multiple rounds of treatment before coming into the study. With regards to -- I apologize, I forgot the second part of your question?

Reni J. Benjamin - Burrill & Company, Research Division

Just when you say that they're starting the third cycle, is that done for 3 months?

Ali Fattaey

So the cycle of treatment is 21 days for this treatment so they would have had at least 42 days of treatment and evaluation. And then gone on to the cycle 3, which would've been another 21 days of treatment and then from there, every second cycle of the patients get investigated makes the decision to continue enrollment. I can tell you that at least one patient has gone on to complete 4 cycles of treatment and being assessed by physicians as well.

Reni J. Benjamin - Burrill & Company, Research Division

Perfect. Okay. And just one last question probably for Mike. The countries -- on territories that Genentech is exploring, can you help just give a little bit more color on what sort of a bear hug Genentech is putting on the world, if you will, to try to get Erivedge to a lot of different countries? I think Dan mentioned the Americas. Is it just Brazil? Is it -- by the end of this year, how many countries do you think will an application have been filed?

Daniel R. Passeri

A specific number I can't really comment on. What I can say is there are approximately a dozen or so including the U.S., where there has been regulatory submissions -- of those Mexico, Israel, South Korea and the U.S. has been approved obviously positive recommendation from CHMP in Europe and we're expecting an approval decision still in Q2 in Australia. So I think we'll have additional territories, including some that are very significant for basal cell -- Brazil, Russia, that could come on this year early next. In addition, I think over the next year or 2, we'll really come to appreciate Roche's global strength there. They are really, without disclosing details, really aggressively pursuing a global registration strategy for this compound for Erivedge.

Operator

[Operator Instructions] And am showing our next question is a follow-up question from the line of Jim Birchenough with BMO Capital.

Nicholas Abbott - BMO Capital Markets U.S.

Just a quick one really. And it relates to combination therapy for 907 specifically for multiple myeloma. Do the preclinical data indicate that the ability or the role of PI3 kinase in certain subsets of patients or certain therapies just concerning resistance. And so when do you expect to start some combination therapy trials even if it were just for HDAC?

Ali Fattaey

Sure. That's a good question. I think the goal of our Phase I trial in this setting with lymphoma and multiple myeloma is really to try and identify a population that we would potentially focus on for further development of the drug. I mean, I think you specifically identified potentially the multiple myeloma index or other. I think we've gone that far to say multiple myeloma is certainly the next population that we would go after. I think we would wait for the Phase I trial to look at either some populations of lymphoma, or the multiple myelomas to determine which one we would -- which ones we would follow-up with further trials. At the same time, though, we are testing some of this preclinically in animal model to ascertain the ability of the drug to combine with that agents that you mentioned and other agents that are commonly used to treat lymphoma and multiple myeloma patients.

Nicholas Abbott - BMO Capital Markets U.S.

Okay. And then just one last follow-up and that's on Erivedge, obviously. Genentech and National Cancer Institute have surveyed a wide variety of tumors in a wide variety of settings. I don't think any of those are really been positive unfortunately but has anything come out of this survey that gives you hint on where you might be able to use Erivedge outside of basal cell and perhaps medulloblastoma?

Daniel R. Passeri

We're watching that data carefully as well. And to date, nothing has come out definitive pointing a path forward so we're just watching the data as it emerges and we still remain hopeful.

Operator

I'm not showing any further questions at this time. I'd like to turn the call back over to Dan Passeri, for closing remarks.

Daniel R. Passeri

Yes. Thank you, and thanks to everyone, for joining us on our call today. Overall, as we've conveyed, we have a very productive quarter by advancing 907 in Phase I trial and we've made significant progress with the development plans for CUDC-427. The advancing of these 2 programs is our primary priority for the remainder of 2013. And I believe that we are very well-positioned to realize a number of important value creating development milestones across these programs, as well as our partnered programs. At this point, I'd like to thank our employees, directors, investors and partners for your continued support and we look forward to be providing you with further updates on an ongoing basis. And again, thank you for your time and interest and have a good day to everyone. Thank you.

Operator

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program, and you may all disconnect. Everyone, have a great day.

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