Curis, Inc.
Q2 2014 Earnings Call Transcript

Published: 7 Aug 2014

[Operator:]

Good day, ladies and gentlemen, and welcome to the Second Quarter 2014 Curis, Inc. Earnings Conference Call. [Operator Instructions] As a reminder, this conference call is being recorded. I would now like to introduce your host for today's conference Mani Mohindru, Vice President of Corporate Strategy and Investor Relations. Please go ahead.

[Mani Mohindru:]

Thank you, operator. Good morning, everyone, and thank you for joining us. During today's call, we will provide you with an update on corporate plans and development and also discuss our second quarter financial results. Before we begin, I would 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 limitation, statements relating to our strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management; the potential therapeutic benefit of and our plans to develop CUDC-907 and CUDC-427; R & R collaborated Genentech and Roche's expectations regarding the continued development and commercialization of and market opportunity for Erivedge in various territories, and expected growth of Erivedge's sales in 2014 and beyond; and, R & R collaborated Debiopharm's expectations regarding the clinical development of Debio 0932. Actual results may differ materially from those indicated by forward-looking statements in this conference call as a result of various important factors, including those risk factors described in our quarterly report on Form 10-Q for the quarter ended March 31, 2014, 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. I'd now like to introduce Ali Fattaey, our President and CEO, who will provide an overview and summary of the position of the company, including an update on our proprietary drug candidates, CUDC-907 and CUDC-427, as well as our partnered programs Erivedge and Debio 0932. Following Ali's remarks, Mike Gray, our Chief Financial and Business Officer, will review our financial results for the second quarter 2014, after which, we will open the call for questions. [Operator Instructions] Ali?

[Ali Fattaey:]

Thank you, Mani, and thanks to the conference call and webcast participants for joining us this morning. We remain committed to advancing our 2 proprietary drug candidates, CUDC-907 and CUDC-427, which are currently in Phase I clinical development. And we have a first-in-class approved drug, Erivedge, that is being commercialized by Genentech in the United States and by Roche worldwide, outside the U.S., for treatment of advanced basal cell carcinoma. We expect the royalty-based revenue stream to Curis from Erivedge sales to continue for the foreseeable future, and our current cash position should enable us to execute our plans into mid-2016. These are the elements of the company that we'd like to highlight during our call today. I will start with CUDC-907, our orally available small-molecule drug candidate that is designed to selectively inhibit HDAC, as well as PI3 kinase enzymes. We are currently evaluating CUDC-907 in an ongoing Phase I dose escalation and expansion trial in patients with relapsed or refractory lymphomas or multiple myeloma. In this trial, patients have received oral doses of CUDC-907 using 3 different treatments schedules

[Michael P. Gray:]

Okay, thanks, Ali. We reported a net loss of $1.9 million, or $0.02 per share on both the basic and fully diluted basis, for the second quarter of 2014, as compared to a net loss of $1.3 million, or $0.02 per share, for the same period in 2013. Revenues for the second quarter of 2014 were $4.8 million, as compared to $5.4 million for the same period in 2013. The decrease was primarily due to a $1 million decrease in license revenue due to $3 million and $4 million milestone payments that we earned upon certain Erivedge development -- Erivedge-related development objectives during the second quarters of 2014 and '13 respectively. During the second quarter of 2013, we also received a $550,000 milestone payment from the Leukemia & Lymphoma Society related to our achievement of certain objectives in our ongoing Phase I study of 907. Offsetting these decreases, royalty revenues recorded on Genentech and Roche's net sales of Erivedge increased to $1.8 million in the second quarter of 2014, as compared to $800,000 during the same period in 2013. Operating expenses for the second quarter of 2014 were $6.3 million, as compared to $6.1 million in Q2 2013. Research and development expenses were $3.3 million for the second quarter of 2014, as compared to $3.2 million for the second quarter of 2013. The increase in research and development expense was primarily due to increased spending on our CUDC-907 and CUDC-427 programs. Offsetting these increases, stock- based compensation decreased by $200,000 when compared to Q2 2013. G&A expenses remained unchanged to $2.9 million for the second quarter of 2014, as they were in second quarter of 2013. Other expense comprised primarily of interest expense related to a loan made by BioPharma-II to Curis Royalty, a wholly-owned subsidiary of Curis, was $351,000 for the second quarter of 2014, compared to $588,000 for the second quarter of 2013. The decrease in other expense is the result of a decrease in the fair value of a warrant liability during the second quarter of 2014, when compared to the second quarter of 2013. We ended the second quarter with cash, cash equivalents, marketable security and investments of $59 million, this excludes the $3 million Erivedge related milestone payment that we received in July. And there are approximately $86 million shares of our common stock outstanding. We currently anticipate that we will end 2014 with cash, cash equivalents and investments of between $47 million and $50 million, this includes a $3 million milestone payment that we received in July from Genentech. This projected estimate excludes any other potential future milestone and royalty payments from existing or new collaborators, including royalty revenues related to net sales of Erivedge. Curis Royalty is required to pay BioPharma-II up to $2 million per quarter of the royalty revenues that it receives from Genentech and Roche in 2014, under the terms of the Erivedge royalty secured debt transaction, but would retain royalty revenues that exceed that amount, if any. With that, I'd like to turn it back to the operator and open it up for Q&A.

[Operator:]

[Operator Instructions] And our first question comes from Adnan Butt from RBC Capital.

[Adnan S. Butt:]

One high-level question and then a specific. First, at what point do you think the company will have enough to decide on a Phase II dose for 427 and 907? Is that feasible by the end of the year? And then, secondly, how commonplace are PI3-kinase mutations in breast cancer? Is there a specific class that's involved more than others sort of that makes you think that 907 is appropriate?

[Ali Fattaey:]

Thank you, Adnan, and thank you for the well wishes as well. So with regards to the broader question of data that will be available for CUDC-907 and 427 with regard to selection of dose and schedule for going into the expansion, we certainly are expecting to have those determined this year, and have the expansion stages for both drugs to be initiated this year. So as we indicated for CUDC-907, we are currently completing the 150-milligram dose cohorts in the twice weekly and 3 times weekly. We believe we're very close to dose at this point for CUDC-907, and a decision on dose and schedule will be made for that expansion certainly before the end of this year. With regards to CUDC-427 as well, really we are testing 3 doses of the drug in the escalation 100-milligram, 200-milligram and 300-milligram. As we indicated, we're currently in the 200-milligram dose cohort, and we certainly expect to be using one of the 3 doses for the expansion stage of the study for 427 as well, and that should also occur within this year. With respect to the second question of PI3 kinase and breast cancer, as I mentioned, with regard to CUDC-907 and our interest in solid tumors, in general, and specifically for the estrogen-receptor positive breast cancers, this is an interest that we've been articulating for a period of time now, but we feel if CUDC-907 is getting close enough to dose that we've implemented the plan for initiating and treating patients with breast cancer in the study at this point. Regarding the activity, there is ample data for a potential benefit that HDAC inhibition provides, specifically in this population, the hormone-receptor positive breast cancer. With respect to PI3 kinase mutations as well, I believe roughly 41% of the breast cancer mutations -- PI3 kinase alpha mutations that occur are in the ER-positive population of breast cancer. In the hormone receptor-negative population, there is less of an incidence of PI3 kinase mutations. That is also part of the drive that drives for us to test the that, specifically in the ER-positive setting. So I think you're familiar, very familiar, on the call also, very familiar with the fact that PI3 kinase alpha inhibitors are clearly being developed right now in the breast cancer population for treatment of that. So we do feel that the estrogen receptor-positive population is where the convergence of both PI3 kinase mutations and potential benefit from HDAC inhibition come together.

[Operator:]

Next question comes from Boris Peaker from Cowen.

[Boris Peaker:]

Just on Erivedge, specifically in IPF. When will we see some initial data, be it some kind of pre-clinical data supporting mechanism, or certainly interested in initial human data?

[Ali Fattaey:]

Yes. Thank you, Boris. With regards to IPF, I think there is a healthy amount of literature indicating the activity or activation of the Hedgehog pathway in general. Levels of Hedgehog itself, the ligands being high in IPF disease tissue. And also the Hedgehog-driven Gli transcription factor gene expression being high, again, and activated in IPF disease itself. I think that's been documented in the literature, and I think that's a fairly established data around that. With regards to Erivedge itself being tested in the patients, as we indicated, IND has been filed. I believe at least one site is now also open and recruiting patients into this study. I believe it'll take an amount of time, obviously, to get the number of patients that is expected to be enrolled in here, roughly 130 patients. So our assumption is that there won't be 2014 data certainly around this at this point. But as the data comes in and we find additional metrics from Genentech and Roche as well, we will be sharing those with people. I should point out that the end point of the study is to look at the disease after 52 weeks of treatment. So the end point of the study is after 1 year of treatment with Erivedge in this disease setting, so the end point won't be reached for quite a period bit of time.

[Boris Peaker:]

Now what's interesting is, I'm sure, you know in the IPF space, there's 2 drugs that are likely going to be launched next year. And I'm just curious, if you were doing any kind of pre-clinical work in trying to see which one would be the better combination, just in case this ongoing study of Erivedge monotherapy works out. Do you think you'll advance Erivedge as monotherapy going forward? Or would you have to then actually combine it with something already available? And if so, kind of what are your thoughts on that?

[Ali Fattaey:]

We don't have specific guidance from Genentech and Roche. Squarely, as you point out, there is the opportunity for both monotherapy and combination. And our assumptions and our expectations are that both of those are ongoing. Clearly this study -- current study will be looking at monotherapy and combination, potentially to be evaluated later as well.

[Operator:]

Our next question comes from Brian Skorney from Robert Baird.

[Morgan Haller:]

This is Morgan filling in for Brian. I just had a quick question regarding the 907 dose. Do you have a theory as to why you haven't had the go-forward dose yet in intermittent schedule?

[Ali Fattaey:]

I'm sorry, Brian -- sorry, Morgan, can you repeat your question?

[Morgan Haller:]

Sure. I was just wondering if you had a theory around why you haven't hit the go-forward dose with the intermittent schedules?

[Ali Fattaey:]

Oh, sure. So really -- I mean, a lot of the selection of dose for going to the next phase of the development is dependent on multiple factors as everyone knows. First and foremost, the safety and the tolerability profile. Secondly, we are evaluating biomarkers fairly closely in this study, as well, from patient sample. And obviously, the pharmacokinetics profile of the different doses as well. As we indicated in the daily dose, we did hit the maximum tolerated dose already that was done at the initial dose of the drug for the daily. The types of adverse events that we saw in the daily dose, which included thrombocytopenia, some amount of diarrhea and some fatigue associated with treatment. And of course, the thrombocytopenia and diarrhea where at levels that merited those limiting level. Although we've seen a similar adverse event profile in the intermittent dosing twice weekly or 3 times weekly, meaning some drop in platelet number, some amount of GI and some amounts of fatigue. None of those have been dose-limiting, thus far, up to the 150-milligram dose. That's from that level. We do see inhibition of our targets, both for the HDAC inhibition, as well as the PI3 kinase inhibition. We believe that, at the moment, it continues to be dose-dependent, and therefore, meriting, going forward, both from a safety perspective and also from a biomarker perspective. So we'll continue to refine this. Obviously, as you know, Phase I is an important part of this, which is where, how we, at what dose and schedule, and how we administer a drug becomes important. So we're very carefully observing both the safety, as well as the pharmacodynamics of the drug, for dose selection.

[Operator:]

Next question comes from Joe Pantginis from Roth Capital.

[Joseph Pantginis:]

First, question on 907, more on the profile of the drug. Obviously, the landscape of PI3K inhibitors, and even HDAC's as well, has grown significantly over the last several months. I guess, my question would gain -- or go to the potential combinations you'd be thinking of especially in the lymphoma setting because of the advent of multiple new drugs.

[Ali Fattaey:]

Certainly. Thank you, Joe. And I could comment on that with regards -- in the lymphoma setting. As we indicated, both from the perspective of the data that we presented at ASH in December 2013, where one patient with diffuse large B-cell lymphoma at that time had a response -- an objective response, as well as the other 2 patients that were treated at that time, having some tumor shrinkage associated with the patients with the DLBCL. And the fact that on the daily doses, as I mentioned, the one patient with DLBCL that's been on the drug now with stable disease for 21 cycles. All of those have pointed us to be very interested in diffuse large B-cell lymphoma as an indication that we will expand into. And certainly thinking about the landscape of this, how we could position CUDC-907 in this disease indication from a regulatory strategy. Certainly, we look at the drug at the moment from a monotherapy perspective, simply because it brings 2 different activities to bear already, so the HDAC inhibition and PI3 kinase inhibition. We would look at the drug in the expansion cohort as monotherapy, and based on the clinical -- level of clinical benefits and particularly response rate, we would determine whether we would go down a monotherapy path or whether we would combine and go down a combination treatment path. Preclinically, obviously, we are examining all possible combinations in the diffuse large B-cell lymphoma setting, combining CUDC-907 with various treatment strategies that are currently being employed for -- in diffuse large B-cell lymphoma. And I think, the expansion cohort and the expansion that we will do with CUDC-907 and DLBCL will determine our path, whether it will be monotherapy or combination.

[Joseph Pantginis:]

Do you...

[Michael P. Gray:]

I think we lost Joe. [Technical Difficulty]

[Operator:]

And so far we have connected with Brian Klein from Stifel.

[Brian Klein:]

So just a couple of quick ones. Can we expect to see some data at ASH this year on 907?

[Ali Fattaey:]

I think we're collecting all the data for CUDC-907. Our -- we are certainly desiring to present data at ASH, but we've not made that commitment, Brian, at this point.

[Brian Klein:]

Okay, great. And then on 427, are you considering presenting or publishing the safety data that you submitted to the FDA to have the partial clinical hold removed?

[Ali Fattaey:]

Not necessarily publishing yet. I think we've been sort of -- we will be happy to discuss it openly. I can give you a summary of the findings that we have found with regards to it. I don't think we found a venue for trying to disseminate or distribute that data for that. I think we would be certainly open to discussions. If you would like, we can give a summary of it as well. Whether this is the right place to do it or not, I'm perfectly happy to give you summary of it.

[Brian Klein:]

No, we can hold off for another opportune time. And then maybe last question here is, can you just remind us when does the expiration the Erivedge royalties occur? And if it's dependent on additional indications or if there's a hard stop?

[Michael P. Gray:]

It's generally driven by a composition matter, which goes through the end of 2028.

[Brian Klein:]

But even if they were to receive additional orphan protection, your exposure to that revenue stream stops, is that correct?

[Michael P. Gray:]

Yes. I mean, yes.

[Operator:]

Our next lesson comes from Nick Abbott from BMO Capital Markets.

[Nicholas Abbott:]

I want to ask you, Ali, as one of the most thoughtful and diligent leaders in biotech here. Firstly on PD, and that is, quite often, people just to look at blood and skin and call it good. But really the key sites of disease, and these malignancies are either at the bone marrow and/or lymph nodes. So when you think about PD as you want to select the recommended Phase II doses, are you able to access some of these more difficult to access sites? Or are you really just relying on your skin and blood? And I have follow-up?

[Ali Fattaey:]

Certainly. Thank you, Nick. I think we certainly agree with you that, in general, and certainly for CUDC-907, it is important to get at the diseased tissue as well. We did amend our protocol several months ago to include and request for patient's tumor samples, including lymph node possibilities, as well as on staging of patients with multiple myeloma to get access to the bone marrow samples that would be potentially available. So we've requested those, and any that are available and would come in, we analyze those as well. I also want to extend this to the context of our plans to treat patients with breast cancer into this. And specifically, this has been a topic of discussions for us with investigators, and this really does provide us additional opportunity to examine the biomarkers and the availability of the drug itself in the disease tissue, in the breast tissue. And certainly, possibly, pre and post treatment. Those are all high in our minds. We have requested access to lymph issue, bone marrow tissue and, certainly for the breast cancer, to the tumor tissue pre and post treatment.

[Nicholas Abbott:]

Okay. And then my follow-up really is just more in terms of looking out at what development programs are likely ongoing as we get to mid '16. So what study are you assuming you can support? And I'm interested to know if that might include another asset coming out of your pipeline, and whether you'd still want to focus on these very novel HDAC bio-specific compounds, or do you have a different platform or even both? So what are likely to be looking at towards the end of next year in the pipeline?

[Ali Fattaey:]

Thanks for that question, Nick. I think, for the most part, and historically, you know that Curis brought forward a different drug candidate from the dual inhibitor technology of HDAC and kinase inhibition, which we stopped clinical development of last year. I think from this perspective, we look at CUDC-907 as a good drug candidate on its own, and not necessarily being a representative of a platform per se. So it is the drug candidate that we are taking forward on its own, and I don't think we have any plans of bringing additional drug candidates with dual activities of HDAC and kinase inhibition at this point into the clinic. I should also -- with regards to your question of what our pipeline would potentially look like and what else we look at, I do want to point to the fact that CUDC-427, obviously, came from our taking opportunities outside of our core technology, if you will, and in-licensing CUDC-427. Curis took that opportunity and brought that drug candidate in and is in development. I don't think we would be changing our strategy in that regards, meaning we will continue to remain very opportunistic and evaluate other drug candidates and product opportunity for Curis in the future as well.

[Nicholas Abbott:]

And so in terms of -- what trials are you likely to have ongoing then by the end of next year?

[Ali Fattaey:]

That's a good question too. So if you look at it from a time perspective in that regard, frankly, we spent pretty much last year -- the last 12 months with evaluating dose and schedule for the 2 drug candidates, CUDC-907 and 427. Really, later this year and probably the front part of 2015 is going to be looking at those drug candidates in very specific populations

[Operator:]

And our next question comes from Chris Marai from Oppenheimer.

[Christopher N. Marai:]

The first question really on 907, obviously, HDAC and solid tumors have had less-than-stellar results. I'm still wondering, what your thoughts are with respect to 907. What makes a difference and gives you confidence that it might have activity in a solid tumor setting?

[Ali Fattaey:]

Thank you, Chris. I think as I pointed out, one of the things that we found towards CUDC-907, we certainly saw this in the preclinical setting and now also see it in the -- from the Phase I study in patients in the CUDC-907, very rapidly and almost entirely distributes to solid tissue. In the animal, we can certainly see this in all solid tissues that we look at, in any of the solid organs, there is ample amounts of the drug. For tumor-bearing animals, the tumor also is very highly loaded with the drug in its issues. Obviously, we've looked at the lymph nodes of the animals and also the bone marrow, and there is copious amounts of the drug in there as well. To the extent that, as I think you guys have seen in the past when we've shown the pharmacokinetic profile of CUDC-907, there's very little of the drug in plasma itself of CUDC-907. So it very uniquely amongst these types of drugs, very specifically and almost entirely distributes to tissues. That is not the same property for a number of HDAC inhibitors. So that's one of the first property that makes us want to look at this drug in solid issues. Secondly, CUDC-907 is a very potent HDAC inhibitor. And we've shown that both preclinically and, obviously, clinically as well, some of side effects that I mentioned can very well be attributed to HDAC activity. Thirdly, we've certainly seen PI3 kinase inhibitory activity in the preclinical setting and associated benefit in the preclinical setting. We certainly see from our pharmacodynamic analysis that CUDC-907, in the clinical setting as well, does address its targets, PI3 kinase based on our assessments of phospo-Akt biomarker activity. All of those things make us -- the high tissue distribution and the activity of the drug makes us very compelled to test it in solid tumors. The specific reason for hormone-receptor positive breast cancers, as I mentioned, was because we think that this is one of the places where either one of those inhibitory activities has shown some benefit, and secondly, it represents a disease setting where the convergence of the 2 activities could provide benefit. Obviously, we have preclinical studies ongoing that have examined this, and we do see activity of the drug in that setting, and it behooves us to test it in the clinical setting as well. In general, though, I do agree with you that certainly on the HDAC site, solid tumors and ability of those drugs to address solid tumors has not been very strong. However, CUDC-907 represents a different kind of drug, high HDAC activity, PI3 kinase activity and high tissue distribution.

[Christopher N. Marai:]

Great. And then just a follow-up, 427, we obviously saw some very interesting results in the MALT lymphoma case. You'd mentioned that you're going to be looking at potentially bringing them to the clinic, in MALT lymphoma. Will you be looking at a particular subset of patients, genetically defined, translocation or other alteration? Or will that just be part of the stratification of patients in that trial?

[Ali Fattaey:]

Certainly. Thank you. In the MALT lymphoma itself, specifically from a disease background, let me be -- I'll start to say, we're not preselecting MALT lymphoma patients at this stage, or don't expect it in the expansion either. The reason for that is, at least for the MALT lymphoma, a high percentage of the patients either have amplification or translocation that involves the cIAP2 gene itself, which is a target for the drug. That is one of the reasons we would like to continue evaluating MALT lymphoma, along with the fact that we did see clinical benefits from the Genentech-sponsored study in one MALT lymphoma patient. So because of the high incidence of the genetic alteration in MALT lymphomas, I don't think we need to do that selection. However, we are evaluating all patients that are getting treated with CUDC-427 for their genetic status. And in particular, all IAP proteins, as well as any genes that are involved in apoptosis induction, to try and identify any signatures that we can, both from a genetic mutation, as well as gene expression profile analysis to see whether we can identify a signature for selection of patients. But in the MALT lymphoma, specifically itself, right now, we're not doing a selection.

[Operator:]

And I'm not showing any further questions in queue. I'd like to turn it back to management for any further remarks.

[Ali Fattaey:]

Thank you, everyone. We would very much like to thank our employees, our directors and our investors and partners for their continued support, and we look forward to providing you all with further updates on our progress over the coming months. Thank you very much.

[Operator:]

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