Curis' Management Presents at Deutsche Bank BioFEST Conference (Transcript)

Dec. 2.13 | About: Curis, Inc. (CRIS)

Curis, Inc. (NASDAQ:CRIS)

Deutsche Bank BioFEST Conference

December 02, 2013 03:25 PM ET

Executives

Ali Fattaey - President and COO

Analysts

Mohit Bansal - Deutsche Bank

Mohit Bansal - Deutsche Bank

Thank you all for joining us. I am Mohit Bansal, one of the members of biotech team at Deutsche Bank. I am joined today with Mr. Ali Fattaey; he is President and COO of Curis Incorporation. Thank you for joining us. So for those who are on webcast, you can email me questions at mohit.bansal@db.com, I'll read them anonymously.

So Mr. Ali for those -- for the benefit of those who are new to the story could you please start with a brief overview of the company and the programs?

Ali Fattaey

Thank you Mohit and thank you for being in the audience and also on the webcast listening. An overview of the Company really see ourselves as having a business model that's very balanced in regards to the pipeline the internal pipeline which are proprietary programs, we have two of those which we'll describe for you today and [go through] some of the questions. But also we have two very important partnerships, the key one at this moment being a partnership with Genentech and Roche regarding the drug Erivedge that's approved for advanced basal cell carcinoma and also a partnership with Swiss company Debiopharm early clinical Hsp90 inhibitor.

So the balance between the internal pipeline that's totally owned and revenue generating partnerships that we currently have really defines the company in that perspective.

Mohit Bansal - Deutsche Bank

So can you please start with CUDC-427 and then could you please help us understand in terms of what are the key differences between the trial Genentech conducted and the trials you are conducting right now.

Ali Fattaey

As you know the CUDC-427 designated drug is an IAP antagonist that we in-licensed from Genentech, Roche roughly a year ago exactly at this time, at the time of the in-licensing Genentech had completed the study in 42 patients [Alzheimer’s] patients, solid tumor and lymphomas and is really based on that clinical data as well as the very large supply of pre-clinical data that we developed our initial trial of CUDC-427. To give you the perspective on the Genentech sponsored study at the time of the in-license Genentech tested their drug as a single agent giving the drug once daily in a 21-day cycle using 14 days on treatment, seven days off. That regimen was selected based on the desire from the Genentech Roche side really to combine CUDC-427 with Xeloda in a population of breast cancer patients, that the regimen that was selected for that which matches Xeloda very well, we obviously intend to develop drug in that indication as well.

Based on the Genentech study once daily 14 days on, seven days off and the dosing that Genentech tested was in 11 different cohorts starting at the low dose of five milligram all the way to 600 milligram dose. From -- just to give you a perspective on the dosing we consider anything north of 90 milligram dose to be therapeutically relevant based on full engagement of the biomarkers as has been looked at either in peripheral blood mononuclear cells or in the tumor tissues itself, the target seems to be engaged. And Genentech was able to take it as we indicated up to 600 milligram dose on that same schedule with fairly tolerable regimen.

There was a few things that was remaining to be addressed with regards to the monotherapy treatment of the drug. One of those was whether the drug holiday was necessary that Genentech had implemented in their study as indicated there is a seven day holiday between that really meant to match the drug much more to the capecitabine Xeloda regimen that's used in the clinic. We wanted to address that as one of the parameters.

Secondly, the half life of the drug in the Genentech study was determined to be roughly 6 to 7 hours, therefore there was an interest in determining whether maintaining the drug trough levels at higher levels by using bi-daily dosing would be more advantageous. And finally we wanted to test the drug in a population of patients including predominantly ovarian cancer patients that may have certain genetic alterations. So really those were the three goals we wanted to address in the trial that we initiated. Therefore, our trial which started in July used a bi-daily continuous dosing of the drug versus the Genentech sponsored study that was with a holiday and once daily dosing, that was the major difference.

Question-and-Answer Session

Mohit Bansal - Deutsche Bank

Got it. So maybe regarding the liver enzyme elevation issue you saw in your clinical trial. So do you see similar types of issues in Genentech trial as well or was it a surprise?

Ali Fattaey

Yes, that's a very good point, obviously any Phase I study or first in man study that’s conducted with a drug, the main goal of that is to determine the safety profile of the maximum tolerated dose as well as the tolerability of the drug. So safety MTD and tolerability are key factors in determining that. The Genentech study in terms of dose limiting toxicities there was only one form of those limiting toxicity which was a grade III fatigue at the higher doses of the drug, in terms of common adverse events, there was some amounts of rash that was observed in a number of patients and also two patients at the higher doses of the drug, including the 450 mg dose as well as 600 mg dose that Genentech tested, one patient in each of those cohorts experienced a grade III elevation of AST and ALT liver enzymes. The important thing about it those experience was that, upon discontinuation of the drug the AST/ALT levels returned to normal in that regards.

If I can just fast-forward to our drug -- to our trial and experience with that, we conducted our study by -- as I mentioned treating patients on a bi-daily continuous dosing regimen, the patients were treated at a dose of 200 mg bi-daily for a total of 400 mg, and there were no DLTs associated with that cohort.

We escalated to a dose of 300 mg bi-daily for a total of 600 similar to Genentech had done at their top level. And there also appeared to be no dose limiting toxicities associated with that cohort within the first cycle. And hence we escalated to the 400 mg which was a top dose that we were going to test bi-daily, for a total of 800. It’s really during this dosing period that a breast cancer patient with the disease disseminated to her lung, bone, ovaries and liver, that was enrolled in the 300 mg bi-daily dose experience and AST/ALT increase in the liver enzymes, similar level, similar timing as what Genentech had seen in the past and we also took the standard course of cautionary measure of discontinuing the drug for that patients.

And her liver enzymes also appeared to begin to come down and be underway to stabilize. But unfortunately several days after discontinuation of our drug, her liver enzyme levels as well as her bilirubin blood levels began to rise again. We should clarify that obviously we discontinue our drug but many of the cancer patients do take multiple different drugs, not necessarily for their cancer but for other side effects including pain, including other factors and there was no discontinuation of her other drugs. These as well as the extent of her disease, the nature of her disease, the pharmacokinetics of our drug within this patient, is all being evaluated of course as part of the analysis of the course of this particular adverse event in this particular patient at this point.

Mohit Bansal - Deutsche Bank

So in the fact that this patient had liver enzymes at normal levels -- reduced after you discontinued the drug and then after that -- after only certain period of time this patient had a rise in liver enzymes. So how important is that factor when you just go back to FDA and then talk about releasing the hold?

Ali Fattaey

It’s a very good point. Anytime, I should actually point out, anytime in a case of Phase I study, these types of adverse events that occur, it becomes very-very difficult to pinpoint exact cause and exact reasons behind some of the adverse events. And as I mentioned in the past, in the Genentech study as well, out of 42 patients two patients had experienced AST/ALT increases which is not unexpected based on the mechanism of this drug and especially at the higher doses. However, not all patients show that.

So it’s a little bit of a trick to figure out what is really causing it, what are the contributing factors. In a sense we sort of think about it as three different sets of factors that can contribute in general. One of those of course is our drug. Our drug was something that this patient was taking and we are very closely looking at that. As I mentioned the exposure of the patient, the metabolism of the drug, if any, all of those is being looked at.

Secondly is the nature of the disease that the patient had. As I mentioned the patient did have liver metastasis in the past. There has been other patients that had been treated with liver metastasis including patients that we treated, not all of them have had alterations in their liver enzymes. But it is important to look at the nature of the patient’s disease and the degree of dissemination as one factor.

And then thirdly, which is an important factor as well is what else the patient may have been taking, and that could have potentially contributed alongside these other factors. So our drug, the nature of the disease with the patient, as well as other drugs that the patient were taking are all potential contributors here. We’re clearly evaluating that. The nature of the fact that this patient’s liver enzyme levels rose significantly after we had discontinued our drug, gives us some clues to certainly look at her disease, and certainly look at her other medications that she was on as contributing factors and all of that will be part of the package that we’ll submit to the FDA. I should point out that we do intend and are on track would be able to submit a full response to the FDA before the end of year, certainly before the holidays and that’s our current projections for that. As a form of process of post-submission, the FDA has up to 30 days for a review and analysis of our package for their decision to lift the hold or ask additional questions if needed.

Mohit Bansal - Deutsche Bank

And then do you think in any way the fact that in this trial, the patients were on continuous dose could have been a reason behind this liver enzyme issue?

Ali Fattaey

Certainly, it’s possible. As I mentioned, the patient is on our drug whether a drug holiday for [indiscernible] and the Genentech study, the regimen that was meant to be used in combination with capecitabine happens to be the better regimen with the drug holiday certainly something that we’re considering. I think when we look at the timing and the nature of initial AST and ALT increases in the patients in our study as well as in the patients that were in the Genentech study, they seem to be a similar profile similar timing. I think it’s possible that’s a drug holiday can benefit the patient. I don’t think we have any hard data to address that. I can’t say one thing though is that we don’t see any compelling evidence that bi-daily treatments is providing any advantage beyond daily treatment of the drug whether a drug holiday is something that’s prudent and something we should look at in terms of going forward when we started rolling new patients that’s being serious considered and evaluated.

Mohit Bansal - Deutsche Bank

That’s helpful. So moving onto your other compound in your pipeline which is CUDC-907, it’s a dual PI3K and HDAC inhibitor. So I believe this is in collaboration with LLS. So could you please talk a little bit about the collaboration and then what kind of money you get from LLS?

Ali Fattaey

Yes that’s a very good point and thank you for that. CUDC-907 is a drug candidate that’s again proprietary within the company fully owned by Curis. It is a dual targeting agent that targets the HDAC enzymes as well as certain PI3 kinase enzymes and is designed to that in one molecular entity. We do as you indicated work with the Leukemia and Lymphoma Society and are very grateful for their support and participation in with us and then seeing the value and benefit for this potential drug.

It is a collaboration that’s started at the time of when the drug was in preclinical setting. The support from LLS could be up to $4 million in monetary contribution of which we have so far recognized, I believe roughly 1.5 million or so of that to Curis. And the support will go from preclinical all the way into Phase 2 clinical study. Again, we really do appreciate the contribution not only from the monetary side they have been very-very good advisors and they do have the reach with lymphoma DAC that’s we very much appreciate networking with as well.

Mohit Bansal - Deutsche Bank

That’s great. So maybe, I mean, PI3K is a hot space right now so maybe you -- so people know about – everyone knows about idelalisib and IPI-145 and these are the drugs which come to mind when you talk about PI3K. So could you please talk about the key differences and similarities between your PI3K and the others?

Ali Fattaey

So it’s a good point then I should say that CUDC-907 is really -- as I indicated is really a dual inhibitor that brings a PI3 kinase inhibitory moiety and marries that in one molecule with hydroxamic acid based HDAC inhibitory moiety into one molecule. When we look at it from PI3K kinase inhibitory activity, our inhibitor CUDC-907 targets the PI3 kinase alpha and delta mostly potently, to some extent PI3 kinase beta in no appreciable inhibition of PI3 kinase gamma.

When compared to what’s reported for idelalisib as well as IPI-145 as you mentioned other PI3 kinase inhibitors, idelalisib is reported to be much more selective for PI3 kinase delta and IPI-145 from my understanding is much more targeted towards PI3 kinase delta and gamma. So right away, there are quite relatively clear differences between the three drugs with respect to their PI3 kinase inhibitory activity. What’s sets CUDC-907 further part of course is the addition and bringing of the HDAC inhibitory activity which we believe can address some of the other pathways that can result in scape from PI3 kinase inhibition in that regards.

Mohit Bansal - Deutsche Bank

Could you please in terms of science combining of PI3K and HDAC, how do you think that they will have a synergistic activity in terms of advocacy and why do you think that there should be higher responses compared to using the single molecule?

Ali Fattaey

So that’s a good point as well. So mechanistically once we start looking at pathways that get, signaling pathways that get altered in response to a PI3 kinase inhibitor, versus pathways and signaling, pathways that gets affected when an HDAC inhibitor is introduced and then what happens when you combine the two. One of the things that we right away see and this has been published from Curis in the pre-clinical setting at least is the fact that with the PI3 kinase inhibition we get a very potent inhibition of the PI3 kinase AKT survival pathway. That's certainly the case and I think that's fairly common among PI3 kinase inhibitors.

What is attractive with bringing the HDAC inhibitory activity as well alongside with the PI3 kinase, is that we see a fairly profound inhibition of the Mek Erk, a signaling arm of the receptor tyrosine kinase signaling that is not seen with PI3 kinase inhibitors and furthermore in certain subsets of hematologic cancers we also see inhibition of the JAK/STAT signaling pathway.

Now one thing that we do find is that when the two things are combined either independently with the PI3 kinase and the HDAC inhibitor or when CUDC-907 is administered in culture cell is that we get a fairly profound induction of apatosis with the combination of the two, versus each one independently. And this can occur, certainly we’ve shown that in the setting of the indications that we're looking at, clinically we see CUDC-907 in the context of lymphomas as well as in the context of multiple myelomas and we see that’s readily happening. So we do think it's a synergy between the inhibition of different pathways that result in better induction and fairly robust induction of apatosis by combining the two either separately or in the case of CUDC-907.

Unidentified analyst

We have got a question. Given other PI3 kinases will be combined as well with all sorts of combinations, like -- and do you see your drug which is seeing two different targets being combined with something else, how do you see that pulling out?

Ali Fattaey

That's a good point, we're already in one drug coming in as a combination, and I think one of the favorite things at the moment is in fact of course the potential combination of in this preclinical setting at least, potential combination of PI3 kinase inhibitors as well as HDAC. This is something that I've indicated the CUDC-907 does as one drug and that we've published on the potential for energy in that regard.

Now developing that in one molecule allows us to develop the drug in essence as a combination from the very-very beginning. This is, in one case a preferred combination that people would like to do, we’re already developing that in one drug from the very early on. Therefore all the dosing, all the scheduling of the circumventing side effects and every optimization is done in the combination.

In the context of when drugs are developed as a monotherapy and later on combined, each one of those drugs gets optimized for itself as a monotherapy and then later on has to be backtracked to be optimized as a combination again, and that you know when we look at into the field, this is a fairly nascent part of the field in terms of combining targeted agents and how do you actually best combine them, what regimen, what schedule, what dosing. For us it's all beginning from the very beginning with one drug with one pharmacokinetic profile and with one side effect profile and hopefully one efficacy profile.

Unidentified analyst

I've got a follow up. Verastem was mentioning that maybe some of the mechanism resistance for PI3 kinase [indiscernible] pathway, so targeting both pathways is important, for HDAC is there any reason why if you target -- by targeting HDAC as well that somehow you're able to down-regulate into a pathway or you'll have a different resistance mechanism.

Ali Fattaey

It’s a good point, there are multiple resistance mechanisms to fairly specific PI3 kinase inhibitors and I think taking those into consideration and addressing those and then targeting different drugs into those populations that have that is an important one. One example that we see, obviously it's fitting is in the case of that's not published more and more is in the case of for example mantle cell lymphoma, this is a setting where at presentation the disease is primarily driven by PI3 kinase delta signaling, whereas on relapse the PI3 kinase alpha signaling has, seems to have picked up quite a bit which fits a lot more into potential treatment with a drug that PI3 kinase alpha as well as the other circumventing pathway such as I mentioned JAK/STAT and/or MEK inhibitory pathways being picked up as [shared] mechanisms, again the HDAC potentially providing that in certain indications. Those are all things that we take into consideration and try to direct our drug into those avenues as well.

Mohit Bansal

Great, so in the audience anyone has any questions?. So what are your next steps for 907 and what are we going to see at ASH.

Ali Fattaey

It's a good point, for CUDC907 we will have a presentation as a preliminary phase one or interim phase one results at ASH, the presentation will be one week from today in New Orleans on Monday and what we intend to present is really every one of our drug that's in development we think about it in terms of their data with regards to their pharmacokinetics, pharmacodynamics and biomarkers, their safety profile as well as any clinical benefits and those are the parameters that we intend to present to the extent that we have it and as many patients as are evaluable at that time.

We have given some indications from the early start of this trial, it was a patient with multiple myeloma that has been continued to be treated beyond multiple cycles I think cycle 12 or 13 now, each cycle being 21 days, that patient continues to be on study. There is a patient with defused large B-cell lymphoma that at the time of presentation will be beyond cycle 8 or so I believe as well. And we will present the full context or the full compilation of any clinical benefit and activity for the study as well as the safety we've seen both from the daily dosing regimen where we started this study as well as to the extent available data from the intermittent of dosing twice weekly and if possible three times weekly dosing schedules on that as well. Those results will be presented at ASH.

Obviously, when we look into 2014 our goals are to complete these dose escalation phase certainly in the intermittent schedules which seem to alleviate some of the safety adverse events that we've seen as well as we have mentioned in the past the half-life of the drug or the resident time of the drug seems to be beyond 24 hours. These intermittent dosing cycles allow us to look at the drug in a more suitable dosing schedule. Once this escalation is completed we do look forward to expansion cohorts of the drug potentially in the indications as we just mentioned where we have seen some amount of clinical benefit in the hematologic cancer [study]. That will be closer to the mid-year timeframe for that drug.

Mohit Bansal - Deutsche Bank

The space is turning into a big big pharma biotech game with J&J, Gilead I mean all these big players are in there. So do you think -- how do you think about partnering a program after you have certain amount of data. So what are your thoughts on that?

Ali Fattaey

Historically, Curis has done a couple of partnerships as I mentioned earlier in the case of Erivedge with Genentech and Roche and we have always credited to the fact that at the time of that partnering which was in 2003 Genentech and Roche partnering was an important one, because that really made that preclinical compound become a clinical candidate and eventually becomes a drug, that was an important part.

However, now we look at Curis as a company that has seen a drug go all the way through and become approved if not something that Curis did on its own certainly the discipline and the -- if you will the development by osmosis has certainly occurred and we have a very good development team in the organization now.

Our goals, should we consider partnering or partners become interested in this is to retain as much of the development of the drug as possible, we certainly have an A rated team, first class team that has now recently joined Curis in clinical development, Jay Viner our new Chief Medical Officer very astute in terms of development of drugs all the way through to later stages. And also potentially for Curis these two pipeline drugs are fully owned and we intend to be able to retain as much of the commercial rights in the U.S. and minimum as possible.

Those are some of the things that we look to should partner and get going. We're not at the moment engaged in any partnering discussions, but we also don't look at them as being exclusive if you will. We don't necessarily have to develop all of it.

Clinical data is important, recognizing that the drug has activity and -- the drugs are active and able to be given to patients is an important part of evaluation and we certainly welcome that as well as part of the course of developing the drug.

Mohit Bansal - Deutsche Bank

So maybe one question on -- last question on your royalty arrangements on Erivedge. And, maybe you could inform the audience about what kind of royalty arrangements are there? And then could you provide some sense of what kind of peak revenues you -- peak opportunities?

Ali Fattaey

So the arrangements the licensing arrangement with Genentech and Roche, the partnership that we have, I think we have indicated we do earn certain milestones and much of that has been recognized additional ones to be recognized still, in terms of the royalty stream the royalty starts at 5% and escalates in several steps to higher single digit. The highest level is way below or substantially below the 1 billion total sales mark for the drug that we would earn. We at the moment continue to earn the 5% royalties, in terms of guidance and in terms of the sales of the drugs and I think we have provided any guidance nor have Genentech and Roche and we look to them to provide some of that.

But suffice it to say that with the current efforts that Genentech has shown in the marketing of the drug in the U.S., a very strong commitment to filings and approval of the drug globally for advanced BCC. And the trial that they have conducted in the operable suboptimal setting, the results of which will be presented in the first quarter of next year, and the additional study that they have just recently initiated in AML and high risk MDS patients with Erivedge. Really it’s a test to the fact that Genentech and Roche do see this drug as a very important drug with potential for significant sales which really translates into significant revenues in the coming future for Curis as well.

Mohit Bansal - Deutsche Bank

Great, so thanks a lot for joining us

Ali Fattaey

My pleasure.

Mohit Bansal - Deutsche Bank

Thanks.

Ali Fattaey

I appreciate it. Thank you very much.

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