Infinity Pharmaceuticals, Inc.
Q1 2014 Earnings Call Transcript

Published: 7 May 2014

[Operator:]

Ladies and gentlemen, thank you for standing by. Welcome to the Infinity Pharmaceuticals Conference Call to discuss the company's financial results for the first quarter of 2014. My name is Stephanie, and I'll be your operator for today. [Operator Instructions] Please be advised that this call is being recorded at Infinity's request. At this time, I'd like to introduce your host for today's call, Ms. Jaren Madden, Director of Investor Relations and Corporate Communications at Infinity. Please go ahead.

[Jaren Madden:]

Thank you, Stephanie, and good afternoon, everyone. Welcome to today's call to discuss our recent business progress and review our first quarter 2014 financial results. With me here today are Adelene Perkins, President and Chief Executive Officer; Julian Adams, President of R&D; and Larry Bloch, Executive Vice President, CFO and CBO [ph]. Following our remarks, we will open up the call for Q&A. The press release issued earlier today details our results and is available on our website at infi.com. Please note that during this call, we may make forward-looking statements about our future expectations and plans, including clinical development milestones, the therapeutic potential of our product candidates and financial projections. It is possible that our actual results may differ materially from what we project today due to the considerations described in the Risk Factors section of the quarterly report on Form 10-Q for the first quarter of 2014 that we filed this afternoon. While these forward-looking statements represent our views as of today, they should not be relied upon in the future as representing our then current view. We may update the statements in the future, but are not taking on an obligation to do so. Now I would like to turn the call over to Adelene.

[Adelene Q. Perkins:]

Good afternoon, everyone, and thanks for joining us. On our last call, we summarized the very encouraging clinical data from IPI-145, our PI3 kinase delta/gamma inhibitor, and Infinity's lead program. These data show that IPI-145 is highly active across a broad range of hematologic malignancies. And on the basis of these data, we are now in registration-focused studies as part of DUETTS, a worldwide development program in heme malignancies. We have a 3-part vision for the development of IPI-145. The first component is to enable a rapid path to marketing approval for IPI-145 as a monotherapy in both indolent non-Hodgkin's lymphoma or iNHL and in chronic lymphocytic leukemia or CLL through our DYNAMO and DUO trials, respectively. The second component of our vision is to develop targeted chemo-free treatment regimen for patients with heme malignancies. We are enabling this strategy by developing IPI-145 in combination with existing non-chemotherapeutic standards of care. To drive this strategy forward, we will be initiating DYNAMO+R, our Phase III trial of IPI-145, in combination with rituximab in relapsed iNHL. While eliminating the need for chemotherapy-based treatments would represent a significant advance, patients are still and importantly, in need of a cure. In an effort to achieve this, the third component of our vision is to combine IPI-145 with other novel targeted agents. We have an extensive translational research program and have identified several potentially synergistic combinations of novel therapy, which we will describe in conjunction with announcements regarding additional development plans. A final component of our vision is directed to our ultimate goal of achieving cures in these patients. This year will also be critical for the development of our PI3 kinase portfolio in inflammatory diseases, and we anticipate reporting top line data from 2 studies by year end. These include ASPIRA, a Phase II study of IPI-145 in patients with moderate-to-severe rheumatoid arthritis, and our Phase IIa exploratory study in patients with mild allergic asthma. The results of these 2 studies will help determine the best path forward for the development of IPI-443, our second PI3 kinase delta/gamma inhibitor. We are continuing to build our team and capabilities reflecting our growth and progress as a late-stage development company. Earlier this year, we promoted Dr. David Roth to Chief Medical Officer from Senior Vice President of Clinical Development and Medical Affairs. To most effectively advance our expanding portfolio of clinical trials, we also recently hired Ross Pettit as Senior Vice President, Development Operations and Dr. Kai Chan as Vice President, Global Medical Affairs. Ross has over 25 years of experience in drug development, operations and commercialization, and was most recently Vice President, Clinical Operations at AMAG Pharmaceuticals. Kai has over 10 years of experience in the pharmaceutical industry, and was previously the head of the European medical affairs at ARIAD Pharmaceuticals. In addition, we appointed 2 new members to the Infinity Board of Directors who bring important expertise as we approach potential regulatory approval and commercialization of IPI-145. Dr. José Baselga, Physician-in-Chief at Memorial Sloan Kettering Cancer Center, is the newly elected president of AACR and a globally recognized leader in oncology, including the PI3 kinase pathway. Jeff Berkowitz, President of Walgreens Boots Alliance Development, brings to Infinity substantial experience in global healthcare commercial operations and reimbursement. These important additions to our team enable us to expand and accelerate the development of IPI-145, including our goals to finish this year with a total of 10 trials to support initial and subsequent registration; 7 of which will be Phase II or Phase III studies. The combination of an active, well-tolerated drug, a robust development strategy and strong teams has positioned us well to engage in discussions around potential strategic partnerships. In summary, we're well on our way and remain committed to our mission of delivering important new medicines to patients that make a meaningful difference in their lives. Now I'll turn it over to our President of R&D, Julian Adams to walk through our development programs.

[Julian Adams:]

Thanks. As Adelene mentioned, we have generated data demonstrating encouraging activity in tolerability of IPI-145 across a broad range of hematologic malignancies. Adverse events have been predominantly low-grade or asymptomatic, manageable and consistent with the co-morbidities associated with these diseases. On the basis of these data, we've initiated a global development program with potential registration studies in iNHL and CLL, where there remains a significant need for better treatment. DYNAMO is our first registration-enabling study. This Phase II trial is expected to enroll approximately 120 patients with refractory iNHL. IPI-145 is administered at a dose of 25 milligrams twice daily, and the primary endpoint is the overall response rate. Let me remind you that these patients have exhausted all current therapies, and therefore, IPI-145 is intended to be a rescue treatment for these patients. Building on this potential patient benefit, we believe that the initial investigation of IPI-145 as a monotherapy in the refractory setting will help us to confirm its single-agent activity and potentially enable a rapid path to approval and commercialization upon consulting with the FDA. Importantly, DYNAMO also builds on the foundation for additional development opportunities in combination with anti-CD20 antibodies like rituximab, as well as other therapeutic modalities. We are complementing our monotherapy strategy with a Phase III combination study DYNAMO+R, designed to increase the potential use of IPI-145 in relapsed iNHL. DYNAMO+R will be a randomized double-blind placebo-controlled study comparing IPI-145 in combinations with rituximab versus placebo plus rituximab. This trial also has the potential to serve as a confirmatory trial if IPI-145 earns accelerated approval based on the data from DYNAMO. We plan to initiate DYNAMO+R in the second half of this year, and the primary endpoint of this study is progression-free survival. To further expand the potential of IPI-145 in iNHL, we expect to initiate a Phase II trial in treatment-naive patients later this year. We have prioritized the initiation of this trial along with DYNAMO+R as chemo-free regimens which could be particularly meaningful in iNHL where patients are being treated for many years. Moving to our program in CLL, IPI-145 has shown encouraging activity in the relapsed and refractory setting, as well as interesting early data in the treatment-naive setting. We are currently enrolling DUO, a Phase III randomized open-label study in approximately 300 patients with relapsed or refractory CLL. This registration-supporting study is intended to evaluate the safety and efficacy of IPI-145 administered at 25 milligrams twice daily compared to ofatumumab, with progression-free survival as the primary endpoint. Beyond iNHL and CLL, we have observed activity in additional patient populations, including those with T-cell and aggressive B-cell malignancies including diffuse large B-cell lymphoma. Looking across our program and at the field more broadly, what I am most encouraged by is the potential for a total paradigm shift in the treatment of these diseases. We are participating in the development of precision medicines which could change the face of cancer treatment and displace chemotherapy. At Infinity, I am inspired by and committed to advancing our understanding of the biology of these diseases and the way in which they are treated. We have an extensive translational research effort, internally and with external collaborators, focused on 2 areas. The first is to more fully understand the role of PI3 kinase delta and gamma inhibition such that we can leverage the unique profile of IPI-145. The second focus of our work is to identify synergistic combinations of novel targeted therapies, potentially enabling us to achieve minimal residual disease and possibly cure these patients. I look forward to the opportunities to present new translational research at the AACR special conference, targeting the PI3 kinase mTOR network in cancer in September. On the research side, our dedicated team of scientists has developed a -- has helped build a portfolio of an additional PI3 kinase delta and/or PI3 kinase gamma inhibitors. We have identified IPI-443 as a second development candidate. I think both 145 and 443 gives us important strategic optionality to optimally position our PI3 kinase delta/gamma franchise in oncology and inflammation. After we analyze the data from our ongoing inflammation trial [indiscernible] we plan to develop -- to determine our development strategy for IPI-443. So we believe we are in excellent position to leverage the promise of IPI-145. To emphasize the strategy that Adelene and I have described in the near term, we are focused on gaining approval and achieving chemo-free regimen. Our longer term vision is to identify potential cures for these patients through our growing understanding of the biology of PI3 kinase delta and gamma inhibition in novel synergistic combinations. Beyond hematology, we anticipate data readouts from both our trials and information. And with that, I'd like to turn the call over to Larry to discuss the financials for our board.

[Lawrence E. Bloch:]

We continue to be in a strong financial position to execute on our strategic development plans. As of March 31, 2014, we had total cash, cash equivalents and available-for-sale securities of $132.1 million compared to $214.5 million at the end of 2013. In addition, we have in place a $100 million debt facility with Deerfield announced earlier in the first quarter this year, which provides important financial flexibility and allows us access to these funds through February 2015, without any obligation to do so. To date, we have not drawn down any funds under this facility agreement. I'd now like to provide an overview of financial results for the first quarter of 2014. R&D expenses for the quarter was $34.5 million, compared to $20.2 million for the same period last year. G&A expenses for the quarter was approximately $6.8 million compared to $7.4 million for the same period last year. And net loss for the quarter was $42.3 million, or a basic and diluted loss per common share of $0.87, compared to $27.3 million or a basic and diluted loss per common share of $0.57, for the same period last year. Our financial guidance for 2014 remains unchanged. In addition to our strong financial position, we have full ownership of worldwide rights to IPI-145 and the opportunity to evaluate value-creating strategic partnerships. Our key objective would be to access the financial and operational resources necessary to accelerate and expand our global development of IPI-145. So in closing, we had very encouraging global activity with IPI-145 providing the basis for potential registration trials now underway, in addition to develop chemo-free regimens with an aspiration to achieve actual cure to these patients. We also have strong intellectual property protection through 2030. And all of these components taken together provide a solid foundation on which we are building a fully integrated biotech company. With that, we'll open the call up for Q&A.

[Operator:]

[Operator Instructions] Our first question comes from Cory Kasimov with JPMorgan.

[Whitney G. Ijem:]

This is actually Whitney on for Cory today. Just wondering, I guess first off, if you can give us any updates on DYNAMO and DUO enrollment and whether or not those are kind of tracking as expected?

[Julian Adams:]

The trials are in fact tracking as expected. I can't give you precise numbers, but what I can tell you is we've accounted for enrollment. In fact I just spent a day with investigators. We had investigators from Australia, New Zealand and North American investigators, and there's a great deal of enthusiasm for the participation in these trials.

[Whitney G. Ijem:]

Got it. And then, in terms of a novel-novel trial start, what are sort of the rate-limiting steps to get that off the ground?

[Julian Adams:]

I'm sorry, can you repeat the question?

[Whitney G. Ijem:]

Yes, the timeline to a novel-novel combo trial start. Just kind of what are the rate-limiting steps or what are -- what do you need -- what do you still need before kind of starting a combination trial?

[Julian Adams:]

So some of these trials are in development, protocol development. We reviewed the regulatory requirements and believe we have all the information that we need, and we will be announcing the start of those trials once they're ready to go.

[Operator:]

Our next question comes from Michael Yee with RBC Capital Markets.

[John Chung:]

This is actually John on for Michael Yee. So for the DYNAMO trial in iNHL, I recall it required 6 months follow-up after the last patient. And so given your comments that it is tracking -- the enrollment is tracking as expected, do you have any updated thoughts on the timing of this study? Would it be a 2015 event in your view?

[Julian Adams:]

Again, we're not providing specific guidances to when we will complete enrollment and have a readout from the study. But what I can tell you is that we're just very encouraged that the study is progressing well.

[John Chung:]

Okay. And then, for the DUO study in CLL, then, is there an interim analysis built in just like PCYC's RESONATE?

[Julian Adams:]

We are again not commenting on the specifics of the conduct of the trial. We anticipate that there are challenges to enrollment in that trial in North America, and we've accounted for that by having this trial be an international study, and the majority of the patients will be enrolled primarily in Europe as well as Southeast Asia.

[John Chung:]

Okay, then just one last question. I think at the beginning of the year, I remember you mentioned that potential combination approaches for aggressive lymphoma such as DLBCL, not necessarily novel-novel combinations, but with already approved agents, so what is your updated thoughts here and what is the gating factor to start these studies?

[Julian Adams:]

So we think a lot about this. We had, really, an encouraging signal, but as you correctly point out, as a single agent -- it's not sufficient to go ahead with a single agent. And we're reviewing in the laboratory, doing a lot of combination studies, to try to pick the optimal combinations. You can imagine that, given all the agents in development and even approved agents, pair-wise combinations could lead to multiple trials. And what we're trying to do is prioritize what we think will be the best trials to select going forward.

[Operator:]

Our next question comes from Joel Sendek with Stifel.

[Joel D. Sendek:]

I had a couple of questions. First of all can you go over any data you have at ASCO, and then, with regards to the Rituxan combination study, I was expecting that earlier than the second half of this year. Is that expectation wrong or is there a bit of delay there?

[Julian Adams:]

I don't think we provided guidance that it would be earlier in the year. I appreciate that because it is a registration study, and we've had a lot of consultation with both FDA and EMA, we are taking great pains to make sure that we're running a trial with the appropriate endpoints and trial design, and are making sure that it's all harmonized between the -- for a global registration. And to your first point, we have 2 abstracts at ASCO but they're not data abstracts, but basically abstracts describing the details of the DYNAMO and DUO trials.

[Operator:]

Our next question comes from Mike King with JMP Securities.

[Michael G. King:]

Just a couple of questions. I do want to follow up a bit on the novel-novel thought process that you're undertaking. The -- I'm just curious if you could be more specific because I'm just trying to think about what -- I mean, are you obviously cannot access competitor molecules like a BTK or a ABT-199, et cetera, or am I incorrect in that assumption? And secondly, how would you run those trials? Would they be run as Infinity-sponsored trials or are you thinking more along the lines of investigator-sponsored studies?

[Julian Adams:]

We think obviously a lot about this, and we think this is an opportunity to leapfrog and bypass trials that have chemo-containing regimens. Just as an example, we had an abstract at ASH delineating in-vitro combination with ibrutinib. And so we saw profound synergy in a number of different cell lines, and that represents the kind of work we're doing preclinically. I would remind you that ibrutinib is in fact is on the market. It is commercially available. That is not an issue. And with regards to novel-novels where the 2 agents are not approved, there's a very specific FDA guidance around that. And that requires us working cooperatively with the other sponsor, and we have our eyes opened and are very much desirous of doing such collaborations.

[Adelene Q. Perkins:]

And those collaborations, Mike, they could either be part of that strategic relationship or those can be arms length collaborations, where we just work with other innovators and put our drugs together per the FDA guidance that Julian referenced.

[M. Ian Somaiya:]

Okay, but to come back to Julian's point about, if you're ready to do something with ibrutinib, for example, you have to actually purchase the ibrutinib for any kind of study in humans, correct?

[Julian Adams:]

Or it's in a collaboration. We could -- the Pharmacyclics or J&J could be this -- provide ibrutinib as part of the collaboration and it would be a joint effort.

[Michael G. King:]

And then just a quick question on DYNAMO R -- DYNAMO+R, maybe talk about what's the outcome needs to look like for you to feel that there's a true differentiating effect between competitor PI3K delta inhibitors?

[Julian Adams:]

So the trial is being designed so that, first of all, it's approvable and it has a -- it's of registration quality. Just as a background, the anticipated monotherapy with Rituxan in this population is anywhere between 12 and 16 months. And -- so you could imagine that a substantial improvement over that -- the magnitude of improvement over that is important for registration. And then, from a commercial and competitive nature, obviously, we have to demonstrate that the best-in-class PI3 kinase inhibitor is also revealed in this combination, and therefore, our data should be -- should reflect that.

[Michael G. King:]

Okay. And then, if I may, just one quick question on 443, and then I'll get off is, I was under the impression that your development path for 443 was a bit more settled than it appears to be in the language in the release. So am I mistaken in that regard or has something served to change your sort of strategic focus with 443?

[Julian Adams:]

So we've made a sort of a portfolio decision wanting to concentrate our primary efforts on IPI-145 in heme malignancies. I will remind you that we are running both the ASPIRA trial and the asthma trial with IPI-145. We have enabled 443 in terms of its manufacture and its IND and its preclinical tox studies, so that if IPI-145 should prove to have a significant signal in either of these inflammation indications, we're well positioned to make a strategic decision around 443.

[Adelene Q. Perkins:]

We discussed in the past, Mike -- yes, we discussed in the past strategically if there's a compatible dose of IPI-145 in oncology and inflammation, we might take that forward. But we still have to see what signal we get in inflam and at what dose to determine, as Julian mentioned, a portfolio of the -- which molecule we take into inflammation.

[Operator:]

Our next question comes from Jason Kantor with Crédit Suisse.

[Jeremiah Shepard:]

This is Jeremiah filling in for Jason. In regards to this -- going to the novel-novel combinations that potentially you can be looking at, a lot of the works are done with in vitro experiments. How much clinical data would you need to get comfortable with a combination? And then, at what point would you be willing to commit to that combination and move forward to larger pivotal studies?

[Julian Adams:]

Excellent question. So clearly, you got it right, we are first assessing the combination in in-vitro and there are mouse models as well, but nothing will be as compelling as seeing those combination in human clinical studies. And for the synergy to be really reflected, we would expect dramatically better activities in the single agents alone, so true synergy seen even in the Phase I study. And the magnitude of that benefit will drive the decision-making towards pivotal studies.

[Jeremiah Shepard:]

And then, you talked about using these novel-novel combinations in iNHL. So is there a possibility that certain combinations could be more optimal in specific subset of iNHL, for example, follicular, just have one combination that's better or would you -- are you planning on just going after one combination first for all types, or do you expect [indiscernible] specialized medium?

[Julian Adams:]

We have a broad preclinical program examining combinations in a variety of different malignancies. And depending on what we see and the clinical need, we'll make those decisions for clinical development, either specifically by disease histology or by other -- by certain -- driven by certain biomarkers. There's a lot more that goes into that than just a broad iNHL foray.

[Jeremiah Shepard:]

Okay. And the last question is, you mentioned that you hope to have 10 trials up and running by the end of the year, if I understood that right. Could you speculate on potentially how many ISTs could be expected by the end of the year?

[Julian Adams:]

Until the trials actually begin, we're not announcing ISTs. We have several in the works. But we would only make those announcements once the trial actually has begun. And that's being mindful of the fact that our -- the IST is being -- not conducted by the company but by the investigator, and we don't want to prejudge when an investigator is going to be ready to initiate their study.

[Operator:]

Our next question comes from Katherine Xu with William Blair.

[Y. Katherine Xu:]

So I'm just wondering about the partnership. Are we still kind of expecting a partnership this year, and do you have parallel plans in financing? That's the first question.

[Lawrence E. Bloch:]

So we have not provided guidance for a partnership in our annual 2014 guidance. But certainly, working towards strategic collaboration is one of our priorities after initiation of the Phase III registration studies that Julian and Adelene discussed, and we have multiple discussions ongoing. Obviously, the -- for us, the critical thing is finding the [indiscernible] the right partner who shares our vision for optimizing IPI-145 across the broad range of indications where it's shown activity. It obviously is a unique and valuable asset, the fact that it's a Phase III program with IPL [ph] to 2013 that's been significantly de-risked and has significant and broad activity. So in terms of you guys touched about additional plans, that was really the purpose of putting in the Deerfield financing is that this provides us with real optionality and financial flexibility because we have the right but not the obligation to access $100 million anytime over the next period between now and the end of February 2015. So we think we're in a fine position to be able to make that determination of if and when to pull down those funds.

[Y. Katherine Xu:]

Can you give some indication of how the partnership discussions are going?

[Julian Adams:]

We're very pleased with the breadth and the depth of the discussions we're having. Again, it's no surprise that after Onyx was acquired that on all the charts I'm sure that you're intimately familiar with, IPI-145 is the most advanced wholly-owned hematological oncology asset. This has advanced data, so it's a rare and valuable asset. And it's being recognized as such in the pharmaceutical markets.

[Y. Katherine Xu:]

The iNHL development program is very comprehensive. You have a monotherapy -- single-arm study and you have DYNAMO+R following for the full approval and you're starting the frontline study as well. Whereas for CLL, you only have just one study. You have to start [indiscernible] with RESONATE which is Pharmacyclics is going to report data at ASCO this year. And so do you -- so for CLL it looks like, not sure whether you could exceed Pharmacyclics in terms of potency and profile, and also you are few years behind. Just curious what the plans there are and do you plan to have your partner to kind of broaden that program in CLL going forward?

[Julian Adams:]

So in CLL, as we mentioned, we do have DUO, so the first trial that will get us approved, and that creates optionality for being able to combine with other anti-CD20 therapies similar to the design of RESONATE if you wish. However, we have begun also to enroll patients who have progressed well in ibrutinib. And so we're collecting data and still continuing to learn from our clinical experience with -- in CLL. What I can tell you and what we reported at ASH is that resistance to ibrutinib is not cross-reactive to IPI-145 treatment.

[Adelene Q. Perkins:]

And as you mentioned, we do have a comprehensive program in iNHL because we do -- we're really building on the strongest monotherapy data that's been shown in that disease across a number of different -- inhibitors across a number of different targeted mechanisms. So that's what we're really focused on, to really win in indolent and non-Hodgkin's, and our vision for CLL is to be the best PI3 kinase, but we recognize it's a more crowded space. So we're really trying to seize the opportunity in indolent as our top priority.

[Y. Katherine Xu:]

Right, great. And one last question, if I may. I'm just curious. Julian mentioned a few times about the potential cure of the diseases, I'm just wondering from a pre-clinical or a clinical level, do we know, from a scientific aspect, what is the threshold to achieve that you could actually potentially achieve a cure?

[Julian Adams:]

So the clinical and scientific community are very much now focused on MRD, and MRD negativity with undetectable disease including in the bone marrow. And there are a lot of -- there's a lot of interest that we got in CLL. There was a FDA workshop last year in this regard, and a similar effort is being mounted for indolent lymphoma as well.

[Operator:]

Our next question comes from Navdeep Singh with Goldman Sachs.

[Lisa Zhang:]

This is Lisa in for Navdeep. Given your cash position, do you think now is the appropriate time to secure a commercial partner for IPI-145?

[Lawrence E. Bloch:]

This is Larry. We don’t feel that the cash position is a driver for securing a potential partner. We think that the fact that we now are in registration-enabling studies, and as Julian and Adelene pointed out, we're enabling the novel-novel combination, now is a point where a partner in both financial and operational resources can help broaden the IPI-145 clinical campaign. And so that's really the driver for accessing the appropriate partner. But we want to get the right partner who shares the vision for IPI-145, who also importantly shares our mission -- support our mission to help us to continue to develop as a fully integrated bio-pharmaceutical company including having important commercial role in important commercial markets. And so, that's the process we're undertaking this year.

[Lisa Zhang:]

Got it. And what are your thoughts on the early launch commentary with Pharmacyclics [indiscernible] and what does that mean for you as potentially there to market?

[Adelene Q. Perkins:]

We are not in a position to comment on others' progress, so I think that's a question better directed to the Pharmacyclics and Janssen team.

[Lisa Zhang:]

Okay. And then lastly, what are your thoughts on 145 activity in T-cell lymphoma, and could we expect any registrational quality studies?

[Julian Adams:]

So we are the first to show that a targeted agent in the PI3 kinase class has shown -- has demonstrated clear activity in T-cell lymphoma. It's a very challenging disease because particularly patients on our study will be very heavily pretreated, some patients getting as many as 10 or 11 prior treatments. So we saw a very advanced population with patients progressing with even within a month of their last -- while on their last therapy. So what we need to do is to determine whether monotherapy is appropriate for these very aggressive diseases. And if not, what is the best approach to enable a combination therapy, and which combination specifically, in T-cell. There are a few approved agents you may know. There is chemotherapy in that setting, but there are also HVAC inhibitors. And so we are still in the planning stages and discussion stages with key opinion leaders on how to enable that.

[Operator:]

[Operator Instructions] Our next question comes from Eun Yang with Jefferies.

[Eun K. Yang:]

Question on the DUO study. Julian you mentioned that patient enrollment has been challenging in North America. Can you give us the reasons why it has been challenging?

[Julian Adams:]

No, no. I didn't say it was challenging. I said we expect it to be more challenging given the fact that there is now a treatment option from Pharmacyclics and J&J with the commercial availability now of ibrutinib. And so we had always considered that and had planned that the majority, probably 80% of our enrollment will be x U.S. They're enrolling well so far in the U.S. at this time.

[Eun K. Yang:]

Okay. And then another question on DUO study. So when you look at PI3 kinase inhibitor they did it in combination with Rituxan, and I'm kind of wondering what is your rationale behind going for monotherapy versus a combination? And for CLL, whether PI3 kinase might be better with a combo than single agent?

[Julian Adams:]

Well, we believe our data are superior based on our Phase I data. And a combination -- you're talking about 2 different lines of therapy. So in the relapsed refractory setting in DUO for CLL, we believe the strength of our data support a monotherapy head-to-head study versus ofatumumab.

[Eun K. Yang:]

Some of the physicians that we spoke with, they feel ofatumumab is really not a good comparison because it's not being used that much?

[Julian Adams:]

However, it is a very adequate regulatory comparison to establish our fastest path to approval. I agree with you that it's not the end game, it's the beginning of our investigation. And we've harmonized this opinion internationally.

[Operator:]

Thank you, and I'm showing no further questions. At this time, I will now turn the call back over to Adelene Perkins for closing remarks.

[Adelene Q. Perkins:]

Thank you, everyone, for joining us today, and we look forward to providing further updates on IPI-145 in the coming weeks and months. Operator?

[Operator:]

Thank you. Ladies and gentlemen, that does conclude today's conference. You may all disconnect, and everyone, have a great day.