Infinity Pharmaceuticals, Inc.
Q2 2013 Earnings Call Transcript

Published: 8 Aug 2013

[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 second quarter of 2013. My name is Ben, and I'll be your operator for today's call. [Operator Instructions] Please be advised that this call is being recorded at Infinity's request. At this time, I would 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, Ben, and good morning, everyone. Welcome to today's call to discuss our recent business progress and review our second quarter 2013 financial results. With me here today are Adelene Perkins, President and Chief Executive Officer; Julian Adams, President of R&D; and Larry Bloch, CFO and CBO. 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 Form 10-Q for the second quarter of 2013 that we filed this morning. 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 views. We may update these statements in the future but are not taking on an obligation to do so. And with that, I'd like to turn the call over to Adelene.

[Adelene Q. Perkins:]

Thanks, Jaren. Welcome, everyone, and thank you for joining us on the call today. The second half of this year has a number of important milestones for Infinity, with multiple anticipated trial read-outs and the expected initiation of our first Phase III study of IPI-145. Today, we are pleased to announce that following consultations with global regulatory authorities, we can now share our second anticipated registration path. We expect to initiate a Phase III monotherapy trial of IPI 144 -- IPI-145 in patients with Relapsed/Refractory Chronic Lymphocytic Leukemia, referred to as CLL, in the fourth quarter of this year. Last quarter, we announced the initiation of a Phase II monotherapy trial of IPI-145 and Refractory Indolent Non-Hodgkin Lymphoma or iNHL. In addition, we were recently granted orphan drug status by the FDA for IPI-145 in follicular lymphoma, the most common subtype of Indolent Non-Hodgkin Lymphoma, adding to the CLL and small lymphocytic leukemia or SLL, orphan designations that we received from the FDA and EMA earlier this year. Both of these potential registration paths are based on very encouraging data from our ongoing Phase I study of IPI-145 in patients with advanced hematologic malignancies. These data give us confidence that IPI-145 has the potential to be the best-in-class PI3 kinase inhibitor in this indications. Julian will review these trials in more detail shortly. While monotherapy offers an important treatment option for patients and is often the fastest path to approval, ultimately, we anticipate studying IPI-145 together with established standards of care, as well as with targeted agents now in development. Our vision for IPI-145 is to offer a meaningful improvement to the treatment paradigms available for patients with heme malignancies. We hope to replicate the tremendous advances made in treating patients with other hematologic malignancies, such as CML, in which patients have an enhanced life expectancy following treatment. Enabling patients to live with Indolent Non-Hodgkin Lymphoma and CLL at chronic conditions would represent an important step towards our ultimate goal of finding cure for these patients. Furthermore, the potential to treat -- provide treatment benefits to patients over an extended period represents a significant commercial opportunity for Infinity. We are also studying IPI-145 in inflammation, which Julian will review shortly. In our Hsp90 program, we anticipate reporting top line data from our Phase II study of retaspimycin hydrochloride in patients with non-small cell lung cancer by the end of this year. If data from our Hsp90 trial are positive, we have the potential to add a Phase III study in non-small cell lung cancer to our growing portfolio of potential registration paths. In summary, by year-end 2013, we expect to have multiple mid- to late-stage clinical trials underway, including the Phase II trial of IPI-145 in Indolent Non-Hodgkin Lymphoma, the Phase III trial in CLL and the Phase II trial in rheumatoid arthritis. Our experienced management team and all of the talent citizen owners of Infinity are excited about the prospects before and remain committed to our vision of building a sustainable, fully integrated, biopharmaceutical company. With a solid financial foundation and worldwide rights to our entire portfolio, we believe we are well-positioned to rapidly advance our programs to their next key value inflection point. With that, I'll turn the call over to Julian.

[Julian Adams:]

Thank you, Adelene. This morning, I will review our pipeline with a focus on IPI-145, our potent oral PI3 kinase delta gamma inhibitor. We're continuing to make important strides in rapidly advancing IPI-145 with a late stage clinical development program focused on iNHL, as well as CLL. We have also submitted both clinical and preclinical data for presentation at ASH, where we hope to share further updates in December. We are very pleased to be able to provide more details about our anticipated registration path for 145, and the clinical team is focused on initiating our planned Phase III trial of IPI-145 in patients with CLL in the fourth quarter of this year. We are sharing these plans with you following consultations with FDA and EMA, the European authorities, during which we'll review the study protocol. This is a global Phase III randomized monotherapy study designed to evaluate the safety and efficacy of IPI-145 administered at 25 mg twice daily or BID. In the study, approximately 300 patients with relapsed refractory CLL will be randomized to either IPI-145 or ofatumumab. The primary endpoint is progression free survival as assessed by independent radiological review. Importantly, if the data are positive, IPI-145 would be the first PI3 kinase inhibitor to demonstrate superiority to ofatumumab. In conjunction with this trial, we are also planning an extension study for patients with confirmed radiologic progression on either arm of the study so that they will have an opportunity to cross over to receive other IPI-145 or ofatumumab. The data reported to-date from our Phase I trial of IPI-145 in advanced hematologic malignancies provided the basis for moving forward with this Phase III trial in CLL. In June, we reported that 145 was well tolerated in this patient population and showed a 55% response rate with 12 partial responses amongst 22 patients available for response as defined by the International Workshop on Chronic Lymphocytic Leukemia or IWCLL criteria. These responses occurred early with a median time to response of 1.9 months. We also reported stable disease in 9 patients, 7 of which, have no new responses, which means greater than 50% shrinkage of their lymph node. Our second area of focus for potential registration is iNHL. We are enrolling patients in a Phase II monotherapy trial that began in June. This open label single-arm study is designed to evaluate the safety and efficacy of IPI-145 administered 25 mg BID in approximately 120 patients with Indolent Lymphoma, whose disease is refractory to radio immunotherapy or to both rituximab and chemotherapy. This trial has rigorous eligibility criteria, and patients enrolled in the study has to progress within 6 months of receiving their last therapy and were, therefore, refractory to their last treatment. The primary endpoint of the study is response rate according to the International Working Group or IWG criteria, as assessed by independent radiologic review. Data reported in June showed that IPI-145 was well-tolerated in this patient population with a 68% response rate consisting of 3 complete responses, 10 partial responses among 19 patients evaluated for activity. Similar to CLL, responses occurred quickly with the median time to response of 1.8 months. PI3 kinase, and more broadly B-cell receptor inhibitors, represent promising therapeutic areas, so we are continuously assessing the competitive landscape and the opportunity for IPI-145. We believe that IPI-145 has the potential to be the best-in-class PI3 kinase inhibitor in lymphoma and CLL. These trials reflect this belief, based on the data we have generated to-date and our monotherapy strategy, reflects our goal of rapidly advancing IPI-145 for patients and physicians. In addition, Adelene mentioned, we expect combination studies to play a key role in further demonstrating the clinical potential for IPI-145. As part of our combination strategy, we are supporting an ongoing investigator-sponsored Phase Ib open label dose escalation study of IPI-145 in patients with advanced hematologic malignancies. This study is designed to evaluate the safety, pharmacokinetics and clinical activity of IPI-145 in combination with rituximab, bendamustine or both rituximab and bendamustine combined. Beyond hematologic malignancies, there's a strong biological rationale for developing IPI-145 in inflammation, in which we have 2 clinical trials underway. In May, we began enrolling patients in the ASPIRA study, a Phase II double-blind placebo-controlled trial designed to evaluate efficacy, safety and pharmacokinetics of 3 different dose levels of IPI-145 twice daily on a background of methotrexate versus placebo plus methotrexate in more than 300 patients, with moderate to severe rheumatoid arthritis. The primary efficacy endpoint measured at 12 weeks is the ACR 20 response rate, which is defined as the proportion of patients who received at least a 20% improvement in the American College of Rheumatology or ACR response criteria. We are also conducting a Phase IIa trial in IPI-145 -- of IPI-145 in patients with mild allergic asthma and expect to provide an update on this study in the second half of this year. In addition to our clinical efforts, we have an ongoing internal research program directed to identifying additional PI3 kinase inhibitors, which would complement IPI-145. We are continuing to advance our second PI3 kinase delta gamma inhibitor, IPI-443 through preclinical studies, which, if successful, could enable Phase I development. IPI-443, an additional PI3 kinase discovery efforts have the potential to provide us with important strategic flexibility and optionality as we pursue dual development pathways in both hematology and inflammation. Finally, I will briefly review the ongoing Phase II study, double-blind, randomized placebo-controlled trial of our potent and selective Hsp90 inhibitor for retaspimycin hydrochloride in non-small cell lung cancer. This trial is designed to evaluate the safety and efficacy of docetaxel plus retaspimycin compared to docetaxel plus placebo in 226 second or third line patients, who are heavy smokers and who are naive to docetaxel treatment. The study has 2 co-primary endpoints, overall survival in the total population and overall survival in patients with squamous cell histology. A secondary endpoint includes the analyses of an undisclosed prespecified biomarker assay in a CLIA-certified lab. We anticipating -- we anticipate reporting top line data from this study in the second half of 2013. In summary, 2013 is an important year for our R&D programs, and we are pleased with the progress we've made so far. We appreciate that there's still a lot of work to do and we look forward to updating you on our clinical milestones in the balance of this year. And with that, let me turn the call over to Larry to review our financial results.

[Lawrence E. Bloch:]

Thank you, Julian. It's indeed a strong position, with a rapidly developing pipeline, more than $275 million in cash investments to start this quarter and worldwide commercial rights to all of our programs. We're excited about our portfolio of product candidates, particularly the opportunity before us with IPI-145 in hematologic malignancies. As a result of the significant progress in our clinical development efforts with IPI-145, we are updating our financial guidance for 2013. However, before I discuss our updated guidance, I'll briefly review our financial results for the second quarter of 2013. We did not record any revenue during the quarter. Total revenue was $21.9 million for the same period in 2012, which was composed of $20.9 million for reimbursed R&D services performed under our previous strategic alliance with Purdue and Mundipharma and $1 million from the amortization of deferred revenue associated with the grant of rights in-licenses under this alliance. R&D expense for the quarter was $26.1 million compared to $28.5 million for the same period in 2012. The decrease in R&D expense in the quarter compared to same period in 2012 was primarily related to discontinuation of development of the company's hedge funds pathway program. G&A expense was $6.7 million for the quarter compared to $7.7 million for the same period in 2012, and the decrease in G&A expense in the quarter compared to same period in 2012 was primarily due to lower consulting expenses. Net loss for the quarter was $32.6 million or a basic and diluted loss per common share of $0.68 compared to $14.7 million or a basic and diluted loss per common share of $0.54, the same period in 2012. As of June 30, 2013, we had total cash, cash equivalents and available-for-sale securities of $277.2 million compared to $303.1 million as of March 31, 2013. I'll now conclude by reviewing our updated financial guidance for 2013. These updates are due to our rapid advancement of IPI-145, including the anticipated increased clinical cost associated with our decision, following our consultations with the FDA and EMA to initiate a Phase III randomized trial of IPI-145 compared to ofatumumab, which anticipates to commence in the fourth quarter of 2013. In addition to the cost associated with purchasing of ofatumumab and the cost of the extension phase of this trial, the anticipated start of this Phase III study would trigger a $10 million milestone payment as part of our license agreement with Millennium. Our financial expectations for 2013 are now as follows

[Operator:]

[Operator Instructions] Our first question comes from the line of Michael Yee of RBC Capital Markets.

[Michael J. Yee:]

Two quick questions on the Phase III plan. How are you thinking about the speed of enrollment? Is this going to take about a year or so? Should we think about 2015 as a timeframe for data? And should I assume that FDA and all these agencies have seen all the data that we've seen at ASCO? And the second question is, I know there's a lot of interest in patients who have failed other drugs such as ibrutinib or GS-1101, do you have any more information on those types of patients in your studies and maybe you can talk to that?

[Julian Adams:]

Sure. Let me -- Michael, and thanks for your question you're multiple questions. So first of all, the FDA had seen a very comprehensive briefing book prior to our discussions with them and of course, have all of our data, so that's 1 point. We do allow patients -- to your last question -- who have progressed on ibrutinib. We have such patients in our Phase I trial right now, and hopefully, they will benefit from treatment of IPI-145. There are independent mechanisms, that's at least what we've seen in the lab. And then lastly, guidance to enrollment, I can just say that this is an international study. We've done extensive feasibility together with our CRO, and we will be hopefully enrolling patients as quickly as possible in multiple countries, and we'll provide further guidance as once the trial commences.

[Operator:]

Our next question comes from the line of Yigal Nochomovitz of Morgan Stanley.

[Yigal D. Nochomovitz:]

A few questions on the design of the study. Number one, could you discuss in more detail on the primary endpoint of PFS, what the powering assumptions are for OFA [ph] and 145? Number two, could you discuss what the plans are for prophylaxis in this Phase III and will they -- would that be mandated? And then will you allow for enrollment of L17p patients? And finally, should we take this to mean, given that you're going to 25 milligram BID that the 75-milligram dose is sort of not in the picture, even though you're still expanding in the Phase I.

[Julian Adams:]

It's a little -- a lot of questions. I hope I would be able to remember all of them, but please jump in and remind me. So we have not provided guidance on powering assumptions of the trial, other than what's in the OFA label, which is the PFS of 6 to 9 months. That's the experience of both the label and the previously published studies. So it looks like ofatumumab has a progression-free survival in that range of 6 to 9 months. We are mandating prophylaxis. We have been very careful to try to understand the issue of prophylaxis and to relieve the community of confusion. The majority of the major medical institutions have prophylaxis as part of their guidelines. I'm referring to a paper by Penn [ph] in 2007, reporting that at MD Anderson, they have adopted prophylaxis, Memorial Sloan-Kettering has adopted prophylaxis, and we think this is in the best interest of patients. Now please appreciate, prophylaxis is for bacterial and certain viral infections. It is not a panacea. We cannot -- we know that there are certain prevalent infections about pneumocystis or herpes viruses or cytomegaloviruses can be prophylaxis treated. Obviously, we can't prophylax for the common cold and many other types of illnesses, but we think that this will bode well for the treatment and management of patients. Your third question referred to 17p patients and we are allowing 17p dilution patients in our trial and are currently enrolling those patients also as a part of our Phase I trial and have seen a very good and robust responses in 17p direct patients. You have asked also a question about 75 milligrams. 75 milligrams is not dead. We think 25 milligrams has adequately performed based on response rate, clinical responses, as well as biomarker analysis which do not distinguish it from the 75 milligrams. But we're still pursuing the 75 milligrams in our prespecified expansion cohorts in our Phase I trial and we always have the advantage of being able to look at those data. And if those data materially require us to change or modify the trial, we would do so. But we were -- feel extremely comfortable with our 25-milligram data. This was discussed with the agency. The agency is also very comfortable with this dose because we both have robust clinical responses, as well as we made our biomarkers in terms of the PK, assure that we have maximum inhibiting delta and get -- and achieving an IC-50 for gamma inhibition.

[Adelene Q. Perkins:]

And Yigal, I think, you may have also asked if we will be enrolling idelalisib or ibrutinib failures, and the answer to that is yes.

[Julian Adams:]

We will enroll ibrutinib failures but not idelalisib failures. Prior to the kinase experience, with delta inhibitors is excluded from this trial. It is not excluded from the Phase I trial.

[Yigal D. Nochomovitz:]

Got it. And then if I may, just 2 quick follow-ups. Could you tell us the approximate ratio of U.S. to x U.S. clinical size for this study, the Phase III? And then so the 10 million milestone that's triggered for the initiation, how much will cover for the cost of the trial? Will that be enough to cover it or not?

[Julian Adams:]

So we're still dotting the i's and crossing the t's with our CRO in terms of the mix of sites. It's not just the numbers game. It is a question of quality sites and quality patients. So that's much more of our focus than what is the number and the ratio. We believe we can enroll a substantial portion of this trial in the U.S. but we feel that we also need to go x U.S. to get full enrollment of 300 patients in a timely fashion.

[Lawrence E. Bloch:]

Yigal, in terms of your question clarifying the milestone payments. So under our restructured restated amended agreement with Millennium, Takeda, we owe a total of $25 million of pre-NDA milestones. We already paid $10 million of those prior to the initiation of this anticipated Phase III trial. So this Phase III trial would then trigger the second $10 million total for a total of $20 million of the contractual $25 million due under the contract, but none of those milestone payments would be allocated towards the frame of the cost of the trial. So those will be additional costs, which is why our guidance has gone up more than the $10 million milestone payments.

[Operator:]

Our next question from the line of Cory Kasimov of JPMorgan.

[Cory William Kasimov:]

My first one is on your anticipated regulatory strategy. And with Gilead's recent disclosure that they're filing in 4Q, how are your plans with iNHL change, if at all, if Gilead gets accelerated approval or if they got full approval or if they're unable to gain approval at this time?

[Julian Adams:]

So our plans don't change. We have -- we believe we have a high response rate and a more active agent. We wish them all the best with an accelerated approval, because that opens the door from a regulatory perspective. If they should win accelerate an approval, then we may also be candidates down the road. If they don't achieve accelerated approval, we mean to -- with our trial, irrespectively because we believe you have a very active agent that provides meaningful clinical benefit of patients.

[Cory William Kasimov:]

Okay. And then from the CLL side of things, with this pending Phase III trial, if it is indeed successful, how do you think this will help differentiate 145 label versus idelalisib?

[Julian Adams:]

Idelalisib, I would remind you is not going -- is not performing the same trial. They are combining with ofatumumab versus ofatumumab, so this is monotherapy, so they're very different designs, and they're able to reflect the combination requirement with ofatumumab, and we're hoping to show significant superiority to ofatumumab and perhaps more similar activity to what we are seeing with ibrutinib.

[Lawrence E. Bloch:]

I do appreciate, the ofatumumab is not a widely prescribed therapy in the CLL context. So it's not a dominant therapeutic option for patients.

[Julian Adams:]

Yet, it represents a regulatory standard, and it's something we discussed with FDA and EMA and represents a very legitimate path forward and we're taking advantage of this.

[Adelene Q. Perkins:]

Julian mentioned in his prepared remarks, we do hope with success in this trial will be the first PI3 kinase to show superiority in ofatumumab.

[Cory William Kasimov:]

Exactly, okay. And if I can sneak one more, and you mentioned your anticipated beginning of some combination studies, you didn't provide details there. But do you have any plans to explore 145 in combination with ibrutinib once that's approved ?

[Julian Adams:]

So first of all, we have already commenced the Phase Ib study to enable future combinations with both rituximab and bendamustine. And of course, we're contemplating all kinds of additional combinations, both with approved agents, perhaps ibrutinib soon to be approved, and with experimental agents. So it's not restricted to Rituxan and bendamustine. We think there's a broad potential for combining targeted therapies with different mechanisms of action to really choke off the escape mechanisms for cancer cells -- the hematologic cancer cells that escape therapies.

[Operator:]

Our next question comes from the line of Mike King of JMP Securities.

[Michael G. King:]

Julian, could you remind us at 25 milligrams, what percentage of inhibition should we expect kind of PI3 kinase delta? And maybe talk about intra- and inter-patient variability as well?

[Julian Adams:]

At 25 milligrams, Mike, we should expect and we have recorded that PI3 kinase delta is fully suppressed. We're above the IC90 around the clock. And for PI3 kinase gamma, we are about half maximum or 50 -- at the IC50 -- above the IC50 for most of the treatment period and above the IC50 again around the clock.

[Michael G. King:]

Okay. And then the CLL study is a randomized 1

[Julian Adams:]

1

[Michael G. King:]

Okay. And then I just had a question on retaspimycin. Have you talked about what proportion of survival event you're expecting before you conduct your analysis? And can you say anything about what proportion of survival events have been recorded in the trial so far?

[Julian Adams:]

The trial is a double-blind, placebo-controlled trial. So we are fully blinded to the data. We have a very detailed statistical analysis plan, which we have not shared. It is rather complex because there are multiple tested analysis being formed. As I said, the primary endpoint is overall survival in the total population and overall survival in the patients with squamous cell histology. In addition, layered on to that is a preplanned analysis of a yet undisclosed biomarker on top of the primary endpoint. So we have a complex series of analysis that again, are prespecified in their statistical analysis plan, but we remain fully blinded to the patient populations. And when we lock the database and unblind, we will provide top line data in a very timely manner.

[Michael G. King:]

But you're not going to perform the analysis until all of those things are fully lined up? Is that what you're saying?

[Julian Adams:]

We cannot. Because we are blinded. We can't do the analysis while we remain blinded to the treatment groups and the placebo groups. So we can't do any analysis right now because we don't know which -- it's hard to do the analysis without knowing the coding for who's receiving 504 and/or retaspimycin and who's receiving placebo.

[Michael G. King:]

Sure. I guess my question is what then what triggers the analysis?

[Julian Adams:]

It's an event-driven trial. So when we reach the requisite number of events, that triggers -- and clean the data and lock the database. That's what triggers the analysis.

[Michael G. King:]

All right, but you haven't said what number or what proportion of events will do that, right?

[Julian Adams:]

We haven't, but it is in our statistical analysis plan. And it will provide, again, top line data and all will be revealed when we perform the detailed analysis, and it will be done one time.

[Lawrence E. Bloch:]

And just a reminder, we've guided to this -- the analysis will be completed during the balance of this year. And it is overall survival endpoint, and so we can control the timing of those events. But based on the trajectory that we've seen during the balance of this year, we feel confident that we will be able to provide the top line analysis that Julian described during the second half of 2013.

[Operator:]

Our next question comes from the line of Ian Somaiya of Piper Jaffray.

[M. Ian Somaiya:]

I had a couple of questions. First, I want just to revisit the data presentation to the ASCO, yours, as well as the 2 more advanced competitors. I was hoping you could give your perspective on how 145 compares from a safety standpoint to those 2 other agents at the 25-milligram dose? And then maybe expand on the answer you gave previously, which was why are you pursuing 25 milligrams versus the 75 milligrams or 50 milligrams or 75 milligrams, and specifically what are response rates we are seeing at those 2 higher doses and how the 25 milligrams compares to that.

[Julian Adams:]

Okay. First, let me tackle safety. We have done a very detailed analysis of our own safety data. We obviously do not have access to the safety databases of the 2 competitors you've mentioned, but we are relying purely on their published data. And specifically for ibrutinib on data published in the New England journal in June and for idelalisib data presented over this period of several years and the final presentation at ASCO and [indiscernible] for Indolent Lymphoma. So across the board, we're seeing very similar profiles. They differ -- idelalisib and IPI-145 from a safety perspective, we cannot see any major differences in safety. For ibrutinib, there's a higher propensity for GI toxicity, which is not seen with PI3 kinase inhibitors, but that's the only distinguishing feature, I think, of between the 3 drugs. They are all 3 of immunosuppressive therapies. And all -- and in the settings of CLL and in lymphoma, that concern would be the propensity for infection. All 3 drugs have recorded and published data that they have a similar infection rates in the neighborhood of 20% to 25% rates of infection. And they are similar infections. You see the similar kinds of bacterial pneumocystis, zoster infections. But it is also part of the underlying disease. So we see this as a background in patients with CLL and indolent lymphoma because they have compromised bone marrows.

[M. Ian Somaiya:]

And that would lead to my next question, Julian. So why not pursue the higher doses with the 145, if the safety at 25 mg seems to be comparable doing better?

[Julian Adams:]

So we did an internal analysis of the data at 25 milligrams, which is much more mature, although not fully mature, and the data at 75 milligrams. And what we presented at ASCO is that the responses at 25 milligrams were very rapid within the first 2 months of treatment, literally prior to their first scan, the majority of the responses occurred very rapidly. In addition, we looked at biomarkers like phospho AKT and a panel of cytokines and could not distinguish 25-milligrams from 75-milligrams in terms of inhibition of phosphorylation of AKT, the proximal downstream signaling molecule from PI3 kinase. And therefore, concluded that we may well be at the optimal biological dose of 25 milligrams. Now we have not given up on 75 milligrams in the cohort expansions, pre-specified in our Phase I plan. We are enrolling patients at 75 milligrams. The data there are far less mature. We shall have maybe a better understanding of those data perhaps by the ASH timeframe or maybe even later next year. But we think that the 25-milligram is a well-qualified dose based on clinical responses and biomarker analysis and PK.

[Adelene Q. Perkins:]

And now we just highlight, Ian, that's the reason, given that we don't yet have the data to assess the 75 mg BID dose but what we really like what we've seen at 25 milligrams, the reason we've chosen to go forward in both Indolent Non-Hodgkin's and CLL is perceived. So we want to get those trials going quickly. We want to be -- we're going as fast as we can on these registration paths.

[M. Ian Somaiya:]

Okay. If I could just ask one last question. Is there any read-through in terms of your Phase III strategy designing a trial versus ofatumumab and how we should think about GA-101 when it reaches the market. Is that the similar trial strategy that you would employ?

[Julian Adams:]

That's a terrific question and very prescient on your part. Because if and when GA-101 gets approved and perhaps becomes a new standard anti-CD 20 therapy, that now puts all of us at the starting gate. Meaning, if we were to combine with GA-101 maybe the best anti-CD 20 therapy, both ibrutinib, idelalisib and IPI-145 would have the opportunity to conduct trials with GA-101, and so no one's behind in that case.

[Operator:]

Our next question comes from the line of Joel Sendek.

[Joel D. Sendek:]

A couple of questions. The first on the Phase III trial. I was wondering since it's designed at a crossover, with PFS as a primary endpoint, whether the -- what that means about -- what kind of implications it has to finding and survival result and whether you're going to discuss that. I'm assuming you discussed that with the FDA with your thoughts on that and I have a follow-up.

[Julian Adams:]

Yes, we did, in fact, discussed this very point in the way to best accomplish this analysis for PFS, which was adopted as a legitimate endpoint and has always been a legitimate endpoint for all of CLL trials, and all CLL approvals was to do an extension study. So it's patients who progress on either arm ofatumumab or IPI-145 have documented progression are then deemed eligible and have the opportunity to go on to the extension trial but under no obligation to do so. So that separates out the issue for -- and obviously, we will continue to monitor survival, but that is only a secondary endpoint and does not compromise our ability to file based on the trial we announced this morning, which is based on progression-free survival.

[Joel D. Sendek:]

Okay, and then just looking at the Phase II and the Phase III, I'm wondering any sense as to which one might finish first and enable you to file? And have you thought about that and which would you wait for both because ever since you're going for speed here, I'm just wondering what how they might take -- how long each might take?

[Julian Adams:]

Game on. The indolent team -- the indolent lymphoma team versus the CLL team. We have an internal contest at Infinity. So indolent lymphoma got a head start, that's all I can say. We're going obviously as fast as we can and we -- I just want to reiterate and not be so glib about this. What we really want are quality sites to get quality patients, so that the data are unequivocal, and hopefully, meaningful and meritorious for consideration for future registration.

[Adelene Q. Perkins:]

And the one thing, Joel, we can be definitive about, though, is we will not wait to have both of them. We are going as fast as possible. And whichever one wins first gets filed first.

[Lawrence E. Bloch:]

We'll get some insight into -- the point of which one could potentially file first. As we -- one of the benefits of being third when it's not them, there are always benefits as to we see the regulatory reactions to other potential competitors' filings. And as Julian pointed out earlier, in the call, if the regulatory authorities are open to an accelerated approval pathway for the monotherapy program for GA-101, that could preface [ph] the ability for us to have a similar conversation.

[Joel D. Sendek:]

That's interesting. Okay. And then, I guess, the final piece of that is obviously everyone wants you to move as fast as possible, but looking at the increase in the spend, looks to me like you have about 2 years cash or should be considered less than that because presumably with these trials, hoping you're going to be burning them at an accelerated rate into next year. Would that be fair to say?

[Lawrence E. Bloch:]

We'll give our guidance for 2014 at the end of the year. But I think it's important to note that we've been investing significantly in Hsp90 during the last year. And if the trial reads out positively, our guidance does not include additional expenses. That would be outside our current guidance. But our Hsp90 investment has been going down. As you pointed out, our IPI-145 has been ramping up. But in the event where Hsp90 will not be positive, obviously, there will be no further investment in that one. But based on our current guidance and plans, we have cash that goes into 2015.

[Operator:]

Our next question comes from the line of Matthew Andrews with Wells Fargo securities.

[Matthew J. Andrews:]

I have 2. First of all, can you discuss the rationale for studying 25 milligrams and the high-risk 17p treatment naïve elderly patients you announced at ASCO? As it appears, neither Pharmacyclics or Abbvie have data or studies undergoing in this population. Did the regulatory authorities encourage you to study this population based on the data at ASCO? And do you think that this could serve as a registration path for 145?

[Julian Adams:]

So we did announce at ASCO that we are starting this cohort of patients of 17p dilution. That's the dilution of the P53 gene, and that's the poorest prognosis group in CLL. We did so based on Phase I data, in which we had 17p patients who did respond and did well on the drug. I would correct, I think that ibrutinib is studying the 17p and has an abundance of data in 17p deletion patients. And the discussion with the agency included 17P dilution to be included in our trial. However, the primary driver for us is this is the greatest patient population of greatest need, because they have the poorest prognosis. So it was incumbent on us based on activity we've seen, based on the mechanism of actions of the drug, which de-marginates those cells and kills those cells in the lymph node or stops them from proliferating, where we see good activity and is not dependent on the P53-based mechanism that we would opt to study these patients and provide future treatment options for these particular patient groups. Does that answer your question?

[Matthew J. Andrews:]

Yes. But the cohort you announced is in treatment naïve elderly, correct?

[Julian Adams:]

It's in treatment naïve but 17p. It's high-risk, meaning 17p deletion or patients with P53 mutations.

[Matthew J. Andrews:]

Okay. Second question is, are there any x U.S. sites in the refractory iNHL study that you announced in June? And do you -- if so, do you believe that this could support registration in Europe, considering it's a single arm study?

[Julian Adams:]

Good question. This trial is being conducted in the U.S. So clinicaltrials.gov is our kind of the lead site, but there's -- that's all that's mentioned in clinicaltrials.gov, but we have a network of sites in the U.S. to be able to enroll this study. With regards to your -- the potential for conditional approval in Europe, we have no guidance on that. We're not providing any guidance on that. It's obviously a discussion with regulators down the road. And depending on the data, of course.

[Operator:]

Our next question comes from the line of Navdeep Singh of Goldman Sachs.

[Navdeep Singh:]

You mentioned that you're conducting a Phase Ib trial of 145 in combination with bendamustine, Rituxan or bendamustine plus Rituxan. When do you think you'll have data from that? And I have a couple of follow-ups as well.

[Julian Adams:]

We haven't provided any guidance of when we will have data. It's an open label study. We're enrolling patients as part of an IST or investigator-sponsored trial. So we don't control enrollment in that trial. The purpose of this trial is really -- it's an enabling trial for future randomized studies, and we leave it to the investigator to -- well when they feel confident and ready and have enough data to present at a medical meeting, our investigator doctor, Ian Flinn, will do so.

[Adelene Q. Perkins:]

And as you know, Navdeep, it's particularly challenging in dose escalation studies to predict the completion because it depends on how well tolerated the combo is and how many dose escalation cohorts you need to go through.

[Navdeep Singh:]

Is it possible to see data at ASH from this study or no?

[Julian Adams:]

We're not aware of any abstract that has been submitted, but we're not providing any guidance on this.

[Navdeep Singh:]

Okay. And then as a follow-up. On its earnings call, Gilead announced that it's going to file for FDA approval idelalisib and relapsed refractory CLL based on the Phase III trial of Rituxan plus and minus idelalisib. I'm just wondering, why didn't you choose a combination approach for your study versus the monotherapy approach? And what is your level of comfort on safety of a potential combination approach with the 145?

[Julian Adams:]

So the most expeditious and most rapid path to approval would be a monotherapy randomized study that trial we described. There's obviously room -- always room for combination trials, and we have every intention to conduct combination trials in the future, but they're not on the critical path to our first approval. In terms of toxicity of a combination, that's why we're doing the Ib study. The purpose of that study is to enable combinations, and we are studying safety pharmacokinetics and activity of that combination. It's all sort of hand-in-glove type of strategy to enable further and future development. Ultimately, the goal is to have very long-term clinical benefit and duration of response, keeping patients in remission and with the ultimate goal of getting to cure.

[Adelene Q. Perkins:]

And while, Navdeep, we need to do those trials to determine the tolerability of the combination just based on the fact that as a monotherapy 145 is quite well tolerated, we're very optimistic about the ability to do a robust number of combo trials with a number of agents.

[Navdeep Singh:]

Okay. That's helpful. And then, my final question is on the Synta data presented at ASCO, Synta Hsp90 inhibitor in non-small cell lung cancer. Any take on that data? And then I think the Synta Hsp90 inhibitor provided greater benefit in Eastern European patients. Can you please provide the geographic breakdown of patient enrollment for your study?

[Julian Adams:]

I can't comment on the Synta trial. Frankly, I don't understand it, so I'm not going to say another word. In terms of our trial, it's an international study, which has a substantial number of patients in the U.S., Western and Eastern Europe, and we will provide a comprehensive analysis of the data. Once we have locked the database unblinded, we will provide top line data first, but we will do one analysis on the trial and give a comprehensive report on the clinical benefit of our trial.

[Operator:]

Our next question is from the line of Jason Kantor of Crédit Suisse.

[Jason Kantor:]

A lot of them have been asked. But on the Phase III CLL study, could you give us an outline of what the key stratification factors are, whether it's 17p or ibrutinib? And do you plan to have -- is there a plan to interim analysis in that study?

[Julian Adams:]

So we have not provided any of those, the stratification guidelines. We will do so in the future. Please appreciate, we're dotting I's, crossing T's getting final -- getting to final protocol. And so once we commence the study, we'll be in a better position to provide scant but some more detail on these studies.

[Jason Kantor:]

And then regarding an interim?

[Julian Adams:]

Again, I'll defer to -- once we start the study, we'll give further guidance on how the study is to be conducted.

[Jason Kantor:]

And then in terms of combinations, you've mentioned obviously the bendamustine and Rituxan, but this is, I think -- I feel this is going to get a very competitive, very quick with some of the new drugs. I'm wondering, what is your strategy for kind of novel, novel combinations? Are there business development arrangements that can be made with some of these companies that have competitive but potentially complementary products where you could get going sooner rather than later on those combinations? What's your thinking around that?

[Adelene Q. Perkins:]

Yes, Jason. We are really committed to both combining with existing agents, as well as future agents. We have a huge effort going on at the laboratories here to look at some of mechanistic perspective, where there might be synergistic combinations and that's often with other agents that are in development, and we will pursue many different strategies to put those together because as was mentioned earlier, that's where we could actually be out in front and establish a leadership position in the combination with some of those novels. And we're evaluating all of those options. And when we move forward on the MAs then we'll be sure to let you know.

[Jason Kantor:]

I guess, and just finally on this combination approach, the current combo study is in investigator-sponsored trial, but it would seem that this is an area where you'd want to have significant corporate control over moving the programs forward quickly. So I'm just wondering when we might see a corporate-sponsored combination study even if it's just another Phase I-type study.

[Julian Adams:]

So we're very mindful of exactly what you just said. And we are taking that under advisement. And when we have such a trial, we will report it to you. But we understand your point.

[Lawrence E. Bloch:]

Of course, as Julian pointed out, the IST trial is intended to be enabling of future combination studies.

[Operator:]

Our final question today comes from the line of Katherine Xu of William Blair.

[Katherine Xu:]

I'm just curious, do you have any data on 145 ibrutinib failures these days? And what would you predict from the method of action?

[Julian Adams:]

So from the mechanism of action, there are independent pathways, so we would -- I don't want to make a prediction about the clinical activity, but I don't see any basis for redundancy in the 2 pathways, so there -- and we are allowing ibrutinib -- patients who had progressed on ibrutinib to enter our study in the Phase I, as well as the Phase II, Phase III study. So we expect to get more data over time. Obviously, very many fewer patients have been treated with ibrutinib. And so the numbers of those patients are scarce right now. Obviously, it will increase over time.

[Katherine Xu:]

All right, and on the other question, Julian, can you comment on the dose that you're using in RA and asthma and how gamma inhibition is playing a role there?

[Julian Adams:]

The top dose in RA is 5 milligrams twice daily or 10 milligrams per day. And those doses, we do suppress delta and have minimal suppression of the gamma.

[Operator:]

And ladies and gentlemen,, that does conclude our time for Q&A today. I would like to turn the conference back over to Ms. Adelene Perkins for any closing remarks.

[Adelene Q. Perkins:]

So thank you for going -- joining us on the call today and for all the good questions. We look forward to updating you on our anticipated milestones in the coming months. Operator?

[Operator:]

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