Infinity Pharmaceuticals Inc (INFI) 2013 Q2 法說會逐字稿

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 will be your operator for today's call. (Operator Instructions). 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.

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 CBL.

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 infinity .com. Please note that during this call, we may make Forward-looking statements about our future expectations and plans including clinical development(inaudible) 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. Though these Forward-looking statements represent our views as of today, they should not be relied upon in the future as representing our then current viewsWe may update the statements in the future , but are not taking on an obligation to do so. With that, I would like to turn the call over to Adelene.

Thank you, Jaren. Welcome everyone, and thank you for joining us on the call today. The is second half of this year has a number of important milestones for Infinity with multiple anticipated trial readouts 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-145 1.5 in patients with relaxed 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 in refractory indolent non-Hodgkins lymphoma, or INHL.

In addition, we were recently granted orphan-drug status by the FDS for IPI-145 in (inaudible) lymphoma, the most common sub-type of indolent non-Hodgkin lymphoma adding to the CLL and small lymphocytic lymphoma or SLL orphaned 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 the ongoing Phase I study of IPI-145 in patients with advanced hematologic malignancies.

These data gives us confidence that IPI-145 has the potential to be the best in class PS(inaudible) exhibitor in these indications. Julian will review the 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 (inaudible) 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-Hodgkins lymphoma and CLL as chronic conditions would represent an important step toward our ultimate goal of finding a cure for these patients.

Furthermore, the potential to treat provide treatment benefit 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 A2P90 program we anticipate reporting top line data from our Phase II study of retaspimycin hydrochloride in patients with non-small cell one cancer by the end of this year. If data from our 815-90 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 talented citizen owners of Infinity are excited about the prospects before us, and remain committed to our vision of building a sustainable fully integrated bio pharmaceutical 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 the next key value inflexion points. With that, I will turn the call over to Julian.

Thank you, Adelene. This morning I will review our pipeline with a focus on IPI-145 our potent oral PI-3 kinase delta gama inhibitor. We are continuing to make important strides and rapidly advancing IPI-145 with a late stage clinical development program focused on IMHL as well as CLL. We have also submitted both clinical and pre-clinical 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 reviewed 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 milligrams twice daily or BID.

In this study, approximately 300 patients with relapsed refractory CLL will be randomized to either IPI-145 a Ofatumumab (inaudible) the primary endpoint is progression-free survival as assessed by independent radiological review. Importantly, if the data are positive IPI-145 will be the first PI-3 kinase inhibitor to demonstrate superiority to Ofaltumumab. 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 either 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 the 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 not valuable 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 nine patients, seven of which have noted responses which means greater than 50% shrinkage of their lymph nodes. Our second area of focus for potential registration is IMHL. We are enrolling patients in a Phase II monotherapy trial which began in June.

This open labeled single arm study is designed to evaluate the safety and efficacy of IPI-145 administered 25 milligrams BID in approximately 120 patients with similar lymphoma whose disease is refractory to radio- immunotherapy or to a rituximab and chemotherapy. This trial has rigorous eligible criteria, and patients enrolled in the studymust have progressed within six months of receiving their last therapy and were therefore refractory to their last treatment. The primary endpoint of this 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 three complete responses, ten partial responses among 19 patients available for activity. Similar to CLL, responses occurred quickly with a median time to response of 1.8 months. PI3 kinase in more broadly B-cell receptor inhibitors represent promising therapeutic areas, and 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 I-B open label dose escalation study of IPI-145 in patients with advanced hematologic malignancies. this study is designed to evaluate the safety, pharmacokinetic and clinical activity of IPI-145 in combination with Retuximab and Bendamustine or both Retuximab and Bendamustine combined . Beyond Hemalogic malignancies there is a strong biological rationale for developing IPI-145 and informationin which we have two clinical trials underway.

In May we began enrolling patients in the Espira study a Phase II double blind placebo controlled trial designed to evaluate efficacy, safety, and pharmacokentics of three different levels of IPI-145 twice daily on a background of methotrexate versus placebo plus methotrexate in more then 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 II -A 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 compliment our IPI-145. We are continuing to advance our second PI3 kinase delta gamma inhibitor, IPI-443 through pre-clinical studies which is successful, could enable Phase I development. IPI-443 and additional PI3K kinase discovery efforts has the potential to provide us with important strategic next 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 Retatmicyn Hydrochloride in non-small cell lung cancer. This trial is designed the evaluate the safety and efficacy of Dosetaxel plus Retastimycin compared to Docetaxel must placebo in 226 second and third line patients who are heavy smokers and who are naive to Dosetaxel treatment. The study has two-coprimary endpoints, overall survival in the total populations, and over survival in patients with Squamous cell histology.

A secondary endpoint includes the analysis of an undisclosed pre specified bio marker assay in a Kleeia certified lab. We anticipate reporting topline data from this study in the second half of 2013. In summary, 2013 is an important year for our R&D program, and we are pleased with the progress we have made so far. We appreciate that there is still a lot of work to do, and we look forward to updating you on our clinical milestones in the balance of this year. With that, let me turn the call over to Larry to review our financial results.

Thank you, Julian. Infinity is in a strong position with rapidly developing pipeline, more than $275 million in cash and investments at the start of the quarter and worldwide commercial rights to all of our programs. We are 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 will briefly review our financial results for the second quarter of 2013. We did not record any revenue during the quarter.

Total revenue was $29.9 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 Perdue and Mundipharma and $1 million from the amortization of deferred revenue associated with the grant of rights and 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 this quarter compared to the same period in 2012 was primarily related to discontinuation of development of the Company's hedgehog 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 the 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 basic and diluted loss per common share of $0.54 for 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 will now conclude by reviewing our updated financial guidance for 2013. The updates are due to our rapid advancement of IPI-145 including the anticipated increased clinical costs 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 anticipated to commence in the fourth quarter of 2013.

In addition to the costs associated with the purchasing Ofatumumab and the cost of the extension phase of this trial, the anticipated start of the Phase III study would trigger a $10 million milestone payment as part of our licensing agreement with Millennium. Our financial expectations for 2013 are now as follows. We expect operating expenses to range from $135 million to $145 million compared to our prior expectations of $115 million to $125 million.

We expect our net loss to range from $135 million to $145 million compared to prior expectations of $115 million to $125 million. We expect to end the year with a cash investment balance ranging from $190 million to $200 million compared to our prior expectations of $210 million to $220 million,and based on our current operating plans, and exclusive any development activities, we believe we have the cash fundway into 2015. With that, I will turn the call over to the operator for questions.

Thank you. (Operator Instructions). Our first question comes from the line of Michael Yi of RBC Capital Markets. Your line is open. Please go ahead.

Hello, guys. Thank you. Congratulations on that Phase III development plan. Two quick questions on the Phase III plan. How are you thinking about speed of enrollment? Is this going to take about a year or so? Should we think about 2015 as a time frame for data?

And should I assume that FDA and all these agencies have seen all of the data that we have seen at ASCO? And the second question is, I know there is a lot of interest in patients who have failed other drugs such as Abrutinib or GS-1101. Do you have any more information on those types of patients in your studies and maybe can talk to that? Thanks.

Hello Michael and thanks for your questions. Multiple questions. First of all, the FDA has seen a comprehensive briefing book prior to our discussions with them and of course have all of our data. So that is one point.

We do allow patients - - to your last question who have progressed on Abrutinib. 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 and that is at least what we have seen in the lab. Lastly, guidance to enrollment, I can just say this is an international study. We have done extensive feasibility together with our CLO, and we will be hopefully enrolling patients as quickly as possible in multiple countries and will provide further guidance once the trial commences.

Okay. Thank you.

Our next question comes from the line of Yigal Nochomovitz of Morgan Stanley. Your line is open. Please go ahead.

Hello, everyone. Congratulations on the Phase III announcements. Good to hear. A few questions on the design of the study. Number one, could you discuss in more detail on the primary endpoints of CSS what the powering assumptions are for Ofa and 145. Number two, could you discuss what the plans are for prophylaxis in the Phase III, and will that be mandated? Will you allow for enrollment of (inaudible)17P patients? Finally, should we take this to mean given that you are going to 25 milligram BID that the 75 milligram dose is sort of not in the picture even though you are still expanding in the Phase I?Thank you.

There were a lot of questions. I hope to be able to remember all of them, but please jump in and remind me. We have not provided guidance on powering assumptions of the trial other than what is in the Ofa label which is the PFF of six to nine months.

That is the experience of both the label and in previously published studies. It looks like a Ofatumumab has a progression pre survival in that range of six to nine 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 institutions have prophylaxis as part of their guidelines. I am referring to a paper by TAM in 2007 reporting that at MD Anderson they have adopted prophylaxis, Wellstone(inaudible) has adopted prophylaxis, and we think this is in the best the interest of patients. Now, please appreciate prophylaxis is for bacterial and certain viral infections. It is not a panacea.

We know there are certain prevalent inflections like pneumocystis or herpes virus (inaudible)viruses that can be prophylaxis treated. Obviously, we cannot prophylax for the common cold, and the other types of illnesses. We think this will bode well for the treatment and management of patients. Your third question referred to 17 P patients, and we are allowing 17 P deletion patients in our trial, and are currently enrolling those patients also as part of our Phase I trial and have seen very good and robust responses in 17 P patients.

You asked also a question about 75 milligrams. 75 milligrams is not dead. We think 25 milligrams has adequately performed based on response rates, clinical responses as well as bio marker analysis which do not distinguish it from the 75 milligrams.

But we are still pursuing the 75 milligrams in our pre-specified expansion cohorts in our Phase I trial, and we always have the advantage of being able to look at those data. If those data materially require us to change or modify the trial, we would do so. But we 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 nail our bio markers in terms of the PK, assure that we are maximally inhibiting delta and get and achieving IC50 for gamma inhibition.

You might have also asked if we will be enrolling (inaudible) or Abruntimab failures, and a the answer to that is, yes.

We will enroll Abrutimab failures but not (inaudible) with delta inhibitors is excluded from this trial. It is not excluded from the Phase I trial.

Got it. And then if I may, just two quick follow-ups. Could you tell us the approximate ratio of US to ex-US clinical sites for this study, the Phase III? And then, so the $10 million milestone that is triggered for the initiation. How much will be -- will cover the cost of the trial? Will that be enough to cover it or not?

So we are still doting the I's and crossing the T's with our CRO in terms of the mix of sites. It is not just a numbers game. It is a question of quality sites and quality patients. That is much more of our focus than what is the number and ratio. We believe we can enroll a substantial portion of this trial in the US, but we feel that we also need to do ex-US to get full enrollment of 300 patients in a timely fashion.

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 or pre-NDA milestones. We already paid $10 million of those prior to the initiation of the anticipated Phase III trial. 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 deferring the cost of the trial itself. Those would be additional cost which is why your guidance has gone up more than the $10 million milestone payments.

Okay, great. Thank you very much.

Our next question comes from the line of Cory Kasimov of JPMorgan. Your line is open. Please go ahead.

Good morning, guys. Thank you for taking the question. My first one is on your anticipated regulatory strategy and with Gilliad's recent disclosures that they are filing in 4Q. How do you plans with INHL change if at all if Gilliad gets accelerated approval or if they get full approval or they are unable to gain approval at this time?

Our plans do not change. We have- - but we believe we 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 accelerated approval, then we may also be candidates down the road. If they do not achieve accelerated approval we mean to continue with our trial irrespectively because we believe we have a very active agent that provides meaningful clinical benefit to patients.

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

Idelelexi, I remind you is not performing the same trial. They are combining with Olfatumumab, versus Olfatumumab. This is monotherapy. So they are very different designs. And their label will reflect the combination requirement with olfatumamab. We are hoping to show significant superiority to Olfatummab and perhaps more similar activity to what we are seeing with a Abrutinib.

As you appreciate,Olfatumumab is not a widely free scribed therapy in the CLL context. So it is not a dominant therapeutic option for patients.

Yet it represents a regulatory standard, and it is something we discussed withed FDA and EMA and represents a very legitimate path forward. We are taking advantage of this.

Okay and --

As Julian mentioned in his prepared remarks, we do hope with success with the trial to be the first PI3 kinase that shows superiority to Olfatumumab.

Exactly. And then if I could just sneak one more in. You mentioned you anticipated beginning of some combinations studies, but you did not provide details there. Do you any plans to explore 145 in combination with Abrutinib once that is approved?

First of all, we have already commenced the Phase I-B study to enable future combinations with both Rituxin and Bendamustine, and of course we are contemplating all kinds of additional combinations both withapproved agents, perhaps Abrutinib soon to be approved and with experimental agents. It is not restricted to Rituxin and Bendamustine. We think there is a broad potential for combining targeted therapies with different mechanisms of action to really choke off the escape mechanisms for cancer cells for hematologic cancer cells that escape therapies.

Great. Thank you.

Thank you. Our next question comes from the line of Mike King of JMP Securities. Your line is open. Please go ahead.

Thank you for taking my questions. I hope you can hear me okay?

Yes. Good morning, Mike.

Can you hear me?

Yes, very well.

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

At 25 a milligrams, Mike we should expect and we have recorded that PI 3 kinase delta is fully suppressed above the IC90 around the clock and P!3 Kinase gamma we are at half maximal or at the IC50 - -above the IC50 for most of the treatment period and above the IC 50 again around the clock.

Okay. And then the CLL study is randomized one to one or two to one?

One to one.

Plus one.

Okay. And then I just had a question on Retaspimycin. Have you talked about what proportion of survival events you are expecting before you conduct your analysis? Can you say anything about what portion of survival events have been recorded in the trial so far?

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 (inaudible) analysis being performed.

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 bio marker on top of the primary endpoint. So we have a complex series of analyses that again our pre-specified 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 topline data in a very timely manner.

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

We cannot because we are blended. We cannot do any of the analyses while we remain blinded to the treatment groups and placebo groups. So we cannot do any analyses right now because we do not know which -- how you to do the analyses without knowing the coding for who is receiving 404 or Retacymycin and who is receiving placebo.

I guess my question is then what triggers the analysis?

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

All right. But you have not said what number or what proportion of events will do that, right ?

We have not. But it is in our statistical analysis plan . And we will provide again topline data, and all will be revealed when we perform the detailed analysis, and it will be done one time.

Just a reminder, we have guided that this will the analysis will be completed during the balance of this year. And it is overall survival endpoint, and so we obviously cannot control the timing of those events. But based on the trajectory that we have seen, during the balance of this year, we feel confident that we will be able to provide the topline analysis that Julian described during the second half of 2013.

I understand. Thank you.

Thank you. Our next question from the line of Ian Somaiya from Piper Jaffray. Your line is open. Please go ahead.

Thank you. I had a couple of questions. First, I wanted it revisit the data presentations at the ASCO, yours as well as the two more advanced competitors. Hoping you could give your perspective on how 145 compares from a 50 standpoint to the two other ought agents at the 25 milligram dose. Maybe expand on the answer you gave previously which is why are you pursuing 25 versus the 75 or 50 or 75? Specifically what the response rate are seen at the two higher doses, and how the can 25 compares to that?

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 two competitors you have mentioned. But we are relying purely on their published data and specifically for Abrutinib on data publish in the New England Journal in June. And for(inaudible) data presented over the period of several years and the final presentation at ASCO, and then in Lugano for indolent lymphoma.

Across the board, we are seeing very similar profiles. They differ, (inaudible)and IPI-145 from a safety perspective. We cannot see any major differences in safety.

For Abrutinib there a higher propensity for GI toxicity which is not seen for PI3 kinase inhibitors, but that is the only distinguishing feature I think between the three drugs. They are all three immunosuppressive therapies, and in the settings of CLL and indolent lymphoma, the concern would be the propensity for inflections. All three drugs have recorded and published data that they have 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 (inaudible) infections. But it is also part of the underlying disease. We see this as a background in patients with CLL and indolent lymphoma. Because they have compromised bone marrows.

And it that would lead to the next question. Why not pursue the higher doses with 145? If the safety at 25 seems to be comparable to your two competitors?

So we did and internal analysis of the data at 25 which is much more mature although not fully mature, and the data at 75. And what we presented at ASCO is that the responses had at 25 were very rapid within the first two months of treatment. Literally prior to the first scan, the majority of the responses occur very rapidly. If addition, we look the at bio markers like phospholytic AKT, and a panel of sydocoms could not distinguish 25 milligrams from 75 milligrams in terms of inhibition of phospolytion of AKT the proximal balance stream signaling molecule from the PI 3 kinase. 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 should have maybe a better understanding of those data perhaps by the ASH time frame. Or maybe even later next year. But we think that the 25 milligram is a well qualified dose based on clinical responses and bio marker analyses and PK.

Okay.

And. I would just highlight, Ian that the reason given that we do not yet have the data to assess the 75mg BID dose, but we like we what we seen at 25. The reason we have chosen to go forward in those indolent non-Hodgkins and in CLL at 25 is vine for speed. So we want to get the trials going quickly. We want to be going as fast as we can on these registration paths.

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 Olfatumumab and how we should think about GA101 when it reaches the market is that similar to trial strategy that you would employ?

That is a terrific question and very prescient on your part. 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 Abrutinib and IPI-145 would have the opportunity to conduct trials with GA 101. So no one is behind in that case.

Thank you very much.

Thank you, Ian.

Thank you. The next question from the line of Joel Sendek of Stifel. Your line is open. Please go ahead.

Thank you a lot. A couple of questions. the first on the Phase III trial. Just wondering, since it is designed as a crossover with PFS as a primary endpoint - - what that means about what kind of implications that has to finding survival result and whether you had discussed that? I am assuming you discussed that with the FDA, but your thoughts on that. And I have a follow-up, thank you.

Yes. We did in fact discuss this very point. And 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 CLL trials and all CLL approvals was to do an a extension study. Patients who progress on either arm of (inaudible) 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 - - obviously we will continue to monitor survival, but that is only a secondary endpoint and it is not -- does not compromise our ability to file on based on the trial we announced this morning which is based on progression-free survival.

Okay. Thank you. And then just looking at the Phase II, the Phase II and Phase III. I am wondering any sense as to which might finish first and enable you to file? Have you thought about that? Do you wait for both and how do you both - - I mean since you are going for speed here. I am wondering how they might take -- how you long they might each take?

Game on. The indolent lymphoma team versus the CLL team. We have an internal contest at Infinity. Indolent lymphoma got a headstart. That is all I can say.

We are going obviously as fast as we can. I want to not be sort of 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.

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.

We will get some insight into which one could potentially file first as we -- when the benefits of being third when this is not - - always benefits as we need to see the regulatory reaction to other potential competitors filings. and as Julian pointed out earlier in the call, if the regulatory authorities are open to approval pathway for the monotherapy program for GS-1101 that could push us where for us to have a similar conversation.

That is interesting. Okay. And then I guess the final piece of that is obviously everyone wants you move as fast as possible. But looking at the increase in the spend looks to me like you have about two years cash or, should we consider it to be less than that because presumably with these trials open burning at an accelerated rate into next year.

Would that be fair to say?

We will give your guidance at the for 2014 at the beginning of the year. It is important note thatwe have been investing in HSP90 during the last year. If the trial reads out positively, our guidance does not include additional expenses. That would be outside of our current guidance. our Hsp90 investment has been going down. As you pointed out the IPI-145 has been ramping up. In the event Hsp90 would not be positive obviously there would be no further investment that one. Based on our current guidance and plans, we have cash that goes into 2015.

Thank you a lot.

Thank you. Our next question comes from the line of Matthew Andrews of Wells Fargo Securities. Your line is open. Please go ahead.

Yes, good morning. Thank you for taking the questions. I have two. First of all, can you discuss the rationale for studying 25 milligrams in the high risk 17 P treatment naive elderly patients you announced at ASCO? As it appears that neither have (inaudible) 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 this could serving serve as a registration path for 145.

We did announce at ASCO that we are starting these cohort of patients in 17 P deletions. That is a deletion of the P -53 gene, and that is the poorest prognosis group in CLL. We did so based on Phase I data in which we had 17 P patients who did respond and did well on the drug. I would correct, I think (inaudible) is studying the 17 P and has an abundance of data in 17 P deletion patients. The discussion with the agency included 17 P deletions 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. It was incumbent on us based on the activity we have seen, based on the mechanism of action of the drug which demarginates thyself and tiers thyself in the lymph node or stops them from proliferating where we see good activity, and is not dependent on the P-53 based mechanism. But we have to study both of these patients and provide future treatment options for these particular patient groups. Does that answer your question?

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

It is in treatment naive, but 17-P

17P. It is high risk meaning but 17 P deletions or patients with P53 mutations. Okay. Second question is are there any ex-US sites in the refractory INHL study that you announced in June? And if so, do you believe that this could support registration in Europe considering it as single arm study?

Good question. This trials being conducted in the US.

Okay.

(inaudible) is the lead site, but that is all that is mentioned in trials, but we a network of sites in the US to be able to enroll the study. With regards to the potential for conditional approval in Europe, we have no guidance and on that, and we are not providing any guidance on that. It is obviously discussions with regulators down the road.

Okay. Great thank you.

Depending on good data of course.

Got it, thank you.

Thank you. Our next question comes from the line of Navdeep Singh of Goldman Sachs. Your line is open. Please go ahead.

Hello guys. Thanks for taking my questions. You mentioned you are conducting a Phase I B trial of 145 in combination with (inaudible) when do you think you will have data from that?I have a couple of follow ups as well.

We have not provided any guidance of when we will have data. It is an open labeled study. We are enrolling patients as part of an ISP or investigative sponsored trial. So we do not control enrollment in that trial. The purpose of this trial is really it is an enabling trial for future randomized studies. And we leave it to the investigator to -- when they feel confident and ready and have enough data to present at a medical meeting, our investigator Dr. Ian Flynn will do so.

And as you know, Navdeep, it is 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 to.

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

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

As a follow-up on its earnings call Gilliad announced it is going to file for FDA approval (inaudible) based on the (inaudible) plus or minus (inaudible) just wondering why didn't you choose a combination approach for your first study versus the monotherapy approach? And what is your level of comfort on safety of a potential combination of (inaudible)145?

So the most expeditious and most rapid path to approval would be a monotherapy randomized study the trial we described. There is obviously room for - - always room for combination trials, and we have every intention to conduct combination trials in the future. But they are not on the critical path to our first approval. In terms of toxicity of a combination, that is why we are doing the 1 B study. The purpose of that study is to enable combinations, and we are studying safety, pharmacokinetics and activity of that combination.

Okay.

So it is 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.

Okay.

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 toll rated we tolerated. We are optimistic about the ability to do a number of robust number of combo-trials with a number of agents.

That is a helpful. My final question on the (inaudible) data presented at the ASCO, Hsp90 in non-small non-small cell lung cancer. Any take on that data? And then the HSP90 inhibitor provided greater benefit in Eastern European patients. Can you please provide the geographic breakdown of patient enrollment for your study? And then I will hop back in the queue.

I cannot comment on the (inaudible) trial. I am not going to say another word. In terms of our trial, it is an international study in which has a substantial number of patients in the US, Western and Eastern Europe, and we will provide a comprehensive analysis of the data once we have locked the database, unblinded - - . We 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.

Okay. Thank you so much.

Thank you. Our next question is from the line of Jason Cantor of Credit Suisse. Your line is open. Please go ahead.

Great. Thank you for taking the question. A lot of them have been asked. On the Phase III CLL study. Could you give us an outline of what the key stratification factors are whether 17 P or prior Abrutinib? And is there a planned interim analysis in that study?

We have not provided any of those the stratification guidelines. We will do so in the future. WE are doting I's crossing T's getting to final protocol. Once we commence the study, we will be in a better position to provide scant, but some more detail on these studies.

Regarding an interim?

Again, I defer to once we start the study, we will give further guidance on how studies could to be conduct.

And then in terms of combinations, you have mentioned obviously the Bendamustine and Rituxin, but this a field that is going to get very competitive very quick with some of the new drugs. I am wondering what is your strategy for kind of novel combinations.

Are there business development arrangements that could be made with some of these companies that have competitive but potentially complement products where you can get going sooner rather than later on the combinations? What is your thinking around

that?

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

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

We are 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.

(inaudible) the ISP trial is intended to be enabling of future combination studies.

Right. Okay. Thank you.

Thank you. and our final question today comes from the line of Katherine Shue of William Blair. Your line is open. Please go ahead.

Thank you, good morning. Just curious, do you have any data on 145 Abrutinib failures these days? And what would you predict from the mechanism of action?

From the mechanism of action, they are independent pathways. So we would -- I do not want to make a prediction about clinical activity. But I do not see any basis for redundancy in the two pathways, and we are allowing Abrutinib patients who have progressed on Abrutinib to enter your study in the Phase I as well as the Phase III study. So we expect to get more data over time. Obviously fewer patients have been treated with Abrutinb, and the numbers of those patients are scarce right now. Obviously that will increase over time.

On the other question, Julian. Can you comment on the dose that you are using in RA and asthma, and how gamma inhibition is playing a role there?

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

Thank you.

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

Thank you for everyone joining us on the call today and for all of the good questions. We look forward to updating you on anticipated milestones in the coming months. 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.