Jounce Therapeutics, Inc.
Q4 2018 Earnings Call Transcript

Published: 6 Mar 2019

[Operator:]

Good morning, ladies and gentlemen and welcome to the Jounce Therapeutics Fourth Quarter and Full Year 2018 Earnings Conference Call. At this time all participants are in a listen-only mode. Later we will conduct a question-and-answer session and instructions will follow at that time. As a reminder, this conference call is being recorded at the company’s request. I will now turn the call over to your host, Komal Joshi with Jounce Therapeutics. Please go ahead.

[Komal Joshi:]

Thank you, operator. Good morning and welcome to the Jounce Therapeutics fourth quarter and full year 2018 financial results conference call. This morning, we issued a press release, which outlines the topics that we plan to discuss today. The release is available in the Investors and Media section of our website at www.jouncetx.com. Speaking on today’s call will be our CEO and President, Dr. Rich Murray, who will discuss our pipeline progress and key milestones for 2019, followed by our CMO, Dr. Beth Trehu, who will provide an update on the clinical and preclinical development activities, lastly, our CFO, Kim Drapkin, will review our full year 2018 financial and review our 2019 financial guidance. We will then open the call for your questions. Before we begin, I would like to remind everyone that today’s discussion will include statements about our future expectations, plans and prospects that constitute forward-looking statements for the purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including the risk factors discussed in our SEC filings. In addition, any forward-looking statements represent our views only as of today, March 6, 2019 and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change. With that, I will now turn the call over to Rich.

[Rich Murray:]

Thanks, Komal and good morning, everyone. 2018 was an important year for Jounce. We accomplished several key milestones, two of which centered around our most advanced product candidate, vopratelimab or vopra formally JTX-2011, our ICOS agonist. We reported several data readouts from the ICONIC trial at ASCO and SITC, which demonstrated important insights into vopra’s mechanism of action and strong scientific rationale for the next stage of clinical development. As we recently announced, we represent three posters at the upcoming AACR annual meeting which will include an important validation of our ICOS biomarker demonstrating improved progression-free survival and overall survival in patients with the biomarker. Using our Translational Science platform, we analyze clinical and biomarker data to develop new scientifically driven clinical trial designs based on rationale combination strategy and new potential predictive biomarkers. We began enrollment of safety dose escalation combination cohorts with ipilimumab and with pembrolizumab in June 2018 and today we are pleased to announce that we have established safety in combination with both thus supporting new Phase 2 studies. We also continue to advance our broader pipeline of first-in-class immunotherapies. In 2018 we announced the advancement of our first tumor associated macrophage candidate, JTX-8064 into IND-enabling studies. JTX-8064 targets LILRB2 also known as ILT4, a macrophage target, which we see as analogous to a macrophage checkpoint. JTX-8064 represents an example of our vision to discover new therapies and pathways that involve multiple immune cell types and we are excited by the data we have seen so far. We look forward to providing more information about JTX-8064 in a poster at the AACR annual meeting in a few weeks. We also advanced our JTX-4014, our PD-1 inhibitor at Phase 1 clinical trials and completed enrollment in the first cohort in the fourth quarter of 2018. As previously stated, we believe combination therapy will be the mainstay of cancer immunotherapy. And at PD-1 checkpoint inhibitors like JTX-4014, we are playing an important role in combination with our future product candidates. We hope to transform the treatment of cancer and provide long-lasting benefit to patients and believe more than ever that success in immunooncology will likely come from a highly scientific and reverse translational approach. On that note, let me highlight what we believe to be three key elements of this approach and later on Beth will give you direct examples of each. First and foremost, this will identify the right patients. Early in the development process we used our translational science platform to evaluate multiple potential predictive biomarkers. More importantly once clinical and biomarker data are available from the clinical trial, we then use our platform to identify the unique characteristics of the mechanism of action in any association with responding versus non-responding patients. Second, we believe it is necessary to move beyond the PD1 inhibitor centric approach, our focus on combinations with a strong scientific rationale irrespective of whether they included PD1 inhibitor. Third, it’s critical to address the unmet need in tumors that do not have T-cells. Some of these tumors which may either be cold or dominated by immunosuppressive macrophages do not respond well to T-cell directed immunotherapies. We are building a diverse pipeline targeting multiple immune cell types including immunosuppressive macrophages T regulatory cells and stromal targets. Our approach and pipeline address all three of these important elements. In January our partner Celgene announced an agreement under which Celgene may be acquired by Bristol Myers Squibb. As a reminder, in 2016, we have received a non-refundable upfront payment of $225 million and an equity investment of $36.1 million from Celgene. Jounce funds conducts and leads all activities prior to any partner opt-in. Celgene continues to be a great partner for us and assuming BMS Celgene acquisition closes as planned, we look forward to working with BMS. We understand that there is overlap in our lead clinical programs and BMS’ pipeline, but regardless we see any outcome as having positive consequences for Jounce. We will either have a strong partner in the IL field in BMS or we will retain 100% of the worldwide rights for any un-option program and have the opportunity to advance it on our own more potentially with the new partner. I would like to now turn the call over to Beth to discuss our pipeline and science in more detail. Beth?

[Beth Trehu:]

Thanks Rich and good morning everyone. This is an exciting time for Jounce as we translate the important learnings from our preclinical analyses and clinical trails into clinical progress. Our reverse translational work has provided us with a strong scientific rationale for future trails and I am pleased to provide an update on our progress from 2018 and our plans going into 2019. I would like to start with vopra and the ICONIC trial. In the Phase 1, 2 ICONIC trial tumor reductions were associated with an ICOS pharmacodynamic biomarker specifically emergence in the peripheral blood of a population of ICOS high CD4 T cells which have the characteristics of activated CD4 T effector cells. This pharmacodynamic biomarker has been critical in interpretation of our clinical data and in informing the next set of Phase 2 studies for vopra. We have shown that emergence of these activated CD4 T effector cells is due to vopra and not PD1 inhibitors. In a few weeks at AACR we will present two posters on vopra. One providing more details about the characteristics of these cells and one providing clinical data showing improved progression free and overall survival in ICONIC patients who have emergence of these cells. In separate analyses, we have demonstrated that vopra only activates CD4 T cells if they express high levels of ICOS. The relationship between the emergence of ICOS high CD4 T cells and clinical benefit and the requirement for these cells to be present for vopra activity has led to two development paths. First, since CTLA inhibition has been shown to induce the population of ICOS high cells in the peripheral blood, while PD1 inhibitors do not, there is strong scientific rationale of the ongoing clinical development of vopra in combination with ipilimumab. Based on this important reverse translational work, we will be initiating new Phase 2 studies this year of vopra in combination with ipilimumab in both non-small cell lung cancer and bladder cancer. The second path is based on patient selection for new predictive biomarkers that may enrich the patients who are more likely to benefit. We have identified candidate predictive biomarkers to a comprehensive analysis of baseline blood and tumor samples from a subset of patients treated in the ICONIC trial, with an emphasis on understanding the differences between the baseline characteristics of responders all with emergence of ICOS high CD4 T cells and non-responders and whom these cells did not emerge. We believe that applying our platform to reverse translational analysis of clinical trial data to inform our patient selection strategy is more relevant than relying on preclinical data. As mentioned at AACR the vopra clinical data being presented shows that ICONIC patients with emergence of ICOS high CD4 T cells have improved progression-free and overall survival. This finding further validates the role of this ICOS pharmacodynamic biomarker in directing the next stage of the clinical development strategy for vopra. We plan to initiate the new Phase 2 studies in 2019 with preliminary efficacy data expected in 2020. I would now like to turn to our next first-in-class program, JTX-8064, which targets tumor-associated immunosuppressive macrophages. At Jounce, we believe that targeting different immune cell types may allow us to develop innovative therapies for tumor types that are not responsive to T cell directed therapies alone. Our goal is to convert the immunosuppressive tumor micro environment to an immune-activating anti-tumor environment which is likely to require targeting multiple cell types. When LILRB2, the target of JTX-8064 binds to its ligands, an immunosuppressive state is created. Similar to other immune checkpoints such PD1 and CTLA4, LILRB2’s ligands may also be an immune evasion strategy employed by tumors. By inhibiting the binding of LILRB2 to its ligands, we hope to release the breaks on this immunosuppressive interaction resulting in a reprogramming of the macrophages from an immunosuppressive or M2 phenotype to immunostimulatory or M1 phenotype. We believe this is analogous to a macrophage checkpoint. As mentioned in just a few weeks at AACR, we will also present a poster on JTX-8064 that will describe the preclinical evaluation of this exciting product candidate and its role in reprogramming tumor associated macrophages within the tumor micro environment. We expect to file the IND and initiate the Phase 1 study of JTX-8064 later this year and look forward to updating you on our continued progress. Finally, I would like to touch on our PD-1 inhibitor JTX-4014 for which we remain on track to identify the recommended Phase 2 dose later this year. In today’s update, I hope that we have conveyed the unique way in which Jounce approaches the development of first-in-class immunetherapies, applying our Translational Science platform to incorporation of pharmacodynamic and potential predictive biomarkers from early preclinical through clinical development and to reverse translational analysis of clinical data to inform continued clinical development. Now, I would like to turn the call over to Kim for a discussion of our full year 2018 financial results and review of our 2019 guidance. Kim?

[Kim Drapkin:]

Thanks, Beth and good morning everyone. As we reported in this morning’s press release, we ended 2018 with cash, cash equivalents and investments totaling $195.9 million compared to $257.9 million for 2017. This is in line with our 2018 financial guidance of $185 million to $195 million. The decrease in cash was due to increased operating costs incurred during the year offset by the receipt of state and federal income tax refunds. Turning to the P&L, our collaboration revenue was $65.2 million for the full year 2018 compared to $71.6 million for 2017. Recall that collaboration revenue currently non-cash, reflects a recognition of the Celgene upfront payment receipt in July 2016. During 2018, we incurred $70.1 million in research and development expenses compared to $67.8 million in 2017. The increase in R&D expenses for the full year 2018 was due to $3.1 million of increased employee compensation costs and $3 million of increased external clinical and regulatory costs offset by $2.1 million of decreased external R&D costs and $2 million of decreased lab consumables purchases. General and administrative expenses were $26.4 million for 2018 compared to $23.1 million for 2017. The increase in G&A expenses is primarily the result of increased employee compensation costs. Net loss for 2018 was $27.4 million or a net loss per basic and diluted share of $0.84 as compared to a net loss of $16.4 million for 2017 or a net loss per basic and diluted share of $0.57. This increase was driven by a decrease in non-cash collaboration revenue and an increase in operating expenses. We would reiterate the 2019 financial guidance we provided in January. We continued to expect cash burn on operating expenses and capital expenditures for the full year 2019 to be approximately $80 million to $95 million. We also continued to expect non-cash collaboration revenues of approximately $50 million to $60 million. Our strong balance sheet allows us the flexibility to drive our innovative immunotherapy pipeline plus efficiently execute against our strategic plans and goals. Based on our current operating plans, we expect our existing cash, cash equivalents and investments will be sufficient to enable us to fund our operating expenses and capital expenditure requirements for at least the next 24 months. With that, I will turn the call back over to Rich.

[Rich Murray:]

Thanks Kim. Before opening the call to your questions, I would like to reiterate that 2019 will be focused on advancing our pipeline as we report important incremental data and execute on our anticipated milestones. Importantly, we are well capitalized to drive our development candidates and bring additional new programs forward. We have built the strong culture with the team of dedicated and talented professionals who remain focused on discovering and developing innovative therapies that bring durable benefits to cancer patients. As such we have a lot coming up this year for our three lead development candidates into our discovery pipeline. To reiterate, we plan to report updated PFS and OS data form the ICONIC trial of vopra at AACR, initiate new Phase 2 studies of vopra, establish safety, tolerability and the recommended Phase 2 dose of JTX-4014, file the IND and initiate Phase 1 of JTX-8064 and continued to work on advancing our next development candidate into IND enabling studies. With that, we would like to now open the call for your questions. Operator?

[Operator:]

Thank you. [Operator Instructions] And our first question comes from Cory Kasimov of JPMorgan. Your line is now open.

[Unidentified Analyst:]

Hi, this is Carmen on for Cory. Thanks for taking my question. So for 4014 I apologize if I missed this, when might we would be able to get a first look at the data from the ongoing trial, is that something you would present when you make the decision to what’s the dose you take to Phase 2?

[Beth Trehu:]

Hi. This is Beth, so given that it’s a Phase 1 dose escalation, we would like to move into Phase 2 as quickly as possible. And I am not sure at this point when we will decide to disclose the Phase 1 data, we may wait and just present Phase 2 data, but we haven’t disclosed that right now.

[Unidentified Analyst:]

Okay. Thank you. And then for 2011 I just wanted to clarify you mentioned kind of two potential paths forward one combination with Ipi in lung and bladder and then the second path was just identifying patients more likely to benefit, would that be kind of a tumor agnostic approach or how are you thinking about that if you could provide more detail?

[Rich Murray:]

Sure. I will comment on that, but this is Rich speaking. Yes. We – with the combination with Ipi we have got through the indications and we have got a lot of work done with KOLs and our internal science and technology committee as to indications landing on non-small cell and bladder. In the predicted biomarker space, we are certainly looking in a manner that could be tumor agnostic. We think that there is the potential for the immune system of course as it cuts across indications to offer those types of opportunities to find the right patience. So, that’s good direction we would had, but more details on that later.

[Unidentified Analyst:]

Okay, great. Thank you.

[Operator:]

Thank you. And our next question comes from Boris Peaker of Cowen. Your line is now open.

[Boris Peaker:]

Great. Good morning. My first question is as you noted the observation of peripheral T cell associated with vopra activity, I am just curious is that something that could be used as a biomarker to monitor the efficacy of the drug shortly upon starting of treatment?

[Beth Trehu:]

Yes, that’s a great question, Boris. I think it has multiple potential uses. So it’s certainly something that we can monitor on treatment, particularly if we are combining with other agents such as ipi, we can monitor the degree to which we see these cells, after ipi, after vopra, it gives us a good way to look at other potential drugs that we could combine with vopra with a similar strategy, but importantly, it also then allows us to start looking for potential predictive biomarkers that can help us identify the patients in whom those cells may emerge, but yes, it certainly can be a good tool and potentially looking at it in real-time can give the investigators a sense of whether to keep their patients unsteady or not.

[Boris Peaker:]

Got it. And second question on the biomarker, you have obviously done a lot of work on the ICOS biomarker, I am just curious do you feel confident that you have derived of what a clear definition of ICOS high is or is that threshold still kind of evolving moving target?

[Rich Murray:]

Yes, I will take that one Boris. Yes, so from the data that we have seen, we do see associated with vopra, we do see a clear pattern of emergence, it’s a robust population that emerges. So we have set criteria in conditions around kind of how this assay is run and have validated that for all the purposes that Beth went through. So, we feel comfortable that, I mean, the convenience of it being in the blood and not the tumor is obvious as well, but we feel confident that when we see that positive – kind of that positive population, it really is positive. I will add maybe one kind of note that helps also to frame the kind of type association of benefit in biomarker is we have seen and reported at SITC and there will be more at – upcoming at AACR we have seen in patients that have kind of achieved a stable disease state. When those patients lose the population of cells, then the patients progress, so there is kind of continued maintenance of the cell population in the long durable responses and then there is this relatively kind of type association of having the cells and losing the cells in the correlation with then progressive disease.

[Boris Peaker:]

Got it. And lastly just on that biomarker, is it possible that this biomarker and what you just mentioned about losing the cells, it’s kind of indicative of overall immune health and so you would expect it to just decline with progression of disease as the cancer kind of defeats the immune system, how do we know that kind of the perspective versus just correlative properties of the biomarker?

[Beth Trehu:]

Sure. So as we have presented at SITC, we did a separate study where we looked at 77 patients who were receiving either PD1 or PDL1 inhibitors and we did intensive profiling of their peripheral blood and did not singed it in any of those patients on treatment with a PD1 inhibitor, including 6 patients who had confirmed responses. So if it were just a marker of immune cell health, we think we would have seen it in at least some of those patients, particularly in the responding patients, but we did not see it. And that’s consistent with the biology, the PD1 inhibitors being more active on CD8 cells really than on CD4 cells and it’s also something that we have seen emerge on treatment, although as you heard we do think we have ways to maybe find out, which patients may have some of those primed or ICOS high cells at the beginning using a predictive biomarker, but in all the work we have done, it does appear to be something that’s directly associated with vopra.

[Boris Peaker:]

Great. Thanks very much for taking my questions.

[Beth Trehu:]

You are welcome.

[Operator:]

Thank you. And our next question comes from James Birchenough, Wells Fargo. Your line is now open.

[James Birchenough:]

Yes, hi guys. Congrats on all the progress with the reverse translational work. I guess the first question is just in terms of the ipi inducing ICOS high CD4 response, have you looked at that in the safety study that you have done with vopra and just interest if you have insights into the time course of how long does it take for ipi to induce that ICOS high state?

[Beth Trehu:]

Sure. Yes, we are definitely looking at that in the dose escalation studies, the safety study, with vopra and ipi. Most of the data on the kinetics of its emergence or its induction by ipi come from the literature from publications by Pam Sharma, Jeff Weber, others who have shown kind of the timing. And it generally appears during the first 1 or 2 cycles of ipi therapy.

[James Birchenough:]

And I just saw in that combination back with ipi, one of the things that struck us from the iconic results is if you could dose vopra long enough, you seem to get some benefit, how has that gone in terms of in combination with ipi, can you dose the two drugs long enough to get the expected results?

[Beth Trehu:]

Yes. So, we are not really sharing the data from the dose escalation at this point, but as Rich mentioned, we do have tolerable safety profile with vopra and ipi and it supports moving forward to the next phase of the study. So, that’s something we will obviously be monitoring, but as I mentioned earlier being able to give the investigators’ feedback on whether those cells are emerging and other biomarker data we think will be helpful in helping to maintain patients on treatment long enough to benefit. And Rich you want to add anything?

[Rich Murray:]

Yes. Jim, I think another angle on that is also as we move two lines of therapy in patient populations as opposed to being in the relapsed refractory population, there will be kind of a healthier patient population if you will that we think could track to being able to stay on therapy long enough for these immune mechanisms to kick in.

[James Birchenough:]

And then just finally just trying to tie the biology in altogether, if you look at patients that have the peripheral ICOS high CD4 cells, have you looked at whether those CD4 cells are infiltrating the tumor? And I guess the second part of the question is just looking at the PFS and OS data we will get at AACR, should we also look for tumor response data not necessarily resist response, but just stable disease or tumor shrinkages as an important metric as well?

[Rich Murray:]

Yes, I will take the first one and then Beth can comment on the last part of that question. So, yes, we have got two posters at AACR with vopra, one would be clinical data, the PFS and the OS that they will pickup on that, but then also we will have a more mechanistic poster, looking at the characterization of these cells we continue to find them to have all the characteristics that one would expect for kind of a cycling activated T Effector cell. And in addition, we will be kind of tracking various means the periphery as well as tumor location of the cells kind of tracking them in different ways. I can’t say too much more before that comes out, but would refer you to the abstract which is published on our second vopra JTX-2011.

[Beth Trehu:]

Yes. And then with respect to your question about responses, so yes, there is updated data particularly on the durability of the responses that we have previously reported. And we have had them centrally reviewed now, but I think what we feel is the most compelling really getting to the core of why immunotherapy is so exciting is really the durability and the PFS and OS that we are seeing in correlation with the biomarker. But there will be obviously more data than just that and we will also be digging into the characteristics of the patients, so that you kind of see what the baseline characteristics of these patients are and then that will help you put the data in context.

[Rich Murray:]

Yes, yes, that leads into the earlier question about kind of the tumor agnostic potential.

[James Birchenough:]

Great. Thanks for taking the questions.

[Rich Murray:]

Sure.

[Beth Trehu:]

You’re welcome.

[Operator:]

Thank you. And our next question comes from Mike Ulz of Robert W. Baird. Your line is now open.

[Mike Ulz:]

Hey guys, thanks for taking the question. Maybe you can just talk about the current status of the ongoing Phase 1 dose escalation for the JTX-2011 combinations? And if you can maybe your current thinking in terms of the go-forward dose for Phase 2 just based on the press release it sounds like you’re maybe considering some different schedule there?

[Beth Trehu:]

Yes. So, as you know the dose escalation started in June and we have determined the dose to take forward in the new studies that’s safe and well tolerated. And yes, we’re not providing a lot of details, but yes, we do feel that some changes in the dosing schedule makes sense based on the biology and we’ll be providing more details about them in the future.

[Rich Murray:]

Yes, part of that Mike is that we are looking kind of back to the kinetics and how to – how we think we could optimally kind of create that lower threshold for priming from the ipi dose and then come in for the expansion of these populations of cells with vopra.

[Mike Ulz:]

Got it. That’s helpful. Thanks.

[Operator:]

Thank you. And our next question comes from Debjit Chattopadhyay of H.C. Wainwright. Your line is now open.

[Debjit Chattopadhyay:]

Hey, good morning. So, just to clarify, the requirement for this particular phenotype, T cell phenotype, was that implemented in the ipi combo initiated in June of 2018 or this is something that’s getting implemented in – for all future studies?

[Beth Trehu:]

So, no, it was not included in the dose escalation studies, those are purely safety to make sure that we could give the two drugs together safely. And going forward, well, we will be looking at the emergence of the ICOS hi CD4 T cells in all of our studies, but looking at a potential predictive biomarker to select patients will be in one particular biomarker-driven study. And the ipi studies will be looking at baseline that won’t necessarily be selecting patients because we think that ipi will be serving that function of generating those cells that can then respond better to vopra, but we do anticipate a separate – sorry, go ahead, yes.

[Debjit Chattopadhyay:]

Yes. So, just following up on that in terms of the expression of this phenotype, are there specific tumor types that you would think that this is likely to show up in or are these your traditional ipi-sensitive tumors, and also in terms of the prior lines of therapy that these patients have had, would – does that make a difference in ipi’s ability to induce this? And the other one would be in terms of just looking at your current dataset, what percent of patients actually have this biomarker – predictive biomarker?

[Beth Trehu:]

So, we’re – in terms of more details about the predictive biomarker, we’re not prepared to disclose a lot of information on that. We looked at these ICOS hi CD4 T cells in a subset of patients and what we’ve shown is data from about 50 patients in this study and in that group, all the people who had tumor reductions had emergence of this cell type and the people who did not didn’t, and it was present in 18 of the 50 patients who actually had emergence of it. So, in terms of the induction of these cells, Pam Sharma has shown it in several different tumor types. It’s been demonstrated in bladder cancer, which is obviously important since that’s one of the tumors we’re going into, it’s also been shown in melanoma, and in very small series, it’s been shown in other tumor types. So, we don’t think this is particularly a tumor-specific phenomenon. And I think – did I answer all of your questions. Is there more to it.

[Debjit Chattopadhyay:]

Yes, there was the one in terms of the impact of prior lines of therapy –

[Beth Trehu:]

Oh, yes, yes. Yes, thank you. Well, actually what’s really interesting from our ICONIC data is that we saw tumor reductions and durable stable disease in some non-small cell lung cancer patients who had failed PD1 inhibitors and had emergence of these cells. And the patients in our study were also very heavily pretreated, but we will actually be providing specifics about that lines of therapy, types of prior therapy and more of patients based on characteristics and their relationship to the emergence of these cells in the poster to AACR. So, hope you will come by and see the poster, I think you will get a lot more information from that.

[Debjit Chattopadhyay:]

Yes. Just [Technical Difficulty] on again expanding into, would this primarily be PD1 low and on obviously cisiplatin in eligible patients?

[Beth Trehu:]

No, we are going into PD1 experience patients, so patients who have received and progressed on or after a PD1 inhibitor.

[Debjit Chattopadhyay:]

Great.

[Beth Trehu:]

As you know, that’s a really – I am sorry go ahead.

[Debjit Chattopadhyay:]

Go ahead. I just had one more.

[Beth Trehu:]

Yes. So as you know that’s a growing unmet need as the PD1 inhibitors move into earlier lines of therapy, the PD1 experienced patient population is now one for whom there is not really a standard of care. And so it provides – it’s an opportunity for us to address the large unmet need, but also to the point Rich made before we think by moving into these less heavily pretreated patient populations, we will be treating patients who are a little healthier able to remain on steady longer and hopefully reap the benefits of at the immunotherapy combination that we are treating them with.

[Rich Murray:]

Yes. Maybe just one other point on that related to the non-small cell lung cancer, we did see and again in more detail that at AACR, in fact PD1 experienced patients who show benefit as well as induction of the cell population from non-small cell lung cancer, so looking at the mechanism if you will of the ipi and CTLA4 and ICOS as a mechanism that’s not necessarily depended on PD1.

[Debjit Chattopadhyay:]

Great. And one last one for me, are you hearing anything from your investigators regarding the GSK program and any differentiation versus yours in terms of strategy and what they might have seen with the GSK stuff, which obviously seems to gaining some traction as well?

[Beth Trehu:]

We don’t try to get that kind of information. Yes, so we only know what GSK has said publicly and we know that they are actually putting a lot of investment into their ICOS program and are very excited about it. And to-date we haven’t seen anything that leads us to think that there is a big difference in terms of what they are seeing clinically, but it’s really hard to tell, because they haven’t presented that much information.

[Rich Murray:]

Yes, we are anticipating information from GSK later this year I think at…

[Beth Trehu:]

Second half of the year.

[Rich Murray:]

Second half of the year.

[Debjit Chattopadhyay:]

Thank you so much.

[Beth Trehu:]

Thank you.

[Operator:]

Thank you. [Operator Instructions] And our next question comes from Steven Seedhouse of Raymond James. Your line is now open.

[Steven Seedhouse:]

Good morning. Thank you. You mentioned the upcoming AACR presentation will show improved PFS and OS in the ICOS high piece of patients, can you just clarify what that is in relation to historical controls or to the non-ICOS high patients?

[Beth Trehu:]

Yes, it’s looking at the ICOS high versus the ICOS low patients.

[Steven Seedhouse:]

Okay.

[Beth Trehu:]

And also looking at the overall steady population.

[Steven Seedhouse:]

Okay, thank you. And just trying to understand the biology of this biomarker, have you identified a patient ever in ICONIC or in the archived samples that you have looked at from CTLA4 treated patients, where the actual T cell, the ICOS high T cell population itself was present before treatment?

[Beth Trehu:]

From the published data there, I am not aware of any data suggesting the ability to detect these cells in the peripheral blood prior to treatment.

[Steven Seedhouse:]

Okay.

[Rich Murray:]

Steve, maybe I could comment on that. I think one thing that or at least the way we are thinking about the biology here is that wouldn’t necessarily be kind of unusual if there was an expanded population and a patient or a person it could be from an influenza vaccine or the variety of reasons why you could have expanded populations. But we think the key there is particularly in the ipi combination is that ipi is lowering the thresholds for kind of new priming events which hopefully would include tumor specific T cells. It’s been that kind of next sequence of how do you quickly expand that population of cells that could hopefully get to the tumor. So that’s kind of the way we are looking at the biology. We haven’t seen and nor had there been published reports of pre-existing, but that’s obviously something we will continue to look at.

[Steven Seedhouse:]

Okay. And just lastly again on the biomarker, were any of the CTLA4 treated patients that you looked at complete responders and if so does the biomarker persist or would the biology suggest it might persist in a patient with a durable complete response?

[Beth Trehu:]

Yes. So I am not sure what you mean in terms of the CTLA4 patients that we have looked at, but in the literature that was one of the things that got us interested in ICOS at the very beginning when Pam Sharma showed data that showed that induction of ICOS high CD4 cells correlated with improved survival. But really importantly and this gets to what Rich was saying earlier that the stable disease patients you had to have persistence of those cells. And we know that at some point after you stop ipi which can’t be given definitely you do start to lose those cells, whereas with JTX-2011 I would say vopra being so far in our hands very safe and it’s something that you can keep giving and maintain that population of cells.

[Steven Seedhouse:]

Okay. Thanks for clarifying and thanks for the questions.

[Beth Trehu:]

Thank you.

[Operator:]

Thank you. And that concludes our question-and-answer session for today. Ladies and gentlemen, thank you for participating in today’s conference. This does conclude the program and you may all disconnect. Everyone have a great day.