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Edited Transcript of JNCE.O earnings conference call or presentation 6-Mar-19 1:00pm GMT

Q4 2018 Jounce Therapeutics Inc Earnings Call

CAMBRIDGE Mar 8, 2019 (Thomson StreetEvents) -- Edited Transcript of Jounce Therapeutics Inc earnings conference call or presentation Wednesday, March 6, 2019 at 1:00:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Elizabeth G. Tréhu

Jounce Therapeutics, Inc. - Chief Medical Officer

* Kimberlee Cobleigh Drapkin

Jounce Therapeutics, Inc. - CFO & Treasurer

* Komal Joshi

Jounce Therapeutics, Inc. - Head of IR & Strategic Finance

* Richard Murray

Jounce Therapeutics, Inc. - President, CEO & Director

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Conference Call Participants

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* Boris Peaker

Cowen and Company, LLC, Research Division - MD and Senior Research Analyst

* Carmen Marie Augustine

JP Morgan Chase & Co, Research Division - Analyst

* Debjit D. Chattopadhyay

H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst

* James William Birchenough

Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst

* Michael Eric Ulz

Robert W. Baird & Co. Incorporated, Research Division - Senior Research Analyst

* Steven James Seedhouse

Raymond James & Associates, Inc., Research Division - Research Analyst

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Presentation

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Operator [1]

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Good morning, ladies and gentlemen, and welcome to the Jounce Therapeutics Fourth Quarter and the Full Year 2018 Earnings Conference Call. (Operator Instructions) 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.

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Komal Joshi, Jounce Therapeutics, Inc. - Head of IR & Strategic Finance [2]

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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 Tréhu, who will provide an update on the clinical and preclinical development activities; lastly, our CFO, Kim Drapkin, will review our full year 2018 financials 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.

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Richard Murray, Jounce Therapeutics, Inc. - President, CEO & Director [3]

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Thanks, Komal, and good morning, everyone. 2018 was an important year for Jounce. We accomplished several key milestones, 2 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 vpora's mechanism of action and strong scientific rationale for the next stage of clinical development.

As we recently announced, we will present 3 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 analyzed clinical and biomarker data to develop new scientifically driven clinical trial designs, based on rational 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're pleased to announce that we've established safety in combination with both, thus, supporting new Phase II studies.

We also continued to advance our broader pipeline of first-in-class immunotherapies. In early 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're excited by the data we've 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, into Phase I 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 that PD-1 checkpoint inhibitors, like JTX-4014, will play 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 at immuno-oncology will likely come from a highly scientific and reverse translational approach.

On that note, let me highlight what we believe to be 3 key elements of this approach, and later on, Beth will give you direct examples of each. First and foremost, is to 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 nonresponding patients.

Second, we believe it is necessary to move beyond the PD-1 inhibitor-centric approach. Our focus is on combinations with a strong scientific rationale, irrespective of whether they include a PD-1 inhibitor.

Third, it's critical to address the unmet need in tumors that did 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're building a diverse pipeline targeting multiple immune cell types, including immunosuppressive macrophages, T Regulatory cells and stromal targets. Our approach in pipeline address all 3 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 received a nonrefundable upfront payment of $225 million and an equity investment of $36.1 million from Celgene.

Child's funds conducts and leads all activities prior to any partner opted. Celgene continues to be a great partner for us, and assuming the BMS Celgene acquisition closes as planned, we look forward to continue to working with BMS. We understand that there is overlap in our lead clinical programs and BMS's pipeline, but regardless, we see any outcome as having positive consequences for Jounce. We'll either have a strong partner in the IO field in BMS or we will retain a 100% of the worldwide rights for any unauctioned program and have the opportunity to advance it on our own or potentially with the new partner.

I'd like to know turn the call over to Beth to discuss our pipeline and science in more detail. Beth?

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [4]

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Thanks, Rich, and good morning, everyone. This is an exciting time for Jounce as we translate important learnings from our preclinical analyses and clinical trials into clinical progress. Our reverse translational work has provided us with a strong scientific rationale for future trials, and I am pleased to provide an update on our progress from 2018 and our plans going into 2019.

I'd like to start with vopra and the ICONIC trial. In the Phase I/II 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 II studies for vopra. We have shown that emergence of these activated CD4 T Effector cells is due to vopra and not PD-1 inhibitors.

In a few weeks, at AACR, we will present 2 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 benefits and the requirement for these cells to be present for vopra activity has led to 2 development paths. First, since CTLA-4 inhabitation has been shown to induce the population of ICOS high cells in the peripheral blood, while PD-1 inhibitors do not, there is strong scientific rationale for the ongoing clinical development of vopra in combination with ipilimumab. Based on this important reverse translational work, we will be initiating New Phase II studies this year of vopra in combination with the 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 for patients who are more likely to benefit. We have identified candidate predictive biomarkers through a comprehensive analysis of baseline blood and tumor samples from the 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 nonresponders in 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 II studies in 2019 with preliminary efficacy data expected in 2019.

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 antitumor 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 as PD-1 and CTLA-4, 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 brakes on this immunosuppressive interaction, resulting in a reprogramming of the macrophages from the 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 a Phase I study of JTX-8064 later this year and look forward to updating you on our continued progress.

Finally, I'd like to touch on our PD-1 inhibitor, JTX-4014, for which we remain on track to identify the recommended Phase II dose later this year. In today's update, I hope that we have conveyed the unique way in which Jounce approaches development of first-in-class immunotherapies, 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?

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Kimberlee Cobleigh Drapkin, Jounce Therapeutics, Inc. - CFO & Treasurer [5]

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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 a $195.9 million compared to $257.9 million for 2017. This is in line with our 2018 financial guidance of a $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 noncash, reflects the recognition of the Celgene upfront payment received 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 is driven by a decrease in noncash collaboration revenue and an increase in operating expenses.

We reiterate the 2019 financial guidance we provided in January. We continue 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 continue to expect noncash 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.

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Richard Murray, Jounce Therapeutics, Inc. - President, CEO & Director [6]

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Thanks, Kim. Before opening the call to your questions, I'd like to reiterate that 2019 will be focused on advancing our pipeline as we report important and 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 built a strong culture with a 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 3-lead development candidates and our discovery pipeline.

To reiterate, we plan to: report updated PFS and OS data from the ICONIC trial of vopra at AACR; initiate new Phase II studies of vopra; establish safety, tolerability and the recommended Phase II dose of JTX-4014; file the IND and initiate Phase I of JTX-8064; and continue to work on advancing our next development candidates into IND-enabling studies.

With that, we'd like to now open the call for your questions. Operator?

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Questions and Answers

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Operator [1]

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(Operator Instructions) And our first question comes from Cory Kasimov of JPMorgan.

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Carmen Marie Augustine, JP Morgan Chase & Co, Research Division - Analyst [2]

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This is Carmen on for Cory. So for 4014, I apologize if I missed this, when might we 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 select a dose to take to Phase II?

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [3]

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This is Beth. So given that it's a Phase I dose escalation, we would like to move into Phase II as quickly as possible. And I'm not sure at this point then when we'll decide to disclose the Phase I data. We may wait and just present Phase II data, but we haven't disclosed that right now.

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Carmen Marie Augustine, JP Morgan Chase & Co, Research Division - Analyst [4]

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Okay. And then for 2011, I just wanted to clarify, you mentioned kind of 2 potential path forward. One, combination like ipi and 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 details?

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Richard Murray, Jounce Therapeutics, Inc. - President, CEO & Director [5]

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Sure, I'll comment on that. That's Rich -- this is Rich speaking. Yes, we -- with the combination with ipi, we've got through the indications, and we've got a lot of work done with KOLs and our internal science and technology committee as to indications, landing on small cell and better. In the predictive biomarker space, we're 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 patients. So that's the direction we would head. But more details on that later.

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Operator [6]

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And our next question comes from Boris Peaker of Cowen.

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Boris Peaker, Cowen and Company, LLC, Research Division - MD and Senior Research Analyst [7]

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My first question is as you noted the observation of peripheral T cells associated with vopra activity. I'm just curious, is that something that could be used as a biomarker to monitor the efficacy of the drug shortly upon starting of treatment?

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [8]

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Yes, that's a good question, Boris. I think it has multiple potential uses, so it's certainly something that we can monitor on treatment, particularly for 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.

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Boris Peaker, Cowen and Company, LLC, Research Division - MD and Senior Research Analyst [9]

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

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Richard Murray, Jounce Therapeutics, Inc. - President, CEO & Director [10]

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Yes, I'll take that one, Boris. Yes, so from the data that we've seen, we do see a -- associated with vopra, we do see a clear pattern of emergence, it's a robust population that emerges. So we have set criteria and 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'll add maybe one kind of note that helps also to frame the kind of tight association of benefit in biomarker is, we have seen and reported at SITC and there'll 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 the kind of continued maintenance of the cell population and the long durable responses, and then there is this relatively kind of tight association of having the cells and losing the cells in correlation with then progressive disease.

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Boris Peaker, Cowen and Company, LLC, Research Division - MD and Senior Research Analyst [11]

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Got you. And lastly, just on the biomarker. Is it possible that this biomarker, and what you just mentioned about losing these cells, is 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 the kind of the prospective versus just correlative properties of the biomarker?

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [12]

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Sure. So as we've presented at SITC, we did a separate study where we looked at 77 patients who were receiving either PD-1 or PD-L1 inhibitors, and we did intensive profiling of their peripheral blood and did not find it in any of those patients on treatment with a PD-1 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 with PD-1 inhibitors being more active than CD8 cells really than on CD4 cells. And it's also something that we've 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 high ICOS size cells at the beginning using a predicted biomarker, but in all the work we've done, it does appear to be something that's directly associated with vopra.

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Operator [13]

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And our next question comes from Jim Birchenough, Wells Fargo.

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James William Birchenough, Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst [14]

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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've done with vopra? And just interested, do you have any insights into the time course of how long does it take for ipi to induce that ICOS high state?

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [15]

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Sure. Yes, we're 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.

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James William Birchenough, Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst [16]

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And then just on that combination, Beth, with ipi, one of the things that's struck us from the ICONIC results is if you could dose vopra long enough you see to get some benefit. How has that gone in terms of in combination with ipi? Can you dose the 2 drugs long enough to get the expected results?

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [17]

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Yes, so we're not really sharing the data from the dose escalation at this point, but as Rich mentioned, we do have a tolerable safety profile, with vopra and ipi. And it supports moving forward to the next phase of the study. So that's something we'll 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, do you want to add anything?

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Richard Murray, Jounce Therapeutics, Inc. - President, CEO & Director [18]

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Yes. And Jim, I think another angle on that is also as we move to lines of therapy in patient populations as opposed to being in the relapse refractory population, it'll be kind of the 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.

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James William Birchenough, Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst [19]

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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 will get at AACR, should we also look for tumor response data, not necessarily resist response, but just stable disease or tumor shrinkage as an important metric as well?

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Richard Murray, Jounce Therapeutics, Inc. - President, CEO & Director [20]

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Yes, I'll take the first one, and then Beth can comment on the last part of that question. So yes, at the -- we've got 2 posters at AACR with vopra. One would be the clinical data, the PFS and the OS, Beth will pick up 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 locations of the cells, kind of tracking them in different ways. I can't say too much more before the -- before that comes out, but would refer you to the abstract, which is published on our second vopra JTX-2011.

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [21]

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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've previously reported, and we've had them centrally reviewed now. But I think what we feel is the most compelling, really, getting to the core by immunotherapy still exciting, is really the durability and the PFS and OS that we're seeing in correlation with the biomarker. But there will be obviously more data than just that. And we'll 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.

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Richard Murray, Jounce Therapeutics, Inc. - President, CEO & Director [22]

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Yes, that links into to the earlier question about kind of the tumor agnostic potential.

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Operator [23]

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And our next question comes from Mike Ulz of Robert W. Baird.

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Michael Eric Ulz, Robert W. Baird & Co. Incorporated, Research Division - Senior Research Analyst [24]

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Maybe you can just talk about the current status of the ongoing Phase I dose escalation for the JTX-2011 combinations? And if you can maybe your current thinking in terms of the go-forward dose for Phase II, just based on the press release, it sounds like you may be considering some different schedule there?

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [25]

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Yes. So as you know, the dose escalations 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 make sense based on the biology, and we'll be providing more details about them in the future.

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Richard Murray, Jounce Therapeutics, Inc. - President, CEO & Director [26]

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Yes, a 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 population of cells with vopra.

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Operator [27]

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And our next question comes from Debjit Chattopadhyay from H.C. Wainwright.

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Debjit D. Chattopadhyay, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [28]

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So just to clarify, the requirement for this particular phenotype -- detail 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?

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [29]

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So no, it was not included in the dose escalation studies, those are purely safety to make sure that we could give the 2 drugs together safely. And going forward, well, we will be looking at the emergence of the ICOS high 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, we'll be looking at baseline but 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...

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Debjit D. Chattopadhyay, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [30]

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So just to follow up...

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [31]

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Sorry, go ahead. Yes.

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Debjit D. Chattopadhyay, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [32]

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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, 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 data set, what percent of patients actually have this biomarker -- predictive biomarker?

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [33]

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So we're -- in terms of the -- more details about the predictive biomarkers, we're not prepared to disclose a lot of information on that. We looked at these ICOS high CD4 T cells in a subset of patients, and what we've shown is data from about 50 patients in the 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 another tumor types, so we don't think this is particularly a tumor-specific phenomenon. And I think -- did I answer all of your question? Is there more to it?

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Debjit D. Chattopadhyay, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [34]

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Yes, there was the one, the impact of prior lines of therapy...

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [35]

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Oh, yes, yes. Thank you. 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 PD-1 inhibitors and had emergence of these cells. And this -- the patients in our study were also very heavily pretreated, but we'll actually be providing specifics about that lines of therapy, prior -- types of prior therapies and more patient baseline and characteristics and their relationship to the emergence of these cells in the poster at AACR. So hope you'll come by and see the poster, I think you'll get a lot more information from that.

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Debjit D. Chattopadhyay, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [36]

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Yes. Just a quick follow up on the bladder (inaudible) we are expanding into, would this primarily be PD-1 low -- and I'm obviously (inaudible) in eligible patients?

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [37]

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No, we are going to PD-1 experienced patients. So patients who have received and progressed on or after a PD-1 inhibitor. As you know that's a really...

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Debjit D. Chattopadhyay, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [38]

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Great. And does...

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [39]

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I'm sorry, go ahead.

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Debjit D. Chattopadhyay, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [40]

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Go ahead. I just had one more follow-up.

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [41]

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Yes. So as you know, that's a growing unmet need. As the PD-1 inhibitors move into earlier lines of therapy, the PD-1 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 a large unmet need, but also the point Rich made before, we think by moving into these less heavily pretreated patient population we'll be treating patients who are little healthier, able to remain on study longer, and hopefully, reap the benefits of the immunotherapy combination that we're treating them with.

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Richard Murray, Jounce Therapeutics, Inc. - President, CEO & Director [42]

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Yes, maybe just one other point on that related to the non-small cell lung cancer. What we did see, and again, more details at AACR, in fact, PD-1 experienced patients who showed benefit as well as induction of the cell population from non-small cell lung cancer. So we're looking at the mechanism, if you will, of the ipi and CTLA-4 and ICOS as a mechanism that's not necessarily dependent on PD-1.

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Debjit D. Chattopadhyay, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [43]

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

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [44]

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We don't try to get that kind of information from our investigators. Yes, so we only know what GSK has said publicly, and we know that they're 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's a big difference in terms of what they are seeing clinically, but we -- it's really hard to tell because they haven't presented that much information.

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Richard Murray, Jounce Therapeutics, Inc. - President, CEO & Director [45]

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Yes, we're anticipating information from GSK later this year I think at ESMO.

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [46]

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Second half of the year.

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Richard Murray, Jounce Therapeutics, Inc. - President, CEO & Director [47]

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Yes, yes. Second half of the year.

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Operator [48]

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(Operator Instructions) And our next question comes from Steven Seedhouse of Raymond James.

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Steven James Seedhouse, Raymond James & Associates, Inc., Research Division - Research Analyst [49]

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

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [50]

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

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Steven James Seedhouse, Raymond James & Associates, Inc., Research Division - Research Analyst [51]

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Okay.

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [52]

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And -- yes, and also looking at the overall study population.

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Steven James Seedhouse, Raymond James & Associates, Inc., Research Division - Research Analyst [53]

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Okay. And then just trying to understand the biology of this biomarker. Have you identified a patient ever in ICONIC or in the archived samples that you've looked at from CTLA-4 treated patients, where the actual T cell -- the ICOS high T cell Corporation itself was present before treatment?

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [54]

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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.

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Steven James Seedhouse, Raymond James & Associates, Inc., Research Division - Research Analyst [55]

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Okay. And is there...

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Richard Murray, Jounce Therapeutics, Inc. - President, CEO & Director [56]

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And one -- Steve, maybe I could add a comment on that, I think one thing that -- or at least the way we're thinking about the biology here is that, wouldn't necessarily be kind of unusual if there was an expanded population in a patient or a person, it could be from a 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 if ipi is lowering the thresholds for kind of new priming events, which hopefully would include tumor-specific T cells, it's then 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're looking at the biology. We haven't seen and nor had there been published reports of preexisting, but that's obviously something we'll continue to look at.

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Steven James Seedhouse, Raymond James & Associates, Inc., Research Division - Research Analyst [57]

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Okay. And just lastly, again, on the biomarker. Were of the CTLA-4 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?

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Elizabeth G. Tréhu, Jounce Therapeutics, Inc. - Chief Medical Officer [58]

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Yes. So I'm not sure what you mean in terms of the CTLA-4 patients that we've 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 about the stable disease patient, you had to have persistence of those cells. And we know that at some point after you stop ipi, which can't be given indefinitely, you do start to lose those cells, whereas with JTX-2011 -- sorry, vopra being so far in our hands very safe, it's something that you can keep giving and maintain that population of cells.

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Operator [59]

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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 now disconnect. Everyone, have a great day.