Five Prime Therapeutics Inc
Q4 2016 Earnings Call Transcript

Published: 24 Feb 2017

[Operator:]

Good day, ladies and gentlemen and welcome to the Five Prime Therapeutics Fourth Quarter And Fiscal Year 2016 Earnings Call. As a reminder, this conference maybe recorded. I now like to introduce your host for today's conference, Miss Heather Rowe, Senior Director Investor Relations and Corporate Communications. You may begin.

[Heather Rowe:]

Good afternoon and thank you for joining us. I'd like to welcome everyone to our conference call to discuss results for the fourth quarter and full year 2016. We issued a press release this afternoon and also posted slides to accompany this presentation. The slides can be found under the Investor Relations section of our website, under Events and Presentation. Joining me today are Dr. Rusty Williams, Chief Executive Officer; Dr. Robert Sikorski, Chief Medical Officer and Mr. Marc Belsky, Chief Financial Officer. Today's conference call will include forward-looking statements under the Private Securities Litigation Reform Act of 1995, including statements regarding our research and development programs and financial outlook. Actual results may differ from those indicated by these forward-looking statements due to numerous factors, including those discussed in the Risk Factors section of our SEC filings. Our expectations and assumptions could change. While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so even if our views change. I will now turn the call over to Rusty.

[Rusty Williams:]

Thanks, Heather. Good afternoon, and thanks for joining us today as we discuss Five Prime’s results from the fourth quarter and fiscal year 2016. I like to start by reminding you of the pretty dramatic progress we’ve made in expanding and advancing our pipeline which is shown on slide three. You will notice that in addition to our pre-clinical programs we’ve also added three IND candidates that we announced at our R&D day in December. The three key messages today I’d like for you to take home. First, I’m so impressed by the great progress made by our development team who have kept their trials on track so that we can announce data from each of our three clinical programs throughout this year. Second, our investment in research is truly paying off. We’ve added considerably to our pre-clinical pipeline and we have three drug candidates at the IND enabling stage. And third, as we showed at R&D day in December, our platform is producing numerous discoveries that we expect will fuel future growth in our immune oncology pipeline. Now I would like to tell you about some key highlights beginning with Cabiralizumab, Cabira. This is our CSF1 receptor antibody that blocks macrophages in tumors. We and our partner BMS are studying Cabira in combination with PD1 checkpoint inhibitor OPDIVO. In October, Five Prime initiated a large Phase 1b expansion portion of the trial in seven different tumor setting. This large trial is enrolling very well and we expect the complete enrolment in all of the phase 1b cohort by the end of the year. In addition to this immuno-oncology trial we are on track with our Phase 2 trial of Cabira and orphan disease, Pigmented Villonodular Synovitis or PVNS. We recently announced that the European Commission granted orphan drug designation to Cabira for PVNS. This designation which adds to the FDA orphan drug designation already granted in the U.S highlights the need for new treatments to help patients with this rare neoplastic joint disease for which there are no currently approved medical therapy. We expect to announce clinical data from both Cabira trials in 2017 and Bob will go into more detail on this in a few minutes. We are also advancing our FPA 144 program; recall this 144 is isoform-selective antibody which we are developing as a targeted immuno-therapy for tumors that over express the big splice variant of FGF receptor 2. In the second half of 2016, we added new gastric and bladder cancer cohorts to the current monotherapy 144 trial. As a reminder, we added a bladder cancer cohort after a patient diagnosed his fate for bladder cancer achieved a durable complete response. We are delighted that this patient still remains on FPA 144 more than a year and a half after starting this therapy. Bob will describe our future plans for the development of FPA 144 in a few minutes. Regarding our earlier stage programs, we have three new pre-clinical programs advancing in IND enabling activities. These new programs included two antibodies for which we plan to file INDs by the end of this year and one FC Fusion protein for which we plan to file an IND in 2018. I will describe these very briefly. I’ll start with FPA 150, an antibody to B7-H4 which is shown on slide four. This targets the member of the B7 family of checkpoint inhibitors which includes proteins like PD-L1. There are number of tumors such as ovarian cancer and breast cancer that have high levels of B7-H4 expression on the surface of the cancer cell. So we engineer this antibody to have two different mechanisms of action. First, we’ve shown that it blocks the immune suppressive function of B7-H4 acting on CD8 T cells. Second, we engineered it to drive ADCC and recruit NK cells to kill tumor cells that express B7-H4. Our next 2017 IND candidate is FPA154, our GITR agonist antibody which is shown on slide five. While there are a number of other companies with GITR antibody programs we think our GITR antibody program is differentiated because our antibody has four GITR binding sites, compared with a conventional anti GITR antibodies that have only two GITR binding sites. We’ve shown that our Tetravalent antibody increases GITR cost making and therefore results in higher activation of CD80 cells as compared to bivalent antibodies. We believe this is an advantage over our competitor’s antibodies. In addition, in preclinical tumor models we found that combining [Indiscernible] of FPA154 with a PD-1 Pathway blocker produced profound anti tumor effect. And finally, I’d like to mention FPT155 this is a soluble CD80 fusion protein, it’s shown on slide six. Using our unique In Vivo screening approach we tested 500 candidates Immuno regulatory proteins to identify those that have the ability to shrink tumor in mice. CD80 stood out as a protein that when expressed in the isoform [ph] has potent anti tumor activity. It’s a natural immune regulatory molecule that has evolved to have multiple actions. We believe FTP155 enhances T cell responses through three mechanisms. First, it activates CD28 importantly without superagonism, second it blocks the immunosuppressive effect of CTLA4, third it blocks the PD-1 checkpoint pathway by binding the PDL-1. We believe these mechanisms may lead to the striking anti tumor effect we see in multiple pre clinical models and might explain our observation that treatment with FPT155 causes non inflamed tumors to become inflamed. Last, a word about our financials. Our cash balance at the end of 2016 was approximately $420 million, which is in keeping with our previous guidance. I will now turn the call over to Bob to give a more detailed update on our progress.

[Robert Sikorski:]

Thank you Rusty. First I’ll briefly talk about the Cabira IO clinical trial in advanced cancer patients. As Rusty mentioned, we have made notable progress in this trial that is studying Cabira in combination with the anti PD-1 antibody OPDIVO. Recent highlights from the program can be found in Slide seven and the trial design can be found in Slide eight. Concurrently in the Phase 1b portion of the trial, evaluating the safety, initial efficacy and biomarker changes in multiple cohorts of patients receiving Cabira in combination with OPDIVO. Pre-designed 1b cohorts include, non-small cell lung cancer, squamous cell carcinoma of the head and neck, pancreatic cancer glioblastoma, renal cell carcinoma, and ovarian cancer. Should any of these show clinical activity, we can advance the development in that setting to the next phase independently of the rest of the trial. There are different rationales for each of these indications, in some settings such as non-small cell lung cancer, renal cell carcinoma in head and neck cancer OPDIVO has already obtained regulatory approval. These settings could represent relatively straight forward development paths In other settings there is high unmet net medical need and strong scientific rationale. Pancreatic cancer and ovarian cancer for example are reported to have high levels of tumor associated macrophages, the target for Cabira therapy. 2017 is an important year for Cabira and for this trial. We expect to complete Phase 1b enrolment in the second half of the year, some of the cohorts fully enrolling by the first half. We plan to work with BMS on the initial data release of clinical trial data in the second half of 2017. In under IO trial we are actively study Cabira in patients with the rare neoplastic joint disorder, PVNS. You can see this on slide nine. There is strong scientific rationale for Cabira as the monotherapy in PVNS, the disease that is driven by CSF-1R signalling. PVNS is characterised by local over expressed CSF-1 which recruits macrophages into the joints performing a non malignant tumor mass. It can be associated with a significant pain and debilitation and there are currently no proved therapies for this condition. Slide 10 illustrates our trial design. We are presently in the Phase 2 portion of the ongoing trial, in which we are evaluating response rate, pain and range of motion in approximately 30 PVNS patients with the diffused form of the disease. Similar to the IO program, 2017 will be important for the PVNF program. We expect to complete phase 2 enrolment in the first half of 2017. We also plan to seek regulatory agency guidance on the design of a pivotal trial. In addition, we have submitted an abstract for this study to ASCO for the June meeting. I’ll now turn to 144. Slide 11 shows an overview of the phase 1 trial in which we are studying 144 in gastric and bladder cancer. 144 is an antibody that specifically targets the FGFR2b splice variant, which is over expressed in some tumors. We think this specificity can avoid toxicity seen with less selective FGFR2 small molecule and antibody therapy. As shown in slide 12, we are currently in the expansion portion of the trial where we are dosing gastric and bladder cancer patients with 15 milligrams per kilogram of 144 every two weeks. There are three main aspects to our 144 program. First, we are executing on the current monotherapy trial in gastric and bladder cancer. Second, we are preparing to launch a monotherapy trial in Japan where the incidence of gastric cancer is high. Currently we planning combination studies including initiating a chemotherapy combination trial in 2017 to move 144 into earlier lines of therapy. We announced clinical data from our phase I trial at ASCO GI and at ASCO last year we submitted an abstract with updated 144 data to ASCO this year as well. Finally, I will conclude with a few remarks that FP-1039 and FGF ligand trap, this is shown in slide 13. FP-1039 is currently being combined with cisplatin and pemetrexed in the Phase 1b trial as first line therapy in patients with malignant pleural mesothelioma. In June 2016, GSK concluded trial recruitment with 25 patients enrolled at the 15 milligram per kilogram dose. GSK continues to dose and follow the remaining patients on this trial .We are trying to make decisions on future development of FP-1039 in mesothelioma after objective response rate, disease control rate progression free survival data mature. In addition we are factoring other considerations such as drug supply and manufacturing. We plan to submit updated clinical data to this year’s ESMO meeting in Spain. In summary, we are very excited by the significant progress in our clinical development effort across all of our trials and we look forward to providing future updates as data becomes available. I will now turn the call over to Marc to review our financials.

[Marc Belsky:]

Thank you, Bob. The full details of our financial results can be found in the press release issued this afternoon, as well as Slide 14 and 15. We have a strong balance sheet. Cash, cash equivalents and marketable securities totaled $421.7 million at December 31, 2016 compared to $517.5 million on December 31, 2015. Net loss for the fourth quarter of 2016 was $20.1 million or $0.73 per basic and diluted share. Full year 2016 net loss of $65.7 million or $2.44 per basic and diluted share. Recorded in the fourth quarter of 2015 we received and recorded its revenue of $350 million upfront payment under our Cabira collaboration with BMS. Colloboration and license revenue was $8.3 million for the fourth quarter of 2016 and $30.7 million for the full year 2016. Collaboration and license revenue was $363.3 million for the fourth quarter of 2015 and was $379.8 million for the full year 2015. R&D expenses totalled $29.1 million for the fourth quarter of 2016 and totalled $94.1 million for the full year 2016. This increase over the prior year was primarily related to advancing our Cabira program in immunocology in PVNS, our FPA144 program in the phase 1 monotherapy clinical and advancing internal immuno-oncology research and pre-clinical program. G&A expense totalled $10.5 million for the fourth quarter of 2016 and totalled $35.8 million for the full year 2016. This increase over the prior year was primarily due to increases in personal related expenses including stock based compensation. As you can see in our condensed statement of operation, we have a $31 million income tax benefit for 2016 because we are able to carry back our 2016 losses to the 2015 tax year. As a result we have maximized our ability to obtain a refund of income taxes paid in 2016 related to our 2015 taxable income. And looking ahead, we expect full year 2017 net cash used in operating activity to be less than $120 million. We estimate ending 2017 with approximately $300 million in cash, cash equivalents and marketable securities. I’ll now turn the call back to Rusty for closing remarks.

[Rusty Williams:]

Thanks Marc. In my opening remarks, I mentioned the great progress made in our clinical trials and I also talked about the considerable expansion of our pipeline. 2016 was also our most productive year in the discovery of new immuno-oncology targets and therapeutic candidates using our discovery platform. We undertook a bold and successful immune-oncology screening effort to fuel our future pipeline. First, we performed functional cell based screen of our entire library of 5700 extra cellular proteins, to find modulators of both Treg and T Effector cells. These screens are similar to the ones that allowed us to identify CSF1 receptor as the key regulator of macrophages which will add to our clinical Cabira program. Second, we conducted new in vivo screen of approximately 700 immune related extracellular proteins in three separate mouse tumor model looking for immune protein had a good target for shrinking tumors. In addition, we created what we believe to be the first map of binding interactions to immune cells with each other and with tumor cells. We did this by identifying the 700 cell surface protein that we thought were most likely to be regulators with immune cells and then we tested the binding of each of these 700 to each other. This nearly half a million of experiment and our platform made it possible for us to do this twice. Notably, we thought the known interaction such as PD1 with PDL-1 and PDL-2 giving us confidence that the new interactions we discovered are more likely to be – are most likely to be biologically important. This map for the immuno interactions helps us find new targets and enhances our interpretation of our other screens, the functional screens and in vivo screens. We expect that our discoveries will translate the multiple therapeutic protein campaigns. We maintain our goal of filing at least one IND for new therapeutic protein in each year for the foreseeable future. Finally, I’ll draw your attention to slide 16, which highlights our recent and anticipated milestone including our expected clinical data disclosures. I’m extremely pleased with our progress in both our clinical and preclinical programs and look forward to productive year. Finally before opening the call up for questions, I’d like to express my gratitude to our Five Prime employees as well as to the many patients and investigators involved at our clinical trial. And now, I’ll open it up for questions.

[Operator:]

[Operator Instructions] Our first question comes from the line of Kennen MacKay with Credit Suisse. Your line is open.

[Rusty Williams:]

Hi, Kennen.

[Slanix Alex.:]

Hi. This is Slanix Alex on for Kennen. Kennen, she could not make it. Thanks for taking the question. The first question on FPA008, as we look toward the data release in the second half, want to get a sense from you all in terms of what the efficacy bar might be for the combo and what sort of benefit you would be looking for to make that go or no go decision to move forward in a particular indication?

[Rusty Williams:]

Yes. So, thanks for the question, Mike [ph]. Let me give up a high level answer to that. Then I’ll turn it over to Bob. The trial is focused on multiple tumor settings, and this was delivered to cast a broad net, to test out the number of different hypothesis. And broadly speaking, we wanted to test the hypothesis that in some tumor settings that we can enhance the activity of our OPDIVO where there is already activity. And in other settings we specifically went into them because checkpoint inhibitors haven't had high response rate. And so each cohort can reviewed or each setting can be reviewed separately with respect to the bar. We don't have prescribed bars that will tell us -- criteria that will tell us, yes, move forward or no, don't go. But it will evaluate each setting separately. Bob, you want to add.

[Robert Sikorski:]

Yes, roughly. There’s no one-size-fits-all here, that’s I think the theme, because you have settings such as, let’s take two bookings may be a lung cancer that PD-1 naïve. We have that that cohort there and the response rate across all of the PD-1, PD-L1 inhibitors let’s say it’s around 20%. You need to be that also if you look then at the PD-L1 resistant lung cancer where arguably there should be any responses. What’s clinically meaningful for those patients is arguably lower. So I think that kind of bookings are thinking reasonably, you know you look at something likely over the last 12 months, pancreatic cancer, very high unmet medical needs, but there are different settings and we look at them completely differently and I think patients do as well.

[Slanix Alex.:]

Got it. Understood. Thanks. And just a quick question on 144 as well, given that you guys are now looking towards for guidance on a path forward in combination with chemotherapy, I just wanted to get your thoughts on what the priorities are in terms of that being – perhaps the main priority in terms of pivotal development or the mono, or the potential for a monotherapy and how that kind of displays?

[Rusty Williams:]

Yes. The key thing we're looking for in terms of the setting for pivotal trial is how we can best benefit patient and how we can get the most out of our drug, FPA144. And that’s rationale for going into chemo combination, moving to early lines therapy so that you can really -- gastric cancer are terrible cancer, we really like to catch these patients early. We have that preclinical data that’s combination with chemo at least additive but not synergistic, and so that the rationale for going into the early lines of therapy -- early lines of therapy in combination with chemo. We have more patients, we can catch patients earlier in their disease. We have more to offer for patients for that stuff of thinking. Bob, you want to. Go ahead, yes, go ahead.

[Slanix Alex.:]

And just to follow-up on, just one real quick, as it relates bladder cancer just wanted to get a sense from you, how you might position it given that now you're seeing a number of new agents enter the space, especially you have the ADCs from Seattle Genetics who have shown some very promising data in the settings. So I just want to understand how you might see 144 fitting into the treatment paradigm there?

[Robert Sikorski:]

Yes. This is Bob. I can take that question. One of the preclinical pieces of data that we have shows that the 144 draws in NK cells tumors, it also up regulates PD-L1 as well, causes the inflamed tumor essentially preclinical model. But that would imply that combining 144 with the PD-1 inhibitor may augment that activity, that just logic from the preclinical data. And if you look in bladder cancer, I mean, clearly you can see the influx of PD-1 inhibitors, the recent approval of the OPDIVO in this setting. So that seems like clinically a nice combination. Whether monotherapy is enough we don't know, we’re generating that data right now. We have one patient who has a complete response and as Rusty pointed out that patient is still continues on the drug. Encouraging, but what we do want to do is give the maximum clinical benefits to these patients, whether that monotherapy or combination they're both sort of in player.

[Slanix Alex.:]

Great. Thanks for taking the questions and congrats for all the progress.

[Robert Sikorski:]

Thank you.

[Operator:]

Thank you. Our next question comes from the line of Jim Birchenough with Wells Fargo. Your line is open.

[Unidentified Analyst:]

Good afternoon. It’s Nick [ph] in for Jim. And apologies for you and up turning the call late.

[Robert Sikorski:]

No problem.

[Unidentified Analyst:]

Can I just go over the registration plan, Rusty for 144? Is that, or you thinking a monotherapy. I heard just mentioned to the previous questions about chemotherapy combination, but I'm assuming that would be more exploratory?

[Rusty Williams:]

Well, we are interacting with the FDA this year and discussing pivotal trials and what that would look like and what the path would be. We – as I was mentioning a few minutes ago we think that we have the most offer to patient-size combining with chemotherapy in early-lines of therapy, and we’ll be able to have a broader patient population to address, and you also potentially have patients we can treat longer. And so we think that going and we have preclinical data guiding us towards this combination. So that seems to be the best path for a pivotal trial for us, but we will be talking to FDA. We have interaction with them and we’re just talking with them about this.

[Unidentified Analyst:]

So, would that be as a second line trial you think or you would try and discuss right upfront?

[Rusty Williams:]

We haven’ given specific guidance on this, but we are interested in getting through as early as we can get in the treatment paradigm.

[Unidentified Analyst:]

Okay. Good luck.

[Robert Sikorski:]

Yes. We saw like certainly. I can answer that. There’s obviously two lines of therapy, here is a different chemotherapies and the endpoints maybe slightly different. So, it’s an easy question to answer without some discussion with regulatory agencies. But again I think if you look at these patients who were late-line therapy, that they're incredibly sick. They progressed very quickly. We’ve shown that data. Whether we can provide the best benefit for them as a monotherapy or these combinations is where we are now.

[Unidentified Analyst:]

Okay. And then on PVNS, is your plan to sort of follow [Indiscernible] with a six-month placebo-controlled trial or do you think you have a different design that would be accessible to the agency?

[Robert Sikorski:]

Yes. This is Bob. That seems reasonable. You know our current trial that we have now the Phase 2, we treat for six months. That data as we've noted will be presented this year. So, we want to build on that. I think its reasonable best case. Again we haven’t handy discussions with the FDA. We are in the processes advancing these. So, we would look forward to having a pivotal trial that may look similar.

[Unidentified Analyst:]

Okay. And then maybe just last one 1039, are we awaiting mature data because GSK now actually look to the data in long time or is there a particular threshold and a particular event rate that you’re looking forward which will trigger an analysis. It just seems like this trial is going on long time which perhaps could be interpret [ph] is being positive?

[Rusty Williams:]

Well, so I can answer that question clearly, and the reason we’re waiting for data because patients are still on drug, some patients. And it has taken a long time, but we have GSK enrol 25 patient and its single-line [ph] trials combination with chemo, but the fact that patient is still on drug is encourage certainly for those patients and so we’ll give an update towards some venue like ESMO towards second half of the year. So GSK hasn’t been withholding any information from us. They’ve been forthcoming for the most.

[Unidentified Analyst:]

And should you consider that this would be an internal development candidate or these data were post of view or looking to replace GSK?

[Robert Sikorski:]

We’ll have to look at the data. We have to treat these patients who are still on. We’ll have to look at the data. We’ll have to interpret them in the context of Standard of Care. There still a big that on that need for mesothelioma. And then we will also factor in manufacturing drug material considerations, because GSK didn't manufacture material for the next phase of trials, so we’re factoring that into. And so that options that will have kind of obvious we can either have it as an internal candidates and pursue development ourselves. We can partner it again or we can stop the program. So we’ll gladly update you when we have that information. We don't have we enough data because we want to get these patients continued on until they come up with trial.

[Unidentified Analyst:]

Okay, great. Well, thank you very much and look forward to an exciting year. Thanks.

[Robert Sikorski:]

Yes. Thank you.

[Operator:]

Thank you. Our next question comes from the line of Robyn Karnauskas with Citigroup. Your line is open.

[Unidentified Analyst:]

Great. Thanks. This is Mohit [ph] filling in for Robyn.

[Rusty Williams:]

Hi, Mohit.

[Unidentified Analyst:]

Thanks for taking my questions. So, I have like one simple question on the timing. So you mentioned that there’s a possibility that, I mean, some of the arms and pivotal trial could be enrolled in first half. So is there a possibility that you could move into the – move one of those arms into the next phase of the trial, as you can move them independently before even releasing the data in the second half. Is there a possibility there?

[Rusty Williams:]

Let’s keep in mind that we started this when they, all the cohorts and when they were initiated in October. And so it’s key to look at response rate and durability of responses and depth of responses. So, it’s certainly is possible that a cohort could be move forward without the other cohort, but we’re not giving any guidance on that and we’re still pretty early in the process. And so – but to way this, to way the – our trial is structured, in the way our arrangement with BMS is structured there, it is structure to allow a cohort to head to the next phase before completing all the cohort.

[Unidentified Analyst:]

Got it. And one more follow-up on…

[Robert Sikorski:]

Yes. I was going to add to that, and also Bristol-Myers has the ability to do other clinical development in parallel. So the options here at events are cohorts as you point out, but the options also to launch other trials as well.

[Unidentified Analyst:]

Got it. And then another question and probably bigger picture question because one part is a long time in IO [ph] space and then we have seen a large in last few months. So I mean, like in the new environment where after OPDIVO data, how do you feel about your positioning, and as well as like we have seen some more IDO data as well. So how do you feel about could be their positioning at this point?

[Rusty Williams:]

Let me be sure I understand your question. I think there are two parts to it. So as one part how do we feel about the Cabira being combined with OPDIVO?

[Unidentified Analyst:]

Yes.

[Rusty Williams:]

As oppose to other checkpoint inhibitors. Is that part of the question?

[Unidentified Analyst:]

Yes. That is part of the question and as well as like in the combination phase data there are IDOs and other development, other data we have seen, so how do you think about those competitive position?

[Rusty Williams:]

Okay. Let me start and then I’ll turn over to Bob. So just in terms of our combination with OPDIVO, we still like to pass that the combination and we think that OPDIVO is a very good choice for combination studies. We are – of course, we’re aware of that lung cancer dynamic for OPDIVO and Keytruda et cetera, but we feel that Cabira in our mind is just as active drug as Keytruda is. And so we’re happy with that combination and so we’re happy moving forward with it. With respect to other agents and combination, here as you point out, ton of trials going on with various agents being combine. We think that they’ll rational – our particular combination is very compelling, very strong. I like the concept of removing cells or pathways that are inhibitory to the immune system. And so both OPDIVO and Cabira do that. They remove – they’re not sort of T-cell activators but they remove these inhibitory effects in the tumor microenvironment, and that combination I think is compelling. There are other combinations that have valid premise as well, but I think that mechanistically this combination is different from some of the other combination for example, T-cell agonist. So without going to every agent in the field that’s our broad interpretation of it. We think that this is a compelling rationale.

[Unidentified Analyst:]

Great. Thank you.

[Operator:]

Thank you. [Operator Instructions] Our next question comes from the line of Tony Butler with Guggenheim. Your line is open.

[Tony Butler:]

Hi. Thanks very much. I have three questions and I’ll just go ahead and give you those if that’s okay.

[Rusty Williams:]

Yes, Tony. Go ahead.

[Tony Butler:]

Thanks, Rusty. So in 008 there is a cohort that Bob alluded to in patient in non-small cell lung cancer who had been treated previously with anti-PD-1 or anti-PD-L1 and who had become refractory. And so the question is do you have data, I guess with the -- it supports the utility of 008 and a setting where you have that type of resistance present. So that’s number one. Second question is around 144 and the various types of IHC on partitioning high low et cetera, and I guess the question really is that, would you do that, would you need to do that if in fact you actually move forward in chemo +144. And then thirdly, in your CMA 38 models OPDIVO [ph] trial or what happens if you put 154 008 and an anti-PD-1 together, a triple if you will in that CD-38 and the CMA 38 models, do you get added benefit or another word there’s synergy with the three or does it really matter? Thanks for the time and sorry for the long questions.

[Rusty Williams:]

Thanks Tony. Good question. So just with respect to the first question, the refractory non-small cell lung cancer, data that support treatment. Here the main thought there is that it seems possible that the reason for the failure of checkpoint inhibitors in some patients is because their TAM is present tumor associated macrophage, that are immuno-suppressive and since we saw real synergy and pre-clinical models, there is a good rationale for approaching those patients who are refractory. And so that’s the main thinking behind that. Not only for lung cancer, but also we had two cohorts that are sort of basket cohorts, that are in parallel with this trial where we can put patients who are refractory to checkpoint inhibitors with other tumor type too. And so we think that concept extends beyond this lung cancer melanoma for example, renal. With respect to the second question on 144 and a IC segmentation, I’ll let Bob answer that.

[Robert Sikorski:]

Yes, hi Tony I think your question was on the cut offs. Currently we -- we have cut offs that is moderate and low the question is whether you would add high -- chemotherapy or those low [Indiscernible] we don’t know that yet.

[Unidentified Company Representative:]

[Indiscernible] without selection at all.

[Robert Sikorski:]

Yes, we have some data, you know it’s been generated in South Korea and a large data set that the metastasis have higher over expression of FGFR2b, and that may lead in that direction. Also we are interested in detecting patients by blood who may be easier to find, it’s forward looking and I think that’s an attractive way to get patients. You know I think Rusty alluded to the fact that the earlier lines of patients have a lot of advantages. One, they are more of them; you know these patients get sick and they progress faster. So if you start treating them late line therapy there is fewer [Indiscernible] sicker and you know recent detection methods may allow us to pick them up other ways than I had seen.

[Tony Butler:]

Okay. And third question about MC38 Model, maybe we’ll try a triple whammy. You know in our experiment if we combine 154 with anti PD-1 in that model, basically – the model. So we would have to kind of pull around with the doses to get that tripled. It’s not a bad idea though to look at triple and in some context we are considering that and we haven’t disclosed the details on that, but there especially if we have drugs that are not [Indiscernible] they have a good appear to have a good safety profile. Triple is not out of the question, so Bob you want to ask.

[Robert Sikorski:]

Yes, you know if you look at our CD80 molecule which has nearly three different targets in one molecule, certainly like combinations. We like that one, you know three different pathways, two of which are proven the drug targets, approved agents and [Indiscernible] and in the PD1 pathway we add to that CD28 agonism so combinations or maybe combinations in one molecule.

[Tony Butler:]

It’s really helpful. 155 looks great.

[Robert Sikorski:]

It is. [Indiscernible] Well I guess we are done with the questions. So I’d like to thank each of you for joining us today and for your interest in and support of Five Prime and we look forward to updating you on future calls. Thank you.

[Operator:]

Ladies and gentlemen, thank you for participating in today’s conference. This does conclude the program and you may all disconnect. Everyone have a wonderful day.