Five Prime Therapeutics Inc
Q1 2016 Earnings Call Transcript

Published: 7 May 2016

[Operator:]

Good day, ladies and gentlemen, and welcome to the Five Prime Therapeutics First Quarter 2016 Quarterly Earnings Call. As a reminder this conference may be recorded. I would like to introduce your host for today’s conference, Ms. Heather Rowe, Senior Director of Investor Relations and Corporate Communications. Ma’am, please go ahead.

[Heather Rowe:]

Good afternoon, and thank you for joining us. On behalf of Five Prime, I’d like to welcome everyone as we discuss financial and operational results for the first quarter of 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 & Presentations. Joining me today are Dr. Rusty Williams, Chief Executive Officer; Mr. Aron Knickerbocker, Chief Business Officer; Dr. Robert Sikorski, Senior Vice President, Global Clinical Development; 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. With that, I will now turn the call over to Rusty.

[Rusty Williams:]

Thanks, Heather. Good afternoon, and thank you for joining us today as we discuss our first quarter results. I’m pleased to share our progress in advancing our clinical and our preclinical programs. If you are viewing the accompanying slides, an overview of our programs can be seen on the third slide. First, I’d like to talk you about the progress with FPA008, our anti-CSF-1 receptor antibody that blocks immunosuppressive tumor-associated macrophages. We and our partner BMS are studying 008 in combination with the PD-1 checkpoint inhibitor Opdivo in a variety of tumors. We believe that this combination may have synergistic therapeutic effects in treating cancer. We initiated a Phase 1a/1b clinical trial in September 2015 to evaluate this immunotherapy combination, and Five Prime is continuing to run the trial, that’s important to us, and it’s projected to include about 280 patients. Recall that we designed the trial to be modular and efficient, we want to be able to explore a variety of tumor settings and move quickly if we see activity in any one of them. We recently made favorable amendments to the trial in response to developments in the field, and Bob Sikorski will provide more specifics in a minute. Before he does that I’d like to briefly cover some of the highlights of the changes now. First, we amended the Phase 1b protocol to change some of the tumor types, as Bob will describe. This modification is in response to the rapidly evolving immuno-oncology landscape, and it does reflect our collaborative decision-making process with BMS. Importantly, the Phase 1b remains on track to begin during the second half of this year. In addition, we’re adding more patients to the current Phase 1a portion to study the highest dose of 008 as monotherapy and in combination with Opdivo in patients with certain types of tumors beyond those addressed in the 1b cohorts. These new Phase 1a cohorts will add to the overall dataset and will be done in parallel with the Phase 1b portion of the trial. We and BMS are pleased with the progress, we know that this is a competitive field and we benefit from this flexible trial design, and it allows us to move rapidly and explore options that we believe are clinically important. Now, moving beyond immuno-oncology application of 008, we recently began screening patients for the Phase 2 portion of our clinical trial in the orphan disease pigmented villonodular synovitis or PVNS. Remember, this is a tumor driven by the CSF1 pathway. We expect to dose the first patient in Phase 2 soon. Now, I’d like to turn to FPA144. Remember, this is our isoform-selective antibody in development as a targeted therapy for tumors that over-express FGFR2b. 144 has been engineered to increase direct tumor cell killing by recruiting NK cells. At the April AACR Annual Meeting in New Orleans, we presented pre-clinical data showing that 144 indeed has important immunostimulatory effects on tumors, and this drug appears to be acting as a targeted immunotherapy. At the ASCO GI Annual Meeting in January, we announced initial clinical data demonstrating the safety and tolerability of 144, there were no dose-limiting toxicities and no maximum tolerated dose was reached. Importantly, we’re encouraged by the early evidence of anti-tumor activity in the initial target population and this is patients with gastric cancer, this tumor has expressed high levels of FGFR2b protein. We’re also pleased to see an unexpected radiographic response in a bladder cancer patient, whose primary tumor expressed FGFR2b, this suggests potential activity of 144 in tumors beyond FGFR2 gene-amplified gastric cancer. So, based on these clinical findings, we recently amended the 144 trial protocol to include additional tumor settings, which Bob will go into in greater detail. We look forward to providing updates on these data in an oral presentation at ASCO in June related to 144. And if the maturing data continue to be positive, we plan to pursue accelerated approval for 144 as monotherapy in patients, who have refractory gastric cancer, over-expressing FGFR2b. Importantly, with more than $480 million in cash, we’re well positioned to execute on our strategic objectives and advance our immuno-oncology clinical and pre-clinical programs. And with that, I’d like to turn the call over to Bob to give more detailed updates on the clinical programs.

[Robert Sikorski:]

Thank you, Rusty. First, I want to cover the FPA008 IO clinical trial in cancer patients, which I’ll refer to as the IO study. We’ve made significant progress in the study that is examining the therapeutic potential of FPA008, which I’ll call 008 for short in the combination with the anti-PD-1 antibody Opdivo from BMS. Recent highlights from the 008 program can be found on slide 4. As Rusty noted the immuno-oncology field has evolved since we initially designed this trial. With that in mind in collaboration with BMS, we’ve made some strategic changes to better exploit the opportunities for this exciting combination. First, we removed melanoma in colorectal cancer from the defined Phase 1b cohorts. We have, however, added a new mechanism in the trial that can address these patients which I’ll discuss shortly. Second, we added new cohorts to the Phase 1b portion to include patients with renal cancer and ovarian cancer. These are two examples from the evolving IO field. Renal cancer now represents an attractive potential regulatory path. 008 is being paired with Opdivo in the setting where Opdivo now has a label. Despite these advances for cancer patients, there still remains a significant unmet need in both of these settings that could be served by the 008 plus Opdivo combination. Related to the topic of potential registration paths, note that Opdivo has recently received breakthrough designation by the FDA in advanced squamous cell head and neck cancer. This reduces the regulatory risk for advancing a 008-Opdivo combination, as we believe Opdivo is likely to be approved soon in this setting. As Rusty alluded to, the Phase 1b portion of the IO study will now include the following cancer types

[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 16 and 17. As Rusty said, we have a strong balance sheet. Our cash, cash equivalents, and marketable securities totaled $482 million on March 31, 2016. Net loss for the first quarter of 2016 was $13 million or $0.49 per basic and diluted share. Collaboration revenue for the first quarter of 2016 was $6.5 million, up from $4.3 million in the first quarter of 2015. This was primarily due to revenue recognized under the FPA008 license and collaboration agreement with BMS entered into in October 2015. Recall, BMS is reimbursing us for the immuno-oncology trial expenses. Research and development expenses for the first quarter of 2016 were $18.3 million compared to $11.2 million in the first quarter of 2015. This increase was primarily related to advancing the FPA144 clinical trial, preclinical, and immuno-oncology research program. General and administrative expenses for the first quarter of 2016 were $8.6 million compared to $4.2 million in the first quarter of 2015. This increase was primarily due to stock-based compensation expenses. Looking ahead, we continue to expect full-year 2016 net cash use in operating activities to be less than $120 million, comprising less than $90 million used in operations and less than $30 million used for tax payments. We estimate ending 2016 with approximately $400 million in cash, cash equivalents, and marketable securities. I’ll now turn the call back to Rusty for closing remarks.

[Rusty Williams:]

Thanks Marc. We at Five Prime are working to favorably change the immune landscape of tumors. As a reminder, we have a collection of over 5,700 extracellular and cell service proteins in a library. This includes 700 immune proteins, we call this the immunome. These are the key regulators of immune cells. We’re using this platform along with our screening capability to find new targets and identify new ways and new pathways to manipulate immune cells in the tumor microenvironment. You can see a representation of this on slide 18. So, we already have a macrophage inhibitor with FPA008. We’ve an NK cell recruiter with FPA144 and a T-cell agonist with our GITR agonist antibody, and we’re working hard this year on additional targets for CD8 T cells and T regulatory cells. We plan to study myeloid-derived suppressor cells soon thereafter. One of the most exciting things going on as we have – we are conducting an immunome by immunome screen. In this screen, we determine the interactions of the 700 immunome proteins with each other. So, this should provide a roadmap of the immune regulators in the immune system, and this would be an advantage that others don’t have, and we hope that this will help us make antibodies and new therapeutics in a way never before possible. We’re also screening the 700 immunome proteins as monotherapy and in combinations with PD-1 inhibitors using our proprietary in vivo screening platform. We think that this process will help drive our future immuno-oncology pipeline. In addition, we’re advancing multiple preclinical programs and we expect to have two candidates entering IND-enabling studies by the end of this year. One is potentially our GITR agonist antibody and the other is a molecule that has a mechanism of action that will be new to the clinic. We anticipate filing one IND by the end of 2017 and to have preclinical assets sufficient to keep the pace of one IND per year in the foreseeable future. I’ll draw your attention to slide 19 and this highlights our upcoming data, announcements, and milestones. In summary, we’ve made solid progress in our programs this quarter. We progressed our clinical programs adapting and optimizing the trials and advancing our early-stage programs to build our future immuno-oncology pipeline. We believe that our differentiated pipeline, our unique platform, and our strong balance sheet all position us well to achieve success and to create shareholder value and offer innovative therapies to patients with serious diseases. And finally before opening the call up for questions, I want to express my appreciation to our employees as well as to many patients, investigators, and KOLs taking part in our clinical trials. So, I’ll now open it up for questions.

[Operator:]

Thank you. [Operator Instructions] Michael Schmidt with Leerink Partners. Your line is open, please go ahead.

[Michael Schmidt:]

Hi. Thanks for taking my questions. Rusty, I had one on the changes in the CSF-1R antibody, on FPA008 extension cohorts in Phase 1b. I guess to what degree – it sounds like those changes were driven by predominated by strategic considerations. To what degree does the biology guide your selection for these tumor types?

[Rusty Williams:]

Yes. Hi, Michael. You got it right. The changes were made according to the strategic considerations and evolving landscape. And so, we’ve changed those cohorts to adapt and to give us the best opportunities going forward where we think we’re most likely to see signals and have a good market presence. And we also added the 1a cohort, so that we had additional opportunities, gives us more shots on goal and in a way that we can enroll patients rapidly in the areas of greatest interest to us. So, it’s all strategic changes.

[Michael Schmidt:]

I guess how well understood is the biology of CSF-1R and are some tumors in a more rational based on the science or more have a high likelihood of success in others?

[Rusty Williams:]

Well, you can look at – the short answer to that question is we don’t know yet, but there are several ways to look at this issue, the role of CSF-1R in cancer. Our focus is on this immunosuppressive tumor-associated macrophages that are predominantly M2 tumors that we are studying. All other tumors in our study are tumors that have been reported to have tumor-associated macrophages. So, that’s kind of a starting point. We are doing pre-treatment and post-treatment biopsies as Bob indicated, and in those biopsies, we’re doing a lot of measurements on the cell types, on the type of immune cells in the tumor, on the type of tumor-associated macrophages, so that we can assess going forward the likelihood of responses. So, those data are coming through now and will be continuing to come to us and we’re managing that process and looking at those data. So, we’ll be able to better answer your question about the role of CSF-1R in different tumor settings as we move forward in the trial. One other point of consideration is, we are interested in settings in which there are failures, patients who breakthrough checkpoint inhibitor therapy. That’s an important consideration for us. And in that case, we’re testing FPA008 essentially, as an add-on or a monotherapy and so, those are important populations for us as well in areas where we might in the future be able to see responses we attribute to 008.

[Michael Schmidt:]

Yes. I saw Merck has an ASCO abstract coming up, looking at the combination with the Plexxikon TKI. Would you view – could that validate the targets for [indiscernible]

[Rusty Williams:]

I think any data combining a PD-1 pathway blocker with the CSF-1R pathway blocker would be of interest to all of us working with this kind of combination. And so, there could potentially be some read-throughs or information that would apply to us. I will point out though that especially if you compare small molecules to antibodies in the CSF-1R space, there are key differences. The small molecules are less [precise], they’re more pleiotropic, they hit – at least the Plexxikon TKI for CSF-1R blocks other kinases other than CSF-1R including c-kit for example. And so, has the intended side effects and those limitations. There are other reasons to think that antibodies – they work differently from small molecule TKI. So, as a first approximation, there could be some data from their studies that apply to us, but I think it’s not a one-to-one correspondence.

[Michael Schmidt:]

Great. Thank you very much.

[Rusty Williams:]

You’re welcome.

[Operator:]

Thank you. Our next question comes from the line Kennen MacKay with Credit Suisse. Your line is open, please go ahead.

[Slanix Alex:]

Hi. Good afternoon. This is Slanix Alex calling in for Kennen. Thanks for taking the questions. We just had two quick questions on FPA144. Just quickly want to get a sense of how many patients’ worth of data we can expect from the presentation at ASCO?

[Rusty Williams:]

We haven’t given guidance yet. I’ll let Bob make comment on the ASCO presentation, what the focus is at.

[Robert Sikorski:]

Yes. Great. Thanks for the question. That ASCO presentation will now be an oral, it was elevated as I noted to an oral presentation. What we can – we haven’t given out specific guidance as to what patients, remember this is a data snapshot that we do with an ongoing trial. Suffice it to say we’ll update the dataset that you saw at GI ASCO. We were very interested in what happens to those patients, you can expect that; whether some additional patients will be added will depend on the data snapshot, and I think that’s all. It’s an active study and again, it’s going to be an oral presentation. So, we’re looking forward to that.

[Slanix Alex:]

Sure, sure. Thank you. And just a follow-up question on 144. Could you maybe walk us through the potential registrational pathway for the compound and what your interactions with the FDA have been like, and what’s slated in that sense?

[Robert Sikorski:]

Good, good. Thanks. We have – the trial now would be essentially a first in human trial that’s expanded. Let me cover some of the changes we made to the trial first, as that may be instructive. So, currently the primary focus of this trial is to move forward in a selected – biomarker selected patient population, we believe is monotherapy, and we’re getting activity there. We’ve talked to KOLs. We’ve a reasonable safety profile. Again, these are small numbers. So, I’ve to couch the fact that we have reasonable activity and safety on small numbers, but we want to advance that as aggressively as possible. We’ve also added new cohorts to this trial, and if you look in the slide 13, you’ll see that we really want to see how broad perhaps even in gastric cancer this drug can be applied. We have a very high bar in the current trial. The activity we’ve seen are in IHC3+, we call that IHC high population, but we like to look in medium and low, and we’ve added those cohorts to the trial with that in mind, using our proprietary assay to segment the patients along those three populations. We also were encouraged surprisingly so to find a bladder cancer patient – two things we learned from that bladder cancer patient – one that the patient is outside of gastric cancer. That opened our eyes to other tumor settings, but to the expression of FGFR2b is relatively moderate, let’s just say. So, it’s not as high certainly as we’ve seen in the cohort where we had activity in gastric. And that thinking really did influence to some degree asking or maybe we could broaden the gastric cancer as well. So, we added a new cohort too, we’ll call it a basket cohort, because we are looking for patients who fit a proprietary diagnostic IHC assay cutoff, but they can be in different tumor types. Bladder cancer obviously makes sense, because we have activity there, but it’s not exclusively limited to bladder cancer. Now, going back to registration, so now you have a feel for the trial – the trial is trying to look at other broadening aspects of the drug. We want to focus on getting a dataset of selected patients to particularly the FDA soon, and asking them for an accelerated path forward and working with them collaboratively. This we think, and obviously we’re driving this that a monotherapy setting in refractory patients is attractive. This drug has monotherapy activity. If you look at Cyramza for instance as a benchmark, there’s more monotherapy activity we’ve seen in small patients who have been on Cyramza. So, it makes sense whether that can be – whether that need to be a randomized trial or whether we can go ahead with a single-arm trial. Again, that’s a negotiation with the agency, we’d love to push for the most accelerated path though. I think that’s all I can offer.

[Slanix Alex:]

Great. No. Thank you. That’s perfect. And just one last question now pivoting to the CSF-1R antibody. We haven’t really seen a significant monotherapy data from this class to date, and if you look at Amgen CSF-1R, it didn’t show any responses in their Phase 1 data. Do you think this is something that’s drug specific or more of a class effect and what kind of expectation do you have for single-agent activity from FPA008 potential addition of the cohort as a single agent?

[Robert Sikorski:]

Yes. This is Bob. I’ll take that. We can start with the Amgen data, if you look at that dataset, they only – let’s just take melanoma, they only treated one patient with melanoma. So, the amount that you can extrapolate on tumor types specificity in monotherapy is limited, let’s just say that, and certainly they didn’t have PD-L1 resistant patients in that setting. So, we’ve made changes to the trial. Let’s just go over maybe the 1a changes that we’ve made, so we’re clear here. We think that once we get to the maximal dose of monotherapy and the maximal dose in combination, we want to keep going. We want to keep expanding those patient exposures at those levels in two tracks, we’ve shown that on slide 5, I think that’s a good reference point. So, we will be looking in monotherapy at the highest dose of FPA008, as well as a combination in patient populations that are not represented in the 1b. And I think we’ll address maybe some of those questions, the jury is out on whether monotherapy can move forward. We are not sure that’s actually accurate, and we’re willing to put a few more patients to explore, we’re not over promising here, we’re just exploring further. We learned a lot about the safety, but we’re looking at patient populations, perhaps PD-L1 resistant melanoma, now that you have the nivolumab approved in renal cell cancer, you have approved in melanoma, you – they have an encouraging data as I pointed out in head and neck cancer, really phenomenal, very likely that will be approved there. And Hodgkin’s disease, which is under review now. So, you have a lot of new settings, a lot of new PD-L1 resistant settings that represent new biology for either the combination or the monotherapy.

[Rusty Williams:]

Yes. So, the short answer again is, we don’t think that the monotherapy has been given enough chance to succeed, because the settings now have evolved, and there is more opportunity, and the Amgen trial is what it is. It wasn’t focused on specific tumor types. So, we are not sure, but we think that there still is a possibility for monotherapy, we’ll find out.

[Slanix Alex:]

Okay. Great, thanks for taking the questions and I look forward to seeing the data at ASCO.

[Rober Sikorski:]

Thank you.

[Operator:]

Thank you. And our next question comes from line of Eun Yang with Jefferies. Your line is open, please go ahead.

[Eun Yang:]

Thank you very much. Question on 008, so 008 obviously inhibits tumor-associated macrophages, but macrophages in general depend on CSF1 for differentiation of survivor. So, how do you balance between inhibiting TAMs and preserving macrophages needed for antigen presentation?

[Rusty Williams:]

Hi Eun. Thanks for that question. It’s a – some of this is just empirical and certainly in the preclinical models. The observations that we and other groups have made is that the CSF1 receptor inhibitors appear to block the M2 macrophages more than they block the M1 macrophages. And so the net effect in the tumor model as you get a shift in the ratio of M2 to M1, meaning you have that ratio was smaller. So, you still have some M1 cells, but the M2 cells are greatly inhibited. And the bottom line is that you get this synergistic effect in reducing tumor growth. So, I think there is enough evidence that there are M1 macrophages still remaining in the tumor. We assume that those are the ones that would be involved in processing antigen, but there are other antigen presenting cells still in the tumor as well. So, as long as we are in settings where they are M2 macrophages and those are the ones that are blocking, we think that this was a good approach.

[Eun Yang:]

Okay.

[Rusty Williams:]

Bob has some other comments.

[Robert Sikorski:]

Hey, thanks for the good question. Let me add a little bit to that. I think your question was aimed more, although I hear macrophages and I agree with Rusty was saying the subset of macrophages M1 are still going to be preserved likely, but also dendritic cells to different lineage. They are not going to be driven by the same CSF-1R signaling and we don’t think were affecting that. Third, if you look – I’ll just give you a piece of data from our pre-clinical findings. When we treated monkeys with the highest dose of FPA008, we looked after – for macrophages throughout these monkeys, and let’s take the liver for instance, you can still find Kupffer cells, maybe 50% depleted, but not 100%. The study – examples like that would tell you there are subsets of macrophages, and there are subsets of the antigen presenting cells that are not going to be depleted.

[Eun Yang:]

Okay. That helps. I just wanted to make sure that I heard you correctly, so 008 and PVNS, have you selected the optimal dose to move into Phase 2?

[Robert Sikorski:]

Yes. Thanks Eun. Yeah, we’ve obviously initiated Phase 2. So, we’re comfortable – we have a dose that’s active and represents the safety profile we want to move forward in Phase 2.

[Eun Yang:]

Are you disclosing the dose?

[Robert Sikorski:]

No. We haven’t, we’ll disclose it in a publication at some point, but our policy to move for a scientific publication for those kind of details.

[Eun Yang:]

Sure. Thank you very much.

[Robert Sikorski:]

Thank you.

[Rusty Williams:]

You’re welcome.

[Operator:]

Thank you. [Operator Instructions] Our next question comes from the line of Christopher Marai with Oppenheimer. Your line is open, please go ahead.

[Christopher Marai:]

Hi. Good afternoon. Thanks for taking the questions. Just really quickly on 008, I was wondering if you could help us understand maybe some of the decisions to look at different indications, particularly in light of maybe patient selection. I was wondering if you have any data that would support utilization of this product in some patients, but not others, and if heterogeneity of a patient’s tumor microenvironment might impact efficacy, and how you might be able to control for that? Thanks.

[Rusty Williams:]

Thanks, Chris. Let me give a first snapshot of this, and then I’ll let Bob add any that he wants to. First of all, with respect to heterogeneity, in terms of histology, that’s what we’re looking at now. So, we’re getting a lot of data pre-treatment and post-treatment, and we’re not prepared to answer that question yet, but we should have a lot more insight in that in the coming months. And so, with respect to a patient selection otherwise, we haven’t disclosed data yet. And we’re not ready to disclose any data on whether we favor one kind of tumor over another in terms of responses or that kind of thing. So, more to come on that and we’ll gladly share this in the future in collaboration with BMS. Bob, do you have any more to say?

[Robert Sikorski:]

Yes, I could just add strategically how we’re thinking. The patient selection is a combination of two things. Certainly, the science and the biology, but also the tractability of developing a drug going forward, and what we’ve tried to do is, use the patients in this trial very wisely across those two dimensions. So, what we see in there, I think the mix of patients, and I think others have. If you look across the different studies, people are thinking along similar lines. Here, we added, for instance, renal patients to our study for both of those reasons. There’s a biology, but there is really an important new regulatory path that didn’t exist when we started the trial. So, we want to take advantage of that and I think PD-L1 resistant patients, for instance – let’s follow those – they are increasingly going to be available for clinical trials that may never existed before, and what the biology in those are, is really an evolving field. But we want to capture those kinds of patients in our trial and explore them.

[Christopher Marai:]

Okay, and so, is there any work that you’ve done or your partner has done beyond sort of patient identification, biomarkers, anything along those lines?. And then just remind me if you’re tracking any other potential biomarkers while you are dosing patients? Thanks.

[Robert Sikorski:]

We are tracking lot of biomarkers to measure most of the immune cell types you could imagine being in the tumor. And so, it’s a multi-parameter, it’s the chemistry as well as some RNA measurement. So, we have – we’ll know a lot more when we get the aggregate data from this trial. So, we have a lot of things that we’re testing, but again we’re just – we’re not in a position right now to disclose that. We’re still collecting a lot of – we have a lot of information to get.

[Rusty Williams:]

So, we should be able to tell ourselves and you in the future for the different tumor types what the immune landscape is of the tumor, and how that landscape changes with therapy.

[Christopher Marai:]

Okay and then when would we expect to get an update like that, I assume at some scientific venue. Thanks.

[Rusty Williams:]

Yes of course, we would love to share data when they’re available, and at the earliest possible time. We work with our partner, BMS. And we’ve acknowledged with BMS that we would like to share data at the appropriate time. We have also acknowledged with them that some data may be more material to us than the data are to them. And so, it’s a balance with them and when we share data, so the short answer to this is we don’t yet have a plan disclosure date of data – biomarker data, and the response data, safety data from this trial. But we would like to share – we want to share as soon as we’re able to.

[Christopher Marai:]

Great. Thank you.

[Operator:]

Thank you and our next question comes from the line of Jim Birchenough with Wells Fargo Securities. Your line is open, please go ahead.

[Yanan Zhu:]

Hi. This is actually Yanan in for Jim, today. I have a few questions on the FPA008 program. One question on the change in the trial design, has it been – has the change in design been influenced in any way by what you see in the Phase 1a trial, in terms of favorable data, so you had an indication or unfavorable findings that led to taking indication out?

[Rusty Williams:]

We can’t make a comment on the Phase 1a data, sorry.

[Yanan Zhu:]

I see. And another question is on the Phase 1a, whether the biopsy is actually performed in the pre-treatment and post-treatment biopsy that might have – I know it’s implemented in Phase 1b, but I’m not sure whether in the Phase 1a part, it’s also part of the design?

[Robert Sikorski:]

Yes. Good question. This is Bob, I can take that. Absolutely. So, it’s in fact mandated. So, the patients in the Phase 1a, as part of their eligibility consent for a pre-biopsy and post-biopsy, day zero, day 30. We do look for things that are obvious, we look for macrophage, macrophage subsets. We look for PD-L1 status, we look for infiltrates, architecture – just highlighting a few things, and importantly CSF-1R positive cells. So, that dataset obviously we’re accruing that as we’re doing the study, and we really do learn scientifically from not only what’s in the study, but what’s outside of the study in the field and has – although we can’t comment on anything specifically we use all this data obviously.

[Yanan Zhu:]

Got it. And then, in terms of pre-clinical work, do you have some data suggesting that the checkpoint inhibitor failures may respond to a combination approach?

[Rusty Williams:]

Well. This is of course something we’re interested in, just have to leave it at that. But it makes sense that if you think that immunosuppressive tumor-associated macrophages are in the tumor creating an immuno-suppressed environment, that may be a reason why checkpoint inhibitors might fail. So, it does make – it’s rationale to hope for that.

[Yanan Zhu:]

Got it. And last question, in terms of the data readout from the Phase 1a part of the study, should we expect the data before the dose escalation starts or perhaps also in the second half of the year after the Phase 1b started.

[Robert Sikorski:]

We haven’t disclosed yet. We aren’t going to disclose data, we haven’t made a plan for that at this time.

[Yanan Zhu:]

Got it, got it. Thank you, that’s very helpful. Thank you.

[Robert Sikorski:]

I wish I could tell you more about that because I said before we do, as a company, we have an interest in disclosing data probably sooner than a large pharma company would, and we really enjoy our working relationship with BMS, very productive. It’s been helpful in our design of the trial and our redesign of the trials we just described today. But we do want to work with them in terms of data disclosure.

[Yanan Zhu:]

Got it, thanks.

[Operator:]

Thank you and our next is a follow up from the line of Michael Schmidt with Leerink Partners. Your line is open, please go ahead.

[Michael Schmidt:]

Hey, thanks for taking the follow-up. I had just a couple more on PVNS. The first question is on the 25,000 patients, how many of those are addressable, you think rationally with the antibody therapy, and number two, in terms of path registration in the Phase 2 study, could that be expanded into registrational study?

[Rusty Williams:]

Bob, do you want to –

[Robert Sikorski:]

Yes – just will get one at a time here. So, the first question is, how many are addressable? Let me backtrack a little bit how we came up with that number. So, when we – it’s not published yet, but just to give you a feel for it. We made different – you make different assumptions on the patient population. Obviously, there’s local PVNS, which is a surgical disease. And then you make a distinction based on diffuse PVNS, and by diffuse PVNS, let me just – we’re defining that as patients who have had surgery before, and have had repeat surgery. So, that’s the definition of that disease, and that’s important. These aren’t local PVNS patients who are going to be largely cured by surgery. I think this answers your question. So, we think a good set of those could be addressed by the drug. It’s not going to be 100%, I’m not going to say that, but it’s not local PVNS. These are patients who’ve already had surgery and repeat surgery, because that’s the definition we use for that sub-setting. And to your second question – yes, go ahead.

[Michael Schmidt:]

Can you share what the percentages of those types of patients?

[Robert Sikorski:]

I think I’ll leave that to the paper. I don’t want to take away – we have an academic collaborator and we want to make sure that this is presented as an academic venue. But we look in just the local and diffuse, and in fact we’ve broken diffuse into two settings depending on how broadly you look, and the number I gave you is the middle of the road answer, depending on how broad you look, you could make that larger. But we’re safe to say that that’s going to be in the ballpark for patients to be considered. And your second question, Michael?

[Michael Schmidt:]

The path to approval, whether that Phase 2 is sufficient or can be expanded for rapid approval pathway?

[Robert Sikorski:]

Yes. Good question. There’s Plexxikon and Daiichi Sankyo have an ongoing Phase 2 trial in the setting, let’s use them as a reference. They have a little over 100 patients in that trial. It’s a randomized trial, randomized to placebo. So, we think that – if we use that as a benchmark, I think that’s safe as we can be right now. Our plan though is to take the Phase 2 data to the agency and begin a dialog. What we think is the endpoints will be activity – anti-tumor activity plus changes in meaningful endpoints that are clinically meaningful to patients, such as pain and range of motion perhaps, but again, I would just use the Plexxikon’s study as a roadmap for something that’s known already and we’ll figure out with the FDA what we’re going to do.

[Michael Schmidt:]

Sounds good. Thank you so much.

[Robert Sikorski:]

Sure.

[Operator:]

Thank you. And I’m showing no further questions. And I’d like to turn the conference back over to CEO, Rusty Williams, for any closing remarks.

[Rusty Williams:]

Okay. Well, we’d like to thank everybody for joining us and for your support of Five Prime and good questions and discussion. We look forward to further updating you on future calls. Take care.

[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 great day.