Five Prime Therapeutics Inc
Q2 2018 Earnings Call Transcript

Published: 9 Aug 2018

[Operator:]

Good day, ladies and gentlemen, and welcome to the Five Prime Therapeutics Second Quarter 2018 Earnings Call. As a reminder, this conference may be recorded. I'd now like to introduce your host for today's conference, Heather Rowe, Senior Director, Investor Relations and Corporate Communications. You may begin.

[Heather Rowe:]

Good afternoon and thank you for joining us. I would like to welcome everyone to our conference call to discuss results for the second quarter 2018. 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 Presentations. Joining me today are Aron Knickerbocker, Chief Executive Officer, Dr. Helen Collins, Chief Medical Officer; Dr. Bryan Irving, Chief Scientific Officer; and Linda Rubinstein, Interim 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 Aron.

[Aron Knickerbocker:]

Thank you, Heather. Good afternoon and thanks for joining us today to review our second quarter 2018. Highlights appear on Slide 3. We continue to make notable progress across or pipeline as shown Slide 4. We have four drug candidates in the clinic now, now either on our own or with our collaborators and expect to have a fifth by the end of the year. We're not Metoo shop and if you look at our pipeline it's either first-in-class agents or agents that we believe are meaningfully differentiated from the others in the class. And I'll start with cabiralizumab or cabira. BMS is ongoing randomized for arm Phase II clinical trial continues to make progress in evaluating cabira and Opdivo with or without chemotherapy as a second line treatment in patients with advanced pancreatic cancer. We already show in the cabira and Opdivo without any chemotherapy demonstrated deep and durable responses in patients who are receiving their median fourth line treatment for pancreatic cancer. But we'd like to offer even more benefit to more patients with pancreatic cancer by treating their disease earlier in its course. And we know that anti-CSF1R and anti-PD-1 and chemotherapy are synergistic in pre-clinical models of pancreatic cancer. So for these reasons we're very pleased that our partners at BMS are now investigating the use of cabira and Opdivo with and without chemotherapy in patients getting second line therapy for pancreatic cancer and Helen will describe this trial more later. BMS is also supporting several investigator sponsored trials evaluating additional combinations that include cabira. One example is the recently announced clinical trial collaboration by Apexigen and Yale Cancer Center to evaluate Apexigen's CD40 anybody in combination with cabira and Opdivo in patients with melanoma, lung cancer, or renal cell carcinoma who progressed on prior anti-PD-1 or PD-L1 therapy. I am also pleased to share with you today that bemarituzumab or bema has cleared an important hurdle. We've advanced through the Phase I safety lead-in portion of the Phase I/III FIGHT global registration trial. And with our collaboration at Zai Lab are actively preparing to initiate the Phase III portion of the trial soon. We and our investigators are also very excited about FPA150, our first-in-class antibody targeting B7-H4. We are currently testing it as a single agent in a Phase Ia/Ib clinical trial. This novel checkpoint inhibitor could have utility in tumors not well treated by PD-1 therapy such as breast and ovarian cancers and it offers a second mechanism of action with direct tumor killing by enhanced ADCC. In addition, we're pleased that the first clinical candidate from our I-O research collaboration with BMS, the TIM-3 antibody is now in a Phase I/II trial and it's being studied as a single agent and in combination with Opdivo. The candidate is a fully human monoclonal antibody targeting TIM-3, an immune checkpoint receptor that's known to limit the duration and magnitude of T cell responses. FPT155, our first-in-class CD80-Fc fusion protein is engineered to activate T cells through multiple pathways. I am happy to announce that we have completed IND enabling activities for FPT155 and anticipate initiating a Phase I clinical trial in Australia by the end of this year, and beyond these, our other internal and partnered programs that we have yet to disclose. A key differentiator for Five Prime is our discovery platform that we use to identify novel targets and biology in immuno-oncology. Underlying this platform is our collection of thousands of extracellular proteins either secreted proteins or salable forms of subsurface proteins. And over the years, we've built out these extra cellular protein libraries as well as sophisticated ways to screen those libraries in high throughput in cell-based models, by physical assays or animal models. This platform is proving to be an IND engine as evidenced by FPA150 and FPT155 and I have great confidence in the future with Five Prime. Our pipeline is expanding. We have later stage programs that have already demonstrated clear activity as well as exciting new first-in-class agents entering clinical development with more to come. And we have a strong balance sheet with $353 million in cash and no debt. I'll now turn the call over to Helen, to review our clinical programs.

[Helen Collins:]

Thank you, Aron. We continue to be pleased with the progress across our clinical programs. I'll start on Slide 5 with cabiralizumab, our antibody to the CSF-1 receptor on macrophages. We are combining cabira's CSF-1R inhibition with the BMS's PD-1 inhibitor OPDIVO. Last fall, we presented data that demonstrated durable responses of late-line patients with pancreatic cancer as shown on Slide 6. These data are unprecedented for immuno-oncology agents in this patient population as anti-PD1 agents have not demonstrated efficacy in patients with microsatellite stable pancreatic cancer. Given these durable responses in late-line pancreatic cancer BMS is advancing the cabira's Opdivo combination into a Phase II randomized trial in approximately 160 second-line patients. We like this trial design because it has a randomization scheme, an active standard of care compared, and overall survival rate as one of the 10 points. You can see the trial design on Slide 7. BMS is expanding the study into Europe and Asia, which should set this program up for future success. A poster featuring cabira Opdivo pharmacodynamics and genomic profiling data from our ongoing Phase I trial was chosen for oral discussion at the 2018 ASCO annual meeting. Co-written by the scientists at BMS in Five Prime, the poster presented both serum and tissue biomarker data. The data confirm target engagement by cabiralizumab through changes and circulating CSF-1, non-classical monocytes that were dose and schedule dependent. Tumor biopsies showed that the combination of cabira and Opdivo decreased CSF-1R, decreased immunosuppressive into macrophages and increased CDA CD8+ effector T-cells. These changes suggest that cabiralizumab is altering the tumor microenvironment from an immunosuppressive to a pro-inflammatory state. In other words making tumors harder and therefore more susceptible to T-cell mediated tumor cell death. Interestingly, whole genome sequencing also showed that nearly all the patients enrolled in the Phase I had tumors with low tumor mutational burden. These patients are less likely to respond to PD-1 inhibition with Opdivo alone, therefore making any absurd responses even more meaningful. Taken as a whole, the data support further clinical development of the cabiralizumab Opdivo combination in addition oncology indications even beyond pancreatic cancer. We've also been studying cabira as a monotherapy in an ongoing Phase II trial in patients with PVNS, which is a rare locally aggressive, non-malignant tumor of the synovium. More information on this program can be seen on Slide 8. At ASCO last year, we presented preliminary Phase II data that demonstrated efficacy with dosing every two weeks. However, patients were discontinuing treatment early due to tolerability such as eyelid swelling and itching. To try and improve tolerability, we began enrolling a second cohort of patients with a less frequent every four to six-week dosing schedule. Preliminary data from this new cohort suggest efficacy is maintained with a less frequent dosing, but we continue to see discontinuations and dose interruption. For cancer indication this benefit to risk outcome would be acceptable. However, in PVNS, a disease that chronic and non-fatal, the current dosing schedule isn't optimal for advancing into a pivotal trial. We have enough data now to make the decision to not move forward into a pivotal trial in patients with PVNS with this dosing schedule. Let's now move on to bemarituzumab, also known as FPA144. As shown on Slide 9, bema targets FGF2b overexpressing tumors. We designed bema to block growth factors from fueling cancer cell growth and to enhance cancer cell killing through ADCC. We've advanced to the Phase I safety leading portion of the FIGHT trial as Aron stated earlier, and we expect to initiate patient dosing for the Phase III portion of the trial before the end of the year. This trial will include FIGHT in the U.S., Europe and Asia including China, South Korea and Japan countries where the incidence of gastric cancer is high. The trial design can be found on Slide 10. We designed this trial to achieve frontline approval for bema in patients with FGFR2b over expressing advanced stage gastric or GE junction cancer. Recent data supporting the poor prognosis of patients with advanced gastric cancer whose tumors have amplified the FGFR2 gene were presented at ASCO. These data came from a nationwide cancer genome screening project in Japan that showed that patients with advanced stage gastric cancer, whose tumors had FGFR2 amplification had nearly half the survival rate, compared to patients whose tumors did not have this amplification. This study provides additional support for why targeting FGFR2b so important in gastric cancer. The FIGHT trial design is a gold standard double-blind placebo-controlled trial without a crossover and overall survival is its primary endpoint. It will evaluate bema and combination with modified FOLFOX6, standard of care chemotherapy versus placebo plus modified FOLFOX6 and approximately 550 patients. A trial in progress posted for the FIGHT trial was presented at ASCO. Moving on to FPA150, our first-in-class B7-H4 antibody, as shown on Slide 11. We design this antibody to have two potential mechanisms of action. It releases the checkpoint blockade that B7-H4 puts on the T Effector cells and like bema is engineered to have enhanced ADCC. B7-H4 is overexpressed in multiple solid tumors, including breast, bladder, ovarian and endometrial cancer. Because FPA150 is also a targeted therapy, we've developed an IHC assay to identify patients who might benefit most from treatment. We continue to dose patients with that FPA150 monotherapy and solid tumors in the dose escalation phase of the Phase I trial. During dose escalation we will be opening an exploratory basket cohort to investigate FPA150 monotherapy in patients with any solid tumor that overexpresses B7-H4. The dose escalation will be followed by expansion in pre-specified cohorts of patients whose tumors have high B7-H4 expression level. The initial targeted tumors for the expansion cohorts are breast, ovarian, endometrial and bladder cancers. Our investigators are enthusiastic enrolling patient since it's a first-in-class checkpoint inhibitor and to date there are no I-O therapies approved in breast, ovarian or endometrial cancer. You can see the trial design on Slide 12. I will now turn the call over to Bryan to review our research and pre-clinical efforts.

[Bryan Irving:]

Thank you Helen. At Five Prime, our scientists exploit our comprehensive library although were 6,000 secreted in extracellular proteins to perform high throughput functional screens to identify novel target was functionally modulate nearly any disease biology of interest or in vitro screens can be designed to test the entire protein library in a highly focused manner utilizing any primary cell types of choice. Our in vivo screens can also ask a library to agnostically identify targets that integrate the complex functions of multiple cells in the tumor microenvironment. We've conducted numerous immunooncology screens across several systemic tumor models and have identified targets with previously unappreciated roles in modulating or regulating immune function. While early in vitro of vivo screens included primary effector T-cells T-regs and macrophages. We are currently optimizing screens to study the impact of our library on the function of dendritic cells. The antigen presenting cells most adept at activating effective and anti-tumor T-cell responses. I'm excited by the platforms potential to identify novel and differentiated drop targets in this competitive but still nascent IO space. And as a complement to our screens we are conducting experiments to better understand the immune context within the tumor microenvironment and to examining Immune profiles and Gene signatures that are associated with the positive and negative responses to or relapse from treatment with checkpoint blockade. Our most insure pre-clinical program FPT155 continues to advance. FPT155 which I may refer to as 155 is a first in class CD80-Fc fusion protein engineered to activate T-Cells multiple mechanisms. You can see it on Slide 13. FPT155 was identified in one of our in vivo tumor screens of over 700 immune related proteins as one of the most potent activators of tumor immunity. CD80 is a costimulatory molecule expressed on antigen-presenting cells that primarily regulates the activity of the dominant costimulatory receptor CD28. 155 use the binding interactions of soluble CD80 to directly engage CD28 to enhance its costimulatory activity, importantly though without the super agonism that was observed with the CD28-targeted antibody. And second, to block CTLA-4 from competing for endogenous CD80, and thus allowing CD28 signaling to prevail in T-cell activation. 155 efficiently costimulates primary human T-cells in vitro, but only in the presence of T-cell antigen receptor engagement. In vivo 155 and uses a strong single-agent activity in multiple pre-clinical models and synergistic efficacy when combined with anti-PD-1 therapy. Moreover, 155 retained significant anti-tumor activity independent of its engagement with CTLA-4. So we expect its direct interaction with the CD28 to differentiate from CTLA-4 blocking antibodies. We are on track to initiate Phase I clinical trial in Australia by year-end. Finally beyond 155, we've continued to pursue multiple additional targets that various stages of research. We anticipate our research and future product pipelines are remain robust as we expand our immunooncology screens and continue to identify our additional treatments for patients both on our own and partners. You can see this on Slide 14. We are currently in the lead generation stage for multiple programs on our own end with BMS. I will now turn the call over to Linda to review our financials.

[Linda Rubinstein:]

Thank you Bryan. Further details regarding our financial results can be found in the press release issued this afternoon as well as on Slide 15 and 16. We ended Q2 with a strong balance sheet. Cash, cash equivalents and marketable securities totaled $353 million on June 30, 2018, compared to $293 million on December 31, 2017. This increase reflects $108 million in net cash proceeds from our equity offering in January and $34.5 million in milestone and upfront payments that we've received from collaboration partners, net of cash used in operations. Net loss for the second quarter of 2018 was $34 million or $0.99 per basic and diluted share. Collaboration and license revenue was $7.6 million for the quarter, which was slightly less than the $7.8 million for the second quarter of last year. As compared to last year we've recognized less under our cabiralizumab collaboration agreement with BMS and our Fibrosis and CNS collaboration with UCB. This was offset by collaboration and license revenue from our China collaboration with Zai Lab. R&D expenses totaled $33 million for the quarter, which is a decrease from the $42 million of R&D expenses in the second quarter of 2017. This was primarily related to decrease preclinical program expenses offset by an increase in clinical expenses as we advanced FPA150 from preclinical development into clinical development. G&A expenses totaled $9.8 million for the quarter, a slight increase from $9.4 million a year before due to increased consulting and facility costs offset by reduced personnel cost including stock-based compensation. Looking ahead, we continue to expect full-year 2018 net cash used in operating activities to be less than $135 million. We estimate ending 2018 with approximately $250 million in cash, cash equivalents and marketable securities. I will now turn the call back to Aron for closing remarks.

[Aron Knickerbocker:]

Thank you, Linda. As you heard during this we advanced our clinical and other programs throughout the quarter and we will build on this momentum throughout the rest of the year. The initiation of the Phase III portion of our first registrational trial will begin soon and our other programs continue to advance as well. Our expected milestones could be seen on Slide 17. Five Prime's overarching clinical development philosophy is to design our trials to get clear answers as quickly and efficiently as possible to make rational portfolio decisions as evidenced by our PVNS decision that we announced today. Moreover, we are financially disciplined and have multiple levers to fund the company including the potential for additional strategic collaborations. Our IND engine continues to fill our and our collaborators pipeline and we are well capitalized as Linda just noted. So I remain very confident in the future of Five Prime. And finally, before we open up the call for questions, I want to thank the patients and investigators participating in our clinical trials, our Five Prime employees and our strategic collaborators. I will now open it up for questions.

[Operator:]

Thank you, sir. [Operator Instructions] Our first question comes from Chris Shibutani from Cowen. Please go ahead.

[Unidentified Analyst:]

Hi. This is [indiscernible] on for Chris. I had a quick question about the pipeline - actually maybe a couple. The first one can you remind us regarding the study that you started in Australia, when we might expect to see studies elsewhere and what the rationale was for that decision?

[Helen Collins:]

Yes. This is Helen Collins. I'll answer that. So we've chosen it in Australia for our 155. This is the CD80-Fc protein drug that Bryan described in some detail of the preclinical rationale. We decided to go there for a few reasons. One is for those of you who may know, Australia is really has a long history of very efficiently conducting Phase I trial, so it's often just the way that their regulatory and their Ethics Committees are set up very quickly. You can get a trial up and going there. So part of it was speed. The second part was because we are - this is a drug that's in the I-O space and in many ways the patient population in Australia is similar to the U.S., but in other ways in terms of what drugs are available to those patients, it's different. And so we very quickly want to get proof-of-concept for this drug. And so we think by going to Australia that will allow us to do that because of the availability - the commercial availability of some of the I-O drugs such as PD-1 and other CTLA-4. So those are really the two main reasons.

[Aron Knickerbocker:]

Their investigators are experienced with I-O therapies and our initial conversations with investigators there shows that they're enthusiastic about FPT155. Yes, the fact that there are so many more checkpoint inhibitor naïve patients is an important given the mechanism of 155 and we are looking to see activity as a single agent with 155. As to your second question about opening elsewhere in the world, we will guide later on that. The Australia plan is really focused primarily on dose escalation, but at some point we will go beyond Australia.

[Unidentified Analyst:]

Thank you. And can I ask just one more question about the pipelines for 150? Can you talk about the rationale for pursuing breast, ovarian, endometrial and bladder there?

[Helen Collins:]

Yes, so again this is Helen. I'll answer that. So really of course when we're looking at something that's clearly targeted against - in this case B7-H4, we're looking at tumor types where there is the highest expression. And we're lucky or just so happens that the tumor types were the highest expression are no tumor type to breast, ovarian, endometrial, and bladder, and again it just so happens. Those are diseases where PD-1 audit approved. So our investigators are really enthusiastic. The patients who are enthusiastic as you may know particularly breast, ovarian, endometrial tend to be a younger healthier patient population who are very vested in their health, so the trial is going very well.

[Aron Knickerbocker:]

And we've used the translational evidence to support this. So when we look at the expression of this target across multiple tumor types, it tends to be highly over expressed in a reasonable fraction of those tumor types that we name, breast, bladder, ovarian, and endometrial. And it is not very expressed normal tissue. So we are hopeful about the potential therapeutic index of this product given the differentiated - differential expression on tumor.

[Unidentified Analyst:]

Thank you very much.

[Operator:]

Thank you. Our next question comes from Jim Birchenough from Wells Fargo. Please go ahead.

[Nick Abbott:]

Good afternoon. It's Nick in for Jim this afternoon. In terms of the ongoing Phase I/II cabira AA study, Opdivo AA study. Can you give us guidance on what we should expect as a read out? Will it be a comprehensive or port on the six remaining cohorts or will it be disease specific reports?

[Aron Knickerbocker:]

Yes, so that trial is ongoing. As we've mentioned, we did finish enrollment at the end of 2017, but the study continues as for data disclosure that will be at BMS' discretion.

[Nick Abbott:]

Okay. And then maybe just in terms of you mentioned NK mechanism of action on bema and FPA150, obviously in cancer patient with NK cells - somewhat dysfunctional, so do you have good evidence that in cancer patients, the NK cells can really be engaged these antibodies and that's segue to asking a related question, which is 2015, you licensed antibody to Bluebird or Clarty. Do you consider licensing these all collaborating with the Clarty company with the cellular therapies based on antibodies such as bema and FPA? Thank you.

[Aron Knickerbocker:]

On the ADCC question, I think there are precedent examples of antibody is working via ADCC in cancer Herceptin for example is Ivivva rituxan as well as technologies or antibody's that incorporate this same technologies. So we use the Potelligent technology and Kyowa Hakko does have a CCR4 antibody approved in Japan using that same technology. So I think given that there is precedent for engaging on T-cell in patients with cancer. We're reasonably optimistic about that and we do see good activity preclinical with this agent. So to doing other party collaborations, at the moment we are not planning anything in particular yet. But we are opportunistic and should cell therapy be a preferred mechanism for any of these targets. We would consider that. But at the moment we're focused on getting this antibody through dose escalation and into selected patients with B7-H4 of expression, same goes for bema getting that into the pivotal trial and beginning the Phase III work ASAP.

[Nick Abbott:]

So may be just one for me, and that is in your prepared comments you mentioned, Bristol has a several IT trials ongoing with Cabira and you mentioned the Apexigen CD40I think. Anyway can you elaborate on what other term IIT trials are ongoing with Cabira?

[Aron Knickerbocker:]

Yes, we don't have involvement in those. So I think it's better to refer you to Bristol-Myers Squibb, but there is going to University of Chicago, which is a biomarker driven study [indiscernible] study and Cabira is part of that. So that's one, but I would refer you to clinical trials start to look at what other trials are ongoing and also that Bristol as we don't participate in those directly.

[Nick Abbott:]

Okay, great. Thank you very much.

[Aron Knickerbocker:]

Thank you, Nick.

[Operator:]

Thank you. Our next question comes from Robin from City.

[Greg Harrison:]

Hi, this is Greg Harrison on for Robin. Thank you for taking the question. With regard to the anti TIM-3, I wondering if you could get any update on enrollment of that trial and when we might be able to see the combination data with Opdivo and then if you have any commentary on what could differentiate their versus other countries?

[Aron Knickerbocker:]

Yes. So this is anybody arose from an ongoing collaboration that we have and I-O discovery collaboration with BMS that is focused on three checkpoint pathways. We haven't disclosed what the other two are the anti TIM-3 program is the first two enter the clinic from that relationship. But under this relationship Bristol-Myers Squibb is responsible for development of commercialization and we have economic participation by means of milestone payments and royalties. But we are not involved in the development or commercialization of the TIM-3 anybody. So we can't guide or update on enrollment or for data from the Opdivo combination. In terms of differentiation a lot of this is confidential but we can say is that Five Prime applied its technology and its ability to decipher binding interactions to select a particular TIM-3 anybody that we believe disrupts its binding with undisclosed partner. So that is what we think could be unique about this program, but we can't review of the specifics of it.

[Greg Harrison:]

Great. Thank you.

[Aron Knickerbocker:]

Thanks Greg.

[Operator:]

Thank you. Our next question comes from Kennen MacKay of RBC Capital Markets. Please go ahead.

[Kennen MacKay:]

Thank you for taking the question. Wondering if you can comment on how compliance differs between PVNS and some of the solid tumor indications either in the Phase I or expansion portions of the Phase I/II trial?

[Aron Knickerbocker:]

Sure. Thanks Kevin. I'll turn it to Helen to…

[Helen Collins:]

Yes. I mean I think as you know we've been talking about this all along as we're talking about PVNS when we found the high discontinuation rate giving the drug every two weeks in PVNS, the data that we presented in 2017 at ASCO versus the data that we presented in the oncology indication last fall and clearly there is a significant difference not just in the grades of the adverse events, but then the patients tolerability. So we obviously haven't disclosed the details of the updated - the data I was referring to today. But it's similar to what we were seeing before. So the number one reason for discontinuation PVNS has been periorbital edema. And our previous data that we presented that was happening somewhere around a third of patients are discontinuing for some reason and that being the most common whereas I believe we presented our oncology data and was 10% I have my number right here. Yes, thank you 7% of patients who discontinued. So there's a big difference and we only had one patient who specifically discontinued for periorbital edema lated to cabira when we presented that data, so again a big difference between the two.

[Kennen MacKay:]

Gotcha.

[Helen Collins:]

No, I am going to say I mean I think some of that as we talked about before just also so it appears to be two things. I just want to make sure I was clear. Both the frequency of the actual reporting of the adverse events, so the actual adverse event itself is much less frequent oncology we don't know why. But the secondary which is the most important thing is for the patients of PVNS they discontinue their drugs. So they get a periorbital edema they start taking care.

[Kennen MacKay:]

In the press release excited dose interruptions as well as discontinuations. Is there any commentary you can provide on interruptions or reduction in terms of different between the PVNS and solid tumor oncology experience?

[Helen Collins:]

Yes. I think what we try to do when we did this amendment as we wrote that patients could receive the drug every four to six weeks and we got that flexibility and based on I think as you may recall where we noticed that in our first cohort patients getting the drug every two weeks. If they discontinue drug it was taking six, eight and something little bit longer than that for the disease to grow back. So we gave this window because we wanted to give a little bit of flexibility we could see that patients needed to have individualize treatment to some extent. But what we allowed is if a patient had something like periorbital edema and they wanted to be off longer than that we were allowing. treatment interactions for longer than the six weeks. Our first cohort, if somebody discontinued for that long they had to go off trial. So we're trying to make a distinction between patients who discontinue permanently versus patients who are getting drugs less and every six weeks. But in terms of going on to a pivotal trial with a scheduled set regimen and scheduled either way, this would not allow us to go forward, but you need a set regimen and a set schedule to do a pivotal trial.

[Kennen MacKay:]

That's clear and very helpful color. And then a second question on bemarituzumab, in the FIGHT trial as this advances from sort of the Phase I portion that you are expecting to complete by the end of the year to Phase III. Is there sort of a FDA meeting the needs to take place before that officially sort of advances into the Phase III meeting? And wondering if the statistical plan for that Phase III portion of the trial has been finalized with the FDA?

[Helen Collins:]

So this trial was a Phase I/III and it is all one protocol, so the trial that it's not stopping a Phase I and starting a Phase III. So obviously we need to make sure that all the T cross in dose are on it, as they say before we start that Phase III, but it is all one protocol, we do have a finalized protocol.

[Kennen MacKay:]

Okay. Thank you.

[Operator:]

Thank you. Our next question comes from Salveen Richter from Goldman Sachs. Please go ahead.

[Unidentified Analyst:]

Yes. Hi guys. This is [indiscernible] for Salveen. I have a couple of quick ones. One of them, as I was wondering, how you're thinking about the timelines for the Phase II trials in the earlier line patients in pancreatic for cabira and Opdivo. And I also wanted to sort of check a little bit about the design of the trial. You mentioned that overall survival is one of the endpoint would be as has been other one and how we're thinking about the duration of the trial based on that? And I think I also heard that there was a reduced headcount; I was just wondering what was the reason for that? Thanks a lot.

[Aron Knickerbocker:]

Maybe I'll start with the last one. We haven't reduced headcount.

[Unidentified Analyst:]

Thank you.

[Aron Knickerbocker:]

Okay. So on the Phase II randomized trial in second line pancreatic cancer, we don't provide guidance on the timeline for that, but we are pleased with the pace of site activation and you could see it online, if you're in clinicaltrials.gov kind of the sites that are open and those that are planned to be open. We do know from our own experience in treating patients with pancreatic cancer in the late-line study, where we are investigating cabira and Opdivo that we were able to fill our second cohort very rapidly just given the strong investigator interest in putting patients on this regimen likely due to the clear signal that we've already demonstrated with the doubling in late-line pancreatic cancer. So while we can't provide guidance on the Bristol trial, we do know there's significant interest in oncology community and treating patients with cabira and Opdivo and we would expect that trial to move briskly. And then you had questions on the design, the OS endpoints and others.

[Helen Collins:]

Yes. I mean I think second line, so the most recent thing approved in second-lines Onivyde right, there we know the response rate is 7%, PFS three month, survival six months. So this is a trial that should readout quickly. Pancreatic patients unfortunately did that poorly. So again it depends on how quickly it's enrolling, but we have and it's not our trial, but I'll reiterate we have every indication that it's enrolling quicker.

[Unidentified Analyst:]

Got it. Thank you very much.

[Aron Knickerbocker:]

Thank you.

[Operator:]

Thank you. Our next question comes from Eric Joseph from JPMorgan. Please go ahead.

[Eric Joseph:]

Thanks for taking the questions. Just a couple from us. I know you're looking to guide on the cabiralizumab and Opdivo combination trial? Just curious to know whether you would anticipate an additional readout from the later line pancreatic cohort having and enrolled an additional 35 patients? And then I'll follow-up on bemarituzumab?

[Helen Collins:]

I think it's the good and the bad about the BMS being more interested in this combination is that any further communication about any of the data on that study will be based on BMS.

[Eric Joseph:]

Got it, okay. And on the FIGHT trial with Lamari, could you - are you going to provide a little color on what you saw the safety read portion, whether that's are really profile is generally sort of in line with what you observed in the immunotherapy in Phase I and what dose along with bemarituzumab. Are you intending to move forward with in the Phase III portion? Thanks.

[Helen Collins:]

So right now we haven't provided any of that detail. We should be able to assume, but right now, I can't give any more detail.

[Eric Joseph:]

Okay.

[Helen Collins:]

Other than we're very confident we should be getting our Phase III study going on schedule very soon certainly before the end of the year.

[Aron Knickerbocker:]

And we have selected the dose.

[Helen Collins:]

Yes, we have selected it.

[Eric Joseph:]

Okay. And that dose will be made public when you want to presumably be public once initially the three portions?

[Aron Knickerbocker:]

We'll make it public at some point whether it's right our initiation, I'm not sure that will show up on that - online. But we will reveal it once here in Phase III.

[Eric Joseph:]

Okay. Thanks for taking the question.

[Aron Knickerbocker:]

Thank you, Eric.

[Operator:]

Thank you. Our next question comes from Steven Seedhouse from Raymond James. Please go ahead.

[Steven Seedhouse:]

Hi, good afternoon. Thanks for taking my questions. Just a follow-up quick on one of the Eric's question, did you have a good representation of gastric cancer patients and there is one portion of FIGHT?

[Helen Collins:]

Again Phase I of FIGHT - yes absolutely. I mean the study did not - the Phase I did not require patients who have gastric cancer and did not require patients to be FGFR2b. But if the patient had to be patient getting FOLFOX and of course that is a common regimen for gastric cancer.

[Aron Knickerbocker:]

So yes we had good representation.

[Steven Seedhouse:]

Okay, and just on the PVNS decision, just curious that the decision by the [indiscernible] to file the NDA for pexidartinib surprise you at all and just given the Phase III enrollment and air trial was stopped early for safety and did that affect your no go decision? And I know you mention you're considering alternative dosing schedule still, so just wondering how to interpret that and is that a result of the pexidartinib that are in a competitive development?

[Aron Knickerbocker:]

I think the IT program it's good for patients that there might be an alternative for treating disease, which is currently not addressed with any approved pharmacologic product. So in that sense it's good. We do think that the profile of that agent is very different than ours. It's a small molecule tyrosine kinase inhibitor and as such has a different spectrum. EEs them we see with cabira, our decision not to move forward in 2019 to pivotal trial with cabira was not influenced by pexidartinib per se rather we want to find a tolerable and acceptable schedule for our drug, which we think has a very different spectrum EEs is associated with it. So we didn't make the decision based on the EEs experience with pexidartinib. But we are of course mindful of what they've done with pexidartinib and find it instructive for study design and conceptualization of this program.

[Steven Seedhouse:]

Okay.

[Helen Collins:]

Yes, I mean I'm going to say I can just corroborate that I mean I think that that what pexidartinib are in terms of response of durability response, exactly what we thought what their what's in their struggle, but we do know there's been a long time between when they stopped enrollment and then what never filing, so to speak to again in benign disease or non-cancer disease that risk benefit ratio is a lot different than it is an oncology. And so I think just to put one Aron saying, there are no surprises to us in terms of what's happened with pexidartinib, in terms of what we are at the disease.

[Steven Seedhouse:]

Okay, that's helpful. And then just one last high level question I had about to CSF1R is a target in oncology in general. So we're already seeing now the triple combos, whether is to be a mass trial with chemo or an now this new anti-CD40 triple combo study, and there's some preclinical work obviously with a different agency, even so just given all that combo work, I'm wondering how complex you anticipate clinical development becoming for CSF1R, not just in pancreatic cancer, but across the board and just a high level thought on what it at unique to CSF1R or is this just an inevitable end game for novel therapies going forward?

[Aron Knickerbocker:]

I think the triple combinations at this point are more exploratory. We do know pre-clinically and as well clinically that we see activity from CSF1R and PD-1, when they're combined and as we say that pancreatic cancer, but also beyond pancreatic cancer. As for triple combos, I think they may make sense if you're trying to address other cell types in the tumor microenvironment as the anti-CD40 in addition may do. Because right now we're working primarily two times and CD8 effectors T cells. Bryan, do you have any thoughts on triple combinations such…?

[Bryan Irving:]

Well, I think addressing the different mechanism. The CD40 is - which should an activating the generator cells or increasing antigen presentation. The era is not be leaving a break on T-cells that macrophages providing the tumor microenvironment. I think - I don't think if you need to IO, I think we have to take lessons from the anti-viral sort of their reason if we're going to be successful against cancer, we have to hit multiple key non-overlapping dose and I that I think that's the goal of these - triple combination.

[Helen Collins:]

Yes. And also say from a clinical perspective, I mean I think that it's pretty clear these PD-1s are moving earlier line therapy, so they're getting added to chemo. So we want to quickly be able to figure out if we can add to the PD-1 plus chemo right. That's a way that move quickly to an earlier line of therapy. And as you heard us talk about earlier going with our 155 program to Australia finding patients that have not received a PD-1 also becomes harder and harder late lines. So I think it's the way the whole area of I-O therapy is going to earlier lines of therapy.

[Aron Knickerbocker:]

Yes. I think they're rational, so the chemo will kill the tumors cell, CD40 will increase Antigen presentation and the cabira and PD-1 will leave innovation on the T-cells. So I think these are very rational combinations.

[Steven Seedhouse:]

Appreciate the question guys. Thanks very much.

[Bryan Irving:]

Thanks Steven.

[Operator:]

Thank you. [Operator Instructions] Our next question comes from Robert Driscoll from Wedbush. Please go ahead.

[Robert Driscoll:]

Thanks. Good afternoon. Just a quick one, can you elaborate at all on the proposed design Phase I study for FPT155 and how quickly you might be able to going on the PD-1 combination there just given data and what you just suggest in a lack of response to an ant- PD-1 is at least, in part due to a lack of sufficient stimulation? Thank you.

[Helen Collins:]

All I can do is say we designed our Phase I to go as quickly as possible. And obviously going to a place where we think that patients are, the investigators are enthusiastic. And again, obviously we think that PD-1 combo is down the line. That really all the detail. And give you 155, our B7-H4 is any example of what our team can do. We should go very quickly.

[Robert Driscoll:]

Great. Thank you very much.

[Operator:]

Thank you. I'm showing no further questions at this time. I'd like to turn the call back over to Aron Knickerbocker, Chief Executive Officer for closing remarks.

[Aron Knickerbocker:]

Okay. Thank you all for joining us today and also for your support of Five Prime. And we look forward to updating you on future calls.

[Operator:]

Thank you, ladies and gentlemen for participation in today's conference. This concludes the program and now you may disconnect. Everyone have a good day.