Five Prime Therapeutics Inc
Q4 2018 Earnings Call Transcript

Published: 27 Feb 2019

[Operator:]

Welcome to the Five Prime Therapeutics Fourth Quarter and Fiscal Year 2018 Earnings Call. As a reminder, this conference call is being recorded. I'd now like to introduce your host for today's conference, Martin Forrest, Vice President, Investor Relations and Corporate Communications. You may begin.

[Martin Forrest:]

Thank you, Scarlett. Good afternoon and thank you for joining us. A press release with the company's fourth quarter and full year 2018 financial results was issued earlier today and can be found on our company website and we've also posted slides on our website on the Events and Presentation page that we will refer to during our prepared remarks. Today, joining me today are Aron Knickerbocker, Chief Executive Officer, Dr. Helen Collins, Chief Medical Officer; Dr. Bryan Irving, Chief Scientific Officer; and David Smith, our 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:]

Thanks, Martin. Good afternoon, and thanks for joining us today. Before we get started, I'd like to welcome to new colleagues to our team. David Smith is our new Chief Financial Officer. David brings an impressive breadth of experience having worked at both large and small biotech companies. And Martin for us who just heard is our new Vice President of Investor Relations and Corporate Communications and I know they'll be strong additions to our leadership team here at Five Prime. It's been an exciting and productive time for Five Prime and I'm pleased to share with you today our 2019 will be a year of multiple data readouts, critical milestone events and continued development of novel biologics for patient facing cancer. On our call today, I'll review the highlights of our five clinical programs touching on key 2018 accomplishments, 2019 milestones, and our expectations for data disclosure from our clinical pipeline. Helen will provide a clinical update focusing on our more advanced programs and Brian will discuss the CD80 and Tim-3 assets. And David will review our 2018 financial results and cash guidance for 2019 and then we'll turn to Q&A after that. So turning to Slide 4, I'll begin by summarizing 2018 and 2019 highlights from our clinical programs which are divided into Five Prime Controlled and Fully Partnered programs. All Five programs are uncorrelated and we are systematically drugging the tumor micro-environment by targeting different cell types including tumor cells, tumor associated macrophages, natural killer cells and T cells. So let's start with the Five Prime Controlled programs. Bemarituzumab or bema is our most advanced program and is a targeted antibody to FGFR2b, which is overexpressed in approximately 10% of gastric and gastroesophageal junction cancer patients. Last month, we presented safety leading data for the Phase 3 FIGHT trial at the ASCO GI conference. And we expect the trial will be enrolling across nearly 200 sites globally by the end of 2019. Next is FPA150, which is our first-in-class antibody targeting B7H4. This target is in the same family of checkpoint molecules is PD-L1. However, we found that B7H4 is overexpressed in tumors such as breast, ovarian and endometrial cancers that are not well served by checkpoint inhibitors. This month, we completed FDA150 dose escalation, selected 20 milligrams per kilogram every three weeks as the Phase 1b dosing schedule and just last week initiated dosing in the monotherapy expansion cohorts. We're also implementing the next stage of our development plan, which involves opening a cohort, testing the combination of FPA150 and keep true to in patients with B7H4 for positive ovarian cancer. We estimate that we will begin enrollment in this cohort around midyear. Let's turn to FPT155, which is not an antibody, but a CD80-FC fusion protein. CD80 is as a co-stimulatory lag end of CD28, which is the dominant co-stimulatory pathway by which T cells are activated. This program is now in a Phase 1a dose escalation trial in solid tumors. Turning to the Partnered programs, Bristol-Myers Squibb is making good progress with cabiralizumab, which is our antibody that depletes tumor associated macrophages by blocking the CSF-1 receptor. Cabira is now in a randomized Phase 2 trial as a second line treatment for advanced pancreatic cancer. The trial is comparing the combination of Cabira and Opdivo with and without chemotherapy to standard of care chemotherapy alone. And finally BMS-986258 is an antibody to Tim-3 which has been developed by BMS. Tim-3 is involved in suppressing the normal immune response to dying cells including cancer cells. BMS-986258 relieves the suppression of the immune response mediated by phosphatidylserine on the dying cancer cells. This antibody specifically blocks the phosphatidylserine in Tim-3 interaction. Our partners at Bristol-Myers Squibb are now testing this agent in a Phase-1/2 trial as part of our collaboration that is focused on three checkpoint pathways, Tim-3 being the first of those to produce a clinical candidate. Slide 6, summarizes data disclosures and activities across all five clinical programs. So starting with the Five Prime Controlled programs on the left, we've already presented the safety leading data from the FIGHT trial for bema. In 2019, we expect to make to data disclosures for our FPA150 program at ASCO and ESMO. Helen will provide the details about those later during this call. Looking to FPT155, we plan to present data from the dose escalation portion of the Phase 1 trial at the SITC conference in November. As for our BMS collaborations, we're pleased with the continued progress of both the cabira and the Tim-3 programs. Throughout the year, we maintain ongoing dialogue with many companies about potential business development deals. While we do not guide to any deal or specific timing, we continue to explore strategic alliances that may create shareholder value and allow us to broaden and accelerate our programs. So with that, I'll not turn the call over to Helen to review highlights from our clinical programs in more detail.

[Helen Collins:]

Thank you, Aaron. Progress was made across all five of our clinical programs in 2018. First on Slide 8, is our most advanced program bemarituzumab, our first-in-class, isoform-selective antibody with enhanced ADCC which is in development as a targeted therapy for tumors that overexpress FGFR2b. As Aron mentioned we presented safety lead-in data from the Phase 3 FIGHT trial of bema and modified FOLFOX6 chemotherapy at the ASCO GI meeting in January. We did not observe any dose limiting toxicities with the combination and the safety lead-in and chemotherapy did not impact the bema pharmacokinetics. We observed signs of clinical activity in both of the known patients with advanced gastric or gastroesophageal cancer whose tumors overexpressed FGFR2b and who had previously received modified for modified FOLFOX alone. Data from the safety lead-in is summarized on slide 11. These safety lead-in data allowed us to move into the frontline FIGHT Phase 3 three trial and the design of this trial is summarized on Slide 12. The FIGHT trial is a randomized pivotal global registration trial evaluating the combination of bema and modify FOLFOX6 chemotherapy for the treatment of advanced gastric and gastroesophageal junction cancers. We're using tissue based IHC and blood a ctDNA testing to identify the estimated 10% of patients whose tumors overexpress FGFR2b. It is an event driven trial with overall survival as the primary endpoint. In China, where gastric cancer is common, we're collaborating with Zai Lab to identify and enroll patients. We invite already have over 70 sites recruiting patients in Asia, the US and Europe and we're on track to open nearly 200 clinical sites in 18 countries by the end of the year. The global geographic distribution of gastric cancer is summarized on slide 13. Moving on to FPA150, this is our first-in-class B7HR antibody. This antibody is designed to target tumor cells through to mechanisms of action, by blocking B7H4 from sending an inhibitory signal to CD80 cells and by enhancing killing of B7H4 overexpressing tumors to enhance ADCC. B7H4 is frequently overexpressed in breast, ovarian and endometrial cancers as depicted on slide 16. Moving on to slide 17, this slide summarizes our ongoing Phase 1a, 1b clinical trial designed to identify activity against B7H4 overexpressing tumors. In the 1b expansion, we are evaluating a 20 milligram per kilogram dose of FPA150 administered once every three weeks as monotherapy in various disease specific cohorts of patients whose tumors overexpress B7H4 such as hormone receptor positive breast cancer, triple negative breast cancer, ovarian and endometrial cancer. Last year we presented preclinical data supporting synergistic activity of the combination of PD-1 and B7H4 antibodies at the AACR annual meeting in 2018. Slide 18 shows that 50% of mice had a complete tumor response with a combination of mirroring FPA 150 and anti-PD-1. Not shown here, but also presented at AACR that these mice remain tumor free up to the end of the study at 120 days. Based on this data and the safety observed to date and the dose escalation, we plan to test the combination of the anti-PD-1 drug keytruda with FPA150 in patients with B7H4 over expressing ovarian cancer. We expect to begin enrollment of this combination cohort midyear. As Aaron mentioned, we plan to make to data disclosures on the FPA150 program this year. We expect the first data disclosure to be in June at ASCO. This will include safety and PK data from the Phase 1a dose escalation in all solid tumors and some preliminary data at doses of three and 10 milligrams per kilogram from the exploratory cohort of B7H4 positive patients. Later in the year at ESMO, we plan to disclose additional data from the exploratory cohort and preliminary data from the monotherapy expansion cohorts at the full 20 milligrams per kilogram dose. We also hope to have at least some safety data from the keytruda combination available for ESMO. Next is FPT155 shown on slide 21, this is our first in class CD80-Fc fusion protein molecule which Brian will be discussing further. We have initiated dose escalation in our Phase 1a, 1b clinical trial and we plan to present preliminary safety data at SITC in late November. Turning to our partner programs, cabiralizumab is our antibody that inhibits CSF1R and it's been shown to block the activation and survival tumor associated macrophages. This mechanism of action is illustrated on slide 25. Based on promising Phase 1, our partner BMS, has advanced development of cabira in pancreatic cancer. Slide 27 shows the Phase 2 trial design of cabira Opdivo in second line pancreatic cancer. BMS has been enrolling patients in this randomized, controlled safe-to-trial across sites in the US, Canada, Europe and Asia. And it's expected to enroll approximately 160 patients with locally advanced or metastatic pancreatic cancer. BMS, has demonstrated further commitment to cabira by initiating additional trials in multiple indications as shown on Slide 29. I'll now turn the call over to Bryan to review the preclinical rationale for the CD80 program and Tim-3 programs and a new discovery program.

[Bryan Irving:]

Thank you, Helen. At Five Prime, we have a unique platform that gives us a competitive advantage to identify new targets, address new cell types and ultimately develop protein therapeutics. Our dynamic screening platform is helping us discover differentiated therapies that we aim to advance rapidly into clinical development toward proof of concept. We also have multiple state of the art technologies to generate monoclonal antibodies as well as other protein therapeutics such as fusion proteins. One program I'd like to talk about is FPT155, as it was showing on slide 21, is the first-in-class CD80Fc fusion protein that is expected to potently enhance antitumor immunity as a monotherapy. We discovered FPT155 in vivo screen of approximately 800 immune associated secreted extra cellular domain proteins from our library which we call the immune. We screen these proteins individually and tumor bearing mice to identify those that enable tumor growth by immune dependent mechanisms. One of the most potent single agent proteins that we tested was CD80 as is shown on Slide 22. In FPT155, the CD80 extracellular domain is fused to the IgG1 Fc domain of an antibody to optimize its pharmacologic and PK properties. This drug candidate does two things. First, it's the natural receptor or binding partner for CD28, the key co-stimulatory receptor needed in addition to the T cell receptor for effective activation of T cells. So by applying the CD28 ligand exogenously with our drug, we can provide the co-stimulation T cells need to respond against the tumor. Importantly, we don't see super organism with its accompanying cytokines release that we're seeing with the CD28 targeted antibody. This is because the FPT155 requires co engagement of the T cell androgen receptor in addition to CD28 binding for its activity. Secondly, FPT155 blocks CTLA4 from competing for endogenous CD80 allowing CD28 signaling to prevail in T cell activation. FPT155 behaves differently than CTLA4 antibodies such as ipilimumab and tremelimumab because it directly interacts with CD28. In contrast to CTLA4 antibodies, FPT155 is not dependent on endogenous expression of CD28 ligands for its activity. So we can co-stimulate T cells in the tumor micro-environment where the CD28 ligands are often limiting. We know from preclinical work in tumor bearing mice that we pre-block CTLA4 with an antibody lacking effective function and therefore lacking efficacy as a single agent and then we administer FPT155 and FPT155 retains most of its activity independent of that engagement with CTLA4. Secondly in preclinical models, FPT155 has demonstrated strong single agent activity across a wide range of syngeneic tumor models including the B16-F10 model which is notoriously refractory to immune therapies that includes single agent entity deal for anti PD-1. So we believe this is a very different drug than anti-CTLA4 and could represent an important addition to immuno-oncology treatment options. The second program I'd like to talk about is Tim-3, which is illustrated on Slide 31. The Tim-3 antibody program that is partnered with Bristol-Myers Squibb is the first of three targets for our early stage research collaboration to enter the clinic and represents a novel mechanism of action that is generating strong interest. A unique structural feature of the Tim family confers binding to phosphatidylserine a phospholipid that in healthy cells is confined to the inner leaflet of the plasma membrane, but flips to the outer membrane upon program cell death. The exposure of phosphatidylserine is a signal for Tim-3 to bind and deliver an inhibitory signal that contributes to suppressing the immune response against the dying tumor cells. We believe this is the dominant interaction that explains the Tim-3 mechanisms of action and BMS-986258 has been confirmed to block Tim-3 binding to phosphatidylserine. In addition to these early stage clinical programs, we continue to advance later stage research programs. We currently have three undisclosed by Five Prime Controlled programs in lead generation. In addition, one exciting early stage area focuses on dendritic cells, the gatekeepers of the T cell response. We're working to identify proteins and enhance their antigen presenting capacity and their ability to activate an effective anti-tumor T cell response. So I continue to be excited by the potential of our platform that identifies normal targets leading to biologics that systematically drug the tumor micro-environment. I'll now turn the call over to David Smith to review our financial.

[David Smith:]

Thank you, Bryan. Details regarding our financial results can be found in the press release that we issued this afternoon as well as on Slides 34 and 35. Turning to our cash position, we finished 2018 with a strong balance sheet. Cash, cash equivalents and marketable securities totaled 270.1 million on December 31, compared to 292.7 million on December 31, 2017. The decrease was primarily attributable to cash used in operations which was offset in part by the 107.6 million in net proceeds from the January 2018 public offering of our common stock. Collaboration and license revenue for the fourth quarter of 2018 decreased by 9.2 million or 70% to 4 million from 13.2 million for the fourth quarter of 2017. The decrease was primarily due to Five Prime's recognition in the fourth quarter of 2017 of a 5 million milestone from BMS under the immune-oncology research collaboration, lower revenue under the cabira collaboration agreement and lower research and development funding from several older collaboration agreements partially offset by an increase from our collaboration with Zai Lab. Collaboration and license revenue for the year ended December 31, 2018, increased by 10.4 million or 26% to 49.9 million from 39.5 million for the year ended December 31, 2017. This increase was primarily due to 25 million of revenue recognized under our cabira collaboration agreement with BMS for BMS's achievement of the development milestone for the dosing of the first patient in the Phase 2 clinical trial of cabira in combination with Opdivo and an increase from our collaboration with Zai Lab that was partially offset by lower research and development funding from several older collaboration agreements. Research and development expenses for the fourth quarter of 2018 increased by $2 million or 6% to 34.7 million from 32.7 million, primarily due to increased clinical expenses associated with our FIGHT trial and FPA150 program partially offset by lower companion diagnostic development costs. Research and Development expenses for the year ended December 31, 2018 increased by 5.4 million or 4% to 156.3 million from 150.9 million for the year ended December 31, 2017. This increase was primarily related to milestone payments associated with the first patient dose in our FIGHT trial and companion diagnostic development costs that were partially offset by lower manufacturing and preclinical expenses. General and administrative expenses for the fourth quarter of 2018 decreased by $0.9 million or 9% to 9.6 million from 10.5 million, primarily due to lower compensation expenses. General and administrative expenses for the year ended December 31, 2018, were 39.7 million, which was essentially flat with the prior year. Net loss for the fourth quarter was 38.8 million or $1.12 per basic and diluted share, compared to a net loss of 29.2 million or $1.04 per basic and diluted share for the fourth quarter of 2017. Net loss for the full year 2018 was 140.4 million or $4.13 per basic and diluted share, compared to a net loss of 150.2 million or $5.38 per basic and diluted share for the full year 2017. Total shares outstanding were 34.7 million as of December 31, 2018. The weighted average shares outstanding for the full year 2018 was 34 million. Looking ahead, we expect full year 2019 net cash used in operations to be between 117 million and 122 million and estimate ending 2019 with cash, cash equivalents and marketable securities between 148 million and 153 million. Since the beginning of the year, we presented at investor conferences including JP Morgan and Guggenheim and will be in Boston next month at the Cowen Healthcare Conference. In the coming months, I look forward to meeting our investors at the conferences and other events that we will attend throughout the year. Now I'll ask the operator to open the call for Q&A and then Aron will end with closing remarks.

[Operator:]

[Operator Instructions] Our first question comes from Jonathan Chang with Leerink. Your line is now open.

[Unidentified Analyst:]

Hi, this is David Rich [ph] dialing in for Jonathan. Thanks for taking my questions and congratulations on the progress. Could you give investors any context on what to expect from the FPA150 dose escalation data at ASCO this year, specifically for patients unselected and then B7H4 expression, how many we can expect from each tumor type et cetera?

[Aron Knickerbocker:]

Yeah. David thanks for your question. And I think it is important to set expectations appropriately for ASCO. I'll turn it to Helen to describe what we intend to present there.

[Helen Collins:]

Yeah. So I think we're really happy with how fast this enrolled, I mean, you may recall we started our - this first patient went in at the very end of March last year and we had to start very low because this is a novel therapeutic. And so we're pleased to gotten to all our dose escalation, you're right that the dose escalation was an all comers. In this day and age, you try and advise your investigators to put patients who you think might turn out to be B7H4, but we didn't pre-screen patients. So we did get some patients in our dose escalation that are B7H4 positive and of course most of them will be dosed to the low dose. So whatever we have, we will present. Again, this is a wholly-owned, wholly-controlled molecule for us, so we won't be holding back on anything. In terms of the expansion which is going to be the pre-selected B7H4 patients and the specific tumor types. I think what we're all interested in, in terms of knowing about whether there's really efficacy that just we announced last week, just started enrolling, so that's why we really want to downplay that we're going to have much data for ASCO because as you know, by the time you do a data cut in the scan, et cetera, so we think the efficacy data is really going to be an ESMO story. But anything we have we'll present and hopefully have some PD data as well.

[Unidentified Analyst:]

Great, fair enough. And so it's safe to expect those efficacy data at ESMO then for the Phase 1b.

[Helen Collins:]

Yeah. Yeah. And again we enrolled really quickly on the dose escalation because we didn't have to pre-screen and we don't quite have a sense for how fast will enroll the 1b, now that we're making people pre-screen, but so we'll probably get a better sense of that over the next month or two.

[Unidentified Analyst:]

Great, thank you. And just one more question, given kind of the evolving gastric cancer landscape and some of the potential additions to frontline treatment options in the future, could you just provide some general context on how you view bemarituzumab is differentiated in the frontline setting moving forward? Thank you.

[Aron Knickerbocker:]

Yeah, maybe I'll comment and turn it to Helen. One is that this is the only agent that is specific for this target in development in front-line gastric cancer. And the presence of this target either by protein overexpression or detected by gene application is associated with reduced survival. So we know it's a poor prognostic factor to have FCFR2b overexpression, bema directly targets it and has two mechanisms of action in preventing the growth factors that signal to that receptor from binding, but also engaging the NK cells with enhanced ADCC due to its glycoengineering. So in that sense, it's a very differentiated drug and it specifically addresses this bad prognostic factor. That said, you're right, the gastric cancer landscape is constantly evolving including in frontline possibilities, but what we see is, for example, with FR2 which is the other target of anybodies for gastric cancer, we see very limited overexpression between the FR2 and FCFR2 to be very limited overlap and overexpression. And similarly for high PD-L1, we see very limited overlap between FCFR2 to be overexpression and for example, CPS10 or higher PD-L1. And Helen you can add anything else.

[Helen Collins:]

Yeah. No, I mean I think that is important in terms of the patient population. I mean, again, I love to see how those I-O trials read out. I think seeing how well this asked chemotherapy. I mean it again it's no gastric cancer, these patients have generally a - general very poor prognosis, right? The average survival I think and they ran trial and their control over again with 10 months. So 10 months and then if you think these patients would have FTFR2 may do worse than that, we're certainly - so again, I think we'll just have to see, right. Not much more to add actually to what Aron said.

[Unidentified Analyst:]

Great, no, that's very helpful, thank you and congrats again.

[Aron Knickerbocker:]

Thank you, David.

[Operator:]

[Operator Instructions] Our next question comes from Steve Seedhouse with Raymond James . Your line is now open.

[Steven Seedhouse:]

Hi, good afternoon. Aron, I'd be curious to hear your view of the Bristol acquisition of Celgene and any potential impact it might have on your collaborative relationship. Like, for example, are there any obvious synergies with any other Celgene pipeline, do you know programs or otherwise or on the other hand are you anticipating any reallocation of Bristol's resources away from certain collaboration programs with Five Prime?

[Aron Knickerbocker:]

Sure. Well, we've not seen anything with respect to the latter. In fact we're very pleased with what our partners are doing both with cabira and with Tim-3 and there's been no change to either of those programs in light of the Celgene merger announcement. First, that merger is not closed and may not close until the second half of the year. And as far as we can tell, there's no integration yet happening until that closes. But one thing to notice when both Bristol-Myers Squibb and Celgene made their joint presentation at the start of the year in which they announced this merger, they cited high potential agents and pipeline assets to watch and the CSF1R cabira program was on that list. So you can take that for what you will, but we think it's a priority program for BMS and it's one that they're looking at as an asset to watch and guiding investors accordingly. In terms of synergies of course Abraxane is a Celgene drug and that is one of the drugs that's been tested in combination with cabira and Opdivo in the second line pancreatic cancer Phase 2 trial. So that's a possible synergy, for instance, enhanced efficacy as seen with Abraxane in Gemcitabine. But beyond that we haven't seen specific synergies yet that we think would impact either of our programs, but of course we'll be mindful and watching for those. But just to reiterate there's been no diminution of prioritization or emphasis or resources for either of the programs.

[Steven Seedhouse:]

Okay, appreciate that. Thanks. And just regarding FPA150, so I understand you're going to be doing pre end-on treatment biopsies to look at PD markers in the tumor micro-environment, so tumor immune infiltrates and cytokines, so maybe Aron or Helen I was just curious about that experiment. Are there specific biomarkers you're looking for? Is this more just sort of an exploratory analysis and what time post treatment are you going to be taking biopsies and what would be positive data I guess that would emerge from that experiment? How would you characterize positive data?

[Helen Collins:]

Yeah, that's a great question. I mean, because this is this is a drug that has a very specific biomarker already, right. That's the B7H4 and I think on our slide deck you can see that when you see it, it tends to be very homogeneous and fairly highly expressed. So these really are exploratory biomarkers and they're getting a baseline and on treatment. So it's nice. I mean, so it won't be at the time of progression, it's one that's actually on treatment. And it's not an all the patients, but a proportion. So it's exploratory, we haven't said more about it, but what we have we will present at ASCO.

[Steven Seedhouse:]

Okay, is every patient getting tested at the same time post treatment or is it flexible?

[Helen Collins:]

No, it's at the same time, so it's really looking at on treatment effects right. Are there any PD effects, mechanism of action kind of effect.

[Steven Seedhouse:]

Okay. And maybe just one last question for David. Are there any further restructuring changes, I guess in 2019 contemplated in the cash used in yearend '19, estimated cash guidance you guys provided?

[David Smith:]

No, we don't have any other - anything like that contemplated in any of our guidance.

[Steven Seedhouse:]

Okay, great. Thanks, guys. Appreciate the questions.

[Aron Knickerbocker:]

Thanks, Steve.

[Operator:]

Our next question comes from Jim Birchenough with Wells Fargo. Your line is now open.

[Unidentified Analyst:]

Good afternoon, it's Nick on for Jim this afternoon. So starting with 1b, it looks like in the expansion cohorts that no longer a bladder expansion cohort. Why is this and also can you remind us what the trigger is to start enrolling patients into the expansion cohorts?

[Helen Collins:]

Yeah, so I can answer that. So the bladder was actually a couple of things. One was that when we as opposed to what may be out there initially published when we actually looked at the frequency of B7H4 was not as high as had been published by the people. The other is just the bladder space in terms of the high PD1 and I think the path to getting something quickly approved, so it was just deprioritized, so I wouldn't say it's off the list it was just deprioritized. And then in terms of trigger for enrollment for 1b, so that was really based on a - mostly going on our preclinical predictive models in terms of where we thought we would see efficacy and of course then on - and the safety and tolerability and again more to come in at ASCO about that safety and tolerability.

[Unidentified Analyst:]

Sorry, I meant in terms of timing actually when - what's trigger for opening the cohorts?

[Helen Collins:]

So that opened last week. So we've enrolled our first patient, actually opened a couple of weeks ago and the first patient was dosed last week in the 1b.

[Unidentified Analyst:]

That's the exploratory. Sorry, I talked about - I was meaning the designs breast, ovarian and endometrial cancer.

[Helen Collins:]

Yeah. No I'm sorry, if I wasn't clear. Yeah, so we did 1a dose escalation, all comers. We had some exploratory at lower than our final dose and then we've completed dose escalation. We have actually opened the pre-specified ovarian, breast, endometrial cancer cohorts with the first patient dosing last week.

[Aron Knickerbocker:]

So those are the 1b's, just to be clear, all at 20 milligrams per kilogram.

[Unidentified Analyst:]

Yeah. Okay, in the exploratory, I mean, did you enroll the 10 target patients already in that?

[Helen Collins:]

We have and at the very end, so again happily the investigators were very interested in the trial. So those we're enrolling in parallel with the dose escalation. And again, so yes, we will have some of that data. That's why we're sort of downplaying about some of that data for ASCO because, again, the dose escalation went so quickly that it's not going to be patients who've been on. They're going to be lower than the final dose, and for not very much time. So what we have will present, just don't - we don't have that data.

[Unidentified Analyst:]

So none of the exploratory cohort made it to 20?

[Helen Collins:]

That was on purpose. So on purpose we were putting some B7H4 positive patients at what we thought would be lower than the final dose. Again, it would give you a little more information potentially about mechanism of action. They have the biopsies, toxicity, if there was some long-term late toxicity, we would have more patients at some of those doses. So those are a few reasons to do that.

[Aron Knickerbocker:]

Yeah, but all below 20.

[Unidentified Analyst:]

And then one more question on 150 and that is, so you're going to have two different ovarian cancer cohorts monotherapy pembro combo. Are those the same population's ovarian cancer patients or are they two different populations?

[Helen Collins:]

Yeah, they're - the inclusion criteria are very similar because PD1s or not approved. PD1 or PDO1 in ovarian cancer, so we're looking at - they're similar in terms of inclusion criteria.

[Unidentified Analyst:]

And this gives you the opportunity to ask a question, what is pembro adding on top of 150?

[Helen Collins:]

Yeah, exactly.

[Unidentified Analyst:]

Okay and then just quickly switching to bema, I see that you just listed a single patient expanded access program and well done to you for doing that. Now, how long is this patient on bema and why do you think this patient's tumor is not mutating away from its dependence?

[Helen Collins:]

Nick, that is a great - you're right, that's a $64 million question, that's a great question. We have a patient that's doing very well, has been on - for people on the call, on the Phase 1 dose escalation and we wanted to close that trial down as everybody else has asked towards this single patient trial is allowing that patient to remain therapy. It's a Phase 1 trial, so we're limited what information we have about the patient. I'm afraid I can't give you much information. I mean, it's great that they're still doing well, but.

[Unidentified Analyst:]

And roughly how long they've been on?

[Helen Collins:]

Three years, I would have to look that up. I would look that.

[Aron Knickerbocker:]

Over two.

[Unidentified Analyst:]

Over two is good enough. Thank you. Thank you for taking the questions.

[Helen Collins:]

Thank you, Nick.

[Helen Collins:]

It's a safe drug.

[Operator:]

Our next question comes from Salveen Richter with Goldman Sachs. Your line is now open.

[Unidentified Analyst:]

Yes, hi. It's Maryann [indiscernible] for Salveen. Thanks for taking my question and congrats on the progress. I have two quick ones, one was on bema [indiscernible] that is a safe drug that I wanted to understand that had the rationale and the decision to go forward with the dose from the Phase 1 study and a little bit on the safety profile from what you discovered in Phase 1. And I have a follow up.

[Helen Collins:]

Yeah. No, I'm glad actually you asked that because certainly we have limited data before we say a drug is safe, so we've done the dose escalation and that was monotherapy. And then the data we presented at ASCO GI was looking at the combination of bema with chemotherapy and so -

[Aron Knickerbocker:]

We tested two dose levels.

[Helen Collins:]

Yeah, we tested two dose levels and the dose that we ended up was a dose similar to what was the maximum dose in the Phase1, so there was no added toxicity that was identified today with adding the two together. But again the Phase 3 trial will really be the trial that answers the question in terms of a large number of patients and its tolerability and safety.

[Unidentified Analyst:]

Got it and then a quick one on restructuring, we just wanted understand from the announcement, how do you think that the restructuring is going to down between the R&D and the SG&A? Thank you.

[David Smith:]

Sure. So as we announced at the time of the restructuring, the focal areas were we reduced headcount, reduced force were in research, pathology and manufacturing. That said, we did close some open positions in G&A, so we made a decision not to sell some of those open positions, but the actual positions that were reduced came primarily from research as well as a few from pathology and manufacturing.

[Unidentified Analyst:]

Thanks a lot.

[David Smith:]

And the intent of that just to remind you was to refocus our resources on - or emphasize resource in the clinical stage programs, the late stage research programs and some very focused efforts in discovery, for example dendritic cell program, the brand briefly described today.

[Unidentified Analyst:]

Got it, thanks for the color.

[David Smith:]

You're welcome. Thanks Maryann.

[Operator:]

Our next question comes from Kennen MacKay with RBC Capital Markets. Your line is now open.

[Kennen MacKay:]

Hi, thanks for taking the question. On bema and data there was at ASCO GI earlier this year, I was wondering if you could discuss the congruence and sort of the expected congruence between the two diagnostic techniques the IHC versus circulating tumor DNA and ultimately sort of how you expect to make a choice for companion diagnostic there? And then secondarily on that Phase 1 preliminary data, can you help us understand maybe what FOLFOX could be expected to do there from a response rate perspective and any thoughts that you have on the PR being the - for patients with negative FGFR2b would be future I appreciate it. Thank you.

[Aron Knickerbocker:]

Sure. Thanks, Ken and nice to hear from you. So we can start with IHC and ctDNA. We didn't use that in the safety lead-in.

[Helen Collins:]

Yeah, so it's Helen. So the first question in terms of for the Phase 3 trial, so the reasoning for using the IHC and ctDNA has to do with the data from our monotherapy trial where on that study, all the patients were selected based on having high immunity to chemicals, protein expression on the outside of the tumor cell. What we found was all the patients who were IHC were also amplified. And so the fair amount of data was convention. Amplification can be picked up by ctDNA. And what we know is that if you just use IHC and patients nowadays usually just get a small core biopsy at the time of diagnosis that in gastric cancer, these protein overexpression, whether it's FR2 , FGFR2 whatever it may be is very heterogeneous, so you may miss that. And so what we found was that if you looked at the IHC and the ctDNA that these were like a Venn diagram overlapping patient populations, but they are slightly different and that by using both of them we expect to get 10%. In terms of the trial designs that both of these would be CDXs if the drug is approved and that patients for a clinical trial can be diagnosed by either being IHC positive or ctDNA positive because again there are some patients who will only be IHC because their tumor doesn't shed, there'll be some patients who are ctDNA positive because the biopsy missed it and then there are some patients who are positive for both. In terms of what you saw now on the ASCO GI poster, that our safety lead-in adding bema to chemotherapy did not require patience to be FGFR2 positive, but retrospectively, we collected tissue on those that we could and we collected ctDNA on those that we could. And so I think what you see there is a reflection in some ways of what we may see as we're trying pre-select patients and our Phase 3 trial, but some patients will be positive of one or the other. In terms of the colorectal cancer patient, all I can do is say these patients are getting FOLFOX, I would have to go back and look and see what this patients prior therapy is, whether they'd had FOLFOX previously or whether this is the first time that they were receiving FOLFOX. I think we pointed out it is interesting that the two patients with gastric cancer who are on this - had received FOLFOX previously and it's interesting that they both had evidence of activity to the combined therapy even though they previously received for FOLFOX, but I'd have to go back to the colorectal cancer patient and see if they received FOLFOX previously.

[Kennen MacKay:]

Got you, thank you, that's really helpful color.

[Helen Collins:]

Yeah.

[Operator:]

At this time I'm showing no further questions. I'd like to turn the call back over for closing remarks.

[Aron Knickerbocker:]

Thanks, Scarlett. As I said at the beginning of the call, it's an exciting time at Five Prime. We have a very robust pipeline of Five Prime Controlled and Fully Partnered programs targeting multiple cell types in the tumor micro-environment. We have a year of many expected data readouts and milestones and the financial resources to achieve our goals. And with that, I'd like to thank you all today for joining us. And also I'd like to thank the patients and investigators participating in our clinical trials, our Five Prime employees and our strategic collaborators who all contribute to the continued advancement of our clinical programs. We look forward to updating you on future calls. Thank you.

[Operator:]

Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program. You may not disconnect. Everyone have a great day.