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Edited Transcript of FPRX earnings conference call or presentation 26-Feb-19 9:30pm GMT

Q4 2018 Five Prime Therapeutics Inc Earnings Call

San Francisco Mar 20, 2019 (Thomson StreetEvents) -- Edited Transcript of Five Prime Therapeutics Inc earnings conference call or presentation Tuesday, February 26, 2019 at 9:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Aron Marc Knickerbocker

Five Prime Therapeutics, Inc. - President, CEO & Director

* Bryan Irving

Five Prime Therapeutics, Inc. - Executive VP & Chief Scientific Officer

* David V. Smith

Five Prime Therapeutics, Inc. - Executive VP & CFO

* Helen Louise Collins

Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer

* Martin Forrest

Five Prime Therapeutics, Inc. - VP of IR & Corporate Communications

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Conference Call Participants

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* David Simms Ruch

SVB Leerink LLC, Research Division - Associate

* Kennen B. MacKay

RBC Capital Markets, LLC, Research Division - Co-Head of Biotechnology Research

* Maryana Ilya Breitman

Goldman Sachs Group Inc., Research Division - Research Analyst

* Nicholas M. Abbott

Wells Fargo Securities, LLC, Research Division - Associate Analyst

* Steven James Seedhouse

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

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Presentation

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Operator [1]

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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.

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Martin Forrest, Five Prime Therapeutics, Inc. - VP of IR & Corporate Communications [2]

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Thank you, Skyler. And good afternoon, everyone, 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 & Presentations page that we will refer to during our prepared remarks.

Today joining me today are Aron Knickerbocker, Chief Executive Officer; and 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.

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Aron Marc Knickerbocker, Five Prime Therapeutics, Inc. - President, CEO & Director [3]

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Thanks, Martin. Good afternoon, and thanks for joining us today. Before we get started, I'd like to welcome two 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 Forrest, who we 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 how 2019 will be a year of multiple data readouts, clinical milestone events and continued development of novel biologics for patients facing cancer. On our call today I'll review the highlights of our 5 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 Bryan 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 5 programs are uncorrelated and we are systematically drugging the tumor microenvironment 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 lead-in 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 B7-H4. This target is in the same family of checkpoint molecules as PD-L1. However, we have found that B7-H4 is overexpressed in tumors such as breast, ovarian and endometrial cancers that are not well served by checkpoint inhibitors. This month we completed FPA150 dose escalation, selected 20 milligrams per kilogram every 3 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 KEYTRUDA in patients with B7-H4 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 a co-stimulatory ligand 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 CSF1 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 is being developed by BMS. TIM-3 is involved in suppressing 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 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 3 checkpoint pathways, TIM-3 being the first of those to produce a clinical candidate.

Slide 6 summarizes data disclosures and activities across all 5 clinical programs. So starting with the Five Prime controlled programs on the left, we've already presented the safety lead-in data from the FIGHT trial for bema. In 2019, we expect to make 2 data disclosures for our FPA150 program at ASCO and ESMO. Helen will provide the details about those later during this call.

Looking to FTP155, 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've maintained ongoing dialog 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 will now turn the call over to Helen to review highlights from our clinical programs in more detail.

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [4]

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Thank you, Aron. Progress was made across all 5 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 FOLFOX-6 chemotherapy at the ASCO GI meeting in January. We did not observe any dose-limiting toxicities with the combination in the safety lead-in and chemotherapy did not impact 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 FOLFOX alone.

Data from the safety lead-in is summarized on Slide 11. These safety lead-in data allowed us to move into the front line FIGHT Phase 3 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 modified FOLFOX-6 chemotherapy for the treatment of advanced gastric and gastroesophageal junction cancers. We're using tissue-based IHC and blood-based 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 Labs to identify and enroll patients. We and Zai already have over 70 sites recruiting patients in Asia, the U.S. 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 B7-H4 antibody. This antibody is designed to target tumor cells through 2 mechanisms of action, by blocking B7-H4 from sending an inhibitory signal to CD8 T-cells and by enhancing killing of B7-H4 overexpressing tumors through enhanced ADCC. B7-H4 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 B7-H4 overexpressing tumors. In the 1b expansion, we are evaluating a 20 milligram per kilogram dose of FPA150 administered once every 3 weeks as monotherapy in various disease specific cohorts of patients whose tumors overexpress B7-H4, 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 B7-H4 antibodies at the AACR Annual Meeting in 2018. Slide 18 shows that 50% of mice had a complete tumor response with a combination of murine, FPA150 and anti-PD-1. Not shown here but also presented at AACR is that these mice remained tumor free up to the end of the study at 120 days. Based on this data and the safety observed to date in the dose escalation, we plan to test the combination of the anti-PD-1 drug KEYTRUDA with FPA150 in patients with B7-H4 overexpressing ovarian cancer. We expect to begin enrollment of this combination cohort in a year.

As Aron mentioned, we plan to make 2 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 3 and 10 milligrams per kilogram from the exploratory cohort of B7-H4 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 milligram 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 Bryan 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 partnered programs, cabiralizumab is our antibody that inhibits CSF1R and has been shown to block the activation and survival of tumor-associated macrophages. This mechanism of action is illustrated on Slide 25. Based on promising Phase 1 data, our partner BMS has advanced development of cabira in pancreatic cancer. Slide 27 shows the Phase 2 trial design of cabira plus OPDIVO in second line pancreatic cancer. BMS has been enrolling patients in this randomized controlled Phase 2 trial across sites in the U.S., Canada, Europe and Asia and is 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.

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Bryan Irving, Five Prime Therapeutics, Inc. - Executive VP & Chief Scientific Officer [5]

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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 illustrated on Slide 21, FPT155 is a first-in-class CD80-Fc fusion protein that is expected to potently enhance anti-tumor immunity as a monotherapy. We discovered FPT155 in an in vivo screen of approximately 800 immune-associated secreted and extracellular domain proteins from our library, which we call the Immunome.

We screen these proteins individually in tumor-bearing mice to identify those that inhibit 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 2 things.

First, it's the natural 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 superagonism with its accompanying cytokine release that was seen with the CD28 targeted antibody. This is because FPT155 requires co-engagement of the T-cell antigen receptor in addition to the CD28 binding for its activity. Secondly, FPT155 blocks CTLA-4 from competing for endogenous CD80, allowing CD28 signaling to prevail in T-cell activation.

FPT155 behaves differently than CTLA-4 antibodies such as ipilimumab and tremelimumab because it directly interacts with CD28. In contrast to CTLA-4 antibodies, FPT155 is not dependent on endogenous expression of CD28 ligands for its activity. So we can co-stimulate T-cells in the tumor microenvironment where the CD28 ligands are often limiting.

We know from preclinical work in tumor-bearing mice that if we pre-block CTLA-4 with an antibody lacking effector function and therefore lacking efficacy as a single agent, and then we administer FPT155, FPT155 retains most of its activity independent of that engagement with CTLA-4. 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 include single-agent anti-CTLA-4 or anti-PD-1. So we believe this is a very different drug than anti-CTLA-4 and could represent an important addition to immune 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 3 targets from 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 a suppressing of the immune response against the dying tumor cells. We believe this is the dominant interaction that explains the TIM-3 mechanism 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 3 undisclosed Five Prime controlled programs in lead generation. In addition, one exciting early stage area of focus is on dendritic cells, the gatekeepers of the T-cell response. We're working to identify proteins that enhance their antigen presenting capacity and their ability to actively affect an anti-tumor T-cell response.

So I continue to be excited by the potential of our platform that identifies novel targets leading to biologics that systematically drug the tumor microenvironment. I'll now turn the call over to David Smith to review our financials.

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David V. Smith, Five Prime Therapeutics, Inc. - Executive VP & CFO [6]

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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 immuno-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've presented at investor conferences including JP Morgan and Guggenheim and we'll 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 to Q&A and then Aron will end with closing remarks.

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Questions and Answers

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Operator [1]

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(Operator Instructions) Our first question comes from the Jonathan Chang with Leerink.

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David Simms Ruch, SVB Leerink LLC, Research Division - Associate [2]

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This is David Ruch dialing in for Jonathan. Thanks for taking my questions and congratulation 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 those with the B7-H4 expression, how many we can expect from each tumor type, et cetera?

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Aron Marc Knickerbocker, Five Prime Therapeutics, Inc. - President, CEO & Director [3]

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Yes, 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.

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [4]

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Yes, so I think we're really happy with how fast this enrolled. I mean you may recall we started, 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 have gotten through 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 B7-H4, but we didn't pre-screen patients. So we did get some patients in our dose escalation that are B7-H4 positive. And of course, most of them are going to be dosed at a low dose. So whatever we have, we will present. Again, this 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 preselected B7-H4 patients in 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 and the scan, et cetera. So we think the data, the efficacy data is really going to be an ESMO story, so safety [and efficacy]. But anything we have we'll present and hopefully you have some PD data as well.

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David Simms Ruch, SVB Leerink LLC, Research Division - Associate [5]

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Great. Fair enough and so it's safe to expect those efficacy data at ESMO then for the Phase 1b?

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [6]

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Yes, and again, we enrolled really quickly on the dose escalation because we didn't have to prescreen and we don't quite have a sense for how fast we'll enroll the 1b now that we're making people prescreen. So we'll probably get a better sense of that over the next month or 2.

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David Simms Ruch, SVB Leerink LLC, Research Division - Associate [7]

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Great. 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 as differentiated in the frontline setting moving forward?

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Aron Marc Knickerbocker, Five Prime Therapeutics, Inc. - President, CEO & Director [8]

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Yes, maybe I'll start and turn it to Helen. But one is that this is the only agent that is specific for this target in development in frontline 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 FGFR2b overexpression. Bema directly targets it and has 2 mechanisms of action in preventing the growth factors that signal it through that receptor from binding, but also engaging the NK cells with enhanced ADCC due to its [glycol-]engineering. 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 any frontline possibilities. But what we see is for example with HER2, which is the other target of antibodies for gastric cancer, we see very limited overexpression between HER2 and FGFR2b, very limited overlap in overexpression. And similarly for high PD-L1, we see very limited overlap between FGFR2b overexpression and for example CPS 10 or higher PD-L1. And Helen can add anything else.

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [9]

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Yes, no, I'm going to think that is important in terms of the patient population. I mean again, we'll have to see how those I/O trials readout. I think seeing how well this adds to chemotherapy, I mean as you know, gastric cancer, these patients have in general a very poor prognosis, right? The average survival I think from the ramu trial, their control arm again was 10 months. So and then if you think these patients with FGFR2 may do worse than that, we're certainly -- so again, I think we'll just have to see, right? I don't have that much more to add, actually than what Aron said.

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Operator [10]

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(Operator Instructions) Our next question comes from Steve Seedhouse with Raymond James.

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Steven James Seedhouse, Raymond James & Associates, Inc., Research Division - Research Analyst [11]

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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 of the Celgene pipeline, Juno 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?

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Aron Marc Knickerbocker, Five Prime Therapeutics, Inc. - President, CEO & Director [12]

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Sure. Well, we have 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. Of course that merger is not closed and may not close until the second half of the year. And as far as we can tell, there is no integration yet happening until that closes. But one thing to note is 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 being tested in combination with cabira and OPDIVO in the second-line pancreatic cancer Phase 2 trial. So that's a possible synergy, for instance, if enhanced efficacy is seen with ABRAXANE and 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.

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Steven James Seedhouse, Raymond James & Associates, Inc., Research Division - Research Analyst [13]

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Okay, appreciate that. And just regarding FPA150, so I understand you're going to be doing pre and on-treatment biopsies to look at PD markers in the tumor microenvironment, 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 or is the 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?

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [14]

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Yes, that's a great question. I mean because this is a drug that has a very specific biomarker already, right? That's the B7-H4 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 baseline and on-treatment, so it's not actually -- so it won't be at the time of progression. It's while they're actually on-treatment. And it's not on 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.

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Steven James Seedhouse, Raymond James & Associates, Inc., Research Division - Research Analyst [15]

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

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [16]

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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 effects?

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Steven James Seedhouse, Raymond James & Associates, Inc., Research Division - Research Analyst [17]

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Okay, and maybe just one last question for David. Are there any further restructuring changes, I guess, in 2019 contemplated in the cash use and year-end '19 estimated cash guidance you guys provided?

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David V. Smith, Five Prime Therapeutics, Inc. - Executive VP & CFO [18]

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

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Operator [19]

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Our next question comes from the Jim Birchenough with Wells Fargo.

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Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Associate Analyst [20]

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It's Nick on for Jim this afternoon. Just starting with 150, it looks like in the expansion cohort there's no longer a bladder expansion cohort. Why is this and also can you remind us of what the trigger is to start enrolling patients into the expansion cohorts?

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [21]

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Yes, 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 B7-H4 it was not as high as had been published by other people. The other is just the bladder space in terms of the highs of PD-1 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 mostly again 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 at ASCO about that safety and tolerability.

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Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Associate Analyst [22]

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

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [23]

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

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Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Associate Analyst [24]

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

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [25]

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Yes, so no. I'm sorry if I wasn't clear. Yes, 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 and we have actually opened the pre-specified ovarian, breast, endometrial cancel cohorts with the first patient dosing last week.

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Aron Marc Knickerbocker, Five Prime Therapeutics, Inc. - President, CEO & Director [26]

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

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Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Associate Analyst [27]

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Okay, and in the exploratory, did you enroll the 10 target patients already in that?

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [28]

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We have and at the very end, so again, happily the investigators were very interested in the trial. So those were 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 it. We'll have 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 have been lower than the final dose and for not very much time. So what we have we'll present. We just don't have that data yet.

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Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Associate Analyst [29]

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So none of the exploratory cohort made it to 20?

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [30]

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That was on purpose. So on purpose, we were putting some B7-H4 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 some long-term late toxicity, we would have more patients at some of those doses. So there's a few reasons to do that.

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Aron Marc Knickerbocker, Five Prime Therapeutics, Inc. - President, CEO & Director [31]

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Yes, but all below 20.

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Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Associate Analyst [32]

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And then one more question on 150 and that is, so you're going to have 2 different ovarian cancer cohorts, monotherapy, pembro combo. Are those the same populations of ovarian cancer patients or are they 2 different populations?

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [33]

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The inclusion criteria are very similar. Because as you know, PD-1s are not approved, PD-1 or PD-L1 in ovarian cancer. So we are looking at they are similar in terms of inclusion criteria.

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Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Associate Analyst [34]

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

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [35]

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Yes, exactly.

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Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Associate Analyst [36]

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

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [37]

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Oh, Nick, that is a great-- like you're right. That's a $64 million question. That's a great question. Yes, we have a patient that is 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 is off. And so this single patient trial is allowing that patient to remain on therapy. But it's a Phase 1 trial. So we're limited in what information we have about the patients. So I'm afraid I can't give you much information. I mean it's great that they're still doing well. But--

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Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Associate Analyst [38]

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And roughly how long have they been on [currently]?

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [39]

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How long? 3 years? I would have to look that up.

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Aron Marc Knickerbocker, Five Prime Therapeutics, Inc. - President, CEO & Director [40]

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Over 2.

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Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Associate Analyst [41]

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Over 2 is good enough.

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [42]

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It's a safe drug.

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Operator [43]

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

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Maryana Ilya Breitman, Goldman Sachs Group Inc., Research Division - Research Analyst [44]

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It's Maryana Breitman for Salveen. Thanks for taking my question and congrats on the progress. I have two quick ones. One was on bema safety again. I mean you just mentioned that it's a safe drug. But I wanted to understand better the rationale behind the decision to go forward with the dose from the Phase 1 study and a little bit on the safety profile from what you've discovered in Phase 1. And I have a follow-up.

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [45]

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

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Aron Marc Knickerbocker, Five Prime Therapeutics, Inc. - President, CEO & Director [46]

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We tested 2 dose levels.

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [47]

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Yes, we tested 2 dose levels and the dose that we ended up with is a dose similar to what was the maximum dose in the Phase 1. So there was no added toxicity that was identified to date with adding the 2 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.

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Maryana Ilya Breitman, Goldman Sachs Group Inc., Research Division - Research Analyst [48]

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

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Aron Marc Knickerbocker, Five Prime Therapeutics, Inc. - President, CEO & Director [49]

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Sure. So as we announced at the time of the restructuring, the focal areas where we've 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 fill 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. And the intent of that, just to remind you, was to refocus our resources on -- or emphasize resourcing the clinical stage programs, the late stage research programs, and some very focused efforts in discovery, for example, the dendritic cell program that Bryan briefly described today.

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Operator [50]

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Our next question comes from Kennen MacKay with RBC Capital Markets.

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Kennen B. MacKay, RBC Capital Markets, LLC, Research Division - Co-Head of Biotechnology Research [51]

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On bema and the data that was at ASCO GI earlier this year, I was wondering if you could discuss the congruence and sort of the expected congruence between the 2 diagnostic techniques, the IHC versus the circulating tumor DNA and ultimately sort of how you expect to make a choice for a 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 in the colorectal patient who is negative for FGFR2b would be hugely appreciated.

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Aron Marc Knickerbocker, Five Prime Therapeutics, Inc. - President, CEO & Director [52]

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

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Helen Louise Collins, Five Prime Therapeutics, Inc. - Senior VP & Chief Medical Officer [53]

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Yes, so it sounded like -- 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 immunohistochemical protein expression on the outside of the tumor cell.

What we found was all the patients who were IHC high were also amplified. And so there's a fair amount of data. Well as you can imagine, 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 HER2, FGFR2 or whatever it may be; is very heterogeneous. So you may miss that. And so what we've 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 is designed that both of these would be CDX's when and 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 will 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 patients 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 to pre-select patients in our Phase 3 trial. Some patients will be positive, 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 patient's 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 2 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'd previously received FOLFOX. But I'd have to go back to the colorectal cancer patient and see if they'd received FOLFOX previously.

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Operator [54]

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

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Aron Marc Knickerbocker, Five Prime Therapeutics, Inc. - President, CEO & Director [55]

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Okay, thanks, Skyler. As I said at the beginning of the call, it's an exciting time at Five Prime and we have a very robust pipeline of Five Prime controlled and fully partnered programs targeting multiple cell types in the tumor microenvironment. 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.

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Operator [56]

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Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everyone have a great day.