Five Prime Therapeutics, Inc. (NASDAQ:FPRX) Q3 2018 Earnings Conference Call November 6, 2018 4:30 PM ET
Heather Rowe - Senior Director of Investor Relations and Corporate Communications
Aron Knickerbocker - Chief Executive Officer
Helen Collins - Chief Medical Officer
Bryan Irving - Chief Scientific Officer
Linda Rubinstein - Interim Chief Financial Officer
Nick Abbott - Wells Fargo
Jonathan Chang - Leerink Partners
Alex Heller - Jefferies
Justin Burns - RBC Capital Markets
Eric Josephs - JPMorgan
Steve Seedhouse - Raymond James
Good day, ladies and gentlemen, and welcome to the Five Prime Therapeutics Third Quarter 2018 Earnings Call. As a reminder, this conference may be recorded.
I'd now like to introduce your host for today's conference, Heather Rowe, Senior Director, Investor Relations and Corporate Communications. You may begin.
Good afternoon and thank you for joining us. I would like to welcome everyone to our conference call to discuss results for the third quarter 2018. We issued a press release this afternoon and also posted slides to accompany this presentation. The slides can be found under the Investor Relations section of our Web site under Events and Presentations.
Joining me today are Aron Knickerbocker, Chief Executive Officer, Dr. Helen Collins, Chief Medical Officer; Dr. Bryan Irving, Chief Scientific Officer; and Linda Rubinstein, Interim Chief Financial Officer.
Today's conference call will include forward-looking statements under the Private Securities Litigation Reform Act of 1995, including statements regarding our research and development programs and financial outlook. Actual results may differ from those indicated by these forward-looking statements due to numerous factors, including those discussed in the Risk Factors section of our SEC filings.
Our expectations and assumptions could change. While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so, even if our views change.
I will now turn the call over to Aron.
Thanks Heather. Good afternoon and thanks for joining us today to review our third quarter 2018.
Highlights appear on Slide 3. Our teams are executing extremely well across the pipeline. The current status of which is shown on Slide four. All of our Five Prime sponsor trials are meeting or beating their original development timelines, which is a testament to the integrated efforts of our teams and our relentless focus on only pursuing high value medically important studies.
We now have five drug candidates in the clinic that we are developing either on our own or with our collaborators. Typically our product candidates are only in class, first in class or meaningfully differentiated in other ways. We look for single agent activity or clear activity in for example tumor types that are rarely sensitive to Checkpoint inhibitors.
Our immuno-oncology drug candidates address multiple immune cell types in the tumor microenvironment.
I will start my review of our programs with bemarituzumab or bema our most advanced drug candidate. In the third quarter, we completed the Phase 1 safety lead-in portion of our FIGHT global registration trial and with our partner Zai Lab began the Phase 3 portion of the trial. You can see our bema market assumptions on Slide 5. We think this represents an attractive global market opportunity.
Next is cabiralizumab or cabira, BMS' ongoing randomized forearm Phase 2 clinical trial continues to enroll. This trial is evaluating cabira and OPDIVO with and without chemotherapy as a second line treatment in patients with advanced pancreatic cancer. We have already shown that cabira and OPDIVO without any chemotherapy demonstrate deep and durable responses in patients who are receiving their median fourth line treatment for advanced pancreatic cancer. And we hope to provide even more benefit by adding chemotherapy which we know to be synergistic and preclinical models of pancreatic cancer.
The current trial could generate data that would support a frontline and or a second line pivotal trial. And importantly BMS has opened and continues to open sites around the world including in the United States, Europe and Asia. BMS' partner in Asia, Ono has opted into the development of cabira.
Slide 6 shows the estimated incidence of pancreatic cancer by line of therapy in the major markets. We think that commercial opportunity for cabira in pancreatic cancer is significant. We were pleased to hear BMS on their most recent earnings call mentioned cabira when expressing their sense of urgency to help patients find new treatment options. BMS referred to the cabira and OPDIVO trial in pancreatic cancer as an example of a randomized Phase 2 trial designed to isolate the impact of the new regimen.
In this case cabira and OPDIVO as an antibody doublet or on top of chemo versus chemo alone in a setting such as pancreatic cancer. In their words, this is an example of an area that is screaming for innovation and where the market and patients are demanding new options. They made the point that this is especially true in microsatellite stable pancreatic cancer.
BMS is also supporting several investigator sponsored trials evaluating additional combinations that include cabira. One example is a trial sponsored by UCSD and supported by Stand Up To Cancer and BMS. This trial called the GemCaN can trial is a randomized Phase 2 frontline maintenance trial to determine whether the combination of gemcitabine with cabira and OPDIVO can provide prolonged disease control in patients with advanced pancreatic cancer compared to gemcitabine alone.
Another example is the clinical trials sponsored by the Yale Cancer Center and supported by Apexigen and BMS. This trial is evaluating Apexigen CD40 antibody in combination with cabira and OPDIVO in patients with melanoma lung cancer or renal cell carcinoma who progressed on prior anti-PD-1 or PD-L1 therapy. Beyond bema and cabira, our FPA150 and FPT155 programs also have the potential to address multiple tumor indications.
I will start with that FPA150, which is our first-in-class antibody targeting B7H4. This target is in the same family of checkpoint molecules as PD-L1. In fact, B7H4 behaves pretty clinically a lot like PD-L1 and that it strongly inhibits T-cells. B7H4 is generating a lot of excitement in the investigator community because it's expressed in multiple cell types, multiple tumor types including tumor types that are not well served by immunotherapy today such as breast and gynecologic cancers.
Our plan is to move as fast as possible to generate proof-of-concept and then hopefully to later stage development and we are moving quickly. In October, we initiated dosing in an exploratory basket cohort of our Phase 1a/1b clinical trial to investigate FPA150 monotherapy in patients with any cancer whose tumors over express B7H4. Our goal and trial overall is to find a dose and then to look for potential single agent activity with an initial focus on tumors that over express B7H4 and constitute large patient populations with high unmet medical need as shown on Slide 7.
FPT155, our first-in-class CD80-Fc fusion protein is engineered to activate T cells through multiple pathways. We have opened enrollment in the Phase 1 clinical trial in Australia. Similar to FPA150, we are looking to find an FPT155 dose and then assess potential single agent activity.
In addition, we're pleased that the first clinical candidate from our immuno-oncology research collaboration with BMS, the TIM-3 antibody designated BMS-986258 continues to advance in a Phase 1/2 trial. The candidate is a fully-human monoclonal antibody targeting TIM-3 and immune checkpoint receptor that is known to limit the duration and magnitude of T cell responses. BMS' TIM-3 abstract poster number p684 will be presented at the SITC conference later this week.
As you can see our pipeline is advancing and building momentum. We're moving fast with our portfolio of mechanistically distinct product candidates. We are systematically engaging cells in the tumor microenvironment beta tumor cells, T cells, macrophages or natural killer cells. We have later stage programs that have already demonstrated their activity as well as exciting new first-in-class agents in early clinical development. And we have a strong balance sheet with no debt.
We have increased our year-end guidance and now expect to end the year with approximately $265 million in cash and investments compared to our previous estimate of approximately $250 million.
As we announced yesterday, I'm delighted to welcome David Smith to Five Prime as Executive Vice President and Chief Financial Officer. David brings more than 20 years of CFO and senior financial leadership experience in biotechnology. His wealth of industry and financial experience will serve Five Prime and our stakeholder as well. David will join us after Thanksgiving.
I also want to thank Linda Rubinstein for her excellent work as Interim CFO. Having her here allowed us to be thoughtful and deliberate in our search to find the right individual for the permanent CFO role. It's been wonderful to work with her and we thank her and wish her well in her future endeavors.
With that, I'll now turn the call over to Helen to review our clinical programs.
Thank you, Aron.
As Aron as highlighted we continue to make notable progress across our clinical programs. First on Slide 8 in our most advanced program bemarituzumab, our first in class FGFR2b antibody with enhanced ADCC for tumors that over express FGFR2b.
In the third quarter, we completed the Phase 1 safety lead-in and initiated enrollment in the FIGHT trial, our randomized controlled Phase 3 global registration study. You can see the trial design on Slide 9. The FIGHT trial will evaluate bema in combination with FOLFOX6 against placebo and combination with FOLFOX6 and approximately 550 patients with advanced gastric or gastroesophageal junction cancer.
Bema is a targeted therapy against tumors that over express FGFR2b and we are using tissue IHC or blood ctDNA tests to identify the estimated 10% of patients who are eligible for this trial. Last week, we had our U.S. investigator meeting and have heard firsthand the enthusiasm to screen patients enrolling in this trial. As you know, several therapeutic agents have failed recently in the frontline gastric cancer setting. But as we heard from the investigators bema is different from those agents because it has demonstrated single agent activity and it is an antibody targeting a selected patient population. This is most analogous to trastuzumab which was globally approved for the treatment of frontline HER 2 positive gastric cancer.
Additionally the investigators appreciated the design of the trial with the ability to screen patients with a simple blood test of tissue samples are often limited in size or hard to track down the five trials being conducted in North America, Europe and Asia. In China where gastric cancer is common we're collaborating with Zai Lab to identify enroll patients which should shorten the overall time to complete the trial.
An abstract featuring the Phase 1 safety lead-in chemo combination data has been accepted for a poster presentation at the ASCO GI conference in January.
Moving on to Slide 10, cabiralizumab is our antibody to the CSF1 receptor on tumor associated macrophages. We're combining cabira CSF1R inhibition with BMS' PD-1 OPDIVO
Last fall we presented data that demonstrated durable responses in late line patients with pancreatic cancer as shown on Slide 11. These data are unprecedented for immuno-oncology agents in pancreatic cancer in the absence of chemotherapy. Anti-PD-1 agents have not demonstrated efficacy in the approximately 98% of patients with microsatellite stable disease.
More recently whole exome sequencing analysis has shown us that these tumors had low tumor mutations burden. In other words based on known predictive biomarkers for single agent anti-PD-1 activity these patients would not be expected to respond to OPDIVO alone.
On the basis of this promising pulmonary data, BMS' advanced development of cabira and pancreatic cancer. Slide 12 shows their trial design. They're now enrolling patients into a second line randomized controlled Phase 2 trial of approximately 160 pancreatic cancer patients from the U.S., Canada, Europe, Japan, Korea and Taiwan.
As Aron mentioned in their recent earnings call, BMS reiterated their urgency to find new treatment options in areas where there is high unmet need such as pancreatic cancer and use this trial as an example. This momentum is reinforced by the initiation of additional trials with cabira including the pancreatic cancer frontline maintenance trial sponsored by Stand Up to Cancer and BMS and Apexigen and BMS supported study of anti-CD40, cabira and OPDIVO in multiple solid tumors.
Moving on to FPA150, our first-in-class B7H4 antibody is shown on Slide 13. This antibodies designed to target tumor cells through two mechanisms of action by blocking B7H4 from sending an inhibitory signal to CD80 cells and by enhancing the killing of B7H4 over expressing tumors through ADCC.
B7H4 is a cell surface marker frequently over expressed in breast, ovarian and endometrial cancers as depicted on Slide 14.
Moving on to Slide 15, we have an ongoing dose escalation Phase 1a study to evaluate the safety of FPA150 unselected patients. In addition, last month after clearing a dose level which may be efficacious based on our preclinical models, we opened an exploratory basket cohort of up to 10 patients whose tumors over express B7H4. We intend to investigate the potential activity of FPA150 monotherapy in these patients.
After completing the Phase 1a dose escalation portion of the trial, we plan to initiate Phase 1b expansion portion of the trial in this portion. We will test FPA150 in various disease specific cohorts of patients whose tumors over express B7H4 such as hormone receptor positive breast, cancer triple negative breast cancer, ovarian cancer and endometrial cancer. We look forward to presenting Phase 1 data at a medical conference in 2019.
Next is FPT155 shown on Slide 16, preclinical models suggest FPT155 has the potential to be a potent T cell co-stimulator with strong monotherapy anti-tumor activity and they also have synergistic efficacy when combined with anti-PD-1 therapy.
Bryan will review this molecule in more detail and you'll see why we are excited that this novel product candidate is entering the clinic. We just opened enrollment for the Phase 1a/1b clinical trial for FPT155 in Australia in patients with solid tumors and plan to dose our first patients soon. Similar to FPA150, the design of this Phase 1 trial will include an exploratory cohort at a dose at which efficacy was observed in preclinical models.
In the exploratory cohort, we will investigate FPT155 monotherapy activity in patients with solid tumors. Once the 1a dose escalation is completed we will initiate the Phase 1b expansion portion of the trial where we plan to evaluate FTT155 in various disease specific cohorts. We'll update you on the specific cancer types chosen at a future date.
I will now turn the call over to Bryan to review our research and preclinical efforts.
At Five prime, we have a truly unique platform that gives us a competitive advantage to find new targets, address new cell types and ultimately develop protein therapeutics. We have multiple state-of-the-art technologies to generate monoclonal antibodies as well as other protein therapeutics such as fusion proteins. Our dynamic screening platform is helping us discover differentiated therapies that we aim to advance rapidly into clinical development and to proof-of-concept.
One such example is FPT155. This is a first-in-class agent that we discovered by screening approximately 800 secreted and extracellular domain proteins in our library which we call the immuno. These are proteins that are expressed by immune cells or associated with immune cells and we screen them individually to identify those that inhibit tumor growth by immune dependent mechanisms.
One of the most potent single agent proteins that we've tested is CD80. In FPT155 the CD80 extracellular domain is fused to the IgG1 Fc domain of an antibody to optimize its pharmacological 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 [login] [ph] exogenous sleep with our drug we can modulate the degree of co-stimulation T cells received.
Importantly we don't see super agonism with the accompanying cytokine release that we've seen with a CD28 targeted antibody. And second, FPT155 block 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 interacts directly with CD28.
We know from preclinical work in tumor-bearing mice that if we preblock CTLA4 with an antibody that lacks effective function and therefore lacks efficacy as a single agent and then we administer FP1555. FPT155 retains the majority of its activity independent of its engagement with CTLA4.
Secondly in preclinical models FPT155 is demonstrated strong single agent activity across a wide range of single agent tumor models including the B16F10 model which is notoriously refractory to immunotherapies that include single agent anti-CTLA4 or anti-PD-1.
So we believe this is a very different drug than anti-CTLA4 and could represent an important addition to the immuno-oncology treatment armamentarium. You can see some of our clinical results on Slide 17 and 18. We continue to fuel our pipeline and our collaborators pipeline with additional programs that are at various stages in research.
You can see this on Slide 19, our early in vitro immuno-oncology screens included primary human effector T cells, T-RACs and macrophages. We are now optimizing screens to studying the impact of our library on the function of dendritic cells. The antigen presenting cells most adept at activating an effective anti-tumor T cell response.
I'm excited by the platform's potentials identify novel and differentiated drug targets in this competitive, but still emerging Io space emphasizing drug targets that can lead to antibodies or other biologics that have the potential to demonstrate single agent activity.
I will now turn the call over to Linda to review our financials.
Thank you, Bryan.
Further details regarding our financial results can be found in the press release issued this afternoon as well as slides 20 and 21.
We ended Q2 with a strong balance sheet cash, cash equivalents and marketable securities totaled $322 million on September 30 compared to $293 million on December 31 of last year. This increase reflects $108 million in net cash proceeds from our equity offering in January and $34.5 million in milestone and upfront payments that we've received from collaboration partners net of cash used in operations.
Collaboration and license revenue was $5.8 million for the quarter which was less than $8.3 million for the third quarter of last year. As compared to last year, we recognized less under our cabira collaboration agreement with BMS and our fibrosis and CNS collaboration with UCB. This was offset by collaboration and license revenue from our China collaboration with Zai Lab. We triggered a $2 million milestone payment from Zai Lab in the third quarter of 2018 for the first patient dosed in the Phase 3 FIGHT trial which is mostly reflected in deferred revenue and will be recognized as revenue over time.
R&D expenses totaled $45 million for the quarter a 5% increase from the $43 million of our R&D expenses in the third quarter of 2017. This increase included $10.4 million in milestone payments triggered by the dosing of the first patient in the Phase 3 FIGHT trial increased clinical expenses to advance our development programs and employee compensation offset by decreased spending on preclinical programs.
G&A expenses totaled $9.8 million for the quarter a slight increase from $9.7 million in 2017 due to increased patent, legal and consulting expenses offset by reduced personnel and other miscellaneous costs.
Net loss for the third quarter of 2018 was $47 million or $1.37 per basic and diluted share.
Looking ahead, we continue to expect full year 2018 net cash used in operating activities to be less than $135 million. Five Prime is revising our guidance and we now estimate ending 2018 with approximately $265 million in cash, cash equivalents and marketable securities an increase from our previous guidance of approximately $250 million.
Also today, we filed a new shelf-registration statement on Form S3. The registration statement covers the sale of up to $250 million of our common stock. This is a good housekeeping step and we have no plans to draw from the shelf at this time.
I will now turn the call back to Aron for closing remarks.
As Bryan mentioned the key differentiator for Five Prime is our discovery platform that we use to identify novel targets and biology in immuno-oncology. Underlying this platform is our collection of thousands of extracellular proteins. These are secreted proteins or soluble forms of cell surface proteins.
Over the years, we've built out these extracellular protein libraries and developed sophisticated ways to screen these libraries in high throughput cell-based models about physical assays and in vivo models. Our screens often leverage our extensive robotics and computing power and generate big data, which we then assess agnostically to identify the very best targets. These discoveries drive our pipeline.
We expect to build on this momentum throughout the rest of the year and into next. We have talented committed people and we continue to push the tempo on all of our programs as we bring forward novel medicines to patients in need.
You can see our expected milestones on Slide 22. We are well-funded and financially disciplined and we have multiple levers to fund the company including the potential for additional strategic collaborations. We regularly engage in business development discussions. I remain very confident in the future of Five Prime.
And finally, before we open up the call for questions, I want to thank the patients and investigators participating in our clinical trials, our Five Prime employees and our strategic collaborators.
I will now open it up to questions.
Thank you. [Operator Instructions] And our first question comes from Chris Shibutani with Cowen & Co. Your line is now open.
Hi. Yes. Thanks for taking the question. This is [indiscernible] on Chris Shibutani. It looks like there's lots of progress being made across the pipeline. One thing we're curious about is there's a lot of interest going on clinical development and CSF1R antagonist these days. Can you help us understand, how cabiralizumab may be differentiated from all the competition and all the other indications trial designs that are going on out there? Thank you.
Yes. Thanks TJ. I think you've called out some of the possibilities -- variables between the programs, so there are mechanisms, there are development strategies and combinations. With respect to cabira, we selected an antibody that bound to an epitaph on CSF1 receptor which is where the two lag end binds, CSF1 and Interleukin 34 and thereby we turn off signaling through the CSF1 receptor. And it's known the TAMs depend on that signaling to proliferate and activate. So we've already shown that we can successfully deplete TAMs. We presented some of those data at ASCO this year and a poster with our colleagues at BMS.
So mechanistically we think we have a good molecule in cabira. Secondly, we feel that we've found a dose and a schedule that's effective clinically. And so that's now being advanced in Phase 2 trials. That's the 4 milligrams per kilogram every two weeks dose. So there are of course other CSF-1R inhibitors both antibodies and small molecules. We think that cabira's profile is very attractive.
We're also in a leading position now as being the first program to get into a randomized Phase 2 trial and the first to combine with chemotherapy. We're aiming to be hopefully first to market.
We also selected tumor types that we think are important with respect to the infiltration of TAMs into the micro environments of pancreatic cancer being one of those of course. And that's where we're now in two Phase 2 studies with cabira but others as well. And you can see that our partners at Bristol are exploring things like renal, long and melanoma.
So we are quite confident in the mechanism and the dosing schedule. We've already shown a signal as we announced last year in terms of clinical efficacy in a patient population and setting in which you would expect to have no activity from a checkpoint inhibitor like in vivo. And particularly as Helen mentioned in patients who are microsatellite stable and have low tumor mutation burden. But that trial then led to the Phase 2 study that's ongoing as well as other programs that are ongoing with cabira.
I don't know that I have too much to add to that. I mean I do think that the dosing is important now. And as you know some of these other ones are being looked at Q3 and Q1 and Q4 and we really think we spent some time and we're quite confident about the Q2 dosing being important in terms of the therapeutic window of this drug.
And then, again, just to reiterate it's the same different tumor types, so I think all we can really know in detail is our own trial and of course it's that the results you see are unequivocal. I mean the combination showed responses in a disease that had not shown responses with Io therapies. So…
And at the level, the micro environment we do know that we change it from a tolerant -- tumor tolerant microenvironment to an inflamed more immunological active microenvironment so we see a shift in polarization from M2 type TAMs to M1 macrophages that's what we want to have happen. We see CD8 cells infiltrate the microenvironment, the T cells can carry out the attack.
So we know that we're changing the micro environment in a positive way the gene expression also signals pro-inflammatory markers coming up in the microenvironment, patients who've been treated with this combination.
So with that I will stop. But did that answer your question TJ?
Yes. That's great. I will hop back in the queue. Thank you.
Thank you. And our next question comes from Jim Birchenough with Wells Fargo. Your line is now open.
Good afternoon. It's Nick in for Jim, this afternoon. I'd like to maybe talk a little bit about FPA150 and so the exploratory cohorts that's ongoing, it's great news that has started. So 10 patients this is really trying to establish a recommended Phase 2 dose, obviously, get some initial signal or efficacy what are you hoping to show in this exploratory cohorts?
Thanks Nick. Helen take that.
Yes. So I think and I'm sorry not remembering off the top of the head, the slide number you'll see that we're doing all kind of dose escalation is what we did initially and that's continuing. So that -- and there if you know, it will stop if we -- if we know or when we hit a DLT just to get a tolerability.
We did what we're calling an exploratory because we know we're doing this at a dose that probably is lower than what will end up being our recommended Phase 2 dose. But we're taking as we're calling it a basket any patient who has a very high B7H4 score. And we're calling this a basket because we certainly know about breast ovarian, endometrial et cetera. But there are some other less common tumors that also highly over express B7H4, I don't know how public we've gone about those. So we're allowing patients like that to go on or with one of these tumors that we know about. So the point of this is really just trying to get a little bit of -- a little bit of data at some of these lower doses.
And again, what our final recommended Phase 2 dose will be -- could be at the same dose as one of these exploratory, but will probably be higher, but this is really a chance we're hoping to get some proof of concept get some baseline on to in biopsies and be able to get earlier than we would otherwise get it just as a sense of how good is this single agent activity going to be.
Okay. And then for the Phase 1b, do you think they might be able to start in 1H '19 and are you considering sort of Simon 2 stage design for these cohorts to get an early tumor specific look at efficacy?
I think you know even our cabira trial as well, we pride ourselves on being able to write these trials to be as flexible as we think we can be. So I think all of those are reasonable thoughts and that will be a balance right. I mean it's depending on how and some of that will be -- so I'm being vague on purpose because our protocols are written to be quite vague. But I think those are our expectations. I would certainly be disappointed if we didn't start out 1b in the first half of next year. How's that.
We are in final steps of those levels. So we're making great progress this trial as I mentioned as one of those, it's gone much faster than our original timeline and I think that is reflective of a strong interests in having B7H4 antibody for these patients. But, given that we are at dose level 7 of 8, I think it's reasonable to expect that we could be into Phase 1b in the first half of the year.
And then maybe just a quick question on the biology. So the counter receptor is not known, what do you know about co-expression of B7H4 with other checkpoints on immune calls?
Are you referring to maybe you say PD-L1 expression.
Yes. Things like that. Exactly.
Yes. There's not a direct overlap. There is a subset of tumors that can co-express them, but they're clearly not often co-expressed. And we know that PD-L1 one is induced by gamma interferon. We're still trying to figure out what 784 is up regulated by that. We do think it's intriguing that it seems to be an indications where PD-L1 is not prevalent. So maybe we're hoping it will be a dominant receptor in these unique indications that are served by PD-1 blockers.
Sorry. These are soluble version of the receptor.
Yes. I think there has been reported or shared B7H4. Yes, you can't see it in the serum. It's not at extreme high. High levels in fact we thought of using that as a potential PD marker for optimal dosing. But it's infrequent enough and not exhibition levels to be able to use it for that purpose.
Okay. Thank you.
Just want to add Nick that even if the tumor cell is expressing other checkpoints such as PD-L1, we still think or anybody could be active as monotherapy to ADCC components, so we recruit and case cells into the tumor and they can then attack B7H4 positive cells. So kind of two ways to win with FPA150.
Okay. That's very clear. Thanks.
You are welcome.
Thank you. And our next question comes from Jonathan Chang with Leerink Partners. Your line is now open.
Hi. Thanks for taking my questions. First question given the faster than expected progress being made in the FPA150 study, can you provide any more granularity on when in 2019 you might see initial clinical data?
So, this is Helen. I think you heard, we're starting to enroll patients out of -- the minimally efficacious dose. And so it's reasonable to think that we'll have some data by the middle of the year. How informative that data will be hard to tell? Certainly by the end of the year, we think we should have a fair number of patients that have enrolled in the B7H4. So I know that's been kind of vague again but I think it really depends on how quickly we get data from these next couple of cohorts.
Great. Thanks. Second question with the abstracts published this morning. Can talk about your view on the TIM-3 competitive landscape and how do you view your TIM-3 partner with Bristol positions. Are there meaningful points of differentiation that you need to highlight?
Yes. Thanks Jonathan. I'll start and my colleagues may have some things to add, so our partners at Bristol are presenting a preclinical poster on the TIM-3 program. That said it is in a clinical trial now in a Phase 1/2 study with dose escalation occurring in the monotherapy portion, and then, combination will be with up OPDIVO in the Phase 2 part. And, of course, Cicero has a TIM-3 temporary program as well.
We don't know exactly how their antibody behaves but what we know about our antibody and with our partners at Bristol. We selected it to prevent and interaction with a particular binding partner in the tumor microenvironment. So we know it does that we think that's an important binding partner. I will let Bryan comment as well on this.
Well, there have been at least three molecules that have been shown to interact with TIM-3. I think there's still debate in the field about which one or which ones are functionally important or relevant. One of those is Galectin 9 and other is CEACAM-1 and the other is [indiscernible]. We don't know what each of the competitors targets. Some of them are not reporting. I don't know that we've reported on the posters, so I'm not going to say what we think we're targeting. But we believe we're targeting the dominant important interaction with TIM-3.
Great. Thank you. And just one last one if I may, for FPT155, how should we think about the risk of super agonism and also can you provide more color on the Phase 1 development strategy for this program?
Yes. The risk of super agonism, yes we assess that pre-clinically and Bryan can comment on those studies.
There's an assay that now the FDA wants people to view with almost all T-cell modulars that actually reveal the cytokine storm potential of the TeGenero antibody, the CD28 superagonist antibody. You take PVMCs from human blood and if you quote the drug on a plate you can now reveal this activity of its presence. So we've done this assay with our molecule FPT155 and compared it to TeGenero agonist antibody, the agonist antibody definitely reveals quite high cytokine release whereas ours doesn't. But now if we add TCR simulation, we now see the expected enhancement in cytokine secretion from the T cells. So in an assay that we know is sensitive enough to reveal this super agonism, we know that our drug does not do it.
Then, the Phase 1 strategy.
Yes. And as far as the Phase 1 strategy, again with a novel checkpoint we have to start at a very low dose, of course that was similar to 150. We moved very quickly with 150. So hopefully we moved just as quickly with 155. I think in this case, for 155 there is going to be a much broader swath of tumors that would potentially be sensitive to this drug. I think what we're thinking about aside from obviously the dose escalation being an all tumor types is, except for those tumors that are -- the classic we really, really, really cold tumors that by virtue of how this drug works because it essentially is safe partially CTLA4 and then also this agonism that we should be able to demonstrate clearly better single agent efficacy than you would expect with something such as FTA or CTLA4 lone.
So you can imagine those kind of tumors where maybe those drugs like that have some mild to moderate benefit head, neck at a cellular non-small cell lung cancer et cetera that this may have a more significant single agent activity. But -- and that's those are the kind of things that we'd look at in our exploratory cohorts.
Thank you. That's helpful.
Thank you. And our next question comes from Robin Karnauskas with Citi. Your line is now open.
Hi. This is Nicole on for Robin. For this trial, can you just remind us about the IHC and ctDNA tests you were using identify the patient? And going forward, how could you also explain how they're differentiated and will you be developing its diagnostic for this indication?
I think I got the first two questions and then -- well, first of all, there are two -- so there are two diagnostics to identify the patients. The patients all get tissue sent in and again these are newly diagnosed patients, so they should have tissue sitting around somewhere and then a blood sample sent in as long as they are positive for FGFR2b either way. So if the tissue stays positive by IHC or if the blood demonstrates amplification of FGFR2b that patients would be allowed to enroll. We do not expect complete overlap although we expect significant overlap in both of these tests. But that's how we end up with about 10% of the patient population. So the IHC being done with a Ventana and the ctDNA with PGDx.
I think your last question is about -- whether those would be companion diagnostics, is that right?
Yes. So the answer is yes. That they're being developed in conjunction with bema and they would be part of the approval. And it's our strategy to have these available commercially -- bema is available commercially it would allow for patient selection again by either test.
People do not have to be positive by both just one or the other.
Okay, great. Thank you.
Thank you. And our next question comes from Eun Yang with Jefferies. Your line is now open.
Hi. This is Alex Heller on for Eun. I just had two questions. For cabira, can we expect data from the Phase 2 study in pancreatic cancer in 2019? And will that be first half or second half of 2019? And then secondly for bema, is the Phase 1 data at ASCO GI solely going to be safety data or can we expect any preliminary efficacy data? Thanks.
Okay. Alex thanks. So for cabira Bristol-Myers Squibb, our partners are running the Phase 2 trial. It's our understanding the enrollment is going well. As we mentioned they've got a number of sites, so you can see our clinicaltrials.gov, thirty nine sites are planned worldwide. Many are open. Others are opening. So we expect this trial to enroll quickly.
We also know from our own experience in running pancreatic cancer cohorts those enrolled very quickly just because of the tremendous unmet need in pancreatic cancer and the lack of available alternatives. So we think it's reasonable that the trial could be enrolled next year by BMS. But we can't guide when that would happen or when the data would be presented. That's up to them. But we think they're doing all the right things to get it done quickly.
And then with respect to bema and the ASCO GI presentation that we'll make, I'll turn it Helen.
Yes. So the Phase 1 or the safety lead-in as you may recall we were not anticipating there to be any overlapping toxicity and indeed the fact that we of course come through for the pivotal as the full dose if you will of bema has demonstrated that. So we know that the point of that being that we didn't have to enroll very many patients, so I don't want to make a big deal about what efficacy data we have. This trial did not require for the Phase 1 part that the patients had to have gastric cancer nor did they have to be FGFR2 positive. But we did have some patients that had that so. Yes, we will report on what efficacy we have. But I don't want to overstate that that's a huge amount.
Okay. Perfect. Thank you.
Thank you. And our next question comes from Kennen MacKay with RBC Capital Markets. Your line is now open.
Hi. This is Justin on Kennen. I wanted to follow up on the IHC diagnostic and the FIGHT trial. I was wondering if you could discuss how this diagnostic approach differs at all from the IHC that was used in the Phase 1 trial? Thank you.
So I think the simplest thing is to say the IHC -- we did the Phase 1 trial with an IHC and then moving forward to an actual LTD and developing the CDX. We've done extensive evaluation of -- we had over 600 patients that we screened too for our Phase 1 and also working with Ventana a very large databank of gastric cancer patients samples. So it's really by using those that we've determined where the cut off was when we looked at each score to determine where we were seeing responses and where we weren't and use that as our cutoff for our Phase 3.
Yes. So Ventana did a lot of work to lock-in the assay on their platform that they use worldwide. What we do know is, we see a good concordance with the IHC that was used in Phase 1. So we don't expect huge discrepancies between the rates that we saw for IHC levels in the Phase 1 and what we expect going forward and the FIGHT trial and also upon commercialization at that point.
Now, so we feel very confident about our cutoff in terms of what we need to see to get the potential for response.
Did you also have a question about the ctDNA?
No. It was just the IHC.
Okay. Thanks Justin.
So we looked at thousands of samples.
Thank you. And our next question comes from Eric Josephs with JPMorgan. Your line is now open.
Hey, guys. Thanks for taking the question. Just one on cabiralizumab, it looks as though the focus is increasing on pancreatic cancer with the Stand Up for cancer GemCaN study. I'm just curious to get your take on whether Bristol's optimism that they're communicating with [indiscernible] extends beyond pancreatic cancer. If there are whether other tumor types are potentially on the table from what they're seeing in the ongoing Phase 1 or preclinical data or pancreatic cancer is primarily the focus going forward. Thanks.
Sure. Thanks your question Eric. Well, I mentioned the study in long renal and melanoma. That's one example. The other thing I would point out is that in the poster at ASCO, Bristol did say that the data from the ongoing study, support additional clinical investigation in pancreatic and other tumor types. But at this point we're not in a position to disclose what additional work will be conducted in other tumor types. It's not yet public, but we and Bristol remain interested in pancreatic and other cancers.
Is there -- give a sense of when you might be able to kind of update the street on the potential plans as for the pancreatic and other tumors types? Thanks.
We can't guide at this point in time to just given the -- a lot of this is confidential and subject to our collaborative obligations with our partners at BMS. But when we are able to speak we'll certainly inform the street about it.
Great. Thanks for taking the questions.
Thank you, Eric.
Thank you. And our next question comes from Steve Seedhouse with Raymond James. Your line is now open.
Thank you. So my understanding on B7H4 that it's expressed by tumor epithelial cells, but also tumor associated macrophages or expression at least might correlate with TAM Treg infiltration into tumor. So I mean in your slides you have a cartoon, you focus on sort of the tumor autonomous effects whether that's blocking ADCC or checkpoint inhibition. I'm curious to get your broader thoughts on just the complexity of the mechanism in different cell types, how solid are some of those macrophage expression data and are you looking for markers or anything in the clinical program to help you parse out the relative contributions of the microenvironment. And does that even really matter as it relates to choosing indications and sort of designing the next stage of trials?
We don't think we need because of the two mechanisms. But I think the more we can learn about the receptor, the better we can position in the clinical development. I should say in our preclinical mouse models we have not been able to find convincing expression of B7H4 on the infiltrating macrophages. This is consistent with a couple of reports that have been published but we've looked very carefully and we haven't found it.
But that said, we're currently doing human analysis of human tumors to see if we can see it on the macrophages. Now you can sometimes see messenger RNA for the protein but we don't see it on the surface. So it's still a little confusing, but we are doing analysis of human tumors with the intent of looking both directly at the tumor cells and the macrophages.
Okay. Appreciate it.
But I guess, while PD-L1 -- just like PD-L1, we would assume that both the macrophages and the tumor could contribute to inhibition of the T cells and that by blocking it. We would relieve both methods or both modes of suppression.
Okay. That's helpful. And just apologies if this has been asked, but on the -- you mentioned possibility of specific or exploring either Io or chemo combination strategies depending on the Phase 1b data. I'm just curious if you already have specific combination mechanisms in mine based on preclinical data and if there's a specific efficacy hurdle you'd be looking for in certain patients in Phase 1b to move ahead with specific combinations?
Yes, we have some ideas and we've done a lot of preclinical work. I think when we're looking at -- in a single arm study we definitely want to see it -- a doubling of whatever response rate of whatever tumor would be at least that would be something that we would consider at least the bar that you'd want to achieve before you move things forward. We haven't said anything any more details on that though.
Okay. Would be, I mean I guess the obvious candidates just traditional checkpoint inhibitors would be some of the Io combos you'd be considering. Is it something more novel than that?
Preclinically, we definitely see that that PD-1 [Technical Difficulty] going nicely with the B7H4, FPA150. So once you kill the tumor cells and initiate an immune response we would expect PD-1 to be one of the things that inhibits that. So it's may make sense as a rational combination partner for this but we also have looked at other modulators in the tumor microenvironment. So it's not just the one that we're looking at.
And again because B7H4 does not appear to be -- much if any on normal tissues, we aren't anticipating too much in the way of toxicity which potentially would allow it to be combined with things other than PD-1. And I say that more from the point of view of the clinician, which is as you know that particularly these tumors where PD-1s aren't approved, I mean a subpopulation of triple negative breast cancer maybe that caveat. But for the other tumor types that we're looking at they aren't. And so it may be a faster pathway even if the science is there. I smile looking at Bryan but to combine with other things such as your PARP inhibitors or chemotherapy. I think it needs to be a combination always of the science. Obviously, number one but also then what the clinical need is. And how those drug turns out to be. Thank you.
Okay. Thank you. Appreciate the question.
[Operator Instructions] I am showing no further questions at this time. I would like to turn the call back over to Aron Knickerbocker, Chief Executive Officer for closing remarks.
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