Five Prime Therapeutics Inc
Q2 2017 Earnings Call Transcript

Published: 9 Aug 2017

[Operator:]

Good day, ladies and gentlemen and welcome to the Five Prime Therapeutics, Inc. Second Quarter 2017 Earnings Call. As a reminder, this conference call maybe recorded. I'd like to introduce your host for today's conference call, Ms. Heather Rowe, Senior Director, Investor Relations and Corporate Communications. You may begin.

[Heather Rowe:]

Good afternoon and thank you for joining us. I'd like to welcome everyone to our conference call to discuss results for the second quarter 2017. 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 Presentation. Joining me today are Dr. Rusty Williams, Chief Executive Officer; Dr. Helen Collins, Chief Medical Officer; Mr. Aron Knickerbocker, Chief Operating Officer; and Mr. Marc Belsky, Chief Financial Officer. Today's conference call will include forward-looking statements under the Private Securities Litigation Reform Act of 1995, including statements regarding our research and development programs and financial outlook. Actual results may differ from those indicated by these forward-looking statements due to numerous factors, including those discussed in the Risk Factors section of our SEC filings. Our expectations and assumptions could change. While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so, even if our views change. I will now turn the call over to Rusty.

[Rusty Williams:]

Thanks Heather, and I appreciate those of you who are on the phone for dialing in and joining us this afternoon. Our agenda will include my opening remarks, followed by clinical trial discussion by Helen Collins, and then a brief commercial analysis by Aron Knickerbocker; financial summary by Mike Belsky, and I will make some additional comments at the end of our formal presentation. We had a very productive second quarter. Our teams continue to execute on all fronts and our programs are well on track. For those following along with our posted slide deck, an overview can be found on our pipeline chart shown on slide 3. Our overarching focus is to advance our key clinical programs as quickly as possible, in a manner supported by compelling science and medical rationale. We are lucky to have multiple clinical and preclinical opportunities to pursue, and so we want to strike a balance between moving fast, maximizing optionality, and wisely managing our expenses. We are not just throwing spaghetti against the wall to see what's fixed, as some would argue, it is a trend in Immuno-Oncology. We are using science and clinical thinking. I will now highlight the progress made on select programs during the quarter, which are listed on slide 4. Let's start with Cabiralizumab our CSF1 receptor antibody that blocks immunosuppressive macrophages. We and our partner, Bristol-Myers Squibb are studying Cabira in combination with the PD-1 checkpoint inhibitor OPDIVO in seven different tumor settings. We have already completed enrollment with some of the cohorts, and are on track to complete enrollment in all the Phase 1b cohorts by the end of the year. In addition, we and BMS are pleased, to announce that we plan to present initial clinical data at the Society for Immunotherapy of Cancer or SITC meeting in November. To our knowledge, this will be the first public disclosure of clinical data from any combination of CSF-1 receptor antibody and a checkpoint inhibitor. We are pleased with the momentum of this program, and look forward to future updates, as we get more data. We are also studying Cabira in the chronic joint disease, pigmented villonodular synovitis or PVNS. At the recent ASCO meeting, we announced preliminary data that demonstrated, that about half the patients had more than a 30% reduction in their tumor, and almost all patients showed some degree of tumor shrinkage. We know that treating PVNS is different from treating metastatic cancer. In a chronic disease management setting like PVNS, it's important to not only control tumor size, but to also relieve the patient's pain, and improve the function of affected joints. Our quantitative clinical outcome score, shows Cabira did just this, pain release and improvement in function were reported, even for patients who had only a modest tumor shrinkage. As Helen will describe in more detail, we are optimizing the therapeutic index of Cabira as a potential chronic treatment for this lifelong, non-lethal disease. In a few minutes, Aron will provide color on the market for a PVNS drug like Cabira. We are also advancing FPA144, as a targeted immunotherapy for gastric and bladder tumors, that over express the B splice variant of FGF receptor 2. We estimate that 10% of metastatic gastric cancer patients have this splice variant over-expressed, and this is associated with a poor prognosis. At ASCO, we announced updated results from this trial, which demonstrated clear evidence of monotherapy activity in a heavily pre-treated patient population. We are planning to combine FPA144 with chemotherapy and to move into front-line therapy, which gives us the potential to benefit more patients for a longer period of time, with potentially higher response rates and better survival than in a late line setting. This strategy is supported, not only by strong scientific rationale and by our KOLs, who have consistently encouraged us to take this approach. One key element of our FPA144 strategy is to include Asia, where they observed incidents of gastric cancer is higher than in other populations. We recently initiated a Phase 1 safety trial in Japan, and we are pursuing development in China as well. There are a large number of gastric cancer patients in China, which allows us to increase the rate of trial enrollment and increase the total number of patients enrolled, thus improving the probability of success of our trial. We are evaluating the regional partnership with companies, who have a strong presence in China, and this may have the added benefit of offsetting some of our trial costs. Now, I will provide a brief update on our preclinical programs, which was the first successes of our early Immuno-Oncology discovery efforts initiated three years ago. We discovered promising new targets, some of which have the potential to yield first-in-class drugs. The programs we disclosed, are the most advanced. But there are numerous earlier programs that we haven't yet made public. We have three potential preclinical therapeutic candidates in IND-enabling studies and plan to file an IND for one of these by the end of this year. The first is FPA150, an antibody to B7-H4, you can see this on slide 5. We believe we will be the first to file an IND for B7-H4 therapy. Certain tumors, such as ovarian, breast and endometrial cancers have high levels of B7-H4 expression on the surface of the cancer cells. Furthermore, B7-H4 has been show to act as a checkpoint, that suppresses CD80 directly. We engineered this antibody to block the immunosuppressive function of B7-H4, acting on CD80 cells, as well as to drive ADCC to kill tumor cells that express B7-H4, so two mechanisms. This program will be the subject of an all panel discussion at the ASMO meeting in September. Another pre-IND program is FPT155, this is a soluble version of CD80, which is a natural immune regulatory molecule shown on slide 6. This program came from our in vivo screens, which demonstrated that a soluble form of CD80 was striking, and it's potent in vivo anti-tumor activity, we will compare it to 500 other immuno-proteins. We are excited about the potential of FPT155, because it appears to enhance detail response through three possible mechanisms. First, it activates CD28, that's the CD80 known activity, and it does this activation of CD28, importantly, without any superagonism. Second, it also binds the CTLA4, and they block it's immunosuppressive effects. And third, it can block the PD1 checkpoint pathway, because it binds directly to PDL1. We believe these mechanisms may lead to the striking anti-tumor effect we see as monotherapy in multiple pre-clinical models. We have submitted an abstract in this program with a AACR, MCI, EORTC, otherwise known as a triple meeting, which will be in October. The third pre-IND program is FPA154, our GITR agonist antibody, this is shown on slide 7. We think our tetravalent GITR antibody is differentiated from others, because it has four GITR binding sites compared with a conventional anti-GITR antibodies, that have only two GITR binding sites. Our Discovery platform remains very productive and it's continuing to yield new and interesting targets, for which we have initiated new antibody campaigns, and this will help fuel our future pipeline. Now I'd like to turn the call over to Dr. Helen Collins, to discuss our clinical programs in a little more detail.

[Helen Collins:]

All right. Well thank you, Rusty. I will briefly review the status of our clinical programs, starting with the Cabiralizumab IO trial in advanced cancer patients. As Rusty mentioned, we are making significant progress in the stage 1, setting Cabira in combination with the anti-PD1 antibody OPDIVO. The trial design can be found on slide 8, and recent highlights from this program on slide 9. We initiated the Phase 1b in October 2016 and are very pleased with our progress. We have completed enrollment in some of the Phase 1b cohorts, and expect the complete enrollment in all pre-specified cohorts by the end of the year. We and BMS also plan to announce initial clinical trial data at the SITC meeting in November. This will be preliminary data, remember, not all cohorts are enrolled yet. In addition, we and BMS are conducting in-depth tissue biomarker analyses to further inform future developments. We are pleased with the overall momentum of this program and our collaboration with BMS. For example in May, BMS and Ono initiated a Phase 1 combination safety trial of Cabira and OPDIVO in Japan. And in addition, BMS is now manufacturing Cabira in their in-house production facility. As we know, there are many IO combinations in clinical trials. We believe that successes or failures in most of these combinations, especially those where both patients are directly targeting the T-cell, don't serve the read-through to our program. Recall, Cabira has a different mechanism of action, as it targets tumor suppressive macrophages. We have designed our trial to target tumors that have high levels of tumor associated macrophages or TAM. The rationale, is that the combination of our macrophage inhibitor Cabira, with a checkpoint inhibitor OPDIVO, may be effective in tumors, where macrophages have an immune inhibitory effect in the tumor micro environment. The tumor types we chose to evaluate fall into three categories; the first category includes tumors where OPDIVO is already approved, such as non-small cell lung cancer, renal cell, and head/neck cancer. The second category is tumors that are resistant or have become resistant to checkpoint inhibitors, such as previously treated non-small cell lung cancer. And the third category, includes tumors where checkpoint inhibitors aren't approved, such as ovarian, pancreatic and glioblastoma. We believe the bar is lowest in the lower two categories, where any evidence of efficacy could be meaningful. I will now discuss our Phase 2 PVNS trial in more detail. Slide 10 illustrates the PVNS trial design. PVNS is a rare joint disease, in which the tumor mass is composed of normal macrophages that accumulates, because abnormal synovial cells secrete high levels of CSF1. While the trial is assessing objective response rate for MRI, patient reported outcomes are often very important in control of pain and improvement in functional status are the top priority for patients. On slide 11, you could see program highlights. We reported initial clinical data at ASCO, in which Cabira demonstrated clinical benefit in patients with PVNS. These data are shown on slide 12. Most patients enrolled at the 4 milligram per kilogram dose experienced tumor reductions, and five out of 11 had a radiographic response. Four which were confirmed, with a second scan at least eight weeks later. Importantly, most radiographic responders and non-responders demonstrated an improvement in composite clinical outcomes, assessment of pain, synovitis, range of motion and function. Also, there were no dose-limiting toxicities or DLTs observed at doses up to 4 milligrams per kilogram. However, some of the patients discontinued treatment after the DLT window due to tolerability. Based on pharmacokinetics, pharmacodynamics and clinical data from our current trials, we think it will decrease the dosing interval to approximately once every four weeks, we will reduce the discontinuation rates. We also think that if we require pain as an inclusion criteria, this will also decrease the discontinuation rate. To optimize the therapeutic benefit of Cabira, we plan to begin enrolling additional patients in the fourth quarter, to evaluate a less frequent dosing schedule, and in this way, we also hope to increase the probability of success of a future pivotal trail. Based on these preliminary results, our investigators remain enthusiastic about the potential for Cabira to provide taking benefit, which indicates there are no approved therapy. Next, I will discuss our progress with FPA144, our antibody that specifically targets the FGFR2b splice variant which is over expressed in some tumors. Results report that the specificity of 144 with the toxicity, seen with less selective FGFR2b small molecule therapeutics. As shown on slide 13, we are currently in the expansion part of the Phase 1 trial, where we are dosing gastric and bladder cancer patients with 15 milligrams per kilogram of 144 every two weeks. Slide 14 shows highlights on the ongoing Phase 1 trial. At ASCO this year, we presented updated clinical data as seen on slide 15. FPA144 is more tolerated and there were five partial responses, four confirmed and one unconfirmed in 21 patients across three dose levels. The objective response rate was 19%, and median duration of response was 15.4 weeks and a very heavily pre-treated patients, who had a median of three prior lines of therapy. For patients with metastatic gastric cancer, we believe the greatest benefit will be in frontline treatment, by combining 144 with chemotherapy. As Rusty mentioned in his opening remarks, we are focused on advancing our agents quickly. This is one such example. In our view, this approach will provide the opportunity for a faster path to potential approval. We estimate, there are at least three times the number of patients in front line setting compared to late line, and so the enrollment in the front line study, could be achieved more quickly. Aron will provide more color on the market opportunity shortly. But more importantly, moving to the frontline setting also offers the opportunity to benefit patients for a longer period of time. There is also a strong scientific rationale to support the chemotherapy combination. Our preclinical data, demonstrate the combination of chemo and 144's additive, as shown on slide 16. And further supporting the rationale, other targeted antibody therapies such as Herceptin, Cyramza and Avastin, report greater benefit, when combined with chemotherapy than used as monotherapy in gastric cancer. We are preparing for Phase 1 trial to test the safety of attendee doses of FPA144 in combination with chemo, to begin by the end of 2017. We expect results from the Phase 1 trial will support the start of a global registrational Phase 3 trial of FPA144 in combination with chemotherapy for frontline gastric cancer therapy. Slide 17 depicts a potential trial design, which includes a control arm because of the overall poor prognosis of these patients. Asia is a key market in this setting, because of high unmet patient need. We recently launched the Phase 1 safety trial for FPA 144 in patients with gastric cancer in Japan, where the incidents of gastric cancer is high. Completion of this Phase 1 trial is intended to enable the inclusion of Japanese patients, in a planned global Phase 3 trial. China has more patients with gastric cancer than any other country, and they are also taking the necessary steps to include Chinese pivotal trials. We clearly selected patients through their tissue based IHC test alone. The IHC test identifies FGFR2b protein expression in the tumor biopsy. You will also need a blood based diagnostic tool, to measure circulating tumor DNA or ctDNA, to detect FGFR2 gene amplification metastatic signs [ph]. By adding the ctDNA, we believe it will double the eligible patient population to 10% from the previous 5% identified by IHC testing alone. You can see this concept illustrated on slide 18. In summary, the combination of moving frontline therapy as well as adding a blood based test to identify more patients, could lead to a faster path to approval and a larger commercial opportunity. Beyond gastric cancer, we are also studying 144 on patients with bladder cancer. We are currently adding additional trial sites to specialize in bladder cancer to facilitate enrollment. Finally, I will conclude with a few remarks about FP-1039 as shown on slide 19. FP-1039 is a ligand trap that blocks FGF2 and other cancer promoted FGF. It is currently being combined with cisplatin and pemetrexed in a Phase 1b trial in its first line therapy in patients with malignant pleural mesothelioma. Updated safety and efficacy data from this trial has been accepted at the oral presentation at ESMO in September. In summary, we are excited by the significant progress in our development efforts across all our clinical trials, and we look forward to providing future updates, as data becomes available. I will now turn the call over to Aron, to discuss our partner strategy and initial commercial discussions.

[Aron Knickerbocker:]

Thanks Helen. I will now briefly discuss our preliminary commercial assumptions and partnering strategy. I will start with the partnering characteristics for PVNS, an overview can be seen on slide 20. PVNS tumors are located in joints, such as the knee, wrist or hip. Patients tend to be young in their 30s and 40s and diagnosed and active. Unfortunately, PVNS can affect patients for the rest of their lives. Symptoms include pain, lack of mobility, slowing, fatigue and disfigurement. Patients report that they are most impacted by the pain and lack of mobility. Patients are initially diagnosed by orthopedists or orthopedic oncologists. Surgery is currently the primary treatment for PVNS. But as patients progress, they are typically referred to medical oncologists. However, there are no approved drugs to treat PVNS, resulting in high unmet patient need. We recently conducted a market research study of almost 50 patients and physicians. Highlights from this study can be found on slide 21. Both patients and physicians were enthusiastic about a non-surgical treatment option for progressive diffused PVNS to delay or prevent repeat surgery. In addition, Cabira's potential efficacy profile was attracted to oncologists, and they didn't see any major barriers to prescribing an injectable for PVNS, especially given the lack of approved drugs. Historically, the incidents and problems of this rare disease have been poorly characterized, and so we undertook an epidemiology study, using a very large patient registry. Results suggest that the U.S. prevalence for diffused PVNS may be as high as 25,000 patients, and also suggest that the prevalence rate outside of the U.S. would be similar, when adjusting for population. We lead in fund development for PVNS and believe it is an attractive investment for Five Prime. We are eligible for milestone payments, as we advance the program, and BMS will reimburse our development costs, if Cabira is approved in PVNS. Additionally, we would receive tiered royalties ranging from the high teens to the low 20s percentages on sales in all indications, including PVNS. We are also eligible for an additional low single digit percentage royalty on net sales in the United States, if we exercise our co-promotion [ph] option. Next, I will discuss FPA144. We believe that in metastatic gastric cancer, the greatest benefit to patients will be in the frontline setting, if we combine 144 with chemotherapy. Patients with advanced gastric cancer have a poor prognosis, with an overall survival of only 10 to 12 months. Approximately half of the patients don't even make it to second line therapy, and approximately 75% of patients don't make it to third or later line therapy. The few patients who do make it to third and later line therapy tend to progress very quickly. In addition, we know that FGFR2b over-expression or FGFR2 gene amplification, are associated with a poor prognosis. So patients with FGFR2b positive gastric cancer are even less likely than the typical gastric cancer patient, to survive long enough to receive third line therapy. So overall, there are far fewer treatable late line patients. Additionally, patients receiving frontline therapy stay on treatment for a longer duration. The median progression free survival or PFS of 4 or 5 chemotherapy alone in frontline gastric cancer treatment, is from six to seven months. We would hope for a significant increase over that. In contrast, for patients receiving third line or later therapy, the median PFS is typically two months or less. The commercial opportunity for FPA 144 in front line treatment of FGFR2b positive gastric cancer is attractive for Five Prime. Slide 22 illustrates the number of estimated treatable frontline metastatic gastric and gastro oesophageal junction adenocarcinoma patients. As you can see, we believe there are approximately 17,000 U.S. patients, and approximately 39,000 EU patients annually. We estimate that compared to the United States, there are approximately four times the number of patients in Japan and 10 times the number of patients in urban China. We believe 10% of these patients would be treatment eligible. While premature to provide any pricing guidance, we note that global prices for recently launched biologics and gastric cancer range from around $6,500 to more than $14,000 per month. I noted the size of the Asian markets. Completion of our recent minutiae [ph] at Phase 1 safety trial in Japan is intended to enable the inclusion of Japanese patients in the planned global Phase 3 trial. We also intend to enroll a number of patients from China in its registrational trial, and are evaluating regional collaboration opportunity with potential partners, who have access to and experience interacting with the CSEA. I am also happy to inform you, that we are now working with two companion diagnostics providers, Ventana for IHC testing and PGDX for ctDNA testing, to identify the 10% of gastric cancer patients eligible for FPA144 therapy. Both providers have business models that allow for global testing to support the trial and potential commercialization. We continue to refine our commercial expectations and we believe attractive and tractable markets exist for our drug candidates. Moreover, we are judicious of our partnering, and this provides great optionality and potential cost savings. With that, I will turn the call over to Marc, to discuss our financials.

[Marc Belsky:]

Thank you, Aron. The full details of our financial results can be found in the press release issued this afternoon, as well as slides 23 and 24. We continue to have a strong balance sheet. Our cash, cash equivalents and marketable securities totaled $350.7 million as of June 30, 2017. Net loss for the second quarter of 2017 was $44.3 million or $1.58 per basic and diluted share, compared to a net loss of $13.1 million or $0.49 per basic and diluted share for the second quarter of 2016. Collaboration revenue for the second quarter of 2017 was $7.8 million, down from $9.2 million from the second quarter of 2016. This was primarily due to completing the research term of our research collaboration with GSK in respiratory diseases in July 2016, offset by revenue recognized under the 2015 Cabira collaboration agreement with BMS, under which Five Prime is reimbursed for the expenses from the Cabira Immuno-Oncology trial. Research and development expenses for the second quarter of 2017 were $41.7 million compared to $22.2 million from the second quarter of 2016. This increase was primarily related to advancing Cabira in the Phase 2 clinical trial in PVNS and the Phase 1a, 1b clinical trial in Immuno-Oncology and advanced improved clinical development programs towards IND filings. General and administrative expenses for the second quarter of 2017 were $9.4 million compared to $8.1 million in the second quarter of 2016. This increase was primarily due to increases in payroll and stock based compensation expenses. Looking ahead, we continue to expect full year 2017 net cash used in operating activity to be less than $120 million. We estimated ending 2017, with slightly less than $300 million in cash, cash equivalents and marketable securities. I will now turn the call back to Rusty for closing remarks.

[Rusty Williams:]

Thanks Marc. Beyond the progress that we discussed today in our preclinical and clinical programs, we are excited about our Discovery platform, which continues to fuel our pipeline. Our ability to find new targets and generate new protein drug candidates is of strategic advantage for us, especially in an era, when pharma companies look for novel agents to fill their pipelines. We have a lot of opportunities to pursue, but we are disciplined in our prioritization of the early programs. We are making great progress and are well on track to achieve our goal of filing at least one IND application for a new molecule each year for the foreseeable future beginning this year. Slide 25 summarizes these expected INDs, as well as our expected data disclosures that we have described on this call. Importantly, over the next three months, we plan to present data from four different programs at major scientific conferences. I'd like to close with a word about a recent announcement regarding my planned transition to Executive Chairman of the Board at Five Prime. Starting last year, I began discussing with the board, my desire to make this transition, while still maintaining an active role with Five Prime. As part of the ongoing succession planning, the transition is expected to occur in 2018. At that time, I will continue to be very involved as executive chairman, as chair of the Five Time Scientific Advisory Board, and in leading a small internal innovation group, focused on generating potential new therapeutic approaches in Immuno-Oncology, quite excited about this. Now is the right time for me to play a more strategic and innovative role and for the company to select a new CEO, who can bring additional insights and expertise to build upon the already strong Five Prime foundation. Five Prime is in a strong position. I chose this time to initiate the transition, based on the progress we have made, advancing our programs, the strength of our financial position and our pipeline and the capabilities of our leadership team. Moreover, our programs are on track. We are moving full steam ahead, and our future is promising. Finally, before we open up the call for questions, I'd like to express my appreciation to our Five Prime employees as well as the numerous patients and investigators participating in our clinical trials. I will now open it up for questions.

[Operator:]

[Operator Instructions]. Our first question comes from Michael Schmidt with Leerink Partners. You may begin.

[Michael Schmidt:]

Hey guys, thanks for taking my question. I had a couple. Maybe first on Cabiralizumab, regarding the upcoming SITC data presentation, just wondering what expectation should be for investors, with regards to the quantity of the data maybe? For example, will you present data on all cohorts at this point, or maybe to some cohorts? If you could just provide some color on that, that would be helpful?

[Rusty Williams:]

Yeah thanks Michael. If you can remember, we started this on the cohort that the -- all the cohorts in October of last year, still been active for much less than a year. And as we have discussed, we haven't fully enrolled all of our cohorts. We do plan to get full enrollment by the end of the year. Now if you just look at the pace of that, you can imagine, we won't be able to show data on all the cohorts. So that can sort of start, but I think we won't do. So we won't be in a position, just because we don't have the data on all the cohorts. So this will be an initial data disclosure. We haven't given guidance yet, as to which segments of the trial we are going to present data on. It will include data from the 1b, and we of course, work with our partner, BMS and the leasing data for this and we look forward to the SITC presentation, and I apologize, we will just have to wait for them to get more granularity on that, but I appreciate your question.

[Michael Schmidt:]

Okay, fair enough. Thanks. And then a question regarding the work that has been ongoing in PVNS, specifically around the dosing schedule. You have been talking about optimizing the therapeutic window and dosing frequency and I guess my question is, is that driven purely by trying to improve patient retention and the overall experience, or have there been toxicities that have been seen, that drove that decision to essentially reduce the dose, if you decrease the frequency? Thanks.

[Rusty Williams:]

Yeah. Let me just give a high level answer and then I will let Helen give the details. You have really landed on the two issues, and one is, we are aiming for finding a good solution, long term solution for patients with this disease. As I said, it's chronic management. We envision long term therapy for these patients. So we are going to find a solution, a regiment and a solution that will be appealing to patients and their treating physicians. We did have some discontinuations, and if you look at those discontinuations, we have started the trials, with our initial trial, we didn't require pain for example. And so the threshold for discontinuing might be lower in a patient's mind and a physician's mind than patients who are getting treatment for pain. And so, we do want to make those -- the regimen more tolerable, so that patients stay on the drug longer. And then we are -- I will let Helen elaborate on this, we are -- it's a different kind of disease, than malignant or metastatic cancer, because in PVNS, you are not worried about the disease getting away from you, so to speak. The cells and the tumor -- the bulk of the cells are normal macrophages, drawn in by the expression, the overproduction of CSF-1. They are not mutated cells. They are not going to metastasize, and so you'd have a little more leeway, in terms of the way you treat the disease. You focus on the patients, symptoms and function and tumor shrinkage, and so you are not as worried as you are in metastatic cancer about sort of the disease getting away from you. I will let Helen.

[Helen Collins:]

Yeah, I mean, I don't think I can add as thorough [ph] as Rusty's saying maybe it's that, from a patient perspective, the difference between tolerability and toxicity if you will. So that if something, I am probably reiterating what we have been saying, is that if it's a chronic, lifelong disease, but not a life-threatening disease, what that we would see is, although we had no dose-limiting toxicities and we had responses that patients would discontinue, and they would discontinued for –things that -- I mean let's say as an oncologist, I would not expect to see cancer patients discontinue the treatment for. And again, that has really been the feedback from our investigators, who say that is the case. And so -- and what we also noticed, and that would be presented on our poster at ASCO, was that limitations did discontinue drug, for the time that the tumor would take to grow back, but certainly not at the two weeks, but more like on the month level. So we know, we don't need to get the drug every two weeks. So that's what I meant by saying, based on the pharmacokinetics, based on the pharmacodynamics, that you also look at circulating monocytes. And then based on the clinical data, assume how long it would take for the tumor to come back. We know we just don't need to get this every two weeks. So I think that's what we are talking about. But the dose, we believe that was right. The 4 mgs per kg, we think is the right dose, just think they don't need it so quickly. And again, for a lifelong, potentially a lifelong therapy, that kind of makes sense from a lot of perspectives as well.

[Rusty Williams:]

So we'd like to take this opportunity to just get it right, before we do our pivotal trial. And I think it's a good -- that's the best way to proceed.

[Michael Schmidt:]

And again, is it mainly should be the inconvenience of IV infusion for those patients or are there -- have there been specific probability factors that have played a role, and which one for the --?

[Rusty Williams:]

IV infusion is a convenience issue and every four weeks is obviously more convenient than every two weeks.

[Helen Collins:]

Well, I think in a clinical trial, unfortunately, we can't really judge that, right, because we want them coming in labs and all these things, so they are coming in, getting poked and a lots of visits. I think Aron can speak to, whether or not, based on your research, just in general about whether an ingestible is any kind of hurdle?

[Aron Knickerbocker:]

Yeah. Well first off, the short infusion, where patients are not in the chair for hours and hours, so that's one point to bear in mind. But we have, from our market research encountered acceptance for an IV solution to the V and the sorts of physicians who would administer that, are the ones who do now see PVNS patients from time to time. Medical oncologists use off label [indiscernible] for instance, but would like something better, and they deliver most medications by infusion. And similarly, rheumatologists who occasionally see PVNS patients, also deliver infusional drugs, such as Remicade and Rituxan for example.

[Helen Collins:]

And then I will just add, I mean, I don't -- again, we are giving IV not an oral, but at least from what we know, the oral is not going to be something, where patients -- in oral drugs, the patients are going to have to come in and be seen by the physician and get frequent laboratory exams. So it's not going to be like, give them some antibiotics and you go away, right? So I think that also is one of the issues with the as we bring in new patients regardless of their treatment. Who are going to come in and be seen, evaluated and --

[Michael Schmidt:]

Okay, great. Thanks. Thanks for the added information.

[Operator:]

Thank you. Our next question comes from Eun Yang with Jefferies. You may begin.

[Carmen Augustine:]

Hi, this is Carmen on for Eun. Thanks for taking our questions. For FPA144, previously you had mentioned running a safety will be part of the pivotal trial. Just wondering, what kind of tips the scales towards running a separate Phase 1? And could you provide any more details on the design and duration of the trial, and what you would want to see over -- out of that to support initiation of the pivotal trial in 2018?

[Helen Collins:]

So thank you for that question. So actually it is still a plan to do a safety lead in. I think we were explaining it differently, because we want to make it clear, that we can be fairly confident about when we start a Phase 1, but of course, can be less confident about when that Phase 3 starts, right, depending on how many dose levels you have to do, etcetera. So it is still planned to be this one study. And then your second question --

[Rusty Williams:]

Well, just on that point of read. FPA144 to-date has been a pretty well tolerated drug, and so we don't anticipate any problem with that combination. There is no reason to believe, that the combination is going to be -- there are going to be overlapping toxicities. So while we can't really predict exactly the timing of the Phase 3, I think we are going to -- one would predict that we will be in good shape from that safety trial. So go ahead --

[Helen Collins:]

And then, I apologize, the second question, was about the design and duration? So I think we haven't -- other than putting the example of what would be a frontline study, a standard platinum 5-FU versus a platinum 5-FU plus 144, we have not specifically opted that.

[Rusty Williams:]

But we are in a hurry to do the trial well. But part of the reason for adding China as a -- at the Chinese sites and a Chinese partner, is to be able to enroll more patients and do it more quickly. So we are going to do this as fast as we can.

[Carmen Augustine:]

Okay, great. Thanks. And then one on FP-1039. For the data presentation at ASMO, could you speak to how many patients you expect to have from the escalation and expansion portion, and what kind of efficacy you would want to see, to support further development?

[Rusty Williams:]

So that trial, as you remember, has been run by GSK, our former partner, and the presentation will be on 25 patients, with mesothelioma in combination with chemo; with 1039 combination with chemo. Does that answer your question, Carmen?

[Carmen Augustine:]

Yeah. Could you make any comment on what kind of efficacy you would want to see to support further development?

[Rusty Williams:]

We haven't given any comments on that yet, so I apologize for not being able to give you much guidance on what the threshold for further development would be for 1039.

[Carmen Augustine:]

Okay. No problem. Thanks for taking the questions.

[Helen Collins:]

I will just add, because some of that also, I mean, it has to do with the type of patients who may know mesothelioma, like a lot of tumors, as we learn more and more about it, can become heterogeneous. So it does have to do with the overall, that some of the individual pieces of information, how many of the patients -- the sarcomatic version, etcetera. And again, this study was run by GSK.

[Rusty Williams:]

We are actually still getting information from them, and part of our reason for not having more clarity on this, is we are still getting information.

[Helen Collins:]

Yeah. Those details will be important to us.

[Rusty Williams:]

Okay.

[Operator:]

Thank you. Our next question comes from Chris Shibutani with Cowen. You may begin.

[Chris Shibutani:]

Thank you. Hi guys. On the Cabira plus OPDIVO solid tumor, we are looking forward to getting that update on SITC to try and ask the question for another layer. I guess, obviously, looking for response rates. Do you think we will have the sufficient body of data in terms of patient numbers and what not, to be able to make any assessments about durability of responses?

[Rusty Williams:]

Well thanks Chris. I guess you can do the math, on when we started and how much data we will have, as you can might imagine. So we started in October, and as we described before, some of the cohorts enrolled worked faster than others. You might imagine cohorts at tumors without many options -- therapeutic options would be the ones that might enroll the fastest. And so, our intent is to show meaningful data. And so, I guess, you will have to look at the data when they come out, for everybody's opinion about what's meaningful and what the durability is. But of course, in Immuno-Oncology, we and, definitely, BMS recognized that the key issues are, not only response rate, but durability, and that's what we are looking for.

[Chris Shibutani:]

Okay.

[Rusty Williams:]

Still relatively early, just want to give you that caveat still, just time wise, because we have been at this since October.

[Chris Shibutani:]

Understood. No, we remain keenly watchful. On FPA144, that's helpful to understand your further work on the diagnostics, in terms of using both IHC and the ctDNA in gastric, and how that may help you identify a broader group of patients. Can you comment about that with bladder? The release mentioned IHC, however in particular, do you see potential for ctDNA in the bladder population, and is that part of the planning?

[Rusty Williams:]

You know, currently it's not part of our planning. The way we got into this and gastric is actually kind of interesting. As it turns out, the number of gastric cancer docs, especially in the U.S. -- U.S. and South Korea too, have been doing ctDNA measurements on their patients. And so, we had patients who were in our trial early on, who had both ctDNA and IHC. And so, that's one of the ways we got into it. Now, we just found that, bladder cancer physicians, aren't doing that as much, and we are not sure that we would even expect in bladder cancer to see the amplification. As you recall, we have been thinking for years, the field has known for years that this amplification of FGF receptor 2 in gastric cancer is a driver of mutation and has a poor prognosis. That's an amplification, DNA amplification well studied for years. In bladder cancer, the way we got into that was, we happened to have one patient in dose escalation part of our trial, leading into the gastric cancer part, and that patient had bladder cancer, and that one out of one patient had a complete response. Happily, that patient is still doing well, after more than two years. And so we got into that sort of serendipitously, so we don't know quite as much about the molecular biology of bladder cancer, with respect to FGF receptor 2 over expression. But currently, we are selecting patients in bladder cancer by an IHC test that looks at over expression in the primary tumor.

[Chris Shibutani:]

Okay. That's helpful. Then lastly, can I go on the record of starting the process of pestering you for when we might be able to start to see some bladder data? Thank you.

[Rusty Williams:]

Yeah. Well you certainly may go on the record for doing that. You are walking down as one of the first ones, you may not be the very first. But in all seriousness, we started that trial only recently, and so it's still the early phases, and it's premature for us to give guidance on that.

[Helen Collins:]

And as I said, we were at VISUM [ph] that were chosen for gastric physicians, and even those are academic sites, who presumably somewhere in their institution, there is a doctor taking care of bladder cancer. What we found, is that it's a different building, a different whatever¸ and so we really are having to go to sites and get a bladder PI. So we have done that, and we are enrolling. It's not going to be in the next month.

[Rusty Williams:]

We will put you on record as being entrusted in that.

[Chris Shibutani:]

Excellent. Thanks for the progress guys.

[Rusty Williams:]

Thank you, Chris.

[Operator:]

Thank you. Our next question comes from Jim Birchenough with Wells Fargo. You may begin.

[Nick Abbott:]

Hello, good afternoon. It's Nick in for Jim this afternoon. It's a busy afternoon for us all. Just going back to Cabira in PVNS. I know, you are looking at once monthly dosing for [indiscernible]. Could you consider any other options, is there a biomarker strategy that could be used and are you concerned that some physicians might sort of practice a watch and wait strategy for this tumor?

[Helen Collins:]

I mean, again, to me there is actually two questions in your question. One is, what's a study design that we can be confident or what's a regimen that we can test, and then be confident when we go to pivotal trial and get approved, and then what will people actually do, once it's approved, right? So I think, the latter can be -- I will take off my five time -- lot of it is fine. I think if somebody is 35 years old, and has lived to hopefully 95, I will be honest, I think we would expect that they won't intermittently take something, and it will be somewhat individualized, and that's what we'd like. We'd like people to take it as needed, and hopefully, as little as possible, right. From the point of view of there, of just needing treatment for their tumor. From a clinical trial perspective, I think what we have done again is, based our decision of the Q4 weeks. On the PK, the PD, and what we've seen clinically, and so I think that's probably the best I think -- we feel pretty confident that we have got sort of a sweet spot right there, based on that data.

[Rusty Williams:]

Your question about the biomarkers, Nick, it's an interesting question. We have biomarkers, numerous ones actually, for the PD effect of our drug. Your question, maybe related to biomarkers of the disease. And we thought a lot about that. As a fallback, we always have MR as a marker for the disease progression and of course symptoms and function. And so, probably with that, it's enough, because again, we are not worried about the disease getting away from you, and if the tumor starts to -- I would imagine, if the patient starts to get more symptoms, and you get an MRI, you see if the tumor is gradually coming back, and then you may go back on the drug.

[Helen Collins:]

And you know people like with giant cell can grow -- we have giant cell, they will get Denosumab on and off I mean, so, I mean, I think that's kind of an expectation, but that it's a --

[Rusty Williams:]

And we have experience, that patients who responded to CSF-1R inhibition with PVNS and were off that drug, and then we came back and treated with Cabira, we got a response. So it's not as if you -- you don't develop resistance. We would have anticipated, and so I think it's fine to do it the way we describe.

[Nick Abbott:]

So really, on to trying to find a way to get these patients take this drug for a very long time?

[Rusty Williams:]

Yeah. We want to try to find a way through -- manage their disease for a very long time.

[Nick Abbott:]

Sorry. What a way to put that, thanks Rusty. And in terms of the pain criterion, is that on a vast [ph] without analgesics or do you have to have a certain level of pain control medications, and how does this affect your 25,000 patient number?

[Helen Collins:]

Again, I think two questions. So one was really going back to the data that we presented at ASCO. That part of the trial, did not require patients to have any pain at all, and part of that was just a pragmatic one. We were starting a Phase 1 study when this was written and Plexxikon had a trial that was ongoing, that required pain, and there aren't that many patients out there, we just wanted to make sure we got people that start taking it. So we do have patients that came on study, that did not have pain and as Rusty talked about. If you don't have pain, your tumor may get smaller, but you may not necessarily feel much better. So when we are highlighting that there or highlighting it during the earnings call portion, it's to say, when we are going to enroll additional patients, we do want to make sure that they have some clear symptom to begin with, that we can be very confident of the quantitative improvement in those symptoms; because again, we know that's going to be an important endpoint in a pivotal trial. And what we really want to do is, come out of these next number of patients enrolled, we want to come out with very clear and confident in our criteria set of pivotal trial is going to be successful. Again then, your question is, well what about -- and I guess, how people will end up using it. My guess is again, I can't speak for the trial, that would be --

[Rusty Williams:]

But the requirement for pain is a trial strategy at the moment.

[Nick Abbott:]

Okay.

[Rusty Williams:]

And the ultimate view, as Helen said, that we don't rule out that we would have -- that it would be indicated for patients who didn't have pain, who might be more incented to take a drug, if they knew the drug was approved and worked, than currently. So it's a trial strategy at the moment.

[Helen Collins:]

But the trial will certainly allow people who -- pain can be defined as, no you don't have pain, but you are taking 80 milligrams of oxycontin twice. In other words, there -- so we do plan on having decreasing pain medications for improvement in pain being -- pain data that we collect.

[Nick Abbott:]

Okay. And then just last one for me, on the 144 strategy in China. Do you have preferred Chinese partners? I mean, can you just comment on what you think the timing is for Chinese partner? And in terms of satisfying regulators in China, do you have to do a separate PK study in China or will the data you have from the U.S. and Japanese studies suffice? Thank you.

[Rusty Williams:]

I will start by saying that, we have a lot of interest from companies doing -- with cloud capability in China, in partnering us. They have tremendous amount of interest, and so, that's a good starting point for us. With respect to the regulatory issues in China, Helen, do you want to make any comment on that, the requirement? The requirement for manufacturing in China for example, have changed the requirements for what you need in early phase trials have changed. But we would anticipate our partner doing the trials in China, and with the great expertise in fulfilling Chinese regulatory requirements.

[Helen Collins:]

And as far as need for Phase 1, I mean, obviously our ongoing study right now is in Taiwan, South Korea, Japan, and then it goes back up -- South Korea and Taiwan, and of course, with a separate Phase 1. So we think we have enough data, that we do not need to do that. We have built in, that the potential that we might have to do that, we think that we are okay either way. I guess that's probably there. We started early enough in this process that neither is going to be very [indiscernible].

[Nick Abbott:]

So do you think by year end, you will be able to announce a partner then, Rusty?

[Rusty Williams:]

We are going to get the right partner, and we had a lot of discussions. I have heard a long time ago, never to make a deadline for establishing a deal transaction. We will get it right.

[Nick Abbott:]

And you got plenty of space on your passport then, it's not expiring in the next six months?

[Rusty Williams:]

We actually have a new one. So essentially, no problem.

[Nick Abbott:]

Good. Thank you very much.

[Operator:]

Thank you. Our next question comes from Tony Butler with Guggenheim. You may begin.

[Daniel Kilduff:]

Hey, this is Daniel for Tony. Thanks for taking my question. The first one is, how do you see FPT155 in light of the recent MYSTIC failure, and maybe concerning SITC data, can we expect data on IO refractory patients? Thanks.

[Rusty Williams:]

Yeah. Thanks Daniel. So how do we see FPT155 in light of the MYSTIC data. I am going to be sure I interpret your question accurately. I assume that what you are saying, is that the MYSTIC data, where the two agents that worked on two pathways, a CTLA-4 pathway and the PD-1 pathway, and had disappointing results. And how do we see this FPT155 potentially work for two of those pathways. Why do we think this one would work, is that your question?

[Daniel Kilduff:]

Yeah, that's correct.

[Rusty Williams:]

Okay. Well, we do have an ace in the hole there for FPT155 and that's CD28. In fact, CD80, it's mainly famous for activating CD28. You know the way that goes? CD80 activates CD28 on T-cells. They are very powerful interaction. CD28 drives the over-expression of CTLA-4, which is an inhibitory molecule on the T-cell and CD80, and it then quenches CD80's effect by binding the CD80. And by using soluble CD80, we have to get the benefit of both effects, that is blocking CTLA-4 and still activating CD28. You know, nobody has tried activating CD28 except with the top six antibodies, and because it gets superagonism. And it's a very powerful immunestimulant. We don't have that superagonism, we've checked that out every way we can imagine, with lots of consultants, that the TeGenero antibody had. But we think that this is -- we will be the first ones to check the CD28 activator, in combination with CTLA-4 blockade, and perhaps PDL-1 blockade. We can't be sure if all these mechanisms will be acting clinically. But we are most confident that we activate CD28 and CTLA-4, that the PDL-1 blockade may be icing on the cake. So I think we will be the first ones to test that out. So I don't think that MYSTIC reads directly on what we are doing. IO refractory data, could you -- so that was -- do we think Cabira could work in a setting. Let me see if I can paraphrase with more precision. We think that Cabira will work in a setting, in which there is resistance to PD-1 pathways, blockers, is that what you are saying?

[Daniel Kilduff:]

Yeah. If we see that on IO refractory patients.

[Rusty Williams:]

If by IO refractory, you mean, refractory to PD-1 pathway inhibitors? That is one of the things we are testing in this trial.

[Daniel Kilduff:]

Yeah. To PD-1 inhibition, yeah.

[Rusty Williams:]

And mechanistically, that makes some sense. It makes a lot of sense, mechanistically. I can't preview the data though, I can't preview the data that we are going to give.

[Daniel Kilduff:]

Thank you.

[Rusty Williams:]

Apologize for that.

[Operator:]

Thank you. Our next question comes from Christopher Marai with Nomura Estimates. You may begin.

[Christopher Marai:]

Hi. Good afternoon. Thanks for taking the questions. On Cabira here, I guess, you had highlighted Rusty, that it's meaningful data. The different types of meaningful data that could lead to you and your partner BMS going into next trial, that would be considered pivotal in select indications? And then maybe just, could you frame for us that, the general type of data that we may see, thinking about other similar IO datasets in terms of size and the type of data? For instance, data we have seen for [indiscernible] for various indications. And if you can elaborate just slightly on that, if I could beat the dead horse on that, the data at SITC. Thank you. And I have a follow-on.

[Rusty Williams:]

Yeah. Well thanks Chris. Don't worry, the horse is not dead yet. The question is, will BMS move to next phase, based on this data. We can't preempt with BMS on that, in terms of disclosing that. Of course, our intent is, and BMS' intent is to develop this program into the next phase, that has been the target all along. But I can't -- we will have to just give you guidance on the next phases, as we go along in the upcoming months. And then, I forgot the second part of your question.

[Helen Collins:]

Size of data. I mean, again, seven cohorts up to 30 patients. So when we complete our cohorts, 210 patients. Again, I think I will reiterate what Rusty was saying, we started enrolling those 210 in October, and then you can kind of think about, when we need a data cut-off in order to mix up 50, and you can get --

[Rusty Williams:]

This is not the majority. I wouldn't look for a majority of those, it's actually 280 patients that's factored in the 1a, we have report on those either. And so, I wouldn't look for majority of those patients to be included in this, that's about as much guidance as I can give. Simply for a matter of timing.

[Christopher Marai:]

That makes sense.

[Rusty Williams:]

It's not that far -- it's not too far off, abstract to be coming out before the meeting. So I wish I could say more, but it's just not prudent to do that right now.

[Christopher Marai:]

Got it. And maybe then switch gears to the gastric sensor trial for 144, I was just wondering if maybe, you or Helen could comment on some of the functions going into that pivotal trial? I mean, how well can you match the type [indiscernible] to be solid? If you are imagining a combo of chemo to that rainbow trial, that dataset, where it's your expectation right now, that you can best that data, do you think you need to do better than that, I mean obviously [indiscernible], but with that sort of threshold that you are looking to hit. And then -- sorry go on Helen, looking to 1039 in the second.

[Helen Collins:]

Okay. So 1039 question too, go ahead. Yeah go ahead, finish your question.

[Christopher Marai:]

Okay. Yeah on 1039, just wondering obviously, mesothelioma right now, is your plan to, maybe repurpose that for new indication potentially in the future. That's it. Thank you.

[Helen Collins:]

So to answer the Ramucirumab one first, I mean, I think from our perspective, if you look at our single agent response rate, the 19% versus their 3%, and yet -- and so we do think that whether -- that we will have a greater benefit than Ramucirumab will have. We also think that's important, because they are 10% of the patient population. So we will like to have give [ph] incentive if you will, for people who want to do that screening, when patients are initially diagnosed. So we are anticipating better benefit from that. In terms of, again, design of the study and the number of patients, there are quite a few factors that will go into that. We are having regulatory interactions right now. We do feel confident that the design of our study will be something that's clearly approvable, and again, I think in an ageing patient population, especially, the Chinese should make whatever site study we decide upon, able to be executed. I think that's probably the best -- go ahead.

[Aron Knickerbocker:]

Yeah, Chris, it's Aron. I just want to add that Rainbow study was a second line study, so we are not headed there. We are going to the front line, and we want to get in front of Ramucirumab, Paclitaxel.

[Rusty Williams:]

But we think that, relative to other agents that have been used as single agents in late line gastric cancer therapy, we stack up very favorably. I don't have all the numbers in front of me, but much better than Ramucirumab, which is 3% response rate, with 19% so -- as monotherapy.

[Helen Collins:]

Yeah?

[Rusty Williams:]

So the 1039 and other indications, it's a frustration, because I believe that this FGF receptor -- this FGF ligand trap, FGF receptor 1, is particularly useful for a number of indications. And I don't want to throw too many stones at GSK, but we are left in a position in which, there is not much -- there is no material, just to be straight about it. And so, to get to other indications, we have to manufacture materials, and then kind of start all over. So we want to find a way for this drug to be used in other indications, because I think there are a number of them, oncology and non-oncology, where this is an agent that really has activity, has a really good tolerability profile, and clearly has activity anticipated to just inhibit FGF. It reduces their levels and tops them up. And so, we are just -- it's not going to be soon before we are able to do something in other indication. We are interested in it, and we or with a partner or with an academic investigators and -- or with the people at the NIH and so we will be looking into that.

[Christopher Marai:]

Great, excellent. We will see you at SITC.

[Rusty Williams:]

Okay. See you there.

[Operator:]

[Operator Instructions]. Our next question comes from Ian Somaiya with BMO Capital Markets. You may begin.

[Steve Seedhouse:]

Thank you. It's Steve on for Ian. We are hoping, you guys could share your perspective on the IDOL-1 inhibitor data in combination with PD-1's in solid tumors and whether that's a reasonable bar to measure the SITC dataset against? And also -- actually, maybe we will stick there, and then I have a follow-up?

[Rusty Williams:]

I will make one comment and I will let my colleague to chime in. It's a different mechanism; Cabira is a different mechanism from IDOL inhibition. And our broad view of it is that, IDOL inhibition, this could work to enhance -- if you are excited about the data that are out there, that you would say that the place where it's most promising, is situations in which you already get a response to checkpoint inhibitor. We think that the blockage of macrophages in the tumor, may allow you to address tumors where you don't get PD-1 blockade inhibitors, as with even PD-1 blockade effect. And so it's different. So we don't really look at IDOL plus PD-1 as a bar or a metric or a comparator for what we are doing, because we think the mechanisms are so different, and that the mechanistic goals are different. Now we do have settings. As I pointed out, where there is resistance to PD-1 inhibitors that we are testing Cabira plus OPDIVO, obviously, but that's kind of different. So I think mechanistically, we don't make the comparison to IDOL plus PD-1.

[Steve Seedhouse:]

Okay. Thank you. And following up on a previous question for PVNS. You guys shared some of the market research you conducted, which is really nice. I am wondering if you can say, percent of the patients of, call it the 25,000 prevalent pool, you mentioned, do not have pain, by whatever criteria you use, and for patient who doesn't have pain, what would be their primary reason for seeking treatment? Is it to reduce the sizes of tumor or something else, function or some combination thereof? And then lastly, just wanted to ask, maybe you can walk us through what qualities Rusty, you and the board are looking for in a new CEO, is it an executive at a major pharma or somebody with biotech background, or somebody that you've worked with previously? Thanks.

[Rusty Williams:]

Okay, let's -- this is Rusty.

[Helen Collins:]

So first, let me see. So what we have had -- because we allow the patients to come out on our study that did not have pain, what kind of problems would they have? You are absolutely have, it will be, what they will call stiffness, decreased range emotion. We know anecdotally, sometimes it is cosmetic, it is somebody again a 25 year old woman, they don't want to have a swollen knee. So that's what we have seen on our study. I don't know if there is anything from market research, Aron, that you can add in terms of --

[Aron Knickerbocker:]

I will answer that, that this disease can, not only cause deformity and loss of function, they can cause nerve damage, by pinching on nerves, can lead to amputations. So there are all kinds of things besides pain. So we are not saying that ultimately, the drug will only be used in pain. I don't want to mislead you on that. We are just saying that, to design the trial, we think it's simpler to include pain as a criteria at this point in time. And so, there are many dysfunctions that can occur, that would lead you to want to use this drug. And one of it -- and those people don't like to have a gigantically swollen thumb, for example, a wrist. So I think it is idiosyncratic, depending on --

[Helen Collins:]

I am sorry to interrupt. But some of it again is also that regulatory endpoint, versus what people will use it for eventually. So again, some of what I am speaking from, from the point of view of you know, again, you have regulatory interactions about what is going to be an acceptable endpoint. And as you know in cancer, people look at response rate or progression free survival, as a proxy for the clinically meaningful endpoint, which you get right for survival. And in the case of the uses where the patients -- the outcome is not death, then the clinically meaningful endpoint is a functional -- measurable functional. I could not climb a flight of stairs, now I can climb a flight of stairs. And so, we talk about pain, but I think again, the most important thing is understanding now that we have had those interactions, we are very confident exactly what data we need to achieve a regulatory endpoint, right? And again, a patient may choose to take something, and we know they do, because it looks ugly. But that's not going to work for a regulatory endpoint in a pivotal trial, right? So I think that distinction is important in terms of the kind of patients we are enrolling now for this study, versus Aron's market research, which might be slightly different.

[Aron Knickerbocker:]

Yeah. We don't have a firm number on the percent of experienced pain, but it seems to me that, most do at some point. And that pain can be quite significant. But when we ask patients to raise the attributes of a medication for PVNS pain emerge, far and away the number one attributes that they were seeking, release of pain. And they describe their pain as it is, so like intense aching, sharp burning, constant nagging, debilitating. So it's severe and what we have heard from some of these patients, were anecdotes like, I am sitting down, I want a cup of tea, but I don't want to get up to make the tea, because it is painful, or I take my kids to the playground, but I can't play with them. I have to sit on the bench, because it hurts too much and I can't move my joints easily. So it's a composite set of endpoints that we are interested in believing, pain being paramount among us, but also range in motion, stiffness, and of course, just reducing the size of the mass. So pain is a key issue, and it seems that most patients do experience it as they progress.

[Rusty Williams:]

Okay. And then CEO search. So the question is, are we looking -- do we have a specific idea in mind of a large pharma executive or somebody I know. The good news is, I am still old. I know a lot of people. So there is a reasonable probability that somebody we pick, I would know. But we are not limiting to people I know. We are considering internal candidates. Obviously, I know internal candidates. There aren't external candidates. The Board, just in terms of process in all seriousness, the Board has a search committee, there is a subset of the Board. And I meet with that committee, that committee has a life of its own, and is diligently now looking through candidates who are pleased with the roster of candidates that we have. And so we think, at this point in time, it's good progress. We still have a way to go with this, still very early phases. So we don't have a preconceived notion. We are -- the company has evolved. So we want to get a CEO who reflects that evolution of the company. We are going more towards commercial activities. We are in oncology, so we think that whoever comes in the pipeline, has to know something about oncology, and has to also understand how drugs are developed and what the commercial landscape is. And so those are kind of some of the broad attributes. And we have a lot to offer, so the person who comes in here, will be somebody who appreciates the way we are going, and can utilize the considerable assets that we have. Those are our broad criteria.

[Steve Seedhouse:]

Okay, Thank you very much.

[Operator:]

Thank you. Our next question is a follow-up from Tony Butler with Guggenheim Securities. You may begin.

[Tony Butler:]

Yes. Hey Rusty, so I missed a good bit of a commentary. But one of the questions you or Helen alluded to, that I think is really interesting, and I don't know if this is possible. But for FGFR1, can you actually pull -- maybe it's in blood or maybe it's in the tissue. But once patients are treated, can you actually pull that issue and determine that, in fact, TAMs have diminished and TAMs to the tumor have diminished. Is there a way that may be done, and if it's true, then would any of that biology or pathology be available this year, post SITC or at SITC? Thank you.

[Rusty Williams:]

Thanks Tony. Good to talk with you. First of all, yeah, we -- in fact in this trial, we did about a third of the patients in Phase 1b, our target was to do pre and post treatment biopsies, to look at just that issue. Not only how does the tumor associated macrophages change in the tumor, but how do the other immune constituent cells in the tumor change. CD80 cells, TReg cells, etcetera. So we are collecting those kind of data. And we would anticipate, at some point, showing some of those data, when we have enough samples to be statistically meaningful. And I can't really comment on whether those particular data are going to be at SITC, but these are data that are important to us and for BMS. And I have to say, we and BMS are completely aligned on the way we think about this, and that is, we look for clinical responses, and we also are learning about the drug and looking for these kind of changes in the tissue environment, consumer micro environment, to see if the mechanism is what we think it is or what we originally proposed. So we will be able to shed some more light on that in coming months.

[Tony Butler:]

Appreciate it Rusty. Thank you.

[Rusty Williams:]

Thank you, Tony.

[Operator:]

Thank you. I am showing no further questions at this time. I would like to turn the call back over to Rusty Williams, Chief Executive Officer, for closing remarks.

[Rusty Williams:]

Well, thanks to each of you for joining us today and also for your support and interest in Five Prime, and as I said before, we look forward to updating you at future meetings and on future calls.

[Operator:]

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