FibroGen, Inc.
Q4 2016 Earnings Call Transcript

Published: 2 Mar 2017

[Operator:]

Welcome to the quarter four 2016 FibroGen, Inc. earnings conference call. My name is Victoria and I'll be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session. Please note that this conference is being recorded. And I will now turn the call over to Karen Bergman. Karen, you may begin.

[Karen Bergman:]

Thank you, Victoria. Good afternoon everyone and thank you for joining this call. Today we're reporting financial results and corporate updates for the fourth quarter and year end of 2016. The call will be led by Tom Neff, our Chief Executive Officer. Tom will start with an overview of our corporate strategy and execution on product programs in the quarter and the year. We will be joined by Dr. Peony Yu, Chief Medical Officer, who will provide updates on our phase 3 clinical trials in China, our global anemia program in chronic kidney disease, and then on anemia associated with myelodysplastic syndrome. Chris Chung, Vice President of China Operations, will address brand and commercial planning for roxadustat in China. Dr. Seth Porter, Vice President of Fibrosis Therapeutics, will discuss FibroGen's clinical development programs for pamrevlumab in idiopathic pulmonary fibrosis and pancreatic cancer. And Mr. Pat Cotroneo, Chief Financial Officer, will review financial performance. On this call, we expect to make forward-looking statements regarding our business, including our collaborations with AstraZeneca and Astellas, financial guidance, the initiation, enrollment, design, conduct, and results of clinical trials, research and development activities, and certain other business matters. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks, and changes that are difficult to predict, many of which are outside of our control. For risks and uncertainties regarding our business statements made on the call today, as well as factors that may cause differences between current expectations and actual results, we refer you to our Form 10-K for the fiscal year ended December 31, 2015 and quarterly report, including our Form 10-Q for the period ended September 30, 2016 filed with the Securities and Exchange Commission, copies of these filings can be found in the Investors section of our website. We undertake no obligation to update any forward-looking statement whether as a result of new information, future developments, or otherwise. The format for today’s call will include remarks from FibroGen's management team, and then we'll open the lines to take your questions. A webcast of this conference call will be available for replay on the Investors page at FibroGen's website, www.fibrogen.com. At this time, it is my pleasure to turn the call over to our CEO, Tom Neff.

[Tom Neff:]

Thank you, Karen. Good afternoon and thank you for joining us today in our conference call and webcast. And in the fourth quarter and full year of ’16 we made significant progress in our roxadustat and pamrevlumab programs. In January, it was our privilege to report roxadustat top line data from our Phase 3 China trial this year, we expect to report important late stage clinical developments and regulatory milestones for roxadustat in China and for pamrevlumab and IPF, idiopathic pulmonary fibrosis, and in pancreatic cancer. The lead programs we've distilled after many years of clinical research across multiple indications. Roxadustat program -- it’s our first-in-class world oral anemia agent in global phase 3 development. We believe roxadustat has the potential to expand the anemia market beyond the current ESA footprint. ESA use in chronic kidney disease or CKD patients who are not yet receiving dialysis has declined significantly since 2006 when study results highlighted ESA’s safety concerns and the FDA has progressively revised ESA product labels, first in cancer followed by CKD in July 2011. With these package label restrictions, revisions ESA use in the United States at the onset of dialysis declined from 31% in 2006 to below 14% in 2014. An important point here is that ESA use is driven mostly by those patients who are seeing nephrologists. If you think about those CKD patients who are not under nephrology care, only 148 of the patients have been treated with ESA at the transition of dialysis. We believe the anemia and non-dialysis CKD patients is generally not addressed because a majority of CKD patients today are not under nephrology care prior transition to dialysis. Roxadustat not only offers the advantages of access and convenience of an oral therapy but also has the potential to treat anemia without safety and efficacy limitations of ESA to address anemia and CKD. For these reasons we have taken a systematic approach to building the roxadustat product development program from anemia associated with CKD of dialysis and non-dialysis dependent patients and now we are expanding into oncology related anemias. With regard to roxadustat safety, in February 2017 the data safety monitoring board or DSMB which is responsible for safety oversight across our United States and European anemia studies, reviewed our Phase 3 programs and recommended continuation of all trials without protocol modification. We are incredibly excited about the results from our two Phase 2 trials in China for dialysis and non-dialysis dependent CKD patients, we reported our top line data in January 31 -- this year. These data represent the results of first pivotal studies for any HIF-PHI anemia compound anywhere in the world. These data are not only confirmatory of the efficacy results we saw on the Phase two trials in the US but now offer evidence for roxadustat’s potential to overcome inflammation which is compromise the efficacy of ESAs. Our study also showed the promise of roxadustat to be statistically superior to the premium price equal products in China manufactured by Kirin EPO for treatment of CKD anemia and dialysis patients. Markets [ph] in China is positioned for a productive year in clinical development as well as pre-launch commercial planning for roxadustat. We are on track to complete the 52-week safety assessment portion in the second quarter and to complete our India submission in the third quarter of 2017. We have now established a substantial presence in China which includes our manufacturing facilities. Later on, Peony will discuss our global roxadustat program in more detail and will also address our expansion into oncology related anemias. Pamrevlumab is a first in class fully human monoclonal therapeutic antibody that inhibits connective tissue growth factor or CTGF, a central mediator in chronic fibrotic and proliferative disorder. Due to pamrevlumab’s unique activity in the role of CTGF in multiple disease pathologies we've also taken a systematic approach to evaluate its activity in multiple categories of fibrotic disease which now supports our ability to prioritize our development programs on high value indications where there is tremendous unmet medical need. We conducted two expert panel meetings in Q4 2016 for each of the IPF and pancreatic cancer programs. For both indications these experts expressed great enthusiasm for the potential pamrevlumab has shown to provide meaningful benefit for these challenging indications. With respect to clinical trial progress we look forward to results in the third quarter from our Phase 2 randomized placebo controlled study and idiopathic pulmonary fibrosis as well as combination sub-studies with each of the approved medicines in this category and we are pleased to report continued progress in our trial in locally advanced pancreatic cancer. Seth will discuss our progress with pamrevlumab in our two most advanced indications later in this presentation. Regarding corporate updates, let me comment briefly on a patent matter that was resolved earlier this year and about which our shareholders would want to hear. In June of last year, GlaxoSmithKline or GSK filed petitions for Inter partes review of six FibroGen US patents. IPR is one of the newer procedures for patent challenge akin of the 2012 America Invents Act and recent reform to U.S. patent law. These patents relate generally to the use of HIF-PHIs to treat anemia and other conditions and to achieve certain effects on iron-related parameters. In January, the patent and trademark -- the patent trial appeal board or PTAB of the US Patent and Trademark Office ruled against GSK denying all six of the petitions and refusing to initiate IPR challenges against any of these FibroGen patents. We are pleased with these decisions which we see as validation of our pioneering role in the field of HIF-PHI therapeutics. These rulings are final and not appealable. Moving on to finance, I am pleased to report that we ended the year with $342.2 million of cash year end 2016, this is about 10% higher than what we estimated earlier in the year and compares to $336.9 million we reported for year-end 2015. And our most recent projection for 2017, we expect cash at year end to be between $250 million and $260 million. Pat will discuss our financial results for the fourth quarter and full year and I will wrap up later with our comments today on the 2017 milestones prior to calling the call for your questions. I’d now like to turn this over to Peony. Dr. Yu, please?

[Peony Yu:]

Thank you, Tom We have an extensive global Phase 3 program supporting regulatory submissions in the US, Europe, China and Japan. In China, our roxadustat Phase 3 clinical studies for CKD anemia have generated exciting results. In the8-week double blind placebo controlled portion of our CKD non-dialysis study, we saw a highly significant increase in hamoglobin level. As we reported in our press release and 10-K filing, 84% of roxadustat patients achieved hemoglobin response versus zero in the placebo arm, response is defined as at least one gram per deciliter increase in hemoglobin level. In the 26-week active controlled dialysis study, patients previously treated with stable doses of EPO commercially available in China were randomized two to one to roxadustat or to the premium priced Kirin EPO, after meeting the non-inferiority criterion for the primary efficacy endpoint of change in hemoglobin. Our pre-specified stepwise comparison showed roxadustat is superior to Kirin EPO. Roxadustat achieved a larger mean increase in hemoglobin level than EPO throughout the study period. Please note that during the study there was an overall increase in average EPO doses in inflamed patients with respect to baseline. Roxadustat performed remarkably well in the presence of inflammation in a subquib [ph] analysis by baseline C-reactive protein level, or CRP, a marker for inflammation, the hemoglobin levels in patients with inflammations were lower than non-inflamed patients, even though they received higher doses of EPO, in the comparator arm. In contrast, regardless of inflammation status, roxadustat treated patients achieved the desired hemoglobin levels with similar dose requirements. Inflammation is believed to be the main cause of hypo-responsiveness to ESAs in dialysis. Hypo-responsiveness typically leads to higher ESA doses which have been associated with safety issues, inflammation is also a major culprit in anemia of chronic disease, including MDS, cancer and autoimmune diseases. The fact that roxadustat was able to correct and maintain hemoglobin levels in patients with inflammation potentially offers us an opportunity to address anemia in a broad range of patients. We are very pleased about the positive results from both Phase 3 studies in China and look forward to completing our 52-week safety assessment in June. These two studies will be the basis of our China NDA submissions in the third quarter of this year. I’d like to look briefly comment on the expansion of roxadustat development program in China where our next indication is in anemia associated with MDS. Our CTAs for Phase 2/3 trial in MDS anemia is currently under review by the China FDA. We also plan to develop roxadustat for the treatment of anemia in other cancer related conditions in China. Turning to our global program supporting US and European regulatory submissions in CKD anemia, we are working closely with our partners AstraZeneca and Astellas on a total of seven pivotal studies. As you may be aware from AstraZeneca’s recent earnings call, we are on track to submit US NDA in 2018. We have updated our partner patient numbers in the FibroGen and AstraZeneca studies. These changes reflect updated estimates of the number of patients in each study to achieve necessary accrual of events. In Japan, our partner Astellas is consulting six Phase 3 studies; descriptions of these ongoing trials are available on clinicaltrials.gov. We are expanding roxadustat development beyond CKD anemia in the US. The IND in MDS anemia which is our first cancer related indication has been approved by the FDA. We are working on studies further, stay tuned. With that, I’d like to turn the call back to Tom.

[Tom Neff:]

Thank you, Peony. I’d now like to ask Chris Chung to talk about our efforts with AstraZeneca in China to prepare for regulatory milestones and commercialization of roxadustat.

[Chris Chung:]

Thank you, Tom. The Phase 3 top line data represents the culmination of years of planning, building out an organization on the ground in China and an unyielding focus on execution. Over the next few months we will work to ensure that the NDA submission process advances on schedule. This is going to be a very busy year for China and we're committed to meeting these objectives. In parallel, we're working and putting resources to work with AstraZeneca’s dedicated roxadustat marketing and market access teams to refine the commercialization plan for China. We believe we have a compelling opportunity in front of us to introduce a paradigm shift for how CKD anemia will be treated in China in terms of access to treatment, clinical treatment pathway and clinical outcomes. We have over the years invested in developing an extensive network of senior level key opinion leaders and we will continue to work with them to characterize the unmet medical need and educate the broader nephrology community about the HIF mechanism of action. The AstraZeneca market access team has presence in all 31 provinces in China and we have started to craft a reimbursement strategy one which we hope will accelerate reimbursement coverage for roxadustat. We're working with AstraZeneca on brand strategy in a manner that differentiates the HIF mechanism for the combination of ESA and intravenous iron, a brand strategy that will also inform our pricing. It is extremely rare for a first-in-class drug to be approved in China before the United States. The AstraZeneca-FibroGen roxadustat team is working to ensure a successful first launch of our HIF-PHI therapeutic. And with that, I now turn the call back to Tom.

[Tom Neff:]

Thanks, Chris. I would now like to introduce Seth Porter who heads up our pamrevlumab and fibrosis therapeutics group. Seth?

[Seth Porter:]

Thank you, Tom. In 2017, we will report the results of our Phase 2b trial for IPF and complete the treatment period for the Phase 1/2 proof of concept trial for locally advanced pancreatic cancer. For IPF, we will complete conduct of the placebo controlled as well as the standard of care portions of the 067 study. We expect to report top line results in the third quarter of this year and hope to subsequently present them at an international pulmonary meeting. Results of the 049 open-label Phase 2 IPF study reported in the European Respiratory Journal in 2016 provide us with a reasonable basis for the results we expect to see in the 067 randomized placebo controlled trial. We also expect to present this fall data from a mouse radiation induced fibrosis model in which we compare efficacy of pamrevlumab with pirfenidone and nintedanib. This mouse radiation induced lung fibrosis model is the same one that previously demonstrated the ability of pamrevlumab to reverse lung fibrosis measured by quantitative high resolution CT imaging and to improve pulmonary function. Those results in many ways predicted the outcomes we observed in the 049 clinical study. For pancreatic cancer, we expect to complete enrollment and the treatment phase of the 069 study this year. In January, we presented updated results from that trial, seven of nine subjects who completed treatment with chemotherapy plus pamrevlumab met protocol defined criteria for treatment response and were considered potentially operable following treatment. Three subjects had complete tumor removal or R0 and one subject had microscopic tumor remaining after surgery, R1. Three were found to have metastasis that had not been detected at study entry. In contrast, of six subjects who received chemotherapy alone, only one met protocol defined criteria for treatment response and had a complete tumor removal, R0. Pamrevlumab continues to be well tolerated with no safety concerns. Differences in overall survival between subjects treated with and without pamrevlumab look encouraging. This is consistent with the results of the 028 clinical trial in pancreatic cancer that we published in The Journal of Cancer Clinical Trials in February 2017. Those published results support a dose related increase in survival in advanced pancreatic cancer and that pamrevlumab can be safely combined with chemotherapy. It's known that for pancreatic cancer patients with locally advanced non-resectable tumors, the median survival is eight to twelve months, whereas for patients with resectable tumors, the median survival approximately doubles to seventeen to twenty seven months. Pancreatic cancer experts in our advisory board meeting agreed that if pamrevlumab treatment can improve the resection rate of locally advanced pancreatic tumors, it would be expected to yield a substantial survival benefit and would probably require only a modestly sized pivotal clinical trial to demonstrate clinical benefit. Based on that we are evaluating design options for a pivotal trial for locally advanced pancreatic cancer. We anticipate the results from the IPF and pancreatic cancer studies will place us in a strong position to possibly initiate pivotal programs in two indications for which there is considerable unmet medical need. Thank you for your time today and now back to Tom.

[Tom Neff:]

Thank you, Seth. Pat Cotroneo, our chief financial officer will now walk through financial highlights for the fourth quarter and full year. Pat?

[Pat Cotroneo:]

Thank you, Tom. As announced today total revenue for the year ended December 31, 2016 was $179.6 million. For the same period, operating expenses were $233.2 million and net loss was $61.7 million or $0.98 per diluted and basic share. Included in operating expenses for the year ended December 31, 2016 was an aggregate non-cash portion totaling $40.7 million, of which $32.1 million was a result of stock based compensation expense. In terms of our total cash balance, we had $342.2 million as of December 31, 2016, as compared to $336.9 million at the end of 2015. For these purposes, total cash refers to cash, including cash, cash equivalents, receivables, investments consisting primarily of investment grade corporate debt and restricted time deposits relating to our building lease. On our balance sheet, the category of long term investments consists entirely of investment grade corporate debt with remaining maturities of up to two years. For Q4 and full year 2016 our financial results show the effect of reaching our funding cap in Q4 2015 with AstraZeneca for roxadustat U.S./RoW developing costs. Most notably we no longer pay the 50% portion of our partners' development costs. Plus we are now able to invoice 100% of agreed upon roxadustat development costs instead of 50% before the cap was reached. These two changes resulted in a net reduction in cash burn of approximately $90 million for 2016. This amount represents the pro forma reduction in 2016 cash burn as if the 50

[Tom Neff:]

Thank you, Pat. As promised, I'd like to preview a number of our current stage [ph] in 2017. Milestones for roxadustat include

[Karen Bergman:]

Operator, if you would open up the call to Q&A.

[Operator:]

[Operator Instructions] Our question comes from Michael Yee from RBC Capital Markets.

[Michael Yee:]

Hi thanks. Good afternoon. Congrats on the progress so far guys. Two questions, the first is on roxadustat. Can you comment on how big the change in enrollment is now, how many patients or what percentage increase in size? And the second question is, have you talked to the FDA about these changes; what is the feedback on amending the protocol, what they said about it and what's the feedback on that? Thanks.

[Tom Neff:]

Thank you, Michael. So Peony, go ahead and address the change in enrollment, please.

[Peony Yu:]

Okay. So I think these numbers, of the five studies being run by FibroGen and AstraZeneca, four of them already have a change in participation numbers that are already reflected on clinicaltrials.gov and one of them is in the process of being changed. AstraZeneca study 001 also known as OLYMPUS new target number is 2700, a change from 2600. Rockies, or also known as study 002, the dialysis study is being -- new target number is 2100, a change from 1425, the one that has not appeared yet which is the FibroGen sponsored incident dialysis study, 063, new number is 900, a change from 750. FibroGen sponsored study 064, in patients on dialysis, new number 820, a change from 600. FibroGen non-dialysis study 360, new target number is 900, a change from 600, which for all three of these FibroGen sponsored study, I believe, Mike, you are aware that we had met our original target enrollment quite some time ago and we have continued to enroll patients.

[Tom Neff:]

Thank you, Peony. With respect to updates and the process we're planning on with FDA, the updates would be that in November we had a very extensive advisory board that went over two days, with a number of senior FDA reviewers who are now retired and very expert in these matters as well as statisticians, that was followed in December by a week of intensive meetings between the companies, as well as in January, if I had to characterize what has happened, the net effect of the advisory boards were to leave the impression with the team of really an increased sense of optimism about the overall picture. I think across the board everybody felt pretty good about what we were hearing and what's going on. With respect to FDA, we do not yet have an ability to comment on that and we won't say anything until we've had the full interaction completed for fear of prejudicing any discussion, so that's the update.

[Michael Yee:]

Generally, when would that be -- later this year, mid-year, summer, that still helps?

[Tom Neff:]

It'll be later this year and we have to see -- people are in the throes of writing briefing materials now, it’s a very large process and the complexity of the process actually slows things down a little bit. But everybody's very focused on getting there.

[Operator:]

And our next question comes from Terence Flynn from Goldman Sachs.

[Cameron Bradshaw:]

Hi, this is Cameron on for Terrence .Thank you for taking our question. Maybe just one quick one. Can you remind us the status of the ongoing European patent dispute you have with Akebia?

[Tom Neff:]

So in Europe we have four active oppositions. And two of them are essentially ongoing still and two are under appeal. The terms of the appeal -- the appellate process are that the patent stays outstanding in full force and the expectation is three to four years until the appeals will be heard. I think that's about all we're willing to say there.

[Operator:]

And our next question comes from Geoffrey Porges from Leerink Partners.

[Geoffrey Porges:]

Thanks very much and just a few quick questions if I may. First, Chris, could you talk about your expectations for what the likely timing of the review cycle will be with the China FDA and then what we should expect in terms of the timing for achieving reimbursement or at least some degree of reimbursement in that market? And then secondly, Tom, should it now be our expectation having gone through the IPR that that GSK is likely to infringe FibroGen’s patents -- HIF patents in the future? And then lastly, for Seth, could you talk about what the path -- the regulatory path might be for pamrevlumab in the IPF and pancreatic cancer indications? Do you have confirmation that resectability is an end point in pancreatic cancer and might the Phase 2b data be sufficient for filing in IPF? Thanks and sorry for all the questions.

[Tom Neff:]

Okay. So Chris, go ahead and take on parts Geoff asked about China.

[Chris Chung:]

Sure. So Geoff, to your first question, which is the expected turnaround time for the NDA review cycle by the Chinese FDA. On the very very aggressive end of things we would like to think that we could move the dial to a twelve to fifteen month timeframe, we're allowing for up to eighteen months. So we're expecting NDA approval by the end of 2018. As you know the Chinese FDA had extensive reforms starting in 2015 that highly favors innovation. We're hoping to take advantage of that to move forward as fast as possible. Second question you had is, what is the expected timing of reimbursement? As we all know the National Reimbursement Drug List was just announced, it’s anyone's guess as to when the cycle will come around again, as you all know, the last time before 2017 it was 2009. However we’ve been informed by our AstraZeneca colleagues that the Chinese government is contemplating different types of innovative mechanisms such as a rolling reimbursement clock. So right now, George, unfortunately it’s a little bit too early to tell and for competitive reasons and not to compromise the regulators, we prefer not to discuss more extensively at this point. But later when we see more, we’ll most certainly come back to you.

[Tom Neff:]

With regard to the GSK patent matter, it is not our policy to speculate on whether or how another party might view our portfolio. These things are very complicated. There's all kinds of issues, the various patent prosecutions going on for over a decade, so we can just tell you the facts and the important facts here are, we are now spending lot of money this year on six IPR processes. Seth, if you want to go ahead and --

[Seth Porter:]

Hi Geoff, thanks for your question. With regard to IPF, our regulatory path is really going to be determined largely from the results from our 067 study that were read out in Q3 and really depends upon the effect size that we see in terms of sample size it will need for pivotal trial and what we want to do in terms of comparator arms. So we're certainly working through a number of potential scenarios and modeling out potential sample sizes but I think we have to wait until we get the results from that randomized trial before -- before we make any kind of definitive statements. With regard to locally advanced pancreatic cancer, interesting question about whether the current study would be sufficient, we don't think so. It's still a relatively modest sized trial, we're very encouraged by the results that we've seen. And if you recall, I don't know if you saw the ASCO GI poster but we're seeing some signs of improvement in survival. But based on those results as I said in my comments, we're getting guidance that if in fact we can continue to see that difference between pamrevlumab plus chemo versus chemo alone, that should lead to a substantial improvement in survival. So we will certainly suggest that that resection be a surrogate endpoint, but our expectation at this point is that, that we may have to show survival either as a primary endpoint or as a commitment after accelerated approval. So we're working again through those scenarios as well. But we think that is a very viable path forward in any case.

[Operator:]

And our next question comes from Joel Beatty from Citi.

[Joel Beatty:]

Hi thanks for taking the questions. Can you tell us more about the impact of the finding in the roxadustat trial in China compared to EPO that showed superiority? What does that mean for the potential of roxadustat in China and is there any read-through to the US?

[Tom Neff:]

That's a good question and I'll try to answer, Joel. The market in China is currently involving numerous EPO compounds, most of which were not knock-offs, not biosimilars. And the Kirin EPO which is priced about three and a half times the others has been seen as the “premium EPO”. We used the Kirin EPO in the controlled arm of our study because we thought it was the best single test in light of what counsel from our regulators was. The result as it relates to sort of superiority, let me point out that the Kirin arm, the Kirin EPO arm patients, the PIs were allowed to increased dose. And if you look in our 10-K filing you'll see that they actually did increase dose to try to stay in the target range of ten to twelve. So there was no restriction on dose. However to be honest we were very surprised at the superiority on efficacy side, we had been expecting non-inferiority. So that's the kind of thing where you’re just sort of amazed at what happens. We do have additional data which I also think is in the filing relating to patients that have high inflammation which is CRP above 5 versus low inflammation. And you'll see that with roxa, the high inflammation patients were -- actually the one arm out of the four that responded the best, and if you look at the dosing over the term of the study, the dosing actually went down as the PIs tried to stay in the range of ten to twelve which they successfully did across the board. And by contrast with the EPO, the high CRP arm did very poorly, it was the lowest performing of the four arms in the study. And the dosing was steadily increased -- it looks like I can't give you an exact number of -- looks like about 30% increase over the entire study given that subset. As it relates to the superiority aspect in efficacy, I don't expect that has much impact on the US. By contrast in China, it’s important to remember that there are very tight restrictions in many ways -- First off, in China there is no public source of transfusion. So most red cells in the U.S. come from transfused blood and probably 95% of them do and in China this is really not part of the standard of care medicine and we've been instructed by our regulators not to include that and control arm assumptions in this study and other studies. With respect to EPO, in the early years the prices were very very high and took a much disagreement between the government and the original innovator which was Amgen to finally get to something that resembled an equilibrium. And what we see is that the knock-offs were brought into the market by the government. They are largely products that are promoted and sold by state-owned enterprises, only one is really a biopharma product. And with regard to the potential and so on what we notice is that at the hospital level the budgets for these kinds of products require provincial level approval and there are very tight restrictions on the use of EPO beyond dialysis where it is used as the government is building out a dialysis system and most other areas it’s very limited. And so as a result, there's a large opportunity in China to be another source of red cell for standard of care medicine. So I think that's all I should probably say for now but I think you get the general idea.

[Joel Beatty:]

Yes, thank you for the explanation. And I have one other question, a housekeeping question. Are there any milestone payments included in the 2017 cash guidance?

[Tom Neff:]

There's one milestone payment which is $15 million associated with the NDA filing in China.

[Operator:]

And our next question comes from Kennen MacKay from Credit Suisse.

[Slanix Alex:]

Good afternoon. This is Slanix Alex calling in for Kennen. Thanks for taking the questions and congrats on all the progress. I had a quick question on the upsizing of the trials for roxadustat and I positively missed this from earlier but could you just go into -- add some color as to the rationale for the upsizing?

[Tom Neff:]

Let me have Dr. Peony Yu address this. Peony, go ahead.

[Peony Yu:]

Okay. Hi, as to the patient numbers these numbers are also reflected in our new 10-K which was filed today. As for rationale for the upsizing, this is primarily to optimize our program in the dialysis patient population. We are adding to patient numbers to ensure sufficient number of incident dialysis patients from the U.S. and there's also -- as you see the number of patients we're adding to the non-dialysis is fairly small, when you -- only a few hundred patients when you look at the overall scope of the program. And this is overall optimization for the right patient mix as well as to optimize our timeline to achieve patients that we need, patient exposure we need for meeting the safety endpoint refinements.

[Slanix Alex:]

And I had a second question on IPF for dialysis [ph]. Was wondering if you could provide some color on some of the differences between the HRCT scans that have been done for some of the marketed or IPF drugs versus what have been done for pamrevlumab and what we might be expecting in the Phase 2 update?

[Seth Porter:]

Thanks for your question, it's a good question and an important one. So for what we've done in the previous open label Phase 2 trial and the trial that we will be finishing up this year, we are doing a quantitative high resolution CT imaging. So we're not just looking at qualitative assessment by eye but we're actually using a validated computer systems to quantify the extent and the changes in fibrosis in the IPF patients. And importantly we stipulate in our trial unlike others that there has to be at least a minimum amount of fibrosis in our IPF patients so that -- if there is reduction in fibrosis we can see it and measure it. As far as we know what's been done in the other trials, we’ve always seen is the sort of the typical qualitative assessment of HRCT imaging which is at best semi-quantitative assessment of changes in fibrosis .And what we've learned from our trial and there is more and more information being published on it, the computer is a far more reliable assessment of extent in change than is the human eye. And we know that other companies have been conducting studies using quantitative HRCT but we haven't seen any results. So we're the only company who has reported results in terms of quantitative HRCT in IPF and changes in fibrosis accordingly. It's also important to point out that our primary endpoint certainly in this randomized Phase 2 study is like the others that changes in efficacy percent predicted, so that's our primary endpoint and that would be the basis of decision making going forward for pivotal trials. But we think that the quantitative HRCT has indicated that at least in some patients, pamrevlumab is in fact disease modifying.

[Slanix Alex:]

And just one follow up question, because of the potential shelf-filing, we thought that come through, just wanted to get a sense from you overall what any potential funds from this might be used for?

[Tom Neff:]

In our corporate planning process we look at scenarios going forward in what is happening both in China and in the U.S. we will see anti-body program, there are data driven opportunities that are emerging and regulatory feedback that’s been very encouraging in various areas where we might choose to end up investing more in various areas than what we planned originally at the time of the IPO. If you recall the time of the IPO, the US/RoW anemia program was actually fully financed. And so we didn't have any going forward financing plans. However in this past year the overall process we realized that there are possibilities here of need for finance and as a result we studied the options and choices were made in the shelf filing that -- it's reported, now actually it was agreed upon a couple of months ago. I think that's all we’ll say for now.

[Operator:]

And our last question comes from Tom Shrader from Stifel.

[Tom Shrader:]

Good afternoon. Thanks for sneaking me in. To go back to the last question, I just wanted to make sure in your own incident dialysis trials, are all those trials done in places where people can give as much ESA as they want or will you run into places where people can stop getting ESA?

[Tom Neff:]

So that's a good question. There's a public order from FDA in 2012 asking for incident dialysis patient enrollment, in prior times it wasn't done. So you don't have any studies, early part of dialysis initiation attempts to correct hemoglobin and what the results were and so on. So FDA wants to see that. As it turns out we've been able to enroll incident patients outside the U.S. and in the U.S. But with regard to the categories that are of particular concern in the U.S., this is the portion of the maintenance dialysis population that uses very high levels of EPO and iron support, the so-called hyporesponsive patients. We had been informed by CMS in 2015 that they viewed -- about this 35% to 40% portion of the maintenance pool as not having adequate standard of care and we were informed that if it turns out that our data supports treatment favorable results for those patients that we would not be expected to be in the bundle but separately reimbursed .And as a result it's very important for us to plumb through the incident population in the U.S. I think it's fair to say that the limitations on use elsewhere produce fewer patients that can survive on dialysis when they have chronic inflammatory disorders. So there's more morbidity, mortality at the time of initiation, or people don't even go on to dialysis because they can't respond to ESAs at normal doses. And I think that narrative is an important issue and I know from the interactions with CMS people that the interest in the possibility that roxa approaches this entirely differently, and because of regulation of Poseidon [ph] and the no impact to inflammation may be a unique solution that's of great importance in the U.S. So we're all very focused on getting the largest number of incident patients possible in the U.S. because of that. Your question -- your question is very insightful, Tom.

[Tom Shrader:]

A quick follow up to Chris, Chris, does this give you hope that there's a significant self pay market in China because of people who just couldn't respond to ESA?

[Chris Chung:]

So yes I think we're very optimistic based on the superiority that Peony presented and as illustrated in the 10-K, that we have a very strong basis of differentiation for not only the patient population that has not responded in the past but also people who have historically been willing to pay for a premium EPO. So yes we're very confident about the self-pay market even more so than we have historically. End of Q&A

[Operator:]

There are no further questions at this time.

[Tom Neff:]

Thank you all for joining our call today. We are excited about and committed to 2017 regulatory and clinical objectives for our lead programs. With China Phase 3 data serving as a very positive start to this year we are looking forward to sharing more news on our late-stage progress in China for roxadustat in addition to staying focused on advancing our Phase 3 programs worldwide. This will also be an important year for pamrevlumab as we complete the Phase 2 enrollment and treatment portion of the trial in locally advanced pancreatic cancer patients and report top line data from our Phase 2 trial in idiopathic pulmonary fibrosis. We are constantly building value in our pipeline while executing on multiple indications in each of our programs. While leveraging our partnerships and managing our resources, it goes without saying that we are dedicated to demonstrating the value of our pipeline programs and the potential to address serious gaps in the treatment of chronic and life threatening conditions. I'd like to thank the FibroGen team in the U.S. and in China for their hard work and our shareholders for sharing this vision and their continued support. I’d like to wish everyone a good afternoon. Thank you.

[Operator:]

Thank you ladies and gentlemen. This concludes today’s call. Thank you for participating. You may now disconnect.