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Edited Transcript of FGEN earnings conference call or presentation 9-May-19 9:00pm GMT

Q1 2019 FibroGen Inc Earnings Call

SAN FRANCISCO May 15, 2019 (Thomson StreetEvents) -- Edited Transcript of FibroGen Inc earnings conference call or presentation Thursday, May 9, 2019 at 9:00:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Elias Kouchakji

FibroGen, Inc. - SVP of Clinical Development, Drug Safety & Pharmacovigilance

* K. Peony Yu

FibroGen, Inc. - Chief Medical Officer

* Karen L. Bergman

FibroGen, Inc. - VP of IR & Corporate Communications

* Pat Cotroneo

FibroGen, Inc. - Senior VP of Finance & CFO

* Thomas B. Neff

FibroGen, Inc. - Founder, Chairman & CEO

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Conference Call Participants

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* Difei Yang

Mizuho Securities USA LLC, Research Division - Executive Director of Americas Research

* Geoffrey Craig Porges

SVB Leerink LLC, Research Division - Director of Therapeutics Research, MD & Senior Biotechnology Analyst

* Joel Lawrence Beatty

Citigroup Inc, Research Division - VP & Analyst

* Michael Jonathan Yee

Jefferies LLC, Research Division - Equity Analyst

* Terence C. Flynn

Goldman Sachs Group Inc., Research Division - MD

* Tsan-Yu Hsieh

William Blair & Company L.L.C., Research Division - Senior Research Analyst

* Xiaodong Zhang

Stifel, Nicolaus & Company, Incorporated, Research Division - Associate

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Presentation

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Operator [1]

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Welcome to the FibroGen First 2019 Financial Results Conference Call. My name is Erin, and I will be your operator for today's call. (Operator Instructions) Please note that this conference is being recorded. I will now turn the call over to Karen Bergman. Ms. Bergman, you may begin.

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Karen L. Bergman, FibroGen, Inc. - VP of IR & Corporate Communications [2]

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Erin, thank you very much. And good afternoon, everyone, and thank you for joining our call. Today, we are reporting financial results and corporate updates for the first quarter of 2019.

Joining today's call are Mr. Tom Neff, Chairman and Chief Executive Officer; Dr. Peony Yu, Chief Medical Officer; Dr. Elias Kouchakji, Senior Vice President, Clinical Development, Drug Safety and Pharmacovigilance; and Mr. Pat Cotroneo, Chief Financial Officer.

Following prepared remarks, Tom will discuss upcoming milestones, and we'll open the call to Q&A.

During this call, you may -- we may 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; our regulatory strategies and potential regulatory results; our research and development activities; and certain other business matters. For risks and uncertainties regarding our business and statements made on the call today as well as factors beyond our control that may cause differences between current expectations and actual results, we refer you to our annual report on Form 10-K for the fiscal year ended December 31, 2018 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 statements whether as a result of new information, future developments or otherwise.

The format for today's call includes remarks from FibroGen's management team, and then we'll open the lines up to take your questions.

The press release reporting our financial results and business updates and a webcast of today's conference call can be found on the Investors section of FibroGen's website at www.fibrogen.com. The webcast will be available for 2 weeks from today's date.

And with that, I'd now like to turn the call over to our CEO, Tom Neff.

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [3]

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Thank you, Karen. Welcome, everyone, and thank you for joining us. Today, we are reporting on top line adjudicated results from the 7 Phase III roxadustat studies performed by ourselves and our partners, AstraZeneca and Astellas, including the MACE and MACE+ analysis, which is an important part of the overall benefit/risk assessment regulators will perform.

These results are broken up into 2 safety pools as agreed upon with FDA and EMA. There are 4,000 patients in the pool of CKD patients who are dialysis-dependent, where roxadustat is compared to epoetin alfa and 4,300 CKD patients who are not on dialysis where we are compared to placebo.

We are also reporting results in the subgroup of incident dialysis representing patients who have recently begun dialysis and are not on ESA. This result is especially important as this setting is the most suitable for the comparison of roxadustat in the current standard of care.

In the U.S., we believe that major adverse cardiac events or MACE endpoint, defined as the time of first occurrence of death, myocardial infarction or stroke, will be the primary basis upon which the FDA will assess the safety of roxadustat.

In Europe, we believe that MACE+, which consists of the defined MACE components plus hospitalization due to heart failure or unstable angina, will be the primary endpoint for safety assessment by European regulators.

In the EU, we have agreed with regulators on a non-inferiority margin. And in the U.S., we have had extensive discussions on this topic and expect to finalize standards in our pre-NDA meeting.

We'll discuss today some of the most important initial safety results based on a totality of data that we've analyzed to date. In addition, we want to highlight important results from other clinical measures that we are analyzing, such as change in renal function in non-dialysis patients as measured by change in eGFR, efficacy of roxadustat as compared to epoetin alfa and the presence of patient inflammation and relevant quality-of-life measures in non-dialysis compared to placebo.

While the FDA and EMA will make their ultimate approval decisions upon their own analysis of benefit/risk profile of roxadustat, the applicable patient populations -- nonetheless, we and our partners believe the data is strongly supportive of the efficacy and safety of roxadustat.

I would now like to walk through our MACE and MACE+ results from the adjudicated pool of Phase III data, which have been reviewed by our -- with our U.S. partner, AstraZeneca; and our EU partner, Astellas.

In dialysis-dependent CKD, in the pooled analysis, roxadustat was shown to be non-inferior to epoetin alfa and MACE+ analysis. For the U.S., where there were several analyses, we believe there was no clinically meaningfully difference between roxadustat and epoetin alfa in MACE risk.

In incident dialysis, as noted above, we've examined the results from the incident populations who are patients in newly initiating dialysis approximately 4 months' time before they initiate anemia therapy. We believe this dialysis subpopulation is the fairest setting for comparison of roxadustat versus ESA as this period of treatment has substantially increased levels of patient mortality, where the stable dialysis population continues twin biases of patients who have survived the incident period and are already on stable doses of ESA after dose titration.

In incident dialysis, roxadustat demonstrated superiority to epoetin alfa and time to first MACE+ analysis. And in the time to MACE analysis, there is a trend towards reduced risk for patients on roxadustat as compared to epoetin alfa.

We would highlight for you this robust result of superiority came from the 1,500-patient pool with 1:1 randomization versus epoetin alfa.

In the NDD CKD population, 4,300 patients were randomized over 3 studies conducted by AstraZeneca, Astellas and FibroGen. These studies represent the first investigation in the CKD population where median eGFR levels are much lower than prior studies. This is a study that was started after FDA restricted the use of ESAs to below hemoglobin 10 and no retreatment at levels above 10. In non-dialysis, roxadustat was shown to be non-inferior to placebo in time to first MACE+. In the MACE safety analysis of this population, we believe there is no clinically meaningful difference between roxadustat and placebo.

Another way to view the NDD population results is to test the ITT analysis with long-term follow-up as the majority of patients in this pool followed through the end of the study. This is a conservative way to evaluate long-term safety in the NDD population. Patients on roxadustat received treatment for longer periods than placebo patients because some of the placebo patients dropped out for lack of efficacy. Since safety data were also collected in the post-treatment period, we were able to add in ITT analysis, one, from follow-up as the majority of the patients in this pool followed through the end of the study. As to the intent-to-treat results, in multiple analyses of both MACE and MACE+, MACE-free survival and MACE+-free survival, CV MACE and CV MACE+, roxadustat was comparable to placebo. These results were below the commonly applied non-inferiority margin of 1.3.

The ITT long-term follow-up analysis is one of several methods that have been discussed with the FDA to address the differential dropout rate.

As to -- apart from MACE data results -- so a correction I have to make which is that we have not yet spoken with FDA. These -- there is a discussion planned with the FDA about these various analyses. So it is planned to be, not has happened.

All of these evaluations help to better understand additional benefits of roxadustat apart from the MACE and MACE+ safety analyses. It is important to note that we enrolled a unique population, eGFR was from 0 to 60, including even the sickest patients with median eGFR in the study pool between 15 and 20, as large prior studies such as TREAT were enrolling patients must healthier. This is the first time a patient population this sick has been studied.

We have results in the eGFR versus placebo comparison for change in renal function over time. We evaluated where the treatment of roxadustat could slow the rate of decline of renal function in a clinically relevant manner. Evaluations were performed across all NDD/CKD populations. We also included the more conventional baseline cutoffs for non-dialysis patients, meaning the patients with eGFR above 10, as well as the population eGFR above 15.

Since receiving the unblinded data after adjudication, we have completed the 1-year analysis of roxadustat versus placebo. Data evaluation in this study continues. In the 1-year data, we have observed statistically significant slower rate of eGFR decline in the roxadustat-treated patients versus placebo-treated patients in the NDD pool as well as both subgroups. In the pooled analysis of eGFR changed over time from the 3 NDD studies in patients with baseline eGFR above 15, they showed a treatment difference from baseline of 1.62 at 12 months. We believe the results observed over time in this analysis suggests that the roxadustat treatment may slow renal function decline in a clinically meaningful manner. We are examining data in more detail, including stratified by a level of disease progression, to understand the degree of difference and the impact of different subgroups at baseline over the longer term.

In other measures of efficacy of roxadustat, we are pleased to have shown statistically significant improvement in the multiple standard Quality of Life measurements and to have confirmed roxadustat's efficacy in the presence of inflammation as measured by CRP where EPO requires increased doses over time. Dr. Peony Yu will describe these results in more detail later in the call.

We are on track for roxadustat's submission for U.S. NDA, September, October time period, with the European MAA submission to follow.

Let me now turn to updates regarding China. Our NDA for roxadustat was approved in December 2018 by the National Medical Products Administration, NMPA, for the treatment of anemia caused by CKD in dialysis patients. We are pleased that all clinical site inspections for the Phase III non-dialysis study have now been completed by the Food and Drug Administration division, or CFDI of NMPA. And we expect the population of non-dialysis CKD patients to be added to the CKD anemia indication in the roxadustat label in mid-2019.

We continue to work closely with our partner, AstraZeneca, to prepare for the launch of roxadustat in China and have much to report in terms of progress.

Our partner, AstraZeneca, has already initiated the aggressive build-out of a dedicated roxadustat field sales force covering 5 regions in China at launch, which will be fully deployed by mid-2019. FibroGen China's medical affairs field staff now numbers over 30 professionals. The central market access team has been in place and active for over a year.

FibroGen is the marketing authorization holder, or MAH holder, in China that is responsible for pharmacovigilance. Our pharmacovigilance infrastructure in China, which includes a pharmacovigilance database and call center, has been active for over a quarter now. The commercial manufacturing readiness for both API and drug product is on schedule. We are confident about the third quarter China launch time frame.

A question we wanted to address is whether we will be added to NRDL List, or National Reimbursement Drug List. We are hopeful that roxadustat may qualify for consideration in 2019 by virtue of receiving market approval at the end of 2018. To be clear, only our dialysis label can be considered as non-dialysis approval has not yet been received. Many factors go into our probability of admission in NRDL such as perceived unmet medical need, clinical value, pharmaco-economic value, pricing, which is to be agreed upon between the State Medical Insurance Agency and the sponsor. We believe NRDL has critical affordability for our patients, so this is a top priority for us. Every effort is being made by the joint AZ and FibroGen team to maximize our chances of success. We expect to have a sense of whether we'll be included and at what price by some time in October.

Finally, in Japan, our partner, Astellas, submitted NDA for roxadustat treatment of anemia in CKD patients on dialysis to PMDA last fall. The application is currently under review, and Astellas anticipates filing the supplemental NDA for the treatment of anemia in non-dialysis-dependent CKD patients in 2019.

With respect to expanded platform opportunities for roxadustat for the treatment of anemia in other disease settings, I'd like to take a moment to update you on our work with roxadustat in myelodysplastic syndromes, or MDS. We have completed the enrollment of 24 patients in open-label lead-in portion of our multicenter, multinational Phase III study in transfusion-dependent, lower-risk patients with MDS. Encouraged by the positive results from the open-label portion, as measured by the proportion of patients who achieved transfusion independence, we have begun enrolling 160-patient, double-blind placebo-controlled portion of the study. Enrollment for the open-label portion of the China Phase II/III study is ongoing.

Turning now to pamrevlumab, our anti-CTGF antibody. We are extremely excited to see data reflecting 1 year of treatment in our ongoing Phase II study evaluating treatment of Duchenne muscular dystrophy in nonambulatory patients. The data is supportive of earlier observed trends and examines multiple parameters of disease progression, including lung function, cardiac function and muscle strength. We believe that these data would show increase in function in certain parameters, will support a pivotal study and we plan to discuss with the FDA in the near future. Dr. Elias Kouchakji will discuss these results in more detail shortly.

Pamrevlumab recently received orphan drug designation for treatment of DMD. Our antibody now has orphan drug designation status in all 3 of the current indications: IPF, pancreatic cancer and DMD and has received Fast Track designation in IPF and pancreatic cancer.

Finally, I will briefly address financial matters here, and Pat Cotroneo, our CFO, will provide more detail later in the call. In the first quarter of 2019, we reported $45.4 million of net loss or $0.53 per basic and diluted share in EPS. So that's negative $0.53 per share. As of March 31, 2019, FibroGen had $712 million in cash.

I would now like to turn this over to Dr. Peony Yu for the discussion of the results from the CV safety pooled analysis and updates on the anemia program.

Dr. Yu, please go ahead.

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [4]

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Thank you, Tom. For the roxadustat program, in the U.S. and EU, we are pleased to share with you the adjudicated cardiovascular pool safety analysis, top line results from the Phase III global roxadustat program. We see these results supporting safety of roxadustat in CKD patients. We also see other benefits beyond hemoglobin increase.

Our MACE and MACE+. To reiterate what Tom outlined earlier is what we are disclosing on the adjudicated safety data, MACE and MACE+ composite endpoints. MACE measures the number of patients with one or more adjudicated positive MACE events, which include death, myocardial infarction and stroke. The MACE+ composite endpoint has 2 more components in addition to the MACE, in which now you also add in heart failure and unstable angina requiring hospitalization. The MACE composite endpoint is what we and our U.S. partner, AstraZeneca, discussed with the FDA for safety assessment. MACE+ is what we and our European partner, Astellas, agreed with EMA.

MACE+ has also been used extensively in safety endpoint and assessment in CKD anemia trials as well as in some diabetes trial in both Europe and in the U.S.

Now what is adjudication? And why is it part of our process? Adjudication is the process of independently and objectively applying clinical standards to consistently determine individual events qualified as MACE or MACE+ events. To maintain objectivity, independent experts in cardiology, neurology and nephrology who are blinded to treatment assignment revealed the patient data and adjudicate the events relevant to their specialty. To maintain data integrity, the process and documents are managed by an independent third-party. We conducted MACE and MACE+ analyses in the following patient pools: dialysis or all-dialysis; Incident dialysis, which is a sub-population of dialysis patients who are just starting out to receive chronic dialysis treatment; and as well as in non-dialysis patient population.

In our dialysis pool of around 4,000 dialysis patients, based on the collective results of the various MACE and MACE+ safety analyses, we believe there is no clinically meaningful difference in MACE and MACE+ risks between roxadustat and epoetin alfa in the all-dialysis patient population. And 95% of confidence interval of the hazard ratio is above -- I'm sorry, of that, 95% confidence interval of the hazard ratio is below 1.3, which is what the conventionally accepted measure in such time to analysis of MACE and MACE+.

In the incident dialysis pool consisting of over 1,500 patients, a subpopulation of the dialysis or all-dialysis pool which we believe offers a better setting for comparing roxadustat to epoetin alfa than the stable dialysis population, roxadustat demonstrated superiority to epoetin alfa in the time to first MACE+ in this subpopulation with fewer patients with MACE+ events was noted. In the time to first MACE analysis, there is a trend towards reduced risk for patients on roxadustat compared to epoetin alfa.

In our CKD non-dialysis pool of approximately 4,300 patients, in the multiple MACE and MACE+ pool, ITT analyses conducted in non-dialysis-dependent CKD patients collectively, we believe there is no clinically meaningful difference in MACE and MACE+ risk between roxadustat and placebo in non-dialysis patients.

Now let's put these safety findings along with the reported efficacy results in clinical context. In our last earnings call, we reported that roxadustat demonstrated efficacy in meeting the primary efficacy endpoint of change in hemoglobin from baseline to mean hemoglobin average between weeks 28 to 52 in each of the 7 Phase III studies conducted by FibroGen and our partners.

For the all-dialysis patient pool, as reported previously, not only was non-inferiority achieved in primary efficacy endpoints in all-dialysis patients. Superiority and efficacy, as demonstrated by statistically significant larger increase from baseline hemoglobin level in roxadustat-treated patients than EPO patients, was achieved in both HIMALAYAS study, which is on incident dialysis, and in SIERRAS conversion dialysis study.

In SIERRAS, roxadustat-treated patients achieved a more physiologic hemoglobin level of 10.7 grams per deciliter versus 10.2 in EPO arm with a 33% reduction in red blood cell transfusion risk.

We believe the lower achieved hemoglobin level in EPO comparator arm results from a combination of the lower target hemoglobin level on ESA label due to FDA's concern regarding ESA cardiovascular safety and EPO hyporesponsiveness in patients with inflammation, as inflamed patients with elevated C-reactive protein require higher doses of EPO than patients with normal baseline CRP levels, although they achieved lower mean hemoglobin level. And as we understand from multiple publications that there's higher risk with higher target hemoglobin when one is using ESA while higher achieved hemoglobin in EPO has been confirmed to better safety when lower doses of EPO is used.

Given the mechanism of our drug being uniquely different than EPO, being able to achieve a more physiologic hemoglobin level should translate into benefit for patients.

Roxadustat's efficacy measured in achieved hemoglobin level and dose requirement are not affected by inflammation status unlike in EPO. This important differentiation from ESA has been observed in multiple Phase III studies including in the U.S.-based SIERRAS study, which we believe is reflective of U.S. dialysis practice under current ESA labeling restriction. And we've also seen this differentiation in our China Phase III studies in dialysis patients. We have also observed a reduction of red blood cell transfusion in our Phase III program.

Although the roxadustat arm in conversion studies start out at a disadvantage, being exposed to patients for the first time and being compared to patients on optimized EPO dosing, the roxadustat-treated patients still showed significant reduction in red blood cell transfusion risk, as measured by time to first transfusion compared to patients receiving stable maintenance doses of epoetin alfa.

Conversion patients comprise a majority in the dialysis or all-dialysis patient pool.

Yet, based on the key MACE and MACE+ analyses, we assess no clinically meaningful difference in the risk of MACE, MACE+ risk between roxadustat and epoetin alfa.

Next, the incident dialysis population is defined as patients who enter dialysis studies within 4 months of starting dialysis treatment. A vast majority of the incident dialysis patients were either ESA-naïve or had very limited prior exposure to EPO. During the transition from non-dialysis to dialysis in the first 4 months of dialysis treatment, patients suffer from mortality and hospitalization rate at twice those of dialysis patients who survived first year of dialysis treatment.

What's also relevant to roxadustat is that initiation of dialysis often also coincides with the initiation of anemia therapy. We and our partners are very happy with the result of superiority to epoetin alfa in the time to first MACE+ and a favorable trend towards reduced risk for patients on roxadustat compared to epoetin alfa in time to first MACE analysis in the incident dialysis patient populations.

We believe roxadustat's favorable results in incident dialysis compared to EPO could enable a safer treatment of anemia in CKD patients initiating and continuing dialysis treatment.

Turning to CKD patients not on dialysis. In the CKD pool analyses from the 3 non-dialysis studies, roxadustat both consistently raised hemoglobin levels to a mean hemoglobin of 11 gram per deciliter in the roxadustat-treated patients and significantly reduced red blood cell transfusion compared to placebo. This is very important for patients to preserve their ability to have kidney transplant later down the road if they need to. Importantly, roxadustat has shown the potential to preserve renal function as there was a statistically significantly smaller decline in eGFR in roxa-treated patients than placebo, with a treatment difference of 1.62 in eGFR units when measuring change at 1 year from baseline in patients with baseline eGFR of 15 or higher. P value is 0.0001 or a reduction of decline by 38% in eGFR relative to placebo arm.

We also observed statistically significant improvements in the various quality of life endpoints at 12 weeks from baseline, including the SF-36 vitality subscale with P value of 0.0002; SF-36 physical functioning subscale P value of 0.0369; FACT-AN anemia subscale with P value of 0.0005; FACT-AN total score P value of 0.0056; EQ 5 DSL, a VAS score with P value of 0.0005 in CKD patients not on dialysis.

Putting together these and other important potential clinical benefits with the safety results that we have seen in comparison with placebo, which is a gold standard for safety measurement; and in comparison to EPO, which is the current standard of care in dialysis but have some limitations, along with the convenience of a pill when treating patients with roxadustat to make treatment much, much more accessible than parenteral route of ESA. We are excited about the potential of roxadustat as an innovative new therapy for CKD patients. We hope this provides some helpful context for you in understanding the significance of the safety top line results announced today.

Tom has already touched on the status of our U.S./EU submission plans. We and AstraZeneca will be in discussion with FDA on NDA submission plan, which we are targeting for September/October time frame. We are also supporting Astellas MAA submission to EMA to be submitted thereafter. For China, in April, [CFDI] inspected our China Phase III CKD non-dialysis study sites. We expect that the roxadustat label on CKD anemia there will be expanded midyear to include non-dialysis as well as dialysis patients.

As Tom mentioned, we are excited about roxadustat's opportunity for market access via this year's NRDL election process in China.

In Japan, the NDA on roxadustat for treatment of anemia in dialysis-dependent CKD patients submitted by our partner, Astellas, in September 2018 is now under review. We anticipate the Japan NDA decision later this year.

For the treatment of anemia in MDS patients, we have an ongoing Phase III study in transfusion-dependent, lower-risk MDS patients in the U.S., Europe and Asia, plus another study, which is Phase II/III in non-transfusion-dependent MDS patients in China. Each has an open-label run-in period. Anemia in MDS is notoriously difficult to treat, and we are striving to make a difference for MDS patients with roxadustat. We have completed enrollment of the first 24 patients in the open-label portion of the U.S./European study. We and our partners are encouraged by the available results as there were a large proportion of transfusion-dependent patients able to achieve transfusion-independence endpoints. And we have already started dosing in the double-blind portion of the U.S./European Phase III MDS study.

Finally, we are on track to start our first clinical trial in chemotherapy-induced anemia with roxadustat. It's a Phase II study in the U.S. to be started shortly in 2019. I believe that all of us are aware and would like to do something about the under-treatment of anemia in patients who have undergone chemotherapy.

I like to now turn the call back over to Tom.

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [5]

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Thank you, Peony. Dr. Elias Kouchakji will now provide an update on pamrevlumab, including additional details on our DMD data, and update us on clinical development activities for pancreatic cancer and for IPF. Elias, please go ahead.

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Elias Kouchakji, FibroGen, Inc. - SVP of Clinical Development, Drug Safety & Pharmacovigilance [6]

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Thank you, Tom. I will start with the Duchenne muscle dystrophy, as Tom mentioned.

In mid-March this year, all 21 patients completed 1-year treatment with pamrevlumab in our Phase II open-label non-ambulatory Duchenne muscular dystrophy study. Soon after, we initiated an administrative analysis of the data in the early second quarter of this year. This is in order to inform our clinical development strategy and we reviewed this study data with key opinion leaders who are experts in the study of the clinical function we tested in this study.

Starting with the pulmonary function test. The complete 1-year results indicate a potential reduction in the rate of decline in FVC% predicted from baseline in our study population, especially when compared to the data published in 2016 by Meier or Ricotti in 2019.

As for the cardiac function test, the results as measured by LVEF, left ventricular ejection fraction, the data suggested a positive mean percentage change from baseline while the published data by McDonald in 2018 showed a mean decline of approximately 1% from baseline in 1 year.

Additionally, we've measured the cardiac fibrosis scores, and we collected the data. The published data by Tandon in 2015 showed a strong correlation between the cardiac fibrosis with LVEF. Our data from the MRI fibrosis score suggests a similar correlation. Similarly, in some of the muscle function tests, the result of this test in the upper arm showed the mean change from baseline was smaller than the published data by Ricotti in 2019.

Based on these results and advice we received from our expert, we are planning to share these results with FDA to develop our clinical development plan for the Duchenne muscular dystrophy.

Moving forward with our other indication. We are planning on beginning enrolling in the Phase III double-blind placebo-controlled of pamrevlumab as neoadjuvant therapy for non-resectable locally advanced pancreatic cancer in the second quarter of 2019. We intend to enroll approximately 260 patients. Randomization of 1:1 to receive either pamrevlumab in combination with gemcitabine and nab-paclitaxel or chemotherapy with placebo.

Also in the second quarter of 2019, we are on track to begin enrolling our double-blind placebo-controlled Phase III trial of pamrevlumab in approximately 500 IPF patients. The primary efficacy endpoint is a change from baseline in forced vital capacity.

We are grateful for the opportunity represented by pamrevlumab in providing a needed therapeutic option for each of these 3 serious and progressive indications: Duchenne muscular dystrophy, pancreatic cancer and idiopathic pulmonary fibrosis.

Thank you for listening. Tom, I'll turn the call to you.

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [7]

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Thank you, Elias. Pat Cotroneo, our Chief Financial Officer, will now discuss financial highlights for the first quarter of 2019. Pat, please go ahead.

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Pat Cotroneo, FibroGen, Inc. - Senior VP of Finance & CFO [8]

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Thank you, Tom. As announced today, total revenue for the quarter ended March 31, 2019, was $23.9 million as compared to $31.9 million for the first quarter of 2018. For the same period, operating expenses were $72.7 million, and the net loss was $45.4 million or negative $0.53 per basic and diluted share as compared to operating expenses of $72.5 million and a net loss of $41.4 million or negative $0.50 per basic and diluted share for the first quarter last year.

Included in operating expenses for the quarter ended March 31, 2019, was an aggregate noncash portion totaling $20.2 million, of which $16.4 million was the result of stock-based compensation expense, as compared to an aggregate noncash portion totaling $12.5 million, of which $10.9 million was the result of stock-based compensation expense for the same period in the prior year.

At March 31, 2019, FibroGen had $712.7 million in cash, restricted time deposits, cash equivalents, investments and receivables. As previously stated, our considered judgment is that the roxadustat NDA and MAA will be filed this year, which will trigger approximately $192.5 million in anticipated milestone payments, of which the vast majority are associated with these filings.

Thank you, and I will turn the call back over to Tom.

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [9]

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Thank you, Pat. With the updates reported to you today, we advanced a number of critical events in the coming months. It is our privilege to have shared with you today roxadustat's CV pooled safety analysis results that we believe support submitting the NDA for both NDD and DD indications, treatment of dialysis-dependent and non-dialysis-dependent CKD, to the FDA in September or October 2019.

In Europe, our partner, Astellas, anticipates submission of the MAA for dialysis-dependent and nondialysis-dependent CKD later in 2019 November, December. And in China, we expect to add nondialysis-dependent CKD patients to the roxadustat label upon approval anticipated in mid-2000 -- Q3 2019. In Japan, Astellas is expecting a decision on NDA approval for roxadustat in dialysis-dependent CKD in fourth quarter of 2019.

For pamrevlumab, we look forward to updating you on our advancement to Phase III in LAPC and IPF and to further findings from our ongoing Phase II study in DMD nonambulatory patients.

With that, let me turn this back to Karen to begin the question-and-answer period.

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Karen L. Bergman, FibroGen, Inc. - VP of IR & Corporate Communications [10]

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Thank you, Tom. Erin, please open up the lines for questions.

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Questions and Answers

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Operator [1]

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(Operator Instructions) Your first question comes from Michael Yee with Jefferies.

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Michael Jonathan Yee, Jefferies LLC, Research Division - Equity Analyst [2]

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Tom and Peony, can you be very clear for us? I think there's some confusion around whether you are statistically noninferior in dialysis and nondialysis on the MACE analysis, which is what is required for FDA? Can you confirm that or discuss that? And if you can also give us the hazard ratios for dialysis and nondialysis on MACE, that will be very helpful.

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [3]

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Okay. So Michael, there's 2 parts to this answer. One is that in the European market, we are doing MACE+, where we have a statistical noninferiority margin, a single margin identified, and we are non inferior in both measures. In the U.S., there are multiple noninferiority margins that are under discussion. These are reflecting the fact that was not incident dialysis and with the nondialysis-dependent CKD patients. We are essentially addressing new indications that have not been investigated previously. So that's incident dialysis and the CKD dialysis. In discussions with our partner, they are very mindful of the phrase of totality of evidence. And so they encouraged the idea that we address this in the form of the evaluation of results versus MACE, where we did not see any clinically meaningful difference, means that it met the safety standards that people were looking for and that's why people are moving forward.

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Michael Jonathan Yee, Jefferies LLC, Research Division - Equity Analyst [4]

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So to be very specific, in dialysis and nondialysis on MACE, are you trending the right way? Are you trending positive? What do you mean by not clinically meaningful differences?

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [5]

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Yes. I think the message there is we're trending favorably. But at the same time, we have to yet agree with our regulator on specific analyses to be done. There are back and forth discussions.

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Michael Jonathan Yee, Jefferies LLC, Research Division - Equity Analyst [6]

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Okay. So it's trending -- it was trending positive, but you just don't have an -- or you just don't have an agreement on what the definition of which analysis you'd have like to have, but it is trending positive.

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [7]

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Michael, I think that's a very fair way to say it.

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Operator [8]

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And your next question, that comes from Andy Hsieh with William Blair.

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [9]

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Before Andy, may I add to Michael's response -- to Michael Yee's question? I just -- I don't know whether we made it very clear that when Tom and I used the number 1.3, we are talking about -- we are not talking about a hazard ratio. I want to make it absolutely clear that the hazard ratio for the MACE+ in the incident dialysis is way below 1. And in -- also, it's below 1 in dialysis, okay? And the upper bound of the 95% confidence interval, when you are below 1.3, that has been a commonly accepted statistical standard for noninferiority.

And for us to state that we are superior in time to MACE+ analysis in incident dialysis, what I mean is the upper bound of the 95% confidence interval is less than 1. And we have a -- when you compare the hazard between roxadustat to that of epoetin alfa, we have a very significant P value. So I hope this helps. Michael, does this answer your question?

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [10]

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Okay.

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [11]

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Okay. Andy?

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Operator [12]

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Andy, perhaps you're muted.

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Karen L. Bergman, FibroGen, Inc. - VP of IR & Corporate Communications [13]

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Andy, are you still on the call with us? This is Karen. I think we lost him.

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Operator [14]

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Your next question comes from Joel Beatty with Citi.

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Joel Lawrence Beatty, Citigroup Inc, Research Division - VP & Analyst [15]

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This question is on the 2 pooled noninferiority MACE analyses required by FDA. Was there a prespecified statistical analysis plan agreed to with FDA?

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [16]

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So Joel, we have had discussions with the FDA on how they -- on the different methods for -- of statistical evaluation of safety endpoints. We believe that we have collected the data that the FDA would like to see. And -- but we wanted to be cautious in stating our agreement with the FDA because as we -- those of us who have interacted with the FDA, oftentimes, the reviewers would like to have the -- would like to look at the totality of evidence, looking at both the safety as well as efficacy. And they -- but the term that is used very commonly is called a review issue. So it's not an issue, but it is -- if I were the reviewer, I would like look at -- like to look at all the data before I would commit to a decision of -- on a drug. And so I hope that answers your question.

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Joel Lawrence Beatty, Citigroup Inc, Research Division - VP & Analyst [17]

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Okay. Understood.

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [18]

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And then to ensure alignment, we will be discussing with FDA on -- in our upcoming pre-NDA meeting to make sure that our preparation of the NDA package will provide the information that -- in a way that is efficient for FDA to review.

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Joel Lawrence Beatty, Citigroup Inc, Research Division - VP & Analyst [19]

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Okay. And then a question on the nondialysis MACE analyses. Did the event rate compare favorably to the comparator arm? And how -- in that analysis, how does it take into consideration the differences in the dropout rate?

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [20]

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Yes. We do -- so first of all, Joel, that's a good question. So we have -- because our drug is so efficacious and so well tolerated, patients really like staying on our drug. Now -- but we all know that placebo doesn't work too well. However, this is -- I want to go back and remind everyone that this is a double-blinded study. And so even -- so many patients -- these patients -- in other words, patients are not -- do not have the treatment assignment information. We have many patients who are on placebo and on roxadustat who remain in the studies to enable a long-term efficacy and safety evaluation. And even -- we did see a high -- a somewhat higher dropout rate in placebo-treated patients.

However -- and to have some anticipation this could happen, we have collected safety data on patients during the post-treatment period. And that's why we are able to conduct the ITT analysis. And this will be -- of course, the final assessment in -- and the statistics will be discussed with the FDA.

And I just wanted to share that in the -- so what we have mentioned in the ITT analysis in the nondialysis patient population, it is -- will be considered a relatively conservative analysis. And the fact that we had -- we are able to show noninferiority to placebo under such conditions really illustrates the strength of our drug's safety. And I wanted to also remind us that placebo is considered the gold standard for safety.

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [21]

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Go ahead. Andy, are you there?

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Tsan-Yu Hsieh, William Blair & Company L.L.C., Research Division - Senior Research Analyst [22]

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Yes, I'm here. Can you guys hear me?

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [23]

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Yes.

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Tsan-Yu Hsieh, William Blair & Company L.L.C., Research Division - Senior Research Analyst [24]

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Yes. I'm sorry, Tom and to the team that I pressed the wrong button. So -- yes, it caused a little confusion so I apologize. So my question has to do with just looking at it from a bigger-picture perspective. You have -- on the MACE perspective nonclinically -- well, I guess, not -- no clinical difference between both arms, roxadustat versus EPO, roxadustat versus placebo. But this is -- from a -- I don't know if this is the correct way to think about it, but transitive property of equality, we know that placebo is not, from a clinical perspective, does not equal to EPO. So how do you kind of think about this discordance and what you just disclosed on the call?

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [25]

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So let's do this in a simpler groundwork, which is MACE+. And I'm doing this because we have very defined criteria of MACE+. The findings are, with incident dialysis pool, you have statistically significant advantage over ESA; with the entire dialysis pool, noninferior; and then in the NDD nondialysis pool, you have noninferior. So you have these comparisons. We think of the nondialysis pool comparison to placebo, it's essentially similar. This -- the idea there is that it's hard to argue that there's an incremental safety risk because placebo is what happens with CKD patients every day right now. They don't have medicines. So it's not as if you can infer an incremental statistically proven risk in nondialysis.

In the dialysis pool, the broader population, noninferior and in the incident population, which we think is the unbiased comparison, we have statistical superiority. We don't expect that MACE will be particularly different than this. It's just that with U.S., we have an agreement with our partner, AstraZeneca, to evaluate under the totality of evidence basis. So it makes it harder to sum this up in one sentence or 2 sentences. It's sort of a pretzel logic challenge to try to describe this accurately, but I think you can sort of look at the MACE+ results. And from our point of view, if we thought the MACE results were going to be a lot different, we would say so. But it doesn't seem that way. It seems very similar. So I would say, with the U.S., attributed to the fact that we do not have a single agreed endpoint -- one of the questions we asked with these newly defined populations in incident dialysis and in CKD was whether or not the entire analysis, the entire risk/benefit analysis should work a little differently than in the conversion dialysis patients that have been using EPO forever. And the FDA basically said, "That's a review issue. You need to spend some time showing us the benefit/risk analysis that you see from your data."

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [26]

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I -- yes. So Tom, may I supplement this a little bit? I apologize if we used too much of this statistics mumbo jumbo. But I will -- I just wanted to add, even though we are saying that there's no clinically meaningful difference in MACE and MACE+ in our dialysis, I'm just going to give one example, okay?

And even though we are saying that, it is a very conservative way of expressing our data. In absolute terms, we have -- for example, in our dialysis pool, we have fewer patients. And now we look at on treatment analysis, and there are fewer patients who died on the roxadustat compared to EPO. We have fewer -- numerically fewer patients with a MACE event or with MACE+ events. So that's sort of I'm trying to give you a little color to what we are saying. It doesn't -- but I hope this is helpful.

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Tsan-Yu Hsieh, William Blair & Company L.L.C., Research Division - Senior Research Analyst [27]

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So just kind of digging deeper and helping us kind of understand the totality of data. Different components, death, MI, stroke. On top of that, unstable angina leading to a hospitalization, heart failure. Can you confirm that all of these measures are trending in the right direction? Or maybe there are some that's not. Maybe can you comment on that?

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [28]

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So with the MACE+ data, I believe we have numeric advantage in these categories. So there's 5 categories.

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [29]

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Each and single one of them, Tom.

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [30]

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Every one of them, we have numeric advantage over ESA. Is that clear enough?

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [31]

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Numeric advantage, meaning lower.

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [32]

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Fewer events in roxa versus ESA and deaths. Fewer events in roxa versus ESA in myocardial infarction. Fewer strokes in roxa than ESA. Fewer unstable angina hospitalizations. Fewer congestive heart failures resulting in hospitalizations.

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Tsan-Yu Hsieh, William Blair & Company L.L.C., Research Division - Senior Research Analyst [33]

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Yes. That's actually super helpful. And just one last question about the quality of life measures. 12 weeks into that, given that this is a chronic condition, is that clinically relevant? Or should you be looking at a longer time frame?

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [34]

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Peony, what were the length of the quality of life studies?

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [35]

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Yes. So the quality of life number that I quoted was at 12 weeks. Quality of life measures is actually quite -- is quite difficult to measure over long term. And because you have -- you wanted to measure in the same patient population that you start out the study with. And also, on the subjective measures that where a patient report to you how they feel, when you carry it over a much longer period of time, there's -- patients tend -- not only patients, I may have forgotten how things -- how bad things were like a couple months ago. And so generally, it is reasonable. 3 months is a very reasonable period to record patient-reported outcome.

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Operator [36]

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And your next question comes from Terence Flynn with Goldman Sachs.

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Terence C. Flynn, Goldman Sachs Group Inc., Research Division - MD [37]

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Maybe just a follow-up. I think that your answer to the last question regarding the dialysis population was pretty clear. But in terms of the nondialysis comparison of roxa versus placebo, I guess, I'm still a little bit confused in terms of how the -- I understand you didn't have a prespecified comparison. You're looking at a number of different ways. But could you maybe just walk through how those event rates compare on MACE for roxa versus placebo across the different analyses? Were there -- did they all line up? Were they all favorable? Was there anything out of line?

And then when you look at the separate studies, again, I remember back from the Omontys studies, they had one trial that they showed fewer events and one trial they actually had more events in the nondialysis setting. So again, was there consistency across the 3 studies that you pooled as well?

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [38]

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Yes. So Terence, we recognize that this is a terribly difficult area to state in a succinct manner for a call like this. Having said that, in thinking about how to describe the situation most effectively, we decided to describe the ITT results. This is MACE, MACE+, MACE CV, time to MACE+, time to MACE. So there's several different measures. And in each case, the result of the analysis was at a ratio below 1.3, which is a standard noninferiority comparison in ITT.

And so when I say below 1.3, I mean like 1.18 or 1.21 or 1.27 or 1.28. Not above 1.3, but below 1.3. And I know, speaking as someone involved in this partnership for a long time, that people in each of our partners' executive management group, great confidence and strength in seeing these results because these are -- even though these are maybe aren't the measures that ultimately will be the ones that are evaluated, they are -- and ultimate safety evaluation standard that FDA usually asks for, whether you pose it or not. So everybody felt like this is something that's very descriptive and very informative. I would hesitate to do anything else beyond talking about the ITT results because we do not have a specific agreement with FDA on method of analysis. And as such, it's a little presumptuous.

And I think the challenge for any of these statistics that would be like OT 7 or OT 28 or whatever it is that you have a placebo dropout rate, it's very different than the roxa stay-on study rate. There is agreement from regulatory body that we can make statistical adjustments. We've gotten that in print from our reviewers. And there's certain things like covariance or IPCW adjustments that have been suggested as ways that there's an acknowledgment this placebo dropout rate is an issue that needs to be evaluated. Peony, why don't you go ahead from there?

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [39]

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Yes. So FDA specifically suggested for us to do an exposure-adjusted safety analysis. So if you have more patient exposure time on one arm than another, how do you compare the number of patients who have how many events? And so when we -- so that's why the ITT evaluation is one of the ways that we make such comparison.

Another way will be exposure-adjusted to match the follow-up time on the 2 arms. When we do that, we again see very, very reassuring safety data. And there's no -- and we see there -- this certainly looks noninferior in our assessment.

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Terence C. Flynn, Goldman Sachs Group Inc., Research Division - MD [40]

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Okay. Can I maybe just have a few follow-ups?

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [41]

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Sorry. You want to give one more. Terence, you get one more. What is it?

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Terence C. Flynn, Goldman Sachs Group Inc., Research Division - MD [42]

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Okay. Sure. Just again, so below 1.3. So that was for each of the 3 studies? Just to be crystal clear on that. Or that was on a pooled basis or we're talking about the nondialysis population?

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [43]

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This is all nondialysis and its evaluations. MACE, MACE+, MACE CV. Peony, do you want to add to that?

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [44]

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Yes. So Terence, so the agreement we had with our regulators is that for MACE and MACE+ type of analysis will be based on pool analysis across the 3 studies and that is...

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [45]

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The 3 nondialysis.

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [46]

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The 3 nondialysis studies and with a total sample size of about 4,300 patients.

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Terence C. Flynn, Goldman Sachs Group Inc., Research Division - MD [47]

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Okay. So you can't give us any more detail about the individual studies, I guess, at this point in terms of what the individual numbers look like. Like, if they -- I'm just trying to understand if they're consistent across the 3 studies.

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [48]

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Okay. So Terence, there is consistency across the 3 studies in that we met primary efficacy endpoints in all 3 studies in hemoglobin endpoints and that we achieved transfusion superiority, which is clinically very important. And each of the individual -- none of the -- each of the individual study, safety trends were -- overall safety trends were acceptable. And I just wanted to share that for MACE and MACE+ events, you need a certain powering statistics -- adequate statistical power to have meaningful comparison. So this is why we are reporting the pool result rather than individual study result.

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Operator [49]

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And your next question comes from Geoffrey Porges with Silicon Valley Bank Leerink.

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Geoffrey Craig Porges, SVB Leerink LLC, Research Division - Director of Therapeutics Research, MD & Senior Biotechnology Analyst [50]

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Appreciate all the color that you're providing. Peony, could I ask you to pivot to the dialysis population? And you've broken out the incident dialysis population, where you seem to have superiority on MACE+ and trended benefit on MACE. Could you give us a sense of what you see in the stable dialysis patients? Particularly, provide us reassurance that the number of -- or whatever, however you measure it, the number of deaths, MIs and strokes in the stable dialysis patients who are switched to roxadustat, still favors roxadustat. Because obviously, you don't have the same power or same apparent benefit in the pooled dialysis as you do in the incident.

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [51]

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Okay. Geoff, yes, I wanted to -- first of all, I think we agree that the conversion dialysis study design is biased against the study drug. But even so, when we look at subgroup analysis of the -- between incident dialysis versus the stable conversion dialysis, we are quite comfortable with the safety result when looking at MACE and MACE+. We -- does that help?

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Geoffrey Craig Porges, SVB Leerink LLC, Research Division - Director of Therapeutics Research, MD & Senior Biotechnology Analyst [52]

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Could you provide the same -- is the rate of deaths, MI and stroke in that population lower in the roxa-treated patients?

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [53]

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Yes. So I don't have the exact number sitting in front of me, but I would think that, from memory, they seem to be not that far off from one another.

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Geoffrey Craig Porges, SVB Leerink LLC, Research Division - Director of Therapeutics Research, MD & Senior Biotechnology Analyst [54]

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Okay. Peony, could I just follow up? Could you just talk a little bit about...

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [55]

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We have a lot of numbers here, Geoff.

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Geoffrey Craig Porges, SVB Leerink LLC, Research Division - Director of Therapeutics Research, MD & Senior Biotechnology Analyst [56]

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Yes, I understand. Could you just talk about the overall rate of events that you're seeing compared to expectations? And also, whether there are any geographic variances in the comparison depending upon geography, North America, Europe, et cetera.

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [57]

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Geoff, I'm sorry. Just a second. I think there's -- Geoff, I want to get clarity on the question you just asked, but I think Peony wants to clarify one thing. Peony, go ahead.

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [58]

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Yes. So Geoff -- yes, so we -- when we tested the -- I wanted -- even though I'm not giving you exact number of patients for each category, right, but I am willing to share with you that in the subgroup analysis, when we tested time to -- for example, time to MACE+ and MACE, roxadustat was at least noninferior to epoetin alfa even in the conversion stable dialysis patients.

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [59]

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So if you take the subgroup of incident patients away, the remainder pool was tested as noninferior consistently.

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [60]

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Correct.

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [61]

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So that's the clarification. Now Geoff, please state the geography question again. It surprised us. I don't think I heard the whole thing.

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Geoffrey Craig Porges, SVB Leerink LLC, Research Division - Director of Therapeutics Research, MD & Senior Biotechnology Analyst [62]

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I just want to -- could you just comment on the overall rate of events that you've observed compared to expectations? And then whether there were any variations in the comparison between the different arms in the -- when you look at the subsets by geography.

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [63]

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Geoff, we're at this -- we are still on the -- releasing the top line results. The fine granular geographic subgroup analysis and more detailed analysis are -- still needs to be conducted. But we plan to between now and NDA submission, it will be completed before then.

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Geoffrey Craig Porges, SVB Leerink LLC, Research Division - Director of Therapeutics Research, MD & Senior Biotechnology Analyst [64]

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Okay. And the overall event rate or rates?

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [65]

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The question was, do you observe any difference in overall event rate by geography?

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [66]

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We have not done that subgroup analysis by geography yet.

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [67]

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Okay.

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Operator [68]

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And your next question comes from Difei Yang with Mizuho Securities.

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Difei Yang, Mizuho Securities USA LLC, Research Division - Executive Director of Americas Research [69]

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I'll apologize upfront that I may be a little slow. I'm trying to get some of the answers. So Tom and Peony, maybe you could help me think about 3 patient populations. There's the DD, NDD and incident dialysis. Is incident dialysis patient population as a possible indication in the U.S.? I'm focusing on the discussion just for U.S. filling alone. Are we dealing with 3 patient populations in terms of getting approval? Or are we dealing with 2, really, either it's DD or NDD?

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [70]

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So Difei, thank you. That's a very good question. We have already -- we have had initial discussion with the FDA regarding the 3 patient populations and the understanding is that the incident dialysis population is one that is -- I mean, the understanding is that all 3 patient populations for indication are under discussion that will be -- that is ongoing with the FDA. And we believe that the results will help drive the decision.

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Difei Yang, Mizuho Securities USA LLC, Research Division - Executive Director of Americas Research [71]

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Okay. Okay. Now for the indication in the U.S., if we just think about DD and NDD for now, for the MACE -- now we can forget about the MACE+ situation. Just for the MACE measurement, have you reached a statistical noninferiority on -- against either placebo or EPO?

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [72]

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So Difei, we -- so whether you reach statistically significant in noninferiority, it really depends on what the noninferiority margin is.

And in Europe, we are more clear on the noninferiority margin, and we believe that we have achieved that.

And for -- now for the incident dialysis, the nice thing about having achieved superiority is that no matter what the noninferiority margin it is, once we can demonstrate superiority, we have already crossed it. And we are using the conventional standards of noninferiority, which is widely published for assessment of CKD anemia and have previously been used by U.S. regulator for assessment of cardiovascular safety in similar types of composite endpoints that we -- that standard has been 1.3 for upper bound of 95% confidence interval. If we use that standard, the answer is yes, we have achieved noninferiority. And so the reason that we are not as explicit in saying that is because we got -- we wanted to be transparent when we state what we mean by noninferiority. I hope this helps.

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Difei Yang, Mizuho Securities USA LLC, Research Division - Executive Director of Americas Research [73]

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This is very, very helpful. So then if I could ask a question on quality of life measurement. Do you see superiority or nonsuperiority on the ID and DD patient population? I think NDD, you said you've achieved superiority. Is that the right understanding?

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [74]

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So Difei, the reason that we focus on testing quality of life in nondialysis is that we are testing against placebo, and we do superiority testing. In dialysis, it's not as meaningful because when we are comparing against an active comparator, that clearly does not have a label for quality of life. I mean, even if you're noninferior, what does that mean? It's not going to get us a label. And trying to go for superiority, that doesn't make sense either. So that's why we focus on quality of life measures in the nondialysis patient population.

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [75]

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So just to be clear, we only tested quality of life in nondialysis, the 4,300 patients in nondialysis, not in dialysis. Okay?

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Difei Yang, Mizuho Securities USA LLC, Research Division - Executive Director of Americas Research [76]

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Okay. That's very helpful. So my final question is that it sounded like you plan to file NDA in September, October time frame. But before then, there will be FDA meeting. Would you update us? Or do you have plans to update investors before the NDA submission when you have more clarifications on the data analysis, et cetera?

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [77]

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So Difei, I'm looking at my colleague heading regulatory, and we normally do not do a press release before or necessary when we go see the FDA. However, we will certainly update our investors when we submit NDA. And I see Wayne nodding his head.

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [78]

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And I would also say that if there is a meaningful change in the time line assumptions, which now are September, October submission time, we will let investors know.

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Operator [79]

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And your next motion comes from Adam Walsh with Stifel.

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Xiaodong Zhang, Stifel, Nicolaus & Company, Incorporated, Research Division - Associate [80]

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This is Edwin Zhang on for Adam. Congrats on the data. A couple of questions for me. First, based on this MACE data, how do we think of the label language if approved? Are we confident to avoid a black box?

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [81]

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Adam, thank you for...

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [82]

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Not Adam. Edwin.

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [83]

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Oh, you're Edwin. Okay. Sorry, Edwin. So thanks for the question. Now when -- now what FDA puts on the label is something that they -- that we may not have much control over, except that we have developed a package that will target a certain label. And so we -- FDA has advised us that the evaluation of efficacy, primary efficacy, will be based on individual studies, and we have checked that box. And the evaluation of safety is -- FDA may -- will look at various aspects of safety. And based on what we have seen, we are pretty comfortable with safety. This adjudicated composite safety endpoint was something that we have discussed with the FDA. And at this time, we are quite happy with the result.

The fact that we believe that the CV safety endpoints in our studies in the nondialysis, when compared to the gold standard of placebo, we are not seeing increased risks that makes me think that we have a chance of avoiding some of the -- those terms that is currently on the EPO label. However, this is what we are targeting when we selected placebo as a comparator. But at the end, the assessment is really -- depends on the medical reviewer at the FDA. And there will -- if there were an Advisory Committee, then there will be input from the Advisory Committee if the FDA chooses to.

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Xiaodong Zhang, Stifel, Nicolaus & Company, Incorporated, Research Division - Associate [84]

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Okay. In term of the totality of the data, the additional positive benefit in NDD is certainly impressive, like a slower eGFR decline, the quality of life or even efficacy in the inflamed patient, which are not seen in the EPO treatment. What do you think of -- as the agency when you look at this benefit from roxa? Do you think that we will have to open a larger market for roxa in DD?

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [85]

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Yes. So this is a great question. We have discussed with the FDA on how to look at the drug, and the FDA has explicitly advised us that a benefit will be taken into consideration as they evaluate each drug based on the combination of benefit/risk. And we are hopeful of being able to reach more CKD patients in need with this highly accessible drug that is just a pill and not have to go drive to the doctor's office regularly to get shots.

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Xiaodong Zhang, Stifel, Nicolaus & Company, Incorporated, Research Division - Associate [86]

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And when do we expect to see the full MACE data?

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K. Peony Yu, FibroGen, Inc. - Chief Medical Officer [87]

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We are -- that's a very good question. Right now, we are sharing with you some very, very top-level results. And we'll be in discussion with our partners to -- so there are 2 key places where we'll be sending the pooled MACE data. One is to the health authority to try to get the drug approved. And two, submit to major conferences. And since we just got the data, we are in discussions with partners on which conference and which journal to submit manuscript to. This will be a lot of fun.

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Xiaodong Zhang, Stifel, Nicolaus & Company, Incorporated, Research Division - Associate [88]

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I'll ask one question on DMD. I don't want it overshadowed by the MACE question. When are we going to see the data, the DMD data? And from the next study, what is your planed dosing regimen, the new endpoint? And what kind of control arm will you use?

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [89]

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Yes. So I think there is a lot to talk about here. An important idea is the left ventricular ejection fraction, LVEF, we have positive numbers. This is sort of a big deal, right? But in terms of what's going to happen next, I will let Dr. Elias Kouchakji speak to this plan.

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Elias Kouchakji, FibroGen, Inc. - SVP of Clinical Development, Drug Safety & Pharmacovigilance [90]

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So as we talked and then mentioned by Tom, that is we are -- first is we are looking to go and talk with the FDA about the next step in -- with this data. And at the same time, we are looking to collect this additional natural disease history data, which is very important. And from there, we, hopefully soon after, we will be publishing our data and have this one, a disease arm -- or data that we collected in this patient population. We are looking for the earliest conference as possible that is we could bring some of our data out, which is most likely we'll be doing in the World Muscle Society.

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Operator [91]

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Okay. And we have no further questions at this time so I would like to turn the call back over to Tom Neff for closing remarks.

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Thomas B. Neff, FibroGen, Inc. - Founder, Chairman & CEO [92]

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Thank you all for joining us on this call today. These data represent the culmination of many, many years of hard work on the part of our team in FibroGen, in some cases, measuring a decade or more. Thank you all for your dedication to and belief in our program. We actually believe we have very good data. I also would like to thank all the physicians, investigators and patients who participated in the clinical development programs, our collaboration partners and our investors for patience and continued support. We look forward to keeping you updated on our progress throughout 2019. I'd like to wish everyone a good afternoon and evening. Thank you for joining our call.

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Operator [93]

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Thank you, ladies and gentlemen. This concludes today's conference. Thank you for participating. You may now disconnect.