FibroGen Inc (FGEN) 2018 Q2 法說會逐字稿

Welcome to FibroGen Incorporated Second Quarter 2018 Financial Results Conference Call. My name is Daryl, and I will be the operator for today's call. (Operator Instructions) For opening remarks and introduction I will now turn the call over to Karen Bergman, Vice President, Investor Relations and Corporate Communications. Karen, you may begin.

Thank you, Daryl. Good afternoon, everyone. And thank you for joining call today. We will be reporting financial results and corporate updates for the second quarter of 2018. Joining me on the call today are Tom Neff; Chairman and Chief Executive Officer; Dr. Peony Yu, Chief Medical Officer; Ms. Christine Chung, Managing Director China Operations; Dr. Elias Kouchakji, Senior Vice President Clinical Development, Drug Safety and Pharmacovigilance; and Mr. Pat Cotroneo Chief Financial Officer. Following our prepared remarks, Tom will close with a discussion of upcoming milestones and we'll open the call to Q&A. During this call, 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 our clinical trials; our regulatory strategies and potential regulatory results; our research and development activities and certain other business plans. 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, 2017, and our quarterly report on Form 10-Q for the fiscal year ended June 30, 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 statement, 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 will open the lines to take your questions. The press release reporting our financial results and business update and a webcast of today's call can be found on the investors section of FibroGen's website at www.fibrogen.com. And the webcast will be available for 2 weeks from today. And with that, it's my pleasure to turn the call over to our CEO, Tom Neff.

Thank you, Karen. Good afternoon, all thank you for joining us. Today, we are going to concentrate on our most recent achievements and timelines for our late-staged programs across multiple indications: roxadustat for the treatment of anemia and pamrevlumab for the treatment of fibrosis and fibroproliferative disease. I would like to start with an update on roxadustat development in the U.S., Europe and Japan.

In the U.S., we have completed patient enrollment in Phase III studies designed to support U.S. new drug application for roxadustat and treating CKD anemia in dialysis-dependent patients and non-dialysis-dependent patients. The U.S./EU Phase III clinical program sponsored by FibroGen and our partners Astellas and AstraZeneca has enrolled a total of approximately 9,000 patients and all studies will complete shortly. We look forward to reporting top line results from these studies before year-end 2018. We are also on target to report on MACE endpoint analysis in early 2019 followed by a submission of our NDA for roxadustat to the U.S. Food and Drug Administration in the first half of 2019.

In Japan, we, together with Astellas, our partner in Japan and for the EU announced that Astellas' fourth Japan Phase III dialysis study for roxadustat met its primary endpoint.

This study evaluated the efficacy and safety of roxadustat compared to darbepoetin alfa in hemodialysis-dependent CKD patients previously treated with recombinant human erythropoietin. Roxadustat was effective in maintaining hemoglobin levels and met primary efficacy endpoint in the study with safety results that were consistent with previous studies. Dr. Peony Yu will provide more details on these results shortly.

Astellas anticipates submitting the first NDA for roxadustat in Japan for anemia associated with dialysis-dependent CKD later in 2018. In the non-dialysis-dependent program, Astellas is conducting two Phase III studies and expects top line results in the first of these studies in the fourth quarter of 2018.

In China, FibroGen China has made significant strides working with regulators and preparing for the anticipated approval in dialysis-dependent and non-dialysis-dependent CKD by the year-end 2018.

We are pleased to share with you the good news that the technical review agency, the CDE has been progressing steadily in this multi-step review process, and we are advancing now to final regulatory activity prior to a decision. We still believe a year-end 2018 approval is achievable. We have a strong operational team in China with more than 150 employees, many of whom are working closely with AstraZeneca to commercialize a first HIF-PHI therapeutic in the world. Christine Chung, Managing Director of China is here with us today and she will provide updates on our regulatory manufacturing and pre-commercial efforts supporting roxadustat in China.

Moving on to pamrevlumab. In the second quarter, we have had end of Phase II meetings on IPF and LAPC with FDA, and we have completed enrollment in our Duchenne muscular dystrophy Phase II trial.

By inhibiting the activity of CTGF, which is a known central mediator of fibrosis, pamrevlumab has the potential to be a targeted therapy for Idiopathic Pulmonary Fibrosis. We met with FDA in an end of Phase II meeting regarding IPF. We are generally pleased with the results of this meeting. However, we will defer any comment until we have received our minutes from FDA.

In pancreatic cancer at ASCO 2018, we presented our latest clinical update on pamrevlumab and the treatment of LAPC. As a result, the response from academic and treating physicians, patients and advocacy groups has been overwhelming positive as pamrevlumab may represent a novel treatment with the potential to transform nonresectable patients into surgical candidates.

Surgical resection is generally recognized as an important goal and effective means to extend overall survival in this population.

We recently met with FDA and came to agreement on the design and size of our pivotal program. We received guidance from the FDA on the basis for consideration of accelerating approval based on the resectability and resection rate.

Dr. Elias Kouchakji will provide more detail on our pivotal IPF and pancreatic cancer program later on this call.

On the financial side, at June 30, FibroGen had [$733.7 million] (corrected by company after the call) in cash. This sum represents an increase in our ending cash quarter-over-quarter, and in addition, we have increased the cash forecast for the full year in 2018. These changes in results are due to the proceeds from the first shipment of commercial grade roxadustat API supply to Astellas for Japan in the second quarter. Pat will discuss further details on our cash position and projected for year end 2018 later on this call. And I would now like to turn this over to Dr. Peony Yu for updates on the anemia program. Peony, please go ahead.

Thank you, Tom. We're entering an exciting time in the roxadustat development. So let's go right to the status and timeline of our program in the various geographies. Chris will talk about China shortly.

To begin with CKD in the U.S. and Europe. Last quarter we announced the enrollment completion of over 9,000 patients in our global Phase III clinical program.

We are now finishing up the multiple studies required for registration in the U.S. and Europe. With the last patient visit planned for September, we are on track to report top line study results in the fourth quarter of this year.

We plan to report results of adjudicated pool MACE analysis early in 2019. We have been asked why MACE results will be reported after the individual study data instead of being done at the same time. Typical clinical data such as hemoglobin or adverse events may become available once the lab tests have been performed and reported or when the adverse events have been reported by the study sites. However, MACE adjudication takes additional time even after the potential MACE event has been reported. The adjudication process requires obtaining relevant relevant documents from clinical sites where the events occurred, supplying the documents to external independent experts, who then need to review and come to sufficient consensus in order to complete the adjudication process.

Lastly, since 2014, our DSMB has been conducting periodic safety reviews of our Phase III clinical studies. In our most recent and final DSMB review, before study completion this September, we once again, received the recommendation to continue studies as per current protocols.

We are working diligently with AstraZeneca towards our goal of submitting the U.S. NDA to FDA in the half of 2019 and with Astellas working on preparation for MAA submission.

Turning to Japan. There are 6 Phase III roxadustat studies for supporting Japan registration. To date, Astellas has completed the four Japan Phase III dialysis studies to be included in the Japan NDA for treatment of anemia in CKD patients on dialysis. The most recently reported study, 307, is a 6-month double-blind, double dummy randomized active- controlled study in 303 hemodialysis patients, whose hemoglobin levels have been maintained between 10 to 12 grams per deciliter with ESA. Then randomized one-to-one to receive roxadustat or darbepoetin. Average hemoglobin levels were effectively maintained at 10.99 grams per deciliter from weeks 18 to 24 in roxadustat treated patients. The primary efficacy endpoint was met with demonstration of non-inferiority in the change in average hemoglobin levels from baseline to weeks 18 to 24.

It was negative 0.04 grams per deciliter in roxadustat treated patients versus 0.03 grams per deciliter -- I am sorry, minus 0.03 grams per deciliter in the darbepoetin comparator arm. The lower bound of the 95% confidence interval of the treatment difference were greater than a pre-specified non-inferiority margin of negative 0.75 grams per deciliter.

Roxadustat was well tolerated in this study and its safety profile was consistent with that observed in previous studies. Astellas is on track to submit the NDA in Japan for anemia associated with dialysis-dependent CKD in 2018.

Turning to anemia beyond CKD. For those of you following FibroGen, no doubt you have heard about our plans to expand roxadustat into other anemia indications, including oncology-related anemia. This last quarter we began dosing in a Phase 2/3 study in China in non-transfusion-dependent anemic MDS patients. And we have already separately started a Phase III U.S./EU study in transfusion- dependent MDS patients. I would like to turn the call back to Tom.

Thank you, Peony. Chris Chung who heads our China operations will now provide updates on activities and timing. Chris, please go ahead.

Thank you, Tom. It's great to join my colleagues here on this call today. We have made significant head way on the NDA review process in China. We now have the following major regulatory activities to complete prior to market authorization.

Final review meeting between FibroGen, the Center for Drug Evaluation and a panel of clinical experts.

On-site inspection of our API and drug product manufacturing in Beijing by the Center for Food and Drug International inspections or the CFDI. Analytical testing of the API and drug product material to be manufactured during the inspection by the National Institute of Food and Drug Control or the NIFDC.

Inspection of 808 nondialysis clinical trial sites.

With these final steps for approval in sight we're intensifying our efforts with AstraZeneca China on launch readiness.

Under the China partnership with AstraZeneca, FibroGen leads the regulatory clinical and CMC matters, and AstraZeneca leads in product commercialization. Efforts to prepare the market for a strong launch are well underway. Communicating the scientific differentiation of HIF-PHI in anemia therapy. Collection of real-world evidence to support roxadustat's value proposition in China, development of a pharmacoeconomic model to support favorable reimbursement, as well as identification of high priority target sites.

During 2018, the Chinese central government introduced significant reforms in the health care sector, including acceleration of reimbursement and expansion of access to urgently needed innovative medicines. FibroGen believes these changes are highly favorable to a novel first-in-class drug like roxadustat.

We are planning to gain acceptance of roxadustat into the government's reimbursement programs. Timing can be unpredictable, based on early signals from the Chinese government, at this moment in time, we believe, the next reimbursement opportunity will come in the 2019 to 2020 time frame.

On behalf of our team in China and myself, we recognize the significance of China potentially becoming the first approval country for any HIF-PHI in the world, and we eagerly anticipate the opportunity to introduce a new treatment paradigm for the treatment of anemia in Chronic Kidney Disease patients. We, of course, look forward to updating you on our progress at FibroGen China in the upcoming quarters. Thank you again for your time. Tom?

Thank you, Chris. Dr. Elias Kouchakji will now discuss recent developments for pamrevlumab and our IPF and pancreatic cancer programs. Elias, please go ahead.

Thank you, Tom, and thank you, everyone. We have continued to work intensively this quarter on pamrevlumab development in idiopathic pulmonary fibrosis and locally advanced and resectable pancreatic cancer.

In IPF, we reported additional positive Phase II clinical and efficacy data, which include quantitative measure of lung fibrosis measured by HRCT, and quality applied by St. George's Respiratory Questionnaire. We reported in multiple poster presentations at the 2018 American Thoracic Society conference in May.

These results, in combination with the previously reported positive results from this 48 week study, provide a strong justification for the development of pamrevlumab as monotherapy for IPF. As Tom mentioned, we met with the FDA on the Phase III trial designed for pamrevlumab in the IPF. We are looking forward to receiving the FDA meeting minutes. We expect to commence our study in 2019.

Now I would like to transition to the locally advanced pancreatic cancer. At ASCO in June, we presented positive results from the Phase I/II study. Patients who successfully completed the treatment course were evaluated for resectability of their tumor using standard criteria (RECIST and NCCN), as well as a new criteria and changes in PET/CT scan or biomarker CA 19.9.

Success in any one of these criteria provided a basis for surgical assessment. In this study, a higher proportion of patients who received neoadjuvant treatment of pamrevlumab in combination with nab-paclitaxel and gemcitabine became eligible for surgical resection at 70.8%, and underwent successful resection of their cancer at 33.3% than patients who were treated with chemotherapy alone were at 15.4% and 7.7%, respectively. For certain patients whom met the eligibility criteria for surgery after treatment, individual patient condition also contributed to whether resection subsequently occurred.

These results were well received by ASCO attendees. I would like to add here that there is no approved therapy for LAPC.

At our end of Phase II meeting with the FDA, we agreed on a pivotal trial design. In this double-blind study, approximately 260 patients with LAPC will be randomized, one to one to receive pamrevlumab or placebo in combination with gemcitabine and nab-paclitaxel for 6 months. Similar to our Phase II trial this study will assess resectability, resection and the primary endpoint, overall survival.

If the results will get higher resection rate favoring the pamrevlumab combination arm at the end of treatment period, the FDA has agreed to discuss the adequacy of this result to support a marketing application under the provision of accelerated approval.

The study will continue to follow up patients for overall survival. We are currently working on the clinical design and regulatory groundwork needed to start this study in early 2019.

We are making good progress in evaluating pamrevlumab as a treatment for Duchenne muscular dystrophy. As mentioned previously, we have completed enrollment of our Phase II clinical trial for young men adults with non-ambulatory Duchenne muscular dystrophy.

In this trial, we enrolled the Duchenne patients regardless of their genetic mutation. Efficacy measurement include pulmonary function, upper muscle tests and MRI imaging.

We look forward to advancing pamrevlumab into pivotal clinical trials in IPF, LAPC and DMD in hope of providing treatment options for these unmet medical needs. Thank you for your time today and I will return the call back to Tom.

Thank you, Elias. Pat Cotroneo, our Chief Financial Officer will now discuss financial highlights for second quarter 2018. Pat, please go ahead.

Thank you, Tom. As announced today, total revenue for the quarter ended June 30, 2018, was $44 million, as compared to $30.3 million for the second quarter of 2017. For the same period, operating expenses were $67.2 million and net loss was $23.4 million or $0.28 per basic and diluted share, as compared to operating expenses of $60.4 million, a net loss of $31.9 million or $0.46 per basic and diluted share for the same period in the prior year. Included in operating expenses for the quarter ended June 30, 2018, was an aggregate noncash portion totaling $15.2 million, of which $13.2 million was a result of stock-based compensation expense, as compared to an aggregate noncash portion totaling $11.5 million, of which $9.6 million was a result of stock-based compensation expense.

Following the first shipment of roxadustat API to Astellas for the manufacture of commercial drug product in the second quarter, $20.9 million was recorded in accounts receivables and in deferred revenue as of June 30. We anticipate this revenue will be recognized upon execution of an amendment to the Astellas Japan agreement currently anticipated in Q3, 2018.

In the second quarter, pursuant to new revenue recognition guidelines under ASC 606, which we adopted at the beginning of 2018, we are also reporting a $15 million anticipated milestone from Astellas in connection with planned Japan NDA submission later this year.

This is the first time we are recognizing revenue from a milestone payment in a prior period to milestone achievement following adoption of new revenue recognition guidelines. Under the new revenue recognition guidelines, we are required to include estimated consideration, from milestones in the determination of revenue recognition, in the period that milestone achievement become probable, which under U.S. GAAP rules is generally interpreted to be at least 75% to 80% likelihood. As of June 30, 2018, we had $733.7 million in cash as compared to $730.4 million at the end of Q1 2018.

For these purposes, total cash refers to cash as well as cash equivalents, receivables, investments, consisting primarily from investment-grade corporate debt and restricted time deposits related to our building lease. We are currently projecting a year-end cash balance in the range of $650 million to $670 million. The increase in the 2018 cash projection, from what we projected last quarter, is primarily due to the sale of API to Astellas as previously noted, as well as incorporating latest forecast data, which includes cost savings achieved in our clinical trial studies in the first half of 2018. Thank you. And I would like now like to turn the call back over to Tom.

Thank you, Pat. We are continuing to make excellent progress in our late stage roxadustat and pamrevlumab programs.

Looking to the second half of 2018, I would like to take a moment to discuss the upcoming developments and milestones.

Starting with roxadustat. For roxadustat in the U.S. and EU we are on target to report the top line study results in CKD anemia and dialysis-dependent and non-dialysis-dependent patients in the fourth quarter of this year. In Japan, roxadustat is used for treatment of anemia in dialysis, is on track for 2018. In China, we anticipate a market approval decision for roxadustat by year-end 2018.

For pamrevlumab in IPF, we have had our end of Phase II meeting and we look forward to receiving our minutes from FDA. We expect to start the Phase III study in early 2019. In locally advanced pancreatic cancer, we are proceeding with Phase III study planning and target study start in 2019.

With that, I would like to turn the call back over to Karen for a question-and-answer period. Karen, please?

Thank you so much. I think, operator, we would like to open up the lines for questions.

(Operator Instructions)

We're experiencing a technical problem. We are going to fix this just as soon as we can.

Can you guys hear me?

Okay.

(Operator Instructions)

Okay. Hold on one moment.

This is your operator, can you hear me? Can you hear me?

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And ladies and gentlemen, please stand by while the host dials back in. All right. We have our speakers back online. Can you hear me?

Yes. Daryl, thank you, everyone, on the line. We apologize for this technical difficulty. Let's go back to the Q&A portion.

(Operator Instructions) And our first question comes from Joel Beatty from Citibank.

First question is on the pancreatic cancer phase III design. Could you give a sense of the end points like resectability and resection and where things stand with FDA with regards to those being potentially approvable end points?

I think, Elias, you should good at and answer this please.

Yes, sir. As you heard that the FDA has stated that they are willing to take a look at the data if their resectability and their resection rate are significant and favorable to pamrevlumab arm. They are willing to meet with us on the provision for accelerated approval as a surrogate end point.

Thank you. Next question please.

And our next question comes from Michael Yee from Jefferies.

On the follow-up question on pancreatic cancer. Is it the understanding that a significant improvement in resectability and resection is viable, in other words, what is the hurdle? What do you guys deem as the hurdle to be defined as good enough data to discuss? And would the survival data ultimately need to pan out in order to support a full approval. Can you just describe how you would expect that to play out?

Let me ask Elias to go ahead and go over your understanding of resection, resectability as Michael asked.

See Michael, as the FDA looked at the result of the Phase II study and they considered these results as very significant. And since we are looking to maintain a similar results that you have a significant difference in the results between the 2 study arms and that was not specifically designed the percentage of the patients that is hard to maintain, that the resectability and resection should be maintained as both of them significant for the pamrevlumab arm. And if we reach that significance that the FDA considered, that will be sufficient enough for them to review the file under that provision.

Next question, please?

And our next question comes from Geoffrey Porges from Leerink.

It sounds as though you've made a lot of progress in China. I would be interested in an update on what the addressable patient population is immediately after approval. You have discussed in the past the possibility of a private-pay market in China. And would that be immediately addressable? And then secondly, could you clarify your comments about reimbursement? Do you now anticipate full national reimbursement being the path to getting coverage or would it still be on a province by province basis over sort of the 12 to 24 months period?

You can go over your understanding of the dialysis market size as well as a private pay market size and the various options for reimbursement. Please go ahead.

Sure. So thank you for the question. So the first question is what is the addressable market size immediately after approval. We will talk about the timing in the second question. Currently China has over 500,000 dialysis patients. It's the largest patient cohort in the world. There is 80% ESA penetration. We have shown that we are at least non-inferior to ESA, and in early market research, we believe we are very, very competitive. So we believe the entire dialysis feeded ESA population is addressable to us. In terms of the term, immediately, because we're a domestic Class 1.1 drug, we cannot start manufacturing commercial material until after NDA approval. So the launch is in no way immediate after NDA approval unlike in the United States. The second question with regard to reimbursement whether we do a full national reimbursement or provisional reimbursement entirely depends on 2 factors. Number 1, when the government calls for the opportunity to invite participants to be considered for national, and second, whether we are eligible based on the rules that are yet to be discussed.

Okay. Thank you, Chris. Let's go to the next question please.

And our next question comes from Andy Tsai from William Blair.

Number 1, I just want to get a sense of the robustness of the resectability. Can you describe if this measurement is investigator assessed? Or it has to go through an independent third-party blinded review?

Elias, I think you should probably answer that. This is for the Phase III study.

So for the Phase III study there would be an independent adjudication committee for their resectability, and we would still be using the same criteria that we used in the Phase II studies. This criteria was discussed with the agency and was accepted.

Next question, please.

And our next question comes from Difei Yang from Mizuho Securities.

So again, on pancreatic cancer, do you plan on the interim analysis of the trial? And if so what is the rough timeline we should be expecting results?

So Difei, thank you for joining this call from Mizuho, thank you. Elias, go ahead and address this question.

So the timeline of the interim analysis is it would be at the time when all patients completed the assessment of resectability and resection, which is a treatment of 6 months, plus 1 month after that for the resection. So 7 months after last patient is enrolled.

Our understanding is that the point when 260 patients have gone to 7 months of treatment, we'll get to the point that we can do that enrollment.

Yes

Okay. And then for the 260 patients, are they primarily U.S.-based or a global trial?

This is a global trial.

So the question here is, beyond the U.S., are we planning on enrolling anywhere with regard to the pancreatic cancer study? Elias, please?

This is again a global trial as Tom was alluding too. So this is not a U.S.-based. So we are looking forward to include additional countries.

Yes, and we are specifically planning on enrolling some patients in China.

Next question, please.

(Operator Instructions) And we have a question from Geoffrey Porges, a follow-up question.

You moved through the questions quickly. I appreciate the follow-up. Could you just talk about...

Sorry, Geoffrey, you've already had a question so just make the one question please.

Okay. You want me to ask you a question.

You may ask a question.

Thanks, Tom. Specifically on the MACE analysis of the comparison with ESA and a placebo. Could you give us a sense of what the hurdle is? The numbers are going to be small. So is it non-inferiority, numerical difference. How is that going to be presented and measured?

Peony, did you understand the question here?

Not quite. Jeff, can you clarify your question?

For the MACE, for the combined MACE analysis in the first part of next year, what is the hurdle on roxadustat? What do you need to show? Is it going to be a statistical analysis or is a non-inferiority alone? Or is it just going to be a numerical difference? How is that difference going to be presented?

I think we understand it now, please, Peony go ahead.

Yes, so Jeff, for the MACE analysis just to be clear we -- this NDA submission includes both dialysis and non-dialysis indications. The non-dialysis, there will be 2 separate MACE pools. The non-dialysis MACE pool will consist of 3 Phase III studies, and it will be a comparison between roxadustat versus placebo. The dialysis pool will consist of 4 Phase III studies and the comparison will be between roxadustat versus epoetin alfa. So the basis of what we need to show in both pools is a demonstration of non-inferiority in comparison relative to the comparator. So in other words, for safety comparison in non-dialysis we need to demonstrate MACE to be non-inferior to placebo. Now, of course, it will be a bigger home run if we demonstrate better safety than placebo since we do believe that it is beneficial to CKD patients with anemia to have their hemoglobin corrected. And for the dialysis again, it is the safety -- for the safety comparison is non-inferior to EPO.

Next question, please.

(Operator Instructions) And we have no more questions at this time.

Thank you for joining the call today. We feel we have made remarkable progress in the second quarter 2018 in advancing our late-stage pipeline programs through critical, clinical and regulatory development stages. The results of these efforts continue to signal the potential of our therapeutic programs to help patients struggling with anemia associated with chronic kidney disease and myelodysplastic syndromes, as well as of Idiopathic pulmonary fibrosis, locally advanced pancreatic cancer and Duchenne's muscular dystrophy. I would like to take a moment to express my deep appreciation to all of my FibroGen team colleagues in the U.S. and China for their commitment and incredible effort as the work pace has been very, very high this quarter. And my thanks to our partners and investors for their support. We look forward to keeping you informed on program developments. I would like to wish everyone a good afternoon, and a good evening. Thank you.

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