FibroGen, Inc

Good day, and thank you for standing by. And welcome to FibroGen fourth quarter 2021 financial results conference call. At this time, all participants are on a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star 1 on your telephone. Please be advised that this call is being recorded. If you require any further assistance, please press star 0. I would now like to hand the conference over to your host today, Mike Tung, Vice President of Corporate Strategy and Investor Relations. You may begin.

Thank you, Justin. Good afternoon, everyone. I'm Michael Tung, Vice President of Corporate Strategy and Investor Relations at FibreGen. Joining me on today's call are Enrique Quintero, our Chief Executive Officer, Dr. Mark Eisner, our Chief Medical Officer, Juan Graham, our Chief Financial Officer, Dr. John Hunter, our Chief Scientific Officer, Thane Wettig, our Chief Commercial Officer, and Chris Chung, our Senior Vice President of China Operations. The format for today's call includes prepared remarks from Enrique Juan, after which we will open up the call for Q&A. I would like to remind you that remarks made on today's call include forward-looking statements about FibroGEN. Such statements may include, but are not limited to, 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, commercial results and results of operations, risks related to our business, and certain other business matters. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in filings with the SEC, including our most recent Form 10-K and Form 10-Q. Fibrogen does not undertake any obligation to update publicly any forward-looking statements, whether as a result of new information, future events, or otherwise. The press release reporting our financial results and business update and a webcast of today's conference call can be found on the investor section of Fibrogen's website at www.fibrogen.com. And with that, I would like to turn the call over to Enrique Quintero, our CEO. Enrique?

Very good. Thank you, Mike. Good afternoon, everyone, and welcome to our fourth quarter. and a full-year 2021 earnings call. Briefly, before we begin, I would like to highlight that today is Rare Disease Day, which is especially relevant to us given our Panvrelumab Phase III programs and our Roxodustat MDS program. As we enter 2022, we're excited about our future as we continue to advance our Phase III Panvrelumab clinical trials in three indications, continue our strong performance with Roxadustat in China, launch Roxadustat in Europe, and expand our research and development portfolio in the immuno-oncology and autoimmune space. On today's call, I intend to cover recent developments and key events, beginning with Pambrelumab. Juan Graham, our CFO, will then review the financials, after which we will open up the call for your questions. Starting with slide three, Fabergen is positioned to create significant value for patients and shareholders by executing on our three areas of focus. Number one, accelerating the development of pembrelumab in three indications with significant unmet medical need, idiopathic pulmonary fibrosis, locally advanced unreceptable pancreatic cancer, and Duchenne muscular dystrophy. Ensuring commercial success of Roxadustat in patients with chronic kidney disease outside the U.S. while continuing to explore a path forward in the U.S. And number three, increasing our research productivity to advance novel programs that leverage internal expertise and accessing external innovation for additional pipeline opportunities. Let's move to our clinical trials focusing on Pambrello map on slide four. Fandrelumab is a wholly owned asset in Phase III clinical trials for three highly important indications. As we said, IPF, LAPC, and DMD. Today, we announced completion of enrollment of our LAPIS Phase III study of 284 patients with locally advanced and resectable pancreatic cancer. We also completed enrollment of the Relantus-1 Phase III study of 99 patients with non-ambulatory DMD. In the next few weeks, we expect to complete enrollment of the CEPHRS I Phase III study of approximately 340 patients with IPF. Our Phase III CEPHRS study is largely based on our Phase II PRACE study, which demonstrated a meaningful reduction of lung function decline. Each of these diseases represents an important unmet medical need and collectively they constitute a significant market opportunity. We expect multiple Panbrellumab data readouts in 2023 and an interim analysis of LAPC later this year. I'd like to spend a few minutes highlighting our perspective on the significant opportunity we see with Panbrellumab in each of the three disease states, beginning with IPF on slide five. With a diagnosed prevalence of approximately 330,000 patients across the US, EU, China, and Japan, the two key medicines comprising the IPF market generated over $3 billion in net revenue in 2020. Despite this market size, there remains significant unmet need with these two approved therapies, as characterized by continued disease progression and challenging tolerability. There is a sentiment in the IPF community of limitations with the current therapies and a desire for additional therapeutic options. Given the limited number of late-stage products in development, we believe Pumbrello MAP, if approved, is well-positioned to take advantage of this opportunity. If the Phase III CFRS program produces comparable results to the Phase II PRACE trial, we believe Panbreloma has the potential to help a sizable number of patients with IPF and be a very significant product for FibroGen. Turning now to slide six and the locally advanced pancreatic cancer opportunity. Non-metastatic pancreatic cancer represents one of the greatest unmet missing oncology, given the diagnosed prevalence of almost 140,000 patients across the major regions combined with a low five-year disease-free survival rate of around 10%. There have been limited treatment advances in the non-metastatic setting over the last two decades, with therapies failing to demonstrate survival benefits over the current standard of care. Similar to IPF, there's limited late-stage development activity in non-metastatic pancreatic cancer, which creates a meaningful opportunity for panvrelumab if we can demonstrate an improvement in overall survival. As we said earlier, the LAPIS phase three trial is fully enrolled and we look forward to seeing if panvrelumab could provide an important new treatment option for patients. Turning to slide seven. We wrap up the panvrelumab section with a snapshot of the DMD opportunity. Given the devastating nature of DMD and the relentless disease progression, we're hopeful that the LELANTUS clinical trial program can lead to an approved therapy that is so needed by the DMD community. With corticosteroids as the current standard of care, patients commonly deal with troublesome side effects as they continue to experience disease progression and loss of ambulation. While the currently approved exon skipping therapies produce an increased In dystrophin levels, they only target a small proportion of DMD patients. There's clearly need for therapies that can improve muscle function and prolong ambulation by targeting the downstream pathological changes of DMD. We believe the anti-fibrotic mechanism of panbrelumab may be a solution that can help these patients and their families. Now let's move to Roxodustat on slide eight. Following the European Commission approval of Evrenzo for the treatment of adult patients with symptomatic anemia associated with chronic kidney disease, Astellas has launched now in Germany, the United Kingdom, the Netherlands, Austria, and the Nordic countries. The early feedback from healthcare providers prescribing Evrenzo has been positive. The anemia of CKD opportunity in Europe is significant, And Evrenso has an important first-mover advantage relative to other HIV PHIs. Regarding Roxodustine in the US, we and our partner, AstraZeneca, are in discussions on a potential path forward in anemia of CKD. In November, Fabergen and AstraZeneca met with the FDA and discussed next steps following the advisory committee meeting. At this time, we are working together with AstraZeneca to determine those next steps. Moving now to China. As you can see on slide nine, we are reporting total rock-reduced net sales to distributors in China of 32 million for the fourth quarter. The total net rock-reduced sales to distributors in China for 2021 was 186.1 million, significant growth over the 72.5 million in 2020. As a result of the price reduction associated with the NRDL listing renewal, the ROXADUSTA NET sales for the fourth quarter of 2021 reflected a one-time adjustment driven by a revaluation of channel inventory. Fabergen's portion of ROXADUSTA NET product revenue in China was $5.5 million for the fourth quarter and $47.6 million for the full year 2021 on a U.S. GAAP basis. Juan will dive deeper into further detail in the finance updates. We have continued to see broad adoption across the three segments of hemodialysis, peritoneal dialysis, and non-dialysis, and continue to see strong performance of Roxodustad in China. Since the launch of Roxodustad in mid-2019, a primary focus of our commercialization efforts has been to secure hospitalization. which is a right to be prescribed at the particular hospital. As of the end of 2021, we're listed in hospitals that represent approximately 80 percent of the addressable and e-mail CKD market. Roxadustat was included in the 2021 NRDL with a meaningful reduction in price. However, we do expect Roxadustat net sales growth for the full year in China, driven by significant growth in volume. As you can see on slide 10, Roxadusta continues to drive the expansion of the Anemio CKD category and is capturing share in an expanding market. Roxadusta captured the large majority of the category growth for the 12 months ended December 2021 over the same period in 2020. Finally, as shown on slide 11, Roxadusta is the number one branded treatment for anemia of CKD in China for the past 12 months, achieving a value share of 36% in the most recent quarter within that segment that includes all ESA products and Roxadusta currently the only HIF-PHI in the market. We look forward to keeping you updated as we advance our long-term goal of making Roxadustin the standard of care in treating China's CKD anemia patients. I will now turn the call over to our CFO, Juan Graham, for the financial update. Juan.

Thank you, Enrique. While 2021 was a difficult year due to the CRL outcome, I'm inspired by the positive energy and resilience of our team. I'm optimistic about the progress made on our Pembrevlima Phase III clinical trial recruitment, And about the potential opportunity Pamreblumab represents for patients suffering from diseases such as idiopathic pulmonary fibrosis, locally advanced pancreatic cancer, and Duchenne muscular dystrophy. In addition to providing patients with a therapeutic option in these diseases, Pamreblumab also presents a very attractive commercial opportunity for fibrogens. I'm confident we are well-positioned for the future to deliver on our vision to bringing innovative medicines to patients in diseases of significant and med needs. Now diving into our financials, as we announced today, full year revenue for 2021 grew by 33.5% to $235.3 million versus $176.3 million in 2020. Total revenue for the fourth quarter was $16.5 million as compared to $65 million for the same period in 2020. As we go deeper into our revenue performance, and as a reminder, We record four sources of revenue. First, license revenue, which is allocated from license payments and milestones earned or deemed probably of being earned in the period. Second, development revenue, which is revenue from development expense reimbursement and revenue from other development activities. Third, net product revenue, which is the revenue from sales to the distribution entity jointly owned by AstraZeneca and Fibrogen, or JDE, in China, from which we recognize the transfer price as well as our direct sales to distributors. And fourth, drug product revenue, which includes transfer price payments from our collaboration partners for our commercial-grade API or bulk drug product shipments to them. During the fourth quarter, we recorded $10 million in development revenue from our collaboration agreements associated with co-development efforts for Roxadustat. During the quarter, We recorded $5.5 million net product revenue for Roxadustat sales in China. This includes $3.1 million from our sales to the JDE and $2.4 million of direct sales by Virgin made to distributors. It is important to note that based on the NRDL listing renewal, we have updated our estimates and reflected a cumulative downward adjustment in our revenue in the fourth quarter. Providing context for the operating results of our RUXA-DU-STAT business in China, we begin with total RUXA-DU-STAT fourth quarter net sales of $32 million, which includes sales through the JD to its distributors and FiberGen China's direct sales to our distributors. It is important to note that due to the NRL listing renewal, fourth quarter total RUXA-DU-STAT net sales reflect a one-time inventory revaluation adjustment. Despite this adjustment, total Ruxudustat net sales grew by 10% compared to $29.2 million for the fourth quarter in 2020. Focusing on Fibrogen sales to the JDE, as we have previously disclosed, starting the first quarter of 2021, the JDE began selling Ruxudustat to distributors and paying for AstraZeneca's commercialization efforts in China and AstraZeneca's portion of the profit share. Previously, Fibrogen was responsible for these items. As per this agreement with AstraZeneca, Fibrogen recorded a net transfer price from sales to the JDE, which was $12.2 million for the fourth quarter. As we have previously guided, this net transfer price lies within the 30 to 45 percent range of the JDE's Ruxa-Dustat net sales to its distributors. From this net transfer price, $9.1 million is deferred and will be recognized in future periods. After this deferral, Fibrogen recorded $3.1 million in net revenue for the quarter from ROC-seduced at sales to the JDE. We continue to be encouraged by the growth of our China operations and we expect continued strong market penetration with our renewed NRDL contracts 2022 and beyond. For the quarter, We did not have license revenue, and direct product revenue was not significant. As we wrap up with revenue, providing more texture to the fourth quarter revenue variance versus 2020, the major drivers in order of magnitude are, one, lower product revenue in China due to the change from FibreGen's direct sales to distributor model, transitioning to FibreGen sales to the joint distribution entity, which represents nearly 50% of the change. Lower license revenue due to a one-time milestone payment in the prior year period, representing roughly 30% of the change. And three, lower development revenue due to substantial completion of phase three trials for Ruxudustat. Now moving down to the income statement. During the fourth quarter, operating costs and expenses were $151.8 million compared to $123 million a year ago. The primary drivers of the change are R&D costs driven by an increase in Phase III clinical trials, including drug supply costs associated with our Pembrolumab programs and the HiFiBio license. During the fourth quarter, net loss was $134.1 million, or $1.45 net loss for both basic and diluted shares, as compared to net loss of $58.6 million or $0.64 per basic and diluted shares for the fourth quarter last year. At December 31, we reported $590.4 million in cash, cash equivalents, investments, and accounts receivable. As we look forward, we estimate our 2022 ending balance of cash, cash equivalents, investments, and accounts receivable to be in the range of $270 to $300 million. While we are appropriately financed, we are privileged with a wide array of options to consider as we continue to evaluate opportunities that would lead to strengthening our cash position and our balance sheet. Thank you, and I would like to turn the call back over to Enrique.

In closing, we remain committed to advancing Pantrelumab as a potential first-in-class medicine in Phase III development in three indications with significant unmet medical needs. idiopathic pulmonary fibrosis, locally advanced and resectable pancreatic cancer, and Duchenne muscular dystrophy. Roxadustar continues to perform very well in China. Our partner, Astellas, is moving forward with commercialization of Roxadustar in Europe. We have multiple regulatory submissions under review in other geographies. Fabergen and our partner, AstraZeneca, are in discussions to determine next steps in the U.S. As shown on slide 12, we continue to have a strong financial position with approximately $590 million in cash and expect to end 2022 with $200 to $300 million in cash. Additionally, we have multiple options to consider to further strengthen our balance sheet and cash position to ensure long-term success. Now, I would like to turn the call back to the operator for questions. Justin?

Thank you. As a reminder to ask a question, you'll need to press star one on your telephone. So to draw your question, press the pound key. Please stand by, we compile the Q&A roster. And our first question comes from Michael Yee from Jefferies. Your line is now open.

Hi, this is for Mike Yee. Thanks for taking my question. So I guess two from Jefferies. So first one is, how are you thinking about the plans for ROCSA in the United States? And do you have a timeline in mind for the next steps? And could you also give some color on the potential scenarios for future regulatory process down the road? And maybe comment on value proposition in the U.S. as well. And second one, could you also comment on ROCSA in China? especially on recent price adjustments from NRDL, appreciating that's something that may occur every two years. So wondering if you could comment on your strategy to drive more China sales to counter the pricing headwinds. And also, please comment on the patent situation expectations, please. And how should we think about the tail value of ROXA in China? Thank you.

Very good. Thank you for your questions. I'm going to first ask Mark Eisner to comment on the first question about the U.S. and potential scenarios there.

Mark Eisner Thanks for the question, Michael. It's Mark Eisner here. So, in terms of CKD in the U.S., we're continuing to work with our partner, AstraZeneca, and the FDA. Those discussions are ongoing, and, you know, we're continuing to evaluate our options there. In terms of timelines on that, we should be able to provide more information in the upcoming weeks. In terms of regulatory down the road, I think I answered that one, so I'll turn back to Enrique.

Chris, maybe you can provide a little bit about a little bit of color when it comes to China. including anything, you know, how we're thinking about volume growth and what are we doing to counteract some of the price decrease with the NRDL price, new price, and then also how provide some color also on market exclusivity.

Absolutely, Enrique. So, as was expected, you know, the NRDL pricing happens every 24 months. So, this was certainly not unexpected. And a range of price cuts are also not unexpected. So, the company and Roxadustat had plans in place to really address the price cut with extension of duration of treatment. And the lower out-of-pocket price, how we left that to expand the adoption in certain segments of the market, in particular in NDD, where affordability on the out-of-pocket basis might have been challenging for HIF as a class. So we remain very optimistic about the outlook for 2022. We believe the increase in volume growth would offset the pricing, and we are expecting top-line growth in 2022 above 2021, despite the NRDL price cuts. With respect to the patent situation, the patent dates also are known. There are currently a couple of things going on in terms of the patent regulation in China. It is still unclear in terms of what the regulations might be with patent term extension, but we are doing some scenario planning and obviously there are different parties who are actively discussing with the government in terms of what might make sense to continue to encourage innovation in the People's Republic of China, which is one of their major country strategies. So we remain optimistic in terms of what that situation might be.

Thank you.

And thank you. And our next question comes from Annabel Simai from Stifel. Your line is now open.

Hi. Thanks for taking my question. I just had a question about the MDS and the CIA indication. I know that the MDS indication is still ongoing. The CIA, I guess, is still on hold. Have you had any further thoughts about the risk-benefit equation for that population? Is it still wholly owned, or is it something that you could potentially monetize down the line? And then I guess for Hemrevumab, again, are you considering any licensing of these programs? Are you going to stick with owning them singularly? Thanks.

Yep. Very good. Thank you very much, Annabelle. I'm going to ask once again Dr. Eisner to comment on MDS and in particular CIA and in particular to the benefit-based profile?

Sure. So, as you know, the study OA2, the MDS trial, is ongoing. We've communicated that we should have top-line results second half of this year, first half of next. We feel very excited about the potential there. We believe Roxadustat could be a very very efficacious therapy, but that's why we're doing the Phase III trial to evaluate that and provide a more comprehensive assessment of the benefit-risk. In terms of CIA, we announced our Phase II completion not long ago. In terms of Phase III planning, those discussions were ongoing with our partner AstraZeneca in the U.S. and with our partner Astellas for Europe and their territories.

Yeah. I think you also asked, Annabel, whether MDS was fully owned. MDS is part of the partnership agreements with both AstraZeneca and Astellas. In terms of PAM, I think as we shared in the past, we do intend to launch PAMbrelumab in the U.S. as FibroGen, and we are considering partnering outside of the U.S., outside of Canada.

Thank you.

And thank you. And our next question comes from Alex Ramsey from William Blair. Your line is now open.

Hello, this is Alex on for Andy. I just had one question. In the 10-K, the company disclosed that it has received an SEC subpoena. I was just wondering if you could elaborate on that and give us a sense of procedurally how these inquiries will go.

Yeah, we've received a request for documents from the SEC. There's not much that we can say at this point in time other than we are collaborating with the SEC, and at the appropriate time, we will basically update investors as we know more.

Okay, great. Thanks so much.

And thank you. And our next question comes from Jason Gerberry from Bank of America. Your line is now open.

Hey, this is Perry on the line for Jason. Thanks for taking our questions. First, I have a question about the CKD category expansion with ESA and HIFS in China. The current split is around, looks like it's around 70-30. How do you expect this to evolve over time? Do you expect it to, you know, more become, you know, improve towards a 50-50 split? And do you expect that to happen as a result of category expansion overall, or do you expect ROPS to start eroding away at ESA directly based on clinical profile? And then just one other question on the LAPI study and the pancreatic cancer indication for PAMREV. Can you talk about the potential for an accelerated pathway submission post the event-free survival readout? Is there kind of a benchmark that you have to hit to really justify an accelerated pathway submission? Just want to get your thought process on that. Thanks.

Very good. Now, thank you for the questions. I'm going to ask Thayne and Chris to comment on the question about the category expansion in China and the split between ESAs and and what we expect in the future. And then, Mark, if you could offer your some color on LAPIS and event-free survival How are we thinking about that?

Should I start? Sure. I would start and please supplement. So first of all, if we ask ourselves why is there a category expansion, the main idea behind here is we believe the ESA market in China is not equivalent to the anemia and CKD market. The CKD anemia market was under-penetrated because of some of the constraints of ESA because of a safety profile, the fact that it's an injectable, and many other constraints, you know, such as the need for intravenous ion to address inflammation. So the fact that we see category expansion is a direct evidence of the differentiation of the HIF class. So if you ask yourself, will the HIF class eventually take over 100% of the ESA class, the question would be, one, price, and second, what are the subsegments of the population where ESA continues to be sufficient? and what is the equation of price versus value. So in terms of a terminal number, I personally expect the HIF class to continue to help grow the category and increase the share of that category. It's hard for me to guess what the terminal value would be, but I think there's significant differentiation of the HIF class in non-dialysis because of the oral nature and the fact that we could reach target without routine chronic supplementation of iron for that home-based population. Thane?

Yeah, thanks, Chris. Just a couple of additional points to make. You know, if we take a look at the 12 months ending in 2021 versus the 12 months ending in 2020, Roxadustat drove the substantial portion of the category growth. I think Roxadustat's portion of that was over 75%. And so we would expect that to continue. It will continue. based upon the positive experience from clinicians and patients. And then what Chris referred to as well, in terms of the renewal of roxidustat on the NRDL and greater affordability from a patient pocket perspective. And so we do anticipate roxidustat to continue to capture a majority of that category growth. The final point is that we believe that the NDV category is largely untapped. The dialysis segment is very well defined. 90% plus patients who are in dialysis are receiving a treatment for their anemia associated with their chronic kidney disease, but there's still substantial opportunity that remains in the NDD category, and we think that the value proposition for Roxazustep will continue to be tailor-made for more and more patients being treated for their anemia in that NDD population.

Thank you, Zane. And Mark, maybe you can now address the LAPIS EFS question.

Sure. So just to remind everybody, we are planning an interim analysis based on event-free survival, which is comprised of resection, lack of progression locally or distantly of disease, and freedom from mortality or survival. Based on the interim analysis, we do have a predefined threshold for or efficacy that would be utilized to decide whether or not there's potential to file an accelerated approval, a file of ELA for an accelerated approval. And that would be a decision made after FDA feedback as well. So there's a number of steps there that we would take to make that decision.

Very good. Thank you.

Thank you. And thank you. And I am showing no further questions. I would now like to turn the call back over to Enrique Contorno for closing remarks.

Enrique Contorno Very good. Thank you very much for everyone's participation in today's investor call and your interest in FibreGen. Enjoy very much the rest of your day. Bye-bye.

This concludes today's conference call. Thank you for participating. You may now disconnect.