FibroGen, Inc

Hello, everyone, and welcome to the FibroGen fourth quarter and full year 2024 earnings conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To participate, you will need to press star 1-1 on your telephone. You will then hear a message advising your hand is raised. To withdraw your question, simply press star 1-1 again. Please be advised that today's conference is being recorded. Now it's my pleasure to turn the call over to Joanne Greller. The floor is yours.

Thank you, Operator. Good afternoon, everyone. Thank you for joining today to discuss Fribergen's fourth quarter and full year 2024 financial and business results. I'm Joanne Greller from LifeSci Advisors. Joining me on today's call are Thayne Wettig, our Chief Executive Officer, and David DeLuccia, our Chief Financial Officer. Following the prepared remarks, we will open the call to your questions. 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, are 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 FiberGEN's 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 the sale of Fibrogen China and a webcast of today's conference call can be found on the investor section of Fibrogen's website at www.fibrogen.com. With that, I'd like to turn the call over to our CEO, Thane Wettig. Thane?

Thank you, Joanne. Good afternoon, everyone, and welcome to our fourth quarter and full year 2024 earnings call. On today's call, I will provide a status update on the transformation of Fibrogen, which includes the divestiture of Fibrogen China and a laser focus on our U.S. pipeline opportunities, which includes the exciting prospects for FG3246, and FG3180, our potential first-in-class antibody drug conjugate targeting CD46, and our PET imaging agent in metastatic castration-resistant prostate cancer, and for roxidustat in the treatment of anemia due to lower-risk mild dysplastic syndrome. Then, David De La Chia, our CFO, will review the financials, after which we will open the call for your questions. On slide three, I would like to highlight the strategic priorities for our companies. First, the announcement of the sale of Fibrogen China to AstraZeneca for approximately $160 million. This transaction simplifies our operations, allows for the payoff of our term loan facility with Morgan Stanley tactical value, and provides the most efficient pathway to access the company's net cash held in China, extending the company's cash runway into 2027. This is a truly transformative transaction for our company, which we are expecting to close by mid-year. Second, advancing FG3246 and FG3180 in MCRPC remains a key priority. In the second quarter of 2024, we shared important data from two Phase I studies, highlighting the potential of FG3246 as both monotherapy and in combination with enzalutamide. I'll provide a more detailed overview of where we are with the program and the upcoming 2025 catalysts in a moment. Third, we believe that Roxidustat represents an important potential therapy for patients with anemia associated with lower risk MDS. We plan to meet with the FDA in the second quarter of 2025 to further explore this opportunity, which we are considering developing on our own or via a potential partnership. We believe the regulatory interaction with the FDA next quarter will provide important clarity on the best path forward with the aim of realizing additional value for Roxadustat in an indication of significant unmet need. Altogether, we are confident that our refined focus, multiple near-term catalysts across both programs, and our existing strong foundation position us well to create value for shareholders now and in the future. I will now provide a brief overview of our FG3246 and FG3180 programs in MCRPC. Slide 5 highlights the high unmet need in late stage prostate cancer. There are approximately 290,000 men diagnosed with prostate cancer each year in the U.S. Of these, there are 65,000 drug treatable patients where the cancer has metastasized and become castrate resistant. resulting in a grim five-year survival rate of approximately 30%. There remains a significant opportunity for new treatments that can extend survival for these men, with a total addressable market of over $5 billion in annual sales. FTE3246 could be this new treatment option. Turning to slide six, we highlight the novelty of our target, a tumor-selective epitope of CD46. CD46 and this specific CD46 epitope have several distinguishing features. CD46 is upregulated during tumorigenesis and helps tumors evade complement-dependent cytotoxicity. The CD46 epitope is highly expressed in MCRPC tissues with lower interpatient variability and higher median expression compared with PSMA as depicted in the graph on the right-hand portion of the slide. Importantly, the expression of CD46 is upregulated in the progression from localized castration-sensitive prostate cancer to metastatic castration-resistant prostate cancer, and further overexpressed following treatment with androgen signaling inhibitors. And the CD46 epitope is also overexpressed in colorectal cancer and other solid tumors. I would also like to highlight that CD46 was referenced at this year's ASCO-GU meeting as one of the promising non-PSMA targets in advanced prostate cancer due to its high sensitivity, stable expression, and positive correlation to tumor burden. Turning to slide seven, FG3246 is a potential first-in-class ADC in development for metastatic castration-resistant prostate cancer with a novel targeting antibody, YS5, which binds to the tumor-selective epitope of CD46. and an MMAE payload. MMAE is a validated payload that is approved as part of a number of ADCs and other oncology indications. FG3246 represents an androgen receptor agnostic approach, clinically differentiating it from other prostate cancer treatments currently in development. A companion PET imaging agent, FG3180, utilizes the same YS5 targeting antibody as FG3246 and is also under clinical development. In preclinical studies, the PET imaging agent has demonstrated specific targeting of and uptake by CD46-positive tumor cells. We believe that having a patient selection biomarker would not only allow us to better enrich the patient population in the Phase III portion of the clinical development program, It would also enable differentiation of FG3246 in the prostate cancer treatment paradigm. In addition, FG3180 could represent an important commercial opportunity as a companion diagnostic to FG3246, similar to the existing PSMA PET agents. Slide eight recaps the top line results from the phase one monotherapy study reported in the second quarter of 2024. The completed monotherapy study included a total of 56 metastatic castration-resistant prostate cancer patients who were biomarker unselected and were heavily pretreated, receiving a median of five lines of therapy prior to FG3246. In the efficacy of valuable population of 40 patients, we observed a median radiographic progression-free survival of 8.7 months, overall response rate of 20% confirmed by Resyst 1.1, and PSA reductions of greater than 50% in 36% of the patients. Adverse events were consistent with those observed with other MMAE-based ADC therapies. The manuscript describing the Phase I monotherapy trial has been submitted, and we anticipate publication soon. On slide nine, we highlight the performance of FG3246 in its phase one study versus other comparable early stage studies. As highlighted on the previous slide, the phase one study of FG3246 demonstrated an RPFS of 8.7 months across a robust sample size of 40 heavily pretreated patients. While we cannot make direct comparisons to these trials due to differences in study design and prior prostate cancer treatments, we are encouraged by the RPFS results, which is a recognized regulatory endpoint in prostate cancer trials. On slide 10, we highlight interim results of the phase 1B portion of the ongoing investigator-sponsored combination study with enzalutamide as reported at ASCO in June of 2024. These interim results included data on 17 biomarker unselected patients, 70% of which were pretreated with at least two prior ARSI's. In addition to establishing the Phase II dose of FG3246, the IST also demonstrated an encouraging preliminary estimate of 10.2 months of radiographic progression-free survival, with PSA declines observed in 71% of available patients. The trial is continuing to enroll and is now set for top-line results in the second half of 2024, which will also include data on CD46 expression on patients treated with FG3180, our PET biomarker, during the Phase II portion of the IST. On slide 11, we depict a comparison of the initial results from the monotherapy trial in heavily pretreated patients and the combination trial for FG3246 versus the RPFS results from second-line therapies in late-stage trials. Again, while we cannot make direct comparisons to these trials due to differences in study design in previous prostate cancer treatments, we are encouraged that FG3246 demonstrates what we believe to be competitive are PFS results. Slide 12 highlights the Phase II monotherapy dose optimization trial design that is based on our discussion with the FDA. We plan to enroll 75 patients in the post-ARSI pre-chemo setting across three dose levels to determine the optimal dose for Phase III based on efficacy, safety, and PK parameters. It is important to note that FG3180 will be an important part of the study. as we seek to demonstrate the correlation between CD46 expression and response to the ADC in this all-comers population. One other important design element is the primary prophylaxis with GCSF, which is intended to mitigate adverse events associated with neutropenia, commonly seen with MMAE payloads. The addition of GCSF may enable a better tolerated and more consistent treatment with the ADC, thereby extending duration of therapy and potentially enhancing efficacy of the ADC. We are planning an interim analysis in mid-2026, which will include efficacy, safety, PK, and exposure response data, and we intend to share relevant data to all stakeholders as they become available, given the open-label design. Slide 13 highlights the development strategy. for FG3246 and FG3180, which we believe provides significant optionality in prostate cancer. We have a robust phase two monotherapy trial in the pre-chemo setting in MCRPC to further build upon the compelling efficacy data of 8.7 months of RPFS in 40 heavily pretreated biomarker unselected patients from the phase one monotherapy study. The phase two monotherapy trial is designed to select the optimal dose for phase three based upon the benefit-risk profile from this Phase II trial. We believe there are three factors that could drive RPFS even higher than was observed in the Phase I monotherapy trial. First, preliminary evidence of an exposure-response relationship, which allows us to focus our Phase II study on three of the highest tolerated doses from the Phase I dose escalation and expansion study. Second, utilizing primary prophylaxis with GCSF, to combat against neutropenia and allow patients more consistent exposure to the ADC with fewer dose interruptions or adjustments. Third, enrolling healthier patients in earlier lines of therapy versus the median by prior lines of therapy in the Phase I trial. In addition, this study will explore the correlation between CD46 expression and response to the ADC. potentially validating FG3180 as a predictive patient selection biomarker in future studies. We are confident that our development pathway for FG3246 unlocks sequential or parallel registrational pathways, as FG3246 will be evaluated in multiple lines of therapy, in monotherapy or in combination with an ARSI, and in an all-commerce population or patients with high expression of CD46. Slide 14 shows the recent and upcoming catalysts for the FG3246 program. We have potential value inflection points in the near term with the anticipated initiation of the phase two dose optimization study in MCRPC by mid 2025, and the top line results from the phase two portion of the combination study with enzalutamide, which are expected in the second half of 2025. To summarize on slide 15, FG3246 targets a novel epitope on prostate cancer cells with first-in-class potential. It has already demonstrated promising efficacy signals with an acceptable safety profile, both in monotherapy and in combination settings. We are excited for the upcoming milestones and look forward to updating you on the program as the studies progress. Slide 17 highlights the unmet need and the potential for roxidustat in patients with anemia associated with lower risk MDS. There is a lack of effective second line and beyond treatments, given that the currently available therapies are only effective in approximately 50% of patients. In addition, there are no oral options available or in late stage development, which could be a meaningful differentiator for roxidustat and potentially translate into a significant commercial opportunity. Moving on to slide 18, in late 2023, subgroup analysis from the Phase III Matterhorn study of Roxadustat in patients with anemia of lower-risk MDS were presented at the American Society of Hematology annual meeting. In patients with anemia associated with lower-risk MDS who entered the trial with a higher transfusion burden, Roxadustat demonstrated a meaningful difference in transfusion independence versus placebo, results that are highly similar to the pivotal trials for two recently approved therapies for anemia associated with lower-risk MDS. On slide 19, we highlight the significant opportunity for Roxidustat in low-risk MDS. Based on other lower-risk MDS development programs, we believe the indication would support an orphan drug designation, which would provide seven years of data exclusivity in the US. This potential exclusivity, combined with an attractive market opportunity and efficient commercial model, provides a significant economic opportunity for further development of Roxidustat in the U.S. We look forward to our FDA meeting planned for the second quarter of 2025, which could pave the way for developing Roxidustat for anemia associated with lower-risk MDS, either on our own or through a partnership. With that, I will now turn the call over to Dave to discuss the company's financials. Dave?

Thank you, Sam. I will first review the FibreGen China transaction details and then provide the company's financial performance for the fourth quarter and full year 2024. Given the announced sale of FibreGen China, our China operations are now reflected as discontinued operations throughout our financials. We will continue to report our China operations in discontinued operations moving forward. On slide 21, we highlight the summary of key financial terms of the transaction. Under the terms of the agreement, Fibrogen will receive an enterprise value of $85 million, plus Fibrogen net cash held in China at closing, estimated to be approximately $75 million, totaling approximately $160 million. The value of Fibrogen net cash in China includes Fibrogen's portion of Falicong net cash, which is the joint distribution entity owned by Fibrogen and AstraZeneca. Importantly, Fibrogen will continue to accrue cash generated in China until the closing of the transaction. The transaction is expected to close by mid-2025, pending customary closing conditions, including regulatory review in China. The transaction does not include the Illuminex license agreement, whose rights will continue to be retained by Fibrogen going forward. This transaction is truly transformative for FibreGen and allows the company to pay down its senior term loan facility with Morgan Stanley tactical value, fully access our cash in China, and extend the company's runway into 2027 to support U.S. development initiatives. Now onto the company's financials for the fourth quarter and full year 2024. For the fourth quarter of 2024, total revenue was $3.1 million. compared to $3.6 million for the same period in 2023. For full year 2024, total revenue was $29.6 million, compared to $46.8 million in full year 2023. In the fourth quarter of 2024, we recorded $0.4 million in development revenue, compared to $2.6 million during the fourth quarter of 2023. For full year 2024, we recorded $1.9 million in development revenue, compared to $18.4 million during full year 2023. In the fourth quarter of 2024, we recorded $2.7 million of drug product revenue compared to $1.1 million during the fourth quarter of 2023. And for full year 2024, we recorded $27.7 million of drug product revenue compared to $18.8 million during full year 2023. Now for full year 2025, we expect total revenue to be between $4 million and $8 million. Now moving down the income statement. Total operating costs and expenses for the fourth quarter of 2024 were $10.3 million compared to $66.3 million for the fourth quarter of 2023, a decrease of $56 million or 84% year over year. Total operating costs and expenses for full year 2024 were $180 million compared to $369.5 million for full year 2023, a decrease of $189.5 million, or 51% year over year. R&D expenses for the fourth quarter of 2024 were $6.9 million, compared to $48.7 million in the fourth quarter of 2023, a decrease of $41.8 million, or 86% year over year. R&D expenses for full year 2024 were $95.7 million compared to $266.5 million in full year 2023, a decrease of $170.8 million or 64% year over year. SG&A expenses for the fourth quarter of 2024 were $8.3 million compared to $16.4 million in the fourth quarter of 2023, a decrease of $8.1 million or 49% year over year. SG&A expenses for full year 2024 were $49.3 million compared to $86.5 million in full year 2023, a decrease of $37.2 million or 43% year over year. During the fourth quarter of 2024, we recorded a net loss from continuing operations of $8.7 million or eight cents net loss per basic and diluted share. as compared to a net loss of $62.5 million or 63 cents per basic and diluted share for the fourth quarter of 2023. During full year 2024, we recorded a net loss from continuing operations of $153.1 million or $1.53 net loss per basic and diluted share as compared to a net loss of $323 million or $3.32 per basic and diluted share for the full year 2023. As we have previously stated, we initiated a significant cost reduction plan in the second half of 2024 to become laser-focused on our FG-3246, FG-3180, and ROC-seduced assets. We have reduced our headcount by approximately 5% in the U.S. We have moved to a virtual work environment after terminating our lease and substantially reduced our operating costs to maximize our cash runway. I am happy to announce that we have completed our restructuring efforts, and the team will continue to work diligently to find operational efficiencies throughout 2025. Now, for full year 2025, we expect our total operating costs and expenses, including stock-based compensation, to be between $70 million and $80 million, which at the midpoint represents a 58 percent reduction from full year 2024. Now, shifting towards cash. As of December 31st, we reported $51 million in cash, cash equivalents and accounts receivable in the U.S. and $121.1 million in total consolidated cash, cash equivalents and accounts receivable when including balances in China. Given that the company will continue to accrue cash from its China operations until the close of the sale transaction, we expect the company to be cash flow positive. on a consolidated basis in the first quarter of 2025. Upon close of the China transaction, we plan to pay off our senior secured term loan with Morgan Stanley tactical value, resulting in a cash outflow of approximately $80 million. This includes the $75 million principal balance, accrued and unpaid interest, and an applicable prepayment penalty. Post the payoff of our MSCV term loan, we expect the company to have cash runway into 2027. Thank you, and I will now turn the call back over to Fain.

Thank you, Dave. To conclude, we believe the sale of Fibrogen China is a transformative transaction for Fibrogen, and we are excited about the next chapter in the company's story. We are confident that the shift to a lean U.S. organization focused on high-value indications in oncology and oncology-related diseases has the potential to create tremendous value for patients and stakeholders alike. With an extended cash runway into 2027, we plan to advance our exciting pipeline in the coming months, initiating the Phase II monotherapy study for FG3246 and FG3180 in MCRPC, and meeting with the FDA to determine the potential development path for Rapsodustat in the treatment of anemia associated with lower-risk MDS. These events will set the stage for the remainder of 2025 and beyond, which include top line results from the Phase II portion of the IST for FG3246 in combination with enzalutamide in the second half of 2025, as well as interim results from the Phase II monotherapy study in mid-2026. In summary, as a leaner and more focused organization, we will continue to execute on our strategic plan with the aim of achieving evaluation that we believe is more reflective of our first-in-class Phase II-ready CD46-targeting ADC and our potential Phase III-ready opportunity in anemia associated with lower-risk MDS bolstered by our strengthened balance sheet and extended cash runway. We look forward to providing further updates to our stakeholders over the coming months. I would now like to turn the call over to the operator for Q&A.

Thank you so much. And as a reminder, to ask a question, simply press star 1-1 on your telephone and wait for your name to be announced. To remove yourself, press star 1-1 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Andy with William Blair. Please go ahead.

Thanks for taking our questions and congratulations on that transformative deal. Got two quick ones for the ADC franchise. So you mentioned about the fertility analysis that's coming up in mid-year 2026. And I'm just curious if you can characterize the level of stringency for that fertility. So in other words, maybe from an investor perspective, you know, would the passing of that futility analysis be a very good sign from an efficacy standpoint? And second one, it's a quick one. I'm just curious. It's not very clear on the clinicaltrials.gov website, but curious when you said, you know, pre-chemo but post-ARPI, what's the qualification for radioligand. Would a patient who had experience with radioligand be eligible for the trial? On the clinical trial, that website only says no radioligand prior, basically within the prior 28 days. And I have a follow-up on MVS. Thank you.

Thanks, Andy, for the questions. Hope you're doing well. I'll answer the the last one first. In terms of maybe set the stage for this post-ARSI pre-chemo setting, we've learned a lot from some of the KOLs in the past several months about what the sweet spot is for an opportunity like FG3246. And with the ARSI's moving into the castration-sensitive phase, we've also learned that, especially at academic centers, you're seeing less of an ARSI switch regimen. So in other words, it is not uncommon for a patient to be treated with one ARSI and then to be switched to another. And I think what we're hearing, especially from the academic centers, is that the incremental benefit of switching from one to another is not that great. And at the same time, patients are desiring to put off chemotherapy for as long a period of time as possible. So we think in this castration-resistant space, post-ARSI, pre-chemo, that's exactly where the trial is designed to recruit patients. And we are allowing patients who have been treated with Plavicto previously, just not within the prior 28 days. So if they have been treated with Plavicto and are no longer responding, then those patients would be eligible to be enrolled in our phase two monotherapy trial. In terms of the utility analysis, we're not going to speak very much about that at this point in time. Just suffice it to say, that we're going to ensure that when we look at the data, and this will be data on 12 patients at each one of the dose cohorts, that the therapy is being appropriately tolerated and that we're not seeing any untoward adverse events. We're also going to be looking at efficacy parameters at that point in time. Clearly, if we're seeing efficacy results combined with safety results that are not favorable to the patient, then that will be an important consideration. But we're not going to go into detail at this point in time in terms of exactly what that futility analysis is.

Great. That's very helpful. And for MDS, so I'm curious about the ability to leverage some of the safety database from RAS-induced deaths prior to prior clinical programs. I'm just trying to get a sense of how big that MDS program would have to be. So I'm just curious if you can speak to the ability to leverage prior clinical results.

Yeah, thanks for that question. I think we'll learn a lot. I know we'll learn a lot when we speak with the FDA next quarter. Anemia associated with lower risk mild dysplastic syndrome, that patient population is very different than the patient population of anemia associated with chronic kidney disease. What we think that, you know, just based upon not only trials that have been done for loose powder sept and a metal staff, but also, you know, a recent phase three trial that just started, we think the trial size would be roughly about 200 patients. And again, we're going to get some feedback from the FDA both in terms of dosing as well as the patient population that we would aim to target, but about 200 patients. And so the previous safety database for Roxadustat and CKD anemia would be informative, but I don't think that instructive relative to this particular patient population. And I think it's pretty apparent that based upon previous trials that there will be some important safety follow-up. So not only looking at transfusion independence in the first you know, 28 weeks of the trial, then looking at the same efficacy parameter over 52 weeks, but then some safety follow-up that would extend beyond 52 weeks as well.

That's very helpful. Thank you so much for taking our questions. Thank you, Andy.

Thank you. Our next question comes from Matthew Keller with HC Wayne White. Please go ahead.

Yeah, good afternoon, everyone. Congrats on the quarter and Thanks for the update. Just two, again, quick questions from us as well. The first one, I was wondering if the recent cost-saving measures that you commented about and really a strong cash balance open up any possibility for possibly some new assets or any possible new indications in the future?

Yeah, Matthew, one more time on that. I couldn't catch the last part of that.

Oh, yeah, no, it's okay. I was wondering with your strong balance sheet and the cost-saving measures that you're leaving open the possibility or if you're considering any new possible assets to add to the pipeline or possible like new indications to consider as well going forward.

Yeah, thanks for the question. Not at this time. You know, we've got a laser focus, as we stated on the call, advancing FGE3246 and FGE3180 into the Phase II monotherapy trial, waiting for the results. of the FG3246 trial in combination with intralutamide and then seeking FDA feedback on the potential to take roxidustat into further development and lower risk MDS anemia. And so that's where we're going to stay focused. We think if we tried to branch, you know, outside of that, it just wouldn't benefit the programs that we have in front of us right now. We need to stay laser focused on those two programs.

Yeah, no, no, totally makes sense. And just the second one, if I may, switching gears to Roxlyn and Yumi at MDS. But I was wondering if you could maybe provide a little more color or highlight maybe what your expectations are, if you have a wish list kind of going into your upcoming meeting with the FDA.

Yeah, that's a great question. I think our wish list would be that, you know, based upon the previous Phase 2-3 trial, the Matterhorn trial, which was conducted where there was a small amount of kind of dose finding work across 24 patients at three different doses, 1.52 and 2.5 mg per gig of roxidustat, eight patients in each one of those three dose cohorts. 2.5 milligrams per kilogram was chosen to be the dose that was then taken in to the phase three portion of the trial. And then there was an algorithm based upon hemoglobin levels that then let the clinician, allow the clinician to further titrate from there with a maximum of 3.5 milligrams per kilogram. So, our, you know, preferred response to the FDA is that we've done the appropriate amount of dose finding work across the, you know, the more than 100 patients that were treated in the phase 2, size 3 trial, and that we would be able to go in right with a 2.5 milligram per kilogram dose, and then not have to do additional dose finding work as part of another phase 2, size 3 trial. That's the That's the preferred approach. That's what our request is going to be. And then in terms of the specific patient population, we'll have a key question that we'll ask the agency on the most appropriate patient population for this particular trial. We desire to do a placebo-controlled trial just because of the fact that by doing a non-inferiority trial versus physician's choice that would be a much larger and much more expensive trial. But the treatment paradigm has changed a bit since we started the Matterhorn trial a few years ago. You've had luspatercept approved and you've had metal stat approved. And so what we're gonna find out from the agency is in this kind of ESA refractory patient population who has been tried on one additional therapy, let's call it luspatercept, we would then like them to be randomized to either Roxaducet or placebo and not have to go through another therapy before then they would be randomized to Roxaducet and placebo. And so it's what we would call the second-slash-third line in lower-risk MDS, and that would allow us to then do a direct comparator versus placebo and size the trial, as I said to Andy's question, with about 200 patients or so.

Yeah, it totally makes sense, and that was very helpful. Thanks again for taking our questions, and congrats again on the quarter. Yeah, thanks, Matt.

Thank you. And this concludes Q&A session. I will turn it back to Tim Wettig for his final remarks.

Thanks, Carmen. And thanks, everybody, for joining us today for our fourth quarter earnings call and your continued interest in Fibrogen. Enjoy the rest of your day. Thank you.

Thank you all who participated in today's conference. You may now disconnect.