FibroGen, Inc

As a reminder, today's program is being recorded. And now I'd like to introduce your host for today's program, Gaia Shamus from LifeSci Advisors. Please go ahead.

Thank you, Jonathan. Good afternoon, everyone. Thank you for joining us today to discuss FibroGen's second quarter 2025 financial and business results. I'm Gaia Shamus with LifeSci Advisors. Joining me on today's call are Fain Weddy, Chief Executive Officer, David DiLuccia, Chief Financial Officer, and Carol Gedham, Product Team Lead for FG3246, FG3180, and Roxadustat. 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, collaboration with AstraZeneca and Astellas, financial guidance, the initiation, enrollment, design, conduct, and results of clinical trials, regulatory strategies and potential regulatory results, 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 FibroGen's filing 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 company's financial results and business updates and a webcast of today's conference call can be found on the investor section of FibreGen website at www.fibregen.com. With that, I would like to turn the call over to the CEO, Zane Weddick. Zane?

Thank you, Gaia. Good afternoon, everyone, and welcome to our second quarter 2025 earnings call. On today's call, I will provide an update on our ongoing efforts to transform FibreGen with a focus on our three main priorities, the sale of Fibrogen China, the advancement of our lead asset, FG3246, a potential first-in-class antibody drug conjugate targeting CD46 and its companion PET imaging agent in metastatic castration-resistant prostate cancer, and the crystallization of the pathway forward for Roxidustat for the treatment of anemia due to lower-risk mild dysplastic syndromes. 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 update you on our near-term strategic priorities, starting with the sale of Fibrogen China to AstraZeneca. As we've stated previously, this is a truly transformative transaction for Fibrogen, as it 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 cash held in China. At the time of the announcement in February, the total consideration for the sale was expected to be approximately $160 million, which included an equity value of $85 million and expected net cash in China of approximately $75 million upon the close of the transaction. During our Q1 earnings call in May, we increased the guidance of our expected net cash in China by $25 million. We are pleased to share that we now expect the total consideration to be approximately $210 million, which is a $50 million increase from our initial guidance and a $25 million increase from our Q1 guidance due to greater than expected net cash in China at closing. Importantly, this increase in cash further extends the company's cash runway into 2028. The review by the China State Administration of Market Regulation is ongoing, and we expect the transaction to be approved and closed this quarter. Second, we remain hyper-focused on advancing FG3246 and FG3180 in metastatic castration-resistant prostate cancer, or MCRPC, where we continue to progress trial initiation activities and are on track to begin the Phase II monotherapy trial of FG3246 and FG3180 in the third quarter of this year, consistent with the timing of the sale of FibroGen China. Third, we had a positive Type C meeting with the FDA in mid-July and have received formal minutes from the agency. We have alignment on a number of the key elements of a pivotal Phase III trial for Roxidustat for the treatment of anemia associated with lower-risk mild dysplastic syndromes in patients with high transfusion burden. The Type C meeting request was based on the results of a post hoc subgroup analysis from the Matterhorn Phase III trial where Roxiducet demonstrated a meaningful effect in patients with a high transfusion burden at baseline. This group of patients is in need of and would benefit from a convenient and durable treatment. We are working diligently to finalize the study design for the Phase III trial and plan to submit the final protocol to the FDA in the fourth quarter of this year. Ultimately, we remain confident that our refined focus, simplified capital structure, and multiple near-term catalysts across both clinical programs position us to create value for both patients and shareholders in the near term. I will now provide an overview of our FG3246 and FG3180 programs in MCRPC. Slide five highlights the high unmet need in late stage prostate cancer. Approximately 290,000 men are diagnosed with prostate cancer each year in the US. 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. We estimate this translates into a total addressable market of over $5 billion in annual sales in the US alone. FG3246 could be this new treatment option. On slide six, we highlight the novelty of our target, a tumor-selective epitope of CD46, which has several distinguishing features. It is upregulated during tumorigenesis and helps tumors evade complement-dependent cytotoxicity Importantly, the expression of CD46 is also 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. As you can see in the graph on the right, CD46 is highly expressed in MCRPC tissues with lower interpatient variability and higher median expression compared with PSMA, making it an attractive therapeutic target. Turning to slide seven, FC3246 is our potential first-in-class ADC in development for metastatic castration-resistant prostate cancer. The ADC combines the YS5 antibody with an MMAE payload to specifically target the tumor-selective epitope of CD46. FC3246 represents an androgen receptor agnostic approach, clinically differentiating it from other prostate cancer treatments currently in development, most of which target PSMA. The 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 a future Phase III trial, but 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. The study included 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, a mean radiographic progression-free survival of 8.7 months was observed. In addition, there was an overall response rate of 20% confirmed by RESIST 1.1, and PSA reductions of greater than 50% were observed in 36% of patients. Adverse events were consistent with those observed with other MMAE-based ADC therapies. The full results of the study were published earlier this year in the Journal of Clinical Oncology. And altogether, in the phase one monotherapy study, FG3246 showed what we believe to be compelling clinical activity. Putting the results into context on slide nine, when we look across the RPFS results, a recognized regulatory endpoint in prostate cancer treatment of FG3246 in its phase one study versus other comparable early stage studies, 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 these RPFS results. On slide 10, we highlight previously reported preliminary efficacy data from the Phase 1b portion of the ongoing investigator-sponsored combination study with enzalutamide. These interim results included data on 17 biomarker unselected patients, 70% of which were pretreated with at least two prior ARSIs. In addition to establishing the Phase II dose of FG3246, this IST also demonstrated an encouraging 10.2 months of radiographic progression-free survival, with PSA declines observed in 71% of available patients. We remain on track to report the Phase II topline results in the fourth quarter of 2025, which will also include data on CD46 expression in patients treated with FG3180, our PET biomarker, during the Phase II portion of the IST. On slide 11, there is a cross-trial 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. While, again, we cannot make direct comparisons to these trials due to differences in study design and previous prostate cancer treatments, we believe FG3246 shows competitive RPFS results in the monotherapy and the combination therapy settings. Based on these results, slide 12 highlights the Phase II monotherapy dose optimization trial design that will commence in the third quarter this year. We plan to enroll 75 patients in the post-ARSI pre-chemo setting across three dose levels to determine the optimal dose for phase three based on efficacy, safety, and PK parameters. It is important to note that the FG3180 will be an integral 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 use of GCSF as primary prophylaxis to mitigate against grade three or greater neutropenia commonly seen with MMAE payloads and experienced in the phase one monotherapy trial. The addition of GCSF is designed to reduce dose reductions and interruptions and may enable a better tolerated and more consistent treatment with the ADC in the phase two. An interim analysis of the phase two trial is planned for the second half of 2026 and we'll include efficacy, safety, PK, and exposure response data that we will report as they become available, given the open-label design. Slide 13 articulates why we're so optimistic about the potential for our Phase II study to further fund the efficacy in our Phase I study. We believe there are three factors that could drive an improved RPF relative to the 8.7 months that was observed in the Phase I monotherapy trial. leveraging the preliminary evidence of an exposure-response relationship from the Phase I dose escalation and expansion study, thereby enabling the focus of the Phase II study on three of the highest doses from the Phase I trial. Second, utilizing primary prophylaxis, the GCSF, to potentially mitigate against neutropenia, which could enable more consistent exposure to the ADC with fewer dose interruptions or adjustments early in the course of treatment. This could consequently extend duration of therapy and potentially enhance the efficacy of the ADC. Third, enrolling healthier patients in earlier lines of therapy versus the median by prior lines of therapy in the Phase I trial. Together, we believe that these design elements have the potential to improve upon the Phase I results and achieve an RPFS of 10 months or greater, which we believe is the benchmark for commercial competitiveness. Slide 14 depicts our long-term development strategy for FG3246 and FG3180, which in our view provides important optionality in prostate cancer. We have a robust phase two monotherapy trial in the post-ARSI pre-chemo setting in MCRPC to further build upon the compelling 8.7 months of RPFS seen in the phase one study. In addition, The Phase II 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 registration pathways, as FG3246 will be evaluated in multiple lines of therapy, in monotherapy and or in combination with an ARSI, and in an all-comers population or patients with high expression of CD46. Slide 15 highlights the recent and upcoming catalysts for the FG3246 and FG3180 program. We are on track to initiate the Phase II monotherapy trial this quarter in which all patients will be treated with FG3180 to enable assessment of both its diagnostic performance and the potential correlation between CD46 expression and response to FG3246. Additionally, in the fourth quarter, we expect the top-line results from the Phase II IST of FG3246 and enzalutamide, as well as data from FG3180. As I previously mentioned, we expect to report interim results from the Phase II monotherapy trial in the second half of 2026. To summarize, on slide 16, FG3246 targets a novel epitope on prostate cancer cells with potential first-in-class given that there are no other CD46-targeted projects in clinical development. Targeting CD46 with FG3246 has already demonstrated promising early efficacy signals with an acceptable safety profile both in monotherapy and combination settings. We are excited for the upcoming milestones and look forward to updating you on the program as the studies progress. Turning to roxidustat. Slide 18 highlights the unmet need and the potential for Roxidustat in patients with anemia associated with lower risk MDS. Current treatments are only effective in approximately 50% of patients. With no oral options currently on the market or in late stage development, a significant opportunity for Roxidustat exists to offer a potential new treatment that is durable with convenient oral administration to patients in the second line and beyond setting. Moving to slide 19. I would like to elaborate on the substantial opportunity that exists in lower-risk MDS. Based on other lower-risk MDS development programs, we believe the indication would support an orphan drug designation, which, if approved, would provide us with seven years of data exclusivity in the US. This potential exclusivity, combined with an attractive market opportunity and efficient commercial model, represents a substantial economic opportunity. Taken together, we believe these market dynamics could potentially translate into a substantial commercial opportunity for Roxadustat in anemia associated with lower-risk MDS. Moving to slide 20, I would like to highlight data from a post-hoc analysis in a subgroup of patients with anemia of lower-risk MDS who entered the Phase III Matterhorn study of Roxadustat with a high transfusion burden. In this analysis, we used the international working group definition for high transfusion burden of four or more RBC units in two consecutive eight-week periods. This definition is widely accepted by the scientific community and will also be used as the inclusion criteria in our proposed phase three trial. As you can see, roxidustat showed a meaningful difference with 36% of patients on roxidustat achieving transfusion independence for greater than or equal to 56 days versus only 7% in the placebo group with a nominal p-value of 0.041. These results are highly similar to the pivotal trial results for two recently approved therapies for anemia associated with lower risk MDS. As a reminder, in the post-hoc analysis that was previously presented at ASH in late 2023, and which we have highlighted on previous calls, higher transfusion burden was defined as two or more units in four weeks. In that subgroup, 36.1% of patients on Roxazustad achieved transfusion independence versus 11.5% on placebo. The consistency of results from both of these post-hoc analyses give us confidence that roxidustat can demonstrate a meaningful treatment effect in a phase three trial focused on the high transfusion burden population. We had a positive type C meeting with the FDA in July and have received the formal meeting minutes from the agency. We have aligned on important design elements for the pivotal phase three trial summarized on slide 21. As I alluded to in the previous slide, The study population will include patients requiring four or more RBC units in two consecutive eight-week periods prior to randomization who are refractory to and tolerant to or ineligible for prior erythropoiesis-stimulating agents. We also agreed with the FDA on the dose regimen, including the starting dose of 2.5 milligrams per kilogram, and on the management of potential thrombotic risk through trial eligibility, dose modification, and discontinuation criteria. We are currently evaluating 8-week and 16-week RBC transfusion independence as the potential primary endpoint for the trial. Based on the feedback we received from the FDA, the team is actively working on finalizing the pivotal Phase III study design, and we anticipate submitting the final protocol for the Phase III trial, evaluating Roxidustat for patients with lower-risk MDS and anemia with high transfusion burden to the FDA in the fourth quarter of 2025. In the meantime, we continue to explore our clinical development options, which include maintaining Roxadustat as a wholly owned asset and running the phase three trial on our own or partnering the program. We have initiated outreach and will ultimately choose the path that we believe is in the best interest of shareholders. With that, I will now turn the call over to Dave to discuss the company's financials. Dave.