FibroGen, Inc

to FibroGen's third quarter 2023 earnings call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising that your hand has been raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. It is now my pleasure to introduce Vice President of Investor Relations, David DeLucia.

Good afternoon, everyone. Thank you for joining today to discuss our third quarter 2023 financial and business results. I'm David DeLucia, Vice President of Corporate FP&A and Investor Relations at FiberGem. Joining me on today's call are Thayne Wedick, our Chief Executive Officer, Juan Graham, our Chief Financial Officer, Dr. John Hunter, our Chief Scientific Officer, and Chris Chung, our Senior Vice President of China Operations. Following our 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 FibroGem. 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 FibroGen'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 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. With that, I would like to turn the call over to Thayne Wettick.

Thanks, Dave, and good afternoon, everyone. Welcome to our third quarter 2023 earnings call. I would like to begin today's call by acknowledging that November is global pancreatic cancer awareness month, a time when we reflect on the importance of raising awareness about pancreatic cancer and the need for continued research, support, and more effective therapies for this devastating disease. On today's call, I will focus our stakeholders on the four strategic pillars that will guide the company into the future. as well as provide an update on our Pamrevimab and Roxidustat assets. Dr. John Hunter, our chief scientific officer, will then review our exciting early stage oncology pipeline. Last, Juan Graham, our CFO, will review the financials, after which we will open the call for your questions. Starting on slide three, FibroGen has four key strategic pillars that we believe offer significant value today. First is Pamrevelmab with upcoming pivotal trial readouts for two pancreatic cancer indications through the first half of 2024. One readout in locally advanced disease and the other in metastatic disease. Pancreatic cancer represents a significant commercial opportunity with substantial unmet need, and Pamrevelmab has demonstrated effect in both preclinical and early clinical studies, which we will detail in a moment. Second is Roxidustat. Roxidustat is approved in over 40 countries around the world. generates significant net revenue and provides fibrogen with material and growing economics through our partnerships with AstraZeneca and Astellas Pharma. Third is our early stage oncology pipeline. We are very excited about the potential of these programs. FG3246 is a first in class potent antibody drug conjugate or ADC for the treatment of metastatic castration resistant prostate cancer. This opportunity also includes the development of an associated pet biomarker diagnostic. In addition to FG3246, we are also undertaking IND enabling activities on two innovative oncology antibodies with the intention of filing INDs and commencing clinical activities in 2024. Fourth is our strong cash position. In the third quarter, we successfully executed on implementation of our company-wide cost reduction plan. now resulting in an expected reduction of total annualized expenses of $120 million, which provides the company a bridge to achieve a number of key milestones across our portfolio. We have taken necessary steps to improve our financial position and will continue to focus on financial discipline. In summary, we believe there are few biotechnology companies of our market cap that have such a compelling mix of commercial, late stage, and early stage assets. When you combine our assets, our strong balance sheet, and the quality of our talented colleagues at Fibrogen, we believe that we have a strong foundation to drive significant shareholder value creation today and into the future. Moving to slide five, Pamrevimab is a novel anti-CTGF human monoclonal antibody in clinical development for the treatment of locally advanced unresectable pancreatic cancer, or LAPC, and metastatic pancreatic cancer. Pamrevimab has been studied in over 1,000 patients across various conditions, has demonstrated dose and exposure-related responses in an early-stage pancreatic cancer trial, as well as a favorable adverse event and safety profile. On slide six, and before we dive into the pancreatic cancer data and opportunity, I would like to provide a recap of recently announced Pamrevimab results. In August, we reported top-line data from our Phase III Lelantos II study. a placebo-controlled trial of Pamrelvomab for the treatment of ambulatory patients with DMD on background corticosteroids. The study did not meet the primary endpoint of change in the North Star Ambulatory Assessment total score from baseline to week 52. FibroGym would like to thank the patients, caregivers, and clinical trial investigators for their dedication to participating in this important study, which contributes toward the understanding of this devastating disease. Looking ahead, We anticipate upcoming results from two Pamrelvomab trials in pancreatic cancer. We expect results from the LAPAS phase three study in locally advanced disease in the first quarter of 2024, and we expect results from the Pancreatic Cancer Action Network's Precision Promise Registrational Adaptive Platform Trial, evaluating Pamrelvomab in both first-line and second-line metastatic pancreatic cancer in the first half of 2024. I would now like to discuss the Pamrevimab opportunity in pancreatic cancer in more detail starting on slide eight. Pancreatic cancer represents one of the largest unmet needs in oncology with an annual incidence of nearly half a million patients across the major regions combined. This includes approximately 60,000 PDEC patients in the United States. There is an overall five-year disease-free survival rate of only 12.5%. and for metastatic cancer, rates are as low as 3%. On slide 9, we provide an overview as to why we believe Pamrevimab can provide benefits to patients diagnosed with pancreatic cancer. Based on preclinical data, CTGF plays an important role in the growth and progression of pancreatic tumors. Mouse tumor studies have shown that Pamrevimab can have both direct antitumor effects and effects on the surrounding stroma. providing a strong clinical rationale for use in both locally advanced and metastatic pancreatic cancer. Given the upcoming Phase III readouts, we would like to remind investors of what we believe are compelling preclinical and early clinical data that informed our decision to move Pamrevomab forward in pancreatic cancer. On slide 10, Pamrevomab in combination with gemcitabine in a KPC mouse model slowed tumor growth, decreased metastatic burden, inhibited formation of acetates or buildup of fluid in the abdomen, and substantially improved survival. On slide 11, the same mouse model also provided a mechanistic rationale for Pamrevlumab's beneficial effect on animal survival. Pamrevlumab as a monotherapy and in combination with gemcitabine made tumor cells more susceptible to chemotherapy-induced cell death or apoptosis through quantitative reduction in XIAP a protein involved in apoptotic resistance and promotion of cell survival. Moving to slide 12, we would like to reference the data from our open-label dose escalation phase 1-2 trial in patients with locally advanced stage 3 or metastatic stage 4 pancreatic cancer. Most of these 75 patients were, in fact, metastatic, and only 9 had locally advanced disease. Pamivirumab was evaluated in combination with gemcitabine, and erlotinib as first-line therapy. An important observation in the study was that clinical benefit was observed at higher drug exposure levels. Once drug plasma levels reached a trop threshold of 150 micrograms per mL, a number of important results were found. The most notable result in this study was that one-year survival was 37% for patients who had circulating comrevimab levels of 150 micrograms per mL or higher versus 11% for those with lower plasma levels. These results in the higher dose cohort patients with plasma drug levels above the 150 micrograms per mL threshold included improved median overall survival and improved median progression-free survival. Moving to slide 13, pivotal trials are being conducted with Pamrelvimab in both locally advanced and metastatic patients. These patients represent almost 90% of all diagnosed pancreatic cancer patients today, giving Pamrevelmab a potential opportunity to treat a vast majority of patients across this devastating disease. On slide 14, we provide an overview of the global Phase III LAPIS trial, a double-blind, placebo-controlled trial in 284 patients with locally advanced unresectable pancreatic cancer, comparing Pamrevelmab to placebo in combination with standard-of-care chemotherapy. The primary endpoint is overall survival, and we expect top-line data from this study in the first quarter of next year. On slide 15 is an overview of the Pancreatic Cancer Action Network's PRECISION PROMISE trial. This is a Phase 2-3 registrational study that is being executed at the top pancreatic centers in the United States. Like the LAPAS trial in locally advanced disease, the primary endpoint of the PRECISION PROMISE trial is overall survival. Pamrevelmab is being evaluated in both first and second line therapy for metastatic disease and was the first experimental treatment arm in the Precision Promise platform trial to be evaluated in the first line metastatic setting. Moving to slide 16, we show a snapshot of both Pamrevelmab registration of phase three studies. One important difference between the two studies is the dosing regimen of the Precision Promise study. Pamrevomab is dosed in 28-day treatment cycles until progression or discontinuation, which is distinct from lapis in which Pamrevomab was delivered in a neoadjuvant setting and where it was dosed for up to six months. We believe the ability to dose patients until disease progression in the metastatic setting provides a potential opportunity to amplify clinically meaningful increases in overall survival driven by those patients benefiting from Pamrevomab treatment. On slide 17, we reviewed the U.S. commercial opportunity for Pemrevilmab in pancreatic cancer. There have been limited treatment advances over the last two decades in both locally advanced and metastatic diseases with immuno-oncology therapies providing benefit to a small subset of metastatic patients. Using straightforward assumptions, the total addressable market for pancreatic cancer in the U.S. is a multi-billion dollar commercial opportunity for Pemrevilmab if it can demonstrate a significant improvement in overall survival in either locally advanced or metastatic patients. In fact, metastatic pancreatic cancer alone represents a larger market opportunity in the U.S. for pamrevilumab than we were forecasting for IPF. Moving on to roxidustat on slide 19, I would like to provide a recap of recently announced roxidustat results, as well as review our upcoming milestones. In May, we announced positive topline data from our Phase III clinical study of Roxadustat for the treatment of anemia in patients receiving concurrent chemotherapy treatment for non-myeloid malignancies in China. Roxadustat demonstrated non-inferiority compared to recombinant erythropoietin alpha on the primary endpoint of change in hemoglobin level from baseline to the average level during weeks 9 through 12. These data were recently presented in an oral presentation at the ESMO Congress 2023 in Madrid on October 21st. I'm excited to announce that in July, our supplemental new drug application or SNDA for roxidustat in patients with chemotherapy induced anemia has been accepted by the China Health Authority, and we continue to expect an approval decision in mid 2024. Upon approval, FibroGen will receive a milestone payment from AstraZeneca. We believe this indication could represent a meaningful incremental net revenue opportunity on top of the anemia of CKD indication. Moving now to slide 20, Roxidustat for anemia of chronic kidney disease continues to perform extremely well in China. Third quarter total Roxidustat net sales in China by Fibrogen and the distribution entity jointly owned by Fibrogen and AstraZeneca was $77.1 million compared to $59 million in the third quarter of 2022, an increase of 31%. This growth was driven by an increase in volume of 37%. Fibrogen's portion of Roxadustat net product revenue in China was $29.4 million for the third quarter on a U.S. GAAP basis, compared to $17.4 million in the third quarter of 2022, an increase of 69%. Moving to slide 21, Roxadustat continues to expand its category leadership and brand value share in China, rising to 42% in the most recent three-month period ending in August of 2023. The potential addition of the chemotherapy-induced anemia indication would create an additional catalyst to both continued share and volume growth of Roxidustat in China. Given that there have been several generic applications filed in China, I would like to briefly touch on the generic market more broadly in China and the exclusivity of Roxidustat. The impact of a generic approval and launch in China is meaningfully different than in the U.S. market. generic players face lead time and execution risk of market adoption after approval, as they need to be admitted into individual hospital formularies one at a time. Originator products do not experience a meaningful deterioration in business until at least four or more generic products are approved. Even then, originator products in China have historically been able to maintain a stream of net revenues and profits after generics enter the market. Our composition of matter Patents expire in June of 2024, and we do not expect meaningful deterioration of the ROXADUSTAT business in the near term. In addition to the continued outstanding performance of ROXADUSTAT in China, the ROXADUSTAT launch in Europe is accelerating, showing robust quarter-over-quarter growth. We expect this growth to continue to accelerate given the strong competitive position of ROXADUSTAT. ROXADUSTAT is the only HIF-PHI indicated in the EU for the treatment of anemia of CKD in both non-dialysis and dialysis patients, and with GSK's decision to withdraw the MAA for Depra-Dustat, combined with market exclusivity for Roxidustat beyond 2030, Roxidustat is well-positioned to continue its growth and market leadership throughout this decade. I will now hand it off to John Hunter, our CSO, to cover our early stage pipeline. John?