Q4 2024 FibroGen Inc Earnings Call

In This Article:

Participants

Joanne Geller; Investor Relations; LifeSci Advisors

Thane Wettig; Interim Chief Executive Officer, Chief Commercial Officer; FibroGen Inc

David Delucia; Vice President, Corporate FP&A and Investor Relations; FibroGen Inc

Andy Hsieh; Analyst; William Blair & Co LLC

Matthew Keller; Analyst; H.C. Wainwright & Co LLC

Presentation

Operator

Hello, everyone, and welcome to the FibroGen fourth quarter and full year 2024 earnings conference call. (Operator Instructions) Please be advised that today's conference is being recorded.
Now it's my pleasure to turn the call over to Joanne Geller. The floor is yours.

Joanne Geller

Thank you, operator. Good afternoon, everyone. Thank you for joining today to discuss FibroGen’s fourth quarter and full year 2024 financial and business results. I’m Joanne Geller from LifeSci Advisors. Joining me on today’s call are Thane Wettig, our Chief Executive Officer; and David DeLucia, 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 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-ks 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 Investors section of FibroGen's website at www.fibergen.com.
With that, I'd like to turn the call over to our CEO, Thane Wettig. Thane?

Thane Wettig

Thank you, Joanne. Good afternoon, everyone, and welcome to our fourth quarter and full year. 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 US pipeline opportunities, which includes the exciting prospects for FG-3246 and FG-3180, our potential first-in-class antibody drug conjugate targeting CD46, and our PET imaging agent in metastatic castration-resistant prostate cancer, and for Roxadustat in the treatment of anemia, due to lower risk mild dysplastic syndrome. Then David DeLucia, our CFO, will review the financials, after which we will open the call for your questions.
On slide 3, I would like to highlight the strategic priorities for our company. 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 FG-3246 and FG-3180 in mCRPC remains a key priority. In the second quarter of 2024, we shared important data from two Phase 1 studies, highlighting the potential of FG-3246 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 roxadustat 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 as well to create value for shareholders now and in the future. I will now provide a brief overview of our FG-3246 and FG-3180 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 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 with a total addressable market of over $5 billion in annual sales. FG-3246 could be this new treatment option.
Turning to slide 6, 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 abate complement dependent cytotoxicity. The CD46 epitope is highly expressed in mCRPC tissues, with lower inter patient 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 over expressed 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 7, FG-3246 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. FG-3246 represents an androgen receptor agnostic approach, clinically differentiating it from other prostate cancer treatments currently in development.
A companion PET imaging agent, FG-3180, utilizes the same YS5 targeting antibody as FG-3246 and is also under clinical development. In preclinical studies, the PET imaging agent has demonstrated specific targeting of an 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 3 portion of the clinical development program, it would also enable differentiation of FG-3246 in the prostate cancer treatment paradigm. In addition, FG-3180 could represent an important commercial opportunity as a companion diagnostic to FG-3246, similar to the existing PSMA PET agents.
Slide 8 recaps the top line results from the Phase 1 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 FG-3246.
In the efficacy evaluable population of 40 patients, we observed a median radiographic progression free survival of 8.7 months, overall response rate of 20% confirmed by RECIST 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 1 monotherapy trial has been submitted and we anticipate publication soon.
On slide 9, we highlight the performance of FG-3246 in its Phase 1 study versus other comparable early stage studies. As highlighted on the previous slide, the Phase 1 study of FG-3246 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 ARSIs.
In addition to establishing a Phase 2 dose of FG-3246, the IST also demonstrated an encouraging preliminary estimate of 10.2 months of radiographic progression-free survival with PSA declines observed in 71% of evaluable 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 FG-3180, our PET biomarker during the Phase 2 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 FG-3246 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 and previous prostate cancer treatments, we are encouraged that FG-3246 demonstrates what we believe to be competitive rPFS results.
Slide 12 highlights the Phase 2 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 3 based on efficacy, safety, and PK parameters. It is important to note that FG-3180 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 G-CSF, which is intended to mitigate adverse events associated with neutropenia commonly seen with MMAE payloads. The addition of G-CSF 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 FG-3246 and FG-3180, which we believe provides significant optionality in prostate cancer. We have a robust Phase 2 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 1 monotherapy study. The Phase 2 monotherapy trial is designed to select the optimal dose for Phase 3 based upon the benefit risk profile from this Phase 2 trial.
We believe there are three factors that could drive rPFS even higher than was observed in the Phase 1 monotherapy trial. First, preliminary evidence of an exposure response relationship, which allows us to focus our Phase 2 study on three of the highest tolerated doses from the Phase 1 dose escalation and expansion study.
Second, utilizing primary prophylaxis with G-CSF 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 five prior lines of therapy in the Phase 1 trial. In addition, this study will explore the correlation between CD46 expression and response to the ADC, potentially validating FG-3180 as a predictive patient selection biomarker in future studies.
We are confident that our development pathway for FG-3146 unlocks sequential or parallel registrational pathways as FC-3246 will be evaluated in multiple lines of therapy, in monotherapy or in combination with an ARSI and in an all comers population or patients with high expression of CD46.
Slide 14 shows the recent and upcoming catalyst for the FG-3246 program. We have potential value inflection points in the near term, with the anticipated initiation of the Phase 2 dose optimization study in mCRPC by mid-2025, and the top line results from the Phase 2 portion of the combination study with enzalutamide, which are expected in the second half of 2025.
To summarize on slide 15, FG-3246 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 roxadustat 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 roxadustat and potentially translate into a significant commercial opportunity.
Moving on to slide 18, in late 2023, subgroup analysis from the Phase 3 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 roxadustat in lower 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 roxadustat in the US. We look forward to our FDA meeting planned for the second quarter of 2025, which could pave the way for developing roxadustat 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?