FibroGen (FGEN) 12 Nov 242024 Q3 Earnings call transcript

Good day, and welcome to the FibroGen, Third Quarter 2024 Earnings Conference Call. All participants will in in a listen-only mode. [Operator Instructions]. Please note this event is being recorded. I would now like to hand the call over to David DeLucia, Vice President of Investor Relations. Please go ahead.

Good afternoon, everyone. Thank you for joining today to discuss our third quarter 2024 financial and business results. I'm David DeLucia, Vice President of Corporate FP&A and Investor Relations at FibroGen.

Joining me on today's call are Thane Wettig, our Chief Executive Officer; Juan Graham, our Chief Financial 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 FibroGen. Such statements may include, but are not limited to, our collaborations with AstraZeneca and Astellas, financial guidance, the initiation, enrolment, 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 Investors section of FibroGen's website at www.fibrogen.com. With that, I would like to turn the call over to our CEO, Thane Wettig.

Thank you, Dave. Good afternoon, everyone, and welcome to our third quarter 2024 earnings call. On today's call, I will highlight our current strategy for the company and the exciting opportunity for FG-3246 and FG-3180, our first-in-class antibody drug conjugate targeting CD-46 and our PET imaging agent in metastatic castration-resistant prostate cancer. I will also highlight the continued strong performance of Roxadustat in China and the potential for Roxadustat in development for the treatment of anemia due to lower-risk myodysplastic syndrome. Then Juan Graham, 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 pillars for our company.

First, advancing FG-3246 and FG-3180 in mCRPC remains a key priority. In the second quarter of this year, we shared important data from 2 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.

Second, Roxadustat continues to demonstrate very strong performance in China, generating significant net revenue and positive cash flow with robust year-over-year revenue and volume growth. Thanks to this impressive performance, we are reiterating our guidance of FibroGen's full year net product revenue under U.S. GAAP to be between $135 million and $150 million and raising the bottom end of our full year guidance for Roxadustat net sales in China to $330 million to $350 million.

In addition, we anticipate an approval decision from the China authorities in early 2025 for chemotherapy-induced anemia, which, if approved, would represent a meaningful growth opportunity on top of the substantial revenue generated by Roxadustat in anemia associated with chronic kidney disease. If approved, FibroGen will receive a $10 million milestone payment from our China partner, AstraZeneca.

Third, we have a number of partnering opportunities for our remaining pipeline. Regaining the rights to roxadustat from AstraZeneca in the U.S. and ROW, excluding China and South Korea, enables us to pursue internal or external development of certain indications with high unmet need, such as anemia in patients with lower-risk myelodysplastic syndrome. Moreover, we continue to seek partnership opportunities for our early oncology pipeline of the Phase 1-ready FG-3165, an anti-galectin-9 antibody and FG-3175, an anti-CCR8 antibody.

Lastly, due to our significant U.S. cost reduction efforts and the wind down of the pamrevlumab development program, FibroGen exited the third quarter in a solid cash position with $160 million in cash, cash equivalents and accounts receivable.

Assuming additional repatriation of cash from our China operations, we expect our cash, cash equivalents and accounts receivable to fund operating plans into 2026. Altogether, we are confident that our refined focus, along with our strong foundation, position us 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 U.S. Of these, there are 65,000 drug-treatable patients where the cancer is metastasized and become castrate resistant, resulting in a GRI 5-year survival rate of approximately 30%. There remains a significant opportunity for new treatments that can extend survival for these men. FG-3246 could be this new treatment option.

Turning to Slide 6. FG-3246 is a potential first-in-class ADC in development for mCRPC with a novel antibody YS-5, which binds to a tumor-selected epitope of CD-46. CD-46 and the specific CD-46 epitope have several distinguishing features. CD-46 is upregulated during tumor genesis and helps tumors evade complement-dependent cytotoxicity. The CD-46 epitope is highly expressed in mCRPC tissues with lower intra-patient variability and higher median expression compared with PSMA as depicted in the graph in the lower right-hand portion of the slide. This expression 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 CD-46 epitope is also overexpressed in colorectal cancer and other solid tumors. A companion PET imaging agent, FG-3180, utilizes the same targeting antibody as FG-3246 and is also under clinical development. In preclinical studies, the PET imaging agent has demonstrated specific targeting of and uptake by CD-46 positive tumor cells. Slide 7 highlights the importance of the companion PET imaging agent, FG-3180, to the development pathway for FG-3246. 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, would also enable differentiation of FG-3246 in the prostate cancer treatment landscape.

In addition, FG-3180 could represent an important commercial opportunity as a companion diagnostic to FG-3246. Slide 8 recaps the top line results from the Phase 1 monotherapy study and the Phase 1b portion of the investigator-sponsored study of FG-3246 in combination with enzalutamide, both of which were reported in the second quarter of 2024. The completed monotherapy study included a total of 56 mCRPC patients, who were biomarker unselected and were heavily pretreated, receiving a median of 5 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 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 acceptance and publication in the coming months.

Following our recent discussion with the FDA regarding the FG-3246 development program, we are preparing to initiate the Phase 2 monotherapy trial of FG-3246 in the first quarter of 2025. Interim results of the Phase 1b portion of the investigator-sponsored combination study with enzalutamide that is currently being conducted at UCSF were reported at ASCO in June of this year. These interim results included data on 17 biomarker unselected patients, 70% of which were pretreated with at least 2 prior ARSIs.

In addition to establishing the Phase 2 dose of FG-3246, the IST also demonstrated an encouraging preliminary estimate of rPFS of 10.2 months with PSA declines observed in 71% of evaluable patients. The trial remains on track for top line results in the first half of 2025 and will also include CD-46 expression data on patients screened with FG-3180, our PET biomarker during the Phase 2 portion of the IST. On Slide 9, we depict the comparison of the initial results from the monotherapy trial in heavily pretreated patients and the combination trial that show an impressive rPFS versus the existing FDA-approved standard of care in the mCRPC setting.

While we cannot make direct comparisons to these trials due to differences in things such as study design and previous treatments, we are encouraged by these rPFS results.

Moving to Slide 10. We would like to share the Phase 2 dose optimization trial design based on our discussion with the FDA. We plan to enroll 75 patients across 3 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 also be a part of the study as we seek to demonstrate the correlation between CD-46 expression and response to the ADC in this all-comers population. One other important design element is the primary prophylaxis with G-CSF to mitigate adverse events associated with neutropenia commonly seen with ADCs containing an MMAE payload. The addition of G-CSF may enable a better tolerated and more consistent treatment, thereby extending duration of therapy with FG-3246 and potentially enhancing efficacy measures such as rPFS. On Slide 11, we highlight the recent and ongoing studies for FG-3246 and FG-3180.

As I mentioned earlier, we are expecting additional data for FG-3180, our PET imaging agent for multiple studies being run at UCSF, including the Phase 1 imaging development study, which was recently upsized as well as the combination trial with enzalutamide. Slide 12 shows the recent and upcoming catalysts for the FG-3246 program.

As mentioned earlier, we had a productive meeting with the FDA regarding the FG-3246 development pathway and received guidance for the Phase 2 trial design highlighted a few slides earlier.

In addition, IND submissions for FG-3246 and FG-3180 are planned this quarter and next quarter, respectively.

We have potential value inflection points in the near term with the anticipated initiation of the Phase 2 dose optimization study in mCRPC in the first quarter of 2025 and the top line results from the Phase 2 portion of the combination study with enzalutamide, which are expected in the first half of 2025. To summarize on Slide 13, 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 combination settings.

We are excited for the upcoming milestones and look forward to updating you on the program as the studies progress.

Moving now to Slide 15. Roxadustat for anemia of chronic kidney disease continues its robust performance in China.

Third quarter total Roxadustat net sales in China by FibroGen and the distribution entity jointly owned by FibroGen and AstraZeneca totaled $96.6 million, compared to $77.1 million in the third quarter of 2023, an increase of 25%, driven by an increase in volume of 34%. FibroGen's portion of Roxadustat net product revenue in China was $46.2 million for the third quarter on a U.S. GAAP basis, compared to $29.4 million in the third quarter of 2023, an increase of 57%.

Moving to Slide 16. Roxadustat continued its category leadership and brand value share in China, maintaining a 45% share in the most recent 3-month period ending in August of 2024. The potential approval of the chemotherapy-induced anemia indication early next year would provide an important new treatment alternative for patients with CIA, be a meaningful addition to the Roxadustat business in China and will trigger a $10 million milestone payment from AstraZeneca.

Given that there have been several generic applications filed and 2 applications approved in China, I would like to reiterate that the impact of a generic approval and launch in China is meaningfully different than in the U.S. Generic players face lead time and execution risk of market adoption after approval as they need to be admitted into individual hospital formularies one listing at a time. Therefore, originator products do not experience a meaningful deterioration in revenue until they are subjected to volume-based purchasing, which only occurs after at least 4 generic products are approved and the government includes the originator in the BBP process. Even then, originator products in China have historically maintained a stream of net product revenues and profits after generics enter the market. Despite the expiration of our composition of matter patents in June of this year, we do not expect meaningful deterioration of the Roxadustat business in the near term.

In addition to the exceptional performance of Roxadustat in China this quarter, Roxadustat penetration in Europe continues to increase, showing quarter-over-quarter growth.

We expect this growth to continue given the fact that Roxadustat is reimbursed in all EU 5 countries, is the only HIF-PHI indicated in the EU for the treatment of anemia of CKD in both non-dialysis and dialysis patients and has exclusivity until 2036, positioning it for continued growth and hip market leadership over the next decade plus.

Now to Slide 17. We announced earlier this year that we regained all U.S. and ROW Roxadustat rights from AstraZeneca with the exception of South Korea, while the China collaboration agreement remains in place. Regaining the rights to Roxadustat in the U.S. allows us to pursue Roxadustat development opportunities with potential partners or on our own in indications such as anemia associated with lower-risk myelodysplastic syndromes. Slide 18 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 the currently available therapies are 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 significant commercial opportunity.

Moving on to Slide 19. 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 2 recently approved therapies for anemia associated with lower-risk MDS. Based on these results, we believe that Roxadustat represents an important potential therapy for patients with anemia associated with lower-risk MDS. Therefore, we are currently evaluating options for Roxadustat to determine the best path for continued development with the aim of realizing additional value for Roxadustat in this high-value indication. I will now turn the call over to Juan to discuss the company's financials. Juan?

Thank you, Thane. I will focus my remarks with a revenue summary for the third quarter of 2024, subsequently providing financial performance details of our China business for the quarter. And finally, I will wrap up with operating expense results and our cash outlook. I also want to remind everyone that more information on our financial results is available in our press release and our recently filed 10-Q.

For the third quarter of 2024, total revenue was $46.3 million, compared to $40.1 million for the same period in 2023, an increase of 15% year-over-year. We recorded $46.2 million of net product revenue for roxadustat sales in China compared to $29.4 million in the third quarter of 2023, representing an increase of 57% year-over-year. In Q3 2024, we recorded $0.4 million in development revenue compared to $6.8 million during the third quarter of 2023.

As mentioned in prior quarters, after the termination of the AstraZeneca U.S. Rest of the World agreement, we expect quarterly development revenue to be below $0.5 million for the remainder of 2024. In Q3 2024, we recorded negative $0.3 million of drug product revenue compared to $1.3 million during the third quarter of 2023. We recognized $1.1 million from our Astellas royalties in the EU. And at the same time, we recorded a $1.4 million true-up from our Astellas royalties in Japan due to product mix.

Now moving on to our financial performance in China. Total roxadustat net sales from the joint distribution entity or JDE, owned by AstraZeneca and FibroGen and direct to distributor sales from FibroGen was $96.6 million in the third quarter compared to $77.1 million in the third quarter of 2023, an increase of 25% year-over-year. This growth has enabled us to achieve and maintain a brand value share of 45% of the category in China. From total roxadustat net sales in China, FibroGen's net transfer price from sales to the JDE was $29.7 million this quarter compared to $24.2 million in the third quarter of 2023, an increase of 23% year-over-year. Net transfer price is the best reflection of FibroGen's portion of the cash received from roxadustat in China.

During this quarter, we also released $12.5 million from deferred revenue due primarily to changes in forward-looking expectations for roxadustat in China.

As a result, FibroGen recorded $42.2 million in net revenue for the quarter from roxadustat sales to the JDE and $4 million of direct-to-distributor sales for FibroGen China totaling $46.2 million on a U.S. GAAP basis.

For full year 2024, for your models, we reiterate our forecast for FibroGen China net product revenue to be between $135 million to $150 million on a U.S. GAAP basis, FibroGen China revenue assumes a forecast of roxadustat net sales in China to range from $330 million to $350 million, narrowing our prior guidance of $320 million to $350 million.

Now moving down the income statement. Total operating costs and expenses for the third quarter of 2024 were $63.1 million compared to $103.6 million for the third quarter of 2023, a decrease of $40.5 million or 39% year-over-year.

Excluding restructuring charges of $18.6 million in the third quarter, our total operating costs and expenses were $44.5 million. Total operating costs and expenses for the quarter came in below our guidance range of $45 million to $55 million, which reflects a strong execution on cost reduction and disciplined spend. R&D expenses for the third quarter of 2024 were $21.7 million compared to $61.2 million in the third quarter of 2023, a decrease of 65% or $39.5 million year-over-year. Of our $21.7 million of R&D expenses, approximately 42% was related to pamrevlumab, 37% directed to FG-3246, with the remainder directed towards roxadustat and our immuno-oncology asset development activities.

We expect our pamrevlumab and immuno-oncology R&D expenses to decline significantly in the fourth quarter of the year as we have either shut down or reprioritized our R&D spend. SG&A expenses for the third quarter of 2024 were $17.6 million compared to $25.6 million in the third quarter of 2023, a decrease of 31% or $8 million year-over-year, primarily driven by the company's cost reduction efforts.

Finally, cost of goods sold for the third quarter of 2024 was $5.3 million compared to $4.2 million for the third quarter of 2023.

During the third quarter of 2024, we recorded a net loss of $17.1 million or $0.17 net loss per both basic and diluted share as compared to a net loss of $63.6 million or $0.65 per basic and diluted share for the third quarter of 2023.

As we have previously stated, we initiated a significant cost reduction plan to enable our focus on FG-3246, FG-3180 and roxadustat assets.

We have reduced our headcount by approximately 75% 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. With this backdrop, we expect our total operating costs and expenses, including cost of goods sold in the fourth quarter to be between $35 million and $40 million, which includes $1 million to $2 million in restructuring charges in the fourth quarter.

Now shifting towards cash.

As of September 30, we reported $160 million in cash, cash equivalents and accounts receivable. This reflects an increase of $12.9 million quarter-over-quarter. To provide further clarity on our cash balance, in the third quarter, we have invoiced and collected from AstraZeneca $27.7 million for certain historical R&D expenses and milestones owed to FibroGen.

Going forward, we expect to have additional cash collections in the fourth quarter of 2024 and the first quarter of 2025. These collections will be offset through payments for historical co-promotion sales and marketing expenses due to AstraZeneca China. The timing of these payments will be in the fourth quarter of 2024 and the first quarter of 2025. After considering the payments to and from AstraZeneca over the coming quarters, the result will be in a net cash collection of roughly $0.5 million to FibroGen.

For the third quarter, if we exclude the above-mentioned cash inflows, our net operating cash burn was $14.8 million during the quarter.

We have consistently stated our cash balance will enable us to fund our operating plans into 2026.

Assuming additional repatriation of cash from our China operations, which we continuously assess through multiple avenues, we expect our cash, cash equivalents and accounts receivable to fund operating plans into 2026. Thank you. And now I will turn the call back over to Thane.

Thank you, Juan. To conclude, we remain excited about the company's positive outlook and the potential value we can create for stakeholders. Roxadustat continues to perform extremely well in China, where we expect an approval decision of our sNDA for the chemotherapy-induced anemia indication early next year. And our partner, Astellas, continues with the commercialization of roxadustat in Europe, Japan and other markets. Aiming to enhance roxadustat's value to FibroGen, we are actively exploring development in anemia in patients with lower-risk MDS, either by ourselves or through partnership discussions.

Our oncology pipeline of FG-3246 and FG-3180 in mCRPC continues to advance after showing compelling top line data in the Phase 1 monotherapy study and in the interim data from the Phase 1b dose escalation portion of the investigator-sponsored study of FG-3246 in combination with enzalutamide. We look forward to the publication of the Phase 1 monotherapy data in the coming months. The anticipated initiation of the Phase 2 monotherapy dose optimization study in the first quarter of 2025 and the top line results from the Phase 2 portion of the combination IST in the first half of 2025. In summary, we will continue to execute on our current strategic priorities as a leaner and more focused organization as we continue to strive towards a valuation that we believe is more reflective of our current and future roxadustat revenue stream, first-in-class Phase 2-ready ADC and companion PET imaging agent and our strong balance sheet. I will now turn the call over to the operator for Q&A.

We will now begin the question and answer session. [Operator Instructions].

Our first question will come from Andy Hsieh of William Blair.

So in terms of the investigator-sponsored study, the Phase 2 portion, would it be the Stage 1, patients followed by the 15 patients Stage 2 in terms of kind of the top line that can be expected first half of next year? Just trying to get a sense of how you manage expectations and frame the extent of the release of data.

Yes. This is Thane. Yes, so I think that we should expect in the top line results for the IST for the -- in combination with enzalutamide to include not only obviously the patients from the escalation cohort, but also rPFS data from the expansion cohort, which is dosed at 2.1 mg per kg along with 165 milligrams or 160 milligrams per day of enzalutamide.

And so we have to wait for Rahul Agarwal, who is the sponsor of the IST to confirm exactly what data will be available when. In other words, as patients are enrolled, we'll see 6 months rPFS data on some, but maybe not 6 months on others. And then as the trial continues to dose patients, then that the patients who had a 6-month rPFS, then we'll have further rPFS readings. And then those that didn't quite have a 6-month RPFS will then progress to a 6-month data point.

So it will mature over time. But our best guidance at this point in time is that by -- in the first half of next year that we should expect top line results on both the escalation cohort and the expansion cohort, roughly 36 patients in total.

And maybe just a bit on the PET imaging agent.

So obviously, the standard of care now is basically you get either gallium-based or filurine-based agents infused 30 minutes later, you get an image. I'm just curious if that is similar to the serotconium-89, how long do patients typically have to wait to get a PET imaging agent? So just basically kind of on the logistical side of things.

Yes.

So that's what's being explored right now, Andy, as part of the ongoing work at UCSF with the PET imaging agent. The expectation isn't that it will be minutes, it will be days, post exposure to the PET imaging agent. The work in the coming months ahead of the Phase 2 start will determine exactly the number of days, but it won't be 30 minutes ahead and then you administer the first dose of the ADC. It will likely be, let's say, 6 days or so.

The next question comes from Paul Choi of Goldman Sachs.

This is Khalil calling in for Paul. I guess a couple of quick ones from us. Quickly, I guess, on FG -- sorry, on the Phase 2 that you're planning to initiate next quarter or I suppose Q1 of '25.

I think you mentioned 75 patients earlier in this call. I just wanted to clarify, will all of those be imaged as well with FG-3180? And then I had a quick follow-up on roxadustat after that.

Yes. Thanks, Khalil. The majority of them will be treated with the imaging agents at the outset of therapy followed by then treatment with the ADC, not all 75 of them, and that's because we'll be filing the IND for FG-3246 this quarter, and we'll file the IND for the PET imaging agent next quarter.

So we won't have the PET imaging agent ready exactly when the first patient is expected to be dosed in the monotherapy trial, but it won't be too long after that when we will start treating patients with the PET imaging agent.

So the expectation is the majority of them of the 75 will receive the PET imaging agent.

And then my quick follow-up on roxadustat was just on guidance.

I think the midpoint of your China sales sort of imply continued growth into the fourth quarter of roxadustat. But then your -- the net sales guidance you gave of $135 million to $150 million, the high end of that guidance implies a very modest like year-over-year decline in the fourth quarter. I may have missed this earlier, but Juan, if you're still on the line, I think you mentioned the $12.5 million release from the JDE? Can you just touch on that again and just explain what's driving the decrease sequentially that this guidance is implying in the fourth quarter, that would be really helpful for us.

And thank you for bearing with me there with -- my remarks with a little bit of the end of a cold here that I'm having. What I basically alluding to your question, the $135 million to $150 million still somewhat contemplate a potential approval of the CIA indication. If that were to happen the way that our single performance obligation model basically elucidates that we would need to accrue further into deferred revenue given the future expected performance of the asset from an accounting perspective.

So in that sense, our sales would basically -- our sales guidance would have that into consideration as we are providing you this perspective at this point in time.

So we will see over the course of the remainder of the year if we have that approval or not. And if the CIA indication flows into 2025, then we may be on the higher end of the spectrum here.

And I'm so sorry, but just to clarify, the -- you mentioned -- I may have misheard, but did you mention a $12.5 million change in the deferred revenue? Was that an increase or decrease? I think I missed that earlier in the call.

That's an increase to this quarter's revenue, and it's basically a release of our deferred revenue.

However, the way that the single performance obligation model operates is that if, for instance, we get a CIA approval and an enhancement of our future revenue, we would need to defer more revenue and therefore, reduce our revenue for that specific quarter.

So that's kind of like the dynamic of how our single performance obligation model works that if we have future expected revenue that is above and beyond what we're currently expecting, then this quarter or the quarter under which that happens, we will need to accrue further into our deferred revenue and the expectation of that future revenue occur.

This concludes our question-and-answer session. I'd like to turn the call over to Thane Wettig for any closing remarks.

So thank you for joining us today for today's third quarter earnings call and for your continued interest in FibroGen. Enjoy the rest of your day. Thanks, everyone.

The conference has now concluded. Thank you for attending today's presentation, and you may now disconnect.