Scholar Rock Holding Corp Q4 FY2025 Earnings Call

Ladies and gentlemen, thank you for standing by. Welcome to the Scholar Rock Holding Corporation Fourth Quarter 2025 Financial Results and Business Update Call. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. You would then hear an automated message advising your hand is raised, and to withdraw your question, please press 11 again. Please be advised that today's conference is being recorded. I would like now to turn the conference over to Scholar Rock Holding Corporation. Please go ahead.

Good morning. I am Laura Ekas, Vice President of Investor Relations at Scholar Rock Holding Corporation. With me today are David Hallal, Chairman and Chief Executive Officer; Akshay Vaishnaw, President of R&D; R. Keith Woods, Chief Operating Officer; and Vikas Sinha, Chief Financial Officer. During today's call, David will provide introductory remarks and a business update, Akshay will review our R&D progress, Keith will provide an update on our commercial readiness activities, and Vikas will provide a financial update. We will then open the call for questions. Before we begin, I would like to remind you that during this call, we will be making various statements about Scholar Rock Holding Corporation's expectations, plans, and prospects that constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any future date. I encourage you to go to the Investors & Media section of our website for our most up-to-date SEC statements and filings. With that, I would like to turn the call over to David. David?

Thank you, Laura, and good morning. Thanks to everyone for joining our fourth quarter and full year 2025 earnings call. Scholar Rock Holding Corporation is poised for a transformative year in 2026. Our priorities are clear, and we are executing with focus, discipline, and urgency as we seek to deliver the world's first muscle-targeted therapy to children and adults living with SMA while also laying the foundation to realize our ambition to develop life-transforming therapies for patients with additional rare and severe neuromuscular diseases globally. Our highest priority is to bring upitigramab to the SMA community as quickly as possible. We remain relentless on behalf of patients, and we are grateful that important progress continues to be made at a steady and rapid pace. Let me briefly summarize the key events that have occurred since our constructive and collaborative in-person Type A meeting in November. First, a week following our Type A meeting, the FDA issued a warning letter to Catalent in Indiana. Next, Novo Nordisk rapidly responded to the FDA by mid-December. Then following Novo's response, the FDA reached out prior to the holidays to schedule an early Q1 meeting. That meeting has since taken place, and importantly, at that meeting, the FDA had no additional requests to Novo's remediation plan. And most recently, following the meeting with Novo, we were encouraged that the FDA sent a field team to Catalent, Indiana. At the conclusion of the visit, the FDA once again did not have any additional requests to Novo's remediation plan and stated to Novo that it intends to conduct a site reinspection following routine manufacturing activities, which has since resumed in late February. The cadence of activity since our Type A meeting reflects the shared understanding between us, the FDA, and Novo of the high unmet need in the SMA community and a shared sense of urgency to bring upitigromab to children and adults living with SMA as rapidly as possible. We are pleased with the FDA's continued level of engagement, and we expect this momentum to continue. Our team is prepared to resubmit the ipilimumab BLA following a successful FDA reinspection of the Catalent, Indiana facility. We are reaffirming our guidance of BLA resubmission and U.S. launch following approval in 2026. Also, I am pleased that progress with a second fill-finish facility is moving quickly to build redundancy into our supply chain. Engineering runs at the facility are now underway, with additional manufacturing runs to follow. We anticipate filing a supplemental BLA for the second filer later this year. As we advance the regulatory process for upitigromab toward approval for patients with SMA in the U.S., our MAA review continues in Europe, and we expect a decision from the European Medicines Agency in mid-2026. With anticipated regulatory approvals in the U.S. and Europe this year, I would like to now turn to our Scholar Rock Holding Corporation commercial launch preparations. In the U.S., our team is deployed in the field and is educating potential prescribers and payers on the unmet need in SMA and the importance of targeting muscle, the principal organ affected in SMA, while also broadening and deepening relationships with the community. In Europe, we are building momentum with launch readiness activities and engaging with the SMA community. We continue to plan for a launch in the second half of the year beginning with Germany. Keith will discuss substantial progress we are making with commercial preparations and our disease awareness initiatives shortly. We know it is not a matter of if but when upitigramab will be approved for children and adults with SMA. We are emboldened by the commitment we have made to the more than 35,000 patients globally living with SMA who have received an SMN-targeted therapy. We are working expeditiously to deliver on our ambition that globally, any patient with SMA who can benefit from upitigramab should have access to it. This is indeed what we know well and what we do well, and we are confident in the significant opportunity that we have to serve patients with SMA. We are ready now more than ever to usher in the next era of innovation for the SMA community. I would like to now turn to the progress we are making in advancing our world-leading anti-myostatin pipeline. Enrollment and dosing continued in our Phase 2 OVAL study evaluating upitigramab in infants and toddlers with SMA. Our IND for upitigramab in FSHD is cleared, and we are on track to initiate a robust, randomized, placebo-controlled Phase 2 study later this year. With regards to our subQ formulation of upitigramab, we shared the promising results of a Phase 1 study comparing subQ and IV upitigramab in January. We expect to share our clinical and regulatory strategy for the program later this year. And finally, we continue to enroll and dose participants in our Phase 1 study for our highly innovative SRK-439 myostatin inhibitor. We expect to have top-line data from this study in the second half of this year. Turning now to our balance sheet. We were pleased to have ended 2025 with $368 million in cash and cash equivalents. This includes $60.4 million from the exercise of warrants that were set to expire on December 31. We continue to strengthen our financial position to drive our commercial and R&D priorities. And this morning, we are pleased to announce that we have secured a new debt facility for up to $550 million, which Vikas will discuss later in the call. 2026 will be a transformative year for Scholar Rock Holding Corporation. We are ready to resubmit our BLA for upitigramab at any moment. Our U.S. commercial team is working with urgency to prepare the market for the launch of the world's first and only muscle-targeted therapy for children and adults living with SMA. Beyond the U.S., the build-out of our 50-country operating platform is underway in Europe, with other regions and countries to follow. And our highly innovative world-leading anti-myostatin pipeline with upitigramab and SRK-439 is progressing with strong momentum. The opportunity ahead of us to serve patients with SMA and additional rare and severe neuromuscular diseases is significant. We remain steadfast in our strategy, confident in the determination of our team, and energized by the transformative potential of upitigramab and our broader pipeline. The road ahead is one of purpose, progress, and extraordinary possibility. I will now turn the call over to Akshay for an R&D update. Akshay?

Thank you, David, and good morning, everybody. As David noted, we remain focused on our upitigramab BLA registration to bring this important therapy to children and adults with SMA as rapidly as possible. Since being joined by Cure SMA and Novo at our in-person five-day meeting with FDA leadership in November, I have been pleased by the ongoing level of engagement and progress made on the patients. We expect this momentum to continue, and our team is prepared to resubmit the upitigramab BLA following a successful FDA reinspection of the Catalent, Indiana facility. I would now like to provide an update on the status of our second fill-finish facility, which will strengthen supply continuity and support future commercial demand. As we shared late last year, we are working with a world-class U.S.-based manufacturing facility that has a proven track record of successful FDA and EMA site inspections. Importantly, engineering runs are now underway with additional manufacturing runs planned in Q2, and we continue to expect to submit a supplemental PABLA with this facility later in 2026. Outside of the U.S., our upitigramab MAA is progressing through the review process with the EMA, and we continue to anticipate the decision in the middle of this year. Turning to our pipeline, let me start with the Phase 2 OVAL trial evaluating upitigramab in infants and toddlers under the age of two. This trial is enrolling participants who have been treated with an SMN1-targeted gene therapy or who are receiving ongoing treatment with an SMN2-targeted therapy. The study is important for two reasons in particular. First, it is anticipated to expand the impact of upitigramab to the full spectrum of patients currently being treated for SMA, as this is the first time we are evaluating the use of upitigramab in organza-treated patients in a clinical trial setting. Second, we believe early intervention with upitigramab could support muscle during the critical early development phase, complementing SMN-targeted therapy that aims to preserve motor neurons. By promoting muscle growth alongside motor neurons, upitigramab has a unique opportunity to improve motor outcomes in the youngest patients with SMA. To ensure that no patients are left behind, we continue to enroll patients in this study and dosing long ago. Turning now to our next indication for upitigramab, facioscapulohumeral muscular dystrophy, or FSHD. FSHD is a rare, devastating neuromuscular disease with significant unmet need. More than 30,000 patients are diagnosed in the U.S. alone, and there are no approved therapies. FSHD is caused by dysregulation of DUX4, a protein that can cause muscle damage when inappropriately expressed. Symptoms usually begin in adolescence or early adulthood, with muscle weakness in the face and upper body, but FSHD can impact any muscle in the body. An estimated 20% of patients will become wheelchair dependent. We are prioritizing FSHD as the next indication for upitigramab for three key reasons. First, there is significant unmet need in this population for a safe and effective therapy. Second, we have preclinical data from the gold-standard FlexFlow4 mouse model that provides mechanistic rationale for upitigramab in FSHD. Using this mouse model showed that myostatin inhibition can produce robust increases in muscle mass, significant improvements in muscle force, and consistent gains in endurance after 28 days. Third, there are randomized studies in FSHD that suggest muscle mass can increase in treated patients, showing functional benefit. For example, in studies of either rigorous physical therapy or treatment with anabolic agents, patients with FSHD demonstrated increases in lean mass and muscle function. These data suggest that upitigramab as a monotherapy may have the potential to bring important benefit to FSHD patients. The FSHD IND is clear, and our next step is to conduct a robust, randomized, double-blind, placebo-controlled Phase 2 study that is expected to enroll 60 patients. The study, or FORGE, is on track to initiate in the middle of this year. We also continue to advance two additional programs in our world-leading anti-inflammatory pipeline, a subQ formulation of upitigramab, and SRK-429. In our SRK-439 program, we showed some very exciting data from a Phase 1 study earlier this year. In that study, healthy volunteers received upitigramab via subQ at 100 or 800 mg or 800 mg IV. The data demonstrated that 800 mg subQ resulted in an overlapping pharmacodynamic profile with 800 mg IV. Accordingly, subQ upitigramab appears to have favorable bioavailability with a pharmacodynamic profile comparable to IV administration. Additional development activities with subQ upitigramab are underway. We are planning engagements with U.S. and European regulators. Turning to SRK-439, we discovered that by leveraging our world-leading expertise in targeting myostatin. SRK-439 is a subcutaneously administered myostatin inhibitor binding to both pro and latent myostatin with high affinity and selectivity. We recently presented data demonstrating that SRK-439 is 10 times more potent than upitigramab. We have shown in nonhuman primates that SRK-439 leads to changes in whole body lean mass at doses as low as 0.3 mg/kg. We are very excited about this program, and dosing in our Phase 1 healthy volunteer study is well underway. We expect to have top-line data on the study in the second half of this year. In closing, we are executing with focused urgency to bring upitigramab to children and adults with SMA while in parallel investing with discipline to advance our world-leading anti-myostatin pipeline. The strength of our data and the sustained momentum of our programs underpins our confidence that we can shape the future of treatment for patients living with rare neuromuscular diseases. I will now turn the call over to Keith to discuss our commercial launch preparations. Keith?

Thanks, Akshay, and good morning, everyone. As David noted, our team continues to operate with urgency as we prepare for the launch of upitigramab. Our commercial organization remains focused and disciplined, advancing the critical capabilities required to deliver a seamless launch and support patients from day one. Nearly a decade after the introduction of SMN-targeted therapies, the market continues to grow and now represents nearly $5 billion in global annual sales. However, while SMN-targeted therapies have brought much-needed innovation, muscle strength and motor function remain the top unmet need, with 95% of patients continuing to experience persistent and progressive muscle weakness that limits function and independence. Additionally, three-quarters of neurologists believe multiple modalities are necessary to optimally treat patients with SMA. This data underscores the significant opportunity we have with upitigramab, the world's first muscle-targeted therapy. To this end, our U.S. customer-facing team is active in the field, focused on disease education programs that reinforce a broader understanding of SMA as a disease of the motor unit consisting of both the motor neuron and the muscle, which is the principal organ impacted by the disease. We continue to engage across approximately 140 SMA treatment centers, 2,600 prescribing physicians, and their multidisciplinary care teams throughout the U.S., and our SMA disease education efforts remain a core component of our work in the field. In parallel, we are strengthening and advancing the key elements of our commercial capabilities to ensure launch readiness. We have expanded our specialty pharmacy network to enhance SMA patient and caregiver convenience. SMA patients currently receiving an SMN-targeted therapy from a specialty pharmacy will be able to access upitigramab through that same specialty pharmacy. In addition, through our patient access partners, we have established a home infusion network of more than 10,000 affiliated nurses nationwide. We are also working to ensure we mitigate reimbursement and access bottlenecks. This includes preparations to launch our patient services program, which we have named Scholar Rock Supports. This program is designed to provide comprehensive and individualized support to patients, caregivers, and providers. In addition, we remain focused on patient engagement and community activation. In January, we launched the next phase of our disease awareness campaign, called Life Takes Muscle, aligned with our objective to deepen community awareness of the importance of targeting muscle. And finally, we continue to engage with payers, advancing discussions with national and key regional payers as well as Medicare and Medicaid. At U.S. approval and launch, I look forward to discussing our comprehensive SMA Patient Access Support Program in more detail. While we make substantial progress in preparing for the launch in the U.S., we are also advancing launch readiness across key European markets in anticipation of a mid-2026 EMA decision. In Germany, we have established local leadership, initiated our compassionate use program, and are progressing reimbursement planning to enable rapid access following approval. Across the broader region, we are advancing reimbursement dossiers in multiple countries, strengthening our distributor relationships, and we are building out our EMEA infrastructure to support future commercialization. In closing, we have invested thoughtfully to build the commercial foundation necessary to support a world-class launch, and we believe upitigramab is well positioned to play a central role in the next era of SMA care. Our team is prepared to move quickly upon approval and to deliver on our commitment to the SMA community, one patient, one caregiver, and one family at a time. With that, I will turn the call over to Vikas. Vikas?

Thank you, Keith. Our financial objectives for 2026 remain consistent. We are focused on supporting our commercial build to deliver a strong upitigramab launch, funding R&D activity to advance our pipeline and expand our leadership in the myostatin and muscle space, and continuing to evaluate opportunities to strengthen our balance sheet in a way that supports long-term shareholder value. In keeping with these objectives, I am pleased to provide our fourth quarter and full year financial results. For the fourth quarter, we reported $91.9 million in operating expenses, which included $19.4 million in non-cash stock-based compensation. Excluding stock-based compensation, operating expenses were $72.5 million. For the year ended 2025, we reported $384.6 million in operating expenses, which included $75.6 million in non-cash stock-based compensation. Excluding stock-based compensation, operating expenses were $309 million for the year ended 2025. Turning to our balance sheet, we ended 2025 with $368 million in cash and cash equivalents. During the fourth quarter, we strengthened our cash position, adding $60.4 million from the exercise of a warrant that was set to expire on December 31. We continue to strengthen our balance sheet and are pleased to announce today that we secured a new debt facility for up to $550 million with Blue Oak Capital. This debt facility consists of four elements. First, upon closing, $100 million was immediately available to us, which we have used to repay our prior $100 million debt facility with Oxford Finance. Second, an additional $100 million is available to us this quarter, which we expect to draw down by March 31. Then, following FDA approval of upitigramab, we have the option to draw up to $150 million in additional capital. And lastly, we have an option for an additional incremental facility of up to $200 million at the mutual consent of Scholar Rock Holding Corporation and Blue Oak. With that, the facility provides us with additional flexibility as we transition towards a global commercial space company while investing in our pipeline. In addition to the $150 million available from the debt facility upon FDA approval of upitigramab, we will look to monetize a priority review voucher to further strengthen our balance. Looking ahead, we continue to operate with a tight financial plan. Our prioritized investments remain focused on our upitigramab commercial launch readiness in the U.S. and Europe, strengthening our supply chain to support the pipeline and commercial demand for our upitigramab, and advancing our highly innovative clinical programs that Akshay discussed earlier in the call. With that, I will turn the call back to David. David?

Thanks, Vikas. In closing, we remain focused on bringing upitigramab, the world's first and only muscle-targeted treatment to improve motor function, to children and adults living with SMA as rapidly as possible. We are encouraged by the progress that has been made and by the continued momentum across our regulatory, clinical, and commercial priorities. With a strong foundation, clear strategic priorities, and a world-class team, we are well positioned to make 2026 a transformative year for Scholar Rock Holding Corporation as we continue to work with urgency on behalf of children and adults living with SMA. We look forward to updating you on our continued progress throughout the year, and with that, we will now open the line for questions.

Thank you. Star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press 11 again. We ask you please limit to one question. Our first question is going to come from Eric Thomas Schmidt with Cantor. Your line is open.

Thanks for a very comprehensive update. David, just to put a pin in it, is Novo now ready for reinspection, open for reinspection? And then assuming the reinspection does go, quote, well, what would trigger your resubmission? What do you need to see from that reinspection to be able to push the button on the refiling? Thank you.

Thanks, Eric. So, you know, we are gratified really since our Type A meeting in November with the shared sense of urgency and high priority that both the FDA and Novo have made regarding the remediation of the Catalent Indiana facility, and you got a sense from the call just the drumbeat of progress week after week, month after month. We like the high engagement we continue to see. And given the constructive meeting in early Q1 and then the following site visits, the gating item now just is a reinspection following these routine manufacturing activities as Novo moves into full-scale production. As far as our trigger, we would look for, obviously, a successful reinspection as you noted, and we are assuming that given the progress that has been made. That would then trigger us to be ready to submit our BLA submission very, very quickly. But it really would be with some level of confidence that it was a successful reinspection.

And our next question will come from Tazeen Ahmad with Bank of America. Your line is open.

Hi, guys. Good morning. Thanks for taking my question. Not to belabor the point on timing here, but I know you are confident about the ability of Novo to resolve the issue. But in the event that you do have to revert to your backup facility, you have guided to a supplemental filing in the second half of the year. What would happen to timelines if that needed to be the primary filing?

Thanks, Tazeen, very much. As I noted on the call, we are gratified by the rapid and steady progress that has been made, you know, between the FDA and Novo. And we do think of the importance of upitigramab for the SMA community as a key driver in this process. I would say that we are pleased with how rapidly we are moving forward with an additional filer, and our assumption is whether or not it were to be a supplemental BLA, which is our plan, or whether or not we had to fall back, we have always viewed that as an important effort on our part no matter what because we cannot control everything in this process. And we do not believe that the timing would be altered tremendously in terms of if it were not an SBLA. So we thought about it. It is our plan that it will be an SBLA. That is the level of insight, information, and confidence that we have. But, nonetheless, we would be prepared to pivot should the need arise, on behalf of children and adults living with SMA.

Thank you. And our next question comes from Tessa Thomas Romero with JPMorgan. Your line is open.

Hey, guys. Thanks so much for taking the question this morning. So first one is, can you elaborate on what it meant that the FDA sent a field team? What was the purpose of that? And is that routine? And then the second one, just to loop back on sort of better understanding the next procedural steps post the reinspection and what the timelines could be there, will you get verbal communication or is written documentation what you will see similar to a normal inspection? Thanks.

Yeah. Thanks, Tessa. It is a good question because certainly nothing has been completely ordinary about this process. And I do think what has created some level of extraordinary behavior with kind of a constant drumbeat of progress has really been set off by that in-person Type A meeting that we held with the FDA and where there really was, with CURE SMA in attendance and with Novo in attendance, a shared sense of urgency to bring upitigramab to patients. And so while I cannot comment on the overall objective, we do think what it shows is that just weeks after a really constructive meeting with Novo in early Q1, where there were no new requests from the FDA of Novo regarding their remediation plan, we think it just continues to show high priority by the FDA to send a field team out to interact with the site and to indicate that, you know, after routine manufacturing activities, which have since recommenced at the facility, they would be in line for a reinspection. Overall, we just feel good about the drumbeat of progress here, and we are quite pleased, and we would expect, given this sort of rapid and steady pace that we have seen over these last three months, that anything else that follows, whether it is the timing of a reinspection or the timing of resubmission and review, hopefully will continue to reflect the commitment that has been made to rapidly progress the upitigramab file so that we can deliver this drug to children and adults living with SMA. We will certainly keep you apprised on that progress. Thank you.

Thank you. And our next question comes from Mani Foroohar with Leerink. Your line is open.

Hey, guys. You have Ryan on for Mani. Thanks for taking our question, congrats on the update. Maybe just one sticking with the review. Kind of based off your latest conversations with the FDA, I am curious what your expectations are for a turnaround time following BLA submission to eventual approval. Are there any details still need to be worked out regarding label, etc., with regulators? And then maybe just as a second one on the pipeline, can you talk about the strategy for 439? Is this something that you plan to keep in house, look for broader strategic options? Is it best suited in rare neuromuscular diseases, or potential broader applications? Thanks.

Thanks, Thanks, Ryan. Regarding the timing, again, just to remind everybody tuning in today, in our CRL that we received last year, the sole approvability issue was the state of compliance at the Catalent, Indiana facility. So we are certainly very focused on working with the FDA and Novo on that. As I noted earlier in the call, we would and we are planning, and we are ready to rapidly resubmit our BLA following successful reinspection. And we would just point to the evidence of the progress over these last three months and how attentive the FDA has been to remediating this facility and how focused Novo has been on working with urgency as well, and we will keep you apprised on that timing. Regarding the pipeline at SRK-439, yeah. SRK-439 is obviously a very important and exciting drug. It is a high-potency anti-myostatin antibody that appears to be, at least in preclinical work, about tenfold more potent, which could lead to a very low volume, infrequent administration type of drug. So I think that creates very interesting and exciting possibilities in the neuromuscular space for us. At the current time, we think this is a Scholar project, and we have no intentions to partner right there. But we will share further development plans after we get the top-line Phase 1 data.

Thank you. And our next question is going to come from Kripa Devarakonda with Truist. Your line is open.

Hey, guys. Thank you so much for taking my question. Time lines wise, not to be overly repetitive, you expect you continue to expect inspection, BLA resubmission, U.S. launch, everything to happen in 2026. For the launch to be in 2026, can it still happen with a Class 2 submission? Our due diligence suggests this is most likely going to be a Class 2 submission. And in any of your recent conversations with the FDA, was there any hint or mention of a potential priority review voucher for upitigramab? Thank you.

I did not get the last part of that, Kripa. Could you repeat that last question?

Commissioner’s priority voucher.

Oh, the national priority voucher. These are all very good questions, Kripa. And as you might imagine, we have thought about it all. And with all of the information that we have and the progress that is made, we were pleased and confident to reaffirm the guidance that we provided today of a 2026 BLA resubmission and U.S. launch upon approval. We would certainly point to the steady FDA prioritization and progress with Novo over these past weeks and months, and it remains very steady. And I think, like, we have thought about Class 1 versus Class 2, and what we have seen actually in our own analysis is that even when Class 2s are granted, oftentimes the decision is taken up before that six-month timeline. And, again, I am just reminding you that the sole approvability issue for us has been the status of the Catalent, Indiana facility. And, you know, we are planning for the resubmission to happen once we have an indication that it was a successful reinspection. So we will keep you apprised of that, but we are certainly very comfortable with the guidance that we have provided. And then regarding the priority voucher, I would just say that we are staying in close communication with the FDA on all of our different initiatives and keeping at the forefront the very high priority that exists with the SMA community in the United States to gain access to the world's first and only muscle-targeted treatment. We look forward to continuing to keep you guys apprised on our regulatory progress with the FDA.

Great. Thank you so much.

Hey, guys. Good morning. I am not going to ask a submission question. Can you talk a little bit about the expectations for the label as it relates to either ambulatory or non-ambulatory patients and whether there are any issues regarding age subgrouping, given that you had what sounds like a very successful review process and only the CMC was the outstanding part? How should we think about a broad label? And then a follow-up, assuming approval for upitigramab, can you just remind us, given that your drug is a weight-based drug, how to think about the comparable pricing relative to other drugs and if models should reflect anything philosophically as it relates to the differences in how the drugs are administered? Thank you.

Yeah, Michael. You know, we were gratified by all the progress made during the original cycle and we had gone to a very advanced stage with the draft label, and the FDA had really worked hard to get to that. So with the CMC issue being the only outstanding point, we anticipate it relatively straightforward to get aligned with the FDA on the final label after a BLA resubmission. Now all of that being said, the details ultimately are up to the FDA. But we know from the conversations leading up to the September date that kind of the guiding principles are based on what the FDA has shown before in the SMA space, and the trial design that supports the approval is important. We have experience with both non-ambulatory and ambulatory patients, and we have experience in patients on various backgrounds. I think that these are important guiding factors that we will need to finalize upon BLA resubmission and see where we end up. But we have been pleased so far with how straightforward we can get this approach.

Yeah. And then on price, you know, it is not really appropriate for us to comment on specifics at this stage. But I do promise you when we have approval and we have our launch call, we will get very specific about the pricing. But, Mike, as you mentioned, because it is weight-based dosing, you are going to see a range. So it is not going to just be one set price for all. But, look, when we think about pricing of upitigramab, we think about three key factors. And it is the rarity and the severity of SMA, it is the progressive nature of the disease, and, you know, in combination with SMN-targeted therapies, our data from both TOPAZ and SAPPHIRE have just demonstrated compelling clinical benefits. So we will get into all of the specifics on pricing at the launch call.

Thank you.

Hi. Thanks so much for taking our question. So looking ahead to launch, what commercial analogs would you point us to as we think about the initial uptake and launch trajectory? And then maybe another one on subQ apitogramab. Do you think approval will require a full clinical study in SMA, a smaller bridging study, or primarily human factor studies? And if you could give us a timeline to market, that would be awesome.

Thanks very much, Amy. What I would say is that we have been pleased in our engagement with the patient community and the caregiver community, as well as the neurologist's appreciation not only for addressing the motor neuron component of the disease but for the first time, being able to address directly the muscle component of the disease, which is the principal organ that is clinically impacted and affected by this disease. We sense that there is a lot of interest in accessing the drug, and that in and of itself could support a very nice uptake at launch. I think what Keith and I have looked at, though, is this is essentially a Q4 week infusion. It will have a miscellaneous J-code for some period of time. We know that there are payers, for example, Medicaid that could be a little sluggish at launch. We recognize that payers, in and of themselves, it is not a matter of if they reimburse, but sometimes it takes time to reimburse. And so we believe robust demand will be met with initially some access speed bumps that could impact our launch curve. But overall, the long term that we see for upitigramab in the U.S. and beyond seems quite significant for us, and we are really looking forward to the eventual approval and then Keith and the team launching upitigramab to the SMA community. With respect to your question on subQ and clinical regulatory strategy, I will hand that over to Akshay.

Yeah. Thanks, David. For subQ upitigramab, we have very interesting and supportive data that the subQ route is viable, showing excellent bioavailability and a pharmacodynamic profile. Now we know a lot about upitigramab in terms of PK/PD from our prior work, clearly with IV administration. We want to leverage that by demonstrating that this well-characterized drug, with its different administration routes, if we can mimic the appropriate PK/PD, then there is no reason why it cannot be equally safe and effective. These are all discussions we need to have with the FDA. The initial approval of the drug is, of course, very important. But subsequent to that, we hope to get aligned with regulators on that approach. So ultimately, we cannot guide the timelines today, but we are hoping to have progressive discussions with regulators to formulate our final steps.

Thank you. And our next question will come from Jeff Meacham with Citigroup. Your line is open.

Good morning, guys. This is Ryan on for Jeff. Maybe I was thinking about the second fill-finish facility. If you guys were to switch over to that one, would it completely derisk the supply chain from a U.S. and EU launch perspective? And then on the launch, what specific leading indicators of payer and physician readiness are you guys tracking? Maybe if you could give some color on that, it would be helpful. Thanks.

Absolutely. I will start with the second fill-finish, and then, Keith, you might need clarification on the second question. Yes, we are really pleased with the progress we have been making. As I mentioned, tech transfer commenced in Q4, engineering runs are underway, and there are additional manufacturing runs to follow here in the very near term. So we are working urgently. Again, our assumption is this is going to be our second filer. We are going to submit an SBLA. Should we rely on this facility solely, we are confident that we would be derisking our U.S. and EU commercial opportunities. We wanted to be very thoughtful in selecting the right second partner for fill-finish, and we are gratified that we have done that. Also, as I noted, we are really pleased with the rapid progress that is being made. Keith?

Yeah. So first of all, when it comes to the payers, you know, we have been really pleased with the access that our team has been able to get. As I stated in the prepared remarks, we are engaging not just the big national payers, but also regional payers and even some Medicare and Medicaid. While we have had more time, we have been able to have in-depth discussions with them, and our medical team has been able to go through the SAPPHIRE clinical data with them. The bottom line is, just as we have researched and shared lots of the Cure SMA data, both in some of our own markets, neurologists and patients—they want more, and they need more. And that is why we understand that three-quarters of these physicians already believe in the necessity of multiple modalities to optimally treat SMA.

Thank you. And our next question will come from Salvator Caruso with TD Cowen.

Hi. This is Salvator Caruso on behalf of Marc Alan Frahm at TD. Thank you for taking my question. Just one quick question that kind of crossed some Ts and dotted some Is. Regarding the status of the MAA review, will that market also be served by the Novo Catalent Indiana facility? And if so, has the EMA taken any action in response to the FDA inspection findings?

I will start, and then I can hand it over to Akshay. There is a mutual recognition between both the FDA and EMA. So this steady and rapid progress we are making with the FDA serves us very well for the current MAA review with regulators. It is very important that we continue to make this progress forward. As I noted, the continued remediation and, eventually, a successful reinspection will really support our EMA decision near mid-year. If for some reason we were to rely on the second filer, that would also be very important. But for now, we are very excited with the rapid and steady progress that has been made. Akshay, anything to add?

Yeah. You covered it, David. I think the other piece that we can close touch on is reconciling the needs of the MAA with doing the policy with the EMA. So that is really what is important, and we all await those additional responses that will not take approvals.

Thank you. The next question will come from Etzer Darout with Barclays. Your line is open.

Great. Thanks for taking the question. Just a couple for me. Has the FDA requested or could they request additional safety data that could extend review of upitigramab? And then on FSHD, just wondered would you be looking at any functional endpoints in the Phase 2 study that you are planning? And could this be a more appropriate indication for SRK-439 longer term? Thank you.

Thanks, Etzer. Yeah. It is a great comment, and we can remind you that the BLA resubmission will be a fairly rapid and small resubmission. However, there would be an update to our safety database, which was called out in our response letter from the FDA. Akshay can comment on that for FSHD, and then talk about any functional outcome measures.

Okay. Yeah. So we are in line with the FDA, and the budget meeting was useful in many regards, including that and both the safety aspects that need to be updated. That is all agreed to, and so we are ready and prepared for this BLA resubmission. I do not see any brain issues there, but it is a good question, and we will provide the FDA with the latest safety information that we have. Regarding the FORGE Phase 2 study in FSHD, the primary endpoint will focus on increasing lean muscle volume measured very sensitively with imaging techniques. However, we will have home state environment treatment, which is a validated approach in FSHD, to understand the functional impact of any potential changes in muscle mass. We look forward, obviously, to that data as well.

Thank you. Thank you. And our next question will come from Evan Seigerman with BMO Capital Markets. Your line is open.

Hi. Malcolm Hoffman on for Evan. Thanks for taking our question here. Thinking about the financials of the business. I know you mentioned the new debt facility secured with approvals in the U.S. and Europe coming this year. I just wanted to ask, how are you thinking about expectations for time to profitability, whether you anticipate any additional need for financing ahead of that profitability hinge point? Thanks.

Thanks, Malcolm. Vikas?

Yep. Hi, Malcolm. You know, we have not given forward-looking guidance at all here, but, you know, we will follow most likely the normal rare disease kind of revenue trajectory, which leads you into very similar levels of profitability time frames of two to three years from launch. But, you know, it also depends on how our pipeline progresses during that time, and we will weigh into profitability versus investing into the future. However, overall, looking at a fundamental principle of creating long-term shareholder value.

Thanks, Vikas. Thanks, Malcolm.

And our next question comes from Allison Bratzel with Piper Sandler. Your line is open.

Hey, good morning, guys. Thanks for taking the question. Just drilling down on some of the prior discussion around review timing. I know you have talked a lot about the FDA's sense of urgency on upitigramab. Is there good precedent for the FDA spending less than six months to review a Class 2 resubmission, and can you just clarify, does your guidance for commercial launch in '26 assume a Class 2 resubmission and the full six-month review? And then separately, just on OPAL, could you talk to what you are seeing on enrollment trends there and just, you know, what that tells you about the underlying awareness of upitigramab in the SMA community? Thanks.

Thanks, Allison. Maybe I will just point out one example regarding the Class 2 not taking the full time, and I think it is important because it has been mentioned occasionally here during this current journey, with Regeneron. In a CRL received in 2023 at the same facility, Regeneron did have a resubmission. I believe it was a Class 2 resubmission, and yet it was approved within, you know, essentially a sort of a 60-day window. There are more examples than that, and I just point to that. It is relevant given the fact that it was CRL, and it was the same facility, and it had to do with some assessments that followed the facility post-inspection. I think that is noteworthy.

Yeah. Following up on that, enrollment for the OPAL study is going very well. The initial thing to say is people who are engaging with enrollment have shown knowledge and appreciation for a muscle-based approach in the patient community and the prescriber community. Keith has spoken about the fact that there is startlingly high interest from patients, families, and physicians waiting for the approval of this drug. We have verified this with the nice progress we have achieved. I am not going to share details today, but we are seeing a good clip of enrollment. As we get later into the year, we will clarify details once data comes into sight. But the community awareness of the drug and its potential is very good.

And, Allison, I would just add, as Akshay noted in the prepared remarks, we have a deep commitment to the SMA community, and I am really pleased that we are making sure no patients are left behind by opening up this under-two study. We are super excited to be doing this work in the youngest of patients with SMA.

And the next question will come from Kalpit Patel with Wolfe Research. Your line is open.

Hey. This is Dugan on for Kalpit. Previous myostatin inhibitors and FSHD increased muscle mass without meaningful functional improvement. Could you give some color on how upitigramab aims to address this historical hurdle and what clinically meaningful functional improvement might be in the planned Phase 2?

Sure. Yeah. I think you are pointing to earlier generations of myostatin inhibitors that did not have a well-validated mechanism of action and potency safety profile. The earlier generations of agents did not demonstrate the potency and selectivity that upitigramab presents. Additionally, I suspect that Exelon did a study in FSHD and was rejected due to focusing on low feeble in one isolated muscle. No one can expect that to result in global, meaningful functional improvement. However, we know separately that globally applied strategies, such as intense physical therapy or anabolic agents that increase muscle mass, show a clinical improvement. This observation is why we incorporated contractility measures into the Phase 2 study to evaluate muscle function outcomes. The primary approach will still focus on documenting changes in muscle mass by imaging techniques, but we also intend to see the functional impact of that change. We look forward to sharing those data.

Thanks, Akshay.

Thank you. I am showing no further questions at this time. This will conclude today's conference call. Thank you so much for participating, and you may now disconnect.