Scholar Rock Holding Corporation (NASDAQ:SRRK) Q4 2025 Earnings Call Transcript

Scholar Rock Holding Corporation (NASDAQ:SRRK) Q4 2025 Earnings Call Transcript March 3, 2026

Scholar Rock Holding Corporation beats earnings expectations. Reported EPS is $-0.88, expectations were $-0.88252.

Operator: 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.

Laura Ekas: 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?

David Hallal: 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, 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 up ipilimumab to children and adults living with SMA as rapidly as possible. We are pleased with 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 epitigramab 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 abitigromab should have access to opitigromab. 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 ipilimumab in infants and toddlers with SMA. Our IND for upitigromab 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 epitromab, we shared the promising results of a Phase 1 study comparing subQ and IV epitogromab 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 four thirty nine 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 added we we are pleased to have ended 2025 with $368,000,000 in cash and cash equivalents. This includes $60,400,000 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 $550,000,000, 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 epitigramab 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 epitogromab and SRK-four thirty nine 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 upitikramap 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?

Akshay Vaishnaw: Thank you, David, and good morning, everybody. As David noted, we remain focused on our apritamab 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 ipilimumab BLA following a successful FDA reinspection of the Kaplan, Indiana facility. I would now like to provide an update on the status of our second drill 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 PA BLA with this facility later in 2026. Outside of the U.S., our ipilimumab 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 ipilimumab in infants and toddlers under the age two. This trial is enrolling participants who have been treated with an SMN1-targeted gene therapy or who are receiving ongoing treatment with an SNN2-targeted therapy.

The study is important for two reasons in particular. First, it is anticipated to expand the impact of the ipilimumab to the full spectrum of patients currently being treated for SMA, as this is the first time we are evaluating the use of opicumab in the organza-treated patients in a clinical trial setting. Second, we believe early intervention with upivimab could support muscle during the critical early development phase, complementing SMN target therapy that aims to preserve motor neuron. By promoting muscle growth on both motor neurons and muscle, muscles are still maturing, apivolumab 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 ipilimumab, parsioscapular humeral muscular dystrophy, or FSHD. FSHD is a rare, devastating neuromuscular disease with significant unmet need. More than thirty thousand patients are diagnosed in the U.S. with Europe 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 ipilimumab 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 FlexFlow four mouse model that provides mechanistic rationale for a cogumab in FSHD. Using this mouse model showed that mystatin inhibition can produce robust increase 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 hypercapacities to show functional benefit. For example, in studies of either rigorous physical therapy or treatment with anabolic agents, patients with FSHD demonstrated increases in lean mass muscle function. These data suggest that the oprimumab as a monotherapy may have the potential 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 pipigimod, and s r p four twenty nine. In our s r pipilimumab program, we showed some very exciting data from a Phase 1 study earlier this year. In that study, healthy volunteers received ipilimumab v epiva 100 or 800 mg subQ or 800 mg IV. The data demonstrated that 800 mg subQ resulted in an overlap pharmacodynamic profile with 800 IV. Accordingly, sub qpigramat appears to have favorable bioavailability with the pharmacodynamic profile comparable to IV administration. Additional development activities with subcu efiblimab are underway. We are planning engagements with U.S. and European regulators.

Turning after SRP four through nine, we discovered by leveraging our work work leading expertise in targeting mystatin. Four three nine is a subcutaneously administered mystatin inhibitor binding to both pro and latent mystatin with high affinity and selectivity. We recently presented data demonstrating that four twenty nine is 10 times more potent than epinephrine. We have shown in nonhuman primate that four three nine changes in whole body lean map 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 and bring upivimab to children and adults with SMA whilst in parallel investing with discipline to advance our world-leading anti mastectomy 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?

R. Keith Woods: Thanks, Akshay, and good morning, everyone. As David noted, our team continues to operate with urgency as we prepare for the launch of opitigramab. 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 $5,000,000,000 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 epitigramab, 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 epitogromab 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 relationship, 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 epitogromab 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?

Vikas Sinha: Thank you, Keith. Our financial objectives for 2026 remain consistent. We are focused on supporting our commercial build to deliver a strong epididymumab 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 $91,900,000 in operating expenses, which included $19,400,000 in non-cash stock-based compensation. Excluding stock-based compensation, operating expenses were $72,500,000. For the year ended 2025, we reported $384,600,000 in operating expenses, which included $75,600,000 in non-cash stock-based compensation.

Excluding stock-based compensation, operating expenses were $309,000,000 for the year ended 2025. Turning to our balance sheet, we ended 2025 with $368,000,000 in cash and cash equivalents. During the fourth quarter, we strengthened our cash position, adding $60,400,000 from the exercise of a warrant that was set to expire on December 31. We continue to spend on our balance sheet and are pleased to announce today that we secured a new debt facility for up to $550,000,000 with Blue Oak Capital. This debt facility consists of four elements. First, upon closing, $100,000,000 was immediately available to us, which we have used to repay our prior $100,000,000 debt facility with Oxford Finance. Second, an additional $100,000,000 is available to us this quarter, which we expect to draw down by March 31.

Then, following FDA approval of apecigumab, we have the option to draw up to $150,000,000 in additional capital. And lastly, we have an option for an additional incremental facility of up to $200,000,000 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 $150,000,000 available from the debt facility upon FDA approval of apritamab, 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 abalizumab commercial launch readiness in the U.S. and Europe, strengthening our supply chain to support the pipeline and commercial demand for our digital map, 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?

David Hallal: Thanks, Vikas. In closing, we remain focused on bringing ofitigramab, 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.

Q&A Session

Operator: 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.

Eric Thomas Schmidt: 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.

David Hallal: 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 FDA and Novo has has has made 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 sites that that really the gating item now just is a reinspection follows these routine manufacturing activities as Novo moves into full-scale production. As far as you know, 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. And that would then trigger. We are at the ready to submit our BLA submission very, very quickly. But it really would be with you know, some level of confidence that it was a successful rate.

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

Tazeen Ahmad: 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?

David Hallal: Thanks, Tazeen, very much. As I noted on the call, we are we are gratified in the rapid and steady progress that has been made, you know, between FDA and Novo. And we do think of and the importance of ipilimumab for the SMA community is key driver in this. Not the sole driver, but a key driver in this. 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 looked at that as an back. Important effort on our part no matter what because we cannot control everything in this process. And we do not really believe that that 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 need be, on behalf of children and adults living with SMA.

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

Tessa Thomas Romero: 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.

David Hallal: 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 I think it was really set off by that in-person Type A meeting that we held with FDA and where there really was, with CURE SMA in attendance, with Novo in attendance, there was a shared, you know, sense of urgency to bring opitogramab to patients. And so while I cannot really comment on, you know, what was the overall sort of objective, we do think what it shows is, you know, for just weeks after a really constructive meeting with Novo in early Q1, where there were no new requests by the FDA of Novo into 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.

So overall, we just feel good about the drumbeat of progress here, and we are quite pleased, and we would expect, given this, you know, sort of rapid and steady pace that we have seen over these last three months, that anything else that follows, the timing of a reinspection, the timing of resubmission, that review, you know, hopefully, it continues to follow sort of this commitment that has been made to rapidly progress the epitogromab file so that we can deliver this drug to children and adults living with SMA. And we will certainly keep you apprised on that progress. Thank you.

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

Mani Foroohar: 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, label, etcetera, with regulators? And then maybe just as a second one on the pipeline, can you talk about the strategy for April? 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 application? Thanks.

David Hallal: Thanks, Thanks, Brian. Regarding the timing, again, just to remind, you know, 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 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, again, we would just point to without really being able to comment on timing, we would just kind of point to, you know, 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 to really working with urgency as well, and we will keep you apprised on that timing.

Regarding the pipeline at $4.39 auction, Yeah. $4.39, obviously, is a very important, exciting drug. It is a high potency antimyostatin antibody. Appears to us at least in the preclinical work to be about tenfold more potent. So could be a very low volume, small volume, infrequent administration type drug. So I think that creates very interesting and exciting possibilities in the neuromuscular space for us that at least at the current time, we think this is a scholar of the bioreactor, and we have no intentions of harm right there. But we will share further development plans after we get the top-line Phase 1 data rate.

Operator: Thank you.

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

Srikripa Devarakonda: Hey, guys. Thank you so much for taking my question. Time lines wise, not to be over the point, 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 the 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 for a potential CNPV for epitogromat? Thank you.

David Hallal: I did not get the last part of that, Kripa. Could you say any indication of commissioners—

Srikripa Devarakonda: Commissioner’s priority voucher.

David Hallal: Oh. The national priority voucher. The these are all very good questions, Kripa. And as you might imagine, we have thought about it all. Right? And we, 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 sort of this steady FDA prioritization and progress with Novo, you know, over these past weeks and months, and it remains, you know, very steady. And I think, like, we have thought about Class 1 versus Class 2, and what we have seen actually in our own sort of analysis of this, even when Class 2s are sort of granted, oftentimes, the decision is taken up before that six-month timeline.

And, again, I am just reminding you that the sole approvability, you know, issue for us has been the status of the Catalan Indiana facility. And, you know, we are pretty we are planning for the resubmission to be happening once we have indication that it was a successful reinspection. So we will keep you apprised at that, but we certainly are, you know, very, very comfortable with the guidance that we have provided. And then regarding, like, the commissioners, sort of, I would just say that we are just staying in close communication with the FDA on all of our different initiatives and just keeping in 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.

And we look forward to continuing to keep you guys apprised on our regulatory progress there with FDA.

Operator: Great. Thank you so much.

Operator: Thank you. And our next question will come from Michael Yee with UBS. Your line is open.

Michael Yee: 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 nonambulatory and with no issues regarding age subgrouping, given that you had what sounds like a very successful review process and only CMC was the outstanding part? How should we think about a broad label? And then a follow-up, assuming approval, for Vakaast, 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.

David Hallal: Thanks, Michael. Akshay, on the label and then, you know, Keith on the weight-based element of the drug and price action.

Akshay Vaishnaw: Yeah. Michael, you know, we were gratified by all the progress made during the original cycle. He 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 cabin issue being the only outstanding issue, we have to split that 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, that is up to the FDA. But we know from the conversation leading up to the September date that kind of the guiding principles are what—excuse me—what the FDA has shown before in the SMA space, the trial design that supports the approval, that is important. Now if you note that the totality of that package, we have experienced with both nonambulatory and abulatory.

We have experience with children two years and older. They have experience in patients on this decline and this in medicine. And so I think that these are important guiding factors. James also previously tended to look at the full applicability or not of the therapy hypothesis and the next of action of the drug to try and maximize getting these drugs in the terrible disease as many patients as possible. Now those are the kind of guiding principle. I think we have to waive the ultimate BLA resubmission and see where we end up. But we have been pleased so far with how straightforward we can get this approach.

R. Keith Woods: Yeah. And then on price, you know, I guess, first of all, 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 lopidogrelimab, 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 on the launch call.

Operator: Thank you.

Operator: Thank you. And our next question is going to come from Amy Lee with Jefferies.

Amy Lee: 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 subcu api. 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.

David Hallal: Thanks very much, Amy, and yeah, what I would say is that, you know, for sure, we have been pleased in our engagement with the patient community, the caregiver community, as well as, as Keith noted, neurologists’ appreciation that not only addressing the motor neuron component of the disease, but for the first time, to really be able to address directly the muscle component of the disease, which is a 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, like, 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 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, but we think that will be met with initially some access speed bumps that could impact our launch curve. But overall, the long term that we see for opiticlimab in the U.S. and beyond we feel like is quite significant for us, and we are really looking forward to the eventual approval and then Keith and team launching a pitogram to the SMA community. With respect to your question on subcu and clinical regulatory strategy, I will hand that over to Akshay.

Akshay Vaishnaw: Yeah. Thanks, David. So for subQ berivimab, what we have is very interesting and supportive data that the subQ route is viable, shows excellent bioavailability, and a pharmacodynamic profile. Now we know a lot about afliberumab in terms of PK/PD from our prior work, clearly IV administration. Obviously want to leverage that by saying, you know, this is a drug that is well characterized and studied by different administration. But if we can mimic the appropriate PK/PD, then there is no reason why it cannot be equally safe and effective. Now those are all discussions that we need to have with the FDA. The initial approval of the drug, of course, is very important. But subsequent to that, hope to get aligned with regulators on that approach. So, ultimately, we cannot guide the timelines today, but we are hoping you have progressive regulators. Formulate our final time with them. Discuss the path forward.

Amy Lee: Great. Thank you.

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

Jeff Meacham: Good morning, guys. This is Jarway 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 guys can give some color on that, it would be helpful. Thanks.

David Hallal: Absolutely. I will start with the second vial, and then, Keith, you might need clarification on the second. Yes. Can you repeat the second question, please?

Jeff Meacham: Yeah. Sure. What specific leading indicators are you guys paying attention to to indicate, you know, payer and physician readiness that you are tracking?

David Hallal: Great. So second fill finish. We are really pleased with the progress we have been making. As I mentioned, you know, 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 FBLA. Should we rely on this facility solely, we are confident that we would be derisking as well our U.S. and EU commercial opportunities. So we wanted to be very thoughtful in selecting the right second partner for fill finish, and we are gratified that we have done that. And, also, as I noted, really pleased with the progress that is being made at a very rapid pace. Keith?

R. Keith Woods: 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, to not just the big national payers, but also now 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 research, just as what has been shared in a lot of the Cure SMA data in some of our own markets, you know, neurologists and patients, they want more, and they need more. And that is why we understand three-quarters of these physicians already believe in multiple modalities to treat this—to treat SMA.

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

Salvator Caruso: 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?

David Hallal: I will start, and then I can hand it over to Akshay. There is a mutual recognition between both FDA and EMA. And so this steady and rapid progress we are making with FDA actually serves us very well for the current MAA review with regulators. And so it is very important that we continue to make this progress forward. As I noted, the continued remediation and eventual, you know, successful reinspection will really support our EMA decision near midyear. And then as I noted, 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—

Akshay Vaishnaw: Yeah. You covered it, David. I think the other piece that we can close touch with with doing the policy with the—so that is really what it is that is important, and we all await those additional this action by which will obviously not take approvals.

Salvator Caruso: Thank you.

Operator: You. The next question will come from Etzer Darout with Barclays. Your line is open.

Etzer Darout: 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 epitogromab? And then on FHSD, 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 nine longer term? Thank you.

David Hallal: 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, but there would be an update to sort of 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 sort of functional outcome measures.

Akshay Vaishnaw: Okay. Yeah. So we are in line with the FDA. And the budget meeting was useful in many regards, including that and both the which aspect of the safe take place needs to be updated. So that is all agreed to, and so we are ready and prepared with this BLA resubmission. So I do not see any brain issues there, but it is a good question, and, obviously, we should always provide the FDA with a latest safety understanding about which we will do. With respect to the FORGE Phase 2 study in FSHD, the primary endpoint will focus on increasing lead muscle volume measure very sensitive with both imaging techniques. But we will have home state environment treatment, which is a validated approach in FSHD, to understand the functional impact of any potential change in muscle mass. And we look forward, obviously, to those data too.

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

Evan Seigerman: Hi. Malcolm Hoffman on for Evan. Thanks for taking our here. Thinking about the financials of the business. I know you mentioned the new debt facility secured with approvals 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.

David Hallal: Thanks, Malcolm. Vikas?

Vikas Sinha: 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. But overall, looking at a fundamental principle of creating long-term shareholder value.

Akshay Vaishnaw: Thanks, Vikas. Thanks, Malcolm.

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

Allison Bratzel: 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 FDA’s sense of urgency on ipilimumab. I guess, is there good precedent for 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 opitigimod in the SMA community. Thanks.

David Hallal: Thanks, Allison. Maybe I will just, you know, point out one example on the Class 2 not taking the full time, and I think it is important that we have been mentioned occasionally here during this current journey, with Regeneron. In a CRL 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. And so but we have more examples than that. I just point to that. It is a little bit relevant given the fact that it was CRL, and it was the same facility. And I think it had to do with some assessment of the facility post an inspection. So I would just point your attention to that.

Akshay Vaishnaw: Yeah. So yeah. Following up on that is what is my treatment for. The—the enrollment’s going very well. I mean, I think the first thing say actually is people who get enrollment that very, like, knowledge and appreciation for a muscle-based approach in the patient community and the prescriber community. And Keith has spoken about fact is startlingly high and patients, families, and physicians are waiting the approval of this drug. And consistent with that, the stroke throughout the entire patient. They see the, you know, the possibilities age range and disease severity range. As a community and we have verified by the very nice progress we have had. I am not going to share details today, but, yes, we are seeing a good clip of enrollment and, yeah, as we get later into the year, we will clarify, you know, if the sort of comes into sight.

But exactly when we have data and so forth. But are fairly consistent with knowledge of the drug in its potential. It is very good in.

David Hallal: 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, really pleased that we are making sure no patients are left behind by opening up this under two study. So we are super excited to be doing this work in the youngest of patients with SMA.

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

Kalpit Patel: Hey. This is Dugan on for Kalpit. Previous myostatin inhibitors and FSH increased muscle mass without meaningful functional improvement. You give some color on how eptigramab aims to address this historical hurdle and what clinically meaning functional improvement might be in the planned Phase 2?

Akshay Vaishnaw: Sure. Yeah. So I think you are pointing to either drug that did not have a very clear and well validated mechanism of action and potency safety profile. The earlier generations of adenosinemia have a potency, the selectivity. Of drug that has been in our opinion. More importantly, another one is the another point you raised is the Exelon example. I just suspect. Exelon did a study in FSHD, and they reject low fee in one isolated muscle. Now one cannot expect that to result in global, you know, functional improvement. But we do know separately that globally applied strategies like intense physical therapy, or anabolic agents that increase muscle mass, such as those—mastectomy—or rather growth hormone and testosterone and other similar agents, that those kinds of patients clearly show an increase in muscle mass and also increase in functional capacity.

So we incorporated contact myometric testing into the Phase 2 to evaluate changing muscle function. The primary approach, or the primary endpoint, obviously, is to document change in the muscle volume. But we look forward to getting those data, and that is a validated approach to that patient. And we will share the data.

David Hallal: Thanks, Akshay.

Operator: 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.