Q2 2025 Scholar Rock Holding Corp Earnings Call

Okay.

If you would like to ask a question. During this time simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question Press Star one again.

This call is being recorded on Wednesday August six 2025, I would like to turn the conference over this call Iraq. Please go ahead.

Good morning, I'm actually not senior Vice President of corporate Affairs, and Investor Relations at scholar Rock with me today are David Hello, Chairman and Chief Executive Officer, Akshay <unk> President of R&D, Keith Wood, Chief operating Officer, and <unk>, Chief Financial Officer for those of you purchase.

The painting via conference call. The accompanying slides can be accessed by going to the events section of the investors page on our website.

During today's call as outlined on slide two David will provide introductory remarks and provide a general business update Akshay will review, our clinical and regulatory progress Keith will provide an update on our commercial readiness activities for our pedigree Mab and Vikas will provide commentary on our financials and then we will 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 <unk> 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 1095.

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 <unk> media section of our website for our most up to date SEC statements and filings with that I'd like to turn the call over to David David.

Thanks, Robbie and good morning.

Thanks to everyone for joining our Q2 update call today.

This is an exciting time of great strength and opportunity at scholar rock.

We are scaling for the next phase of growth as a commercial stage fully integrated global biopharmaceutical company.

Our three core priorities drive our vision of becoming a global biotech powerhouse.

First <unk> regulatory approvals and following those approvals the U S launch of <unk> for children and adults with SMA.

Followed by a series of country launches in the coming years, starting in Europe with Germany next year.

Second expand the pit at <unk> into additional rare severe and debilitating neuromuscular diseases.

Third disciplined capital allocation to support our high value commercial and development initiatives.

With respect to our ongoing regulatory processes, we are working collaboratively with the FDA and European Medicines agency.

We are also urgently preparing for our U S commercial launch as our BLA has been accepted under priority review with a target action date of September 20 <unk>.

As you are aware DXP inspections are part of the standard FDA review process, including those relating to pre approval inspections clinical trial site inspections and manufacturing site inspections.

These inspections often result in observations requiring responses within the review cycle. The FDA has conducted a full set of inspections and as part of this process noted observations at two of our <unk> on.

On Friday August one another pharmaceutical company disclosed observations as part of an FDA General site inspection at their filler Cadillac, Indiana, which was recently acquired by Novo Nordisk.

Our fill finish for Pilgrim App is conducted at the same site.

The general site inspection of the facility was not specific to a particular map.

Novo Nordisk submitted a robust and comprehensive response earlier this week to the observations noted by the FDA.

For the other CMO observations were received at the conclusion of a pre licensing inspection and a comprehensive response will be submitted within the next week.

We continue to work collaboratively with the agency.

Importantly, the FDA recently completed our late cycle meeting following both site inspections.

We are encouraged by the dialogue with the agency at the late cycle meeting, where the FDA indicated that they are working towards completing the review of our BLA by our September 20.

Could do for date.

Earlier this year, we also filed our MAA for <unk> in the EU and we continue to work with the European Medicines agency and expect a potential approval near mid 2026.

We are planning for Germany to be our first European country launch with an ambition to reach patients with SMA across all of Europe, followed by additional countries in Asia Pacific and Latin America over time.

Good morning, Mages and gentlemen, and welcome to this caller rocks, second quarter 2025 business update conference call.

At this time, all lines are in a listen-only mode.

The global opportunity with <unk> in SMA alone offers the potential for many years of sustainable growth through the end of this decade and into the next.

Following the presentation, we will conduct a question and answer session. If you would like to ask a question during this time, simply press star followed by the number 1 on your telephone keypad. If you would like to withdraw your question, press star 1 again,

Along with Keith Akshay and V costs.

6 2025, I would like to turn the conference over to this caller Rock. Please go ahead.

And the other leaders at the company, we have bolstered scholar rock's capabilities as we advance our mission to deliver a pedigree mab to children and adults with SMA.

This is indeed, what we know well and what we do well.

In addition to the large opportunity to serve patients with SMA, we will continue to expand our pipeline by planning additional opportunities for <unk> for children and adults suffering with additional rare severe and debilitating neuromuscular disorders, which akshay will discuss in more detail shortly.

Good morning, I'm Russian officer, vice president of corporate Affairs, investor relations at scholar rock with me today, are David hallal, chairman and chief executive officer. Akshay vashal president of R&D Heath Woods Chief Operating Officer and vacasa Chief Financial Officer.

For those of you participating via conference call the accompanying slides can be accessed by going to the event section of the investors page on our website.

Importantly to grow scholar rock, we are taking a thoughtful deliberate approach to capital allocation by staging our investments along with our commercial progress in serving the SMA community.

During today's call as outlined on slide 2, David will provide introductory remarks and provide a general business update. Ashay will review our clinical and Regulatory progress.

Keith will provide an update on our commercial Readiness activities for a pedigree map and Vos will provide commentary on our financials. And then we will open the call for questions.

Q2 has been exceptionally productive.

In the quarter when Keith joined our team as our Chief operating officer. He brought a proven track record of building and leading teams to deliver highly successful rare disease global launches in the neuromuscular therapeutic area, including most recently with <unk>.

Before we begin, I'd like to remind you that, during this call, we will be making various statements about scholar, rocks, 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.

Under Keith's leadership, we have assembled an exceptionally experienced talented and patient centric field team committed to the SMA community.

Impressively over just a few months the team is on board trained and deployed and are ready to deliver a <unk> to the SMA community pending approval in September.

I encourage you to go to the investors media section of our website for our most up-to-date FCC statements and filings with that. I'd like to turn the call over to David. David, thanks, Rashmi, and good morning. Thanks to everyone for joining our Q2 update call today.

This is an exciting time of great strength and opportunity at scholar Rock.

Despite currently available treatments that have been approved over the past 10 years, we are acutely aware that muscle strength and motor function are among the top unmet needs in SMA, which we believe can be addressed with the potential approval of <unk>, the world's first and only muscle targeted therapy.

We are scaling for the next phase of growth. As a commercial stage fully integrated global bioharmony.

Our 3, core priorities Drive, our vision of becoming a global biotech Powerhouse.

First a pedag regulatory approvals.

To deliver statistically significant and clinically meaningful improvements in motor function in a pivotal phase III trial.

And following those approvals, the US launch of a pedigree map for children and adults with SMA.

I would like to now turn briefly to the readout of the positive phase II embraced proof of concept study in Q2.

Followed by a series of country, launches in the coming years, starting in Europe with Germany next year.

The goal of Embraer was to understand the role of targeting myostatin in the treatment of patients with obesity.

Second expand, a pedigree AB into additional rare severe and debilitating neuromuscular diseases.

We are pleased that the embrace study met the primary endpoint with patients on <unk> appetite.

And third disciplined Capital allocation, to support our high-value commercial and development initiatives.

<unk> increased lean mass preservation by greater than 54% compared to Sears appetite alone.

With a P value equal to 0.001 with an encouraging safety profile.

With respect to our ongoing regulatory processes, we are working collaboratively with the FDA and European medicines agency.

We are very pleased that the highly selective anti myostatin approach from our innovative platform continues to deliver.

We are also urgently preparing for our us commercial launch. As our bla has been accepted under priority review with a Target action, date of September 22nd.

While we remain focused on advancing <unk> in clinical development for additional rare severe and debilitating neuromuscular disorders embrace raises the exciting possibility to partner, our potent and selective approach to targeting myostatin as.

As you are aware, GXP inspections are part of the standard FDA review process.

Including those relating to pre-approval, inspections of clinical trial sites, inspections, and manufacturing site inspections.

As we communicated at Embraer data readout. In addition to <unk> 439, we have a number of earlier stage research assets, both anti myostatin antibodies and the fusion of those with <unk>, which we think have the potential to be meaningful therapeutic candidates in the future.

These inspections often result in observations requiring responses within the review cycle.

The FDA conducted a full set of inspections, and as part of this process, noted observations at 2 of our CDMOs.

As we look forward, we remain very focused on the nearly 35000 patients with SMA globally that have received SMN targeted therapies.

While we anticipate the global launch will commence in the U S. In Q3 pending regulatory approvals. We are also making preparations to serve children and adults with SMA in Europe Asia Pacific and Latin America.

On Friday, August 1, another pharmaceutical company disclosed observations as part of an FDA general site inspection at their facility in Catalan, Indiana, which was recently acquired by Novo Nordisk.

Our fill finish for a pig is conducted at the same site.

The general site. Inspection of the facility was not specific to a pig or map.

Our ambition at scholar rock is that globally any patient with SMA, who can benefit from <unk> should have access to a pedigree mab.

Novo, Nordisk submitted a robust and comprehensive response earlier this week to the observations noted, by the FDA.

At this point I'll turn the call over to Akshay to provide a more detailed update on our R&D progress akshay, Thanks, David and good morning, everyone.

For the other CDMO observations, responses were received at the conclusion of a pre-licensing inspection, and a comprehensive response will be submitted within the next week.

SMA is a rare severe neuromuscular disease, resulting in an irreversible loss of motor neurons and progressive muscle wasting that causes continuous motor function decline throughout life diminishing the independence of the children and adults.

We continue to work collaboratively with the agency.

Importantly, the FDA recently completed, our late cycle meeting following both site inspections.

There has been progress over the last decade with new therapies for SMA.

However, despite the chronic use of these SMN corrector SMA remains a devastating disease for children and adults and families living with the disorder.

We are encouraged by the dialogue with the agency at the late cycle meeting where the FDA indicated that they are working towards completing the review of our bla by our September 22nd Padua date.

Patients experienced muscle wasting that impacts all aspects of mobility basic activities of daily living like eating Washington, dressing and the ability to live independently.

Continue to work with the European medicines agency and expect a potential approval near Mid 2026.

Multi unit has two key components I mentioned it on itself and muscle.

<unk> targeted therapies aimed at preventing mentioning on loss of muscle principled and effectiveness in may.

Been directly address.

Given that most function dependent not only on the road or signaling, but also muscle responsiveness approaches that target muscle from the stone urgently needed.

We are planning for Germany to be our first European country launched with an ambition to reach patients, with SMA across all of Europe, followed by additional countries in Asia Pacific and Latin America over time.

Yes.

the global opportunity with a pedag app and SMA alone offers the potential for many years of sustainable growth, through the end of this decade, and into the next,

Alpha trial should read those receiving chronic ongoing <unk> targeted therapies are critical map has the potential to reverse the progression of SMA from a loss of motor function <unk> function.

Along with Keith ashay and vikas.

And the other leaders at the company we have bolstered scholar rocks capabilities, as we advance our mission to deliver a pedag, Ab to children and adults with SMA.

Specifically the study demonstrated a statistically significant improvement in motor function as measured by the gold standard Hammersmith motor function scale, while patients on placebo worsened.

this is indeed what we know, well and what we do well,

Importantly patients treated with the political map.

Approximately three fold higher chance of a three point or greater increase in Hammersmith versus those on placebo.

In addition, there was a consistent one eight point improvement in Hammersmith across all ages and a phase III trial.

In addition to the, large opportunity to serve patients with SMA, we will continue to expand our pipeline by planting additional opportunities, for a pig, AB for children and adults suffering with additional rare severe and debilitating neuromuscular disorders, which Axe will discuss in more detail shortly.

Along with the encouraging safety profile to satisfy data suggests that our pet-sitter map has great potential to provide clinically significant benefit to patients with SMA. Despite the current accused of SMN targeted therapies.

Importantly to grow scholar Rock. We are taking a thoughtful deliberate approach to Capital allocation by staging our investments, along with our commercial progress in serving the SMA community.

Q2 has been exceptionally productive.

As David mentioned, our BLA was accepted under priority review, which recognizes the potential of a critical map to be a treatment for a serious or life threatening condition.

To provide a significant improvement in safety or effectiveness over existing treatments IMAX.

Im excited that our team continues to work collaboratively with regulators towards the September 20 <unk>.

In the quarter, when Keith joined our team as our chief operating officer. He brought a proven track record of building and leading teams to deliver. Highly successful rare disease, Global launches in the neuromuscular therapeutic area including most recently, with vyvgart,

With respect to Europe. The MAA was validated by EMA and we look forward to further review and the approval of critical map in Europe in 2026.

Under Keith's leadership, we have assembled, an exceptionally experienced talented and patient Centric. Field team committed to the SMA community.

Turning to the next slide I am pleased to report that we're on track to initiate the phase II <unk> trial in children under the age of two.

Impressively over just a few months. The team is on board trained and deployed and are ready to deliver a pedag to the SMA Community. Pending approval in September.

The study is evaluating two different doses over the course of 48 weeks and we will assess PK PD efficacy and safety.

Enrollment concho abroad in infants and toddlers, maybe enrolled with any approved SMN targeted therapy, including gene therapy.

Early intervention with the political map, India study could support muscle during the critical early developmental phase complementing <unk> targeted therapies that aim to preserve much neurons.

Despite currently available treatments that have been approved over the past 10 years. We are acutely aware that muscle strength and motor function are among the top unmet needs in SMA, which we believe can be addressed with the potential approval of a pedigree map, the world's first and only muscle targeted therapy to deliver statistically significant and clinically meaningful improvements in motor function in a pivotal phase 3 trial,

By promoting muscle growth with both merge neurons and muscle are still forming a political map has a unique opportunity to improve motor outcomes in babies and toddlers with SMA.

I would like to now turn briefly to the readout of the positive Phase 2, Embrace proof of concept study in Q2.

The goal of embrace was to understand the role of targeting myostatin and the treatment of patients with obesity.

Turning to our plans for the study, but put a map in additional rent in severe neuromuscular disease at the outset, let me state that the potential to prevent muscle loss and enhance muscle growth by blocking myostatin holds great potential across a wide array of diseases.

We are pleased that the Embrace study met the primary endpoint with patients on tapete.

A pedigreed. Lean mass preservation by greater than 54% compared to S zeppet alone.

Do you see just two examples of that potential in mouse models of the severe debilitating disorders, duchenne muscular dystrophy, or DMD and fastest scapulohumeral dystrophy or sshd.

With a P-value equal to 0.001 and an encouraging safety profile.

We are very pleased that the highly selective anti-masturbation.

In the PMT model on the left the inclusion of an anti myostatin antibody in mice, receiving an exon skipping all ago is associated with a dramatic increase in the level of dystrophin and the resulting increase in muscle force.

While we remain focused on advancing a pedigree map in clinical development for additional rare, severe, and debilitating neuromuscular disorders, Embrace raises the exciting possibility to partner our potent and selective approach to targeting myostatin.

Sshd is a neuromuscular disease, resulting in patchy changes with affected and unaffected motor fibers.

In the <unk> model and the right treatment with an anti myostatin antibody, resulting hypertrophy of unaffected merch units and once again in passive gain at motor function.

As we communicated at Embrace data readout, in addition to srk 439. We have a number of earlier stage research assets, both anti-motion the fusion of those with glps, which we think have the potential to be meaningful, therapeutic candidates in the future.

We continue our evaluation of an antibody approach in DMD NFS HD as well as in other models of disease and will initiate the study of a political map and then additional neuromuscular indications by the end of 2025.

As we look forward we remain very focused on the nearly 35,000 patients with SMA globally that have received SMN targeted Therapies.

In June we were gratified to announce exciting results from our embrace proof of concept study.

David It's covered those findings, including that the study met the primary endpoint with an encouraging safety profile.

While we anticipate, the global launch will commence in the US and Q3 pending regulatory approvals. We are also making preparations to serve children and adults with SMA in Europe, Asia Pacific and Latin America.

These findings are important as preservation of lean master in GOP, one media to weight loss has the potential to enhance both cardio metabolic and muscular skeletal health.

Our ambition at scholar rock, is that globally any patient with SMA who can benefit from a pedag? Should have access to a pedag app?

Next we continue to advance our world, leading anti Myostatin platform beyond the pivotal map fair.

At this point, I'll turn the call over to AI to provide a more detailed update on our R&D progress, AI. Thanks. David and good morning everyone.

Further to our commitment to neuromuscular disease <unk> hundred nine builds on the validated approach that delivered a critical map.

There is great potential for <unk> 49 to be an infrequent potent subcutaneous anti myostatin antibody and we look forward to exploring its potential another innovative scholar rock therapy for patients suffering with severe neuromuscular disorders.

You need IR, irreversible loss of motor, neurons, and progressive muscle wasting that causes continuous motor function, decline, throughout life diminishing, the independence of both children and adults.

We remain on track to follow the R&D application for <unk> hundred $39 to support the first in human study later this year.

There's been progress over the last decade with new therapies for SMA. However, despite the chronic use of these SMN correctors SMA remains a devastating disease for children adults and their families living with the disorder.

I'd like to conclude by reiterating our key priorities.

Number one drive the U S approval of a critical math in Q3 to <unk> 25, and advanced the EU toward approval in 2026.

Patients experience muscle wasting that impacts. All aspects of Mobility, basic activities of daily living like eating, washing and dressing and the ability to live independently.

Remember to initiate a study of our critical map for infants and toddlers with SMA under the age of two in Q3 25.

Number three initiate clinical development of our bigger map in at least one additional neuromuscular indications by the end of 'twenty five and finally final 90 restaurants, a full 309 in the second half of 'twenty fight.

The motor unit has two key components: the motor neuron itself and muscle. SMN-targeted therapies are aimed at preventing motor neuron loss, but muscle—the principal organ affected in SMA—has not been directly addressed.

Given that motor function. Depends not only on neuronal signaling, but also on muscle responsiveness approaches that Target muscle from the start are urgently needed.

With that I'll turn the call over to Keith to provide a commercial update Keith.

Thanks, Akshay and good morning, everyone with a tenant or a mab advancing through the regulatory processes in the U S and Europe, we are preparing to usher in a new era for the treatment of children and adults with SMA.

Our Sapphire trial showed that in those receiving chronic ongoing SMN-targeted therapies, a pilgrim map has the potential to reverse the progression of SMA from a loss of motor function to a gain of motor function.

This is a progressive and devastating disease that leads to loss of mobility limited activities of daily living and a lack of independence.

Specifically, the study demonstrated a statistically significant Improvement in motor function as measured by the gold standard Hammersmith motor function scale while patients on placebo worsened.

If muscle was left untreated. It can result in irreversible atrophy, we're excited about <unk> potential as the first and only muscle targeted treatment to show clinically meaningful and statistically significant motor function improvements in children and adults living with SMA.

Importantly, patients treated with the pilgrim map had an approximately 3 fold higher chance of a 3-point or greater increase in Hammersmith versus those on placebo.

In addition, there was a consistent 1.8 Point Improvement in Hammersmith across all ages in a phase 3 trial.

The SMA community is calling for a treatment to address progressive muscle degeneration and motor function loss to.

To underscore this a 2025 cure SMA survey showed that 90% of patients report that they are greatest unmet need is to gain muscle strength.

Along with the encouraging safety profile, the Sapphire data suggests that a Pilgrim map has great potential to provide clinically significant benefit to patients with SMA, despite the chronic use of SMN-targeted therapies.

Our market research and interactions with health care professionals tell us that 80% of treating neurologists agree that preserving muscle should start as early as possible in treating patients living with SMA.

As David mentioned, a bla was accepted under priority review, which recognizes the potential of a pilgrim map to be a treatment for a serious or life-threatening condition or to provide a significant Improvement in safety or Effectiveness, over existing treatments.

I'm excited that our team continues to work collaboratively with Regulators towards the September 22nd pedophile date.

<unk> recognized that in the future a treatment approach of dual modalities to target the motor neuron and the muscle will be necessary to treat SMA.

With respect to Europe, the ma was validated by EMA and we look forward to further review and the approval of pedag in Europe in 2026.

We are on track with the preparation of the global launch of <unk>, starting with the U S base.

turning to the next slide and please report that we're on track to initiate the phase 2, opal trial in children under the age of 2,

Based on our September 20, <unk> date, we will execute our commercial launch of <unk> immediately following our FDA approval in Europe. Our MAA is under review by the European Medicines Agency and we are preparing to launch upon approval in 2026.

The study is evaluating 2 different doses over the course of 48 weeks and will assess PK DD efficacy and safety.

I am excited to announce that as of today under the leadership of our U S General manager and Chief brand Officer, Rebecca Macleod, Our U S customer facing team is fully onboard train and now deployed in the field.

Enrollment criteria abroad and infants and to toddlers. May be enrolled with any approved SMN, targeted therapy, including gene therapy.

Early intervention with the Pilgrim app in the OPAL study could support muscle during a critical early developmental phase, complementing SM and Target therapies that aim to preserve most neurons.

Our team is currently engaging with the SMA treatment centers key opinion leaders and both public and private payers.

By promoting muscle growth, when both motor neurons and muscle are still forming a pilgrim. Map has a unique opportunity to improve motor outcomes in babies and toddlers with smas.

We are impressed by the talent the extensive rare disease experience and the passion to serve patients that our new team members bring.

The team is comprised of many professionals that have substantial experience in serving the SMA community or the broader neuromuscular disease community and we are United by our commitment to serving these patients.

Sending to our plans for the study of a pit of map in additional rare and severe neuromuscular disease at the outset. Let me state that the potential to prevent muscle loss and enhance muscle growth by blocking my staff in holds great potential across a wide array of diseases.

Today in the U S. There are approximately 10000 patients living with SMA and roughly two thirds of them have received and SM and targeted therapy.

Yeah, you see just 2 examples of that potential in Mouse models of the severe. Debilitating disorders, duchan muscular dystrophy or DMD and fascia scapula funeral distroy or fshd.

These investments, we are making position us to reach these patients with a <unk> and we will provide a blueprint for our global rollout.

Globally. There are approximately 35 patients with SMA that have already received an SMN targeted therapy, and we have an enormous opportunity to make a meaningful difference with updated roadmap with the potential to reverse progression of SMA from a loss of motor function to a gain of motor function the inter.

In the DMD model. On the left, the inclusion of an antimycin antibody in mice. Receiving an Exxon skipping oligo is associated with a dramatic increase in the level of dystrophin and a resulting increase in muscle Force.

Fshd is a neuromuscular disease, resulting in patchy changes with affected and unaffected motor fibers.

In the fshd model, on the right, treatment with an antimycin antibody results. In hypertrophy of unaffected motor units and once again an impressive gain in motor function

Fire scholar rock team is ready to serve the SMA community and we will move with a sense of urgency to deliver at Pittodrie map to them. Following approval now I will turn the call over to Vikas because.

We continue our evaluations of an antimycin approach in DMD and fshd as well as in other models of disease and will initiate the study of a pilgrim man in an additional neuromuscular indication by the end of 2025.

And good morning, everyone I am pleased to provide our Q2 business update and provide insights into how we're thinking about resource allocation in the future.

Embrace proof of concept study.

The opportunity with Apple, Google Admob and SME loan offers the potential for many years of sustainable growth.

David has covered those findings, including that the study met the primary endpoint with an encouraging safety profile.

And really enable strategic thoughtful investment in our pipeline to develop new indications and new therapies for an increasing number of patients. These pipeline investments will be aligned to our commercial success.

These findings are important as preservation of lean mass during glp1. Mediated weight loss has the potential to enhance both cardiometabolic and muscular skeletal health.

Next, we continue to advance how world-leading anti platform beyond the pilgrim, man.

We ended the quarter with $295 million during the quarter, we continued to increase our investment in infrastructure to support commercial readiness and on the supply of a particular map to support the launch.

Further to our commitment to neuromuscular disease, Srk 149 builds on the validated approach that delivered a Pilgrim map.

As we look ahead, we are prioritizing the commercial launch and our ongoing clinical programs.

There's great potential for srk, 439 to be an infrequent potent. Subcutaneous, antimicro and antibody, and we look forward to exploring its potential as another Innovative scholar Rock therapy for patients suffering with severe neuromuscular disorders.

Have an additional $50 million under our debt facility that we can draw down this year and we also anticipate receiving approximately $16 million from exercise of outstanding common wardens by year end, bringing our anticipated run rate into 2027.

We remain on track to file the and the application for srk 439 to support the first in human study later this year.

I'd like to conclude by reiterating our key priorities.

Additionally, $50 million available under our debt facility post approval to support upcoming launch.

Also anticipate monetizing our priority review voucher following approval.

We continue to operate with a tight financial plan and we'll share more details over the next few quarters. As a reminder, we will continue to focus on driving strong performance with financial discipline mixed.

Number 1, Drive, the US approval of a paragraph in Q3 2025 and Advance the EU toward approval in 2026 and 2 initiatives. Study of a pilgrim map for infants and toddlers with SMA under the age of 2 in Q3 255. Number 3, initiate, clinical development of a bit of a man in at least 1 additional neuromuscular indication by the end of 25. And finally,

File and IMD for srk 439 in the second half of 25.

With that, I'll turn the call over to keys to provide a commercial update.

Investing in capital efficient commercial build out.

And Hartford capital allocation to advance our pipeline with that I will turn it back to David David Thanks.

Thanks for the costs in.

In closing we are committed to successfully executing on these key priorities, which position us to transform scholar rock into a premier global biotech leader.

Please thanks. Ah, shake and good morning. Everyone with a pedigree mab advancing through the regulatory processes in the US and Europe. We are preparing to usher in a new error for the treatment of children and adults with SMA.

This is a progressive and devastating disease that leads to loss of Mobility, limited activities of daily living and a lack of Independence.

First a pedigree or mab regulatory approvals and following those approvals the U S launch of <unk>, our mab for children and adults with SMA, followed by a series of country launches in the coming years, starting in Europe with Germany next year second expanded <unk> into additional rare severe and debilitating neuromuscular diseases and finally.

If muscle is left, untreated. It can result in irreversible, atrophy.

Disciplined capital allocation to support our high value commercial and development initiatives.

We are excited about a pedigree abses potential as the first and only muscle targeted treatment to show clinically meaningful. And statistically significant motor function, improvements in children and adults living with SMA,

On behalf of every member of the scholar rock team.

The SMA Community is calling for a treatment to address progressive muscle, degeneration and motor function loss.

I want to emphasize our unwavering commitment to more than 35000 patients and their families. Our mission is to move with urgency to ensure that no patient with SMA is left behind with that we'll now open the line for questions operator.

To underscore this a 2025, cure SMA survey showed that 90% of patients report that their greatest unmet need is to gain muscle strength.

Thank you we will now begin the question and answer session. At this time I would like to remind everyone in order to ask a question.

Our market research and interactions with Healthcare professionals. Tell us that 80% of treating neurologists agree, that preserving muscle should start as early as possible. In treating patients, living with SMA.

And the number one on your telephone keypad.

And your first question comes from the line of Eric Smith with Cantor. Your line is open.

Neurologists recognize that in the future, a treatment approach of dual modalities to Target, the motor neuron and the muscle will be necessary to treat SMA.

Well, thanks, and good morning, <unk> team appreciate the transparency around your CMO issues can you tell us a little bit more about the specific observation at those two sites, whether you expect that <unk>.

We are on track with the preparation of the global launch of a pedigree AB starting with the US.

A reinspection is going to be required prior to <unk> approval and whether the two facilities right. Now are currently able to release other pharmaceutical products. Thank you.

Based on our September 22nd Padua date, we will execute our commercial launch of a pedag immediately following our FDA approval in Europe. Our MAA is under review by the European Medicines Agency, and we are preparing to launch upon approval in 2026.

Yeah. Thanks, Thanks, very much Eric.

Great to be working with you.

First I think as you know.

Eric GMP inspections are Super standard as part of the FDA review process and in fact out in 2024 based on Fda's inspection data dashboard actually more than 70% of drug quality assurance inspections.

I'm excited to announce that. As of today, under the leadership of our US, general manager, and chief brand officer, Rebecca, McCloud. Our Us customer facing team is fully on board trained and now deployed in the field.

Our team is currently engaging with the SMA treatment centers, key opinion leaders, and both public and private payers.

Resulted in observations noted by the FDA, So as I noted in the call.

We are impressed by the talent. The extensive rare disease experience and the passion to serve patients, that are new team members bring.

Look we're disappointed but we werent surprised to learn.

That two of our sites received observations I think the benefit for us as those observations were.

We're presented well within our review cycle that allow for a response and obviously a green light.

The team is comprised of many professionals that have substantial experience in serving the SMA Community or the broader neuromuscular disease community. And we are united by a commitment to serving these patients.

Always like very difficult to sort of read the tea leaves and try to understand what the FDA with those observations may want to do what they want a reinspection or not at this moment in time given the.

Today in the US, there are approximately 10,000 patients living with SMA and roughly 2/3 of them. Have received an SMN targeted therapy.

These Investments, we are making position us to reach these patients with a pedigree ab, and will provide a blueprint for our Global rollout.

Very constructive late cycle meeting that again was held after these site inspections and after these observations were provided again, the tone and tenor and collaborative nature of that late cycle meeting certainly indicated to us that.

opportunity to make a meaningful difference with a pedigree map, with a potential to reverse progression of SMA, from a loss of motor function to a gain of motor function,

The the agency.

Is.

And very much working toward completing their review of our BLA by the September 20, <unk> date I would also just note that.

We're obviously working on multiple levels with our CMO partners.

We're a skilled team or an experienced team we understand how best to work through situations like this which we are prepared to do.

The entire scholar Rock team is ready to serve the SMA community and we will move with a sense of urgency to deliver a pedigree map to them following approval. Now, I will turn the call over to Vos because, thank you, Keith and good morning everyone. I'm pleased to provide our Q2 business update and provide insights into how we are thinking about resource allocation in the future.

And David do you know whether the two facilities are releasing any product currently.

Very good question. The two facilities continue to operate of course.

The one that.

Given the disclosure on August one.

Not common practice in the industry, nor our common practice for named facilities, but in the case of Catlin, Indiana now owned and operated by Novo Nordisk, Scott certainly as you know Eric that.

The opportunity with oppido map in SMA alone offers the potential for many years of sustainable growth and will enable strategic thoughtful investment in our pipeline to develop new indications, and new therapies for an increasing number of patients, these pipeline investments will be aligned to our commercial success.

That's an important pillar across the board for a number of very important products across the industry.

We ended the quarter with 295 million during the quarter. We continue to increase our investment in infrastructure to support commercial Readiness and our supply of epidural map to support the launch.

We know they continue to be very active and the other facility continues to manufacturer product as well I think I would also note and I think this is probably important for our entire audience.

Our supply chain has produced the <unk> drug supply that has now accumulated over 600 patient years of experience through multiple years of clinical trials, including our pivotal trial in the most recent embrace trial and I think importantly, I would like to note that our launch supply.

As we look ahead we are prioritizing the commercial launch and our ongoing clinical programs. We have an additional 50 million under our debt facility that we can draw down this year. And we also anticipate receiving approximately 60 million dollars from exercise of outstanding common warrants by year end bringing our anticipated Runway into 2027

Additionally, 50 million is available under a debt facility post approval to support the upcoming launch.

Beyond is manufactured wild and ready to go.

We also anticipate monetizing our priority review, voucher following approval.

Thank you very much.

Your next question comes from the line of Allison Brockville with Piper Sandler Your line is open.

Hey, good morning team and thanks for taking the questions.

We continue to operate with a tight financial plan and we'll share more details over the next few quarters. As a reminder, we will continue to focus on driving strong performance with financial discipline. Next,

Firstly could you just further characterize any interactions with FDA.

Ill take a macro view.

Part of the observations at senior most you just discussed.

Any feedback on.

Overall confidence in receiving a properly all would be particularly helpful.

And then I think you talked about expansion of payer outreach. So could you just frame for us.

Investing in capital, efficient, commercial buildout, and thoughtful Capital, allocation to advance our Pipeline with that. I will turn it back to David. David, thanks vas in closing. We are committed to successfully executing on these key priorities, which position us to transform scholar, rock into a premier, Global biotech leader.

Next question is with what's left Congress or calling in just overall receptiveness to coverage of a critical math on top of us along.

Targeting currently thank you.

Yes, no. Thanks, Thanks, Allison and yes, as we noted.

We were very encouraged by our late cycle meeting that we recently had an akshay can provide a little bit more context on that and then as I noted and keep it as well he has just recently deployed.

First, a pilgrim AB regulatory approvals and following those approvals the US launch of a pilgrim app for children and adults with SMA followed by a series of country launches in the coming years. Starting in Europe with Germany next year. Second expand a pilgrim AB into additional rare severe and debilitating neuromuscular diseases and finally disciplined Capital allocation to support our high value, commercial and development initiatives.

On behalf of every member of the Scholar Rock team.

Sensational team and he can comment on some of those payer interactions related to the label and the interactions with the FDA Akshay, yes. Thanks, David.

I want to emphasize our unwavering commitment to more than 35,000 patients and their families.

We had an exceptionally constructive.

Late cycle meeting recently with the FDA.

All the different disciplines that needed to be there with them.

Our mission is to move with urgency to ensure that no patient with SMA has left behind with that. We'll now open the line for questions, operator.

Talk through the different aspects of the BLA I think we were very pleased with the feedback we add.

Thank you. We will now begin the question and answer session.

So.

We're working with them.

As David said in his prepared statement towards September 'twenty two.

At first time, I will like to remind everyone in order to ask a question press star, send the number 1 on your telephone key. Dead.

And look forward to the rest of the BLA review being completed and.

And your first question comes from the line of Eric Schmidt with cancer. Your line is open.

We appear to be doing just that right now.

Yes, Allison and as far as the payers as.

As we've noted before we have a fully staffed payer team our outreach has been progressing.

To be able to be ready for our September 20, <unk> date. The meetings have been joined positive as we've been going through some of the <unk> data and overall response, but importantly, the durability of response is something that payers have found quite impressive.

Well, thanks and and good morning. Sky Rock team, appreciate the transparency around your cdmo issues. Um, can you tell us a little bit more about the specific observation at those 2 sites, whether you expect that a reinspection is going to be required prior to ategra map approval. And, and whether the 2 facilities, right now are currently able to release other pharmaceutical products. Thank you.

Lastly to your other question about <unk>.

Paying for another therapy for SMA I would say that you already have better than 20% of patients that are receiving more than one SMA therapy that is being paid for by payers. At this time. So although the question has come up the unmet medical need.

Is there and therefore, all I can say is that discussions are going positive.

Yeah, thank thanks very much, Eric. And, um, it's great to be working with you. Um, you know, first, I think as you know, um, Eric, uh, GMP inspections are are super standard as, as part of the FDA review process and. And in fact, uh, in 2024 based on fda's inspection data dashboard actually, uh, More than 70% of drug quality assurance inspections, uh, resulted in observations noted by the FDA. So as I noted in the call, we

Thank you.

Your next question comes from the line of David Nearing Carton with Wedbush Securities. Your line is open.

Alright, thanks for taking my questions.

Yes.

One on labeling.

Our review cycle that allow for a response and and obviously a green light.

Had labeling discussions with FDA and <unk>.

Can you discuss.

Possible labels with payers or.

Not to be discussed with.

With the potential data or as we are to date and then the second one is if there is unfortunately, a delay in what to do for this.

It's uh, always like very difficult to sort of read the tea leaves and try to understand what the FDA with those observations may want to do. Would they want to reinspection or not at this moment in time given the

Possibly put the PRP at risk.

Okay.

The budget.

That starts on October one our fiscal year. Thanks.

Yes, maybe I'll take that.

Our last question, David first there would be no change in <unk> and <unk>.

Thank you.

<unk> all come to know US This group of management team.

We think about everything we are a measure twice cut once type of crowd and we would think through.

Any scenarios, even before as we mentioned, we werent totally surprised by observations only because three quarters of the time they happen.

And so we would have been thinking through all of this and there'll be no no impact on the PRP at all which is important and a very good news.

Uh, very constructive late cycle meeting that again was, uh, held. Uh, after uh, these, uh, site inspections and after these observations were provided, uh, again, the tone and tenor, and collaborative nature, uh, of that, uh, late cycle meeting, uh, certainly indicated to us. Uh, that, the, uh, the agency, uh, is, uh, very much working toward, uh, completing their review of our bla, uh, by the September 22nd to do for date. I would also just note that, um, we're obviously working on multiple levels with our cdmo partners. Um, we're a skilled team, we're an experienced team. Um, we understand uh, how best, um, to work through situations like this, uh, which we are prepared to do.

And, and David do you know whether the 2 facilities are releasing any product currently?

Regarding just.

The constructive nature of the dialogue in the label I'll have akshay comment yeah, sorry.

So with respect to that topic again, we had a very good late cycle meeting.

You can expect a late cycle meeting all the different aspects of the BLA.

Leading to a potential approval of discuss including labeling.

The timings around who can expect work we've had those types of attractions I cant get into more detail than that right now, but we were reassured that everyone is working towards September 22.

Great. Thank you.

Next question comes from the line of Tessa Romero with Jpmorgan. Your line is open.

Hi, good morning team.

So jess.

Double clicking back on some of that earlier comments you've made.

What is the right way to think about that the next step. Following these observations given proximity to your Goldie and how likely do you think that the outcome of the review will be possible in light of these findings and remain on time.

No, very good question. Uh, the 2 facilities, uh, continue to operate, of course, uh, uh, the 1 that, um, you know, given the disclosure on August 1st, it's not common practice in the industry, nor our common, practice to name facilities, but in the case of Catalan Indiana, now owned and operated, uh, by Novo Nordisk, uh, certainly. As, as you know, Eric, that's, uh, that's an important filler, uh, across the board for, uh, a number of very important products across the industry and, uh, we know they continue to be very active, uh, and the other facility continues to manufacture product as well. I think I would also note, and I think this is probably important for our, our entire audience. Uh, our supply chain is produced, uh, the epitome of drug Supply that has now accumulated, you know, over 600, patient years of experience, through multiple years of clinical trials, including our pivotal trial, the most recent Embrace trial,

Uh, and I think, importantly, I'd like to know uh, that our launch Supply and Beyond as manufactured viled and ready to go.

And then my second question is what does an ideal.

Thank you very much.

Like for <unk> and at this point why do you believe the indication statement should be thanks.

Your next question comes from the line of Allison bratzeli.

Hey, good morning team and thanks for taking the questions.

Alright, Thank you test great questions.

So, let's kind of letting you into our kitchen, a little bit what you might expect us to be doing is working very closely with our CMO partners. So in other words like being well aware of the observations.

Um, first, could could you just further characterize any interactions with FDA? Um, I'm a paragraph, a paragraph review, outside of the observations at cdmos, you just discussed. Um, you know, any feedback on your overall confidence in receiving, a a broad label would be particularly helpful

Having input.

On the responses to those observations.

And then having levels of.

Transparency, both with the <unk> in their communication.

and then I I think you talked about expansion of payer Outreach. So could you just frame for us? How your discussions with with us? Payers are going and and just overall receptiveness to coverage of a pedigree map on top of SMN. Um, targeting therapy. Thank you.

With the agency as well as our own continued dialogue with the agency through the final stages of our review process and so I would just say that we have substantial talent internally.

Yeah, no thanks. Thanks Allison. And yes, as we noted, uh, uh,

We would always take a no stone left unturned approach to external experts to help us and help our CMO partners.

Through the very best way to respond the observations as I noted.

We're confident that novo submitted.

And we actually have access to those.

You know, we were a very encouraged uh, by our late cycle meeting that we recently had an ache can provide a little bit more context on that and then as I noted and keep it as well, he's just recently deployed a sensational team and he can comment on some of those payer interactions uh, related to the label and the interactions with the FDA auction. Yeah, thanks David. Um, we had an exceptionally constructive, uh, late cycle meeting recently with the FDA, uh, all the different disciplines that needed to be, there were there. Uh, we talked to the different aspects.

Those responses that they made earlier this week.

And the same will hold true for the responses that are going in within the week.

Related to the other <unk>. So we'll have a great visibility into this amendment multiple lines of communication through our CMO partners as well as the FDA directly related to the ideal label.

Of the bla. I think we were very pleased with the feedback we had. Uh, and so, you know, we're working with them. Uh, as David said in his prepared, statement towards September 22, um, and look forward to the rest of the bla review being completed, and, um, we we appear to be doing just that right now.

Turnover to Akshay and Keith at one of the things we've worked very hard on.

By taking a no shortcut approach to the development program is.

It's the robustness.

Our phase II, and then phase III trial.

And so obviously when we think about children and adults with SMA, we think about a widening.

With our partners at cure SMA.

Really for the best interest of the community a broad label is quite important so that all patients who can benefit from a particular map will have access to <unk> for more comments on the label I'll hand, it over to Akshay.

Thanks, David so with respect to that topic.

Sapphire itself started individuals' two years and older to the age of 21. The primary endpoint was for the group that was two to 12 year old.

We obviously hit that primary endpoint, we relate the data again today.

Better than 20% of patients that are receiving more than 1. SMA uh therapy that is being paid for by payers at this time. So although the question, uh, has come up the unmet medical need, um, is, is there? And therefore, all I can say is the discussions are going positive.

The important thing is that the data and the 13th 21 rules entirely consistent with what we saw in the 2% to 12 group and.

Thank you.

Your next question comes from the line of David nearing carton with wet Bush security. Is your line is open.

So I think we can expect that.

Two.

That will not studied may not be in the label, but certainly above two we.

We would like to see that is in the label given the very exciting findings from Sapphire.

All the way up into adulthood and.

Patients in it.

In Sapphire is 21 years old and is experiencing benefit they're not going to suddenly stopped getting benefit when their 'twenty. Two so I think from a logic perspective, two years and older is a way to think about the group that would be eligible but again, we cannot give any final information on that until the FDA has for.

Hey, thanks for taking my questions. I I just had um it's 1 on the labeling. Um, have you had labeling discussions with FDA and and, you know, able to discuss, you know, possible labels with payers or, um, is that to be, um, discussed with the, you know, with, with the Pooh date, or, or as we approached to do with the date. And then the second 1 is if there is unfortunately, a delay in the puf, it is a, um, possibly put the PRP at risk, if a, um, you know, if they're different, uh, changes in, in the budget, um, that that starts, you know, on October 1st of the fisc year, thanks?

Their deliberations, but yes.

And one last thing I would comment on in our <unk>.

Very strong partnership with cure SMA.

They've actually advocated.

With the FDA for many years the importance of sometimes a narrow our clinical trial, but a broader label recognizing the biology of the disease isn't necessarily different as.

Yeah, maybe I'll take that. Um, second or last question David first, um, there would be no change in prv and, uh, I think, uh, you've all come to know us this group of management team. We're a

um,

we think about everything, we're a measured twice, cut once uh, type of crowd and you know, we would think through

Patients get older. We were gratified that our most recent study in adults over 100 adult showed the biology of Myostatin again held up that of course was with the embrace trial, but.

It has been common practice that there can be a slightly narrower patient population in a pivotal trial, but then an acceptance of a broader label and that's what we're working toward the ideal label as Akshay said would be the patients at two years of age and older would have access to the therapy.

Thank you.

And our next question comes from the line of Mark <unk> with PD Cowen Your line is open.

Thanks for taking my questions.

First to push a little bit on the pricing discussion.

With Payors.

Yes.

Any scenarios even before, uh, as we mentioned, we weren't totally surprised by observations only because 3 quarters of the time they happen. Um, and so we would have been, uh, thinking through all of this and there'd be no, no impact on the prv at all, which is important and a very good news, uh, regarding just, um, the constructive nature of the dialogue and, and, and the label, I'll have Asha comment. Yeah, um, so with respect to that topic again, we had a very good late cycle meeting and, uh, as you can expect at the latest like meeting all the different aspects of the bla, um, uh, leading to a potential approval of discussed including labeling, uh and the timings around who can expect what? Uh, we've had those types of interactions. Uh, I can't get into more details on that right now, but uh, we were reassured that everyone is working towards September 22.

I think we are encouraged that 20 plus percent of patients are getting clinical combination therapy today, even without phase III data supporting that.

Okay, thank you.

Question comes from the line.

Test Romero with JP Morgan. Your line is open.

But maybe the ask on the payers as a little bit different with that right because.

Hi, good morning team. So just

Most of that is onetime gene therapy costs that may have already occurred and then on an annual budget basis, just one therapy.

Through how they're kind of thinking through the the budget impact of maybe two SMA type pricing drugs.

Individual patient's happening.

Concurrent and ongoing basis.

And then maybe from the R&D side.

Double clicking back on some of the earlier, comments, you've made, you know, what is the right way to think about about the next step, following these observations, given proximity, to your goal date. And How likely do you think that the outcome of the review will be positive in light of these findings and remain on time?

<unk> a new indication later this year should we.

View that as like one pilot outside of SMA or is that just the first of many and we should expect as we go into 'twenty six additional indications to continue to be added to the pipeline.

And then my second question is, what does an ideal label look like for a pentagram app? And at this point, what do you believe the indication statement should be thanks.

Mark Thanks, very thoughtful questions on the pricing side.

I would note of course as I have in the past that we will consider a number of things when establishing the price.

Certainly the rarity of SMA and you talk about budget impact as an individual patient. We obviously think about just how rare SMA is.

Uh thank you Tess, great questions. Um so just kind of letting you into our kitchen a little bit. What you might expect us to be doing is working very closely, you know, with our cdmo partner. So in other words like being well aware of the observations

Um, having input.

Um,

The severity of the disease, despite the use of.

Over the past 10 years of SMA targeted therapies, where they have shown in some of their long term data and we then again underscored in our phase III trial.

Patients.

Eventually move to a progressive state of motor function loss and how severe.

uh, on the responses to those observations, uh, and then having, uh, levels of, um, uh, transparency both with the cdmos and, and, and their communication, um, with the agency, uh, as well as our own, uh, continued dialogue, uh, with the agency, uh, through the final stages of our review process. And so, I would just say that we have substantial Talent. Um, internally

SMA is despite the use of best known standard of care and then of course, the compelling clinical benefits that we can provide on some of those were underscored by Akshay earlier.

And so we will think about those things, we will think about the budget impact.

And one of the things. We also have a lot of experience with is looking at even.

Sort of pricing quarters for rare disease therapies mono therapies.

Um, we would, uh, always take a no stone left unturned approach to external experts to help us and help our cdmo partners. Um, think through, you know, the very best way to respond, um, observations as I noted, uh, we're confident that Novo, uh, submitted, uh, and we actually have, uh, access to those. Um,

In different settings, and sort of thinking about sort of where the starting point is today, we definitely do not think the ore is then in terms of payers a willingness to support of both physician interest as well as patient interest and accurate and accessing and Keith will comment in a moment on the <unk>.

Importance of dual modality therapy for this devastating disorder Keith.

Thanks, David.

Uh, by taking a no shortcut approach to the development program.

Mark one of the things as you mentioned that this is using to agents, who is just post postal Jens <unk> and I just want to call out that we actually have met with patients and physicians that have tried.

Both rich to plan and spin rozzer simultaneous so they are paying for to current agents at the same time.

Is the robustness, uh, of our Phase 2 and then and then phase 3 trial. Uh, and so, obviously, when we think about children and adults with SMA, we think about aligning, uh, with our partners at cure SMA, uh,

So it's not just post gene therapy. The Bottomline is that over time. These patients on these SME targeted therapies many of them plateau and then they begin to decline and payers are realizing that there is a great deal of unmet medical need that's left.

Think about the factors, David mentioned treating with dual modality and targeting the muscle directly as well as the motor neuron. It gives you an opportunity. It gives you an opportunity to potentially not only increase your responses. We've shown from the Sapphire data, but then also have a durability of response over time.

So that has a meaningful impact that is valuable to payers.

And then mark regarding the other.

Sort of a pipeline in a product strategy that.

Akshay is so skillfully leading I'll have him comment.

Yeah. Thanks, Mark So we see enormous opportunities for antagonizing myostatin and a whole array of neuromuscular disorders.

Really, for the best interest of the community abroad label is quite important so that all patients who can benefit from a pilgrim app will have access to a pedag for more comments on the label. I'll, I'll hand it over to, to Asha. Yeah, thanks David. So with respect to that topic. Um, Sapphire itself, studied individuals, 2 years and older to the age of 21. The primary endpoint was for the group that was 2 to 12 year old. Um, we obviously hit that primary end point. We relayed the data to again today. Um, the important thing is that the data in the 13th to 211 were also entirely consistent with what we saw in the 2 to 12 group. Um, and so I think we can expect that those under 2, uh, that were not studied may not be in the label, but certainly above 2. Uh, we would like to see those in the label. Given the very exciting findings from Sapphire, uh, all the way up into adulthood. And, you know, if a patient in uh, in in Sapphire is

<unk>.

Yes, there'll be many opportunities that youll see is studying will begin with one by the end of the year, but I think it will add in quick succession over time, so much more to come on that.

Okay. Thank you.

And your next question comes from the line of Martin Auster with Raymond James Your line is open.

21 years old in his experiencing benefit. They're not going to suddenly stop getting benefit when they're 22. So I think, you know, from a logic perspective, 2 years and older is a way to think about uh, the group that, that, that would be eligible. But again, we cannot, uh, give any final, uh, information on that until the FDA has finished their deliberations. But, uh, yeah. And, and, and 1 last thing, I I'd comment on, in, in our, you know, very strong partnership with cure SMA.

Hey, Good morning. This is Thomas on for Marty. Thanks for taking my question, maybe just one on the <unk> trial here anything you can say about expected enrollment timelines, there and maybe just frame for us how to think about the significance of that expansion opportunity. If we envision an initial label for <unk> and <unk>.

<unk>. Thank you.

Yes, thank you very much and consistent with our ambition and mission of the company that no patient with lepton.

Ever be left behind.

Including <unk>.

Babies and toddlers. This is an important study for us as Akshay noted so I'll have him comment a little bit further on the study and an expected timelines. Thanks.

They've actually advocated, you know, with the FDA for many years. Uh the importance of uh sometimes a narrower clinical trial, but a broader label recognizing the biology of the disease isn't necessarily. You know, different as um patients get older. We were gratified that our most recent um study in adults over a 100 adults showed the biology of myostatin again held up that of course was with the Embrace trial. But um it has been common practice that there can be a slightly narrower patient population in a pivotal trial. Uh but then in acceptance of a broader label and that's what we're working toward the ideal label is AI said would be the you know, patients at at 2 years of age and and older would have access to the therapy.

So with respect to timelines.

Thank you.

We're going to start enrollment in Q3 as I said on the.

Prepared remarks.

And our next question comes from the line of Mark Sam with TD Cowen. Your line is open.

My usual practices, let's get that going and then in the coming quarter or two as we see momentum build who we are.

Further on the exact completion date of the study.

And with.

With respect to.

Zero to two year old children with SMA in the label.

We didn't study under the age of two in the Sapphire study.

<unk> initiated this study too.

Understand the impact of the drug in that population safety PK PD efficacy.

And as David said, no challenge will be left behind with this disease and we think.

We're going to have kind of have an impact across the entire age range here I think in terms of trying to do good with this drug and helping as many kids as possible. One thing I would note is that the.

Hey, thanks for taking my questions. Let me first to push a little bit on the pricing discussion and it that you're having with payers. Just, you know, I think we are encouraged that, you know, 20 plus percent of patients are getting quote unquote combination therapy today, you know, even without phase 3 data supporting that. Um, but maybe the the ask on the payers is a little bit different with that. Right. Because most of that is 1 time, gene therapy costs, that may have already occurred and then on an annual budget. Basis just 1 therapy just keeps through how they're kind of thinking through the the budget impact of maybe 2. SMA Type pricing drugs and in, in individual patients happening on a, you know, concurrent and ongoing basis.

Prevalent population is much much larger than the incident population.

And then maybe from the R&D side, um, starting a new indication later this year, should we?

And so the zero to two.

<unk> neutral than being born with SMA.

That's dwarfed by the 35000 or greater who currently have SMA are on treatments, we believe could be helped.

View that as, like 1 pilot outside of SMA or, is that just the first of many, and we should expect, as we go into 26. So, you know, additional indications, to continue, to be added to the pipeline.

By a drug like a bit of a map. So there is a.

A lot for us to do once we get <unk> dawn and stopped helping under two and we will begin with two years it holdup.

Thank you.

Okay.

And our next question comes from the line of.

Cooper.

Is there a condo visit Chili's Securities. Your line is open.

Hey, guys. Thank you so much for taking my question.

Wanted to go back to the CMO site inspections.

If there is a need for another inspection do you have a sense of timelines as to when you will get to know that buy and given the Crs have been seen with one of the Pis involved wanted typical timeline for potential resolution of these issues.

Uh, Mark, uh, thank thanks. Very thoughtful questions on the pricing side. Um, I would note, of course, as I have in the past that we'll consider a number of things when establishing the price, um, certainly the, the Rarity of SMA and you talk about budget impact as an individual patient. We obviously think about just how rare SMA is. Uh, the severity of the um disease despite the use of um over the past 10 years of of SMN targeted therapies where um, they have shown in some of their long-term data. And we then again underscored in our phase 3 trial, uh, that patients. Um,

Thank you.

Yes, Thanks Crippa again.

It's hard to predict what the FDA will do.

Thank you all do this for a living.

And as do we and the.

looking at even,

The best way that we can do like you.

As I assess what has happened from time to time in the industry and what could be some of the different scenarios, but I can tell you that from all of our experience and that of our expert.

Advisers that we're working with along with our Cmos.

Very best thing to do initially is have a robust response to those observations and that is what we've been spending a lot of time on.

The robustness of those of those responses.

Obviously.

Can have an impact on whether or not any <unk>.

Reinspection would be required and so.

That's where our effort is being placed and then again I think as I noted we would.

Be gathering information both through our CMO partners, but then also directly with our review Division and we will keep you apprised at that.

But right now given the fact that.

Sort of pricing quarters for uh, rare disease therapies, mono therapies, uh, in uh, different settings and sort of thinking about sort of where the starting point is today, we definitely do not think the error is then, uh, in terms of uh, payers willingness to support both physician interest, as well as patient interests and act and accessing and and Keith will come in in a moment on, uh, the importance of dual modality, uh, therapy. Uh, for this devastating disorder Keith. Yeah. Thanks David. Um, Mark 1 of the things is, you know, you mentioned that this is using 2 agents is just post postal agenda, um, and I just want to call out that we actually have met with patients in Physicians that have tried, uh, both RIS to plan and spin Raza simultaneously, so they're paying for 2, currently, the bottom line is that over time, these patients on these SMN targeted Therapies.

Following these site inspections and following the presentation of those observations.

We held our late cycle meeting the FDA completed that late cycle meeting.

The dialogue the tone the content of the discussion.

It was very encouraging.

With a commitment to move forward.

Toward our.

<unk> date under priority review of September 20, <unk>, and we will certainly keep you and all of our stakeholders apprised on that progress.

Many of them plateau and then they begin to decline and payers are realizing um, that there is a great deal of unmet medical need. That's left. Uh, if I think about the fact is David mentioned treating with dual modality and targeting the muscle directly as well as the motor neuron, it gives you an opportunity. It gives you an opportunity to potentially not only increase your response as we've shown from the sapphire data, but then also have a durability of response over.

Time, and so that is a meaningful impact that is valuable to payers.

Alright, thank you so much.

and then, Mark regarding the other, um,

And our next question comes from the line of Evan <unk> with BMO capital markets. Your line is open.

you know, sort of the pipeline and a product strategy that, um, uh, Ace is so skillfully leading, I'll have him comment.

Hi, two questions from me can you just provide more color characterize the.

The interactions from your late cycle review means today at all talk about.

Just the difference in efficacy we saw between the 20, the 20 milligram and the 10 milligram doses and also the cost one for you as we think about kind of modeling.

Yeah, thanks Mark. So you know we see enormous opportunity for antagonizing myat in the whole array of neuromuscular disorders. And so, um, yes, there will be many opportunities that you'll see us studying, um, we'll begin with 1 by the end of the year, but I think it will add that in in quick succession over time so much more to come on that

Okay, thank you.

The asset post launch how should we think about the cadence in the back half of this year and into next year. Thank you guys.

and your next question comes from the line of Martin auster with Raymond James, your line is open

Yes, Evan great question regarding the the.

The combined dose analysis, I'll have akshay comment on that which.

Which obviously as you know there has been extensive clinical work done with the <unk>. Most recently embrace was 10 akshay.

Yes.

So the lifecycle and traction was indeed, very constructive and positive.

Great. Hey, good morning. This is Thomas on from Marty. Thanks for taking our question. Maybe, uh, just 1 on the opal trial here. Anything you can say about expected enrollment timelines there, and maybe just frame for us how to think about the significance of that expansion opportunity. If we envision an initial label for a pedigree lab and patience 2 years and older. Thank you.

We have discussed the fully including the combined dose analysis with all of you before and.

We've had very constructive discussions with regulators around that as well as you know we hit the primary endpoint. The important thing is both 10 and 20 have enormous identical ponca dynamic effect.

It's unsurprising that both showed.

A positive outcome with efficacy.

And combining the two groups increased statistical power to be able to see the difference versus placebo and obviously, we saw gains in most function with the bigger map versus a decline in our expectations, but given that the regulatory path, who has to approve the lowest dose efficacious and given that both have equivalent pump.

Uh, yeah. Thank thank you very much and, um, consistent with our, um, ambition and Mission at the company that no patient would Left Behind would, would would ever be left behind, uh, including um, you know, babies and toddlers. This is an important study for us and as a noted. So I'll have him comment a little bit further on the on the study and and expected timelines. Yeah, thanks. So, you know, with respect to to timelines, you know, we are going to start enrollment in Q3 as, as I said, on the prepared remarks. Um my usual practice is, let's get that going. And then in the coming quarter to, as we see momentum build will be able to guide further on the exact completion date of the study. Um,

Good dynamic impact.

Would request that 10 milligram per kilogram.

So I'll leave it there.

On the financial side.

Still to do the 2026 budget planning session, but.

As I mentioned in my call is going to be really comfortable about how we go into next year.

Some of the expenses in the nickel side is going to drop out next year.

<unk>.

So prioritization is.

Akshay was laying out in his section.

Moving forward 39, and some of the pipeline forward.

Other indications so that is a key priority and keeping our overall.

And you know uh with respect to uh 0 to 2 year old children with SMA, and the label, we didn't study under the age of 2 in the sapphire study. Um, we've initiated this study to, uh, understand the impact of the drug in that population. Safety PK PD efficacy. Um, and as David said, no child should be left behind with this disease and we think uh, pedagogical app can have an impact across the entire Asia and share. I think in terms of trying to do good with this drug and helping as many kids as possible. 1 thing, I would know is that the prevalent population is much much larger than the incident population. Um and so you know, if the 0 to 2 are the new children being born,

Spending in check.

We do expect it to be similar lines like what we spend this year.

Alright, Thank you ladies and gentlemen, this concludes the Q&A session.

For today's call. Thank you all for joining you may now disconnect.

With SMA, uh, that's dwarfed by the 35,000 or greater Who currently have SMA are on treatments and we believe could be helped, um, by a drug like a pilgrim app. So there's a lot for us to do whilst we get opal done and start helping under 2, uh, and we'll begin with 2 years and hold it.

Thank you.

And our next question comes from the line of spa de Vera with truist security. So remind is open.

Need for another inspection. Do you have a sense of timelines as to when you will get to know that by and no, given the crls that we've seen with, you know, 1 of the peers involved, what a typical timeline for potential resolution of these issues.

Thank you.

Yeah. Thanks kPa again. Um,

Um, it's it's hard to predict what the FDA will do. I mean, I think, you know, you all do this for a living, uh, and, uh, as do we and, uh, you know, the best we can do like you, uh, is assess what has happened from, um, time to time in the industry, and you know, what could be some of the different scenarios. But I can tell you that from all of our experience and that of our expert, um, advisors that we are working with along with our cdmos the very best thing to do initially is have a robust response to those observations. And that is what we've been spending a lot of time on

The robustness of those obser of of those responses. Obviously, um, can have an impact on whether or not, uh, any, uh, reinspection would be required. And so, um, that's that's where our effort is being placed. And then, again, I think as I noted, we would, um, be gathering information both through our cdmo partners, but then also directly with the review Division. And, um, we'll keep you apprised at that. Um, but right?

right now, given the fact that, um, following these site inspections, and following, the presentation, of those observations, um, we held our late cycle meeting the FDA completed that late cycle meeting, uh, the dialogue, the tone, the content of the discussion, uh, was very encouraging, uh, with a commitment to move forward, uh, toward our, um, uh,

Paddu fedate under priority review of September 22nd and we will certainly keep you and all of our stakeholders apprised on that progress.

Great, thank you so much.

And our next question comes from the line of Evan Seager with BMO Capital markets. Your line is open.

I have 2 questions for me, can you come provide more color characterized? Um the you know the interactions from your relate cycle review means the day it all talk about. Um just the the difference in efficacy we saw between the 20, the 20 um, milligram and the 10 milligram Doses. And then also from the cost 1 for you, as we think about kind of modeling, um, you know, the asset post-launch, how should we think about the Cadence and the back half of this year and into next year? Thank you guys.

Yeah. Evan uh, great question uh, regarding the uh, the combined dose analysis. I'll have Ash comment on that. Uh which obviously as you know, there's been extensive clinical work done with the 10 a.m. the 20. Most recently embraced was 10 um a um,

Yeah, um, so the late cycle interaction was indeed very constructive and positive. Um, so, um, we have discussed the file fully, including the combined dose analysis, uh, with all of you before. And, uh, we've had a very constructive discussions with Regulators around that as well. As you know, we hit the primary end point. The important thing is both 10 and 20 have an almost identical pharmco Dynamic effect. Um, and so it's unsurprising that both showed uh, a positive outcome with efficacy. Um and combining the 2 groups increased statistical power uh to be able to see the difference versus placebo. And we saw gain in most function with a bigger map versus a decline. And our expectation is that given the, the the regulatory practice always do approve, the lowest dose that's for efficacious and given that both have equivalent Farm code dynamic impact. Uh we would request that 10, milligram per kilogram is the approved dose. I'll leave you with that.

and when the on the financial side still to do the 2026 budget planning session, but

As as I mentioned, in my calls going to be very thoughtful about how we go into next year. Some of the some of the expenses in the clinical side is going to drop out next year and then we'll replace it with the prioritization as, as, um, Axia was laying out in his section with moving 439 and some of the pipeline forward so that that's, um, you know, other indications forward. So that's our key priority and keeping our overall, uh, spending in in check. Um, we do expect it to be in similar lines like what we spend this year?

Uh thank you, ladies and gentlemen, this concludes the Q&A session and the and concludes today's call. Thank you all for joining you may now disconnect