Q2 2025 UniQure NV Earnings Call

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I would now like to hand, the conference over to your speaker today Keith.

<unk> Russo senior director of Investor Relations. Please go ahead.

Good morning.

You for joining us for unique Harry.

A point on it.

Earnings call.

Earlier. This morning, <unk> released its financial results for the second quarter of 2025, and our press release is available on the investors and media section of our website at <unk> Dot com.

10-Q was also filed with the SEC earlier this morning.

Joining me on the call today are Matt Cabot's, Chief Executive Officer, Dr. Walid, Avi Saab, Chief Medical Officer, and Christine <unk> Chief Financial Officer.

After our formal remarks, we'll open up the call for Q&A.

Before we begin please note that we will be making forward looking statements. During this investor call. All statements other than statements of historical fact are forward looking statements.

They are based on management's beliefs and assumptions and on information available to management only as of the date of this conference call.

Actual results could differ materially from those anticipated in these forward looking statements for many reasons, including without limitation.

As described in <unk>, most recent SEC filings.

Given these risks you should not place undue reliance on these forward looking statements and we assume no obligation to update these statements even if new information becomes available in the future now.

Now, let me introduce Matt Cabotage Unicorn CEO.

Thanks, Chiara and good morning, everyone. Thank you for joining today's second quarter conference call.

The first half of 2025 has been tremendously productive for the company as we advance AMG 130 towards potentially becoming the first disease modifying therapy for Huntington's disease.

Momentum is strong across four key areas clinical advancements regulatory alignment.

Les readiness and commercial launch preparation.

We also made advancements across our broader clinical pipeline, including AMG 191 for Fabry disease, AMG $2 60 for mesial temporal lobe epilepsy, and AMG 162 for solid one AOS.

Isn't that catheter unit current CEO.

Thanks, Chiara and good morning, everyone. Thank you for joining today's second quarter conference call.

With pivotal topline data from AMG 130, and initial clinical data from AMG 191 in Fabry both expected in September we believe the second half of 2025 is shaping up to be an eventful period for <unk>.

The first half of 2025 has been tremendously productive for the company as we advance AMG 130 towards potentially becoming the first disease modifying therapy for Huntington's disease.

Turning to <unk> hundred 30 <unk>.

In Q2, we continued to have productive interactions with the FDA, including receipt of breakthrough therapy designation in April and further regulatory alignment.

Momentum is strong across four key areas clinical advancements regulatory alignment.

Clay readiness and commercial launch preparation.

<unk> remains the only investigational therapy in Huntington's disease to have either breakthrough therapy designation, we're regenerative medicine advanced therapy or <unk> designation granted by the FDA.

We also made advancements across our broader clinical pipeline, including AMG 191 for Fabry disease, AMG $2 60 for museum temporal lobe epilepsy, and AMG 162 for sod one Alex.

In June we achieved alignment with the FDA on both our statistical analysis plan and CMC requirements were planned BLA submission in the first quarter of 2026 our primary.

With pivotal topline data from <unk> and initial clinical data from <unk> 191 in Fabry both expected in September we believe the second half of 2025 is shaping up to be an eventful period for Unicorn.

Efficacy analysis will compare the three year change in CAH, Drs and high dose patients to a propensity score matched external control arm using data from the enrolling HD natural history study.

Turning to AMG 130 <unk>.

In Q2, we continued to have productive interactions with the FDA, including receipt of breakthrough therapy designation in April and further regulatory alignment.

In addition, the FDA agreed that we can leverage our experience from Amgen and.

And validating the AMG 130 manufacturing process and that our process performance qualification can be limited to one such patch.

AMG 130 remains the only investigational therapy in Huntington's disease the.

To have either breakthrough therapy designation, we're regenerative medicine advanced therapy, or <unk> designation granted by the FDA.

Supplemented by additional commercial scale GMP batches.

Following FDA guidance, we've made significant progress in preparing for the planned BLA submission.

In June we achieved alignment with the FDA on both our statistical analysis plan and CMC requirements were planned BLA submission in the first quarter of 2026.

Manufacturing of two scale pre.

<unk> GMP batches is now complete and we've initiated our formal PQ campaign.

Our primary efficacy analysis will compare the three year change in Coh, Drs and high dose patients to a propensity score matched external control arm using data from the enrolling HD natural history study.

We also recently submitted our final statistical analysis plan to the FDA, which will leave will discuss in more detail shortly.

In addition, the FDA agreed that we can leverage our experience from Amgen and.

On the commercial planning front, we continue to make disciplined investments in preparation for a potential 2026 launch.

And validating the AMG 130 manufacturing process and that our process performance qualification can be limited to one such patch.

In June we appointed an experienced leader highly o'keefe as chief customer and strategy officer, and our HR team is actively recruiting key roles across medical affairs market access commercial operations and other critical areas.

Supplemented by additional commercial scale GMP batches.

Following FDA guidance, we've made significant progress in preparing for the planned BLA submission.

The team is making strong progress on an integrated launch strategy and we look forward to sharing more details in the future.

Manufacturing of two scale pre.

<unk> GMP batches is now complete and we've initiated our formal PQ campaign.

Now turning to our broader pipeline in May we shared encouraging early data from the first patient treated with <unk> hundred 60 for medial temporal lobe epilepsy.

We also recently submitted our final statistical analysis plan to the FDA, which will leave will discuss in more detail shortly.

Over the first five months of follow up the patient experienced a 92% reduction in seizure frequency with no significant adverse events.

On the commercial planning front, we continue to make disciplined investments in preparation for a potential 2026 launch.

In June we appointed an experienced leader highly o'keefe as chief customer and strategy officer, and our HR team is actively recruiting key roles across medical affairs market access.

This early result has sparked strong interest among investigators and the epilepsy community I am pleased to say that we have 14 clinical sites in the U S that continue to screen patients for this study.

<unk> operations and other critical areas.

During the second quarter. We also continued to advance our fabry and <unk> studies and look forward to presenting initial fabry data.

Team is making strong progress on an integrated launch strategy and we look forward to sharing more details in the future.

The IC IEM conference in early September.

Now turning to our broader pipeline in May we shared encouraging early data from the first patient treated with AMG $2 60 for medial temporal lobe epilepsy.

Overall, I'm incredibly proud of the team's execution and dedication towards advancing these important therapies in the first half of 2025, we delivered on several key goals and remain on track for what we believe could be a transformational second half marked by meaningful data updates regulatory progress.

Over the first five months of follow up the patient experienced a 92% reduction in seizure frequency with no significant adverse events.

This early result has sparked strong interest among investigators and the epilepsy community I am pleased to say that we have 14 clinical sites in the U S that continue to screen patients for this study.

And continued momentum towards the planned BLA submission of AMG 130.

I will now turn the call over to Walid to provide a more detailed clinical update.

During the second quarter. We also continued to advance our fabry and sad when they are less studies and look forward to presenting initial fabry data at the IC IEM conference in early September.

Thank you Matt.

Good morning, and good afternoon, everyone.

During the second quarter of 2025, we continued to make meaningful advancements across our portfolio of clinical stage gene therapies.

Overall, I'm incredibly proud of the team's execution and dedication towards advancing these important therapies.

Let me start with <unk>.

In April <unk> was granted breakthrough therapy designation by the FDA.

In the first half of 2025, we delivered on several key goals and remain on track for what we believe could be a transformational second half marked by meaningful data updates regulatory progress and continued momentum towards the planned BLA submission of AMG 130.

This recognition first in Huntington disease was based on the phase one two data showing the potential to slow disease progression and underscores both the urgent need for effective treatments for Huntington's disease.

And the potential therapeutic benefits of <unk>.

I will now turn the call over to Walid to provide a more detailed clinical update.

As you know a recent FDA interactions have been highly productive.

Thank you Matt.

Following to type B meetings in the first and second quarter, we announced in July alignment with the agency on the statistical analysis plan and CMC requirements for AMG 130.

Good morning, and good afternoon, everyone.

During the second quarter of 2025, we continued to make meaningful advancements across our portfolio of clinical stage gene therapies.

The FDA agreed that the three of change in <unk> measured against the propensity score adjusted external control constructed using enroll HD dataset.

Let me start with <unk>.

In April <unk> was granted breakthrough therapy designation by the FDA.

This recognition first in Huntington disease was based on the phase one two data showing the potential to slow disease progression and underscore both the urgent need for effective treatments for Huntington's disease.

Serve as a registrational endpoint for accelerated approval BLA.

The agency also endorsed our CMC strategy, stating that it should be possible to validate the A&P 130 manufacturing process by leveraging prior knowledge and experience from Amgen ex unit curious approval approved commercial gene therapy for hemophilia B.

And the potential therapeutic benefits of <unk>.

As you know a recent FDA interactions have been highly productive.

Following to type B meetings in the first and second quarter, we announced in July alignment with the agency on the statistical analysis plan and CMC requirements for AMG 130.

This approach supplemented with data from additional full scale GMP batches in a single successful pp Q run may be sufficient to support process validation for the BLA submission.

The FDA agreed that the three you have change in <unk> measures against the propensity score adjusted external control constructed enroll HD dataset.

As Matt just mentioned, we have completed those GMP batches NDP PTO campaign is currently underway.

As stated in the press release. This morning, we have submitted the final SAP using a propensity score matched external control derived from the enrolling HQ datasets for the primary analysis.

Serve as a registrational endpoints for accelerated approval BLA.

The agency also endorsed our CMC strategy.

Meaning that it should be possible to validate the A&P one manufacturing process by leveraging prior knowledge and experience from <unk> unique cures approval approved commercial gene therapy for hemophilia B.

A number of additional analyses, including a propensity score weighted external control will be submitted as sensitivity and supplemental analysis.

This update reflects the alignment with the FDA stated preference and recommendation for proposing this quarter matched natural history controls.

This approach supplemented with data from additional full scale GMP batches in a single successful PB Q run may be sufficient to support process validation for the BLA submission.

The FDA, where we will receive both the propensity score matched and propensity score weighted analysis as disclosed previously.

As Matt just mentioned, we have completed those GMP batches and DPP <unk> campaign is currently underway.

Turning now to clinical progress I'm incredibly pleased to report that the AMG 130 clinical team has successfully completed the June 30 cutoff date for the three year data keeping us on track for the expected September did uptick.

As stated in the press release. This morning, we have submitted the final SAP using a propensity score matched external control derived from the enrolling HQ datasets for the primary analysis.

I'm also pleased to announce a fourth cohort in the phase one two trial of <unk> hundred 30 expected to initiate in the third quarter.

A number of additional analyses, including a propensity score weighted external control will be submitted as sensitivity and supplemental analysis.

This open label single arm study will evaluate the safety of the high dose of anti 130, and at least six patients with lower sales volumes.

This update reflects an alignment with the FDA stated preference and recommendation for proposing score matched natural history controls.

Patients who would have previously been excluded based on the criteria of a minimum federal volume can now be considered potentially expanding access to treatment.

The FDA, where we will receive both the propensity score matched and propensity score weighted analysis as disclosed previously.

Turning now to clinical progress I'm incredibly pleased to report that the AMG 130 clinical team has successfully completed the June 30 cutoff date for the three year data keeping us on track for the expected September did uptick.

We expect to have full enrollment by the fourth quarter of 2025.

Finally in September we plan to present topline data of our phase one two of <unk>.

We currently plan to disclose safety and Tolerability data through 36 months follow up as well as other topline data, including fee ratios and TFC at both dose levels compared to a propensity score matched natural history control.

I'm also pleased to announce a fourth cohort in the phase one two trial of <unk> hundred 30 expected to initiate in the third quarter.

This open label single arm study will evaluate safety of the high dose of anti 130 net leased six patients with lower sales volume.

We also plan on providing CSF NFL data at both doses compared to baseline at 36 months.

Patients who would have previously been excluded based on the criteria of a minimum federal volume can now be considered potentially expanding access to treatment.

Moving on to AMG 264, medial temporal lobe epilepsy.

In late May we shared initial data from the first subject in the gentle phase one two study at the epilepsy therapies in diagnostics development Symposium.

We expect to have full enrollment by the fourth quarter of 2025.

Finally in September we plan to present topline data of our phase one two of <unk>.

We observed a 92% reduction in seizure frequency over the first five months of follow up with no serious adverse events.

We currently plan to disclose safety and Tolerability data through 36 months follow up as well as other topline data, including <unk> and TFC at both dose levels compared to a propensity score matched natural history control.

While additional follow up on the first trial participant enrollment of additional participants in this trial are needed.

This case study provides an early signal that suggests our RNA based grid to targeted gene therapy can potentially suppressed seizure activity in this type of patients.

We also plan on providing CSF NFL data at both doses compared to baseline at 36 months.

Moving on to AMG 264, mesial federal of epilepsy.

This early data has generated enthusiasm among investigators and trial sites as well as interest within the broader epilepsy community, which is eager for a differentiated novel treatment options.

In late May we shared initial data from the first subject in the gentle phase one two study at the epilepsy therapies and diagnostic development symposium.

So trial recruitment remains challenging I'm very proud to say that additional sites have been activated and we expect to have additional patients enrolled before the end of the year.

We observed a 92% reduction in seizure frequency over the first five months of follow up with no serious adverse events.

Moving to AMG 191 for Fabry disease.

While additional follow up on the first trial participant enrollment of additional participants in this trial are needed.

The phase Iia clinical trial continues to enroll patients and we expect to present initial safety and exploratory efficacy data at the 2025 International Congress of inborn errors of metabolism or IC IEM conference.

This case study provides an early signal that suggests our RNA based Greek to targeted gene therapy can potentially suppressed seizure activity in this type of patients.

September five in Kyoto, Japan.

This early data has generated enthusiasm among investigators and trial sites as well as interest within the broader epilepsy community, which is eager for a differentiated novel treatment options.

Lastly, I'll touch on the <unk> hundred 64 sub one area that we continue to dose patients in the phase one two episodes, one clinical trial and we anticipate sharing the study's initial safety and biomarker data in the first half of 2026.

So trial recruitment remains challenging I'm very proud to say that additional sites have been activated and we expect to have additional patients enrolled before the end of the year.

Now I will turn the call over to Christian for a financial update Chris.

Christian.

Thank you.

Moving to AMG 191 for Fabry disease.

I'll start off pressuring for financial highlights the second quarter of 2025.

The phase <unk> clinical trial continues to enroll patients and we expect to present initial safety and exploratory efficacy data at the 2025 International Congress of inborn errors of metabolism or IC IEM conference.

Please refer to the earnings press release issued this morning in our quarterly filings for additional details.

Revenue for the first quarter was $3 million.

11 1 million.

September five in Kyoto, Japan.

Same period 2020.

Okay.

Lastly, I'll touch on the <unk> hundred 64 sub one area that we continue to dose patients in the phase one two episodes, one clinical trial and we anticipate sharing the study's initial safety and biomarker data in the first half of 2026.

The decrease of $5 million in revenue resulted from a $3 4 million dollar increase.

The license revenue.

A decrease of $7 $1 million from collaborations revenue and a decrease of $1 million from contract manufacturing allogeneic.

Now I will turn the call over to Christian for a financial update Chris.

Baird.

As noted in the first quarter following the divestments.

Christian.

Thank you.

I'll start off pressuring for financial highlights the second quarter of 2025.

<unk> in July 2020 for revenue from contract manufacturing this quarter net cost with an upper expenses.

Please refer to the earnings press release issued this morning in our quarterly filings for additional detail.

Cost of contract manufacturing revenue square Neil for the three months ended June 32025.

Revenue for the first quarter or a $3 million.

Is that $1 million.

Same period.

Compared to $7 2 million for the same period.

Okay.

A decrease of $5 million in revenue resulted from a $3 4 million dollar increase.

24 again following the divestment of production facility in July of last year.

License revenue.

Manufacturing is recorded.

A decrease of $7 $1 million from collaborations.

Okay upper expenses.

Revenue and a decrease of $1 million from contract manufacturing allogeneic, what CSL behring.

Research and development expenses were $5 four.

Million.

Three months ended June 32020.

As noted in the first quarter following divestments.

Five.

Compared to $43 $7 million the same period.

<unk> in July 2020 revenue from contract manufacturing.

24.

The $1 $7 million increase was related to an increase of $6 $3 million in extra program spend and a $4 million higher expenses related to an increase in fair value consideration.

Net cross walking upper expenses.

Cost of contract manufacturing revenue was square Neil for the three months ended June 32025.

Compared to $7 2 million for the same period.

This was offset by a decrease.

'twenty.

Again, following the divestment of electrical facility in July of last year.

$7 million.

Related expenses.

Decrease of $2 1 million for facility expenses and a $1.

Entrepreneurs Vectoring is recorded.

Okay.

$8 million decreased cost related to preclinical supplies.

Senses.

Research and development expenses were $5 4 million.

Selling general and administrative expenses were 13 $5 million a few.

Three months ended June 30.

Five.

Compared to $43 7 million the same period.

Three months ended June 32025.

Compared to $15 $8 million same period 2024.

24.

The $1 $7 million increase was related to an increase of $6 million in extra program expense and $4 million higher expenses related to an increase in fair value contingent consideration.

$2 3 million decrease was primarily related to a $1 $6 million decrease in employee related expenses at the point $6 million decreased professional fees compared to the prior year period.

This was offset by a decrease.

Cash cash equivalents and investment securities totaled $377 million as of June 32025.

$7 million.

Related expenses.

Decrease of $2 1 million facility expenses and $8 million decreased cost related to preclinical suppliers.

<unk> 367 5 million.

Simba first 2024.

Selling general and administrative expenses were 13 $5 million.

The increase was primarily related to the net proceeds $85 million from our first quarter follow on offering.

Months ended June 32025.

Yes.

Compared to $15 8 million same period 2024.

With this strong balance sheet, we believe <unk> is well positioned to execute its clinical and operational priorities, including the planned commercialization of anti <unk> therapy in the U S. In 2026, we expect cash cash equivalents and investment securities will be sufficient to fund operations into the second.

$2 3 million decrease was primarily related to $1 $6 million decrease in employee related expenses at the 6 million dollar decrease in professional fees compared to the prior year period.

Cash cash equivalents and investment securities totaled $377 million as of June 30.

2027.

I'll now turn the call back over to Matt.

Thanks for the update Christian.

Five.

As you've heard today, our strong execution during the first half of 2025 has positioned us for what we believe will be an exciting and pivotal second half of the year.

367 5 billion.

Simba first 2024.

The increase was primarily related to the net proceeds $85 million from our first quarter follow on offering.

We've achieved regulatory alignment on an accelerated approval pathway for <unk> 130 submitted our final statistical analysis plan.

Yes.

<unk> strong balance sheet, we believe <unk> is well positioned to execute its clinical and operational priorities, including the planned commercialization of anti <unk> therapy.

<unk> RP PQ campaign and continued to advance key BLA preparation activities.

Turkey and the U S in 2026.

Very much look forward to presenting top line pivotal data anticipated in September, which we expect will support our planned BLA submission in the first quarter of 2026, and if approved commencing U S. Commercial launch later that year.

Cash cash equivalents and investment securities will be sufficient to fund operations into the second half of 2027.

I'll now turn the call back over to Matt.

Thanks for the update Christian as you have heard today, our strong execution. During the first half of 2025 has positioned us for what we believe will be an exciting and pivotal second half of the year.

At the same time, we're progressing our broader pipeline with encouraging early data and medial temporal lobe epilepsy and initial fabry data on track for September.

Our mission remains clear to deliver transformative therapies for patients with serious unmet needs. We are focused well resource and energized for the opportunities ahead, and we look forward to keeping you updated on our progress in amongst account with.

We've achieved regulatory alignment on an accelerated approval pathway for <unk> 130 submitted our final statistical analysis plan initiated RP PQ campaign and continued to advance key BLA preparation activities.

Operator: Participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer. To ask a question during the session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising your hand To withdraw your question, please press star 1 1 again.

We very much look forward to presenting top line pivotal data anticipated in September, which we expect will support our planned BLA submission in the first quarter of 2026, and if approved commend to U S. Commercial launch later that year.

With that we will open the call to take questions from our research analysts.

Operator. Please proceed.

As a reminder to ask a question. Please press star one one on your telephone.

Your name to be announced.

Your question. Please press star one again in the interest of time, we ask that you. Please limit yourself to one question and one follow up please standby, while we compile the Q&A roster.

At the same time, we're progressing our broader pipeline with encouraging early data and medial temporal lobe epilepsy and initial fabry data on track for September.

Chiara Russo: Please be advised that today's conference is being I would now like to hand the conference over to your speaker today, Chiara Russo, Senior Director of Investor Relations. Please go ahead.

Our mission remains clear.

Our first question comes from Doug <unk>.

To deliver transformative therapies for patients with serious unmet needs we.

Chiara Russo: Good morning, and thank you for joining us for Uniqure's second quarter of 2025 earnings call. Earlier this morning, Uniqure released its financial results for the second quarter of 2025. And our press release is available on the investors and media section of our website at uniqure.com. Part 10-Q was also filed with the SEC earlier this year.

<unk> with Guggenheim Your line is open.

Thank you good morning, and thanks for taking my question I have one on a follow up as well. So number one does the FDA and expect a minimum threshold for clinical benefit versus the enrollments D. On C U S Crs.

We are focused.

Oil resource and energized for the opportunities ahead, and we look forward to keeping you updated on our progress in the months to come.

With that we will open the call to take questions from our research analysts.

Operator. Please proceed.

Well Lee do you want to answer that one sure.

As a reminder to ask a question. Please press star one on your telephone.

Chiara Russo: Joining me on the call today are Matt Kapusta, Chief Executive Officer, Dr. Walid Abi Saab, Chief Medical Officer, and Christian Klemt, Chief Financial After our formal remarks, we will open up the call for Q&A.

And discussions with the FDA.

And minimum clinical.

Your name to be announced.

Effect has not been requested nor has it been included in the plan.

Your question. Please press star one again.

In the interest of time, we ask that you. Please limit yourself to one question and one follow up please standby, while we compile the Q&A roster.

Having said that we would be.

Chiara Russo: Before we begin, please know that we will be making forward-looking statements during this investor call. All statements other than statements of historical fact are forward-looking. They are based on management's beliefs and assumptions, and on information available to management only as of the date of this recording. Their actual results could differ maturely from those anticipated in these four looking statements, for many reasons, including, without limitation, the factors described in Uniqure's most recent estimates.

Submitting the three year data.

Our first question comes from Doug.

Which we expect that we will show a substantial level of.

John <unk> with Guggenheim Your line is open.

Evidence that would support accelerated approval after the FDA review.

Thank you good morning, and thanks for taking my question I have one on a follow up as well. So number one does the FDA expect a minimum thresholds.

I appreciate that and our understanding is that the company has written feedback.

Nickel benefit versus the enrollments D on C U S Crs.

So how certain are you that you have D. As senior leadership, one renege on what's already been communicated to the company.

Well Lee do you want to answer that one sure.

And discussions with the FDA.

Yes.

Chiara Russo: Given these risks, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these statements, even if new information becomes available in the future.

Obviously, we're watching what's going on in the space.

And minimum clinical.

Effect has not been requested nor has it been included in the S&P plan.

Whats.

Publicly available in those situations each of these situations are very nuanced.

Matt Kapusta: Now let me introduce Matt Kapusta, Uniqure's CEO. Thanks, Chiara. And good morning, everyone. Thank you for joining today's second quarter conference.

Having said that we would be.

Submitting the three year data.

All of our interactions with the FDA have been very encouraging and very supportive.

Which we expect that we will show a substantial level of.

And as we said in the past numerous times, we are very clear and unambiguous feedback with the FDA.

Matt Kapusta: The first half of 2025 has been tremendously productive for the company as we advance AMT-130 towards potentially becoming the first disease modifying therapy for Huntington's disease. Our momentum is strong across four key areas, clinical advancement, regulatory alignment, BLA readiness, and commercial launch preparation. We also made advancements across our broader clinical pipeline, including AMT-191 for Fabry disease, AMT-260 for mesial temporal lobe epilepsy, and AMT-162 for SOD1-ALR.

Evidence that would support accelerated approval after the FDA meeting.

I appreciate that and our understanding is that the company has written feedback.

In terms of our situation.

It is different meaningfully in so much that we're moving forward with clinical outcomes data and long term clinical outcomes data as opposed to relying on.

So how certain are you that the Fda's senior leadership.

Todd will make on what's already been communicated to the company.

Yes.

On the surrogate biomarker. So we believe this is a robust approach we're focused on.

Obviously.

We're watching what's going on in the space.

Controlling and executing on what we can control and we're feeling very optimistic about our path forward.

What's public.

Publicly available in those situations each of these situations are very nuanced.

All of our interactions with the FDA have been very encouraging and very supportive.

Thank you.

Matt Kapusta: With pivotal top-line data from AMT 130 and initial clinical data from AMT 191 and FABRI both expected in September, we believe the second half of 2025 is shaping up to be an eventful period for Uniqure.

Thank you. Our next question comes from Joseph Schwartz with Leerink Partners. Your line is open.

And as we said in the past numerous times, we are very clear and unambiguous feedback with the FDA.

Hi, guys. This is Jamie on for Joe. Thank you for taking our question could you walk us through the A&P was any procedure and what this would look like from a patient perspective, including the time commitment.

In terms of our situation.

Matt Kapusta: Turning to AMT 130. In Q2, we continued to have productive interactions with the FDA, including receipt of breakthrough therapy designation in April and further regulatory alignment. AMT 130 remains the only investigational therapy in Huntington's. to have either Breakthrough Therapy designation or Regenerative Medicine Advanced Therapy or RMAT designation granted by the FDA. In June, we achieved alignment with the FDA on both our statistical analysis plan and CMC requirements for a planned BLE submission in the first quarter of 2026. Our primary efficacy analysis will compare the three-year change in CU-HDRS in high-dose patients to a propensity score-matched external control arm using data from the EnrollHD Natural History Study.

It is different.

Meaningfully in so much that we're moving forward with <unk>.

Are you thinking about part two would be appropriate to their surgery, how should we think about the commercial population.

Clinical outcomes data and long term clinical outcomes data as opposed to relying on.

There is a particular subset of patients who are more likely to be early adopters. Thank you.

On the surrogate biomarker. So we believe this is a robust approach we're focused on.

While they do you want to talk about the procedure.

Controlling and executing on what we can control.

Sure.

And we're feeling very optimistic about our path forward.

The procedure is.

Really.

One that is not complicated technically I mean, if you speak to versus those who have done.

Thank you.

Thank you. Our next question comes from Joseph Schwartz with Leerink Partners. Your line is open.

Neurosurgical administration to treat.

Tumors already deep brain stimulation.

Hey, guys. This is Jamie on for Joe. Thank you for taking our question could you walk us through the A&P with any procedure and what this would look like from a patient's perspective, including real time commitment.

This is <unk>.

<unk> fairly low complexity procedure or at least that's how the neurosurgeons describe it to us.

Patients are usually get an MRI ahead of time, so that we can.

How are you thinking about a person who would be appropriate to their surgery, how should we think about the commercial population.

Matt Kapusta: In addition, the FDA agreed that we can leverage our experience from hemgenics in validating the AMT130 manufacturing process. and that our process performance qualification can be limited to one such batch. Supplemented by additional commercial scale GMP batch. Following FDA guidance, we've made significant progress in preparing for the planned BLA submission. Manufacturing of two scale Pre-PPQ GMP batches is now complete, and we've initiated our formal PPQ campaign.

Plan B trajectory, there would be neurosurgery with Brexit.

The trajectory based on the MRI because of course, there is specific anatomical differences for each patient that the surgery need to take into consideration.

Particular subset of patients who are more likely to be early adopters. Thank you.

While the you want to talk about the procedure.

And on the day of the surgery the patient come in to.

Sure.

The procedure is.

<unk>.

Really.

And to the hospital in the morning, and then they get admitted to neurosurgery and using MRI guided.

One that is not complicated technically I mean, if you speak to versus those who have done any neurosurgical administration to treat.

Our registration.

Essentially probes are uncertain the rain under directors utilization of the MRI.

Tumors already deep brain stimulation.

This is.

Then the infusion there we'll be drilling a hole in the brain through which the catheter is abuse is introduced and then through direct visualization. We observed the infusion of the product which is mixed with the contrast material that is MRI compatible gadolinium and that way the neurosurgeon can observe live.

Really a fairly low complexity procedure or at least that's how the neurosurgeons describe it to us.

Matt Kapusta: We also recently submitted our final statistical analysis plan to the FDA, which Waleed will discuss in more detail shortly. On the commercial planning front, we continue to make disciplined investments in preparation for a potential 2026 launch.

Patients are usually get an MRI ahead of time, so that we can.

Plan B trajectories neurosurgery with Brexit the trajectory based on the MRI because of <unk>.

Of course, there is specific anatomical differences for each patient that they certainly need to take into consideration and on the day of the surgery the patient come in to.

Matt Kapusta: In June, we appointed an experienced leader, Kylie O'Keefe, as Chief Customer and Strategy Officer, and our HR team is actively recruiting key roles across medical affairs, market access, commercial operations, and other critical areas. The team is making strong progress on an integrated launch strategy, and we look forward to sharing more details in the future.

Administering the therapy that is actually reaching its target.

Very important aspect in what we do know the infusion has to occur at a slow rate.

Two.

So the hospital in the morning, and then they get admitted to neurosurgery and using MRI guided.

To make sure that the product diffusers appropriately to the right structure and that actually is what consumes most of the time. So so a lot of the time during the procedure, which has to be done six times, because readiness or three times on each side of the brain.

Our registration.

Essentially probes are uncertain the rain under directors utilization of the MRI.

Matt Kapusta: Now turning to our broader pipeline, in May, we shared encouraging early data from the first patient treated with AMT260 for mesial temporal lobe epilepsy. Over the first five months of follow-up, the patient experienced a 92% reduction in seizure frequency with no significant adverse events. This early result has sparked strong interest among investigators and the epilepsy community.

And the infusion there will be drilling of a hole in the brand through which the catheter is abused.

It is what it takes actually most of the time.

Introduced and then through direct visualization, we observed the infusion of the product, which is mixed with the contrast material that is MRI compatible gadolinium and that way the neurosurgeon can observe.

And usually that takes a number of hours at the end of which.

Essentially the patient wakes.

And.

Usually they stay.

<unk> as they are administering the therapy.

24 hours I believe.

Actually reaching its target that's a very important aspect in what we do now.

And then there will be discharged and often.

Matt Kapusta: I'm pleased to say that we have 14 clinical sites in the U.S. that continue to screen patients for this study.

They tend to recover very quickly because again its a very minimal.

Now the infusion has to occur at a slow rate.

<unk>.

To make sure that the product diffusers appropriately to the right structure.

How should I say.

Matt Kapusta: During the second quarter, we also continue to advance our Fabry and SOD1 ALS studies and look forward to presenting initial Fabry data at the ICIEM conference in early September. Overall, I'm incredibly proud of the team's execution and dedication towards advancing these important therapies.

Very minimally invasive from the perspective of the size of the probe that are introduced and often patients.

And that actually is what consumes most of the time. So so a lot of the time during the procedure, which has to be done six times, because readiness or three times on each side of the brain.

We have been few days they get back to work.

That's been our experience and our trial and I'll go back to you Matt for details on the target patient population in the commercial question.

Is what it takes actually most of the time.

And usually that takes a number of hours at the end of which.

Matt Kapusta: In the first half of 2025, we delivered on several key goals and remain on track for what we believe could be a transformational second half marked by meaningful data updates, regulatory progress, and continued momentum towards the planned BLA submission of AMT 134.

Yes, I mean I think the reality is there's nothing for these patients there is no disease modifying therapy.

Essentially the patient wakes.

And.

And so I believe that the.

Usually they stay.

The 24 hours I believe and then they will be discharged and often.

The overwhelming majority of patients that are eligible.

Are going to become informed about it and I think seriously consider therapy.

They tend to recover very quickly because again its a very minimal.

Walid Abi Saab: I will now turn the call over to Walid to provide a more detailed clinical update. Thank you, Matt. Good morning and good afternoon, everyone. During the second quarter of 2025, we continue to make meaningful advancement across our portfolio of clinical stage gene therapy.

In terms of our inclusion criteria, we're largely looking at stage two and stage III patients, which are typically patients that are considered early manifest. So they have developed some.

How should I say.

Very very minimally invasive from the perspective of the size of the probe that are introduced and often patients.

Few days they get back to work.

It's been our experience.

Form of Symptomology, and they've been tested and confirmed genetically that that they have huntington's disease that will become 100% penetrated so that's definitely going to be our focus.

Trial.

Walid Abi Saab: Let me start with AMT1. In April, MT130 was granted Breakthrough Therapy designation by the FDA. This recognition, a first in Huntington's disease, was based on the Phase I-II data showing the potential slow disease progression and underscores both the urgent need for effective treatments for Huntington's disease and the potential therapeutic benefits of AMT130.

I'll go back to you Matt for details on the target patient population in the commercial question.

Yes, I mean I think the.

The reality is there is there is nothing for these patients there is no disease modifying therapy.

And.

And so I believe that the.

And I think it's going to be as I said, it's going to be something that.

The overwhelming majority of patients that are eligible.

Now that there is at least the treatment option.

That is hard to imagine that.

Are going to become informed about it and I think seriously consider therapy.

All or a majority of all patients are going to seriously consider and become informed about our therapy.

Walid Abi Saab: As you know, our recent FDA interactions have been highly productive. Following two type D meetings in the first and second quarter, we announced in July alignment with the agency on the statistical analysis plan and CMC requirements for AMT 130. The FDA agreed that the three-year change in CUHCRS measured against a propensity score-adjusted external control constructed using enrolled HD data sets. serve as the registrational endpoint for an accelerated approval VMI. The agency also endorsed our CMC strategy, stating that it should be possible to validate the AMT130 manufacturing process by leveraging prior knowledge and experience from hemogenics, Uniqure's approved commercial gene therapy for hemophilia.

In terms of our inclusion criteria, we're largely looking at stage two in phase III patients, which are typically patients that are are considered early manifest. So they have developed some.

Thank you that's really helpful.

Thank you. Our next question comes from Paul Matisse with Stifel. Your line is open.

Form of Symptomology.

Great. Good morning, Thanks for taking my questions. We noticed this morning that you said youre going to be using propensity matched.

<unk> been tested and confirmed genetically that that they have huntington's disease that will become 100% penetrated.

His analysis not propensity weighted can you just talk about where that comes from is that.

So that's definitely going to be our focus.

And.

I'm thinking that the FDA requested.

And I think it is going to be as I said, it's going to be something that.

And then specifically.

How does that compare to the data that we saw in the last cut in 2024.

Now that there is at least the treatment option.

That is hard to imagine that.

If it's a different methodology than what we're going to see here or is this going to be apples and orange is the 80% number.

All or a majority of all patients are going to seriously consider and become informed about our therapy.

Walid Abi Saab: This approach, supplemented with data from additional full-scale GMP batches and a single successful PPQ run, may be sufficient to support process validation for the BLA submission. As Matt just mentioned, we have completed those GMP batches, and the PPQ campaign is currently under way. As stated in the press release this morning, we have submitted the final SAP using a propensity score matched external control derived from the EnrollHD data set for the primary analysis. A number of additional analyses, including a propensity score-weighted external control, will be submitted as sensitivity and supplemental analysis. This update reflects an alignment with the FDA's stated preference and recommendation for proprietary score-matched natural history control.

130 still stand and then if you don't mind I just have one follow up thank you.

Thank you that's really helpful.

Thank you.

While they do you want to go I would add to that.

Our next question comes from Paul Matisse with Stifel. Your line is open.

Thanks, Yes, thanks Paul.

We've we've indicated previously when we reported back after meeting with the FDA that the Fda's stated preference was for propensity score matching.

Great. Good morning, Thanks for taking my questions. We noticed this morning that you said youre going to be using propensity matched in this.

Analysis, not propensity weighted can you just talk about where that comes from is that.

We also consulted with our external statistical experts and when we took all of these into consideration we decided to submit the SAP that's aligned with the FDA preference using propensity score matching of the primary endpoint.

Something that the FDA requested.

And then specifically.

How does that compare to the data that we saw in the last cut in 2024.

Having said that.

If it's a different methodology than what we're going to see here or is this going to be apples and oranges, the 80% number for.

The agency will also continue to receive both the propensity score matching and the reports propensity score waiting analyses just as we stated before now.

130 still stand and then if you don't mind I just have one follow up thank you.

Now in constructing.

Constructing.

While Lee do you want to answer that.

The natural history.

Walid Abi Saab: The FDA will receive both the propensity score matched and propensity score-weighted analysis as disclosed previously.

Thanks, Yes, thanks Paul.

Database as we were evaluating.

We've we've indicated previously when we reported back after meeting with the FDA that the Fda's stated preference was for propensity score matching.

Accuse me.

The most.

Most appropriate.

Natural history database to use we have to construct the.

Walid Abi Saab: Turning now to clinical progress, I'm incredibly pleased to report that the AMT130 clinical team has successfully completed the June 30th cutoff date for the three-year data, keeping us on track for the expected September data.

We also consulted with our external statistical experts and when we took all of these into consideration we decided to submit the SAP that's aligned with the FDA preference using propensity score matching the primary endpoint.

Annual decline over a period of three years.

Patients using a variety of methodologies propensity score rating matching exact matching number of these and using the enrolled database. We found that the propensity score methodology in whichever form is quite robust leading very similar estimate of decline after three years regardless of them.

Walid Abi Saab: I'm also pleased to announce a fourth cohort in the Phase 1-2 trial of AMT130 expected to initiate in the third quarter. This open-label, single-arm U.S. study will evaluate safety of the high-dose of anti-130 in at least six patients with lower striator volume. Patients who would have previously been excluded based on the criteria of a minimal serial volume can now be considered, potentially expanding access to treatment. Expect to have full enrollment by the fourth quarter of 2020.

Having said that.

The agency will also continue to receive both the propensity score matching and the reports propensity score waiting analyses just as we stated before.

<unk> so to answer your question I would not expect that the results will be.

Now in constructing.

Constructing.

Materially different if we use prevents us core matching propensity score reading.

The natural history.

Database as we were evaluating.

And considering the Fda's preference, we decided to go that route and be more aligned with them, but we will be somebody growth anyway.

Accuse me.

The most.

Most appropriate.

And that's really through database to use we have to construct.

The.

Okay. Thank you that's Super helpful. And then look I know this is extraordinarily subjective and ultimately in Huntington's right. There is nothing but how are you guys thinking about the bar.

Annual decline over a period of three years.

Walid Abi Saab: Finally, in September, we plan to present top-line data of our Phase 1-2 of AMT 130. We currently plan to disclose safety and tolerability data through 36-month follow-up, as well as other top-line data, including COHGRS and TFC at both those levels, compared to a propensity score-matched natural history control. We also plan on providing CSF and NFL data at both doses compared to baseline at 36 months.

Ah patients using a variety of methodologies propensity score rating matching exact matching number of these.

And in using the enrolled database, we found that the propensity score methodology in whichever form is quite robust leading.

Onto the slowing in this three year analysis and look again understanding that Huntington's doesn't.

Have any disease modifying treatments.

Very similar estimate of decline after three years, regardless of the methodologies. So to answer your question I would not expect that the results will be.

I would think you'd want the data to hold up to some degree right. Just first of all for the best of the drug and second of all to be confident in your regulatory alignment. So.

And analysts were trying to drive this line how would you draw this line.

Materially different if we use for Vince you score matching pharmaceutical reading.

Walid Abi Saab: Moving on to AMT 260, for mesial-temporal epilepsy. In late May, we shared initial data from the first subject in the GENTLE Phase 1-2a study at the Epilepsy Therapies and Diagnostics Development Symposium. We observed a 92% reduction in seizure frequency over the first five months of follow-up with no serious adverse. While additional follow-up on this first trial participant and enrollment of additional participants in this trial are needed, this case study provides an early signal that suggests our miRNA-based GRK2-targeted gene therapy can potentially suppress seizure activity in this type of patient. This early data has generated enthusiasm among investigators and trial sites, as well as interest within the broader epilepsy community, which is eager for differentiated, novel terminology.

Yes.

And considering the Fda's preference, we decided to go that route to be more aligned with that but we will be somebody growth anyway.

Sorry.

I'm going to continue I'm, just kind of give it to Paul.

Yeah.

No go ahead Robby.

Yes, I mean I think.

Okay. Thank you that's Super helpful. And then look I know this is extraordinarily subjective and ultimately in Huntington's right. There is nothing but how are you guys thinking about the bar.

I asked that question a lot it's an important question honestly.

As you said there is nothing for these patients Matt mentioned that before when we talked to a number of kols what they tell US is look anything that is.

On disease slowing in this three year analysis, and look again understanding that Huntington's doesn't.

That would reduce the disease progression by 25% to 30% would be would be great.

Have any disease modifying treatments.

I would think you'd want the data to hold up to some degree right. Just first of all for the best with the drug and second of all to be confident in your regulatory alignment. So investors and analysts are trying to drive this line how would you draw this line.

Potentially many years of quality of life.

These patients who have nothing.

But.

From our perspective, just like you said, we would like our data to continue to show a meaningful.

Yes.

Slowing of disease progression that will be something that the agency will consider.

Sorry.

I'm going to continue I'm, just kind of give it to Paul.

<unk>.

Appropriate for approval, but also the patients will find clinically meaningful.

No go ahead Robby.

Yeah, I mean I think.

We were asked that question a lot it's an important question honestly.

Walid Abi Saab: So trial recruitment remains challenging. I'm very proud to say that additional sites have been activated, and we expect to have additional patients enrolled before the end of the year.

That is we believe in our mechanism of action, we saw the data two years.

As you said there is nothing for these patients Matt mentioned that before when we talked to a number of kols what they tell us is anything that is.

We feel optimistic that the three year data will continue to show a meaningful improvement that will both satisfy patients.

Walid Abi Saab: Moving to AMT 191 for Fabry disease. The Phase 1-2A clinical trial continues to enroll patients, and we expect to present initial safety and exploratory efficacy data at the 2025 International Congress of Inborn Errors of Metabolism, or ICIEM, conference. on September 5th in Kyoto, Japan.

That would reduce the disease progression by 25% to 30% would be would be great.

But also with the FDA.

Potentially many years of quality of life to these.

Thank you. Our next question comes from Joseph Thome with TD Cowen Your line is open.

Patients who have nothing.

But.

Hi, there good morning, Thank you for taking my question.

From our perspective.

Just like you said, we would like our data to continue to show any meaningful.

I have one.

Question on one follow up if I can I guess, just given the back and forth with threat over the course of this week does that change at all your thinking on how you are approaching the launch of anywhere whether you want to do a stage launch target number of surgeons and be a little bit more cautious at the beginning or how youre thinking about that obviously, so many differences between disease states in the age and everything like that but I guess are there any.

Walid Abi Saab: Lastly, I'll touch on AMC 162 for SOD 1 LF. We continue to dose patients in the Phase 1-2, Episode 1 clinical trial, and we anticipate sharing the study's initial safety and biomarker data in the first half of 2026.

Slowing of disease progression that will be something that the agency will consider.

Appropriate for approval, but also the patients will find clinically meaningful.

That is we believe in our mechanism of action, we saw the data two years.

Christian Klemt: Now, I will turn the call over to Christian for a financial update. Christian? Thank you.

We feel optimistic that the three year data, we will continue to show a meaningful improvement that will both satisfy the patients.

<unk> that you've taken from from the past week and then second do you expect there to be a minimal trailer volume on the label.

Christian Klemt: I'll start off by sharing the financial highlights. Please refer to the earnings press release issued this morning and our quarterly filing. Revenue for the first quarter was $5.3 million. 11.1 million in the same period. The decrease of $5.8 million in revenue resulted from a $3.4 million increase. in Licensed Revenue. Preece for $7.1 million from collaboration revenue, and. $1,000,000 from contract manufacturing of hemogenics for CSO Bear.

But also the FDA.

On the asset because I noticed you're initiating a fourth cohort.

With smaller strangle volumes, so kind of just thinking that that's going to be a form of label expansion or if those would be more just to use guideline for clinicians in the field. Thank you.

Thank you. Our next question comes from Joseph Thome with TD Cowen Your line is open.

Hi, there good morning, Thank you for taking my question.

I have one.

Yes, maybe I'll take the first one you take the second one.

A question and one follow up if I can.

Just given the back and forth with threat to over the course of this week does that change at all your thinking on how you are approaching the launch of anywhere whether you want to do a stage launch is targeted number of surgeons and be a little bit more cautious at the beginning or how youre thinking about that obviously, so many differences between disease states and age and everything like that but I guess are there any learnings that you've taken from from the past week.

So, yes, I mean.

Honestly, we've always operated in a way where patient safety is our utmost priority. So it's not like anything going on in the.

The sector is going to is going to change that view I think we've always thought.

Christian Klemt: As noted in the first quarter, following the divestment of the Lexus, Machado, and Claudia Alatsky.

That for AMG 130 that there are going to be.

And then second do you.

You expect there to be a minimal volume on the label.

Christian Klemt: or Revenue from Contract Manufacturing is recorded net of cost within other Cost of contract manufacturing revenues were nil for the three months ended June 30, 2025, compared to $7.2 million for the same period. Again, following the divestment of the... Manufacturing is recorded net of revenue in upper.

At the time of launch centers of excellence that have experience with the.

I only asked because I noticed you're initiating a fourth cohort.

With smaller volumes, so kind of just thinking that that's going to be a form of label expansion or if those would be more just to use guideline for clinicians in the field. Thank you.

Surgical procedure that are that are conducting these procedures.

And we're going to be something that we're going to be continually monitoring as we launch the product but.

Yes, maybe I'll take the first one you take the second one.

So yes, I mean honestly, we've always operated in a way where patient safety is our utmost priority. So it's not like anything going on in the.

At the same time, we treated 45 patients I think we really believe.

The AMG 130 is generally safe and well tolerated I'll also mentioned that.

Our administration of AMG 130 is a local administration so the.

Christian Klemt: Research and Development Experts. $5.4 million for the three months ended June 30, 2025, compared $3.7 million during the same period. The $1.7 million increase was related to an increase of $6.3 million in external program spend and the $4 million higher expenditure.

In this sector is going to change that view I think we've always thought.

Systemic exposure that occurs when we administered <unk> hundred 30 is meaningfully less.

That for AMG 130 that there are going to be.

And then let a gene therapy that is systemically administered.

At the time of launch centers of excellence that have experience with the <unk>.

And we have just simply not seeing any any liver toxicity associated with AMG 130. We're also utilizing <unk> that has been studied.

Surgical procedure that are that are conducting these procedures.

And we're going to be something that we're going to be continually monitoring as we launch the product.

Christian Klemt: Fair Value Contingent Consideration. This was offset by a decrease of $4.7 million. Related Expenses. creates of $2.1 million. Spencer, and a $1.8 million decrease in costs related to preclinical supply. Selling General Administrative $5 million for the three months ended June 30. 5, compared to $15.8 million just the same period. The $2.3 million decrease was primarily related to a $1.6 million decrease in employee-related expenses and a $0.6 million decrease in professional fees compared to the prior year. Cash, Cash Equivalents, and Investment Securities totaled $377 million as of June 30, 2025. compared to $367.5 million as of December 31st, 2024.

With systemic administration vis vis <unk> <unk>.

At the same time, we treated 45 patients I think we really believe.

And we've also not seen any.

Any significant adverse events associated.

The AMG 130 is generally safe and well tolerated I'll also mention that.

With with <unk> or AAV five in that context, as well even with systemic administration. So it's very important to understand these new technical differences differences with administration.

Our administration of AMG 130 is a local administration. So the systemic exposure that occurs will be administered <unk> hundred 30 is meaningfully less.

Nothing's going to change our view that patient safety is always going to be.

Then that a gene therapy that is systemically administered.

At the top of our priorities.

Okay, So on Australia volume.

And we have just simply not seeing any any liver toxicity associated with AMG 130, we're also utilizing an AAV <unk> that have been studied.

Taking a step back the way this came to be was.

As the study was initially designed.

Sub six years ago or so.

With systemic administration vis vis <unk>.

Out of the abundance of caution we wanted to make sure that we have.

Australia volume that would be large enough. So we can safely administer the product to these patients but over the years.

And we've also not seen any.

Any significant adverse events associated.

With with <unk> or <unk> five in that context, as well even with systemic administration.

We've accumulated a lot of experience with more than 40 total of 45 and separate from the administration to date.

So it's very important to understand these new technical differences differences with administration.

The experience that we've accumulated with our neurosurgeons and in discussions with them.

Christian Klemt: The increase is primarily related to the net. $5 million Klingon.

But nothing's going to change our view that patient safety is always going to be.

We are we've decided that we should be.

At the top of our priorities.

Relaxing these criteria and now evaluating.

Christian Klemt: With this strong balance sheet, we believe Uniqure is well-positioned. Clinical and Operational Parts. including the planned commercialization of MQ-130 in the U.S.

Okay. So on the <unk> volume.

A an approach where we.

<unk> taken a step back.

We will use the neurosurgeons clinical judgment, whether they can reach the target structure.

<unk> came to be was.

As the study was initially designed.

Christian Klemt: in 2012.

Sub six years ago or so.

Christian Klemt: expect cash, cash equivalents, and investment securities will be sufficient to fund operations into the second half of 2020.

Without.

Out of the abundance of caution to make sure that we have.

Without fixing a specific minimum volume.

Australia volume that would be large enough. So we can safely administer the product to these patients but over the years.

In order for us to study that we needed to include patients who are otherwise would have been excluded from our trial those with lower sales volume.

Matt Kapusta: I now turn the call back over. Thanks for the update, Christian. As you've heard today, our strong execution during the first half of 2025 has positioned us for what we believe will be an exciting and pivotal second half of the year. We've achieved regulatory alignment on an accelerated approval pathway for AMT 130, submitted our final statistical analysis plan, initiated our PPQ campaign, and continue to advance key BLA preparation activities. We very much look forward to presenting top-line pivotal data anticipated in September, which we expect will support a planned BLA submission in the first quarter of 2026 and, if approved, commence a U.S.

We've accumulated a lot of experience with more than 40 total of 45 and soccer increment administrations to date.

Start generating safety data with us now.

Whether this will be in the label or not those discussions have not taken place with the FDA that would be something that would have to occur later in the review process.

The experience, we accumulated without neurosurgeons and in discussions with them.

We are we've decided that we should be.

Relaxing these criteria and now evaluating.

Of course, generating these data and depending on the outcome of the.

A an approach where we.

The safety profile of this those will be included in the safety update.

Use the neurosurgeons clinical judgment, whether they can reach the target structure.

Part of our discussions with the agency, but it's premature right now to be able to.

AC.

Speculate or give guidance as to what we think the label would look like.

<unk>.

Without fixing a specific minimum volume and.

Thank you. Our next question comes from Sheila Hernandez with Van Kampen.

In order for us to study that we needed to include patients who otherwise would have been excluded from our trial those with lower sale volume to start accelerating.

Matt Kapusta: commercial launch later that year. At the same time, we're progressing our broader pipeline with encouraging early data in mesial temporal lobe epilepsy and initial Fabry data on track for September. Our mission remains clear to deliver transformative therapies for patients with serious unmet needs. We are focused, well-resourced, and energized for the opportunities ahead. And we look forward to keeping you updated on our progress in the months to come.

Yes. Thank you for taking my question.

The data with them.

Now whether this will be in the label or not those discussions have not taken place with the FDA that would be.

So just a follow up on the floor to cohorts and what do you hope to expect to see an expansion population and then second question. What are the next steps for AMC to 16 are you expecting to add more sites. Thank you.

Something that would have to occur later in the review process.

Of course, generating these data and depending on the outcome.

I suppose I'll take both rate yes.

The safety profile of this of those will be included in the safety update I mean part of our discussions with the agency, but it's premature right now to be able to.

So with the fourth cohort.

The expectations and the <unk>.

Short term is to document the.

Operator: With that, we will open the call to take questions from our research analysts. Operator, please proceed. As a reminder, to ask a question, please press star 1-1 on your telephone. Wait for your name to be announced. To withdraw your question, please press star 1-1 again. In the interest of time, we ask that you please limit yourself to one question and one follow-up.

Speculate or give guidance as to what we think the label would look like.

Safety of the procedure that we can administer this safely that the neurosurgeons that we have in the system that we have in place to be able to evaluate whether we can safely administer <unk> 30 for those who would have otherwise been excluded from our trial because they would have lower volume.

Thank you. Our next question comes from Sheila Hernandez with Van Kampen.

Yes. Thank you for taking my question and also just a follow up on the floor to cohorts and what do you expect to see an expansion population and then second question. What are the next steps for AMC to 16 are you expecting to add more sites. Thank you.

Operator: Please stand by while we compile the Q&A rod.

The system is in place it operates well and we cannot.

Debjit Chattopadhyay: Our first question comes from Debjit Chattopadhyay with Guggenheim. Your line is open. Hey, good morning, and thanks for taking my question. I have one and a follow-up as well.

And then of course, we will be monitoring them forward for efficacy and so on so forth, but I personally.

I suppose I'll take both rate yes.

Do not foresee where there would be any difference.

Walid Abi Saab: So number one, does the FDA expect a minimum threshold for clinical benefit versus the enrolled HD on C-UHCRS? Walid, do you want to answer that one? Sure. In discussions with the FDA, a minimum clinical effect has not been requested, nor has it been included in the assessment. Having said that, we will be submitting the three-year data, which we expect that will show a substantial level of evidence that would support accelerated approval after the FDA.

So with the fourth cohort.

Once we establish that the <unk> is actually.

The expectations in the short term is to document the <unk>.

Effective in slowing disease progression. There is no reason for this to be different based on.

Safety of the procedure that we can administer this safely that the neurosurgeons that we have in the system that we have in place to be able to evaluate whether we can safely administer AMG 130 for those who would have otherwise been excluded from our trial because they would have lower volume.

In arbitrary cutoff, Australia volume.

In terms of A&P to 60, yes, indeed, as Matt said, we have increased the number of sites. We now have 14 active there's a lot of activity since we disclosed the data on that first patient will be very positive results.

Received very positively we've seen a very significant uptick in screening activities.

The system is in place it operates well and we cannot.

And then of course, we will be monitoring them for for efficacy and so on so forth.

We really do feel quite confident that we will be getting a number of additional patients in the second half of the year.

I personally.

We'll see where there would be any difference.

Walid Abi Saab: Appreciate that. And our understanding is that the company has written feedback. So how certain are you that the FDA senior leadership won't renege on what's already been communicated to the company? Yeah, Debjit, obviously, you know, we were watching what's going on in the space. We know what's publicly available in those situations, each of these situations are very nuanced. All of our interactions with the FDA have been very encouraging and very supportive. And as we've said in the past numerous times, we have very clear and unambiguous feedback with the FDA.

Once we establish that the <unk> is actually.

Thank you. Our next question comes from Patrick <unk> with <unk>.

Effective in slowing disease progression. There is no reason for this to be different based on.

Your line is open.

Good morning, everyone and congratulations on the project on the progress. This is Luis in for Patrick First question, just thinking ahead of AWN.

In arbitrary cutoff, Australia volume.

In terms of A&P to 60, yes, indeed, as Matt said, we have increased the number of sites. We now have 14 active.

Any are there any differences do you expect any differences from a regulatory path to approval in Europe versus the U S and then on.

A lot of activity since we disclosed the data on that first patient will be very positive results.

The $1 30 and 160.

Received very positively we've seen a very significant uptick in screening activities.

How should we how should we think about the plan.

We really do feel quite confident that we will be getting a number of additional patients in the second half of the year.

The phase III portion of <unk> look like in terms of patients.

We plan to enroll the same disease.

Walid Abi Saab: Thank you. In terms of our situation, you know, it is different meaningfully in so much that we're moving forward with clinical outcomes data and long-term clinical outcomes data as opposed to relying on a surrogate biomarker. So we believe this is a robust approach. We're focused on controlling and executing on what we can control, and we're feeling very optimistic about our path forward.

Stage patients with.

Thank you. Our next question comes from Patrick <unk> with <unk>.

Also include non leesville patients as well thank you so much.

Your line is open.

Yes, just I'll, maybe take the first one while reading you can you can address the second one so we have not yet.

Good morning, everyone and congratulations on the project on the progress. This is Luis in for Patrick First question, just thinking ahead of AWN.

Met with EMA.

To solicit.

Any are there any differences do you expect any differences from a regulatory path to approval in Europe versus the U S. And then on the $1 30 and 116 Hum.

Scientific advice with respect to the Registrational path forward.

Our focus right now is on on the U S and of course, we will expect to have the three year data presented which we think can be also important information.

Debjit Chattopadhyay: Thank you and I will see you in the next one.

How should we how should we think about.

The plan.

Debjit Chattopadhyay: Thank you.

Joseph Schwartz: Our next question comes from Joseph Schwartz with Leering Partners. Your line is open.

Furnish EMA when we have those scientific advice discussion so.

Phase II portion of <unk> look like in terms of patients.

Jenny Gonzalez: Hi guys, this is Jenny on for Joe. Thank you for taking our question.

So when we plan to enroll the same disease.

You will look to have them.

Stage patients with.

Jenny Gonzalez: Could you walk us through the AMT-130 procedure and what this would look like from a patient's perspective, including the time commitment?

In the near term and once we do we'll make sure we provide an update to the market.

Also include non leesville patients as well thank you so much.

Jenny Gonzalez: And how are you thinking about who would be appropriate for the surgery?

Regarding AMG 260.

Yes, just I'll, maybe take the first one while reading you can you can address the second one so we have not yet.

Jenny Gonzalez: How should we think about the commercial population?

In terms of designs of the phase II study.

Jenny Gonzalez: Do you think there's a particular subset of patients who are more likely to be early adopters? Thank you.

It's premature to discuss that the reality is that we.

With <unk>.

To solicit.

We do phase one to learn from it so that will also dictate.

Scientific advice with respect to the Registrational path forward.

Walid Abi Saab: Wally, do you want to talk about the procedure? Sure, the procedure is really one that is not complicated technically. I mean, if you speak to neurosurgeons who have done any neurosurgical administration to treat tumors or any deep brain stimulation, really a fairly low-complexity procedure. At least that's how the neurosurgeons describe it to us. Patients usually get an MRI ahead of time so that we can plan the trajectory. The neurosurgeon will plan the trajectory based on the MRI because, of course, there are specific anatomical differences for each patient that the surgeon needs to take into consideration.

The design of the subsequent trial, but in terms of the patient population, we start with those.

Our focus right now is on on the U S and of course, we will expect to have the three year data presented which we think could be.

Non dominant because.

That way you establish.

Also important information.

The risk benefit profile and then you start branching out to those with dominant disease I think the next natural step we will be also to look at bilateral the reality is that it.

Furnish EMA when we have those scientific advice discussions so.

You will look to have them.

In the near term and once we do we'll make sure we provide an update to the market.

As with dominant in bilateral is where the high unmet need is because those would be unlikely to benefit from <unk>.

Regarding AMG 260.

<unk> therapy, like ablation laser ablation or resection surgery.

In terms of designs of the phase II study.

Mature to discuss that.

Reality is that.

But that's kind of the thinking that we have around expansion.

We do phase one to learn from it so that that will also dictate.

We addressed in the program.

Walid Abi Saab: And on the day of the surgery, the patients come in to the hospital in the morning, and then they get admitted to neurosurgery. And using MRI-guided registration, essentially, probes are inserted in the brain under direct visualization of the MRI. And there will be drilling of a hole in the brain through which the catheter is introduced. And then through direct visualization, we observe the infusion of the product, which is mixed with the contrast material that is MRI-compatible, gadolinium. And that way, the neurosurgeon can observe live as they're administering the therapy that it's actually reaching its target.

The design of the subsequent trial, but in terms of the patient population, we start with those.

Thank you. Our next question comes from Eliana Merle with UBS. Your line is open.

Those.

On the non dominant because.

Is that gasoline for allocating for taking a question.

That way you establish.

The risk benefit profile and then you start branching out to those with dominant disease I think the next natural step we will be also to look at bilateral the reality is that those with dominant in bilateral is where the high unmet need is because those would be.

First can you give any color on what you plan to talk about and learn from the pre BLA meeting with the FDA and breakeven when we get an update.

And then secondly on.

On the Huntington's commercial opportunity how many sites in the U S are capable of doing the administration procedure.

Unlikely to benefit from <unk>.

<unk> therapy, like ablation laser ablation or resection surgery.

Okay.

The study enrollment criteria can you give an estimate of the prevalence of patients that would be eligible in the U S.

But that's kind of the thinking that we have around expansion.

Thank you.

Trends in the program.

Walid Abi Saab: That's a very important aspect. Now the infusion has to occur at a slow rate to make sure that the product diffuses appropriately to the right structure. And that actually is what consumes most of the time. So a lot of the time during the procedure, which has to be done six times because we administer three times on each side of the brain, is what it takes actually most of the time. And usually that takes a number of essentially the patient wakes up and usually they stay like 24 hours, I believe, and then they will be discharged.

Yes, so ill answer the last question first.

Thank you. Our next question comes from Eliana Merle with UBS. Your line is open.

And then you can answer the first question if that's okay.

Is that gasoline for Elliot. Thank you for taking our question.

So.

Yes, I mean in terms of the.

First can you give any color on what you plan to talk about and learn from the pre BLA meeting with the FDA and breakeven when we get an update.

The commercial potential there.

There's 35000 patients that are currently diagnosed with huntington's disease.

And then secondly on.

And then there is probably three times as many people that have huntington's disease, but but have not been genetically confirmed because there's obviously nothing for those patients.

On the Huntington commercial opportunity how many sites and then you actually are capable of doing the administration procedure.

Okay.

The study enrollment criteria can you give an estimate of the prevalence of patients that would be eligible in the U S.

Our view is that there's going to be we'll provide obviously more detail on this but.

Thank you.

The overwhelming majority.

Yes, so I mean.

Walid Abi Saab: And often they tend to recover very quickly because again, it's a very minimal how should I say, very minimally invasive from the perspective of the size of the probe that are introduced. And often patients, you know, within a few days, they get back to work. At least that's been our experience in our trial.

Of the patients that are diagnosed.

Answered the last question first.

Have stage, two and stage three because typically the diagnosis of Huntington's disease happens once their symptom onset.

And then you can answer the first question if that's okay.

So.

Yes, I mean in terms of the.

So there's going to be many thousands of patients.

And the commercial potential there.

There are 35000 patients that are currently diagnosed with huntington's disease.

In our view are going to be eligible.

Matt Kapusta: And I'll go back to you, Matt, for details on the target patient population and the commercial question. Yeah, I mean, I think the reality is there's nothing for these patients. There's no disease modifying therapy. And so, you know, I believe that the overwhelming majority of patients that are eligible are going to become informed about it and I think seriously consider therapy. In terms of our inclusion criteria, we're largely looking at stage two and stage three patients, which are typically patients that are considered early manifest. So they have developed some form of symptomology and they've been tested and confirmed genetically that that they have Huntington's disease that will become 100% penetrative.

For the procedure.

The last part of this what the the number of sites that are capable of doing the procedure you have to be very clear. This is this is not a novel procedure. This is a very standard procedure for a neurosurgeon theres, probably somewhere between 50 and 55 sites.

And then there is probably three times as many people that have huntington's disease, but but have not been genetically confirmed because there's obviously nothing for those patients.

Our view is that there is going to be we'll provide obviously more detail on this but.

Then have the neurosurgical expertise in the imaging equipment to be able to do this procedure.

The overwhelming majority.

Of the patients that are diagnosed.

We don't even think we need to be in every one of those centers to address to address the market and certainly at launch there is going to be a center of excellence strategy.

Have stage, two and stage three because typically the diagnosis of Huntington's disease happens once their symptom onset.

So there's going to be many thousands of patients.

And then I'll hand, it over to <unk> to answer the first part of your question.

Yes. Thank you.

In our view are going to be eligible.

So for the pre BLA meeting, we will be meeting with the FDA of course and sharing with them the topline results from our.

For the procedure.

The last part of this what the the number of sites that are capable of doing the procedure.

The phase III data and also as well as.

To be very clear. This is this is not a novel procedure. This is a very standard procedure for a neurosurgeon there is probably somewhere between 50 and 55 sites.

Matt Kapusta: So that's definitely going to be our focus. And, you know, and I think it's going to be, as I said, it's going to be something that now that there is at least the treatment option, that it's hard to imagine that all or a majority of all patients are going to seriously consider and become informed about our therapy.

Any updates on CMC activities and <unk>.

Discuss with them there are some elements of the.

Typical.

The.

Then have the neurosurgical expertise in the imaging equipment to be able to do this procedure.

Nickel procedures and tactical questions and logistics that way, whether the data that we have it is acceptable to them and whether the totality of the data would support.

We don't even think we need to be in every one of those centers to address to address the market and certainly at launch there is going to be a center of excellence strategy.

Moving forward.

Jenny Gonzalez: Thank you. That's really helpful.

And submitting the BLA.

That's the plan and.

And then I'll hand, it over to wildly to answer the first part of your question.

And as usual after we have meetings with the with the regulators once we receive.

Paul Matteis: Our next question comes from Paul Matteis with Stiefel. Your line is. Great. Good morning. Thanks for taking my questions.

Yes. Thank you.

So for the pre BLA meeting, we will be meeting with the FDA of course and sharing with them the topline results from our.

Feedback.

We usually have always been communicating.

Paul Matteis: We noticed this morning that you said you're going to be using propensity matched in this analysis, not propensity weighted. Can you just talk about where that comes from? Is that something that the FDA requested?

Back to you guys. The outcome of these meetings. So we will do that again.

Phase III data and also as well as.

Any updates on CMC activities and.

Thank you. Our next question comes from Luca <unk> with RBC.

Discuss with them.

Paul Matteis: And then specifically, how does that compare to the data that we saw in the last cut in 2024? If it's a different methodology than what we're going to see here, is this going to be apples and oranges?

Elements of the.

Typical.

Oh, great. Thanks, so much for taking my question, maybe circling back on the regulatory have you actually met or maybe you had some informal conversations with benign Prasad I think many investors argued that the final decision to approve this drug will ultimately come down to the very senior leadership at <unk>.

Technical procedures and tactical questions and logistics that way, whether the data that we have it is acceptable to them and whether the totality of the data would support.

Paul Matteis: Is the 80% number for 130 still stand?

Paul Matteis: And then if you don't mind, I just have one follow up. Thank you.

Moving forward and submitting the BLA.

That's the plan and.

<unk> similar to <unk>.

Walid Abi Saab: Walid, do you want to go and answer that? Thanks. Yeah, thanks, Paul. Yeah, we've indicated previously when we reported back after meeting with the FDA that the FDA's stated preference was for propensity score matching. We've also consulted with our external statistical experts. And when we took all of these into consideration, we decided to submit the SAT that's aligned with the FDA preference using propensity score matching to the primary. Having said that, the agency will also continue to receive both the Provencity Score Matching and the Provencity Score Weighting Analysis, just as we stated.

As usual after we have meetings with the with the regulators whilst we received.

Dr. Peter marks so I was just curious if you already had had interactions with him and if you have any insight you can share there and then maybe second can you just maybe clarify what are you seeing that the ongoing data for Huntington.

Feedback.

We usually have always been communicating.

Back to you guys. The outcome of this meeting so we will do that again.

Full approval, given they're chasing function or is it fair for us to assume that this is going to lead to accelerated approval. That's still the base case scenario and if so if it is et cetera approval can you maybe talk through how you're thinking about the timing of starting a confirmatory trial. Thanks so much.

Thank you. Our next question comes from Luca <unk> with RBC.

Oh, great. Thanks, so much for taking my question, maybe circling back on the regulatory have you actually met or maybe you had some informal conversations with Rene Prasad I think many investors argued that the final decision to approve this drug will ultimately come down to the very senior leadership at <unk>.

Yes so.

Our last interaction with the FDA occurred in late April.

Walid Abi Saab: Now, in constructing the natural history database, as we were evaluating, excuse me, the most appropriate natural history database to use, we had to construct the annual decline over a period of three years of patients using a variety of methodologies, propensity to score, rating matching, exact matching, a number of these. Using the enrolled database, we found that the propensity score methodology, in whichever form, is quite robust, leading very similar estimate of decline after three years, regardless of the methodologies. So, to answer your question, I will not expect that the results will be materially different if we use propensity score matching, propensity score rating, and considering the FDA's preference, we decided to go that route, be more aligned with that.

<unk> was appointed you didn't attend our meeting.

<unk> similar to <unk>.

Dr. Peter marks so I was just curious if you already have had interactions with him and if you have any insight you can share there.

But he he wasn't charge at that point in time.

I have been.

And then maybe second can you just maybe clarify what do you think that the ongoing data for Huntington.

I was fortunate enough to attend the CEO listening tour.

With doctors Macquarrie and Dr Prasad.

Approval, given youre chasing function or is it fair for us to feel that this is going to lead to accelerated approval. That's still the base case scenario and if so if it is et cetera approval can you maybe talk through how you're thinking about the timing of starting a confirmatory trial. Thanks so much.

In Boston.

So I had the chance to meet with them and to understand his perspectives and approaches.

What he made very clear is that.

<unk>.

Very interested and willing to evaluate additional datasets other than randomized controlled studies Dr.

Yes so.

Our last interaction with the FDA occurred in late April.

Dr. Prasad is in is an epidemiologist by training.

M&A was appointed you didn't attend our meeting.

And he deeply understands the use of external controls in.

But he wasn't charge at that point in time.

I have been.

Synthetic cohorts in order to evaluate.

I was fortunate enough to attend the CEO listening tour.

Walid Abi Saab: But we will be submitting both anyway. Okay, thank you. That's super helpful.

Therapeutic benefit.

With doctors Macquarrie and Dr Prasad.

<unk>.

Walid Abi Saab: And then, look, I know this is extraordinarily subjective, and ultimately in Huntington's, right, there's nothing, but how are you guys thinking about the bar on disease slowing in this three-year analysis? And look, again, understanding that Huntington's doesn't, you know, have any disease-modifying treatments, I would think you'd want the data to hold up to some degree, right? Just, first of all, for the best of the drug, and second of all, to be confident in your regulatory alignment. So, you know, investors and analysts are trying to draw this line. How would you draw this line? Yeah, sorry, I assume I'm going to continue.

Hi.

I'm confident that given the statements that Dr. Prasad is made.

In Boston.

So I had a chance to meet with them and to understand his perspectives and approaches.

He is open.

We support them.

Faster accelerated pathways for cell and gene therapies that are addressing severe unmet needs.

What he made very clear is that.

Key.

Very interested and willing to evaluate additional datasets other than randomized controlled studies.

Like Huntington's disease.

Just in terms of the full approval accelerated approval our base case of course.

Dr. Prasad is in is an epidemiologist by training.

We're what we're gonna be seeking is accelerated approval.

And he deeply understands the use of external controls in.

Having said that the FDA did make it very clear to us that the phase <unk> study.

Walid Abi Saab: I'm just going to give it to you. Apologies.

Synthetic cohorts in order to evaluate.

Walid Abi Saab: So go ahead, Wally. Yeah, I mean, I think we're asked that question a lot. It's an important question. Honestly, as you said, there's nothing for these patients. Matt mentioned that before. When we talk to a number of KOLs, what they tell us is, look, anything that would reduce the disease progression by 25 to 30% would be great. It would add potentially many years of quality of life to these patients who have nothing. But, you know, from our perspective, you know, just like you said, we would like our data to continue to show a meaningful slowing of disease progression that will be something that the agency will consider appropriate for approval, but also the patients will find clinically meaningful.

Our results can be used and leveraged to support full approval.

Therapeutic benefit.

<unk>.

I.

So to the extent that additional evidence is going to be required for for confirmation associated with full approval.

I'm confident that given the statements that Dr. Prasad is made then.

He is open.

And support them.

That data can be incremental.

Faster accelerated pathways for cell and gene therapies that are addressing severe unmet need like like Huntington's disease.

To what we already have established in generating from the phase <unk> study thus far.

Thank you. Our next question comes from <unk> Richter with Goldman Sachs. Your line is open.

Just in terms of the full approval accelerated approval our base case of course.

Hi, Good morning. This is will be on for Celgene. Thanks, So much for taking our questions. Just another on <unk>. How does the September update could you just speak to how consistent that two and a half year data has been versus the data. We saw last year. Thank you so much.

We're what we're gonna be seeking is accelerated approval.

Having said that the FDA did make it very clear to us that the phase one two study.

Our results can be used and leveraged to support full approval.

Well.

Yes, Thanks, Jeff.

Walid Abi Saab: That is, you know, we believe in our mechanism of action. We saw the data at two years. We feel optimistic that the three-year data will continue to show a meaningful improvement that will both satisfy the patients, but also the FDA.

So to the extent that additional evidence is going to be required for offer confirmation associated with full approval.

We have not conducted any formal analysis on the data.

One with the June 30 cutoff of 2024.

That data can be incremental.

To what we already have established and generated from the phase <unk> study thus far.

Which served the basis for.

The November 2020 for meeting with the FDA.

Walid Abi Saab: Thank you.

Thank you. Our next question comes from <unk> Richter with Goldman Sachs. Your line is open.

Joseph Tome: Our next question comes from Joseph Tome with TD Cowan.

So you do not have.

Joseph Tome: Your line is open. Hi there. Good morning. Thank you for taking my questions.

The data that you are describing the next analysis will be the one at June 30.

Hi, Good morning. This is Eddie on for <unk>. Thanks, So much for taking our questions. Just another on <unk>. How does the September update could you just speak to how consistent that two and a half year data has been versus the charity that we saw last year. Thank you so much.

Joseph Tome: I have one question and one follow-up, if I can.

This year, which we will be communicating to you guys in September the three year data cut off.

Matt Kapusta: I guess just given the back and forth with Sarepta over the course of this week, has that changed at all your thinking on how you're approaching the launch in any way, whether you want to do a staged launch with a target number of surgeons, be a little bit more cautious at the beginning, or how you're thinking about that?

Thank you as a reminder to ask a question. Please.

Well.

Yes, Thanks, Jeff.

Please press star one on your telephone again that is star one wanted to ask a question.

We have not conducted any formal analysis on the data.

Walid Abi Saab: Obviously, so many differences between disease states and age and everything like that, but I guess are there any learnings that you've taken from the past week? And then second, do you expect there to be a minimal stridal volume on the label? I only ask this because I notice you're initiating a fourth cohort with smaller stridal volumes, so kind of just thinking if that's going to be a formal label expansion or if this would be more just a use guideline for clinicians in the field. Thank you.

Our next question comes from Giannis Zoom with Wells Fargo Securities. Your line is open.

Yeah.

One with the June 30 cutoff of 2024.

Great. Thanks for taking our questions.

Which serve the basis or.

Okay.

The November 2020 for meeting with the FDA.

On the topic.

<unk> matched.

So you do not have.

<unk> one weighted.

The data that you are describing the next analysis will be the one that's 230.

Analysis methodologies I was wondering.

Okay.

Matt Kapusta: Yeah, well, maybe I'll take the first one, you take the second one. So yeah, I mean, honestly, we've always operated in a way where, you know, patient safety is our utmost priority. So it's not like, you know, anything going on in the, in the sector is going to, it's going to change that view. I think we've always thought that for AMT 130, that, you know, there are going to be, at the time of launch, centers of excellence that have experience with the surgical procedure that are that are conducting these procedures. And, you know, we're going to be something that we're going to be continually monitoring as we launch the product.

In the.

This year, which we will be communicating to you guys.

Dave how you have submitted to FDA.

On your S&P proposal.

September the three year data cut off.

Could you.

Comment on whether those two methodologies.

Thank you as a reminder to ask a question.

Please press star one on your telephone again star one to ask a question.

Yeah, David look similar.

And I also im wondering whether.

Our next question comes from Giannis Zoom with Wells Fargo Securities. Your line is open.

The approach of which went to use.

Great. Thanks for taking our questions.

Thanks.

<unk> <unk> four.

On the topic.

On the.

<unk> matched.

And just on the control arm.

Propensity score weighted.

Well once you go ahead and answer those questions.

Atlas's methodologies I was wondering.

Thanks, Matt.

Yes, very good question so.

Okay.

Anytime you have submitted to FDA.

To be clear the SAP.

Matt Kapusta: But at the same time, you know, we treated 45 patients, I think we really believe the AMT 130 is generally safe and well tolerated. I'll also mention that, you know, that our administration of AMT 130 is a local administration. So the systemic exposure, you know, that occurs when we administer AMT 130 is meaningfully less than, than a gene therapy that is systemically administered. And, you know, we, we have just simply not seen any, any liver toxicity associated with AMT 130. We're also utilizing an AV5 vector that has been studied with systemic administration, you know, vis-a-vis hemgenics, and we've also not seen any, any significant adverse events associated with, with, with hemgenics or AV5 in that context as well, even with systemic administration.

That we submitted to the agency does not include the results right that includes the methodologies.

On your S&P proposal.

Could you.

No comment.

What I was trying to describe earlier is in our <unk>.

Whether those two methodologies.

Yeah, the data look similar with each hub.

We are evaluating the natural history protocol.

And I also.

To evaluate which natural history database enroll track HD predict HD would be most appropriate to be compared to we've employed various propensity score methodologies.

Wondering whether.

The approach of which went to use.

Thanks.

Sample size that you can use.

The.

Excellent a control arm.

Two essentially select the patients that meet the baseline criteria for a patient for our subjects in our trial.

Well he once you go ahead and answer those questions.

Thanks, Matt.

Yes, very good question so.

And observe what is the decline after three years using these various methodologies and what we what gives us a lot of confidence both in the methodology itself. The propensity score methodology is the fact that whether we use propensity score waiting or matching and by the way there are multiple ways to match you can.

To be clear the SAP that we submitted to the agency does not include the results right that includes the methodologies.

What I was trying to describe earlier is in our as we are evaluating the natural history protocol.

Matt Kapusta: So it's very important to understand these, these technical differences, differences with administration.

You can have optimal matching you can have greedy matching full matching I can go on and on and we can go into a lot of details maybe offline if you want to.

To evaluate which natural history database and roll track HD predict HD would be most appropriate to be compared to we've employed various propensity score methodologies.

Matt Kapusta: But nothing's going to change our view that patient safety is always going to be at the top of our priorities.

Those will generate various different levels of size of control, but at the end the estimate around the.

Matt Kapusta: Okay, so on the serratal volume, just maybe taking a step back, the way this came to be was, you know, as the study was initially designed some six years ago or so, out of the abundance of caution, we wanted to make sure that we have a serratal volume that would be large enough so we can safely administer the product to these patients. But over the years, and as we've accumulated a lot of experience with more than 44, total of 45 intraparenchymal administrations to date, the experience that we accumulated with our neurosurgeons and in discussions with them, we are, we've decided that we should be relaxing these criteria and now evaluating an approach where we will use the neurosurgeon's they can reach the targeted structure safely without, you know, without fixing a specific minimum volume.

Two to essentially <unk>.

The patients that meet the baseline criteria for a patient for our subjects in our trial.

Cor and Coa Crs Orient Dfc that decline after three years tend to be generally very similar and not materially different and that's what gives us confidence that these methodologies will yield similar results once you.

And observe what is the decline after three years using these various methodologies and what we what gives us a lot of confidence both in the methodology itself the propensity score methodology.

Compare our data and subtract the three year change in our data from the change in the natural history control, but that analysis, comparing our field data.

Is the fact that whether we use propensity score waiting or matching and by the way. There are multiple ways to match. You can you can have optimal matching you can have greedy matching full matching I can go on and on and we can go into a lot of details maybe offline if you want to.

That has not been done yet so I may need to be very clear on that.

In terms of the size of the external control, yes of course.

Those will generate various different levels of size of control, but at the end the estimate around the.

The propensity score waiting is the one that utilizes essentially all of the controls that you have available that meet the criteria for your trial in the case of parole HD, it's somewhere around 3000.

The score and <unk> ordered TFC that decline after three years tend to be generally very similar and not materially different and that's what gives us confidence that these methodologies will will yield similar results once you.

What's the propensity score waiting.

It uses variety of methodology to be able to allow us to include everybody, which contributes to a varying degree.

Walid Abi Saab: And in order for us to study that, we needed to include patients who have otherwise would have been excluded from our trial, those with lower stridal volume, to start generating safety data with this. Now, whether this will be on the label or not, those discussions have not taken place with the FDA. That would be something that would have to occur later in the review process. Of course, generating these data, and depending on the outcome of the safety profile of this, those will be included in the safety update and will be part of our discussions with the agency.

Based on how closely they resemble your sample matched.

Matching users a proportion of those patients and again there are different.

Compare our data and subtract the three year change in our data from the change in the natural history control, but that analysis.

Matching you can have a very simple matching one to one.

Comparing our field data.

So matching one of your patients to maybe 2030 of decontrol, depending on how large a control group is and there are many ways a container of this optimum matching or full matching and so on and so forth and those could lead somewhere around maybe.

That has not been done yet so I may need to be very clear on that.

In terms of the size of the external control, yes of course.

The propensity score waiting is the one that utilizes essentially all of the controls that you have available that meet the criteria for your trial in the case of parole HD, it's somewhere around 3000.

200, 300, if you want to do.

20, or 30 fold your patients in your trial to 600, if you want to do full matching.

Walid Abi Saab: But it's premature right now to be able to, you know, speculate or give guidance as to what we think the label Thank you.

What's the propensity score waiting.

It uses variety of methodology to be able to allow us to recruit everybody, which contributes to a varying degree.

And those are the types of different types of methodologies I apologize I might have gone a bit too much into details, but like that topic. So much that I can speak on it for a long time, but you should rest assured that the the estimate of change after three years tend to be fairly similar regardless of the of the methods of use and that's that.

Sushila Hernandez: Our next question comes from Sushila Hernandez with Van Lanshout Kempen. Yes. Thank you for taking my question. Also, just to follow up on the fourth cohort, so what do you hope to expect to see in the station population?

Based on how closely they resemble your sample matched.

Matching users a proportion of those patients and again there are different.

Matching you can have a very simple matching one to one.

So matching one of your patients to maybe 2030 of decontrol, depending on how large the control group is and there are many ways a container of this optimum matching or full matching and so on and so forth and those could lead somewhere around maybe two.

US very good confidence that the results will not be materially different when we compare them to the change in our patients.

Sushila Hernandez: And then second question, what are the next steps for AMC 260? Are you expecting to add more sites? Thank you.

Thank you. Our next question comes from Sami Corwin with William Blair. Your line is open.

Walid Abi Saab: Madam, I suppose I'll take both, right? Yeah, go ahead.

Walid Abi Saab: So with the fourth cohort, the expectations in the short term is to document the safety of the procedure, that we can administer this safely, that the neurosurgeons that we have and the system that we have in place to be able to evaluate whether we can safely administer AMT-130 for those who would have otherwise been excluded from our trial because they would have lower steroidal volume. The, you know, the system is in place, it operates well, and we can administer. And then, of course, we will be monitoring them for efficacy and so on and so forth.

Good morning, Congrats on the update and thanks for taking my question.

200, 300, if you want to do.

20, or 30 fold your patients in your trial to 600, if you want to do full matching.

I was curious if FDA provided any guidance as to what Theyre looking for.

And those are the types of different estimates apologies I apologize I might have gone a bit too much into details, but like that topic. So much that I can speak on it for a long time, but you should rest assured that the the estimate of change after three years tend to be pretty similar regardless of the of the methods of use and thats that gives.

Nf L for TSS are supported biomarker.

If theyre kind of looking to see if levels return to or below baseline and that'll be sufficient or if that will need to be some specific magnitude of reduction beyond base baseline as shown.

Then I had a follow up I was curious we've seen with some other gene therapy trials one of the key limiting factors for Collateralization same smeby availability of beds as well as hospital staff and if you think that may be a limiting factor for the launch of anti 130 as well. Thank you.

Very good confidence that the results will not be materially different when we compare them to the change in our patients.

Thank you. Our next question comes from Sami Corwin with William Blair. Your line is open.

Walid Abi Saab: But I personally do not foresee where there would be any difference, you know, once we establish that the AMT130 is actually, you know, effective in slowing disease progression. There's no reason for this to be different based on, you know, an arbitrary cut-off asthma.

Yes.

Good morning, Congrats on the update and thanks for taking my question I.

Well you want to answer the first one.

Thanks, Matt.

I guess I was curious if FDA provided any guidance as to what they're looking for.

So to be clear the NFL topic has not been a topic of discussion with the agency. We were the one who brought it up back in November of last year when.

Al four <unk> supported biomarker.

If theyre kind of looking to see if levels return to or below baseline and that'll be sufficient or if they're all going to be some specific magnitude of reduction beyond base may find shown.

Walid Abi Saab: In terms of AMT-260, yes, indeed, as Matt said, we have increased the number of sites. We now have 14 active. There's a lot of activity since we've disclosed the data on that first patient. We'll be very positive results. They've been received very positively. We've seen a very significant uptick in screening activities, and we really do feel quite confident that we will be getting a number of additional patients in the second half. Thank you.

When we ask the question actually whether NFL data could be supportive.

And the FDA, the FDA said, yes.

The NFL data could be supportive, but theres been no discussion at all about.

And then I had a follow up I was curious you know we've seen with some other gene therapy trials one of the key limiting factors for Collateralization seems to be the availability of beds as well as hospital staff and what do you think that may be a limiting factor for the launch of anti 130 as well. Thank you.

Whether there should be any correlation with the Coa crs or what what changed should be from.

From baseline or anything.

The difficulty with this is that.

I think it's a relevant question as well.

Well you want to answer the first one.

Relevant to the update that we're going to have a three years.

Thanks, Matt.

Patrick Trucchio: Our next question comes from Patrick Trucchio with HCP.

So to be clear the NFL topic has not been a topic of discussion with the agency. We were the one who brought it up back in November of last year.

When we presented data to you last time.

Luis: Your line is open. Good morning, everyone, and congratulations on the project, on the progress.

We used two year data because there are.

Data available from an external study looking at longitudinal two year change from baseline in CSF NFL levels.

Luis: This is Luis in for Patrick.

We ask the question actually whether NFL data could be supported.

Luis: First question, just thinking ahead of, are there any differences, do you expect any differences from regulatory path to approval in Europe versus the U.S. And then on the one thirty and on one sixty, how should we, how should we think about the plan phase two portion look like in terms of patients will really plan to enroll the same disease stage patients with or also include non legal patients as well. Thank you so much. Yeah, I'll maybe take the first one while reading.

And the FDA, the FDA said, yes.

Unfortunately, we don't no such data exist for two to three years.

The NFL data could be supportive, but theres been no discussion at all about.

Time point, which will limit interpretation of our upcoming data.

Whether there should be any correlation with the with the <unk> or what what changed should be.

So it becomes a little bit difficult to figure out okay. So what does good look like we know what that looks like an NFL. When you have increases and so on and so forth. We know that patients usually go up by about 15% a year and clearly our data at two years show that we are both doses were below baseline.

From baseline or anything the difficulty with this is that.

I think it's a relevant question as well.

Relevant to the to the update that you're going to have a three years.

So we were looking forward to see what our three data for your data would look like but it would be a bit difficult because we don't have an external competitor, but going back to your original question Theres been no specific discussions with the FDA about what the NFL data should look like.

When we presented data to you last time.

We used two year data because there are data available from an external study looking at longitudinal two year change from baseline in CSF NFL level.

Matt Kapusta: You can address the second one. So we have not yet met with EMA to solicit scientific advice with respect to the registrational path forward. Our focus right now is on the U.S., and of course, we'll expect to have the three-year data presented, which we think could be also important information to furnish EMA when we have those scientific advice discussions.

Unfortunately, we don't no such data exist for two to three years.

But.

We were I guess, our expectations and we are confident in our data that the NFL data will continue to support our primary clinical endpoint of serious showed us.

Time points, which will limit interpretation of our upcoming data.

So it becomes a little bit difficult to figure out okay. So what does good look like we know what that looks like an NFL you know when you have increases and so on and so forth that patients usually go up by about 15% a year and clearly our data at two years show that we are both doses were below baseline.

And maybe just the second question, we don't think capacity.

Walid Abi Saab: So we'll look to have them in the near term, and once we do, we'll make sure we provide an update to the market. Regarding AMT-260, in terms of design of the Phase 2 study, it's premature to discuss that. The reality is that we do Phase 1 to learn from it, so that will also dictate the design of the subsequent trial. But in terms of the patient population, we start with those, you know, on the non-dominant because that way you establish the risk-benefit profile, and then you start branching out to those with dominant disease. I think the next natural step will be also to look at bilateral.

<unk>.

It's something that is going to be a significant factor in the launch of our product I mean remember this is not this is not cell therapy, where you know.

So we were looking forward to see what our three data for your data would look like but it would be a bit difficult because we don't have an external competitor, but going back to your original question. There has been no specific discussions with the FDA about what the.

Patients have to be pre conditioned immuno bladed spend weeks in the hospital.

I've often talked about the last patient we treated earlier this year was admitted to the hospital on a Tuesday morning completed the procedure.

The NFL data should look like.

But.

We were.

Our expectations are and we are confident in our data that the NFL data will continue to support our primary clinical endpoint of series showed us.

On Tuesday, and was discharged from the hospital Wednesday morning. So.

I don't think Thats, that's a factor that we think is going to be immaterial one for our launch.

Yeah, maybe just the second question, we don't think capacity.

Ben.

Thank you. Our next question comes from Kristen <unk> with Cantor Fitzgerald. Your line is open.

It's something that is going to be a significant factor in the launch of our product I mean remember this is not this is not so therapy where patient.

Walid Abi Saab: The reality is that it's those with dominant and bilateral is where the high unmet need is because those would be unlikely to benefit from invasive therapy like ablation, laser ablation, or resection surgery. But that's kind of the thinking that we have around expansion as we advance in the Thank you.

Hi, This is Rick Miller on for Christian Thanks for taking our question just one from US can you kind of walk us through the natural history comparator is that could sort of inform the external comparator that we can see in the September update and how should and should we be expecting to see enroll HD competitors at that time or any other analyses.

Patients have to be pre conditioned immuno bladed spend weeks in the hospital.

I've often talked about the last patient we treated earlier this year was admitted to the hospital on a Tuesday morning.

Eliana Merle: Our next question comes from Eliana Merle with UBS. Your line is open.

We did the procedure.

Yes.

Well.

On Tuesday, and with discharged from the hospital Wednesday morning. So.

Thank you, yes so.

Jasmine: Hey, this is Jasmine on for Ellie. Thank you for taking our question.

I don't think that Thats a factor that we think is going to be immaterial one for our launch.

As part of our meeting with the FDA back in November.

Matt Kapusta: So first, can you give any color on what you plan to talk about and learn from the pre-BLA meeting with the FDA and 4Q, and will we get an update after this meeting? And then secondly, on the Huntington's commercial opportunity, how many sites in the US are capable of doing the administration procedure? And based on the study enrollment criteria, can you give an estimate of the prevalence of patients that would be eligible in the US?

We were we discussed with the FDA how to proceed to evaluate the various natural history databases that we could use and we asked whether we should.

Thank you. Our next question comes from Kristen <unk> with Cantor Fitzgerald. Your line is open.

<unk> enrolled HD because it has a very large database and the FDA encouraged us to do so which we did and the follow up meeting that we had with them back in April.

Hi, This is Rick Miller on for Christian Thanks for taking our question just one from US can you kind of walk us through the natural history comparator is that could sort of inform the external comparator that we can see in the September update and how should and should we be expecting to see enroll HD competitors at that time or any other analyses.

We walk them through all of our assessments.

Comparing the natural history for a variety of reasons, which I could.

Matt Kapusta: Thank you.

Matt Kapusta: Yeah, so I'll answer the last question first, Walid, and then you can answer the first question if that's okay. So yeah, I mean, in terms of the commercial potential, there's 35,000 patients that are currently diagnosed with Huntington's disease, and then there's probably three times as many people that have Huntington's disease but have not been genetically confirmed because there's obviously nothing for those patients. Our view is that there's going to be, we'll provide obviously more detail on this, but the overwhelming majority of the patients that are diagnosed have stage 2 and stage 3 because typically the diagnosis of Huntington's disease happens once their symptom onset.

Perhaps to take offline and walk you through this.

Yes.

The enrolled HD was deemed the one thats the best fit for us to compare to and we made that proposal and the FDA agreed with us that enrollees.

Sure.

Well.

Thank you.

So.

As part of our meeting with the FDA back in November.

Enrollees you will be the comparison so the data that you will see in September will be a comparison of our data to the.

We were we discussed with the FDA how to proceed to evaluate the various natural history databases that we produce and we asked whether we should.

Enrolled HD three year data using propensity score matching.

<unk> enrolled HD because it has a very large database and the FDA encouraged us to do so which we did.

As the primary endpoint is again as I said before we will be including a number of other.

And the follow up meeting that we had with them back in April.

Sensitivity analyses, including a few score waiting as well.

We walk them through all of our assessments.

Submit to the FDA.

This concludes the question and answer session and today's conference call. Thank.

Comparing the natural history for a variety of reasons, which I could.

Thank you for participating you may now disconnect.

Perhaps to take offline and walk you through this.

The enrolled HD was deemed the one thats the best fit for us to compare to and we made that proposal and the FDA agreed with us that enrollees.

Matt Kapusta: So, you know, there's going to be many thousands of patients that in our view are going to be eligible for the procedure.

<unk> will be the comparison so the data that you will see in September will be a comparison of our data to the.

<unk>.

Matt Kapusta: Now, the last part of this was the number of sites that are capable of doing the procedure. Just to be very clear, this is not a novel procedure. This is a very standard procedure for a neurosurgeon. There's probably somewhere between 50 to 55 sites that have the neurosurgical expertise and the imaging equipment to be able to do this procedure. We don't even think we need to be in every one of those centers to address the market, and certainly at launch there's going to be a center of excellence strategy.

Three year data using propensity score matching.

As the primary endpoint is again as I said before we will be including a number of other.

Sensitivity analyses, including a few score waiting as well.

And submit to the FDA.

This concludes the question and answer session and today's conference call. Thank.

Thank you for participating you may now disconnect.

Yes.

Yes.

[music].

Walid Abi Saab: And then I'll hand it over to Waleed to answer the first part of your question. Yep, thank you. So for the PBLA meeting, we will be meeting with the FDA, of course, and sharing with them the top-line results from our phase 3 data and also as well as any updates on CNC activities and, you know, discuss with them there are some elements of the, you know, typical technical procedures and tactical questions and logistics. That way, whether the data that we have is acceptable to them and whether the totality of the data would support moving forward and submitting the PLA.

Walid Abi Saab: That's the plan.

Walid Abi Saab: And as usual, after we have meetings with the regulators, once we receive feedback, we usually have always been communicating back to you guys the updates. So we will do that. Thank you.

Okay.

Luca Issi: Our next question comes from Luca Issi with RBC, Rwanda. Oh, great. Thanks so much for taking my question.

Luca Issi: Maybe circling back on regulatory, have you actually met or maybe had some informal conversations with Vinay Prasad? I think many investors argued that the final decision to approve this drug will ultimately come down to the very senior leadership at CBER, similar to, you know, Sarepta with Peter Mark. So I was just curious if you already had had interactions with him and if you have any insights that you can share there.

Walid Abi Saab: And then maybe second, can you just maybe clarify whether you think that the ongoing data for Huntington can lead to full approval given your chasing function, or is it fair for us to assume that this is going to lead to accelerated approval that's still the base case scenario? And if so, if it is accelerated approval, can you maybe talk through how you're thinking about the timing of starting a confirmatory trial?

Walid Abi Saab: Thanks so much. Yeah, so our last interaction with the FDA occurred in in late April. Vinay was appointed. He didn't attend our meeting, but he, you know, he was in charge at that point in time.

Walid Abi Saab: I have been, I was fortunate enough to attend the CEO listening tour with Drs. Makary and Dr. Prasad in Boston, so I had a chance to meet with him and to understand his perspectives and approaches. What he made very clear is that, you know, he is very interested and willing to evaluate additional data sets other than randomized controlled studies. Dr. Prasad is an epidemiologist by training, and he deeply understands the use of external controls and, you know, synthetic cohorts in order to evaluate therapeutic benefits. So I, you know, I'm confident that, you know, given the statements that Dr. Prasad has made, that he's open and supportive of faster accelerated pathways for cell and gene therapies that are addressing severe unmet needs like, like Huntington's disease.

Walid Abi Saab: Just in terms of the full approval, accelerated approval, our base case, of course, and what we're going to be seeking is accelerated approval. Having said that, the FDA did make it very clear to us that the Phase I-II study results can be used and leveraged to support full approval. So to the extent that additional evidence is going to be required for confirmation associated with full approval, that data can be incremental to what we already have established and generated from the Phase I-II study thus far.

Walid Abi Saab: Thank you.

Salveen Richter: Our next question comes from Salveen Richter with Goldman Sachs. Hi, good morning.

Lydia Erdman: This is Lydia on for Salveen. Thanks so much for taking our questions.

Lydia Erdman: Just another on AMT 130 ahead of the September update. Could you just speak to how consistent the two and a half year data has been versus the two year data we saw last year? Thank you so much. Well, we Yeah, thanks, Lydia. We have not conducted any formal analysis on the data since the one with the June 30th cutoff of 2024, which served the basis for the November 2024 meeting with the FDA. So we do not have the data that you are describing. The next analysis will be the one of June 30th cutoff of this year, which we will be communicating to you guys in September, the three-year data.

Walid Abi Saab: Thank you.

Operator: As a reminder to ask a question... Please press star 1-1 on your telephone. Again, that is star 1-1 to ask.

Yanan Zhu: Our next question comes from Yanan Zhu with Wells Fargo Securities. Your line is open. Great, thanks for taking our questions.

Walid Abi Saab: On the topic of propensity matched versus propensity score weighted Analysis Methodologies. I was wondering, in the data you have submitted to FDA for your SAP proposal, could you comment on whether those two methodologies, the data look similar with each other? And I also am wondering whether the approach of which one to use affects the sample size that you can use for the external control arm.

Walid Abi Saab: Well, Lee, why don't you go ahead and answer those questions. Thanks, Matt. Yeah, very good question. So to be clear, the SAP that we submitted to the agency does not include the results, right? It includes the methodology. What I was trying to describe earlier is, as we are evaluating the natural history protocol, to evaluate which natural history database, enroll, track, HD, predict HD, would be most appropriate to be compared to, we've employed various propensity score methodologies to essentially select the patients that meet the baseline criteria for our subjects in our trial, and observe what is the decline after three years using these various methodologies.

Walid Abi Saab: And what gives us a lot of confidence, both in the methodology itself, the propensity score methodology, is the fact that whether we use propensity score weighting or matching, and by the way, there are multiple ways to match, you can have optimal matching, you can have greedy matching, full matching, I can go on and on, and we can go into a lot of details, maybe offline if you want to. Those will generate various different levels of size of control. But at the end, the estimate around the The score in CUHCRS or in TFC, that the decline after three years tend to be generally very similar and not materially different.

Walid Abi Saab: And that's what gives us confidence that these methodologies will yield similar results once you compare our data and subtract the three year change in our data from the change in the natural history.

Walid Abi Saab: But that analysis, comparing our three-year data to the current one, has not been done yet, so I need to be very clear on that. In terms of the size of the external control, yes, of course, the propensity score weighting is the one that utilizes essentially all of the controls that you have available that meet the criteria for your trial. In the case of a Roll HD, it's somewhere around 3,000. That's the propensity score weighting, and it uses a variety of methodology to be able to allow to include everybody, which contributes to a varying degree. based on how closely they resemble your sample.

Walid Abi Saab: And matching uses a proportion of those patients. And again, there are different types of matching. You can have a very simple matching one-to-one. You have matching one of your patients to maybe 20, 30 of the control, depending on how large the control group is. And there are many ways that you can tailor this optimal matching or full matching and so on and so forth. And those could lead somewhere around maybe 200, 300 if you want to do 20 or 30 fold your patients in your trial to 600 if you want to do full matching. And those are the types of different types of methodologies.

Walid Abi Saab: I apologize, I might have gone a bit too much into details, but I like that topic so much that I can speak on it for a long time. But you should rest assured that the estimate of change after three years tend to be fairly similar regardless of the method you use. And that gives us very good confidence that the results will not be materially different when we compare them to the change in our Thank you.

Sami Corwin: Our next ques- Sami Corwin with William Blair, your line is. Good morning, congrats on the update. Thanks for taking my question. I guess I was curious if FDA provided any guidance as to what they're looking for with NFL for it to be used as a supportive biomarker. If they're kind of looking to see if levels return to or below baseline, and that'll be sufficient, or if there'll need to be some specific magnitude of reduction beyond base baseline shown.

Matt Kapusta: And then I had a follow up. I was curious, you know, we've seen with some other gene therapy trials, one of the key limiting factors for clinicalization seems to be the availability of beds as well as hospital staff. And if you think that may be a limiting factor for the launch of AMT 130 as well. Thank you.

Walid Abi Saab: Wally, do you want to answer the first one? Thanks, Matt. Yeah. So, to be clear, the NFL topic has not been a topic of discussion with the agency. We were the one who brought it up back in November of last year, when we asked the question, actually, whether NFL data could be supported. And the FDA said yes, the NFL data could be supported. But there's been no discussion at all about, you know, whether there should be any correlation with the COACRS or what change should be from baseline or anything. The difficulty with this is that, and I think it's a relevant question as well, relevant to the update that we're going to have at three years, that when we presented data to you last time, we used two-year data because there are data available from an external study looking at longitudinal two-year change from baseline in CSF NFL level.

Walid Abi Saab: Unfortunately, no such data exists for the three years time point, which will limit interpretation of our update. So it becomes a little bit difficult to figure out, okay, so what does good look like? We know what bad looks like in NFL, you know, when you have increases and so on, so forth. We know that patients usually go up by about 15% a year. And clearly our data at two years show that we both doses were below baseline. So we were looking forward to see what our three-year data would look like. But it would be a bit difficult because we don't have an external comparator.

Walid Abi Saab: But going back to your original question, there has been no specific discussions with the FDA about what the NFL data should look like.

Matt Kapusta: But, you know, we were, I guess, our expectations and we're confident in our data that the NFL data will continue to support our primary clinical endpoint of serious Yeah, maybe just the second question. You know, we don't think capacity of beds, you know, is something that is going to be a significant factor in the launch of our product. I mean, remember this is not, you know, this is not cell therapy where, you know, patients have to be preconditioned, immunobilated, spend weeks in the hospital. You know, we've often talked about, you know, the last patient we treated earlier this year was admitted to the hospital, you know, on a Tuesday morning, completed the procedure, you know, on Tuesday and was discharged from the hospital Wednesday morning.

Matt Kapusta: So I don't think that's a factor that we think is going to be a material one for our launch. Thank you.

Rick Miller: Our next question comes from.

Rick Miller: Kluska, Cantor Fitzgerald, Yolana Zagitova, Hi, this is Rick Miller on for Kristen. Thanks for taking our question. Just one from us.

Rick Miller: Can you kind of walk us through the natural history comparators that can sort of inform the external comparator that we could see in the September update? And how should and should we be expecting to see in Roll HD comparators at that time or any other analyses? Thank you. Well, it Thank you. Yes, so as part of our meeting with the FDA back in November, we discussed with the FDA how to proceed to evaluate the various natural history databases that we could use, and we asked whether we should include EnrollHG because it has a very large database, and the FDA encouraged us to do so, which we did.

Walid Abi Saab: And the follow-up meeting that we had with them back in April, we walked them through all of our assessments, comparing the natural history for a variety of reasons, which I couldn't cover.

Walid Abi Saab: you know, perhaps take offline and walk you through this, the EnrollHD was deemed the one that's the best fit for us to compare to. We made that proposal and the FDA agreed with us that EnrollHD will be the comparison. So, the data that you will see in September will be a comparison of our data to the EnrollHD three-year data using propensity score matching as a primary endpoint. As again, as I said before, we will be including a number of other sensitivity analyses including propensity score weighting as well and submit to the FDA.

This concludes the question and answer session and today's conference. Thank you for participating. You may now disconnect.