Q3 2025 Alnylam Pharmaceuticals Inc Earnings Call
Following the presentation, we will conduct a question and answer session.
At any time during this call you require immediate assistance. Please press star zero for the operator also note that this call is being recorded on Thursday October 30th 2025, and I would like to turn the conference over to management. Please go ahead.
Good morning, I'm, Christina can keep corporate Communications officer at an island with me today are Yvonne Greenstreet, Chief Executive Officer, Tobin Engler good commercial.
With regard Chief Research and development Officer, and Jeff Gordon Chief Financial Officer.
Those of you participating via conference call. The accompanying slides can be accessed by going to the events section of the investors page of our website investor Dot online <unk> dot com loss events.
Speaker #1: Good morning , ladies and gentlemen , and welcome to the ALNYLAM PHARMACEUTICALS, INC. . Three , 2025 Earnings Conference Call . At this time , all lines are in the listen only mode .
During today's call as outlined in slide two Yvonne will offer some introductory remarks and provide general context.
Well I will provide an update on our global commercial progress politically review pipeline updates and clinical progress and Jeff will review, our financials and guidance followed by a summary of upcoming milestones before we open the call to your questions.
Speaker #1: note that this call is being recorded on Thursday , October 30th , 2025 and I would like to turn the conference over to management .
I would like to remind you that this call will contain remarks concerning <unk> future expectations plans and prospects.
Constitute forward looking statements for the purpose of the Safe Harbor provision under the private Securities Litigation Reform Act of 1995.
Speaker #1: Please go ahead .
Speaker #2: morning . I'm Christine Akinc chief corporate Communications Good officer at Neelam . With me today are Yvonne Greenstreet chief Executive Officer , Tolga Tanguler chief Commercial officer , Pushkal Garg .
Our results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in our most recent periodic reports on file with the SEC. In addition, any forward looking statements represent our views only as of the date of this recording and should not be relied upon as representing our views as of any subsequent date.
Speaker #2: Chief Research and development officer and Jeffrey Poulton chief financial officer . For those of you participating via conference , call the accompanying slides can be accessed by going to the events section of the investors page of our website .
We disclaim any obligation to update such statements with that I'll turn the call over to alarm com.
Thanks, Christine and thank you everyone for joining the call today.
Items Q3 results announced this morning demonstrate the exceptional progress we are making across all aspects of the business as.
As we continue to evolve into a top tier biotech company. Our focus remains on these three core pillars that we believe will drive sustainable growth and value creation for years to come.
The first is TTM on leadership.
The in vitro cardiomyopathy launch delivered another strong quarter, it's still early but we're very encouraged by the progress and dedicated to establishing long term leadership in ctr.
Next is growth through innovation focused on the potential multi billion dollar opportunities within our pipeline and an R&D engine positioned to deliver sustainable innovation and value creation for many years to come.
The third element is strong financial performance with robust top line growth and disciplined capital allocation, providing us with the opportunity to sustained profitability going forward.
And of course all of this is underpinned by our best in class team and our award winning culture.
The quarterly results announced this morning represent a strong execution on each of these fronts.
Our commercial performance was driven by TCR franchise revenues of $724 million or 135% year over year growth.
With growth largely attributable to the <unk> launch in the U S, where we achieved total TCR revenues of $543 million, representing 194% year over year growth.
As Tony will describe the broader balanced uptake in the second full quarter of launch drove an approximate doubling of ctr cardiomyopathy revenue compared to the prior quarter.
In addition to these commercial results, we continue to advance our leading pipeline of <unk>.
Therapeutics.
Two new phase III trials getting underway.
Xena phase III cardiovascular outcomes trial, exalt D surround and hypertension has initiated and Detroit and <unk> study of <unk> and <unk> will be initiating shortly to complement the Triton cm study that was initiated last quarter.
We're also excited by earlier stage pipeline advancement and bleeding and Urologic disorders.
And with regards to financial performance, our third quarter results show continued growth with $851 million in total net product revenues up 130% year over year.
With growth largely attributable to the amplitude. CM launched in the us where we achieved total PTR. Revenues of 543 million representing 194%, year-over-year growth.
As a result, we have again increased our total net product revenue guidance for 2025 from a range of $2 six 5 billion to $2 8 billion.
As toga will describe the broader balance. Uptake in the second full quarter of launch drove an approximate doubling of CTR cardiomyopathy Revenue compared to the prior quarter.
To a revised range of $2 95 billion to $3.0 billion to $5 billion representing.
In addition to these commercial results, we continue to advance our leading pipeline of rnai Therapeutics.
Renting an increase of $275 million or 10% at the midpoint underscoring our confidence in the <unk> launch and our other commercial products for the remainder of the year.
Now with our northern piece of first by 'twenty five Eric concluding soon.
2 new phase 3. Trials are getting underway the Zenith phase 3, cardiovascular outcomes trial of zaldi surrounding hypertension, has initiated. And the Triton PN study of an increase in hadn will be initiating shortly to complement. The Triton CM study that was initiated last quarter.
We're thrilled by this incredible execution over the past five years, reflecting tremendous progress on these ambitious goals.
We're also excited by earlier stage pipeline advancements in bleeding and neurologic disorders.
and with regard to financial performance,
This is indeed, a strong foundation on which to build our next phase of significant growth and we look forward to harnessing this momentum.
our third quarter results, show continued growth with 851 million in total. Net products revenues up 103% year-over-year.
With that let me now turn the call over to <unk> for a review of our commercial performance toga.
Thanks, Ivan and good morning, everyone.
It is a pleasure to show how we are continuing to bring on islands transformative therapies to patients around the world.
Following an exceptional Q to.
Q3 continued online a strong trajectory of growth and execution.
We delivered $851 million in combined net product revenues, representing 103% growth year over year, and 27% growth versus the prior quarter.
As a result we've again, increased, our total net products Revenue. Guidance for 2025 from a range of 2.65 billion to 2.8 billion dollars, to a revised range of 2.95 billion to 3.05 billion dollars representing an increase of 275 million or 10% at the midpoint underscoring our confidence in the amount of at trcn launch and our other commercial products for the remainder of the year.
now, with our nylon piece of Fists by 25 era, including soon,
Our ctr franchise remains the primary growth engine.
We're thrilled by this incredible execution over the past five years, reflecting tremendous progress on these ambitious goals.
And we're also seeing continued momentum in our rare disease business.
Let me start there.
This is indeed a strong foundation on which to build our next phase of significant growth, and we look forward to harnessing this momentum.
More than five years after launch our rare disease portfolio continues to deliver meaningful impact for patients.
With that, let me now turn the call over to Tolga for a review of our commercial performance, toga?
Our steady performance for our business.
Thanks, Ivonne, and good morning, everyone.
In Q3, there are portfolio achieved $127 million in sales up 14% versus Q3 2024.
It is a pleasure to show how we're continuing to bring all nylon transformative therapies to patients around the world.
Following an exceptional Q2.
Driven largely by ongoing patient demands.
Q3 continued online and strong trajectory of growth and execution.
While the timing of orders and our partner markets created some short term shifts.
The overall trajectory remains strong.
I'm proud of the focus and dedication of our rare disease and partner teams.
Who continued to reach patients with these two transformative medicines globally, even as much of the organization focuses on the TCR growth opportunity.
51 million in combined, net product revenues representing 103% growth year-over-year and 27% growth versus the prior quarter.
With that let's review the <unk> highlights.
Our TTR, franchise Remains the primary growth engine and we're also seeing continued momentum in our rare disease business.
Let me start there.
Q3 was another exceptional quarter for our TCR franchise, continuing the strong launch trajectory we saw in Q2.
Global TCR net revenues reached.
More than 5 years after launch our rare disease, portfolio continues to deliver meaningful impact for patients, and steady performance for our business.
$724 million up 33% versus the prior quarter, and representing 135% growth year over year.
This performance was primarily driven by an increase in U S patient demand.
In Q3 the rare portfolio achieved 127 million. In sales up 14% versus Q3 2024 driven largely by ongoing patient demands.
With an increase in U S channel inventory more than offset by an increase in U S gross to net deductions.
While the timing of orders in our partner markets, created some short-term shifts.
The overall trajectory remains strong.
It is worth noting that the increase in gross to net deductions primarily impacted on Petro reducing U S reported Q over Q growth in our <unk> business relative to our recent quarterly run rate in the U S. Net sales for our TCR franchise grew.
I'm proud of the focus and dedication of our rare disease and partner teams.
Who continue to reach patients with these 2 transformative medicines globally. Even as much of the organization focuses on the TTR growth opportunity,
With that, let's review the TTR highlights.
42% quarter over quarter, and 194% versus Q3 2024.
23 was another exceptional quarter for our TTR franchise continuing the strong launch trajectory we saw in Q2
Reflecting continued robust adoption following the Ohmura ATT RCM label expansion.
Global TTR, net revenues reached.
Before we provide further color on the U S launch, let me quickly share the ex U S dynamics.
724 million up 33% versus the prior quarter and representing 135% growth year-over-year.
Outside the U S revenues grew 13% versus the prior quarter and 46% year over year Underscoring continued global momentum.
Performance was primarily driven by an increase in US patient demand.
With an increase in US Channel inventory more than offset by an increase in US growth in net deductions.
Further international almost for ATT RCM launches are anticipated across 2026.
Following the completion of local pricing and reimbursement reviews.
Having said that we're particularly pleased with the early progress in Japan, where the cm launcher is advancing well and tracking in line with leading launch analogs as strong validation of <unk>, which was profile.
It is worth noting that the increase in growth in net deductions primarily impacted on petrol. Reducing us reported Q over Q growth in our hat. TTR PN business relative to our recent quarterly run rate in the US.
And first line potential.
Net sales for our TTR franchise grew 42% quarter over quarter and 194% versus Q3 2024.
In Germany launch activities remain in the early stages as final reimbursement decisions continue.
Reflecting continued. Robust adoption following the amuta attr-cm label expansion.
And we're encouraged by how the products differentiated profile is resonating at key treatment centers.
Before we provide further color on the US launched, let me quickly, share the xus Dynamics.
More broadly our international performance reflects the continued strength of our <unk> GTR pull neuropathy legacy business, which remains robust despite new competition.
Outside, the US revenues, grew 13% versus the prior quarter and 46% year-over-year underscoring continued Global momentum.
Broader engagement in the category is expanding awareness and diagnosis.
Ultimately benefiting patients and reinforcing all islands leadership role in shaping the field.
Further International almost 380% 2026.
Following the completion of local pricing and reimbursement, reviews.
Building on our global presence, we're positioned to extend our momentum as well with the ATT RCM launches expand worldwide.
Now, let's turn to the U S. I would say the ATT RCM launch, which recently completed its second full quarter and continues to build momentum.
Having said that we're particularly pleased with the early progress in Japan, where the CM launch is advancing well and tracking in line with leading launch analogs, a strong validation of our profile and first time potential.
In Germany launched activities remain in the early stages as final reimbursement decisions. Continue.
In Q3, our U S GTR franchise across both Pn and cm indications delivered $543 million.
And we're encouraged by how the products differentiated profile is resonating at Key treatment centers.
In net product revenues, representing an increase of approximately $160 million versus the prior quarter.
If we assume steady and consistent growth of $50 million quarter over quarter in the Polyneuropathy base business. Then we estimate the cm indication represents approximately $300 million.
more broadly, our International performance, reflects the continued strength of our hatr polarity Legacy business, which remains robust, despite new competition,
Broader engagement in. The category is expanding awareness and diagnosis.
Ultimately benefiting patients and reinforcing all items' leadership role in shaping the field.
Net product revenues this quarter.
Or doubled from Q2.
This reflects sustained launch momentum in <unk>.
Building on our Global presence. We're positioned to extend our momentum as unauthorized trcm launches expand worldwide.
Patient demand roughly doubling compared to Q2 as awareness and physician adoption continue to grow.
Our strength is built on three key pillars as part of our launch strategy.
Now, let's turn to the US on mutra, attr-cm launch, which recently completed, its second full quarter and continues to build momentum.
First health system setup.
It is a complete nearly all of our 170 priority health systems are now using our mitra driving broad utilization.
In Q3, our us TTR franchise across both pm and CM indications.
Combined with our extensive treatment site network.
Delivered 543 million in net product revenues representing an increase of approximately 160 million dollars versus the prior quarter.
Roughly 90% of the U S patients can receive their <unk> treatment within 10 miles of phone.
Anywhere in the U S and meaningful milestone and accessibility.
So again the health system setup is effectively complete as such we plan to no longer report on this launch enabler on future calls.
Pull me up with the base business. Then we estimate the CM indication represents approximately dollars of net product revenues this quarter or doubled from Q2.
Second <unk>.
Access remains strong.
Payer coverage is broad and nearly all patients have access to our Mitra as a first line treatment option, meaning these patients have no step edits.
This reflects sustained launch momentum in Ultra attr-cm with patient demand roughly doubling compared to Q2 as awareness and physician of adoption continue to grow.
Of similar importance.
Most patients pay zero out of pockets.
Our strength is built on 3 key pillars as part of our launch strategy.
First health system setup.
Finally, do with health system setup, and access and affordability in place.
We are focused on treatment choice and the profile of our mutual continues to resonate.
It is not complete, nearly all of our 170 Priority Health Systems are now using our mutra driving broad utilization,
We're seeing broad and balanced adoption across new diagnosed patients and those progressing on stabilizers in both academic and community settings.
Combined with our extensive treatment site Network.
Roughly 90% of U.S. patients can receive their ultra treatment within 10 miles of home.
Anywhere in the US and meaningful Milestone and accessibility
Prescriber growth also remains robust.
Having reviewed the three strategic pillars.
Executing and delivering on them.
So again, the health system setup is effectively complete as such, we plan to no longer report on this launch enabler on future calls.
Patient demand roughly doubled quarter over quarter, reflecting strong sustained momentum for the ultra ATT RCM and U S launch.
Second.
Access remains strong.
In summary.
Payer coverage is brought and nearly all patients have access to ambra at the first line treatment option. Meaning these patients have no step edits
It is still early in the journey, but the results to date highlight the substantial long term opportunity ahead and underscore our strong positioning for leadership in this expanding underserved GTR category.
of similar importance, most patients, pay zero out of pockets.
Finally, do with health system set up and access an affordability in place.
Looking ahead, the majority of ex U S launches are expected to begin in 2006 as pricing and reimbursement processes wrap up.
We are focused on treatment choice and the profile of our mutra continues to Res resonate.
Spanning our global reach and providing a measured contribution to launch momentum.
We're seeing Broad and balanced adoption across new diagnosed patients and those progressing on stabilizers in both academic and Community settings.
We continue to invest in the Ctr category advancing science enhancing patient experience and building a durable foundation.
Prescriber growth also remains robust.
Having reviewed the 3, strategic pillars were executing and delivering on them.
Pushcart and R&D organization are leading that chapter.
With that I'll hand, it over to you <unk>.
Thank you Tony and good morning, everyone and supportive and boots, a strong launch in <unk>, we continue to share new data from the Helios B study that further underscore the unique and compelling profile of this medicine with the aim of cementing and butcher as the treatment of choice for patients with <unk> Atti credit markets.
Patient demand roughly doubled quarter over quarter, reflecting strong sustained momentum for the Arm Mutra, ATTR-CM in the U.S. launch.
In summary. It is still early in the journey but the results to date highlight the substantial. Long-term opportunity ahead and underscore are strong positioning for leadership in this expanding underserved TTR category.
To that end as shown on the left at ESC, We presented new data from Helios B that demonstrate the sustained benefits of <unk> to up to 48 months.
Looking ahead, the majority of exas, launches are expected to begin in. 26, S pricing and reimbursement, processes, wrap-up,
Which includes 12 months from the open label extension.
Specifically as compared to placebo <unk> substantially reduced the risk with a composite of all cause mortality or first cardiovascular event by 37% in the overall population and 42% in the monotherapy group.
Extending our Global reach and providing a measured contribution to launch momentum.
We continue to invest in the TTR category advancing science and enhancing patient experience and building a durable Foundation.
More recently at HSA as shown on the right. We shared important new data from the double blind period, demonstrating that <unk> treatment was associated with a lower rate of gastrointestinal adverse events versus.
Push guard. And the R&D organization are leading that chapter.
With that, I'll hand it over to you. Push call.
Versus placebo across the overall, <unk> monotherapy and baseline to families treatment groups with reductions of 37% to 49%.
This observation is quite important because it suggests <unk> may reduce gi symptoms, which as you can see from the placebo data, we're seeing an approximately 40% of patients.
Thank you, Tolga, and good morning, everyone. In support of AMBRI, we had a strong launch in ATTR-CM, and we continue to share new data from the HELIOS study that further underscores the unique and compelling profile of this medicine, with the aim of cementing it as the treatment of choice for patients with ATTR cardiomyopathy.
To that end as shown on the left at ESC, we presented new data from Helio speed that demonstrate the sustained benefits of Utrecht strength through up to 48 months.
These symptoms arise from the multi systemic nature of ATR cardiomyopathy and are a major source of concern for patients with this disease.
Which includes 12 months from the open label extension.
With these continued insights from Helios B, we are excited about the prospects for RNA therapeutics to become the standard of care.
Specifically as compared to the placebo which is around substantially reduced the risk of the composite of all cause mortality or first cardiovascular events by 37% in the overall population and 42% in the monotherapy group.
GTR amyloidosis.
<unk>, our next generation silencer may offer even greater TTM knockdown with subcutaneous biannual dosing is now being evaluated in the Triton Phase III program.
more recently at hfsa is shown on the right we shared important, new data from the double blind period, demonstrating that nutrition and treatment was associated with a lower rate of gastrointestinal Adverse Events
We announced last quarter, the initiation of the Triton CN trial in cardiomyopathy patients.
Today I'm happy to share additional details about the Triton Pn trial in hereditary <unk>, polyneuropathy patients, which will be initiating shortly.
versus placebo across the overall nutrition monotherapy and Baseline to families treatment groups with reductions of 37 to 49%.
This will be an open label trial of <unk> in approximately 125 patients with <unk> Pn.
This observation is quite important because it suggests, which tree strand May reduce GI symptoms, which is, you can see from the placebo data were seen in approximately 40% of patients.
Patients will be randomized 401 to receive either <unk> dosed every six months or to a reference arm of <unk> dosed every three months.
These symptoms arise from the multi systemic nature of attr, cardiomyopathy and our major source of concern for patients with this disease.
The primary endpoint is the change from baseline in the modified neuropathy impairment score or <unk>, plus seven at month, nine and the <unk> arm as compared to the placebo arm from the Apollo phase III trial of <unk>.
We're excited about the prospects for RNAi therapeutics to become the standard of care in TTR amyloidosis.
You might recall that this is essentially the same study design, we utilized in our Helios, a pivotal study of <unk> and <unk>, which led to its initial approval in that disease setting.
Increase ran our next Generation silencer may offer even greater TTR knockdown with subcutaneous bi-annual dosing is now being evaluated in the Triton phase 3 Program.
We announced last quarter, the initiation of the Triton CN trial in cardiomyopathy patients.
We expect topline results and Triton Pn in 2028.
Look forward to sharing additional details as the trial gets underway.
Today I'm happy to share additional details about the Triton PN trial in hereditary. TTR poly neuropathy patients, which will be initiating shortly.
Now moving on to another exciting program, we made great progress this quarter with our <unk> program in hypertension.
This will be an open label trial of new Creed strand in an approximately 125 patients with hatr PN.
This program represents an amazing opportunity to address some of the major shortcoming of existing anti hypertensive therapies.
By targeting angiotensin agent upstream of the <unk> Cascade. We believe we can help more patients get to go not only in terms of the quantity of blood pressure lowering but also the quality of blood pressure control, reducing blood pressure variability improving adherence and restoring nocturnal dippy.
Patients will be randomized, 4 to 1 to receive either. New crease, ran dosed every 6 months or to a reference arm of a tree. Saran dosed every 3 months.
The primary endpoint is the change from Baseline and the modified neuropathy impairment score or mnus plus 7 at month 9 in the new crease, Orion arm as compared to the placebo arm from the Apollo phase 3 trial. The petites are in
Ultimately, we believe continuous control of blood pressure will drive long term improvements in cardiovascular outcomes.
At ESC in August and shown on the right. We shared results from the Carty III Phase II study.
You might recall that this is essentially the same study design, we utilized in our Helios, a pivotal study of Retreats around in hat trpn, which led to its initial approval in that disease setting.
As you can see treatment with <unk> resulted in clinically meaningful reductions in office systolic blood pressure in patients with uncontrolled hypertension and high cardiovascular risk at the month three primary endpoint with continuous control sustained through month six.
We expect Topline results in Triton PN in 2028 and look forward to sharing additional details as the trial gets underway.
Now, moving on to another exciting program, we made great progress, this quarter with our zaland program and hypertension.
Moreover, the treatment effect was further enhanced in a biologically based enriched subgroup of patients.
This program represents represents an amazing opportunity to address some of the major shortcomings of existing, anti-hypertensive Therapies.
These results are the three met the objective of informing the design patient population and dose.
So the global phase III cardiovascular outcomes trial zenith.
Zenith is a cardiovascular outcomes trial that will enroll approximately 11000 patients to evaluate <unk> at a dose of 300 milligrams given every six months compared to placebo.
By targeting angiotensinogen, Upstream of the RAS Cascade. We believe we can help more patients. Get to goal. Not only in terms of the quantity of blood pressure lowering but also the quality of blood pressure control, reducing blood pressure, variability, improving adherence and restoring nocturnal dipping.
In patients with uncontrolled hypertension with either established were at high risk for cardiovascular disease on tour more anti hypertensive.
Ultimately, we believe continuous control of blood pressure will drive long-term improvements in cardiovascular outcomes.
At ESC in August and shown on the right. We shared results. From the cardio 3 phase 2 study.
The endpoint is event driven.
With a minimum follow up of two years, and we expect to launch assuming a successful study and regulatory approval around 2030.
I'm also excited to share an update today on our <unk> 6400 development program.
As you can see treatment, since I'll be Saran resulted in clinically meaningful reductions in office to solid blood pressure and patients with uncontrolled hypertension and high cardiovascular risk at the month 3 primary endpoint, with continuous control sustained 3, month 6.
<unk> hundred 6400 targets plasminogen and we believe it has the potential to be a universal hemostatic agent that can address significant unmet needs across a range of bleeding disorders.
Moreover, the treatment effect was further enhanced in a biologically based enriched subgroup of patients.
With these results, kardia 3, met the objective of informing, the design patient population and dose.
Effectively becoming a pipeline in a product.
for the global phase 3 cardiovascular outcomes trial zenith
Plasminogen is a genetically validated target.
Hi, circulating levels are associated with increased bleeding and Conversely individuals with loss of function variance have reduced rates of bleeding.
Importantly loss of function is not associated with an increased risk of thrombosis.
Zenith is a cardiovascular outcomes trial that will enroll approximately 11,000 patients to evaluate zeran at a dose of 300 milligrams. Given every 6 months compared to placebo.
As we believe that by lowering plasminogen with Alan 6400, we potentially can slow down the process of fertilizers, thereby stabilizing costs and preventing bleeding without increasing the risk of thrombosis.
In patients with uncontrolled hypertension with either established or at high risk for cardiovascular disease on 2 or more anti-hypertensives.
Today, we're announcing the first indication will focus on with <unk> and 6400 <unk>.
The endpoint is a venture with a minimum follow-up of 2 years and we expect a launch assuming a successful study and Regulatory approval around 2030.
Hereditary hemorrhagic to Atlantic to Asia eight GHT.
I'm also excited to share an update today on our aln 6400 development program.
<unk> is the second most common inherited bleeding disorder affecting individuals of all ages, 90% of HD patients live with recurrent nosebleeds, which can be severe and life threatening and.
Halen 6400 targets plasminogen and we believe it has the potential to be a universal hematic agent that can address significant unmet needs across a range of leading disorders.
And many experienced gastrointestinal and heavy menstrual bleeding as well.
Effectively becoming a pipeline in a product.
And importantly, more than half of patients based on iron deficiency anemia.
So this is a burdensome condition and one for which there are very limited treatment options.
Basin is a genetically validated Target. I circulating levels are associated with increased bleeding and conversely individuals with loss of function variants have reduced rates of bleeding.
Importantly, we've already demonstrated initial proof of mechanism for this program in healthy volunteers in phase one.
Importantly, loss of function is not associated with an increase risk of thrombosis.
On the right are the results from an ex vivo assay has still been a licensed from our phase one study and shows in the top panel without Aon and 6400 clot formation represented by the dark Blue area quickly dissipates.
As we believe that by lowering plasminogen with aln 6400, we potentially can slow down the process of fibrinolysis. Thereby stabilizing clots and preventing bleeding without increasing the risk of thrombosis.
Whereas with <unk> 6400, Theres, an anti fraud analytic effect as represented by the dark Blue area, which extends for a much longer time and this effect is maintained out to 43 days.
Today we're announcing the first indication, we'll focus on with alen 6400.
Hereditary haemorrhagic tanjia. Hht.
We've now moved inland 6400 into a phase II trial in <unk> patients and look forward to providing updates as this program progresses.
Hht is the second most common inherited bleeding disorder. Affecting individuals of all ages. 90% of hht patients live with regard to nose bleeds which can be severe and like threatening
We also continued to advance new programs into clinical development building a pipeline that has the potential to drive sustainable growth and long term value creation.
And many experienced gastrointestinal and heavy menstrual bleeding as well.
More than half of patients, face iron deficiency, anemia.
Today for example, we announced the initiation of a phase one trial of <unk> $5 to 88, which targets <unk> T or tau for Alzheimer's disease and potentially other rare <unk>.
So, this is a burdensome condition and from 1 for which there are very limited treatment options.
Importantly, we've already demonstrated initial proof of mechanism for this program in healthy Volunteers in Phase 1.
The trial will evaluate the drug safety Tolerability pharmacokinetics and pharmacodynamics in adult patients with Alzheimer's disease.
With that let me now turn it over to Jeff to review, our financial results and upcoming milestones Jeff.
On the right, are the results from an xvivo assay of fibrinolysis from our Phase 1 study and shows in the top panel without alen 6400 clot formation represented by the dark blue area quickly disappeared.
Thanks, Chris call and good morning, everyone I am pleased to be presenting a summary of <unk> items Q3, 2025 financial results and discussing our full year upgraded guidance.
Whereas, with alen 6400, there's an anti-politician.
Let's begin with a summary of our P&L results for Q3 2025, compared with the same period in 2024.
We've now moved alen 6400 into a phase 2 trial and hht patients, and look forward to providing updates as this program progresses.
Total product revenues for the quarter were $851 million or 103% growth versus 2024, driven by 135% growth in our GTR franchise, primarily from the continued strong performance of the U S launch of <unk> and ATR cardiomyopathy.
We also continue to advance new programs into clinical development, building a pipeline that has the potential to drive sustainable growth and long-term value creation.
Collaboration revenue for the quarter was $352 million, representing a $294 million increase when compared with last year the.
Today for example, we announced the initiation of a Phase 1 trial of aln 5288, which targets map, t or towel for Alzheimer's disease and potentially other rare toe opties.
The increase was primarily due to revenue recognized under our collaboration and license agreement with Roche, including 300 million of milestone revenue associated with the dosing of the first patient in our phase III cardiovascular outcomes trial with Dolby surround.
The trial will evaluate the drug safety, tolerability, pharmacokinetics, and pharmacodynamics in adult patients with Alzheimer's disease.
with that, let me now turn it over to Jeff to review our financial results and upcoming milestones
Jeff.
Royalty revenue for the quarter was $46 million, representing a doubling compared with last year driven by higher <unk> sales as Novartis continues to successfully grow the product globally.
Thanks, push call and good morning everyone. I'm pleased to be presenting a summary of Elms. Q3 2025 Financial results in discussing our full year upgraded guidance.
Gross margin on product sales was 77% for the quarter compared with 80% in the third quarter of 2020 for.
Let's begin with a summary of our pnl results for Q3 2025 compared with the same period in 2024.
The decrease in margin was primarily driven by increased royalties on in vitro as higher revenues in 2025 resulted in an increase in the royalty rate compared with last year.
For the fourth quarter of gross margin on product sales is expected to decrease as the applicable in vitro royalty rates increase further driven by higher expected sales of in vitro.
Total product revenues for the quarter. Were 851 million or 103% growth versus 2024 driven by 135% growth in our TTR franchise primarily from the continued strong performance of the US launch of ambra and attr cardiomyopathy.
Collaboration revenue for the quarter was 352 million represented at 294 million increase. When compared with last year.
Our non-GAAP R&D expenses of $310 million increased 23% compared to last year, primarily driven by costs associated with the initiation of multiple phase III clinical studies, including the Athena phase III cardiovascular outcomes trial for <unk> in the <unk> phase III study for <unk>.
the increase was primarily due to revenue recognized under our collaboration and license agreement with rosh including 300 million of Milestone Revenue associated with the dosing of the first patient in our Zenith phase 3, cardiovascular outcomes trial which I'll be sending
Our non-GAAP SG&A expenses of $263 million increased 35% compared to last year, primarily driven by increased head count and other investments in support of the <unk> cardiomyopathy launch in the U S.
Royalty revenue for the quarter was 46 million. Representing a doubling compared with last year, driven by higher lectio sales as Novartis continues to successfully grow the product globally.
Gross margin on product sales was 77% for the quarter compared with 80% in the third quarter of 2024.
Our non-GAAP operating income for the quarter was 476 million, representing a $507 million increase compared with last year, driven primarily by strong top line results both in product sales as well as revenue from collaborations as previously highlighted.
The decrease in margin was primarily driven by increased royalties on ambra as higher revenues in 2025 resulted in an increase in the royalty rate compared with last year.
For the fourth quarter. Our gross margin on product sales is expected to decrease as the applicable and buitre royalty rates, increase further.
Continue to be pleased with the progress we are making towards achieving our non-GAAP operating profitability guidance in 2025.
Driven by higher expected sales of ambra.
We ended the quarter with cash cash equivalents in marketable securities of $2 7 billion compared with a similar amount at the end of 2024.
Cash for the quarter was impacted by our refinancing in September we raised more than $600 million via the issuance of new convertible notes, which was more than offset by the use of $1 1 billion of cash to repurchase a large portion of our convertible senior notes due in 2027.
Our non-gaap R&D expenses. Have 310 million increased 23% compared to last year. Primarily driven by costs associated with the initiation of multiple phase. 3 clinical studies including the Zenith phase 3 cardiovascular outcomes trial for lb Saran and the Triton CM phase 3 study for decreased Ram.
Additionally, we also entered into a $500 million revolving credit facility, providing a new source of flexible liquidity if necessary.
Our non-gaap sgna expenses of 263 million increased 35% compared to last year. Primarily driven by increased headcount and other investments in support of the invo tra attr cardiomyopathy launched in the US.
Now I'd like to turn to our financial guidance for 2025, where we are increasing our net product revenue guidance driven by the strong U S launch performance of in vitro and ATR cardiomyopathy with specific details as follows.
Our non-GAAP operating income for the quarter was $476 million, representing a $507 million increase compared with last year, driven primarily by strong topline results, both in product sales as well as revenue from collaborations, as previously highlighted.
We are increasing our net product revenue guidance from a range of $2 65 to $2 $8 billion to a revised range of $2 95 to $3 5 billion, representing a $275 million or 10% increase from the midpoint of the prior guidance the midpoint of the updated guidance.
Continue to be pleased with the progress. We are making towards achieving our non-gaap operating profitability, guidance in 2025.
Ended the quarter with cash cash equivalents and marketable, securities of 2.7 billion compared with the similar amount at the end of 2024.
The combined full year growth compared to 2024 is an 82% increase at the midpoint of the guidance range.
On a franchise level the guidance is broken down as follows.
We're increasing our total PTR guidance range from $2 175 to $2 $2 $75 billion to a revised range of $2 $4 75 to $2 $5 55 billion, representing a 12% increase at the midpoint.
Cash for the quarter was impacted by our refinancing in September. We raised more than $600 million via the issuance of new convertible notes, which was more than offset by the use of $1.11 billion of cash to repurchase a large portion of our convertible senior notes due in 2027.
Additionally, we also entered into a $100 million revolving credit facility, providing a new source of flexible liquidity if necessary.
We are reiterating our guidance range for our total rare franchise of 475 million to $525 million.
We are also narrowing the range of our non-GAAP operating expense guidance.
That product Revenue. Guidance driven by the strong us. Launch performance of ambra and attr cardiomyopathy with specific details as follows.
215 to $2 2 billion as we expect to end the year at the upper end of our original 2025 operating expense guidance.
The remainder of our financial guidance, including collaboration royalty revenue and non-GAAP operating income remains unchanged.
We are increasing our net product Revenue, guidance from a range of 2.65 to 2.8 billion to a revised range of 2.95 to 3.05 billion, representing a 275 million or 10% increase from the midpoint of the prior guidance, to the midpoint of the updated guidance.
Turning now from financials to our key remaining goals for 2025.
Let's push call mentioned earlier at the Triton TN trial of <unk> and <unk> will initiate shortly.
The combined full year growth compared to 2024 as an 82% increase at the midpoint of the guidance range.
On a franchise level. The guidance is broken down as follows.
We also expect to initiate a phase II trial of <unk> in Alzheimer's disease.
Let me now turn it back to Christine to coordinate our Q&A session Christine.
Thank you Jeff Operator, we will now open the call for questions to those style than we would like to ask you to limit yourself to one question each among get back in the queue. If you have additional questions.
we are increasing our total TTR guidance range from 2.175 to 2.275 billion to a revised range of 2.475 to 2.525 billion represented 12% increase at the midpoint,
We are reiterating our guidance range for our total rare franchise of $475 million to $525 million.
Thank you.
Ladies and gentlemen, if you do have any questions. Please press star followed by one on your Touchtone phone you will then hear a prompt that your hand has been raised and should you wish to decline from the polling process. Please press star followed by two.
We are also narrowing the range of our non-gaap, operating expense, guidance to 2.15 to 2.2 billion as we expect to end the year at the upper end of our original 2025 operating expense guidance.
Using a speaker phone please lift the handset first before pressing any Keith. Please go ahead and press Star one now if you have any questions.
The remainder of our financial guidance, including collaboration and royalty revenue, and non-GAAP operating income, remains unchanged.
turning now from financials to our key, remaining goals for 2025
First we will hear from shelving Ritchie of Goldman Sachs. Please go ahead.
Good morning, Thanks for taking my question and could you just speak with regard to try and have the momentum is going in the first line purchase versus switches population and maybe talk about any combo use and any clarity here on ex U S pricing would be helpful. As well. Thank you.
Push call mentioned earlier at the Triton PN trial of new crease ran and hid trpn will initiate shortly.
We also expect to initiate the phase 2 trial of myelin and Alzheimer's disease.
let me now, turn it back to Christine to coordinate our Q&A session Christine,
Yes.
Great question, we're obviously really pleased with the continued momentum that we're seeing with respect.
Thank you, Jeff Operator. We will now open the call for questions from those dialed in. We would like to ask you to limit yourself to one question each, and then get back in the queue if you have additional questions.
Growth in our <unk> business, particularly having doubled the patient demand volume.
Andrew shrink cardiomyopathy in the U S, but Tony why don't you.
Kind of take the question around.
Absolutely hi, good morning solving look we're really pleased with another strong quarter as we indicated demand doubled in cardiomyopathy.
Utilization remains very broad and balanced so let me double click on that but we're really seeing is an adoption across both academic and community settings and also from a wide range of prescribers and patient types and essentially that really demonstrates a very healthy uptick.
Thank you. Ladies and gentlemen, if you do have any questions, please press star. Followed by 1 on your touchtone phone, you will then hear a prompt that you hand has been raised. And should you wish to decline from Napoleon process? Please? Press star followed by 2, and if you're using a speaker-phone, please. Lift the handset first. Before pressing any keys, please go ahead and press star 1. Now, if you have any questions,
First, we will hear from salvian richer at Goldman Sachs. Please go ahead.
Within that what we also like to see is what we do.
Sure.
What we're seeing is.
Good morning. Thanks for taking my question. Um, could you just speak with regard to mutra? Um, have the momentum is going in the, in the first line purchase versus switches population and maybe talk about any combo use and any Clarity here on xus pricing would be helpful as well. Thank you.
We are getting.
In a place of very competitive setting in terms of first line in our first line share continues to grow quarter over quarter, and we are obviously, maintaining a clear leadership in second line among those.
Patients that are progressing or not responding to a stabilizer, so that breadth and balance gives us real confidence in the durability of <unk> momentum.
Yeah, I know this is a great question, you know obviously really pleased with the continued momentum that we're seeing with respect to uh growth in our TTR business. Um particularly having doubled the patient demand volume uh for and cardio Market in the US. But Togo, why don't you
Kind of take the question around.
And in terms of.
Our.
Ex U S pricing.
Still continuing to engage with.
Broad range of car.
Countries in terms of pricing and reimbursement, while we so far seen us.
Really.
A compelling.
Pricing profile for in Japan.
We're also launched in Germany, but we're actually in the early stages of pricing and reimbursement negotiations.
Uh, absolutely. Hi. Good morning Sovine. Uh look, we're really pleased uh with another strong quarter uh as we indicated demand doubled in cardiomyopathy and uh utilization uh remains very Broad and balanced. So let me double. Click on that. What we're really seeing is an adoption across both academic and Community settings and also from a wide range of prescribers and patient types. And essentially that really demonstrates a very healthy uptick uh within that what we also like to see is, uh, what we're we're uh, what we're seeing is
And obviously, what we're really trying to make sure. It's the right value for our innovation is being recognized and in Europe as well as we have in the U S and that remains to be.
Throughout 2006 and as the question on combination use and I think look we're seeing some ease in combination but overall the majority of the use is as a monotherapy and as we've always said is.
We're getting a sense of a very competitive setting. In terms of first line and our first line, share continues to grow further over the quarter, and we're obviously maintaining a clear leadership in the second line among those patients that are progressing or not responding to a stabilizer. So that breadth and balance gives us real confidence in the durability of our trends and momentum.
Fabulous goes generic we anticipate that we'll see increasing combination is.
Thanks for your question.
Next question.
Oh, it will be from Paul Metis at Stifel. Please go ahead Paul.
Hey, there. Thanks, so much this is julian on for Paul.
Just a quick question again on <unk> I guess.
Like what gives you confidence that youre going to continue to see an acceleration in patient adds.
Next year.
And then going into the end of this year and also it seems like there is.
Somewhat of a contribution from Switzerland, Tatra in the U S. This quarter.
Versus last quarter again any color on.
Patient switches from stabilizers.
Would really be helpful. And then just really quick on Matt T. Can you just talk about what led to the decision to pursue that program and your confidence on the target.
To be, uh, seen throughout 26. Yeah, there's a question on, uh, combination use and I think, uh, look, we're seeing some use in combination, but, but overall, the majority of the use is as a, uh, monotherapy. And as we've always said, as, uh, you know, the family disc goes generic, um, we anticipate that we'll see, um, increasing, uh, combination use.
Thanks for your question.
Yes. It does it does it say anything about your <unk> program in Alzheimer's as well. Thank you.
Next question.
Okay. So a couple of questions here, and we will try and kind of unpack them look I think what I'm told.
Will be from palmated at the fall. Please go ahead Paul.
<unk>.
Said in the prepared remarks, we're really towards the features of a very strong launch was obviously, we're delighted by them. We do see kind of a lot more potential ahead of us telco deal too.
Hey there, thanks so much. This is uh, Julian on for Paul. Um
Maybe I can take that one Petro contribution question right.
But I'll look I think actually you're probably misinterpreting.
The oil patch or a decline from the prior quarter and I really was driven by the.
Patrick favorability from last quarter's onetime Medicaid adjustment, which didn't repeat.
So.
That really is the dynamic we're actually seeing a pretty steady.
Quarter over quarter maintenance of our own powertrain business, albeit very minimum and also RPM business remains very very stable. So in terms of.
Just a, a quick question again on on ambra I guess like what gives you confidence that you're going to continue to see an acceleration and and patient ads. You know, next year um and and going into the end of this year and also it seems like there was, you know, somewhat of a contribution from, you know, switches from on patro in the US, this quarter, you know, versus last quarter again, um, any color on you know, patient switches from, you know, stabilizers, um, would would really be helpful and then just really quick, um, on Matt T. He just talked about, you know, what led to, um, the decision to pursue that program and your confidence in the Target. Um, you know, does it, does this say anything about your alnap program and also as well thank you
Our ability to actually continue to robustly.
This momentum.
Look we're only two quarters into this launch.
And we've already raised guidance twice I think that really speaks volume about the depth and durability and our confidence and what how we see this.
Consumer categories continue to.
<unk>.
And as I mentioned I think we do have a very balanced and broad uptake and we certainly look forward to increasing our presence in.
Okay. So a couple of questions here and we'll try and kind of unpack them. And look, I think what um toga shared in the prepared. Remarks were really a lot of the features of a of a of a very strong launch which obviously we're delighted by and we do see kind of a lot more potential ahead of us. Toga do you want to? Yeah maybe I can take that on patrol. Uh contribution question right after the the bed I look, I think actually you're probably misinterpreting uh that on patreon from the prior quarter and that really was driven by the
The first side, which is highly competitive as it is and maintain our.
Leadership in the those patients that are progressing on a stabilizer. Thanks, Sabra and I think the question with respect to <unk> implications for ADP push cope with do you think that yes, absolutely. Yes look we're very excited about bringing map T into the clinic I think as a starting point. This just highlights what we think is the potential of <unk>.
Interference therapeutics to have a really substantial effect in neuro degenerative diseases. So along with <unk>, we have Huntington's program T. Our colleagues at Regeneron are advancing San Juan.
We've just been very excited about the our delivery our ability to deliver safely and with infrequent dosing.
Tau is a genetically validated target both in Alzheimer's disease and <unk>.
Primary Tau Occupancies, which are all neuro degenerative diseases, where we get these neuro fibrillary tangles.
On patra's favorability from the last quarter is 1 time Medicaid adjustment which didn't repeat. So that really is the dynamic. We're actually seeing a pretty steady uh you know uh quarter over quarter uh maintenance of our own Patra business. I'll be it very minimal and and also our PM business, remains very, very stable. So, in terms of uh, our, our ability to actually continue to to robustly uh, continue this momentum. Uh, look, uh, we're only 2 quarters into this launch and and we've already raised guidance twice. I think that really speaks volume about the depth and the durability, and our confidence and what how we see this continue category is continued to grow. Um, and as I mentioned, I think we do have a very balanced and Broad uptake and we certainly look forward to increasing our
That caused neuro degeneration and cognitive decline in patients. So very excited where we're building really a portfolio of therapeutics that we think hopefully can address some of the most intractable diseases and Mannkind and I think this just speaks to the strength of the platform and hopefully being able to deliver a second an additional pillars in 2030 and beyond.
No I think thats great Scott.
Thank you for asking a pipeline question, we really do believe that not only can be thought of very.
Well.
Developing revenue trajectory with respect to our TCR franchise, but we really do have the clinical pipeline that has and number of multibillion opportunities that we're prosecuting in Chris growth organization as expeditious as we can clearly being able to help patients with <unk> Genesis of thesis would be an incredible achievements.
Thank you Pascal next next question.
That does mean Ahmad at Bank of America. Please go ahead.
Presence in, uh, first time, which is highly competitive as it is and and maintain our uh, leadership in in the the those patients that are progressing on a stabilizer. Thanks TOA and I think the question with respect to me and implications for ATP push call. Would you take that 1? Yeah, absolutely. Yeah. Look, we're very excited about bringing map T into the clinic. I think as a starting point this just highlights what we think is the potential of uh, RNA interference Therapeutics to have a really substantial effect in neurodegenerative diseases. So, along with ap, we have a Huntington's program map, te our colleagues at regeneron are advancing sad 1. Uh, we've just been very excited about the, uh, our delivery, our ability to deliver safely and with infrequent dosing. Uh, tau is a genetically validated Target, both in Alzheimer's disease and, uh, primary TOS, which are all neurodegenerative diseases, where we get these neurofibrillary, Tangles, uh, that that cause neurodegeneration and cognitive decline in patients.
Hey, guys. Good morning, Thanks for taking my question.
Good to get some color on payer dynamics.
You get to the launch on now.
Now Barry like your third or fourth quarter MMO.
How are you getting feedback from payers. Our survey work seems to indicate that we're not seeing any pushback yet even ads.
So, very excited. We're you know, we're building, uh, really a portfolio Therapeutics that we think, uh, hopefully can address some of the most intractable diseases in mankind and I think this just speaks to the strength of the platform and, and hopefully being able to deliver a second and additional pillars, uh, in 2030 and Beyond.
That's adopted in formulary, but as Youre thinking about or currently negotiated in 2026 got it.
Can you share with us some of the feedback that you're getting from payers as they are going to be any breath of payers, preferring a stabilizer.
With violence, there or at least.
Ordering which of the products that are currently available they might prefer.
Yes, no. That's a great question I mean look we're delighted that we've really had no payer headwinds.
I think that's great. Um, thank you for asking a pipeline question. We really do. Believe that not only you can be brought a very, um, you know, uh uh, uh, well, uh, developing Revenue trajectory, um, with respect to our TTR franchise, but we really do have a clinical pipeline that has a number of multi-billion opportunities that we're Prosecuting and and push calls organizations expeditious as we can clearly being able to help patients with severe. Newer degenerative diseases would be an incredible achievement. So uh thank you for Scott next. Next question.
<unk>.
<unk> you want to kind of speak to the outlook as we see it as we go into 2026.
Ahmad at the Bank of America, please go ahead.
Hi, <unk> I think.
It's really good to hear that you guys feel like its already been a year almost it's actually only two quarters that.
We've had the launch.
And as Ivan indicated that.
What we're seeing is really no no headwinds in terms of every actually.
Peter piece, whether it's fee for service Medicare advantage or even in the commercial setting I know there has been a lot of debates.
<unk>.
Whether we would be step edited or whether the burden on the patients in terms of co pay would be high and what we're really pleased to see as anticipated based on our experience in the pn.
Payers actually understanding they appreciate the value that this product brings.
Morning. Uh thanks for taking my question. Um I wanted to get some caller on payer Dynamics. Um as you get into the launch on, you know, now Laurie like your third or fourth quarter in almost, how are you um getting feedback from payers or survey work? Seems to indicate that we're not seeing any push back yet even as um, the drug test adopted to formulary, but as you're thinking about or currently negotiating 2026 status, you know, can you share with us some of the feedback that you're getting from payers? Is there going to be any risk of payers preferring a stabilizer? Um to a silencer or at least um, you know, ordering which of the products that are currently available they might prefer thanks.
Clearly highly differentiated in a disease that's actually.
A failure.
<unk> progressing on and both payers and physicians really appreciate that this disease needs to be treated early and effectively and what we're seeing is not only we didn't actually 26, but sorry, but.
<unk> five but also 26 policies are being negotiated.
And it's they're almost final and were seeing a very similar dynamic.
We had anticipated.
Early in the launch.
Thanks, Paul.
That's great next question.
As Maury Raycroft of Jefferies. Please go ahead.
Hi, good morning, Congrats on a great quarter and thanks for taking my question.
Yeah, I know. That's a great question. I mean, look with the lighter that we really had no payer headwinds, um, and uh, uh, perhaps thought that you want to kind of speak to the Outlook as, as, as we see it, as we go into 2026, uh, hi to Zen. I, I think it's, it's really good to hear that. You guys feel like it's already been a year almost. Uh, it's actually only 2 quarters, uh, that we've had the launch. Uh, and as Ivan indicated, uh, that I what we're seeing is really no no headwinds. In terms of every actually, uh, pay your uh, piece, whether it's fee for service, Medicare Advantage, or even in the commercial setting. I know there has been a lot of debate around. Uh, you know, whether we would be step edited or whether the the burden on the patients in terms of copay.
I'm wondering if you can comment more on just the inventory demand number for third quarter and how to think about that for fourth quarter, along with gross to net and can you walk us through your expectations for fourth quarter revenues in the EU and how to think about the ramp up there.
Jeff I think Thats one for you I'll take the question on inventory and gross to net.
Third quarter very similar dynamics to what we saw in the second quarter from an inventory standpoint days on hand stayed pretty constant through the quarter, but there was growth in inventory in the channel and that's because of the way.
Dave on the inventory as calculated based on demand and given the ramping demand thats, what created additional inventory going into the channel for the quarter that was more than offset in the quarter by by an increase in gross to nets toga mentioned on <unk> that was the biggest driver of the increase in gross to net between Q2 and Q3.
Would be high. And what we're really pleased to see as anticipated and based on our experience in the PN, uh, pay is actually understand and appreciate the value that this product brings, uh, clearly highly differentiated in a disease that's actually, uh, fatal and, and highly progressing. And, and both payers and Physicians really appreciate that this disease needs to be treated early and effectively, and what we're seeing is not only within actually 26, but, uh, sorry, but, uh, 25 but also 26 policies are being negotiated. Uh, and it's, they're almost final and, and we're seeing a very similar, uh, Dynamic, uh, that we had anticipated, uh, early in the launch.
Thanks TOA. That's uh, that's great next question.
Is my Ray Ray. Croft at Jeffrey's. Please go ahead.
We see gross to nets for the GTR franchise for the year continues to be mid single digit price decline on a net price basis on a year over year basis I think.
Maybe if you could repeat the other question about about Europe, and maybe told them. They won't take that one in terms of expectations for Q4, I think he was asking about the right Maury.
Hi, good morning. Congrats on the great quarter and thanks for taking my question. Um, wondering if you can comment more on, uh, just the inventory demand number for third quarter, and how to think about that for fourth quarter, along with gross and net. And, uh, can you walk us through your expectations for fourth quarter revenues in in the EU and how to think about the ramp up? Their
Yes, that's right and just how to think about the ramp up in Europe as well.
Right, So I think the.
We're thinking in greater scheme of things the contribution of ex U S market is going to remain relatively modest, especially for fourth quarter given that we only have really two markets that's going to be that's right now available, Germany, and Japan, and Germany, we are continuing to actually have.
Final pricing discussion, so that's obviously going to be rather limited in Japan.
We're very pleased with the momentum that we built but again integrator.
Scheme of things the contribution is going to be very modest so ex U S market is going to be mainly 2026 mid to late 2006.
Story, what I really like seeing as how we are actually maintaining our pm business.
If you look at year over year.
Growth now is 46% in ex U S. In GTR markets that suggests that and this is actually in the presence of a new competitor now.
Jeff, I think that's 1 for you. Yeah, I'll take the the question on inventory and gross to Net in the in the third quarter, very similar Dynamics to what we saw in in the second quarter from an inventory. Standpoint days on hand stayed pretty constant for the quarter but there was growth in inventory in the channel. And that's because of the way that the day on the inventories calculated based on demand and given the ramping demand that's what created additional inventory. Going into the channel for the quarter. That was more than offset in a quarter by by an increase. In, in growth. The Nets toga mentioned uh on Patra. That was the biggest driver of the increase in gross net between Q2 and Q3 where where we see growth to nets for the TTR franchise. For the year continues to be, you know, mid single digit price. Decline on a net price basis on a year-over-year basis. I think the more, maybe if you could repeat the other question about about Europe and maybe toland, they want to take that 1 in terms of expectations for Q4, I think he was asking about, is that right Mory? Yep. Yeah, that's right. And just
How to think about the ramp up in Europe as well.
So look I mean, I think just like what we've done in the U S.
In the Pn markets, we are competing very effectively capturing majority of first line patients and we've actually establish a great ecosystem and these key centers of excellence in Europe.
Really recognize the value of our treatment and the product profile.
I would expect more more to come on that in 2006 that was grateful because look I mean, I think as a company. We've built a really phenomenal R&D engine and I think now we.
Right. So I think the, if, if I were to think in a greater scheme of things, the contribution of xus Market is going to remain relatively modest, uh, especially for a fourth quarter. They're giving that we only have really 2 markets. That's going to be that's uh, right now available uh Germany and Japan. And in Germany we're continuing to actually have uh final pricing discussion, so that's obviously going to be a rather Limited in Japan. Uh
We will stop us towards a very robust commercial engine. So thanks, thanks to Tokyo and his team for their achievements of the last quarter.
Next question.
Next we will hear from Jessica Fye of Jpmorgan Chase. Please go ahead.
Hey, guys. Good morning, congrats on the corner.
I was curious if you could just elaborate on the approach you took to updating the TCR franchise guidance. This time around in light of the fact that as you said, we're still just two quarters into the cardiomyopathy launch. Thank you.
Yes, I'm happy to take that Jess.
The updated guidance. So obviously, what we're really doing here is predicting what we're going to see in the fourth quarter because thats the long time.
<unk>, we got left in the year relative to the guidance that we've just issued and if you look at the the guidance.
It's roughly estimating total GTR global revenue of $850 million to $900 million in the fourth quarter, which would reflect a $125 million to $175 million a quarter on quarter growth on that on that range. The upper end of that range is very close to what we've delivered in both Q2 and Q3 and so I would say that's really how we've.
Uh, majority of the first-time patients. And and we've actually established a great ecosystem. And these key centers of excellence in Europe, uh, really recognize the value of our treatment and the product profile. Uh, so I would expect more more to come on that, in, in 26. That's great. So, because look, I mean, I think, as a company, we built a really phenomenal R&D engine, and I think now we we established a very robust commercial engine. So thanks thanks to Togo and his team for their achievements, over the last quarter.
Next question.
Next, we will hear from Jessica fee at JP Morgan Chase. Please go ahead.
Develop the guidance, we're continuing to learn as toga said, we're two quarters and I think our understanding of the business.
The ability to forecast it is improving as we get more data points.
But we're comfortable with the range and I would think about the midpoint as the most likely outcome for Q4.
Hey guys, good morning. Congrats on the quarter. Um, I was curious, if you could just elaborate on the approach, you took to updating the TTR franchise guidance, this time around in light of the fact. That as you said, we're still just 2 quarters into the cardiomyopathy launch. Thank you.
Yes.
Good.
Next question.
Well be from RB.
RBC. Please go ahead Luca.
Oh, great. Thanks, so much for I think I'm, taking my question and congrats on another fantastic quarter, maybe toll got.
<unk> thousand and proposing to cut reimbursement for QEP scintigraphy, I think by 57% from $300 all the way down to $500.
What was your reaction to that news and that may be related.
Yeah. I'm I'm happy to take that Jess. Um, you know we updated the guidance. So obviously what we're really doing here is predicting what we're going to see in the fourth quarter because that's the only uh time Point. We've got left in the year relative to the guidance that we've just issued. And if you look at the the guidance um it's it's roughly estimating total TTR Global revenue of 850 to 900 million in the fourth quarter, which would reflect 125 to 175 million, a quarter on quarter growth on that
Such efforts from CMS will remain insulated to just the diagnostics side of the equation or you think that CMS lots of them are look also on the therapeutic side of the equation given obviously the cost therapeutics are much higher than the diagnostic side and then maybe Super quick quickly could you just maybe talk about the subpoena from the U S. Attorney generals that you put in the press release.
Thanks, so much guys.
Well look why don't I take the subpoena question really quickly and clearly.
On that range. The upper end of that. Range is very close to what we've delivered in in both Q2 and Q3. And so, I would say that's really how we've developed the guidance for continuing to learn. As toga said, we're 2 quarters in. I think our understanding of the business and ability to to forecast. It is improving as as we get more data points. Um, but we're comfortable with the range and I would, I would think about the midpoint is the most likely outcome for, for Q4.
Thank you, good.
We intend to work with the U S. Attorney's office to produce the documents that have been requested by the subpoena and to understand and address any potential concerns with respect to government price reporting and of course as you know we don't generally comment on legal matters, but thank you for the question I'll hand, it over to <unk>.
Next question.
Will be from Luca, is he at RBC please go ahead. Luca
We'll go to take the remainder of your questions. Yes, So <unk> scans and how they are being currently reimbursed is obviously has been an important driver for the growth of this category, we actually anticipate.
More diagnosis and more scanning.
We need to really fully understand how that reimbursement is actually going to play out we haven't really seen any anxiety or concerns into health systems that we're engaging with so we're obviously again staying in June.
Oh great. Thanks so much for taking my questions. Congrats on another, uh, fantastic quarter, maybe Tolga. You know, CMS is obviously proposing to cut reimbursement for p and geography, but I think by 57%, from 1300 all the way down to 500 dollar, I guess what was your reaction to that news? And then maybe related. Uh, do you think the such efforts from CMS will remain insulated to just the diagnostic side of the equation? Or do you think that CMS would like to look also, in the therapeutic side of the equation given obviously, the cost of Therapeutics are much higher than, uh, the diagnostic side and then maybe super quick quickly. Can you just maybe talk about the subpoena from the US attorney general that you put in the press release? Thanks so much guys.
And I'm sure, we'll be able to manage that.
As the policy becomes more clear.
Thank you so much.
Thank you next question.
Gena Wang of Barclays. Please go ahead.
Thank you for taking my questions also congrats on a great quarter.
So maybe just.
Just wanted to confirm I heard it correct.
That's the price for <unk> will be decline at the mid single digits year over year in the U S and a related question is once you launch HR cardiomyopathy in Europe, how should we think about price change in Europe.
Should we expect a step or largely align with the U S.
And then second question is regarding the <unk>.
Okay.
Cardiomyopathy in the U S. Just wondering if you still share a little more color.
Well, look, why don't I take the subpoena. Um, question really quickly and, and look clearly, um, you know, we intend to work with the US, attorney's office to produce a documents that have been requested by The subpoena and, and to understand and you know, address any uh potential concerns with respect to government price reporting. And of course, as as you know we don't generally comment on on on legal matters but thank you for the question and I'll hand it over to toga to take the remainder of your questions. Yes. So if people scans and how they're being currently reimbursed is obviously has been an important driver for the, the growth of this category, we actually anticipate uh, more diagnosis and and more scanning. Um, we need to really fully understand how that reimbursement is actually going to play out. We haven't really seen any anxiety or concerns in the health systems that we're engaging with. So, uh, we're obviously again, uh, staying in tune. Uh, and and and and and and I'm sure we'll be able to manage that.
The ratio between the first one for Scott.
Talking about roughly 50 50 or second Lions are slightly higher.
Uh, uh, as as as the policy becomes more clear.
Thank you so much, great.
So we've got kind of a number of questions about.
Good doctor. Thank you next question.
About kind of.
Um, Gina Wang at Barkley's, please go ahead.
Price year on year in the U S price in the EU and color on the first line second line space I think all of those ICU Tolga why don't you go ahead.
Sure I mean look.
As we had highlighted before we would actually anticipate.
Our net price to be gradually going time going down over time, and what youre seeing is perhaps some of those impacts and.
And we will continue to provide obviously, what what gross to net actually margins will look like over time, but I wouldn't expect.
Thank you for taking my questions also, congrats on the great quarter. Um, so maybe, um, just want to confirm, I heard it correct. Uh, that the price for and voucher will be declined at the mid single digit year-over-year in the US. And a related question is that once you launch uh, HTR uh, card in biopsy in Europe, how should we think about price change in Europe? Uh, should we expect a huge dip or largely aligned with the US?
So.
As serious or significant shifts in that now when it comes to Europe. Obviously, those negotiations are continuing and what we're making sure that you know.
We are taking into account Amazon and number of others.
Dynamics, and we'll obviously be able to provide a much more broader outlook in terms of how the volume and price is going to play out in the outer years as I said before this is really going to be a mid to late 'twenty six story and your other question is around <unk>.
So we've got kind of a number of questions here uh about kind of you know, pricing on you in the US price in the EU and uh color on the first line, second line. But I think all of those are for you Togo. Why don't you go ahead and
Remind me again.
The ratio of first line and second line some color on yes, I mean look I think what we really like.
To see so far what we've been seeing is we are increasingly getting more competitive in first line.
As second line in terms of stabilizer that obviously is our existing patient pool that has actually.
Started very early in the launch, but what we like seeing is after first month.
Into the launch we start seeing a much more balanced and broad uptake.
Between first and second line and we certainly expect that to continue as we actually increase our <unk>.
First line presence.
In the outer quarters, Yeah, and I'd, just like to add how how well the data from <unk> actually resonating with physicians I mean being Egypt being the first of these sonnenfeld the ctr with rapid knockdown of GTR source I think.
Sure. Okay, I mean, look as Gina as we had highlighted before, we would actually anticipate uh our net price to be gradually uh, going time, uh, going down over time. And what's your seeing is perhaps? It's some of those impact. Uh, and we'll continue to provide obviously, what, what the gross net actually margins. Will will look like over time, but I wouldn't expect a, a, a a, you know, uh, uh, ah, ah, serious or or, or, or, or significant shift in that. Now, when it comes to Europe, obviously those negotiations are continuing and what we're making sure is that, you know, uh, we are taking into account mfn and number of others, uh, uh, Dynamics and, and we'll, uh, we'll obviously be able to provide a much more broader Outlook in terms of the, how the volume and price is going to play out in the outer years. As I said before, uh this is really going to be a mid to late 26 uh story and
Having an impact I think the data that will be continuing to generate is important on the pushcart touched on this in terms of.
37% relative risk reduction in all cause mortality and.
CV events I think Cisco also touch on the multi system nature of the disease with a reduction in Gi events that really is.
Your other question is around, uh, remind me again is uh ratio of first line and second line. Uh, yeah. I mean, look, I I think what we really like, uh, to see so far what we've been seeing is we are increasingly getting more competitive in first line. Uh, the second line in terms of stabilizer that obviously is a existing patient pool. That has actually, uh,
<unk>.
And I think a compelling additional data point for physicians and of course, the quarterly regimen I think also resonates well with physicians.
Physicians can be sure the patients are actually going to receive that drug given the quarterly subcutaneous administered.
Administration. So all in all I think we feel really well positioned in this market.
Started very early in the launch. But what we like seeing is after first month, uh, into the launch, we start seeing a much more balanced and Broad uptake uh between first and second line. And and we certainly expect that to continue. As we actually increase our uh uh first line presence uh uh in the in the outer quarters.
For a growing position in first line is a focus that we are highly competitive here and obviously.
No.
The leading choice for.
Patients who continued to progress on stabilized. So we feel we feel we built medical foundation soon thank you for the question.
I think I think we're onto our Cmos it just two more questions. So ritu.
Apparently you're up next.
Please go ahead Brito morale at TD Cohen.
Hi, guys. Thank you so much for taking the question.
Just back to Europe toga.
Can you talk about what degree of.
Yeah. And I just like to add how how well the data from gdsb actually resonating with Physicians. I mean, being, you know, being being the first and only silencer a TTR with rapid knockdown of TTR resource. I think that's having an impact. I think the data that we continue to generate is important, I mean, push call touched on this in terms of um, you know, a 37% relative risk reduction and uh all cause mortality and uh firstly the event, I think just go also touched on, you know, the multi system nature of the disease with a reduction in GI events that really is I think. Uh um you know, I think a compelling um additional data point for Physicians and of course the the quarterly regimen I think
Commercial investment is needed in Europe to expand beyond the pn indication.
We're trying to figure out how to balance that against any potential lower cost and then just a very quick follow up if we think about that first line dynamics, how much does center type impact first line use basically.
<unk> commercial hospital system.
Hey.
Patient characteristics.
No. That's helpful. Thank you Richard Richard.
So here are a few points around.
You should be thinking about Europe. So we actually had a quite an effective team that has been able to established.
Um, also resonates well where, you know, Physicians can be sure that patients are actually going to receive their drug. Given the, uh, quarterly subcutaneous, uh, Administration. So all in all I think, um, we feel really well positioned in this market. Uh, both for, you know, growing position and first line as, as talker said, we're highly competitive here. And you know, obviously um, you know, uh, you know, the leading choice for for, um, patients who continue to progress on stabilizers. So, you know, we feel we feel. We've got some really good foundations here. Thank you for the question. So I think I think we're on to our to just to Just 2 more questions. So, so read to. Apparently you're up next.
Please go ahead 3 to B at TD Khan.
Our market leadership versus to Fabulous Interpol neuropathy organization and the main reason why that the organization is so effective is because this is a category, particularly in Europe is really managed by centers of excellence.
Perhaps maybe with the exception of Germany and most other.
Our centers. This is in countries. This is really managed by by sensors, albeit Italy or France.
And some other major or other European countries, we know in the UK for US is there was one single center National Amyloidosis Center that manages that so it does require.
Hi guys, thank you so much for taking the question. Um, just back to Europe. Toga, um, can you talk about what degree of um, commercial investment is needed in Europe. Um, to expand beyond the PN indication. Um, we're trying to figure out, you know, how to balance that against any potential lower cost. And then just a very quick follow up as we think about that first line Dynamics, how much does Center type impact? Um, first line use um, basically, you know, if they're in commercial Hospital Systems versus
Patient characteristics. Thanks
In task calibration and obviously.
Scientific engagement, but in terms of the field activity that is rather limited.
And.
The cardiomyopathy.
Cardiomyopathy patients are actually new.
Mostly treated in these centers as well so we wouldn't expect a significant.
Expansion of our European business is now when it comes to Japan look that market is a little more fragmented. So we do actually invest we certainly play to win in that category and we will obviously continue to invest.
Whats necessary to make sure that.
The product's profile is well understood and I appreciate it.
Thanks <unk>.
So one more question, but I'll ask questions coming out.
Last question is from Cory <unk> of Evercore. Please go ahead.
Hi, Good morning, Thank you for squeezing us and this is Eddie on for Corey.
The Communist trends show a clear.
Alex jumped from fourth quarter to first quarter in both clinically and Florida and <unk> five.
By centers, I'll be it easily or France uh and some other major other European countries. We know in the UK for instance there is 1 single Center National mudosa Center that manages that. So it does require uh intense collaboration and and and and and and and obviously uh, a scientific engagement. But in terms of the field activity, that's rather limited uh and and
Should we model a similar jump off for a neutral.
Thinking that is that because.
Because of their body.
Patients in the past year, our normal seasonality.
Thank you.
Yes, so maybe I'll take your question more from a perspective of category growth and what you should be expecting.
First and foremost, it's obviously still early days and only one company has reported so far in terms of their quarter over quarter dynamic, but and we still like to see how Pfizer is going to report.
Cardiac patients are actually mostly treated in these centers as well. So we wouldn't expect a significant uh expansion of our European businesses. Now when it comes to Japan that market is a little more fragmented so we do actually invest. We certainly play to win in that category, uh, and and we will obviously continue to invest uh what's necessary to make sure that uh the the products profile is well understood and appreciated.
Thanks TOA.
so 1 more question but our last question coming up,
Before we draw firm conclusions about how that dynamic is working but that said everything that we're seeing.
Asked question is from Corey Kassab, boss at Evercore. Please go ahead.
The category growth in <unk> is accelerating and it's no surprise because we all know that this is an underdiagnosed and undertreated category and there are a lot of patients are still waiting.
And we also seen this very much on pull neuropathy with just one.
Uh, hi. Good morning. Thank you for, uh, squeezing us and this is Addie on for Corey, um, but the, the family is trying to show a clear, uh, analysis jump from fourth quarter to first quarter in both 2024 and 2025, um, should we model a similar jump up or a router? Um,
What are coming in and on top of US we're seeing the category growing accelerating a lot faster and the good news on Polyneuropathy, we still remain actually this first line.
You know, thinking that is it uh because of Ira Part D uh modifications in the past years or normal seasonality.
Thank you.
Market share leader.
And within the <unk>.
Expected category growth.
I would say we are exceptionally well positioned.
As Ivan and push Gall mentioned, we are well differentiated in terms of our mechanism. We obviously have the robust outcomes supplied by Helios B and importantly, we are continuing to invest in the category, especially on real world evidence and data generation.
Yeah, so maybe I'll I'll take your question more from a prospective of category growth and what you should be expecting. Uh look first and foremost it's obviously still early days and only 1 company has reported so far in terms of their quarter over quarter, uh Dynamic but and we still would like to see how fiser is going to report uh before we drove some firm conclusions about how that Dynamic is working. But that said everything that we're seeing
Across both clinical and real world setting.
So our evidence basis strengthening that really positions us to become a market leader in this category growing category.
Right well.
I think that brings our call to a close and I just like to thank everybody who has joined us today.
Execution of this quarter commercially and with respect to our pipeline I think really demonstrates the new unique trajectory.
Not to become a top tier biotech company and we look forward to sharing with you additional updates as we embark on.
Uh, the categorical growth in attrc is accelerating and it's no surprise because we all know that this is an underdiagnosed and undertreated category and there are a lot of patients that are still waiting. Um uh, and we also seen this very much on Paul neuropathy with just 1 uh, product coming in and on top of us, we've seen the category growing accelerating a lot faster. And the good news is I'm pulling neuropathy. We still remain actually the first line and uh, you know, uh, market share leader.
Uh, and and within the, you know, expected category growth.
Realizing this vision.
Thank you everybody and have a great day.
Thank you ladies and gentlemen, this does indeed conclude your conference call for today. Once again, thank you for attending and at this time, we do ask that you. Please disconnect your lines.
Goodbye.
I would say we are exceptionally well, positioned, uh, as iban and pushkar mentioned, we are. Well, differentiated in terms of our mechanism, we obviously have the robust outcomes Supply by Helios B and importantly, we are continuing to invest in the category into, especially on real world, evidence and data generation, uh, across both clinical and real world setting. Um, so our evidence base is strengthening that really positions us to become a market leader in this, uh, category, uh, growing category.
Great. Well, um, I think that brings our call to a close and I just like to thank everybody who's joined us today. Um, look our execution, this quarter commercially and with respect to our pipeline, I think really demonstrates the unique trajectory we have at our nodame. So to to become a top, tier biotech company, and uh, we look forward to sharing with you, um, additional updates as we embark on on, uh, realizing this Vision. So, thank you everybody and have a great day.
Thank you, ladies and gentlemen. This doesn't be conclude your conference call for today. Once again, thank you for attending. And at this time we do ask that you please disconnect your lines
Goodbye.