Q2 2025 Ionis Pharmaceuticals Inc Earnings Call

July 30, 2025

I would like to turn the call over to eat Wilkey Senior Vice President of Investor Relations to lead off the call.

Please go ahead.

Thanks, Steve.

Before we begin I encourage everyone to go to the investors section of the <unk> website to view the press release and related financial tables, we will be discussing today, including a reconciliation of GAAP to non-GAAP financials.

We believe non-GAAP financial results better represent the economics of our business and how we manage our business. We've also posted slides on our website that accompany today's call.

With me. This morning are Brent <unk>, Chief Executive Officer, <unk>, <unk>, Chief Global product strategy Officer, Richard Geary, Chief Development Officer, and Beth Hougen, Chief Financial Officer.

Eugene Schneider, our Chief clinical development Officer, and Eric Swayze Executive Vice President of Research will also join us for the Q&A portion of the call.

I would like to draw your attention to slide three which contains forward looking language statement. During this call we will be making forward looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties and our actual results may differ materially.

Currency to consult the risk factors contained in our SEC filings for additional detail.

And with that I'll turn the call over to Brett.

Thanks Wade.

Good morning, everyone and thank you for joining us on today's call.

We have continued to build strong momentum across our business highlighted by the excellent early commercial performance of our first independent launch during Goelzer, the first and only FDA approved treatment for familial kind of micro Nemea syndrome.

<unk> exceeded revenue expectations during the second quarter on the market underscoring its strong therapeutic profile, our well executed commercial strategy as well as the significant unmet need <unk> is addressing.

The revenue and commercial performance of <unk> and to date, along with our competition interim goals as continued commercial success.

The increase in our financial guidance for 2025.

Which Pat will cover in more detail shortly.

We're also pleased that from Golar recently received a positive <unk> opinion paving the way to bring this transformative therapy to patients across Europe.

Shifting gears, we anticipate Ananda Larson for hereditary angioedema, our HPE will be our second independent launch by receiving FDA approval next month.

Based on the progress of the review, we believe the approval and subsequent launch remains on track.

<unk> has the potential to become a preferred prophylactic therapy for many patients with strong efficacy and favorable safety and tolerability in the pivotal studies.

Ah patient friendly auto injector in a convenient dosing schedule of monthly or every other month self administration.

We are well positioned to launch <unk> following approval.

Yes.

Additionally, our phase III pipeline continues to advance well with data expected later this year from two wholly owned <unk> programs.

If positive these results, which support the continued steady cadence of independent launches next year, bringing important treatments to patients. These include a second indication for <unk> in severe hyper triglyceride EMEA Rs hcg, a condition with a large patient population and significant unmet need and zillionaires in for Alex.

Andrew diseases severe rare movie distribute with no approved disease modifying therapies.

Together. These programs in addition to two holes in Fcs.

<unk> and <unk> represent major breakthroughs for patients and represent multibillion dollar revenue potential for Iconix.

Additionally, by the end of 2027, and we anticipate for potential launches from our rich late stage partnered pipeline.

<unk> targeting serious life threatening conditions for both rare and highly prevalent diseases.

These will further expand the impact and reach of ion is discovered medicines and have the potential to meaningfully increase total revenue.

With our strong momentum across the business, including <unk> and our upcoming independent and partnered launches.

<unk> is well positioned to bring transformative medicines to patients for years to come.

And in turn achieve sustained revenue growth and positive cash flow and with that I'll turn the call over to Kyle.

Thank you Brett with our first independent launch now well underway on our second launch right around the corner our commercial team is executing on our strategy to capitalize on a significant growth opportunities.

For Ingalls and reported $19 million and net product sales for the second quarter, reflecting a three fold increase in revenues quarter over quarter.

In the second quarter <unk> continued to build launch momentum. This was the result of several factors, including effective patient identification efforts.

Strong product profile.

Favorable payer dynamics and overwhelmingly positive HCP reported experience.

Our patient identification initiatives are paying off the breadth and depth of unique physicians prescribing <unk> continues to grow in many of these physicians have prescribed the therapy to two or more patients underscoring the positive experience of both clinicians and patients.

This demand also spans a broad mix of specialties with cardiologists, and endocrinologists, representing roughly 50% and 30% of prescribers respectively.

And lipid allergist in internal medicine providers, making up the balance.

Overall physician feedback remains highly favorable with significant benefits reported and awareness of <unk> continuing to gain traction.

Coverage and reimbursement trends have remained favorable to date the coverage mix for patients answering Goldman is approximately 60% commercial and 40% government and.

<unk> patients, whether clinically diagnosed or genetically confirmed have gained access.

<unk> have obtained coverage through a growing number of formal policies or via the medical exception process. This highlights both the urgent unmet need and payers' willingness to support access even before a formal policies are in place.

Brett Monia: Of independent launches next year, bringing important new treatments to patients. These include a second indication for olzarsin in severe hypertriglyceridemia, or SHTG, a condition with a large patient population and significant unmet need, and zilganersin for Alexander disease of severe rare leukodystrophy with no approved disease-modifying therapies. Together, these programs, in addition to two roles in FCS and on the worsening HAE, represent major breakthroughs for patients and represent multibillion-dollar revenue potential for Ionis. Additionally, by the end of 2027, we anticipate four potential launches from our rich late-stage partner pipeline, targeting serious life-threatening conditions for both rare and highly prevalent diseases. These will further expand the impact and reach of Ionis Discover Medicines and have the potential to meaningfully increase total revenue.

Important treatments to patients. These include a second indication for <unk> in severe hypertrichosis redeeming our CTG a can.

Additionally, over 90% of patients have paid $0 out of pocket since launch and timelines for patients obtaining the medicine are consistently beating our aggressive internal benchmarks.

Additionally, a large patient population and significant unmet need in <unk> in the per Alexander diseases severe rare lipid dystrophy with no approved disease modifying therapies.

Nearly all patients have opted into our I honest every step support program a testament to the value of the program is providing.

Together. These programs in addition to two holes in FCS and <unk> and <unk> represent major breakthroughs for patients and represent multibillion dollar revenue potential for eye on us.

We established the ion US every step support program to ensure a positive patient experience by providing disease and nutrition education.

Additionally, by the end of 2027, and we anticipate for potential launches from our rich late stage partnered pipeline targeting serious life threatening conditions for both rare and highly prevalent diseases.

<unk> injector training and reimbursement support among other offerings.

For health care providers. The program provides helpful support from insurance authorizations and coverage coordination to reauthorization and refills.

These will further expand the impact and reach of ion is discovered medicines and have the potential to meaningfully increase total revenue.

We're proud of turn goals as early momentum, but we know we are still in the early innings. The vast majority of the estimated 3000 people living with FCS in the U S remain on identified to close that gap, we're continuing to focus on our patient finding efforts and HCP education.

With our strong momentum across the business, including from Volta, and our upcoming independent and partner launches.

Brett Monia: With our strong momentum across the business, including Tringolza and our upcoming independent and partnered launches, Ionis is well-positioned to bring transformative medicines to patients for years to come and, in turn, achieve sustained revenue growth and positive cash flow. And with that, I'll turn the call over to Kyle.

<unk> is well positioned to bring transformative medicines to patients for years to come.

And in turn achieve sustained revenue growth and positive cash flow and with that I'll turn the call over to Kyle.

Our customer facing team has reached over 3000 physicians and over 30000 Hcp's had been targeted through our omni channel capabilities. Both intended to further increase awareness of FCS expand patient identification and educate on the potential benefits of <unk> as a treatment.

Kyle Jenne: Thank you, Brett. With our first independent launch now well underway and a second launch right around the corner, our commercial team is executing on our strategy to capitalize on these significant growth opportunities. Tringolza reported $19 million in net product sales for the second quarter, reflecting a threefold increase in revenues quarter over quarter. In the second quarter, Tringolza continued to build launch momentum. This was a result of several factors, including effective patient identification efforts, a strong product profile, favorable payer dynamics, and overwhelmingly positive HCP-reported experience. Our patient identification initiatives are paying off. The breadth and depth of unique physicians prescribing Tringolza continues to grow, and many of these physicians have prescribed the therapy to two or more patients, underscoring the positive experience of both clinicians and patients.

Backed by an experienced and high performing team, we are well positioned to continue to take advantage of our first mover position to bring Turing goals of the patients in need and keep them on treatment.

For Ingalls are reported $19 million and net product sales for the second quarter, reflecting a three fold increase in revenues quarter over quarter.

In the second quarter <unk> continued to build launch momentum. This was a result of several factors, including effective patient identification efforts.

Building on our early success in FCS, we are advancing toward a potential blockbuster opportunity in severe hypertrophy glyceride EMEA with <unk>.

Strong product profile favorable payer dynamics and overwhelmingly positive HCP reported experience.

<unk> represents a large patient population many of whom struggle to manage their triglyceride levels with current treatments in.

In the U S alone more than 1 million people have high risk <unk> <unk> and includes individuals with triglyceride levels above 880 or above 500, with a history of acute pancreatitis.

With a significant first mover advantage, we believe <unk> is well positioned to address the unmet needs of patients with severe hypertrophy Glyceride EMEA.

Kyle Jenne: This demand also spans a broad mix of specialties, with cardiologists and endocrinologists representing roughly 50% and 30% of prescribers, respectively, and lipidologists and internal medicine providers making up the balance. Overall, physician feedback remains highly favorable, with significant benefits reported and awareness of Tringolza continuing to gain traction. Coverage and reimbursement trends have remained favorable. To date, the coverage mix for patients on Tringolza is approximately 60% commercial and 40% government. Importantly, patients, whether clinically diagnosed or genetically confirmed, have gained access. Patients have obtained coverage through a growing number of formal policies or via the medical exception process. This highlights both the urgent unmet need and payers' willingness to support access even before formal policies are in place. Additionally, over 90% of patients have paid $0 out of pocket since launch, and timelines for patients obtaining the medicine are consistently beating our aggressive internal benchmarks.

This demand also spans a broad mix of specialties with cardiologists, and endocrinologists, representing roughly 50% and 30% of prescribers respectively.

Our commercial team is making excellent progress as we prepare for a potential launch next year.

Turning to loss in our second independent launch has the potential to transform the treatment paradigm for individuals with <unk> as the first and only RNA targeted prophylactic medicine.

And lipid allergist in internal medicine providers, making up the balance.

Overall physician feedback remains highly favorable with significant benefits reported and awareness of <unk> continuing to gain traction.

More than 20000 people in the U S and in Europe are estimated to have <unk> with.

Coverage and reimbursement trends have remained favorable to date the coverage mix for patients answering goals is approximately 60% commercial and 40% government.

With approximately 7000 people in the U S alone.

In the U S. Most patients are currently on prophylactic treatment. However, many patients remain unsatisfied with up to 20% of patients switching therapies each year in search of a more effective and convenient option highlighting our need for new treatments with enhanced profiles. We believe <unk> is unique.

<unk> patients whether clinically diagnosed or genetically confirmed have gained access patients have obtained coverage through a growing number of formal policies or via the medical exception process. This highlights both the urgent unmet need and payers' willingness to support access even before a formal policies are in place.

<unk> positioned to meet this demand.

The <unk> and clinical data have shown durable efficacy and favorable safety and tolerability profile with a patient friendly monthly or every other month self administration with an auto injector.

Additionally, over 90% of patients have paid $0 out of pocket since launch and timelines for patients obtaining the medicine are consistently beating our aggressive internal benchmarks.

Importantly, as we prepare to bring <unk> into market. We are applying the same disciplined and innovative approach.

Kyle Jenne: Nearly all patients have opted into our Ionis Every Step Support Program, a testament to the value the program is providing. We established the Ionis Every Step Support Program to ensure a positive patient experience by providing disease and nutrition education, auto-injector training, and reimbursement support, among other offerings. For healthcare providers, the program provides helpful support from insurance authorizations and coverage coordination to reauthorizations and refills. We're proud of Tringolza's early momentum, but we know we're still in the early innings. The vast majority of the estimated 3,000 people living with FCS in the US remain unidentified. To close that gap, we're continuing to focus on our patient-finding efforts and HCP education.

Nearly all patients have opted into our I honest every step support program a testament to the value of the program is providing.

That has that has made the turn goals to launch a success. We have deployed our field team who are educating and preparing the market for the anticipated approval of <unk> and are energized to successfully execute the launch.

We established the Iona every step support program to ensure a positive patient experience by providing disease and nutrition education.

Auto injector training and reimbursement support among other offerings.

Meanwhile, our market access team is actively engaging with payers and our field medical team continues to delay the central groundwork to ensure a smooth and successful launch.

For health care providers. The program provides helpful support from insurance authorizations and coverage coordination to reauthorization and refills.

We're proud of <unk> goals is early momentum, but we know we're still in the early innings. The vast majority of the estimated 3000 people living with FCS in the U S remain on identified to close that gap, we're continuing to focus on our patient finding efforts in HCP education or.

Our experienced and scalable commercial organization is already delivering excellent results supported by the early success seen with the launch of Pringles in Fcs.

As we build on this momentum we remain focused on maximizing <unk> full potential while preparing to successfully execute three additional launches by the end of next year, including Don <unk> in the coming weeks, enabling island us to reach more people in need with our medicines with that I'll now turn it over to Richard.

Kyle Jenne: Our customer-facing team has reached over 3,000 physicians, and over 30,000 HCPs have been targeted through our omnichannel capabilities, both intended to further increase awareness of FCS, expand patient identification, and educate on the potential benefits of Tringolza treatment. Backed by an experienced and high-performing team, we are well-positioned to continue to take advantage of our first-mover position to bring Tringolza to patients in need and keep them on treatment. Building on our early success in FCS, we are advancing toward a potential blockbuster opportunity in severe hypertriglyceridemia with olzarsin. SHTG represents a large patient population, many of whom struggle to manage their triglyceride levels with current treatments. In the US alone, more than 1 million people have high-risk SHTG and includes individuals with triglyceride levels above 880 or above 500 with a history of acute pancreatitis.

Thank you Kyle.

We are making excellent progress across our pipeline positioning I on us to deliver on our mission of bringing transformational medicines to patients for years to come.

Backed by an experienced and high performing team, we are well positioned to continue to take advantage of our first mover position to bring Turing goals that are patients in need and keep them on treatment.

Let me start with the recent updates from our wholly owned pipeline.

As a reminder, Dana Dorsen is currently under regulatory review in both the U S and EU with submission supported by its robust clinical data.

Building on our early success in FCS, we are advancing toward a potential blockbuster opportunity in severe hypertrophy glyceride EMEA with <unk>.

<unk> represents a large patient population many of whom struggle to manage their triglyceride levels with current treatments in.

We remain confident in the August 20, <unk> date based on the engagement we've had with the FDA at this stage in the process spending.

In the U S alone more than 1 million people have high risk <unk> and includes individuals' with triglyceride levels above 880, or above 500, with a history of acute pancreatitis.

Pending approval, we look forward to making this potential best in class prophylactic treatment available to people living with HIV.

Beyond its approved use in FCS all of <unk> and is also being evaluated for the treatment of severe hypo triglyceride gaming or S. H T. G with three separate phase III studies supporting our planned NDA filing assuming positive data.

Kyle Jenne: With a significant first-mover advantage, we believe olzarsin is well-positioned to address the unmet needs of patients with severe hypertriglyceridemia. Our commercial team is making excellent progress as we prepare for a potential launch next year. Mani Foroohar, our second independent launch, has the potential to transform the treatment paradigm for individuals with HAE as the first and only RNA-targeted prophylactic medicine. More than 20,000 people in the US and in Europe are estimated to have HAE, with approximately 7,000 people in the US alone. In the US, most patients are currently on prophylactic treatment. However, many HAE patients remain unsatisfied, with up to 20% of patients switching therapies each year in search of a more effective and convenient option, highlighting a need for new treatments with enhanced profiles. We believe Mani Foroohar is uniquely positioned to meet this demand.

With a significant first mover advantage, we believe <unk> is well positioned to address the unmet needs of patients with severe hyper triglyceride EMEA.

Our commercial team is making excellent progress as we prepare for a potential launch next year.

Tanya Dolores and our second independent launch has the potential to transform the treatment paradigm for individuals with <unk> as the first and only RNA targeted prophylactic medicine.

May we reported topline results from the essence study, which will help satisfy the regulatory safety requirements for the broadest hcg population.

More than 20000 people in the U S and in Europe are estimated to have HCA with approximately 7000 people in the U S alone.

Essence, primarily enrolled patients with triglyceride levels between $1 50, and 500 milligrams per deciliter, a level of triglycerides that is generally not associated with high risk for acute pancreatitis.

In contrast, the core and core two studies exclusively enrolling <unk> patients.

Dissipates in these studies and triglycerides that were greater than 500 milligram per deciliter with approximately 43% of the participants across both studies with triglycerides greater than 880 milligram per deciliter at baseline.

Is uniquely positioned to meet this demand the.

Kyle Jenne: The Mani Foroohar clinical data have shown durable efficacy and favorable safety and tolerability profile with a patient-friendly monthly or every other month self-administration with an auto-injector. Importantly, as we prepare to bring Mani Foroohar to market, we are applying the same disciplined and innovative approach that has made the Tringolza launch a success. We have deployed our field team, who are educating and preparing the market for the anticipated approval of Mani Foroohar, and are energized to successfully execute the launch. Meanwhile, our market access team is actively engaging with payers, and our field medical team continues to lay the essential groundwork to ensure a smooth and successful launch. Our experience and scalable commercial organization is already delivering excellent results, supported by the early success seen with the launch of Tringolza and FCS.

<unk> and clinical data have shown durable efficacy and favorable safety and tolerability profile with a patient friendly monthly or every other month self administration with an auto injector.

Glyceride at this level put people at high risk for acute pancreatitis.

Importantly, as we prepare to bring <unk> into market. We are applying the same disciplined and innovative approach.

The essence study met its primary endpoint showing statistically significant placebo adjusted mean reductions in triglyceride levels of 61% and 58% at six months with the 80% and 50 milligram monthly dosing respectively.

And the vast majority of participants and chief triglyceride levels below 150 milligram per deciliter, thus, reaching the normal range.

Meanwhile, our market access team is actively engaging with payers and our field medical team continues to lay the central groundwork to ensure a smooth and successful launch.

<unk> also met all key secondary endpoints and demonstrated a favorable safety and Tolerability profile.

Our experienced and scalable commercial organization is already delivering excellent results supported by the early success seen with the launch of <unk> in Fcs.

The results from this study were recently accepted as a hotline session at the ESC Congress 2025, we look forward to sharing additional details from this study then.

Kyle Jenne: As we build on this momentum, we remain focused on maximizing Tringolza's full potential while preparing to successfully execute three additional launches by the end of next year, including Mani Foroohar in the coming weeks, enabling Ionis to reach more people in need with our medicines. With that, I'll now turn it over to Richard.

As we build on this momentum we remain focused on maximizing <unk> full potential while preparing to successfully execute three additional launches by the end of next year, including <unk> in the coming weeks, enabling island us to reach more people in need with our medicines with that I'll now turn it over to Richard.

Now the phase III core and core two studies have enrolled approximately 1100 participants, making this pivotal program the largest ever conducted an S. H T G.

These studies remain on track with topline results expected in September.

Thank you Kyle.

Richard Geary: Thank you, Kyle. We are making excellent progress across our pipeline, positioning Ionis to deliver on our mission of bringing transformational medicines to patients for years to come. Let me start with recent updates from our wholly owned pipeline. As a reminder, Mani Foroohar is currently under regulatory review in both the US and EU, with submissions supported by its robust clinical data. We remain confident in the August 21st fiduciary date, based on the engagement we've had with the FDA at this stage in the process. Pending approval, we look forward to making this potential best-in-class prophylactic treatment available to people living with HAE. Beyond its approved use in FCS, olzarsin is also being evaluated for the treatment of severe hypertriglyceridemia, or SHTG, with three separate phase three studies supporting our planned SNDA filing, assuming positive data.

We are making excellent progress across our pipeline positioning I on us to deliver on our mission of bringing transformational medicines to patients for years to come.

We believe this indication represents a significant opportunity as many <unk> patients are unable to adequately manage their drag glyceride with current therapies physician.

Let me start with the recent updates from our wholly owned pipeline.

Physician feedback continues to highlight strong interest in more effective treatment options for managing triglyceride levels.

As a reminder, Dana Dorsen is currently under regulatory review in both the U S and EU with submission supported by its robust clinical data.

Underscoring the potential value of <unk> in this population.

We remain confident in the August 21, <unk> date based on the engagement we've had with the FDA at this stage in the process spending.

Importantly, this feedback indicates that physicians understand that lowering triglycerides will reduce the risk of acute pancreatitis.

Pending approval, we look forward to making this potential best in class prophylactic treatment available to people living with HIV.

And that they would prescribe <unk> if approved based solely on its ability to substantially lower triglycerides.

Yes.

Beyond its approved use in FCS all of <unk> and is also being evaluated for the treatment of severe hypo <unk> or S. H T. G with three separate phase three studies supporting our planned NDA filing assuming positive data.

Although the core and core two studies were not designed as AP outcome studies.

We are seeing acute pancreatitis events on a blinded basis.

As a result, we expect to have accumulated more combined pancreatitis events for core and core too than we had in the FCS balanced study.

Richard Geary: In May, we reported top-line results from the ESSENCE study, which will help satisfy the regulatory safety requirements for the broad SHTG population. ESSENCE primarily enrolled patients with triglyceride levels between 150 and 500 milligrams per deciliter, a level of triglycerides that is generally not associated with high risk for acute pancreatitis. In contrast, the CORE and CORE2 studies exclusively enrolled SHTG patients. Participants in these studies had triglycerides that were greater than 500 milligrams per deciliter, with approximately 43% of the participants across both studies with triglycerides greater than 880 milligrams per deciliter at baseline. Triglycerides at this level put people at high risk for acute pancreatitis. The ESSENCE study met its primary endpoint, showing statistically significant placebo-adjusted mean reductions in triglyceride levels of 61% and 58% at six months with the 80 and 50 milligram monthly dosing, respectively.

May we reported topline results from the essence study, which will help satisfy the regulatory safety requirements for the broadest hcg population.

This gives us confidence we could have sufficient data to observe at least a favorable trend in <unk> impact on AP within the studies.

Turning our attention to <unk>.

Our medicine to treat Alexander disease, an ultra rare Luca dystrophy that profoundly impact patients and families who today have no approved disease modifying treatments.

In contrast, the core and core two studies exclusively enrolling <unk> patients.

The phase III study remains on track and we're looking forward to sharing data later this year.

Dissipates in these studies triglycerides that were greater than 500 milligram per deciliter with approximately 43% of the participants across both studies with triglycerides greater than 880 milligram per deciliter at baseline.

Given the ultra rare nature of this disease, we implemented an innovative clinical development strategy for <unk> using a seamless phase one to phase III study design.

This is the first study of a disease modifying therapy ever conducted in this patient group.

Glyceride at this level put people at high risk for acute pancreatitis.

Now while this approach allows us to move efficiently toward a potential registration enabling study.

It also means that the upcoming readout will represent the first clinical data in patients with Alexander disease.

As such there is a higher degree of uncertainty associated with this readout compared to other medicines, we're advancing in late stage development.

And the vast majority of participants achieve triglyceride levels below 150 milligram per deciliter, thus, reaching the normal range.

Richard Geary: The vast majority of participants achieved triglyceride levels below 150 milligrams per deciliter, thus reaching the normal range. Olzarsin also met all key secondary endpoints and demonstrated a favorable safety and tolerability profile. The results from this study were recently accepted as a hotline session at the ESC Congress 2025. We look forward to sharing additional details from the study then. Now, the phase three CORE and CORE2 studies have enrolled approximately 1,100 participants, making this pivotal program the largest ever conducted in SHTG. These studies remain on track, with top-line results expected in September. We believe this indication represents a significant opportunity, as many SHTG patients are unable to adequately manage their triglycerides with current therapies. Physician feedback continues to highlight strong interest in more effective treatment options for managing triglyceride levels, underscoring the potential value of olzarsin in this population.

Assuming positive data and approval <unk> would represent the first of what we expect to be many more independent launches from our leading neurology pipeline.

<unk> also met all key secondary endpoints and demonstrated a favorable safety and Tolerability profile.

Ion five to eight two and investigational medicine for the treatment of people living with Angelman syndrome.

The results from this study were recently accepted as a hotline session at the ESC Congress 2025, we look forward to sharing additional details from this study then.

As the newest addition to our late stage pipeline and human syndrome is a serious and rare neurodevelopmental disorder that leads to significant and lifelong physical and cognitive impairments and.

Now the phase III core and core two studies have enrolled approximately 1100 participants, making this pivotal program the largest ever conducted an S. H T G.

And impacts tens of thousands of people living with this disorder.

Supported by the Phase <unk> open label Halo study results, we recently dosed the first patient in the global Phase III reveal study.

These studies remain on track with topline results expected in September.

We believe this indication represents a significant opportunity as many <unk> patients who are unable to adequately manage their triglycerides with current therapies physician.

We plan to have this study fully enrolled next year.

Turning to our partnered programs, we are pleased that higher dose new centers.

Physician feedback continues to highlight strong interest in more effective treatment options for managing triglyceride levels.

Is one step closer to market with FDA and EMA regulatory submissions under review.

Underscoring the potential value of <unk> in this population.

With a well characterized profile of spin Roswell.

Established over the past 10 years.

Importantly, this feedback indicates that physicians understand that lowering triglycerides will reduce the risk of acute pancreatitis.

Richard Geary: Importantly, this feedback indicates that physicians understand that lowering triglycerides will reduce the risk of acute pancreatitis and that they would prescribe olzarsin if approved, based solely on its ability to substantially lower triglycerides. Although the CORE and CORE2 studies were not designed as AP outcome studies, we are seeing acute pancreatitis events on a blinded basis. As a result, we expect to have accumulated more combined pancreatitis events for CORE and CORE2 than we had in the FCS balance study. This gives us confidence we could have sufficient data to observe at least a favorable trend in olzarsin's impact on AP within the studies. Turning our attention to zilganersin, our medicine to treat Alexander disease, an ultra-rare leukodystrophy that profoundly impacts patients and families who today have no approved disease-modifying treatments. The phase three study remains on track, and we're looking forward to sharing data later this year.

10, plus years and the positive data from higher dose spin Raso, we believe spin Ross is well positioned to continue to bring benefit to SMA patients around the world.

And that they would prescribe <unk> if approved based solely on its ability to substantially lower triglycerides.

Our partner Biogen also recently shared positive top line interim results from the phase one study of cylinders and investigational antisense medicine being developed for the potential treatment of spinal muscular atrophy.

Although the core and core two studies were not designed as AP outcome studies we.

We are seeing acute pancreatitis events on a blinded basis.

As a result, we expect to have accumulated more combined pancreatitis events for core and core too than we had in the FCS balance study.

Leveraging the same mechanism of action as spin Rozzer, we designed <unk> with novel lie on this chemistry.

To achieve strong efficacy and once yearly dosing.

This gives us confidence we could have sufficient data to observe at least a favorable trend in all of the <unk> impact on AP within the studies.

And children previously treated with gene therapy once yearly dosing with both the 40 and 80 milligram doses.

Turning our attention to <unk>.

Were well tolerated and led to rapid and substantial slowing of neuro degeneration as shown by reductions in neuro supplement.

Our medicine to treat Alexander disease, an ultra rare Luca dystrophy that profoundly impact patients and families who today have no approved disease modifying treatments.

Exploratory clinical outcome data also showed that children in the study achieved meaningful improvements in function and attain new milestones.

The phase III study remains on track and we're looking forward to sharing data later this year.

Given the ultra rare nature of this disease, we implemented an innovative clinical development strategy for Brazil, Gunnerson using a seamless phase one to phase III study design.

Richard Geary: Given the ultra-rare nature of this disease, we implemented an innovative clinical development strategy for zilganersin, using a seamless phase one to phase three study design. This is the first study of a disease-modifying therapy ever conducted in this patient group. Now, while this approach allows us to move efficiently toward a potential registration-enabling study, it also means that the upcoming readout will represent the first clinical data in patients with Alexander disease. As such, there is a higher degree of uncertainty associated with this readout compared to other medicines we're advancing in late-stage development. Assuming positive data and approval, zilganersin would represent the first of what we expect to be many more independent launches from our leading neurology pipeline. Ion 582, an investigational medicine for the treatment of people living with Angelman syndrome, is the newest addition to our late-stage pipeline.

Biogen is actively engaging with regulatory agency to align on the phase III study design, notably the initiation of a phase III study would trigger a $45 million milestone payment to <unk>. Additionally, our royalty rates for <unk> are significantly higher than for spinner Asa.

This is the first study of a disease modifying therapy ever conducted in this patient group.

While this approach allows us to move efficiently toward a potential registration enabling study.

If approved <unk> would also substantially extend the lifecycle for the ion is Biogen SMA franchise.

It also means that the upcoming REIT readout will represent the first clinical data in patients with Alexander disease.

The progress of this program underscores <unk> deep expertise and oligonucleotide medicinal chemistry.

As such there is a higher degree of uncertainty associated with this readout compared to other medicines, we're advancing in late stage development.

And reinforces the strength of our broader neurology pipeline. It also validates our approach as we advance new medicines with next generation Chemistries <unk>.

Assuming positive data and approval Silga nursing would represent the first of what we expect to be many more independent launches from our leading neurology pipeline.

Including follow on medicines for our wholly owned programs.

I'm on slide eight <unk>, an investigational medicine for the treatment of people living with Angelman syndrome.

With multiple data Readouts and regulatory milestones expected this year and next our advancing pipeline underscores the strength of our science and our commitment to addressing serious diseases with that I'll turn it over to Pat.

As the newest addition to our late stage pipeline Angelman syndrome is a serious and rare neurodevelopmental disorder that leads to significant and lifelong physical and cognitive impairments and.

Richard Geary: Angelman syndrome is a serious and rare neurodevelopmental disorder that leads to significant and lifelong physical and cognitive impairments and impacts tens of thousands of people living with this disorder. Supported by the phase one to open-label HALOS study results, we recently dosed the first patient in the global phase three REVEAL study. We plan to have this study fully enrolled next year. Turning to our partnered programs, we are pleased that higher-dose nucinercin is one step closer to market, with FDA and EMA regulatory submissions under review. With the well-characterized profile of Spinraza, established over the past 10 years, 10 plus years, and the positive data from higher-dose Spinraza, we believe Spinraza is well-positioned to continue to bring benefit to SMA patients around the world.

Thank you Richard.

I am pleased to report that for the second time. This year, we are significantly raising at 2025 financial guidance.

And impacts tens of thousands of people living with this disorder.

Supported by the Phase <unk> open label Halo study results, we recently dosed the first patient in the global Phase III reveal study.

This time driven by strong revenue performance to date, including the early launch success of <unk> and an improved outlook for the year.

We plan to have this study fully enrolled next year.

In the second quarter, we earned revenue of $452 million, a two fold increase year over year.

Turning to our partnered programs, we are pleased that higher dose new centers.

$584 million for the first six months of 2025.

Is one step closer to market with FDA and EMA regulatory submissions under review.

An increase of nearly 70% versus prior year.

With a well characterized profile of spin raso.

Strong second quarter revenue. We earned also enabled us to generate $154 million and non-GAAP net income for the quarter.

Established over the past 10 years.

10, plus years and the positive data from higher dose spin Raso, we believe spin Ross is well positioned to continue to bring benefit to SMA patients around the world.

As you heard from Kyle to early to Ingalls Alliance continues to perform well we are $19 million in product sales, representing a threefold increase over the first quarter.

Richard Geary: Our partner, Biogen, also recently shared positive top-line interim results from the phase one study of Salveen Richter, an investigational antisense medicine being developed for the potential treatment of spinal muscular atrophy. Leveraging the same mechanism of action as Spinraza, we designed Salveen Richter with novel Ionis chemistry to achieve strong efficacy and once-yearly dosing. In children previously treated with gene therapy, once-yearly dosing with both the 40 and 80 milligram doses were well tolerated and led to rapid and substantial slowing of neurodegeneration, as shown by reductions in neurofilament. Exploratory clinical outcome data also showed that children in the study achieved meaningful improvements in function and attained new milestones. Biogen is actively engaging with regulatory agency to align on the phase three study design. Notably, the initiation of a phase three study would trigger a $45 million milestone payment to Ionis.

Our partner Biogen also recently shared positive top line interim results from the phase one study of cylinders.

Royalty revenues increased by approximately 10% to $70 million in the second quarter anchored by meaningful contributions from both Cinryze and <unk>.

An investigational antisense medicine being developed for the potential treatment of spinal muscular atrophy.

Leveraging the same mechanism of action as spin Rozzer, we designed <unk> with novel I honest chemistry.

We also generated substantial revenue from our R&D collaborations, including the $280 million upfront payment for the <unk> license a medicine outside of our core areas of focus.

To achieve strong efficacy and once yearly dosing.

And children previously treated with gene therapy once yearly dosing with both the 40 and 80 milligram doses.

Nearly 100% of this revenue dropped directly to the bottom line underscoring the important financial contribution of our partnered pipeline.

Were well tolerated and led to rapid and substantial slowing of neuro degeneration.

Total non-GAAP operating expenses in the second quarter increased 8% year over year, highlighting our commitment to disciplined investment and driving operating leverage.

Shown by reductions in neuro supplement.

Exploratory clinical outcome data also showed that children in the study achieved meaningful improvements in function and obtain new milestones.

As planned our sales and marketing expenses increased year over year, driven by our investments in the U S launch of <unk>.

In preparation for the upcoming launch of <unk>.

Our SG&A expenses also included our minority portion of renewals and sales and marketing costs.

Richard Geary: Additionally, our royalty rates for Salveen Richter are significantly higher than for Spinraza. If approved, Salveen Richter would also substantially extend the lifecycle for the Ionis Biogen SMA franchise. The progress of this program underscores Ionis' deep expertise in oligonucleotide medicinal chemistry and reinforces the strength of our broader neurology pipeline. It also validates our approach as we advance new medicines with next-generation chemistries, including follow-on medicines for our wholly owned programs. With multiple data readouts and regulatory milestones expected this year and next, our advancing pipeline underscores the strength of our science and our commitment to addressing serious diseases. With that, I'll turn it over to Beth.

R&D expenses decreased year over year at several of our late stage studies have recently concluded.

If approved <unk> would also substantially extend the lifecycle for the ion is Biogen SMA franchise.

Importantly, we continued to strategically fund our advancing pipeline with more than two thirds of our total R&D expenses funding our late stage program.

The progress of this program underscores Iona has deep expertise in oligonucleotide medicinal chemistry.

Based on our continued execution across the board we have increased our revenue guidance range by $100 million and now expect to generate between 825 and $850 million in revenue this year.

And reinforces the strength of our broader neurology pipeline. It also validates our approach as we advance new medicines with next generation Chemistries, including follow on medicines for our wholly owned programs.

Accordingly, our improved revenue guidance is driving our improved operating loss and cash guidance for the year.

Our revenue guidance includes sizable commercial revenue supported by spin Master and the continued strong 10 calls the performance.

We expect to generate between 75 and $80 million entering calls in product sales this year.

Beth Hougen: Thank you, Richard. I'm pleased to report that for the second time this year, we are significantly raising our 2025 financial guidance, this time driven by strong revenue performance to date, including the early launch success of Tringolza and an improved outlook for the year. In the second quarter, we earned revenue of $452 million, a twofold increase year over year, and $584 million for the first six months of 2025, an increase of nearly 70% versus prior year. The strong second quarter revenue we earned also enabled us to generate $154 million in non-GAAP net income for the quarter. As you heard from Kyle, the early Tringolza launch continues to perform well. We earned $19 million in product sales, representing a threefold increase over the first quarter. Royalty revenues increased by approximately 10% to $70 million in the second quarter, anchored by meaningful contributions from both Spinraza and Wenua.

I am pleased to report that for the second time. This year, we are significantly raising our 2025 financial guidance.

We are also on track to add initial product revenue from our second lines with the FDA action date for <unk> and set for August 21st.

This time driven by strong revenue performance to date.

<unk> the early launch success of <unk> and an improved outlook for the year.

Given the timing of approval, we anticipate that <unk> will modestly contribute to revenue this year with a greater contribution next year.

In the second quarter, we earned revenue of $452 million, a two fold increase year over year and $584 million for the first six months of 2025.

We continue to project our full year 2025 operating expenses to increase in the high single digit percentage range compared to last year.

An increase of nearly 70% versus prior year. The strong second quarter revenue. We earned also enabled us to generate $154 million and non-GAAP net income for the quarter.

And by investments to support the success of our multiple ongoing and planned launch it.

With the increase to our revenue guidance, we now project, an operating loss of between 300 and $325 million.

As you heard from Kyle to early to Engulf Alliance continues to perform well.

And a year end cash balance of approximately $2 billion.

Our $19 million in product sales, representing a threefold increase over the first quarter.

Both substantially improved from our previous guidance and full year projected revenue is growing faster than projected operating expenses.

Royalty revenues increased by approximately 10% to $70 million in the second quarter.

The strength of our balance sheet reinforces our disciplined capital management.

Anchored by meaningful contributions from both Cinryze and <unk>.

<unk> enables us to continue to invest for growth.

We also generated substantial revenue from our R&D collaborations, including the $280 million upfront payment for the <unk> license a medicine outside of our core areas of focus.

Beth Hougen: We also generated substantial revenue from our R&D collaboration, including the $280 million upfront payment for the Sapagliersin license, a medicine outside of our core areas of focus. Nearly 100% of this revenue dropped directly to the bottom line, underscoring the important financial contributions of our partnered pipeline. Total non-GAAP operating expenses in the second quarter increased 8% year over year, highlighting our commitment to disciplined investment and driving operating leverage. As planned, our sales and marketing expenses increased year over year, driven by our investments in the US launch of Tringolza and preparations for the upcoming launch of Mani Foroohar. Our SG&A expenses also included our minority portion of Wenua's sales and marketing costs. R&D expenses decreased year over year, as several of our late-stage studies have recently concluded.

Maintaining the strength, we plan to refinance our 2026 convertible debt ahead of the maturity date.

As always we are rigorously evaluating a number of options against our objective to minimize cost of capital.

Nearly 100% of this revenue dropped directly to the bottom line underscoring the important financial contribution of our partnered pipeline.

Is there any of our cash to support our products and pipeline and maintain operational flexibility.

We have historically used convertible debt and believe it remains an attractive option for us.

Total non-GAAP operating expenses in the second quarter increased 8% year over year, highlighting our commitment to disciplined investment and driving operating leverage.

With multiple product launches ahead, a rich pipeline and continued disciplined investment we are well positioned to achieve significant revenue growth, resulting in sustained positive cash flow in the next few years.

As planned our sales and marketing expenses increased year over year.

Driven by our investments in the U S launch of <unk> and.

Positioning <unk> for substantial value creation in both the near and longer term.

In preparation for the upcoming launch of <unk>.

Our SG&A expenses also included our minority portion of we knew as sales and marketing costs.

With that I'll turn the call back over to Brad.

Thank you Beth.

In the second quarter marked another period of strong execution and momentum is the continued excellent performance of trim goes to highlight the strength of our commercial execution and the value of our innovative science and addressing serious unmet needs.

R&D expenses decreased year over year at several of our late stage studies have recently concluded.

Beth Hougen: Importantly, we continue to strategically fund our advancing pipeline, with more than two-thirds of our total R&D expenses funding our late-stage programs. Based on our continued execution across the board, we have increased our revenue guidance range by $100 million and now expect to generate between $825 and $850 million in revenue this year. Importantly, our improved revenue guidance is driving our improved operating loss and cash guidance for the year. Our revenue guidance includes sizable commercial revenue supported by Spinraza and the continued strong Tringolza performance. We expect to generate between $75 and $80 million in Tringolza product sales this year. We are also on track to add initial product revenue from our second launch with the FDA action date for Mani Foroohar set for August 21st. Given the timing of approval, we anticipate Mani Foroohar will modestly contribute to revenues this year, with a greater contribution next year.

Importantly, we continued to strategically fund our advancing pipeline with more than two thirds of our total R&D expenses funding our late stage program.

As we prepare for the potential approval and launch of Donegal, worrisome deepen advancing phase III pipeline, we are well positioned to deliver a steady cadence of independent and partnered launches over the next few years.

Based on our continued execution across the board, we have increased our revenue guidance range by $100 million.

These upcoming milestones reflect the significant progress, we're making towards delivering additional transformative medicines for people with serious diseases.

And now expect to generate between 825 and $850 million in revenue this year.

Building, a sustainable high growth company.

Accordingly, our improved revenue guidance is driving our improved operating loss and cash guidance for the year.

Before I conclude I'd like to provide two additional announcements.

Our revenue guidance includes sizable commercial revenue supported by spin Master and the continued strong cingal is the performance.

On October seven we will be hosting an innovation day in New York City to highlight our pipeline.

<unk> and our drug discovery capabilities and will provide additional insights into our ongoing and upcoming independent launches.

We expect to generate between 75 and $80 million interim goals of product sales this year.

We will provide additional information as the date gets closer for what we believe will be a highly informative event.

We are also on track to add initial product revenue from our second lines with the FDA action date for <unk> and set for August 21.

Additionally, we are eagerly awaiting results from the core and core two phase III studies in this hcg.

Given the timing of approval, we anticipate that <unk> will modestly contribute to revenue this year with a greater contribution next year.

Given that we expect to report the results of both studies at one time in September we will be initiating a quiet period, starting tomorrow July 31.

We continue to project our full year 2025 operating expenses to increase in the high single digit percentage range compared to last year.

Beth Hougen: We continue to project our full year 2025 operating expenses to increase in the high single-digit percentage range compared to last year, driven by investments to support the success of our multiple ongoing and planned launches. With the increase to our revenue guidance, we now project an operating loss between $300 and $325 million and a year-end cash balance of approximately $2 billion, both substantially improved from our previous guidance, as full-year projected revenue is growing faster than projected operating expenses. The strength of our balance sheet reinforces our disciplined capital management, which enables us to continue to invest for growth. To maintain this strength, we plan to refinance our 2026 convertible debt ahead of the maturity date. As always, we are rigorously evaluating a number of options against our objectives to minimize cost of capital, preserve our cash to support our products and pipeline, and maintain operational flexibility.

Our quiet period will be lifted upon data announcements and with that well.

Driven by investments to support the success of our multiple ongoing and planned launch it.

Ill now open it up for questions.

With the increase to our revenue guidance, we now project, an operating loss of between 300 and $325 million.

Okay.

Thank you.

And a year end cash balance of approximately $2 billion.

We will now begin the question and answer session.

Both substantially improved from our previous guidance and full year projected revenue is growing faster than projected operating expenses.

You ask a question Human Press Star then one on your telephone keypad.

If youre using a speakerphone please pick up your handset before pressing the keys.

The strength of our balance sheet reinforces our disciplined capital management, which enables us to continue to invest for growth.

If at any time your questions had been addressed and you would like to withdraw your question.

Please press Star then two.

Maintaining the strength, we plan to refinance our 2026 convertible debt ahead of the maturity date.

At this time, we will pause momentarily to assemble our roster.

Okay.

As always we are rigorously evaluating a number of options against our objective to minimize cost of capital.

Okay.

Is there any of our cash to support our products and pipeline and maintain operational flexibility.

Okay.

First question comes from Gary Nachman with Raymond James. Please go ahead.

We have historically used convertible debt and believe it remains an attractive option for us.

Beth Hougen: We have historically used convertible debt and believe it remains an attractive option for us. With multiple product launches ahead, a rich pipeline, and continued disciplined investment, we are well-positioned to achieve significant revenue growth, resulting in sustained positive cash flow in the next few years, positioning Ionis for substantial value creation in both the near and longer term. And with that, I'll turn the call back over to Brett.

Hi, guys and congrats on the strong quarter.

First just talk a bit more about how the chingola FCS launch is going in terms of finding these new patients and getting them through the reimbursement process and on drug.

So what gives you confidence, we'll see that strong sequential growth in the back half of the year based on the fiscal year guidance of $75 million to $80 million. So first of all a bit more on that.

Positioning <unk> for substantial value creation in both the near and longer term and with that I'll turn the call back over to Brett.

Thank you Beth.

Brett Monia: Thank you, Beth. The second quarter marked another period of strong execution and momentum for Ionis. The continued excellent performance of Tringolza highlights the strength of our commercial execution and the value of our innovative science in addressing serious unmet needs. As we prepare for the potential approval and launch of Mani Foroohar, and with a deep and advancing phase three pipeline, we are well-positioned to deliver a steady cadence of independent and partnered launches over the next few years. These upcoming milestones reflect the significant progress we're making toward delivering additional transformative medicines to people with serious diseases and building a sustainable, high-growth company. Before I conclude, I'd like to provide two additional announcements.

The second quarter marked another period of strong execution and momentum for Aon as we continued excellent performance of Trimble to highlight the strength of our commercial execution and the value of our innovative science addressing serious unmet needs.

And then on the upcoming FH TG readout in September just what.

Level of trig lowering are you expecting to see whether your power to see and what do you believe will be considered clinically meaningful in these patients that physicians want to see and it sounds like you're still confident there'll be enough pancreatitis events across both studies.

As we prepare for the potential approval and launch of <unk> and deepen advancing phase III pipeline, we are well positioned to deliver a steady cadence of independent and partnered launches over the next few years.

So a positive trend.

Do you think physicians need to see that to usage severe high triggs, maybe give us a sense of what youre hearing in the physician community on that.

These upcoming milestones reflect the significant progress, we're making toward delivering additional transformative medicines for people with serious diseases and building a sustainable high growth company.

Thanks, Gary Carl would you start with the FCS.

Before I conclude I'd like to provide two additional announcements on.

Launch and what we're expecting second half of the year, yes. Thanks, Gary So as we communicated we're really off to an encouraging start again with the FCS launch entering goals are for the first half of the year.

Brett Monia: On October 7th, we will be hosting an Innovation Day in New York City to highlight our pipeline, advancements in our drug discovery capabilities, and we'll provide additional insights into our ongoing and upcoming independent launches. We'll provide additional information as the day gets closer for what we believe will be a highly informative event. Additionally, we are eagerly awaiting results from the CORE and CORE2 phase three studies in SHTG. Given that we expect to report the results of both studies at one time in September, we will be initiating a quiet period starting tomorrow, July 31st. Our quiet period will be lifted upon data announcement, and with that, we'll now open it up for questions.

On October seven we will be hosting an innovation day in New York City to highlight our pipeline.

Advancements in our drug discovery capabilities and will provide additional insights into our ongoing and upcoming independent launches.

The $19 million in Q2, and a three fold increase over the previous quarter.

Really demonstrates the early momentum that we're very proud of the <unk>.

We will provide additional information as the date gets closer for what we believe will be highly informative event.

Profile first of all is playing through very effectively the reductions in.

Additionally, we are eagerly awaiting results from the core and core two phase III studies in this hcg.

<unk>.

In April <unk>, three reductions in triglycerides improvements in acute pancreatitis, a reduction in risk of acute pancreatitis and reductions in hospitalizations I mean, all of these things stack up very very favorably in terms of the receptivity.

Given that we expect to report the results of both studies at one time in September we will be initiating a quiet period, starting tomorrow July 31, our.

Our quiet period will be lifted upon data announced in with that.

<unk> golar in the FCS population.

In addition to that our very strong commercial strategy as I referenced.

We'll now open it up for questions.

Our customer facing team has over 3000 physicians that theyre interacting with currently our marketing and our omni channel capabilities, we're reaching greater than 30000, Hcp's right now with that education.

Thank you.

Operator: Thank you. We will now begin the question and answer session. To ask a question, you may press star, then one on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the keys. If at any time your questions have been addressed and you would like to withdraw your question, please press star, then two. At this time, we will pause momentarily to assemble our roster. First question comes from Gary Nachman with Raymond James. Please go ahead.

We will now begin the question and answer session.

When you ask a question Human Press Star then one on your telephone keypad.

And then you also asked about reimbursement access is going extremely well either clinically diagnosed or genetically confirmed patients are going through the process and getting reimbursement very quickly.

If youre using a speakerphone please pick up your handset before pressing the keys.

If at any time your questions have been addressed and you would like to withdraw your question.

<unk> out of pocket expenses greater than 90% of those patients are paying $0 out of pocket.

Please press Star then two.

At this time, we will pause momentarily to assemble our roster.

So overall, what we're seeing is very strong execution from a very strong.

Okay.

Program in terms of the second half the real focus is on additional patient identification and continuing to get those patients diagnosed and through the activities of our commercial team.

Yes.

Okay.

Customer facing and our omni channel and marketing capabilities, we have.

First question comes from getting a Crow with Raymond James. Please go ahead.

Expect that to continue but to continue to identify these upwards of 3000 patients that potentially have FCS is going to take some work and we expect that we will continue that growth throughout the rest of the year.

Hi, guys and congrats on the strong quarter.

Gary Nachman: Hi, guys, and congrats on the strong quarter. So first, just talk a bit more about how the Tringolza FCS launch is going in terms of finding these new patients and getting them through the reimbursement process and on drug. So what gives you confidence we'll see that strong sequential growth in the back half of the year based on the fiscal year guidance of 75 to 80 million? So first, a little bit more on that. And then on the upcoming SHTG readout in September, just what level of trig lowering are you expecting to see? You know, what are you powered to see and what do you believe will be considered clinically meaningful in these patients that physicians want to see? And it sounds like you're still confident there'll be enough pancreatitis events across both studies to show a positive trend.

First just talk a bit more about how the chingola FCS launch is going in terms of finding these new patients and getting them through the reimbursement process and on drug.

Thanks Kyle.

Gary the triglyceride.

<unk> that we're expecting U S H T G I.

So what gives you confidence, we'll see that strong sequential growth in the back half of the year based on the fiscal year guidance of $75 million to $80 million. So first of all a bit more on that.

It's probably going to be similar to what we saw in essence.

Where we saw 58% to 62% reduction based on the dose.

Fifth year versus 80 milligrams.

And then on the upcoming FH TG readout in September just what.

And what we know based on extensive work we've done.

The lipid specialists are the cardiologists endocrinologists that manage these patients what they are looking for or any substantial reductions in triglycerides on top of the treatments that are already giving their patients by Omega three.

Show a positive trend.

Gary Nachman: Do you think physicians need to see that to use it for severe high trigs? Maybe give us a sense of what you're hearing in the physician community on that.

Do you think physicians need to see that to usage severe high triggs, maybe give us a sense of what youre hearing in the physician community online.

Fatty acids or <unk>.

So theyre already recognize that these patients need to be treated and youre not getting much triglyceride lowering with existing treatments are the once that produces substantial lowering of triglycerides.

Thanks, Gary Carl would you start with the FCS.

Kyle Jenne: Thanks, Gary. Kyle, would you start with the FCS launch and what we're expecting the second half of the year?

Anything north of 50% is a big win.

In this patient population on top of standard of care that is what we expect.

Kyle Jenne: Yeah, thanks, Gary. So, as we communicated, we're really off to an encouraging start again with the FCS launch and Tringolza for the first half of the year. The $19 million in Q2 and a threefold increase over the previous quarter really demonstrates the early momentum that we're very proud of. The product profile, first of all, is playing through very effectively the reductions in APOCA3, reductions in triglycerides, improvements in acute pancreatitis, a reduction in risk of acute pancreatitis, and reductions in hospitalizations. I mean, all of these things stack up very, very favorably in terms of the receptivity for Tringolza in the FCS population. In addition to that, a very strong commercial strategy. As I referenced, our customer-facing team has over 3,000 physicians that they're interacting with currently. Our marketing and our omnichannel capabilities, we're reaching greater than 30,000 HCPs right now with that education.

With respect to AP events.

And what we're hearing from physicians with whom exactly what I just said.

The $19 million in Q2, and a three fold increase over the previous quarter.

Is that they do not need to be convinced that.

Substantial lowering that these patients are in harm's way for acute pancreatitis that can be fatal and we need to lower triglycerides substantially to get around that way they don't need to see the AP advanced.

It really demonstrates the early momentum that we're very proud of the <unk>.

Profile first of all is playing through very effectively the reductions in.

<unk>.

However, with that said, although the core on core two studies were not designed as AP outcome studies, we are seeing as Richard mentioned in his formal remarks, we are seeing on a blended basis Q pancreatitis events, and we expect to have more accumulated events.

<unk> gold and the FCS population.

And the combined core <unk> study than we had in the FCS balanced study. This gives us confidence we could have sufficient data to observe at least a favorable trend in <unk> impact on the AP within these studies and we look forward to discussing more when we read out the data in September.

In addition to that the very strong commercial strategy as I referenced.

Our customer facing team has over 3000 physicians that they are interacting with currently our marketing and our omnichannel capabilities, we're reaching greater than 30000, Hcp's right now with that education.

Okay great.

Kyle Jenne: And then you also asked about reimbursement. Access is going extremely well. Either clinically diagnosed or genetically confirmed patients are going through the process and getting reimbursement very quickly. Patient out-of-pocket expenses, you know, greater than 90% of those patients are paying $0 out of pocket. So overall, what we're seeing is very strong execution from a very strong program. In terms of the second half, the real focus is on additional patient identification and continuing to get those patients diagnosed. And through the activities of our commercial team, be it customer-facing and/or our omnichannel and marketing capabilities, you know, we expect that to continue. But to continue to identify these upwards of 3,000 patients that potentially have FCS is going to take some work, and we expect that we'll continue that growth throughout the rest of the year.

Just one quick one on <unk>.

Coming up on August 21st just Youre in labeling discussions so how you feel relative to your expectations.

Do you think the switch data will make it on there so it'll be once every month. Once every other month dosing that option will be available for patients and it sounds like youre ready to launch basically right. After approval. So just confirm everything is in place at all thanks.

<unk> out of pocket expenses greater than 90% of those patients are paying $0 out of pocket.

So overall, what we're seeing is very strong execution from a very strong.

Program in terms of the second half the real focus is on additional patient identification and continuing to get those patients diagnosed and through the activities of our commercial team.

I'll start this is Richard.

We're definitely on track for.

The <unk> date on August 21, everything that we've been discussing with FDA.

Be it customer facing <unk>, our omni channel and marketing capabilities, we have.

Expect that to continue but to continue to identify these upwards of 3000 patients that potentially have FCS is going to take some work and we expect that will continue that growth throughout the rest of the year.

Indicates that that data is on track.

And then.

I can't speak to the launch although everything looks to be in place and we're excited about it.

Thanks Kyle.

Brett Monia: Thanks, Kyle. Gary, the triglyceride lowering that we're expecting in SHTG, you know, is probably going to be similar to what we saw in ESSENCE, where we saw a 58 to 62% reduction based on the dose, 50 versus 80 milligrams. And what we know, based on extensive work we've done with the lipid specialists or the cardiologists or the endocrinologists that manage these patients, what they're looking for are any substantial reductions in triglycerides on top of the treatments they're already giving their patients like omega-3 fatty acids or fibrates. So they've already recognized that these patients need to be treated, and they're not getting much triglyceride lowering with existing treatments, so they want something to produce a substantial lowering of triglycerides. Anything more than 50% is a big win in this patient population on top of standard of care, and that is what we expect.

Gary the triglyceride.

I think your other question.

Lower.

We're expecting U S H T G I.

In regard to what we get in the label.

Probably going to be similar to what we saw in essence.

As a matter of negotiation it always is and so we work with the agency that's certainly been our position, let's get that in there, but we don't need it in the label because it is published and now that we have a publication and it's related to the work that was done in the clinical trials.

Where we saw 58% to 62% reduction based on the dose.

Fifth year versus 80 milligrams.

And what we know based on extensive work we've done.

The lipid specialists are the cardiologists with the endocrinologists that manage these patients what they are looking for or any substantial reductions in triglycerides on top of.

We have an opportunity to promote on that.

Maybe touch on the launch preparations.

The treatments that are already giving their patients great Omega three.

A launch readiness, we are building on the synergies from our FCS capabilities. Our medical affairs teams have been out interacting with allergists and Immunologists treating AAJ. Our sales team is now in place market access marketing patient support operations capabilities. So everything is ready.

Fatty acids or <unk>.

So theyre already recognize that these patients need to be treated and youre not getting much triglyceride lowering with existing treatments are they wants us to produce a substantial lowering of triglycerides.

Anything north of 50% is a big win.

In this patient population on top of standard of care that is what we expect.

Go in terms of launch readiness.

As Richard was describing.

With respect to AP events.

Brett Monia: With respect to AP events and what we're hearing from physicians, we're hearing exactly what I just said, is that they do not need to be convinced that the substantial lowering that these patients are in harm's way for acute pancreatitis that can be fatal and that you need to lower the triglycerides substantially to get them out of that way. They don't need to see the AP events. However, with that said, although the CORE and CORE2 studies were not designed as AP outcome studies, we are seeing, as Richard mentioned in his formal remarks, we are seeing on a blinded basis acute pancreatitis events, and we expect to have more accumulated AP events in the combined CORE and CORE2 study than we had in the FCS balance study.

The program from a regulatory standpoint.

What we're hearing from physicians for whom exactly what I. Just said is that they do not need to be convinced that.

The overall totality of the data here for <unk> is very very strong from an efficacy standpoint in terms of the durability and control of attacks on the tolerability using the easy to use self administered auto injector by the patient and.

Substantial lower that these patients are in harm's way for acute pancreatitis that can be fatal.

We need to lower triglycerides substantially to get around that way they don't need to see the AP events.

In convenience here, we have a program with the longest dosing interval.

With that said, although the core on core two studies were not designed as AP outcome studies, we are seeing as Richard mentioned.

Available potentially that will be available for patients living with HCA.

The formal remarks, we are seeing on a blended basis Q pancreatitis events.

The switch study is going to be helpful.

Obviously, the switch market in the United States. The majority of patients are on a prophylactic treatment today.

And we expect to have more accumulated <unk> events.

And the combined core on core two study than we had in the FCS balanced study. This gives us confidence we could have sufficient data to observe at least a favorable trend in <unk> impact on the AP within these studies and we look forward to discussing more when we read out the data from September.

And what we were able to demonstrate is that number one patients are willing to switch number two they can do so safely and move over to Donnie lorson or they can have an additional reduction of upwards of 62% improvement from baseline on an existing.

Brett Monia: This gives us confidence we could have sufficient data to observe at least a favorable trend in olzarsin's impact on AP within these studies, and we look forward to discussing more when we read out the data in September.

Okay great.

Prophylactic treatment.

Gary Nachman: Okay, great. And then just one quick one on Dani with the BDUFA coming up on August 21st. Just your enabling discussion, so how you feel relative to your expectations, you know, if you think the switch data will make it on there, if it'll be once every month and once every other month dosing, that option will be available for patients. And it sounds like you're ready to launch basically right after approval, so just confirm everything is in place for that. Thanks.

Just one quick one on Donnie with it coming up on August 21st just Youre in labeling discussions so how you feel relative to your expectations.

And 84% of the patients said that they prefer <unk> over the existing treatment that they were on once they were switched so the totality of the data combined with the timing of the launch here upcoming hopefully on August 21, we'll be ready to go.

Do you think the switch data will make it on there so it'll be once every month. Once every other month dosing that option will be available for patients and it sounds like you are ready to launch basically right after approval.

Thanks Carl.

Great. Thanks for all that color.

Thanks, Gary.

Yes.

Everything is in place for that thanks.

The next question is from the line of <unk> from Wells Fargo Securities. Please go ahead.

Richard Geary: Now, I'll start. This is Richard. We're definitely on track for the BDUFA date on August 21st. Everything that we've been discussing with FDA indicates that that date is on track. And then I can't speak to the launch, although everything looks to be in place, and we're excited about it. I think your other question in regard to what we get in the label is a matter of negotiation. It always is. And so we work with the agency. That's certainly been our position. Let's get that in there. But we don't need it in the label because it is published. And now that we have a publication and it's related to the work that was done in the clinical trials, we have an opportunity to promote on that.

I'll start this is Richard.

We're definitely on track for.

Oh, great. Thanks for taking our questions and congrats on a very strong quarter.

The <unk> date on August 21, everything that we've been discussing with FDA.

Perhaps.

Our first question about.

Core and core too.

Indicates that that data is on track.

So I think I heard.

And then.

In our prepared remarks that the cumulative AP.

I can't speak to the launch although everything looks to be in place and we're excited about it.

Right on a blinded basis.

He is now above what you saw in FCS. So I just want to confirm it seems like in the balance study you had 13 events across 66 patients.

I think.

Your other question.

In regard to what we get in the label.

And just wanted to get a sense of.

The core on core to <unk>.

Cross a thousand plus patients.

When you think.

How about a rate above that and could you also give us a sense of that.

We have an opportunity to promote on that.

Based on our core core to patient profile.

What is the expected AP right.

And Carl maybe you could touch on the launch preparations.

Brett Monia: Kyle, maybe touch on the launch preparations.

Kyle Jenne: In terms of launch readiness, we're building on the synergies from our FCS capabilities. Our medical affairs teams have been out interacting with allergists and immunologists treating HAE. Our sales team is now in place, market access, marketing, patient support, operations capabilities. So everything is ready to go in terms of launch readiness. As Richard was describing the program from a regulatory standpoint, the overall totality of the data here for Mani Foroohar is very, very strong from an efficacy standpoint in terms of the durability and control of attacks, the tolerability using the easy-to-use, self-administered auto-injector by the patient, and convenience. Here we have a program with the longest dosing interval available, potentially that will be available for patients living with HAE. The switch study is going to be helpful. This obviously is a switch market in the United States.

In untreated population like that so that we can.

In terms of launch readiness, we are building on the synergies from our FCS capabilities. Our medical affairs teams have been out interacting with allergists and Immunologists treating H E R.

Help us prepare for the data and the AP data.

A follow up on the SCS.

FH TD launch dynamic.

Our sales team is now in place.

Thanks.

<unk> access marketing patient support operations capabilities. So everything is ready to go in terms of launch readiness.

Yeah.

So.

You said.

The rate is higher it's about the right rate is lower of course in this ACG I think thats, what you knew that.

As Richard was describing the program from regulatory standpoint.

We're talking about is the accumulated number of events in the core and core two studies combined.

The overall totality of the data here for for <unk> is very very strong from an efficacy standpoint in terms of the durability and control of attacks.

And I can confirm that there'll be more events in who are core to combine.

Tolerability using the easy to use self administered auto injector by the patient.

And in our FCS balance study.

As far as what we think E&P I mean, we don't really know what the rate is this study will.

And convenience here, we have a program with the longest dosing interval.

First actually.

Available or potentially that will be available for all patients living with HIV.

Really definitive we provide information on what the event rate is.

The switch study is going to be helpful.

<unk> Eugene.

Alright, no outcome data.

Obviously, the switch market in the United States. The majority of patients are on a prophylactic treatment today.

Kyle Jenne: The majority of patients are on a prophylactic treatment today. And what we were able to demonstrate is that, number one, patients are willing to switch. Number two, they can do so safely and move over to Mani Foroohar. They can have an additional reduction of upwards of 62% improvement from baseline on an existing prophylactic treatment. And 84% of the patients said that they preferred Mani Foroohar over the existing treatment that they were on once they were switched. So the totality of the data, combined with the timing of the launch here upcoming, hopefully on August 21st, will be ready to go.

Four.

Four months.

We are waiting.

And what we were able to demonstrate is that number one patients are willing to switch number two they can do so safely and move over to Danny to lorson or they can have an additional reduction of upwards of 62% improvement from baseline on an existing.

Recurring core to readout.

Hello.

Got it got it thanks and on the FCS launch and potentially.

Later launch.

H T G.

Prophylactic treatment.

Congrats on a very strong second quarter of launch.

Yes.

It feels like.

The opportunity in STS is actually pretty sizable.

Given this.

Thanks Carl.

Brett Monia: Thanks, Kyle.

Momentum.

Richard Geary: Great. Thanks for all that, Kyle.

Great. Thanks for all that color.

Can you talk about is this.

Brett Monia: Thanks, Gary.

Thanks, Gary.

Yes.

Opportunity.

Relative to your anticipation is it <unk>.

The next question is from the line of <unk> from Wells Fargo Securities. Please go ahead.

Operator: The next question is on the line of Ionis Zhu from Wells Fargo Securities. Please go ahead.

<unk> are in line and more importantly.

As we think about <unk> going into S. H T G with a much.

Oh, great. Thanks for taking my question and congrats on a very strong quarter.

Yanan Zhu: Oh, great. Thanks for taking our questions and congrats on a very strong quarter. Perhaps a first question about CORE and CORE2. So I think I heard in the prepared remarks that the cumulative AP event rate on a blinded basis is now above what you saw in FCS. So I just want to confirm, it seems like in the balance study, you had 13 events across 66 patients. And I just wanted to get a sense of in the CORE and CORE2, it was across 1,000 plus patients. Are we thinking about the rate above that?

A reduction in the pricing.

<unk>.

Our first question about.

Presumably across the board for both indications.

Core and core too.

So I think I heard.

Any strategy to protect the F C S.

In our prepared remarks that the cumulative AP.

Opportunity.

In terms of the timing of launch and also any way to manage the pricing change.

Right.

I ended basis.

Is now above what you saw in FCS. So I just want to confirm it seems like in the balance study you had 13 events across 66 patients.

That would be super helpful. Thank you.

Yes, let me first talk about the FCS population that you described.

I still believe that its representatives up to 3000 potential patients.

Just wanted to get a sense of.

Core on core was across 1000 plus patients.

Phil early innings. The majority of these patients still are not diagnosed.

When you think thinking.

Obviously.

Thinking about the rate above that and could you also give us a sense that.

Several hundred patients have either participated in a clinical trial or waiting for a medication because they had been previously diagnosed and needed a treatment.

Yanan Zhu: And could you also give us a sense that based on the CORE and CORE2 patient profile, what is the expected AP rate in an untreated population like that so that we can help us prepare for the data and the AP data and as a follow-up on the FCS and SHTG launch dynamic? Thanks.

Based on our core core to patient profile.

What is the expected <unk>.

First mover advantage here is very important not only in FCS, but also S hcg.

Right.

In untreated population like that.

Help us prepare for the data and the AP data.

So our work for the first half of this year was to convert our clinical trial patients, which we did effectively.

A follow up on the <unk>.

Yes.

To help those patients that were previously identified with FCS to go onto treatment.

And <unk> launch.

<unk>.

Thanks.

Yeah.

And then to continue to expand our patient identification efforts.

Brett Monia: Yeah, and then so you said the rate is higher. It's not the rate. The rate is lower, of course, in SHTG. I think that's what you knew that. What we're talking about is the accumulated number of AP events in the CORE and CORE2 studies combined. And I can confirm that there'll be more events in CORE and CORE2 combined than in our FCS balance study. As far as what we think the AP, I mean, we don't really know what the AP rate is. This study will be the first to actually really definitively provide information on what the AP event rate is in SHTG. Ain't that right, Eugene?

No.

You said.

The rate is higher it's about the right rate is lower of course in this ACG I think thats, what you knew that.

We've been spending a lot of time on that as I referenced in terms of reaching greater than 3000 hcp's with our.

What we're talking about is the accumulated number of events in the core and core two studies combined.

With our sales team and reaching greater than 30000 hcp's through our education.

I can confirm that there'll be more events.

Related to our marketing and our Omnichannel efforts, so we're continuing to educate.

Quarter on quarter two combined.

Our Fcs balance study.

The time that we're spending on FCS specifically is with physicians that are treating <unk> patients.

As far as what we think E&P I mean, we don't really know what the rate is this study will.

<unk> will be the first actually.

And so what we're doing is having conversations around the implications of high triglycerides and how these patients present and ultimately looking for a phenotype of in FCS patients in order to either clinically diagnosed them or get a genetic confirmation of their disease.

Really definitively provides information on what the AAP event rate is.

<unk> Eugene.

Eugene Schneider: No, absolutely right. There's no outcome data. We're eagerly awaiting the CORE and CORE2 readout.

So there is no outcome data.

Four.

Four months.

We are waiting.

Recurring core to readout.

So that work is ongoing and Thats, what we will need to do through the second half of this year.

Hello.

Got it got it yes, yes.

Yanan Zhu: Got it. Got it. Yeah, yeah. Thanks. And on the FCS launch and potentially the later launch of SHTG, congrats on a very strong second quarter of launch in FCS. It feels like the opportunity in FCS is actually pretty sizable given this momentum. You know, can you talk about is this opportunity relative to your anticipation? Is it bigger or in line? And more importantly, as we think about you going into SHTG with a much reduction in the pricing, presumably across the board for both indications, any strategy to protect the FCS opportunity in terms of timing of launch and also any way to manage the pricing change? That would be super helpful. Thank you.

We've provided the guidance of $75 million to $80 million this year, which represents not only the patients that we've converted already in the first half, but the ongoing efforts that we believe will be successful with through the second half of this year. So.

Thanks, and on the FCS launch and potentially.

Later launch.

H T G.

Congrats on a very strong second quarter of launch.

Yes.

So I believe that the FCS population is in line with the up to 3000 that we've represented up to this point.

It feels like.

The opportunity in STS is actually pretty sizable.

As it relates to S. H T G.

Given this.

This is a much broader patient population, obviously and the treating physician population is much more significant.

Momentum.

Can you talk about it.

Is this.

Opportunity.

Relative to your anticipation is it big.

Greater than 1 million patients have.

High risk <unk>, which is inclusive obviously of patients over 500 with a history of AP or patients over 880 milligrams.

<unk> are in line and more importantly.

As we think about <unk> going into <unk> with a much.

Milligrams per deciliter. So there is a lot of effort already around education in this population and in working to identify these potential patients within these practices as we go out and have these interactions.

Reduction in the pricing.

Presumably across the board for both indications.

Any strategy to protect the F C S.

<unk>.

In terms of timing of launch and also any way to manage the pricing change.

As it relates to the pricing dynamic.

We're still working through that there is more work for us to understand in terms of the data, which we are still waiting for and then we will work obviously with the payer community to understand the.

That would be super helpful. Thank you.

Yes, let me first talk about the FCS population that you described.

Kyle Jenne: Yeah, let me first talk about the FCS population that you described. I still believe that it's represented as up to 3,000 potential patients. It's still early inning. The majority of these patients still are not diagnosed. Obviously, you know, several hundred patients have either participated in a clinical trial or were waiting for a medication because they had been previously diagnosed and needed a treatment. First-mover advantage here is very important, not only in FCS but also in SHTG. So our work for the first half of this year was to convert our clinical trial patients, which we did effectively, to help those patients that were previously identified with FCS to go on to treatment and then to continue to expand our patient identification efforts.

The budget impact of the patient population their interpretation of the data and obviously the value of that that represents to patients. So that's the work that we will do going into next year and ultimately we will announce price upon the approval of the <unk> indication pending positive outcome there.

I still believe that its representatives up to 3000 potential patients. It is still early innings. The majority of these patients still are not diagnosed.

Obviously.

Several 100 patients have either participated in a clinical trial or waiting for a medication because they had been previously diagnosed and needed a treatment.

Great. Thanks for the color and congrats on the quarter again.

First mover advantage here is very important not only in FCS, but also S hcg.

Thank you.

Thank you. The next question is from the line of Steven Idaho from TD Securities. Please go ahead.

So our work for the first half of this year was to convert our clinical trial patients, which we did effectively.

Hi, everyone. This is Stephen <unk> on for your own Werber, Congrats again on a fantastic quarter.

To help those patients that were previously identified with FCS to go onto treatment.

One more on Dani and on competition, specifically it looks like tax iroh revenues are stable and or the Dio seems to be growing any visibility also as well on the <unk> launch, which was approved on June 16th obviously that drug has a couple of disadvantages.

And then to continue to expand our patient identification efforts.

Kyle Jenne: We've been spending a lot of time on that, as I referenced, in terms of reaching greater than 3,000 HCPs with our sales team and reaching greater than 30,000 HCPs through our education, you know, related to our marketing and our omnichannel efforts. So we're continuing to educate. The time that we're spending on FCS specifically is with physicians that are treating SHTG patients. And so what we're doing is having conversations around the implications of high triglycerides and how these patients present and ultimately looking for a phenotype of an FCS patient in order to either clinically diagnose them or get a genetic confirmation of their disease. So that work is ongoing, and that's what we'll need to do through the second half of this year.

We've been spending a lot of time on that as I referenced in terms of reaching greater than 3000 hcp's with our.

With our sales team and reaching greater than 30000 hcp's through our education.

<unk> monthly dosing versus your two months and also requiring a loading dose, which donnie does not any.

Related to our marketing and our Omnichannel efforts, so we're continuing to educate.

Visibility on their competition and maybe insights from there on what the dawn of <unk> launch could look like thanks.

The time that we're spending on FCS specifically as with physicians that are treating <unk> patients.

Yes, I'd be happy to talk about that this is Kyle.

I think what we know in this marketplace and whats come through very clear is that patients on existing prophylactic treatments are not completely satisfied and that they would be willing to switch to a new therapy.

Recent Harris poll said that greater than 90% of patients actually wood.

So that work is ongoing and Thats, what we will need to do through the second half of this year.

We'd look to switch to into an improved therapy, and I think youre seeing that play out with the newly approved treatment already and we would expect to see the same from.

Kyle Jenne: You know, we've provided the guidance of $75 to $80 million this year, which represents not only the patients that we've converted already in the first half, but the ongoing efforts that we believe we'll be successful with through the second half of this year. So I believe that the FCS population is in line with the up to 3,000 that we've represented up to this point. As it relates to SHTG, this is a much broader patient population. Obviously, in the treating physician population, it is much more significant. Greater than a million patients have high-risk SHTG, which is inclusive, obviously, of patients over 500 with a history of AP or patients over 880 milligrams per deciliter. So there's a lot of effort already around education in this population and working to identify these potential patients within these practices as we go out and have these interactions.

Johnny <unk>.

The profile overall with dining <unk> is very strong as I mentioned not only the efficacy data, but also the ability for patients to self administer as you pointed out.

So I believe that the FCS population is in line with the up to 3000 that we've represented up to this point.

This therapy is going to be potentially prescribed it every four weeks or every eight weeks, depending upon how patients present.

As it relates to S. H T G.

This is a much broader patient population, obviously and the treating physician population is much more significant.

And then how stable they are with their disease. So that is again another key differentiator here.

And then finally I'll just mention the switch study I mean, what we have demonstrated is that patients are willing to switch when they do so they can do so safely they have the potential to improve.

Greater than 1 million patients have.

High risk <unk>, which is inclusive obviously of patients over 500 with a history of AP or patients over 880 milligrams.

The control of their disease and ultimately when they have ended up on dotted alerts and they preferred it over the treatment that they were on before so I believe from from a competitive standpoint, we're in really good shape and we've got a great team. We've hired a sales organization that has experience in the allergy and immunology space, many of whom have direct experience.

As it relates to the pricing dynamic.

Kyle Jenne: As it relates to the pricing dynamic, we're still working through that. There's more work for us to understand in terms of the data, which we are still waiting for. And then we'll work, obviously, with the payer community to understand the budget impact of the patient population, their interpretation of the data, and obviously the value that that represents to patients. So that's the work that we will do going into next year, and ultimately, we will announce price upon the approval of the SHTG indication, pending positive outcome there.

For many years and they.

No the treating physicians and they've got.

Not only existing relationships, but they understand how to competitively sell so we're really excited about the upcoming launch potentially with the approval on August 21.

Thank you very much.

Thank you.

The next question is from the line of Mike <unk>.

With Morgan Stanley. Please go ahead.

Great. Thanks for the color and congrats on the quarter again.

Yanan Zhu: Great. Thanks for all the color. Congrats on the quarter again.

Great. Good afternoon, Thanks for taking the question and congratulations on the strong quarter as well.

Thank you.

Thank you. The next question is from the line of Steven Idle from TD Securities. Please go ahead.

Brett Monia: Thank you.

Maybe just a question on the phase III SSH TG core data previously you suggested data <unk>, you're narrowing that a little bit to September I guess first question just any what's the rationale there or anything behind that and then secondly.

Operator: Thank you. The next question is from the line of Steven Ironov from TD Securities. Please go ahead.

Hi, everyone. This is Stephen <unk> on for your own Werber, Congrats again on a fantastic quarter.

Brendon (for Andy Chen) / Steven Ironov (for Yaron Werber): Hey, everyone. This is Steven Ironov on for your own Werber. Congrats again on a fantastic quarter. One more on Dani and on competition specifically. It looks like Taxiro revenues are stable, and Orlido seems to be growing. Any visibility also as well on the Endeavor launch, which was approved on June 16th? Obviously, that drug has a couple of disadvantages, including monthly dosing versus Dani's two months and also requiring a loading dose, which Dani does not. Any visibility on the competition and maybe insights from there on what the Mani Foroohar launch could look like? Thanks.

One more on Dani and on competition, specifically it looks like tax iroh revenues are stable and Orla Dio seems to be growing any visibility also as well on the <unk> launch, which was approved on June 16th obviously that drug has a couple of disadvantages.

Last quarter, you suggested AP data might not be available in the topline release I guess, just maybe give us a sense of what level of data you plan to share in a topline release in December. Thanks.

Yeah.

Sure Mike.

<unk> monthly dosing versus your versus two months and also requiring a loading dose, which donnie does not any.

So.

Just refining the timeline to September from second half of the year is just blocking and tackling.

Visibility on their competition and insights from there on what the dawn of <unk> launch could look like thanks.

The studies completed database locked claims data cleaned and all that so we just felt it was appropriate to provide more growth more specificity.

Yes, I'd be happy to talk about that this is Kyle.

Kyle Jenne: Yeah, I'd be happy to talk about that. This is Kyle. I think what we know in this marketplace and what's come through very clear is that patients on existing prophylactic treatments are not completely satisfied and that they would be willing to switch to a new therapy. A recent Harris poll said that greater than 90% of patients actually would look to switch to an improved therapy. And I think you're seeing that play out with a newly approved treatment already. And we would expect to see the same from Mani Foroohar. The profile overall with Mani Foroohar is very strong, as I mentioned, not only the efficacy data, but also the ability for patients to self-administer. As you pointed out, this therapy is going to be potentially prescribed every four weeks or every eight weeks, depending upon how patients present and how stable they are with their disease.

On the exact timing so nothing nothing significant behind there.

Operational.

Inducting.

Ah studies.

We will provide a statement on <unk>.

Recent Harris poll said that greater than 90% of patients actually wood.

And our topline press release.

We'd look to switch to into an improved therapy, and I think youre seeing that play out with the newly approved treatment already and we would expect to see the same from.

Our primary endpoint in games is triglyceride lowering.

We will provide top line information triglycerides as well as safety.

Donald <unk>.

<unk> safety.

The profile overall with dining <unk> is very strong as I mentioned not only the efficacy data, but also the ability for patients to self administer as you pointed out.

And we'll provide statement on AP.

What's.

Also I think more important is that we will provide and present the full dataset.

This therapy is going to be potentially prescribed it every four weeks or every eight weeks, depending upon how patients present.

Full dataset.

Any medical Congress in the second half of this year.

And we look to publish the data.

And then how stable they are with their disease. So that is again another key differentiator here.

In the second half of this year.

Kyle Jenne: So that is, again, another key differentiator here. And then finally, I'll just mention the switch study. I mean, what we have demonstrated is that patients are willing to switch. When they do so, they can do so safely. They have the potential to improve the control of their disease. And ultimately, when they've ended up on Mani Foroohar, they've preferred it over the treatment that they were on before. So I believe from a competitive standpoint, we're in really good shape. And we've got a great team. We've hired a sales organization that has experience in the allergy and immunology space, many of whom have direct HAE experience for many years. And they know the treating physicians, and they've got not only existing relationships, but they understand how to competitively sell. So we're really excited about the upcoming launch, potentially with the approval on August 21st.

Very helpful. Thank you.

And then finally I'll just mention the switch study I mean, what we have demonstrated is that patients are willing to switch when they do so they can do so safely they have the potential to improve.

The next question is from the line of Andy Chen from vertical research. Please go ahead.

Hey, Brendan on for Andy.

On renewing polymer neuropathy, where do you think those patients are coming from do you think that there youre winning new.

The control of their disease and ultimately when they have ended up on <unk> and they preferred it over the treatment that they were on before so I believe from from a competitive standpoint, we're in really good shape and we've got a great team. We've hired a sales organization that has experience in the allergy and immunology space, many of whom have direct experience.

<unk>, new to brand share or stealing business from an island.

Going to provide any quantitative splits on those details that'd be great. Thank you.

I'd be happy to talk about that Brandon. Thanks. This is Kyle again.

For many years and.

First I'll just say we knew it continues to perform very well.

No the treating physicians and they've got.

Strong demand the polyneuropathy market as a growth market. The majority of these patients are not diagnosed yet and thats exactly where astrazeneca is spending the time is looking for and educating hcp's around hereditary polyneuropathy patients.

Not only existing relationships, but they understand how to competitively sell so we're really excited about the upcoming launch potentially with the approval on August 21.

Thank you very much.

Brendon (for Andy Chen) / Steven Ironov (for Yaron Werber): Thank you very much.

$44 million in Q2, which obviously was it was growth over Q1.

Thank you.

Operator: Thank you. The next question is on the line of Michael with Morgan Stanley. Please go ahead.

The next question is from the line of Mike <unk>.

Feedback that we're getting from Hcp's has continued to be very positive around quality of life and efficacy and the control of the polyneuropathy symptoms on a consistent basis.

With Morgan Stanley. Please go ahead.

Great. Good afternoon, Thanks for taking the question and congratulations on the strong quarter as well.

Mike Ulz: Great. Good afternoon. Thanks for taking the question and congratulations on the strong quarter as well. Maybe just a question on the phase three SHTG core data. You know, previously you suggested data 3Q. You're narrowing that a little bit to September. I guess first question, just, you know, any, you know, what's the rationale there or anything behind that? And then secondly, last quarter you suggested AP data, you know, might not be available in the top-line release. I guess just maybe give us a sense of what level of AP data you plan to share in the top-line release in September. Thanks.

Maybe just a question on the phase III Sage TG core data previously you suggested data <unk>, you're narrowing that a little bit to September I guess first question just any what's the rationale there or anything behind that and then secondly.

The ability to self administer with auto injector continues to be a differentiating factor and physicians and patients are very much appreciate the opportunity to manage their disease on their own without having to come into the Hcp's office in order to have a simple injection provided to that patient.

Last quarter, you suggested AP data.

So it's so in a simple response here. These are new to brand patients. These are patients that are newly identified predominantly we are seeing some switches as you would expect and we are seeing some combination use along with patients that are progressing on the stabilizers today, but really our focus is growing the polyneuropathy.

It might not be available in the topline release, I guess, just maybe give us a sense of what level of data you plan to share in the topline releases December thanks.

Sure Mike.

Brett Monia: Sure, Mike. So just refining the timeline to September from the second half of the year is just blocking and tackling getting the studies completed, database locked, the data cleaned, and all that. So we just felt it was appropriate to provide more specificity on the exact time. So nothing significant behind there except operational in conducting the studies. We will provide a statement on AP in our top-line press release. Our primary endpoint, again, is triglyceride lowering. We will provide top-line information on triglycerides as well as safety, overall safety, and we'll provide a statement on AP. What's also, I think, even more important is that we will provide and present the full data set, full data set at a medical congress in the second half of this year. And we'd love to publish the data in the second half of this year as well.

So.

Just refining the timeline to September from second half of the year is just blocking and tackling getting the studies completed database locked claims data cleaned and all that so we just felt it was appropriate to provide more growth more specificity.

Market and making sure that newly identified patients get prescribed window.

Next question.

On the exact timing so nothing nothing significant behind there.

The next question is from the line option overhang from Barclays. Please go ahead.

Operational.

Conducting.

The studies.

Thank you for taking my questions also congrats on the very strong quarter.

We will provide a statement on AP and AR topline press release.

I have two questions regarding <unk>.

Our primary endpoint in games is triglyceride lowering.

When I looked at the guidance.

This year $75 million to $80 million, thank you for using $80 million.

We will provide top line information.

Triglycerides as well as safety overall safety.

It seems every quarter is Q4 only $5 million gross so maybe give us a little more color.

And we'll provide statement on AP.

Guidance too conservative there.

Whats also I think even more important is that we will provide and present the full dataset.

Why.

At all with slowdown compared to.

Full dataset.

All lines.

Medical Congress in the second half of this year and we look to publish the data.

That's the first question in a second I don't know if you can comment.

I think that the.

In the second half of this year.

The total cumulative events for <unk> will be more than 13.

Very helpful.

Mike Ulz: Very helpful. Thank you.

Thank you.

So keybanc.

Certainly different disease.

The next question is from the line of Andy Chen from vertical research. Please go ahead.

Operator: The next question is on the line of Andy Chen from Wolfe Research. Please go ahead.

Prior history of <unk>.

Two studies.

Thank you.

Hey, Brendan on for Andy.

Brendon (for Andy Chen) / Steven Ironov (for Yaron Werber): Hey, Brendon for Andy. On Wenua and polyneuropathy, where do you think those patients are coming from? Do you think that they're you're winning new to branch here or stealing patients from an island? If you're going to provide any quantitative splits on those details, that would be great. Thank you.

How much more I would talk to.

Totally.

<unk> polymer neuropathy, where do you think those patients are coming from do you think that there youre, winning new winning new to brand share or stealing business from an island, if youre going to provide any quantitative splits on those details that'd be great. Thank you.

Or could that be 20.

Thanks Janet.

Touch on the $75 million to $80 million guidance.

Yes, actually I think I'll, just toss that to Cal because okay. That's in here.

He is responsible for that.

I'd be happy to talk about that Brennan. Thanks. This is Kyle again first I'll just say we knew it continues to perform very well strong demand at the polyneuropathy market as a growth market. The majority of these patients are not diagnosed yet and thats exactly where astrazeneca is spending the time is looking for and educating.

Kyle Jenne: I'd be happy to talk about that, Brandon. Thanks. This is Kyle again. First, I'll just say Wenua continues to perform very well. Strong demand. The polyneuropathy market is a growth market. The majority of these patients are not diagnosed yet, and that's exactly where AstraZeneca is spending the time, is looking for and educating HCPs around hereditary polyneuropathy patients. $44 million in Q2, which obviously was growth over Q1. The feedback that we're getting from HCPs is continuing to be very positive around quality of life and efficacy and the control of the polyneuropathy symptoms on a consistent basis. The ability to self-administer with auto-injector continues to be a differentiating factor. And physicians and patients very much appreciate the opportunity to manage their disease on their own without having to come into the HCP's office in order to have a simple injection provided to that patient.

I think what's most important here is the way that we've progressed throughout the launch right as I referenced.

Converted the clinical trial patients and we've been working very effectively with patients that were identified prior to the approval.

In order to get those patients are formally diagnosed and put onto to treatment. So.

<unk> around hereditary polyneuropathy patients.

You had a number of patients that were identified.

$44 million in Q2, which obviously was it was growth over Q1.

So where we're at right now with the launch is really looking for a newly identified in newly diagnosed patients right in order to penetrate deeper into that up to 3000, FCS patient population that we believe exists in the U S.

The feedback that we're getting from Hcp's has continued to be very positive around the quality of life and efficacy and the control of the polyneuropathy symptoms on a consistent basis.

So that takes some time it takes a lot of education and it takes a lot of conversations.

The ability to self administer with auto injector continues to be a differentiating factor.

And it also takes a little bit of time for physicians to get potential patients into the practice in order to be either clinically or genetically confirmed with their condition. So we've done a nice job throughout the first half of the year. We expect to continue to identify these patients, but it just might take us a little bit of time because of the complexity of the <unk>.

Physicians and patients are very much appreciate the opportunity to manage their disease on their own without having to come into the Hcp's office in order to have a simple injection provided to that patient.

So it's so in a simple response here. These are new to brand patients. These are patients that are newly identified predominantly.

Kyle Jenne: So in a simple response here, these are new-to-brand patients. These are patients that are newly identified predominantly. We are seeing some switches, as you would expect, and we are seeing some combination use along with patients that are progressing on the stabilizers today. But really, our focus is growing the polyneuropathy market and making sure that newly identified patients get prescribed Wenua.

Their disease that we're dealing with and being first to market and having a great product with positive physician and patient experience is helping us.

We're seeing some switches as you would expect and we are seeing some combination use along with patients that are progressing on the stabilizers today, but really our focus is growing the polyneuropathy market and making sure that newly identified patients get prescribed window.

To increase that that patient identification overtime.

Yeah, Thanks, Kyle and you're on your second question Gena.

We're not going to go more than that.

In this call today, we confirmed that.

We will see more AP events in the <unk> studies combined <unk> balance and we confirmed.

Next question.

Brett Monia: Next question.

That we will make a statement summarizing.

The next question is from the line auction overhang from Barclays. Please go ahead.

Operator: The next question is from the line of Chenow Wang from Buckley. Please go ahead.

To some extent top line summary of it.

Thank you for taking my questions also congrats on the very strong quarter.

Gene (for Chenow Wang): Thank you for taking my questions. Also, congrats on this very strong quarter. So I have two questions regarding Tringolza. When I look at the guidance for FCS this year, 75 to 80 million, even if we're using 80 million, it seems every quarter is 3Q for only 5 million growth. So maybe give us a little bit more color. You know, is the guidance too conservative, or is there a reason that why, you know, the new patient add-on was slowed down compared to 2Q over 1Q? So that's the first question. And a second, I don't know if you can comment. I think you mentioned that the total accumulative events for CORE and CORE2 would be more than 13.

Our findings and core on core to we're not going to go further.

So I have two questions regarding <unk>.

Any more AP events.

We look forward to sharing the data in September.

When I looked at the guidance.

This year 75 to 80 million, thank you for using $80 million.

Thank you.

Next question is from the line of Luke IC from RBC. Please go ahead.

It seems every quarter is Q4 only $5 million gross so maybe give us a little more color.

Oh, great. Thanks, so much for taking my question and congrats on a great quarter here.

Is the guidance conservative there.

Maybe Brad if I can circle back on one statement you made earlier.

Why.

At all with slowdown compared to.

Physicians appreciate that triglycerides are the bad guys, so to speak and they don't need to see stat Sig on acute pancreatitis.

Ones.

That's the first question in a second I don't know if you can comment.

I think that the.

The total cumulative events for quad core <unk> will be more than 13.

Is that a U S comment or do you think that is applicable also to the rest of the world.

Keybanc.

Gene (for Chenow Wang): So giving, you know, certainly a different disease and the prior history of AP in the two studies, so maybe like how much more are we talking about the total AP events? Is it still in the teens, or could that be in the 20s?

Certainly different disease.

Yes in a scenario, where you don't show Stat Sig a strong trend on AEP, how should we think about the uptake of this drug outside the United States and then.

Prior history of <unk>.

Two studies.

Thank you Mike.

How much more I would talk to the total.

Probably pushing my luck here, but you mentioned that Youll have a statement on ADP in the press release press release will that'd be a qualitative statement or quantitative statement. Thanks, so much.

Or could that be 20.

Thanks, Janet do you want to.

Brett Monia: Thanks, Gene. Beth, do you want to touch on the, so we've got the $80 million guidance?

Touch on the 75 to 80 million met our guidance.

Yes, actually I think I'll, just toss that to Kyle and.

Gene (for Chenow Wang): Yeah, actually, I think I'll just pass that to Kyle because that's in his shaft. He's responsible for that.

We're not going to go more than that.

In fact, he is responsible for that so I think what's most important here is the way that we've progressed throughout the launch right as I referenced we converted the clinical trial patients and we've been working very effectively with patients that were identified prior to the approval and.

What we're going to say, we're going to we will we will speak to our findings and core on core to AEP.

Kyle Jenne: No, so I think what's most important here is the way that we've progressed throughout the launch, right? As I referenced, you know, we converted the clinical trial patients. We've been working very effectively with patients that were identified prior to the approval in order to get those patients formally diagnosed and put on to treatment. So you had a number of patients that were identified. So where we're at right now with the launch is really looking for newly identified and newly diagnosed patients, right, in order to penetrate deeper into that up to 3,000 FCS patient population that we believe exists in the US. So that takes some time. It takes a lot of education, and it takes a lot of conversations.

Our topline press release and share for the full data set at a medical Congress. This year. So we're just going to hold off on that one.

Your first question.

In order to get those patients are formally diagnosed in and put onto to treatment. So.

<unk> is very.

Important question.

Because really what youre getting at is payer dynamics outside of the U S.

You had a number of patients that were.

So where we're at right now with the launch is really looking for newly identified in newly diagnosed patients right in order to penetrate deeper into that.

Kyle will address that but I can tell you that in the U S.

And I have spent a lot of time with lipid specialists.

At up to 3000, FCS patient population that we believe exists in the U S.

Over the last two years.

<unk> patients they do not they are convinced that the need to get patients on.

So that takes some time it takes a lot of education and it takes a lot of conversations.

Kyle Jenne: And then it also takes a little bit of time for physicians to get potential patients into the practice in order to be, you know, either clinically or genetically confirmed with their condition. So we've done a nice job throughout the first half of the year. We expect to continue to identify these patients, but it just might take us a little bit of time because of the complexity of the rare disease that we're dealing with. And being first to market and having a great product with positive physician and patient experience is helping us to increase that patient identification over time.

And then it also takes a little bit of time for physicians to get potential patients into the practice in order to be either clinically or genetically confirmed with their condition. So we've done a nice job throughout the first half of the year. We expect to continue to identify these patients, but it just might take us a little bit of time because of the complexity of the <unk>.

On the most effective triglyceride lowering agents possible if their triglyceride.

TG patients because they are convinced they know that their patients who are in harm's way for acute pancreatitis in fact were already treating them.

We're treating them with everything they have.

It would be five rates or Omega threes theyre just not effective so they are looking for something on top of standard of care. As a reminder, our cohort two studies are on top of standard of care.

Rare disease that we're dealing with and being first to market and having a great product with the positive physician and patient experiences helping us.

To get their triglycerides down and Thats true for payers in the United States to outside the U S and maybe focus on Europe.

To increase that that patient identification overtime.

Yeah, Thanks, Kyle and you're on your second question Gena.

Brett Monia: Yeah, thanks, Kyle. And on your second question, Gene, we're not going to go more than that. I mean, in this call today, we confirmed that we will see more AP events in the CORE and CORE2 studies combined than we saw in FCS balance. And we confirmed that we will make a statement summarizing, you know, to some extent, top-line summary of AP findings in CORE and CORE2. We're not going to go further than that on how many more AP events we see. We'll look forward to sharing the data in September.

Little bit more complex rate. It is from a regulatory standpoint, though obviously triglyceride lowering is going to be sufficient for a label in the EU and that filing is there.

We're not going to go more.

That I mean in this call today, we confirmed that.

We will see more events in the quarter to quarter. Two studies combined and we saw an FC is balanced and we confirmed.

Obviously, a positive <unk> opinion and optimistic about the outcome and where that goes in terms of the approval so from a payer and reimbursement dynamic standpoint.

That we will make a statement summarizing.

To some extent top line summary.

Findings.

In the European countries for example.

We're going to we're not going to go further.

It's really about the breadth of the population that you are ultimately going to be able to treat.

Many more AP events.

We look forward to sharing the data in September.

Who to treat and why to treat those patients right is the key thing here in order to demonstrate outcomes and the patient population.

Thank you.

Operator: Thank you. Next question is on the line of Luca Isi from RBC. Please go ahead.

Next question is from the line of Luke IC from RBC. Please go ahead.

One thing Thats very positive already as if we are able to secure an indication in Europe is we've got FCS FCS already has data it already has very strong hospitalization data and.

Oh, great. Thanks, so much for taking my question and congrats on a great quarter here.

Luca Isi / David Lebovitz: Oh, great. Thanks so much for taking my question and congrats on the great quarter here. Maybe, Brett, if I can circle back on one statement you made earlier, you know, the physicians appreciate that triglycerides are the bad guys, so to speak, and you know, they don't need to see a stat seg on acute pancreatitis. Is that a US comment, or do you think that is applicable also to the rest of the world? I guess in a scenario where you don't show stat seg or strong trend on AP, how should we think about the uptake of this drug outside the United States? And then I know I'm probably pushing my luck here, but you mentioned you'll have a statement on AP in the press release. Will that be a qualitative statement or quantitative statement? Thanks so much.

Maybe Brad if I can circle back on one statement you made earlier.

The physicians appreciate that triglycerides are the bad guys, so to speak and they don't need to see stat Sig on acute pancreatitis.

So we've got the information to be able to substantiate the pricing and reimbursement from an Fcs standpoint.

We also have a very strong partner in sobey, who has been in this market for many years and they've navigated pricing and reimbursement very successfully in the FCS population.

Is that a U S comment or do you think that is applicable also to the rest of the world.

In a scenario, where you don't show Stat Sig a strong trend on AEP, how should we think about the uptake of this drug outside the United States and then.

Already across numerous countries across Europe and.

We're very optimistic they will be able to continue that success with the program like like <unk>.

Probably pushing my luck here, but you mentioned that you'll have this statement on a key in the press release press release will that'd be a qualitative statement or quantitative statement. Thanks, so much.

So then the question becomes SHT G. If you have a potential label expansion and what do you need to show there.

Outcomes in AP are obviously going to be important for the for the broad population.

We're not going to go more than that.

Brett Monia: We're not going to go more than that, Luca. What we're going to say, we will speak to our findings in CORE and CORE2 on AP at the end of our top-line press release and share the full data set at a medical congress this year. So we're just going to hold off on that one. Your first question is a very important question because really what you're getting at is payer dynamics outside of the US. That's really, Kyle will address that. But I could tell you that in the US, and I have spent a lot of time with lipid specialists over the last two years who treat SHTG patients.

What we're going to say, we're going to we will we will speak to our findings and core on core to AEP.

But could you potentially look at a.

Different population.

Little bit more narrow than anybody over 500 for example patients that are at high risk SHT G such.

Our top line press release and share for the full dataset at a medical Congress. This year. So we're just going to hold off on that one.

Such as patients over 80 patients of 500, and a history of AP or potentially patients with other comorbidities. So there are a lot of dynamics and things to think through there and pending the data. Obviously, we will work through putting that body of evidence together in supporting <unk> in their pricing and reimbursement efforts across each country as they go.

Your first question.

<unk> is very is.

Important question.

Because really what youre getting at is payer dynamics outside of the U S.

Kyle will address that but I can tell you that in the U S.

And I have spent a lot of time with lipid specialists.

To launch.

Over the last two years, who treat <unk> patients. They do not they are convinced that the need to get patients on.

Got it thanks, so much.

Thanks Luke.

Brett Monia: They do not, they are convinced that they need to get patients on the most effective triglyceride-lowering agents possible if they're SHTG patients because they are convinced they know that their patients are in harm's way for acute pancreatitis. In fact, they're already treating them. They're treating them with everything they have, whether it be fibrates or omega-3s. They're just not effective. So they're looking for something on top of standard of care. As a reminder, our CORE and CORE2 studies are on top of standard of care to get their triglycerides down. And that's true for payers in the United States, too. Outside the US, let me maybe focus on Europe. It's a little bit more complex, right?

The next question is from the line of David Lebowitz from Citi. Please go ahead.

On the most effective triglyceride lowering agents possible if their triglyceride.

Thanks for taking my question given the strong early ramp of <unk> and <unk>.

TG patients because they are convinced they know that their patients who are in harm's way for acute pancreatitis in fact were already treating them.

Are you how are you thinking about the pricing change that would inevitably inevitably happen when it gets.

They are treating them with everything they have.

It would be <unk> or Omega threes Theyre, just not effective so they are looking for something on top of standard of care. As a reminder, our core of or two studies are on top of standard of care.

For severe hyper triglycerides is it just going to be pretty comps drop or are you going to try to find some way to.

Observe the revenues, while youre dropping the price.

To get their triglycerides down and Thats true for payers in the United States to outside the U S. Maybe focus on Europe.

Wrapping up.

Yes, Thanks, David.

So our pricing work is ongoing we've got we've got more work to do there.

Little bit more complex rate. It is from a regulatory standpoint, though obviously triglyceride lowering is going to be sufficient for a label in the EU and that filing is there.

Kyle Jenne: It is. From a regulatory standpoint, though, obviously, triglyceride lowering is going to be sufficient for a label in the EU. And that filing is there, and we've obviously positive CHMP opinion and optimistic about the outcome and where that goes in terms of the approval. So from a payer and reimbursement dynamic standpoint in European countries, for example, it's really about the breadth of the population that you're ultimately going to be able to treat. You know, who to treat and why to treat those patients, right, is the key thing here in order to demonstrate outcomes in the patient population. One thing that's very positive already is if we are able to secure an indication in Europe is we've got FCS. FCS already has AP data. It already has very strong hospitalization data.

What we've communicated up to this point is in a disease that has three to 4 million patients typically in the U S. Payers are accepting of a price somewhere in the 10% to $20000.

Obviously, a positive <unk> opinion and optimistic about the outcome and where that goes in terms of the approval so from a payer and reimbursement dynamic standpoint.

$1 price range.

When we're looking at <unk>, specifically and the data that.

<unk> can potentially have in the <unk> population wed.

In the European countries for example.

It's really about the breadth of the population that you're ultimately going to be able to treat.

We'd like to go back to the payers and do more testing and understand exactly where this price point could land based on the value to patients and value to the payers. So theres more work to do.

Who to treat and why to treat those patients right is the key thing here in order to demonstrate the outcomes and the patient population.

In terms of the execution of that.

One thing Thats very positive already as if we are able to secure an indication in Europe is we got FCS FCS already has data it already has very strong hospitalization data and.

The FCS population ultimately will be.

Consumed within the <unk> population, so it will become anybody over 500.

Should be within the <unk> population.

Kyle Jenne: And so we've got information to be able to substantiate pricing and reimbursement from an FCS standpoint. We also have a very strong partner in Sobi, who has been in this market for many years, and they've navigated pricing and reimbursement very successfully in the FCS population already across numerous countries across Europe. And I think we're very optimistic they will be able to continue that success with a program like Tringolza. So then the question becomes SHTG. If you have a potential label expansion, then what do you need to show there? Outcomes in AP are obviously going to be important for the broad population, but could you potentially look at a different population, a little bit more narrow than anybody over 500?

So we've got the information to be able to substantiate the pricing and reimbursement from an Fcs standpoint.

So there is a question around how do you execute that and in the pricing dynamics and do you bring the price down.

We also have a very strong partner in <unk>, who has been in this market for many years and they've navigated pricing and reimbursement very successfully in the FCS population.

I think regardless of what the decision is there if we do it immediately.

It's done over time.

What we do know is that the <unk> population is quite substantial and I think what we believe is that we'll be able to maintain enough patient population to be able to continue the revenues that we're producing at the time of an <unk> potential approval.

Already across numerous countries across Europe and.

We're very optimistic that we'll be able to continue that success with the program like like <unk>.

So then the question becomes SHT G. If you have a potential label expansion and what do you need to show there.

Thanks for taking my question.

Outcomes in AP are obviously going to be important for the for the broad population.

The next question is from the line of Geos from Oppenheimer. Please go ahead.

But could you potentially look at a.

A different population.

Oh, Hey, congrats on the quarter and thank you for providing this update now.

Little bit more narrow than anybody over 500 for example patients that are at high risk SHT G such.

Kyle Jenne: For example, patients that are at high-risk SHTG, such as patients over 880, patients with 500 and a history of AP, or potentially patients with other comorbidities. So there are a lot of dynamics and things to think through there. And pending the data, obviously, we'll work through putting that body of evidence together and supporting Sobi in their pricing and reimbursement efforts across each country as they go to launch.

Now that you have the early successful launch experience with twin goals.

And you have several other launches that you're planning in the near term how does that impact your thinking about your earlier stage pipeline and deciding between out licensing earlier stage assets versus retaining full ownership and launching them independently.

And then as a follow up can you discuss any plans to build out your ex U S infrastructure for any future global product launches in the long term. Thank you.

To launch.

Got it thanks, so much.

Luca Isi / David Lebovitz: Got it. Thanks so much.

Thanks Lucas.

Brett Monia: Thanks, Luca.

Thank you Jay.

The next question is from the line of David Lebowitz from Citi. Please go ahead.

Operator: The next question is from the line of David Lebovitz from City. Please go ahead.

We have.

And abundance of riches when it comes to.

Thanks for taking my question given the strong early ramp of <unk> and <unk>.

Luca Isi / David Lebovitz: Kyle, thanks for taking my question. Given the strong early ramp of Tringolza and FCS, how are you thinking about the pricing change that would inevitably happen when it gets approved for severe hypertriglycerides? Is it just going to be a pretty prompt drop, or are you going to try to find some way to preserve the revenues while you're dropping the price and ramping up?

Our late stage pipeline.

Are you how are you thinking about the.

Our wholly owned pipeline in our partner pipeline.

The pricing change that would inevitably inevitably happen when it gets.

Nice combination there and in our first independent market is off to a really good start and we're expecting <unk>.

We will first severe hyper triglycerides is it just going to be pretty prompt drop or are you going to try to find some way to.

To be equally successful as well as less hcg coming up next year.

Observe the revenues, while youre dropping the price.

With that said.

Our.

Wrapping up.

Our research organization is incredibly innovative and prolific.

Yeah. Thanks, David So our pricing work is ongoing we've got we've got more work to do there.

Kyle Jenne: Yeah, thanks, David. So our pricing work is ongoing. We've got more work to do there. You know, what we've communicated up to this point is in a disease that has three to four million patients, typically the US payers are accepting of a price somewhere in the $10,000 to $20,000 price range. However, when we're looking at SHTG specifically and the data that olzarsin can potentially have in the SHTG population, we'd like to go back to the payers and do more testing and understand exactly where this price point could land based on the value to patients and the value to the payers. So there's more work to do. In terms of the execution of that, you know, the FCS population ultimately will be consumed within the SHTG population. So it will become, you know, anybody over 500 would be within the SHTG population.

And we have to continue to bring in potentially transformational medicines.

What we've communicated up to this point is in a disease that has three to 4 million patients typically the U S. Payers are accepting of a price somewhere in the 10 to 20000.

Continuously into the early stage pipeline and bring them to phase III development.

In due course.

Our our focus remains as we set out five years ago five years ago to do is to prioritize the wholly owned pipeline.

$1 price range.

However, when we're looking at <unk>, specifically and the data that.

<unk> can potentially have in the <unk> population.

We will continue to do so and we will focus on cardiology and.

He'd like to go back to the payers and do more testing and understand exactly where this price point could land based on the value to patients and the value to the payers. So theres more work to do.

Alright, great cardio cardio metabolic diseases as well as some neurology.

We'll always have room for exceptions microwave or injury demoing, such an excellent drug like <unk>.

In terms of the execution of that.

But those will be our focus.

The FCS population ultimately will be.

Areas will be our focus and it will be the priority.

Consumed within the <unk> population, so it will become anybody over 500 would be within the <unk> population.

With that said.

We still need to ensure that we will.

Within our means.

We have limited our resources are limited.

Kyle Jenne: So there is a question around, you know, how do you execute that and the pricing dynamics, and do you bring the price down? I think regardless of what the decision is there, if we do it immediately or if it's done over time, what we do know is that the SHTG population is quite substantial. And I think what we believe is that we'll be able to maintain enough patient population to be able to continue the revenues that we're producing at the time of an SHTG potential approval.

So.

There is a question around how do you execute that and the pricing dynamics and do you bring the price down.

We are committed to achieving a positive cash flow in the next few years.

I think regardless of what the decision is there if we do it immediately or if it's done over time.

And.

And although we will prioritize our wholly owned pipeline early stage through phase III development.

What we do know is that the <unk> population is quite substantial and I think what we believe is that we'll be able to maintain.

There will always be assets that.

There are outside of our rooms are outside of our priority areas, where we will make.

Enough patient population to be able to continue the revenues that we're producing at the time of an <unk> potential approval.

<unk> seems to partner.

Lot of interest in partnering with our enormous these days are platforms delivering over and over again.

Thanks for taking my question.

Luca Isi / David Lebovitz: Thanks for taking my question.

A great example of that is the sample for some transaction that we did earlier this year.

The next question is from line of Geos from Oppenheimer. Please go ahead.

Operator: The next question is from the line of Jay Olson from Oppenheimer. Please go ahead.

For safety.

<unk> immunotherapy with <unk> $280 million upfront.

Oh, Hey, congrats on the quarter and thank you for providing this update.

Jay Olson: Oh, hey, congrats on the quarter, and thank you for providing this update. Now that you have the early successful launch experience with Tringolza and you have several other launches that you're planning in the near term, how does that impact your thinking about your earlier stage pipeline and deciding between out-licensing earlier stage assets versus retaining full ownership and launching them independently? And then as a follow-up, can you discuss any plans to build out your ex-US infrastructure for any future global product launches in the long term? Thank you.

And we did that because it's outside of our area. Our areas of focus for hematology is not a focused area for us so.

Now that you have the early successful launch experience with twin goals.

And you have several other launches that you're planning in the near term how does that impact your thinking about your earlier stage pipeline.

Youll see us continue to partner, but that's not our priority. Our priority is our wholly owned pipeline early to late stage, and our and our and our launches with respect to outside the U S.

And deciding between out licensing earlier stage assets versus retaining full ownership and launching them independently.

I'd like to just put that went on pause.

We're thrilled with the early launch of <unk> and.

And then as a follow up can you discuss any plans to build out your ex U S infrastructure for any future global product launches in the long term. Thank you.

And we're looking forward to <unk> S hcg launches in the U S.

And.

We'll know when it's time to.

Thank you Jay.

Brett Monia: Thank you, Jane. You know, we have an abundance of riches when it comes to our late-stage pipeline, our wholly owned pipeline, our partner pipeline. So it's a nice combination there. And our first independent launch is off to a really good start. And we're expecting Dani Foroohar to be equally successful as well as SHTG coming up next year. With that said, our research organization is incredibly innovative and prolific. We have to continue to bring in potentially transformational medicines continuously into the early-stage pipeline and bring them to phase three development in due course. Our focus remains, as we set out five years ago, five and a half years ago, to do is to prioritize the wholly owned pipeline. We'll continue to do so, and we will focus on cardiology and cardiometabolic diseases as well as neurology.

We have.

Emerge from the U S and maybe start building.

External.

And abundance of riches when it comes to.

Ex U S commercial.

Structure.

Our late stage pipeline.

But now is not in time to be distracted.

Our wholly owned pipeline our partnered pipeline.

We need to get these launches right. We're committed to get these launches right and we will do so with that said we of course are having discussions internally on when and what that asset might be that we emerged from the U S market.

This combination there.

And our first independent margins are off to a really good start and were expecting the worst.

To be equally successful as well as this hcg coming up next year.

But it's we're in the early innings in those discussions.

Thank you Super helpful. Congrats again on the launch.

With that said.

Our.

Our research organization is incredibly innovative and prolific.

The next question.

On the line of <unk> from Jefferies. Please go ahead.

We have to continue to bring in potentially transformational medicines.

Okay.

Hi, This is <unk> on for cash to lie. Thanks, so much for taking our question.

Continuously into the early stage pipeline and bring them to phase III development.

In the balance study it looks like there was one event that kind of leaked through towards the end of the study and the 80 milligram arm the patient who did have.

Due course.

Our focus remains as we set out five years ago, five and a half years ago to do is to prioritize the wholly owned pipeline.

Lowered on garage, whereas placebo events is seemed to cluster early on earlier on in the first half of the study.

We continue to do so and we will focus on cardiology and <unk>.

Understand really small end here, but how do you have data in some sense of how blinded events like Nokia and <unk>. How confident are you that this kind of variability.

Alright, great cardio cardio metabolic diseases as well as some.

<unk>, we will always have room for exceptions Microgrid theory, Andrew at the moment, such an excellent looking drug Mcdonald with.

Brett Monia: We will always have room for exceptions, like hereditary angioedema, when we have such an excellent-looking drug like Dani Foroohar, but those will be our focus. Those areas will be our focus, and it will be the priority. With that said, we still need to ensure that we live within our means. We have limited, you know, our resources are limited. We are committed to achieving positive cash flow in the next few years. And although we will prioritize our wholly owned pipeline early stage through phase three development, there will always be assets that either are outside of our means or outside of our priority areas where we will make decisions to partner. A lot of interest in partnering with Ionis these days, platforms delivering over and over again.

Swing factor on EEP powering in core wanting to you. Thank you.

But those will be our focus.

I'll start and then Eugene please jump in so we're doing everything we can to power.

Those areas will be our focus and it will be the priority.

With that said.

<unk> increased the power for a PNR study possible.

We still need to ensure that we live within our means.

Our analysis will be combined core in quarter two.

We have limited our resources are limited.

And we'll we'll be at the 12 month timeframe, that's correct right.

We are committed to achieving a positive cash flow in the next few years.

So although the primary endpoint for triglycerides is six months.

<unk>.

Although we will prioritize our wholly owned pipeline early stage through phase III development.

AP secondary endpoint will be at 12 months and a combo.

There will always be assets that.

With corn Corps two combined so we will have the.

Either are outside of our rooms are outside of our priority areas.

Going to do is maximize time and maximize patient numbers.

We will now.

Seems to partner.

Okay.

A lot of interest in <unk>.

Most of them have Brad.

Regarding honest these days our platform is delivering over and over again.

Maxim multiple power will be achieved by combining core on core to ensuring that the partners.

Brett Monia: A great example of that is the SAPPA-BLEUERSEN transaction that we did earlier this year for polycythemia vera with ONO, $280 million upfront. And we did that because it's outside of our areas of focus. Hematology is not a focused area for us. So you'll see us continue to partner, but that's not our priority. Our priority is our wholly owned pipeline, early to late stage, and our launches out there. With respect to outside the US, I'd like to just put that one on pause. We're thrilled with the early launch of Tringolza, and we're looking forward to Dani Foroohar and SHTG launches in the US. And we'll know when it's time to emerge from the US and maybe start building external or ex-US commercial infrastructure. But now is not the time to be distracted with that. We need to get these launches right.

Great example of that is the central for us.

Some transaction that we did earlier this year.

Much larger loan.

Sure.

Or.

Polycythemia, Vera with Ono $280 million upfront.

Thank you.

Our last question comes from David <unk> from Guggenheim Partners. Please go ahead.

And we did that because it's outside of our area. Our areas of focus for hematology is not a focused area for us so.

Hey.

Youll see us continue to partner, but that's not our priority. Our priority is our wholly owned pipeline early to late stage and are.

Good afternoon, sorry, good morning into West Coast.

Wondering if the second interim analysis on the LTA Horizon study has happened already and I believe this was after a 745 events. Thank you.

Our launches are with respect to outside the U S.

I'd like to just put that went on pause.

<unk>.

Thanks, Andrew Yes, it has.

We're thrilled with the early <unk>.

Launch of <unk>.

And there are no more interim analysis plan for the pellet Carson Horizon study so.

<unk>.

And we're looking forward to Donald worse than the mass hcg launches in the U S.

Fully expecting that study to read out in the first half of next year.

And.

We'll know when it's time to two.

And we're very much looking forward so the terminology that we completed.

Emerge from the U S and maybe start building.

External.

Ex U S commercial.

Infrastructure.

So with that I think we'll close the call.

But now is not in time to be distracted.

Thank you everybody for joining us today.

We need to get these launches right. We're committed to get these launches right and we will.

We look forward to building on our strong momentum throughout the year sharing additional achievements progress.

Brett Monia: We're committed to get these launches right, and we'll do so. With that said, we, of course, are having discussions internally on when and what that asset might be that we emerge from the US market with. But we're in the early innings in those discussions.

So with that said we of course are having discussions internally on when and what that asset might be that we emerged from the U S market.

One way and so on.

The next time, we talk thank you again for joining and have a great day everybody.

But it's we're in the early innings in those discussions.

Thank you Super helpful. Congrats again on the launch.

Jay Olson: Thank you. That's super helpful. Congrats again on the launch.

The next question.

Operator: The next question is on the line of Akash Tewari from Jeffries. Please go ahead.

From the line of <unk> <unk> from Jefferies. Please go ahead.

Okay.

Hi, This is <unk> on for <unk>. Thanks, so much for taking our question. So in the balance study. It looks like there was one event that quantum leap through towards the end of the study and the 80 milligram arm the patient who did have.

Ion (for Akash Tewari): Hi, this is Ion for Akash Tewari. Thanks so much for taking our question. So in the balance study, it looks like there was one AP event that kind of leaped through towards the end of the study in the 80 milligram arm in a patient who did have triglycerides lowered on the drug, whereas placebo events seemed to cluster earlier on in the first half of the study. So I understand it's a really small end here, but now that you have the ESSENCE data and some sense of how blinded events are tracking in CORE 1 and 2, how confident are you that this kind of variability won't be a swing factor on AP powering in CORE 1 and 2? Thank you.

Lowered on garage, whereas placebo events in the cluster early on earlier on in the first half of the study.

Understand really small end here, but how do you have to have these data in some sense and outlined at events like vacuum <unk>. How confident are you that this kind of variability.

Swing factor on EEP powering in core wanting to you. Thank you.

I'll start and then Eugene please jump in so we're doing everything we can to power.

Brett Monia: I'll start, and then Eugene, please jump in. So we're doing everything we can to increase the power for AP in our study if possible. AP analysis will be combined CORE and CORE2 and will be at the 12-month timeframe. That's correct, right, Eugene? So although the primary endpoint for triglycerides is at six months, the AP secondary endpoint will be in 12 months in a combo with CORE and CORE2 combined. So we'll have the what we're trying to do is maximize time and maximize patient numbers.

This increase the power for a PNR study possible.

Our analysis will be combined core in quarter two.

And we'll we'll be at the 12 month timeframe, that's correct right.

So although the primary endpoint for triglycerides is at six months.

And AP secondary endpoint will be at 12 months and a combo.

With corn Corps two combined so we will have the.

I would do is maximize time and maximize patient numbers.

Okay.

Most of that growth.

Eugene Schneider: I'll just add that the maximum power will be achieved by combining CORE and CORE2 and ensuring that the N is much larger than two separate.

Maxim not small power will be achieved by combining core on core to ensuring that the amis.

Much larger loan.

Sure.

Thank you.

Operator: Thank you. Our last question comes from Dave G. Chatojay from Guggenheim Partners. Please go ahead.

Our last question comes from David <unk> from Guggenheim Partners. Please go ahead.

Hey.

Dave G. Chatojay: Hey, good afternoon. Sorry, good morning, in the West Coast. I'm just wondering if the second interim analysis in the LPA Horizon study has happened already, and I believe this was after 745 events. Thank you.

Good afternoon, sorry, good morning into West Coast.

Wondering if the second interim analysis on the Lps Horizon study has happened already and I believe this was after 745 events. Thank you.

Thanks, Andrew Yes, it has.

Brett Monia: Thanks, Dave. Yes, it has. And there are no more interim analyses planned for the Telecarson Horizon study. So we're fully expecting that study to read out in the first half of next year. And we're very much looking forward to it. So all of the interim analyses have been completed. So with that, I think we'll close the call. I'd like to thank everybody for joining us today. We look forward to building on our strong momentum throughout the year, sharing additional achievements, progress along the way. And until the next time we talk, thank you again for joining and have a great day, everybody. Goodbye.

And there are no more interim analysis plan for the pellet Carson Horizon study so far.

Fully expecting that study to readout in the first half of next year.

And we're very much looking forward to so potent turn analyses have been completed.

So with that I think we'll close the call.

Thank you everybody for joining us today.

We look forward to building on our strong momentum throughout the year sharing additional achievements progress.

On the way in.

The next time, we talk thank you again for joining and have a great day everybody.

Goodbye.

Q2 2025 Ionis Pharmaceuticals Inc Earnings Call

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