Q4 2024 Ionis Pharmaceuticals Inc Earnings Call
Speaker Change: Good morning and welcome to IONAS's fourth quarter and full year 2024 financial results conference call. As a reminder, this call is being recorded. At this time, I would like to turn the call over to Wade Walke, Senior Vice President of Investor Relations, to lead the call. Please begin.
Speaker Change: And joining us for the Q&A portion of our call will be Eric Swayze Executive Vice President of research and Eugene Schneider, Chief Clinical development Officer.
Wade Walke: I would like to draw your attention to slide three which contains our 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.
Speaker Change: Courage you to consult the risk factors contained in our SEC filings for additional detail.
Now I'll turn the call over to Brett Thanks, Wade and good morning, everyone and thank you for joining us on today's call.
Speaker Change: As we begin a new year I am thrilled to share that <unk> has begun a new chapter as a fully integrated commercial stage biotechnology company with our first independent long term goals are underway.
Speaker Change: With the FDA approval of <unk> in late December adults with familiar archival Micronesia syndrome or FCS for the first time have access to a treatment thats substantially and sustainably reduces triglyceride levels and substantially reduces the risk of life threatening acute pancreatitis.
Speaker Change: Our highly experienced team has been executing the launch flawlessly, which enabled <unk> to be in the hands of patients within a couple of weeks following the December 19th approval.
Speaker Change: And can turn goals is just the beginning we're on track to deliver three additional independent launches over the next three years.
Speaker Change: Don <unk>, a potential treatment preferred treatment for hereditary angioedema later this year.
Speaker Change: A second indication for <unk> in severe hyper triglycerides EMEA, our SAP <unk>, a large patient population with high unmet need and yoga nursing for Alexander disease, a rare lipid dystrophy with no approved therapies.
Speaker Change: These programs collectively provide the opportunity to help tens of thousands of patients and represent multibillion dollar revenue potential.
Speaker Change: In addition to our independent launches. We also expect for launches from late stage partnered programs over the next three years.
Speaker Change: These important medicines are poised to treat a range of serious life threatening diseases, including several that target broad patient populations.
Speaker Change: Hello, Carson for LP little a cardiovascular disease addressing an independent cardiovascular disease risk factor with high unmet need with no approved therapies.
Speaker Change: <unk> for <unk> cardiomyopathy, a progressive fatal condition that continues to be under diagnosed with a significant need for more effective treatments.
Speaker Change: So pure version for chronic hepatitis B virus, a serious disease that affects hundreds of millions of people globally.
Speaker Change: <unk> previously referred to as <unk> in development for Iga Nephropathy, one of the most common causes of chronic kidney disease and kidney failure.
Speaker Change: If approved these important investigational medicines will join our other marketed partnered medicines, including <unk> for SMA and we knew for hereditary <unk>, polyneuropathy, which are generating considerable value for patients and revenue per eye on us.
Speaker Change: Our partnered medicines enable our innovative science to reach even more patients bolster.
Speaker Change: Bolster our strong revenue base and provide substantial growth potential while allowing us to focus our efforts on advancing the medicines, we plan to commercialize.
Speaker Change: I own this is on a path to bring important medicines to patients for years to come and in turn we are positioned to achieve substantial and sustained revenue growth and positive cash flow.
Kyle: Our recent accomplishments and ongoing investments position us well to drive accelerating value for all <unk> stakeholders and with that I'll turn the call over to Kyle.
Kyle: Thank you Brett as we start this important new chapter as a fully integrated commercial stage biotech I cannot be prouder of our team.
Kyle: Theyre seamless execution of initial launch activities ensured that our first independently launched medicine <unk> got to FCS patients quickly.
Kyle: Following the approval of <unk>. The first prescription was written within 24 hours the team got drug and channel within one week and the first patient self administered twin goals of within two weeks of approval.
Kyle: And today, we are encouraged by seeing both genetically confirmed and clinically diagnosed patients on drug.
Kyle: While it is early in the launch we are encouraged by the positive response in several key areas.
Kyle: The breadth of physicians identifying Fcs patients and prescribing <unk>.
Kyle: The mix of prescribers, including endocrinologists and cardiologists with an interest in lipids.
Kyle: And that we're already seeing numerous repeat prescribers.
Kyle: The rapid time from prescription to patients receiving <unk> and coverage by payers for both commercial and Medicare patients.
Our experienced team is laser focused on continuing this momentum as the first ever treatment in the U S. We are capitalizing on our first mover advantage that is enabling us to develop the market.
Kyle: Identify and onboard patients early and create positive treatment experience that encourages long term adherence.
Kyle: Additionally, it has enabled us to establish a strong presence in the patient community all of which we expect will drive long term success for <unk>.
Kyle: The total addressable U S. FCS patient population is estimated to be up to approximately 3000 people and currently the vast majority of the FCS population remains on identified and diagnosed.
Kyle: As a result, there are multiple critical steps that we're taking to get patients identified and entre gold.
Kyle: First our team is focused on patient finding efforts working to identify FCS patients who are not yet diagnosed.
Kyle: Building on these efforts our team is working to increase FCS awareness through HCP education to drive increased diagnosis and our commercial field team is actively engaging with hcp's, who treat patients with high triglycerides.
Kyle: Once patients are identified and diagnosed the team works closely with prescribers and patients to obtain coverage and initiate treatment for <unk>.
Kyle: We have deployed a suite of services to accomplish this anchored by our innovative I honest every step patient support program.
Kyle: As part of this program dedicated patient education managers provide patient disease, and nutrition education Auto injector administration training reimbursement support and more.
Kyle: For Hcp's I honest every step streamlines, the touring Golar prescribing process by offering insurance authorization and coverage assistance as well as coordinating delivery reauthorization and refills.
Kyle: To date, we have had very high engagement with patients sharing their excitement as they now have a treatment and the services that they are experiencing from the program.
Kyle: Our market access and reimbursement teams have been actively engaged with a broad set of U S payers, representing the vast majority of covered lives and through these efforts payers have recognized the significant burden FCS places on patients.
Kyle: With this recognition we are pleased to report that in the early days of the launch patients have received timely access to trim goes up.
Kyle: Finally, our omnichannel capabilities extend the reach of our commercial team and amplify our efforts with patients and physicians.
Kyle: Our launch trajectory will reflect the time it takes to execute on these efforts, which we fully expect will gain momentum as the year unfolds.
Kyle: To realize the full blockbuster potential of <unk>, we plan to further scale, our commercial organization and infrastructure to address the much larger <unk> patient population, where we have substantial first mover advantage.
Kyle: <unk> is comprised of people with triglycerides over 500 milligrams per deciliter and is a symptomatic disease, where people can suffer debilitating chronic symptoms that impact all aspects of their life, including severe abdominal pain and cognitive impairment.
Kyle: And the most severe manifestation S. H T. G patients can suffer from life threatening pancreatitis events that require intensive hospital care as.
Kyle: As a result physicians recognize the importance of lowering severely elevated triglycerides with established guidelines already in place.
Kyle: Many people with <unk> are severely underserved by current treatment options and in many cases are unable to reduce triglyceride levels to current recommended guidelines with available options.
Kyle: This is why we are excited about the potential <unk> could offer to people with S. H T G.
Kyle: Today. The team is focused on pre commercialization activities ahead of an anticipated launch next year.
Kyle: We knew our co commercialize medicine with Astrazeneca for hereditary <unk> Polyneuropathy has now been on the market for about a year and we couldnt be more pleased with the strong progress of the launch.
Kyle: <unk> delivered accelerating sequential growth throughout last year, including strong demand in the fourth quarter with product sales nearly doubling compared to the third quarter.
Kyle: Uptake continues to be strong with the majority of top centers of excellence prescribing renewal and broadening use into the community setting.
Kyle: Patient growth continued to come from patients new to treatment as well as switches and patients, adding <unk> to their existing therapy.
Kyle: We consistently receive positive feedback from physicians about their patients' experience with way newer including patient's quality of life improvements their ability to rapidly access we knew.
Kyle: And patients' ability to easily self administer we know.
Kyle: And we are pleased with the reimbursement and affordability dynamics, we saw in 2020 for the vast majority of patients who initiated way new of treatment, regardless of insurance type paid $0 out of pocket.
Kyle: We and Astrazeneca are confident we will continue to provide a differentiated experience for patients.
Kyle: The growing global ATR Polyneuropathy launch sets the foundation for our efforts to address ATR cardiomyopathy, a substantial opportunity with 300 to 500000 people estimated worldwide.
Kyle: Switching gears to dining to Larson with the potential approval just six months away. The team is preparing for our second independent launch in fact, we recently hired the head of <unk> sales and plan to add the customer facing team soon ensuring that they will be ready to bring <unk> to patients quickly after anticipated approval.
Kyle: Our team is also leveraging and building upon the way new entering goals of launches.
Kyle: For example, we will expand our innovative I honest every step patient support program to include the needs of <unk> patients.
Kyle: Our medical Affairs team has been in the field meeting with physicians. This includes ensuring high visibility at key medical conferences building awareness of <unk> platform technology and presenting the positive clinical data generated from our robust phase III program ahead of our anticipated launch.
More than 20000 people are estimated to have <unk> in the U S and Europe and the U S. While the AG market is well defined prophylactic treatment continues to grow with a meaningful segment of patients switching treatment in search of a better option.
Kyle: Based on <unk> strong clinical data, including the positive data in patients switching from current prophylactic treatments to down into Lawson and the simplicity of monthly or every two months self administration via an auto injector. We believe <unk> offers the attributes that many people with HIV are looking for.
Kyle: And while we expect the <unk> launch ramp to take time as we work to convert patients from existing treatment. We believe <unk> has the potential to be a preferred prophylactic treatment for many patients.
Kyle: We have built a highly experienced efficient and scalable commercial organization with the <unk> FCS launch underway. We are focused on delivering its full potential while preparing to successfully execute our three additional launches planned over the next three years with more to follow positioning I honest for sustained growth and long term some.
Richard: With that I'll now turn it over to Richard.
Richard: Thank you Kyle.
Richard: We had many important pipeline achievements in 2024 that position us well for success in 2025.
Richard: These included numerous positive late stage data readouts with resulted in multiple regulatory submissions and our first independent launch.
Richard: Additionally, as our pipeline advances.
Richard: We're on track for multiple late stage data Readouts and regulatory actions. This year and next positioning I honest to bring transformational medicines to people with serious diseases for years to come.
Richard: Starting with <unk>, the first ever approved treatment for adults with FCS in the U S.
Richard: The positive data from the phase III balanced study formed the basis for triangles. This approval and the balanced study triangles 80 milligrams.
Richard: Demonstrated substantial and sustained triglyceride reductions.
Richard: <unk> meaningful reductions in acute pancreatitis.
Richard: A substantial reduction in all cause hospitalization in days spent in the hospital and a favorable safety and Tolerability profile in people with FCS. We believe these positive data underscore the tremendous benefit trend goals that can bring to adults with Fcs.
Richard: And while we are starting with FCS, we expect to quickly expand to a second broader indication S. H T G.
Richard: Many <unk> patients are unable to manage their triglycerides with currently available treatments and physicians are eager for a more effective treatment.
Richard: As a reminder.
Richard: We have three separate studies, we expect to report top line results from essence are supportive safety exposure study <unk> with data expected in mid this year essence is being conducted primarily in patients with triglyceride levels between $1 50, and 500 next per deciliter.
Richard: So we're not at high risk for acute pancreatitis.
This is not the patient population, we're targeting commercially rather the essence study was designed to satisfy the regulatory requirements for a safety database to support a highly prevalent disease.
Richard: We look forward to data from our pivotal studies core and core too to truly understand the <unk> profile and S. H T. G. These studies are evaluating <unk> in our target patient population, who have triglycerides greater than 500 milligrams per deciliter.
Richard: We are on track.
Richard: For data from core and core two in the second half of this year and once we have data in hand for both of these studies. We will report the results and assuming these data are positive we plan to submit our NDA before year end.
Richard: With significant first mover advantage in both FCS and that's H T G and compelling results already demonstrated in FCS coupled with our expectation for similarly.
Richard: Positive data NSX T. G. We believe <unk> could be the standard of care for both diseases.
Richard: Following closely behind <unk> goals is dawning Dolores.
Speaker Change: A potential advance for patients with hereditary angioedema.
Speaker Change: We're pleased to garner Dolores and is now under regulatory review in both the U S and EU regulatory submissions were based on positive data generated from our phase II and phase III studies, including a separate switch study.
Speaker Change: In the phase III program long term Donna divorce and treatment demonstrated substantial reductions in HAE attack rates of more than 90% with both monthly and bimonthly dosing and a favorable safety and Tolerability profile.
Speaker Change: These reductions translated to a high level of disease control and clinically meaningful improvements in quality of life measures.
Speaker Change: In the switch study patients who switched it on at Dolores and from prior prophylactic treatment showed a further reduction in HAE attack rates from baseline with nearly 85% of the patients surveyed preferring donatella.
Speaker Change: With a <unk> date of August 21.
Speaker Change: We look forward to bringing this potential preferred prophylactic treatment to HAE patients later this year assuming approval.
Speaker Change: Rounding out our I own a cell and late stage pipeline is <unk>.
Speaker Change: Our medicine to treat Alexander disease, an ultra rare Luca dystrophy that profoundly impacts patients and families and has no approved disease modifying treatment.
Speaker Change: Last year <unk> was granted fast track designation by the FDA, reflecting the serious unmet need that exists for this rare disease.
Speaker Change: We're looking forward to reporting phase III data for this program late this year.
Speaker Change: The rest of our rich pipeline is also making excellent progress.
Speaker Change: This includes ion five eight to our wholly owned investigational medicine for Angelman syndrome, which.
Speaker Change: Which we believe has transformational potential for the tens of thousands of patients living with this serious rare disorder.
Speaker Change: Last year based on the positive early results from the Halo study of ion 582 in children and adults with Angelman syndrome, we reached alignment with FDA to conduct the most robust and comprehensive phase III study in this patient population to date.
Speaker Change: Our study will focus on clinical endpoints that reflect the most pressing and meaningful outcomes for people living with Angelman syndrome.
Speaker Change: <unk> endpoints that showed positive results in our Halo study.
Speaker Change: We remain on track to start ion 582 phase III study in the first half of this year.
Speaker Change: As we look to our key value driving events, we have already made excellent progress. In addition to launching <unk>. We are pleased that higher dose Newson Ericsson is one step closer to the market with the recent FDA and EMA acceptances of Biogen's regulatory submissions.
Speaker Change: With the well characterized profile of spin Ross has established over the past 10, plus years and the positive data from the anchor dose spin Rosa. We believe spin rise is well positioned to continue to bring benefit to SMA patients around the world.
Speaker Change: To summarize key near term value driving events, we anticipate many late stage data readouts significant regulatory actions and numerous product launches.
Speaker Change: By the end of 2026, we expect seven phase III data readouts, including <unk> owned medicines. This year <unk> for the broad S. H T G indication in <unk> for Alexander disease.
Speaker Change: Next find by honest discovered medicines are on track for phase III data most of which are for very broad patient populations.
Speaker Change: If positive these groundbreaking medicines could start to reach patients as soon as next year and we expect to have five launches underway, including four independent launches.
Speaker Change: All of this sets us up.
Speaker Change: Bring a steady cadence of new I honest medicines to patients for years to come with.
Beth: With that I'll turn it over to Beth.
Thank you Richard we've made excellent progress advancing our strategic growth priorities, including executing our first independent launch timing.
Speaker Change: Simultaneously upholding our commitment to drive operating leverage.
Speaker Change: This important progress as reflected in our strong financial results for last year.
Speaker Change: Our outlook for this year, both of which I am happy to share with you today.
We delivered a non-GAAP operating loss of $345 million, a significant improvement compared to our 2024 guidance. We also substantially exceeded our 2020 for revenue guidance by more than $130 million.
Speaker Change: Turning revenue at $705 million last year.
Speaker Change: During 2024, and rather remain the primary source of commercial revenue with $216 million of royalties for the year.
Speaker Change: We were encouraged by spin <unk> performance and look forward to the anticipated lines at the higher dose option.
Speaker Change: Wayne Miller product revenue achieved accelerating sequential growth throughout last year, driven by strong underlying demand.
Speaker Change: Notably, we newer product revenue increased 84% in the fourth quarter compared to the third quarter.
Speaker Change: Well, a newer product sales were $85 million for last year, which we earned for which we earned $20 million in royalties.
Speaker Change: As planned our non-GAAP operating expenses increased slightly for 2024 over 2023.
Speaker Change: 12% increase year over year in sales and marketing expenses reflected our investment in the U S lines had shingles and.
Speaker Change: In preparation for the upcoming launch of <unk>.
Speaker Change: Our SG&A expenses also included our minority portion of Lea newest sales and marketing costs, which are in the high teens to low 20% range.
Speaker Change: In line with our plan, we kept R&D expenses stable year over year, while appropriately funding our rich pipeline.
Speaker Change: Our excellent progress last year, coupled with our disciplined financial management positions us well for continued growth and value creation.
Speaker Change: Our financial guidance for this year reflects our evolution to a fully integrated commercial stage biotech company focused on maximizing the value of our innovative medicine, while remaining steadfast in our commitment to deliver strong operating leverage.
Speaker Change: We project to earn more than $600 million in revenue from numerous sources.
Speaker Change: Including the shift toward commercial revenues with the addition of <unk> product revenues and initial diamond tillerson product revenues assuming approval.
Speaker Change: With <unk>, it's important to remember that FCS is a rare and under recognized disease and we anticipate an initial gradual buildup of launch momentum, especially in the first few quarters.
Speaker Change: Our efforts aimed at driving physician awareness and patient identification progress. We expect the number of new patients diagnosed with FCS to increase which in turn will translate to an acceleration of our launch progress.
Speaker Change: We're also looking forward to adding <unk> product revenues beginning in late Q3, assuming approval in August.
Speaker Change: And since this is primarily a switch market. We expect the launch to reflect the time it takes to convert patients from their existing therapy to Danny <unk>.
Speaker Change: From our partnered programs, we anticipate earning substantial royalties from medicines on the market today.
Speaker Change: Including <unk>, which continues to be our largest commercial revenue sorry.
Speaker Change: We expect the Brazilians have been rising has demonstrated to continue and our royalties to reflect that.
Speaker Change: And this also includes a new App, which we expect will continue its upward trajectory this year.
Speaker Change: With these expected launch dynamics, coupled with the resetting of the royalty rate for spin master at the beginning of each year, we anticipate that our commercial revenue will increase as the year progresses.
Speaker Change: Our R&D revenue remains a meaningful contributor to our total revenue guidance, although we expect it to be lower this year than it was last year.
Speaker Change: With a rich pipeline and many partnered programs advancing we have the potential to earn numerous milestone payments.
Speaker Change: And based on the timing of anticipated milestones, we expect to earn much of our R&D revenue in the second half of the year.
Speaker Change: Additionally, as we continue to conduct the cardio transform study we will continue to earn revenue from Astrazeneca for a 55% share of the study costs.
Speaker Change: We project, our 2025 operating expenses to increase in the high single digit percentage range compared to last year.
Speaker Change: This modest increase reflects our commitment to bring our medicines directly to patients and advance our pipeline, while also continuing to exercise sound fiscal stewardship.
This is in 2024 are planned.
Speaker Change: <unk> growth will come from increases in our sales and marketing expenses and as we invest to support the success of our multiple ongoing and planned launch it.
Speaker Change: We expect our R&D expenses to remain steady in 2025 similar to last year at.
Speaker Change: As several of our late stage studies have recently concluded or are on track to wrap up. This year, we are able to reallocate our resources toward our next wave of opportunities just as we have done for the phase III development of <unk> 500, ADC for Angelman syndrome.
Speaker Change: The sizable revenues and modest expense growth, we are projecting a non-GAAP operating loss of less than $495 million.
Speaker Change: We project to end the year with cash and investments of approximately $1 7 billion.
Speaker Change: Our projected year over year change in cash reflects our investments to bring our medicines directly to patients. In addition to advancing our wholly owned medicines in development, while exercising prudent fiscal responsibility.
Speaker Change: Looking beyond 2025 with the numerous opportunities before us we are on track to deliver substantial and sustained revenue growth.
This revenue growth combined with our commitment to drive operating leverage positions us well to also generate positive cash flow.
Speaker Change: To achieve our goal we expect to continue making significant investments to advance our pipeline and bring our growing portfolio of medicines directly to patients.
Speaker Change: Estimate that the programs in our pipeline today have a combined multibillion dollar peak revenue potential.
Speaker Change: This includes estimated annual peak sales of more than $3 billion.
Speaker Change: From our ion <unk> owned medicines, including <unk> and ion 582.
Speaker Change: Additionally, based on our partner's peak sales estimates, we could earn more than $2 billion annually and royalties from our late stage partnered medicines.
Speaker Change: So as you can see with robust revenue growth potential we have a clear path to achieve positive cash flow with that I'll turn the call back to Brent.
Brent: Thank you Beth.
Speaker Change: Becoming a fully integrated commercial stage biotechnology company.
Speaker Change: Mired the commitment and hard work for all employees and we expect to continue our great progress as we enter this next exciting chapter for <unk>.
Speaker Change: Innovation has always been a key differentiator for eye on us and through innovation, we've established a proven and prolific discovery and development engine that has provided us with a rich pipeline of medicines with transformational potential.
And this will continue.
Speaker Change: Our pipeline is consistently delivering with three important FDA drug approvals and just under two years Cal Saudi for Sard, when AOS weigh newer for ATT, our Polyneuropathy and now turn goals for FCS and afford FDA approval anticipated later this year down to the worsen for a J.
Speaker Change: We've also achieved several important approvals outside the U S and we expect a great deal more this year and in coming years.
Speaker Change: And with an advancing late stage pipeline, we have delivered several positive phase III data readouts with more expected. This year and next that are being developed to treat both rare and broad patient populations and today, we have a scalable highly experienced innovative commercial organization in place currently launching turn goals for Fcs.
Speaker Change: And positioned for three additional launches over the next three years.
Speaker Change: This progress provides us with a clear path to achieve positive cash flow driven by our expectations for substantial top line revenue growth.
Speaker Change: This sets us up to deliver accelerating value for all stakeholders.
Speaker Change: Stakeholders and with that will.
Speaker Change: I'll now open the call up for questions.
Speaker Change: Thank you we will now begin our question and answer session.
Speaker Change: To ask a question you May press Star then one on your telephone keypad, if youre using a speakerphone. Please pick up your handset before pressing the keys to withdraw your question. Please press Star then two.
Speaker Change: In the interest of time, we ask that analysts limit themselves to one question then they may return to the queue.
Speaker Change: We will pause momentarily to assemble our roster.
Speaker Change: Today's first question comes from Michael <unk> with Morgan Stanley. Please go ahead.
Speaker Change: Hey, guys. Thanks for taking the question and congratulations on all the progress.
Speaker Change: Maybe just one on <unk> S. H T. G. Just given the essence study as opposed to readout sort of mid year ahead of the core studies and I realize it's more of a safety study enrolling a different population, but what kind of read through could we make from essence to your core studies. Thanks.
Speaker Change: Thank you Mike.
Speaker Change: The essence study.
Speaker Change: Just as a reminder.
Speaker Change: Ah patient population.
Speaker Change: <unk>.
Speaker Change: As Richard described.
Speaker Change: Before.
Speaker Change: Our targeted commercial patient population, it's mildly elevated triglycerides 150 to 500.
Speaker Change: Our target patient population is <unk> 500 milligrams per deciliter triglycerides and above so it is a safety study as you say, Mike as for read through.
Speaker Change: Safety will certainly be a key regroup.
Speaker Change: To demonstrate and we think confirm further validate the safety that we've seen in the FCS patient population. So that's very important as well.
Speaker Change: The apoc III reductions that we expect in that study we.
Speaker Change: We of course will be looking at triglyceride reductions in that study.
Speaker Change: <unk>.
Speaker Change: That as a predictor of what we'll see MSH TG is.
Speaker Change: Somewhat less direct but we still think it will be.
Speaker Change: Sure.
Speaker Change: Still an indicator of what to expect and S. ICD to some extent a lesser extent because it is a different slightly different patient population.
Speaker Change: But we're really focused on the.
Speaker Change: Safety in that study and the target engagement as a read through to <unk>.
Speaker Change: Helpful. Thank you.
Speaker Change: The next question comes from Jessica Fye with J P. Morgan. Please go ahead.
Jessica Fye: Hey, guys. Good afternoon. Thanks for taking my question I was hoping you could talk a little bit about what youre seeing in the TCR Polyneuropathy market. For example, what proportion of new starts do you think youre capturing there. Thank you.
Speaker Change: Yes, Thanks Jess.
Beth: As Beth communicated.
Speaker Change: Communicated earlier, we are so excited about the continued progress here with the launch of Windows.
Speaker Change: <unk> polyneuropathy the growth quarter over quarter, or an increase of 84% and $42 million in Q4 and $85 million on the year I think what that speaks to is the strong demand and the continued growth that's within that category right now.
Speaker Change: Currently new to brand share is about 40% for <unk>.
Speaker Change: So we are continuing to to capture in terms of new patient starts a significant portion of those and we expect that to continue to grow over time.
Speaker Change: We're seeing not only centers of excellence, but also community physicians begin prescribing so the expansion narrows and cardiologists are both prescribing.
Speaker Change: We're still seeing a mix of naive switches as well as combination treatment for <unk>.
Speaker Change: So 2025 is really setting up I think to be a very strong year for way to see the continued growth that we saw in 2024 quarter over quarter.
Speaker Change: Thank you.
Speaker Change: The next question is from a cost to worry with Jefferies. Please go ahead.
Speaker Change: Hey, Thanks, so much can you talk a little more about your design for <unk> the phase III.
Speaker Change: Mentioned previously the enrollment rate and that trial is tenex that of FCS what does that imply for the effects size empowered for particularly on acute pancreatitis severe abdominal pain.
Speaker Change: And really how does the event rate assumption, maybe differ versus FCS, but also that essence study that you mentioned isn't necessarily representative of.
Speaker Change: There are other trials and then any feedback from Kols on what would be a clinically meaningful reduction would be very helpful. As well. Thank you.
Speaker Change: Okay.
Kash: Thank you Kash, let me.
Speaker Change: Take a stab at that there were a few things there to unpack are very important.
Kash: Our questions, but then also Eugene.
Speaker Change: <unk> jumped in so.
Speaker Change: Our study.
Speaker Change: <unk> phase III study core and core to our powered of course, well powered for triglyceride reductions, which is our primary endpoints.
Speaker Change: As far as acute pancreatitis.
Speaker Change: Impact on acute pancreatitis events.
Speaker Change: U S. H D. G core studies this has really never been studied before.
Speaker Change: <unk>.
Speaker Change: We did not believe we were well powered.
Speaker Change: For a positive APL come in FCS and we were pleasantly surprised to see what a.
Speaker Change: Tremendous impact we had at reducing AP events in that patient population, even though it's a very small study.
Speaker Change: The higher the triglycerides in patients.
Speaker Change: The greater the risk of acute pancreatitis, that's obvious and well established.
Speaker Change: The <unk> population has somewhat milder.
Speaker Change: Triglycerides on average compared to FCS. So you might expect a lower rate of acute pancreatitis in that study in that patient population.
Speaker Change: Nevertheless, we have more than 10 times the number of patients in our core studies.
Speaker Change: <unk>.
Speaker Change: Which of course allows us to accumulate potentially more events.
Speaker Change: So.
Speaker Change: Although we're not necessarily powered and no one's ever studied this before so it would be difficult to power a study on reduction of AP and AR http. Certainly the balance FCS daily lenses.
Speaker Change: Some confidence that we'll see a significant.
Speaker Change: Meaningful signal in acute pancreatitis and S hcg.
Speaker Change: I'd like to add anything to that no not really.
Speaker Change: There was another question about clinical meaningfulness of reduction of course.
Speaker Change: That said, it's not really clear there is no particular threshold is considered to be clinically meaningful in terms of BP reduction.
Speaker Change: So we're hoping to see is really any significant reduction.
Speaker Change: Overall.
Speaker Change: So those broad set of course, the powering of the study.
Speaker Change: It is not.
Speaker Change: It's something that we were able to model based on any existing data.
Jan: The next question comes from Jan <unk> with Wells Fargo Securities. Please go ahead.
Jan <unk>: Oh, great. Thanks for taking our questions and congrats on the quarter.
Jan: First I wanted to have a quick follow up to a prior question.
Speaker Change: We knew.
Speaker Change: Polyneuropathy, 84% quarter over quarter growth.
Speaker Change: How much of that growth is driven by switching.
Speaker Change: I did hear a theyre, both naive patient in Switzerland patient, but wondering how much.
Speaker Change: <unk> is the switch from FARA and <unk>.
Speaker Change: My main question.
Speaker Change: I think Biogen announced a couple of.
Speaker Change: Updates to neurology collaboration.
Speaker Change: <unk>.
Speaker Change: Could you provide a little more color and what's the plan for those programs. Thank you.
Speaker Change: Sure Kyle please take the call.
Kyle: On a quarter over quarter growth, what's driving that.
Speaker Change: Happy to comment on Biogen, yes, the growth as we know in this market less than 20% of the patients are currently being treated in the Polyneuropathy space.
Speaker Change: With the therapy today, so the opportunity here remains to grow this market and Thats really what were seeing and thats. The focus that astrazeneca and our team is half in terms of identifying newly diagnosed patients and getting those naive patients started on treatment.
Speaker Change: We are hearing consistently from physicians is that there is improvement in quality of life.
Speaker Change: The safety profile and the Tolerability of <unk> is very strong and access to treatment is extremely strong the majority of patients as I highlighted have a zero dollar out of pocket expense thats, regardless, if they are commercial or Medicare patients so to be able to afford the medication on top of the profile.
Speaker Change: And the ability to self administer we knew it.
Speaker Change: <unk> of their choosing continues to resonate extremely well so as the market expands physicians are choosing <unk> over some of these other treatments now in the instances where there are switches from other therapies. The main driver for that really is the ability to self administer.
Speaker Change: Seeing very good access and very good coverage and if patients are able to do this on their own and not have some of the challenges associated with site of care and they can do this at a place of their choosing physicians and patients are choosing way new up so with a very highly performing medication combined with.
Speaker Change: The ability to self administer it's really making a differentiation possible quarter over quarter, and we're seeing that growth due to that.
Speaker Change: And then regarding the other part of your question, yet and we Couldnt be more pleased retained global rights for both of these programs. These programs that you're referring to.
Speaker Change: Our our Alpha Nucleon program.
Speaker Change: Is in development in Phase II development.
Speaker Change: Multiple system atrophy and the work two program, which is indicated for Parkinson's.
Speaker Change: We couldn't be more thrilled to retain.
Speaker Change: Full control of these programs.
Speaker Change: Just a little color.
Speaker Change: To add to these the.
Speaker Change: Alpha some nuclear program.
Speaker Change: We required the decision by Biogen to opt in.
Speaker Change: In on these based on park.
Speaker Change: Partial data.
Speaker Change: The study that's ongoing and in fact, they really only had access to the low dose cohort at the time. This is this was based on the contract.
Speaker Change: And for this particular program and like I said, we're thrilled to have full control of this very important drug.
Speaker Change: Going forward the <unk>.
Speaker Change: Program was a very small study.
Speaker Change: 12 weeks of treatment, obviously, youre not going to have any clinical data meaning.
Speaker Change: Meaningful data.
Speaker Change: And a 12 week study in PD patients.
Speaker Change: The study was designed for safety and target engagement.
Speaker Change: We're very pleased with what we saw in safety, we're very pleased with the magnitude of the hard work to reductions we saw in the study drug.
Speaker Change: Definitely deserves to be further developed and we're looking forward to.
Speaker Change: Forging a path forward for both programs.
Speaker Change: Arc, <unk> and Annapolis nucleus per ounce nucleus, we're having we're expecting to have data.
Speaker Change: MSA.
Speaker Change: Later this year.
Speaker Change: Our partnership with Biogen remains remains very strong and this was essentially a R&D prioritization decision bye.
Speaker Change: By Biogen.
Speaker Change: Great. Thanks, a lot of the car.
The next question comes from Jay Olson with Oppenheimer. Please go ahead.
Jay Olson: Oh, Hey, congrats on all the progress and thank you for taking the question.
Jay Olson: For <unk> I think you mentioned 3000 patients in the U S. Could you just talk about how many of those patients are currently diagnosed and available for treatment and if it's not too early how many of those patients are on treatment or any other important metrics you could share to help track the launch.
Jay Olson: <unk>. Thank you.
Speaker Change: Yes, Thanks Jay.
Jay Olson: I can't be more excited than to.
Jay Olson: Kind of talk about <unk> goals, obviously, a rare disease population, we're doing a lot of work right now.
Jay Olson: Number one identify number to diagnose and then finally get prescriptions written and get these patients on drug.
Jay Olson: The launch is going very very well when you look at the label that we received a very broad label its a clean label.
Jay Olson: It allows the physicians to prescribe <unk> for clinically or genetically diagnosed patients.
Jay Olson: We have a pea in the label demonstrating substantial reductions in acute pancreatitis and we've got first mover advantage, which allows us to develop this market and to take the patients that you are asking about and move them onto touring goals are very quickly.
Jay Olson: The feedback that we're receiving already is that all of the stakeholders be it patients hcp's the advocacy groups payers et cetera have been very very positive about <unk>.
Jay Olson: They are they are really excited to have a treatment option when they've never had a treatment option before.
In terms of execution around this plan.
Jay Olson: We have product and channel before the end of the year, we launched in 2024 and everything that.
Jay Olson: We've been trying to do to be able to deliver treatment to these patients is going very well now up to 3000 patients. There are several hundred right. Now that are currently identified and they are continuing to come in as I mentioned and become diagnosed formerly in and get prescriptions written for us. So we've got some time.
Jay Olson: In terms of the momentum and the launch ramp here.
Jay Olson: On the.
Jay Olson: On the metrics, we're not disclosing too many metrics. Obviously this is a competitive market that we're in but what we're really encouraged by right. Now is the number of physicians that we've seen identifying and prescribing. So we've got a good breadth of prescribers, we are seeing a mix of.
Jay Olson: Specialties prescribing as well, so we have endocrinologists and cardiologists.
Speaker Change: Does that have an interest in lipids and also Pancreatotomy G.
Jay Olson: Our prescribing train goals, which was to be expected.
Jay Olson: The other thing that we're keeping an eye on is time to prescription and how long. It takes to go from prescription to actually getting the drug filled into the patient and that's going very very quickly faster than we had expected here early on and what that's telling us is that the FCS diagnosis, if it's either clinical or genetic is.
Jay Olson: Confirming these patients and physicians are working through the medical exception process in order to justify the prescription in getting these patients on treatment quickly.
Jay Olson: The final thing I'll say is.
Jay Olson: Our I honest every step program is executing very well and that allows us to interact directly with patients and do disease education and product education and support them through the reimbursement process.
Jay Olson: And patients are giving us very positive feedback about the ability to self administer with an auto injector on a monthly basis and the profile of the drug is playing out very positively here in the first couple of weeks of launch so thanks for asking.
Jay Olson: Thank you.
Speaker Change: The next question comes from Jason <unk> with Bank of America. Please go ahead.
Speaker Change: This is chi on for Jason Thanks for taking our question.
Speaker Change: I guess I would like to fall off during the course of launching the Fps. Thanks for all the commentary on the early launch.
Speaker Change: So far.
Speaker Change: I'm QE is based.
Based on early launch experience, what insurance company you're seeing.
Speaker Change: Ill requirement in terms of documentation.
Speaker Change: First of all in consideration with sometimes done some dock chest on one thing that we have purchased that genetic confirmation is the most straightforward documentation to guests insurance company at one four it somewhat a bit of a gray area. When it comes to clinical diagnosis part of it as a lack of contest this diagnosis.
Speaker Change: Some of it as one insurance company X SAP as clean clinical diagnosis.
Speaker Change: Criteria.
Speaker Change: Talk about that and when you talk about several hundred patients currently identify them become formerly diagnosis, formerly God knows how many of those are getting genetically confirmed how many of those are.
Speaker Change: Gavin clinically diagnosed and if you can talk about that mix within that 3000 patients Praful I think you have to estimate that would be great as well. Thanks. So much.
Speaker Change: Yes, Thanks Chi.
Speaker Change: First let me just touch on the insurance process. The first three to six months as is typical.
Speaker Change: Going to go through a medical exception process. So there are really there are very few plans so far that have established formal criteria.
Speaker Change: To say this is what's absolutely required. So then the question becomes.
Speaker Change: What is the history of the patient what steps is the physician gone through to actually.
Speaker Change: Substantiate and validate that this truly is an FCS patient so that they can get the coverage.
Speaker Change: By the plan and ultimately get the drug approved.
Speaker Change: The most straightforward is a genetic confirmation I think thats the easiest one.
Speaker Change: However, we have seen both clinically and genetically diagnosed patients work through the medical exception process very efficiently with justification of outpatient triglyceride levels the history of the patient.
Speaker Change: Age of diagnosis symptoms to symptomatology right abdominal pain.
Speaker Change: Pancreatitis potentially in their history. So there are a lot of other things to unpack in terms of the patient presentation that ultimately will justify or qualify that patient for <unk>.
Speaker Change: For an approval from the health plan and as I mentioned as well we're seeing this through both the commercial and Medicare segments of the business. So we're most optimistic about is that physicians are doing this the right way, they're identifying FCS patients are justifying it through one of those two means and supporting that patient through the process very quickly.
Speaker Change: Yeah.
Speaker Change: I don't have a number that I can share with you in terms of how many have been clinically versus genetically confirmed at this point.
And then I have gone through our process.
Speaker Change: But yes, obviously both are being approved.
Speaker Change: In terms of.
Speaker Change: Of getting that approval.
Speaker Change: Lack of consensus we have not heard yet.
Speaker Change: Using the <unk>.
Speaker Change: FCS scoring tool that doctor heavily published at the end of last year.
Speaker Change: It seems to be a pretty straightforward tool for them to be able to use and substantiate and validate for these patients is what we're seeing based on the fact that it has been published.
Speaker Change: So.
Speaker Change: Not to not to break out the mix, but other than that I'm very encouraged here early on at the coverage.
Speaker Change: There's more to learn in terms of coverage and then payers will be establishing criteria throughout the first six months or so and we're working directly with the payers in order to make sure that there is a reasonable reasonable path forward for these patients to be able to have access to <unk>.
Speaker Change: Thanks, Karl and thanks very much.
Speaker Change: Two points that I will just add to that.
Speaker Change: We're very pleased with the speed to genetic diagnosis that we're experiencing.
Speaker Change: So far in one to two weeks for the genetic diagnosis. When we go that route and I also think it's reasonable to assume that any aspect of diagnosis that physicians are unfamiliar with today. They will become more familiar with as time goes on and we're driving a lot of that work, especially utilizing the north American <unk> diagnosis.
Speaker Change: Syria to.
Speaker Change: To build that familiarity with physicians, so so I expect that to improve.
Speaker Change: As we go forward.
Speaker Change: Great. Thanks, so much.
Speaker Change: The next question comes from David Leibowitz with Citi. Please go ahead.
Alright. This is <unk> on for David Lebowitz. Thanks for taking the question I also have one on the <unk> readout. It's regarding the 12 month time point and the trial is on the primary so we know that these <unk> patients, they're going to be coming in lower.
Speaker Change: With much lower TG level has been in FCS and likely different rates of Aps at baseline as well and so I'm wondering if there is no clinical consensus on how much TG lowering is actually beneficial as you said just wondering what the reasoning was behind the selection of that 12 month timeline and just overall what is our understanding in this part.
Speaker Change: Relation so far as to what they need.
Speaker Change: Thanks.
Speaker Change: So.
Speaker Change: Thank you for the question.
Speaker Change: And Richard.
Speaker Change: Blow up with anything.
Speaker Change: You wanted to touch on answer my comments. So the primary endpoint is triglyceride lowering it six months to full.
Speaker Change: Study readout is at 12 months, so the primary endpoints at six months on Tg's.
Speaker Change: We have a very rapid response on <unk> III reductions substantial lowering of apoc III substantial and rapidly lowering of triglycerides based on our previous clinical data.
Speaker Change: For <unk> as well as our balance FCS data so.
Speaker Change: Where are we strongly believe we're very well powered on the primary endpoint.
Speaker Change: Regarding acute pancreatitis as I mentioned earlier.
Although.
Speaker Change: The rate.
Speaker Change: Our rate of AP and <unk> patients is not well documented in the literature, we will be after our phase III outcome.
Speaker Change: We believe that we have we're in a good position based on our FCS REIT data as a read through.
Speaker Change: To show clinically meaningful reductions in acute pancreatitis in this study.
Speaker Change: Based on what we saw on balance I think that's driving a lot of it I thought you Richard.
Speaker Change: Yes.
I would also say that we see events being.
Speaker Change: Sure.
Speaker Change: Adjudicated by our independent Adjudication Committee and the events are accruing over the course of this study.
Speaker Change: And it's looking very good.
Speaker Change: The other thing I would say about triglycerides and clinically meaningful that has been determined by the regulatory agencies.
Speaker Change: Certainly the FDA has has said significant risk occurs above 500 and in increases as the triglyceride levels increase so by decreasing triglyceride levels.
Speaker Change: Whatever the amount is.
Speaker Change: <unk> decreasing.
Speaker Change: The risk for these patients having an acute pancreatitis.
Speaker Change: So I think that's the primary.
Speaker Change: Youll have the study obviously is to reduce their triglyceride and risk for acute pancreatitis, and we'll be able to monitor that and CD.
Speaker Change: So it's very soon yes, let me add to that from a commercial viewpoint.
Speaker Change: Currently patients with severely elevated triglycerides.
Speaker Change: Our on fiber its official oils and other things status to try to reduce their triglycerides.
Speaker Change: <unk> cardiologists and endocrinologists are not getting these patients low enough they need a better more effective triglyceride lowering treatment in order to meet the established guidelines that are already in place. So the guidelines are there already let's say you need to be below 500 in order to get out of risk as Richard was talking about from a regulatory standpoint.
Speaker Change: But most importantly from a commercial standpoint, we know that physicians are trying to get there and they're treating hundreds of thousands of patients already and Theyre just unfortunately.
Not able to do so because they don't have a therapy that sufficient in order to accomplish that and thats, what we hope to be able to bring to the market here shortly with an approval in <unk> with all is awesome.
Speaker Change: Yeah, I think it's also important to emphasize that.
Speaker Change: <unk> is not a asymptomatic disease, it's a very serious symptomatic disease that in addition to acute pancreatitis. These patients suffered from serious cognitive often serious cognitive impairment serious body pains.
Speaker Change: Nausea, and so forth and often land in a hospital, even without an AP event because they are in such fear of having an <unk> event, because the body pain and we think that.
Speaker Change: That will go a long way in the <unk>.
Speaker Change: Success commercial success.
Speaker Change: <unk> and S. H T G.
Speaker Change: The next question is from Gary Nachman with Raymond James. Please go ahead.
Gary Nachman: Hi, Thanks, and my congrats as well on the progress so as you prepare for new launches for Dani in it.
Speaker Change: And all of those Austin and S. H T G I.
Speaker Change: Talk about how you're scaling the commercial organization following the FCS launch.
What's in place versus what you need to add.
Speaker Change: Specifically in terms of reps.
Speaker Change: The programs.
Speaker Change: And then just for the Angelman program, just what's your expectations for enrollment timing given the competitive dynamics there. Thank you.
Speaker Change: Yes, Gary Thanks for the question I'll start this is Kyle.
Speaker Change: Fortunately with the co commercialization I'll weigh newer than we were able to build towards our FCS readiness internally. So.
Speaker Change: We've got teams around commercial operations and our market access group and we have our capability with our I honest every step patient support program. Those are kind of the core fundamental foundational components to the commercial team that we've got in place and Theyre ready to go that allow us to scale accordingly, whenever we add.
Speaker Change: Add on new commercial therapies into the mix such as Dani.
Speaker Change: <unk> later, this year and <unk> to follow.
Speaker Change: Where we're at right now for example, with dining dine in Lorson is we've hired the vice president of sales.
Speaker Change: We will build out our regional director team and ultimately our customer facing field teams from there and that is in time and in sequence with what we're doing for the regulatory process for the anticipated approval on August 21.
Speaker Change: So I mean, I think right now as we build its been a sequential build over time and it's been a purposeful build and it's been an intentional build as well to make sure that we're building the right capabilities at the right time and also investing the right amount within those respective functions when we get to <unk>. It will it will grow exponentially as you.
Speaker Change: Would expect based on the size of the market that will be entering into but we'll be able to at our customer facing and field teams at the right time and I'm just excited about the talent and the tremendous accomplishments that we have already had with our teams that are in place and the good product that we have within the commercial group overall.
Speaker Change: And Gary.
Speaker Change: Angelman.
Speaker Change: Enrollment so we're still well on track.
Speaker Change: To initiate.
Speaker Change: Our phase III study in the first half of this year, if things are going well.
Speaker Change: We've also established internal metrics.
Speaker Change: To achieve with respect to enrollment this year by our team.
Speaker Change: That sets us up for completing enrollment in 2026 next year we.
Speaker Change: We do not believe that this trial will be difficult to enroll there's pent up demand and we're really encouraged by the enthusiasm by the community.
Speaker Change: Acquiring about our program when they will be able to enlist enrolling study.
Speaker Change: And this is a relatively large patient population with tremendous unmet need. So that's those are our expectations for enrollment.
Speaker Change: Great. Thank you.
Speaker Change: The next question comes from Yaron Werber with Cowen. Please go ahead.
Speaker Change: Yes.
Yaron Werber: Yeah, Hey, Thanks for taking my question I have a quick question also.
Speaker Change: Okay.
Speaker Change: Do you think about how do you go power.
Speaker Change: Phase III study.
Speaker Change: Given the non preferred trial design, yet, but Unexpressive communications and then maybe for Beth as you think about revenue as you mentioned, it's more second half weighted are there particular milestones we need to keep in mind that are driving that thank you.
Speaker Change: Eugene would you comment on the powering.
Speaker Change: And of course were to jump into yes sure.
Speaker Change: As you know our primary endpoint is expressive communication as assessed by <unk> four.
Speaker Change: There is quite a bit of natural history.
Speaker Change: Data are available utilizing slightly older version of daily, but nonetheless, as we are able to see and.
Speaker Change: And kind of make estimates on how the patients are expected to progress.
Speaker Change: With regard to the ability to communicate which is.
Speaker Change: Unfortunately.
Speaker Change: Unknown primary deficiency in this population they have little to no expressive communication.
Speaker Change: So that combined with our phase two.
Very encouraging phase two data really.
Speaker Change: Allowed us to make some assumptions on the treatment effect size, but we're expecting to see placebo controlled setting for phase III.
Speaker Change: As you know we're also testing two two dose levels.
Speaker Change: Two to one randomization, but essentially about that.
Speaker Change: And the knowledge of natural history.
Speaker Change: Trajectory.
Speaker Change: And this patient population is what we used in our assumptions.
Speaker Change: Are they both are both doses powered against placebo.
Speaker Change: Yes, so our right our goal is to see.
Speaker Change: And effectiveness of both doses. So the two doses are in the same two doses that we studied in the phase II Halo study both of which showed.
Speaker Change: Really really encouraging evidence of efficacy across all domains that we examined using all instruments, whether it be daily for Vineland, SaaS, CGI et cetera Orca.
Speaker Change: And as a reminder, expressive communication.
Speaker Change: Uniformly demonstrated the greatest best outcome in our phase two Halo study, which which that combined with the fact that this is.
Speaker Change: This endpoint is.
Speaker Change: Part of this Angelman phenotype is the most burdensome on pet families that coupled with that's where we sort of even the greatest magnitude is why we settled on the express its communication in our phase II study in that and that certainly was very important.
Along with the natural history data that Eugene mentioned and the power and our powering assumptions for our study which is nearly 300 patients three cohorts in the phase III study design.
Speaker Change: It does.
Speaker Change: Randomized one to one to one or two to one when you're on treatment versus placebo.
Speaker Change: But that you had.
Speaker Change: There's also a question from your own.
Speaker Change: Yes, so on the revenue guidance.
Speaker Change: For this year I think just to answer.
Speaker Change: So to reemphasize.
Speaker Change: We anticipate a shift to commercial revenue this year with <unk> continuing to grow.
Speaker Change: Quarter over quarter.
Speaker Change: <unk> tangles that revenues and in the back half of the year.
Speaker Change: The tiny doors revenues, assuming approval as we think about R&D revenues as you know we have lots of different partnerships and lots of medicines in development under those partnerships.
Speaker Change: No. One particular medicine has a very significant milestone and so there is there is no.
Speaker Change: Sort of wired to milestones that I could point to that are going to.
Speaker Change: Really is a cornerstone for our R&D revenue this year.
Speaker Change: Big piece of it will be the continued R&D funding, we get from Astrazeneca as we conduct the cardio transform phase III study, we get <unk>.
Speaker Change: 55% of those all in cost.
Speaker Change: Members to us from Astrazeneca and that we book as revenue and then there is a whole host of partnered programs, particularly with Biogen.
Speaker Change: Others with Astrazeneca.
Speaker Change: That as they advance we would anticipate seeing milestones over the course of the year.
Speaker Change: As I said much of that being backend loaded.
Speaker Change: Thanks, Brad Thank you Ron.
Speaker Change: Have time for one more question.
Speaker Change: Today's last question will come from Myles Minter with William Blair. Please go ahead.
Speaker Change: Hi, This is Jake on for Myles. Thank you so much for taking my question.
Speaker Change: A couple for you.
Speaker Change: First is on <unk>, we were wondering if we could get some color on your plans for potential ex U S launch and.
Speaker Change: Whether you would be.
Speaker Change: Sort of comfortable going it alone or whether youre looking to find a partner in that as you did for <unk>.
Speaker Change: And then second we wanted to.
Speaker Change: Any updates you have on the next generation <unk> targeting asset with Novartis and weather clinical development, our clinical entry.
It's contingent on a positive readout from the Horizon study. Thank you.
Speaker Change: Thanks Jake.
Speaker Change: Before we get into ex U S S hcg.
Speaker Change: Let me start with FCS for both Fcs.
Speaker Change: And then subsequently <unk>.
Speaker Change: Turning to secure a commercial partner like we did for Dominic.
Speaker Change: Discussions are progressing very nicely.
Speaker Change: And it's consistent with.
Speaker Change: Our commercial strategy that we laid out five years ago.
Speaker Change: That initially we will focus on the U S market and secure our U S commercial partners for our programs.
Speaker Change: We bring to the market.
Speaker Change: Selves.
Speaker Change: And that will evolve and that will change in due time and we're working on that now where we will emerge from the U S market, but today, we will secure an O U S partner to commercialize.
Speaker Change: <unk> for FCS and S. H T G.
Speaker Change: Outside the U S.
Speaker Change: I really do not have much to offer with respect to whether or not novartis will wait for the pellet Carson's readout before initiating clinical testing for our follow on molecules that we provided to them and then license them last year.
Speaker Change: Right with the molecule as its pellet cars, but.
Speaker Change: But the follow on really does.
Speaker Change: It looked like a best in class molecule with respect as compared to everything that's been publicly disclosed to date.
I don't think it matters much on the timing because pellet Carson, who isn't that far away.
Speaker Change: First half of.
Speaker Change: Of next year and the <unk>.
Speaker Change: Follow on molecule for LP Little a CBD that we provided is starting IND supporting toxicology studies now so that has to run its course through there and then and then preparing for clinical testing. So that's really the questions more specifically that's best suited for our Novartis, but thank you. Thank you for the questions and thanks to.
Speaker Change: Everybody, who joined us today and participating in our call. We're really looking forward to an outstanding year ahead, and sharing our progress along the way with you.
Speaker Change: But until then thanks, again and everybody have a great day.
Speaker Change: Goodbye.
Speaker Change: The conference has now concluded. Thank you for your participation you may now disconnect your lines.