Q4 2024 Insmed Inc Earnings Call
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Speaker Change: Good day, everyone and welcome to today's conference call, where we will discuss in the med fourth quarter and full year 2024 financial results and provide a business update.
Speaker Change: I'm joined today by will Lewis, Chairman, and Chief Executive Officer, and Sara <unk>, Chief Financial officer through each provide prepared remarks, after which they will be joined by Martina Flammer, Chief Medical officer for the Q&A session.
Speaker Change: Before we start please note that today's call will include forward looking statements based on our current expectations. These statements represent our judgment as of today and inherently involve risks and uncertainties that may cause actual results to differ materially from the results discussed please.
Speaker Change: Please refer to our filings with the Securities and Exchange Commission for more information concerning the risk factors that could affect the company.
Speaker Change: The information we will discuss on today's call is meant for the benefit of the investment community. It is not intended for promotional purposes and it is not sufficient for prescribing decisions.
Will Lewis: I'll now turn the call over to will for prepared remarks.
Will Lewis: Thank you, Brian and welcome everyone.
Will Lewis: 2024 was an historic year for Eaton Smith, while we celebrated the outcome of one major clinical trial. We also remained focused on laying the foundation for continued success in 2025 and beyond we.
Will Lewis: We believe we are just at the beginning of the realization of more than a decade's worth of work that has put us in a position to have several clinical and commercial catalysts, all hitting major inflection points in quick succession.
Will Lewis: At the heart of our accomplishments in 2024 was the impressive phase III data from the Aspen study for Brent So cat had been bronchiectasis historically when a company has validated our new mechanism of action with the potential to address significant unmet needs across multiple indications. This accomplishment as a resulted in meaningful.
Will Lewis: Patient benefit and consequent value creation, sometimes in the tens of billions of dollars or more.
Will Lewis: Often the phase III readout is just the beginning of the value creation curve. We believe this could be the case for brands, who Canada with the Aspen readout, representing just the beginning of the future potential for D. P. P. One inhibition.
Will Lewis: Aspen success was only part of what made 'twenty 'twenty four special we also welcomed the first data from T. P. I P. In ph ILD, which began to reveal this compounds potential as a best in class treatment for pulmonary hypertension we.
Will Lewis: We also drove steady enrollment across our ongoing mid to late stage trials for Air case, Brent So Canada N T. P. IP all of which remain on track or ahead of schedule for readout.
Will Lewis: Meanwhile, Eric is quietly and steadily produced the most impressive performance in its six year commercial history with record setting revenues that came in higher than even our own internal projections.
Will Lewis: Finally in 'twenty 'twenty four we took actions to deliberately strengthen our balance sheet positioning and submit for success as we accelerate into the year ahead.
Will Lewis: In 2025, do you expected U S launch of <unk> in bronchiectasis in the third quarter is going to take center stage, but you can also expect phase III data for TPI P and P. H in the middle of the year and phase two data for <unk> and Crs without nasal polyps, which we estimate will read out by the end of the year.
Will Lewis: It is worth noting that this string of significant clinical and commercial catalyst does not end in 2025 in the first quarter of 2026, we expect our phase III encore trial for aerospace to read out holding the potential to expand our label to include all patients with Mac lung infection.
Will Lewis: Also in 2026, we expect to share updates from our phase two trial of Brent, So, Canada and hidradenitis Suppurativa from several of our gene therapies, including DMD ALS and Star Guard disease and from our next generation DPP one programs.
Will Lewis: While we launched <unk> Academy in Europe, the U K and Japan, assuming we secure approvals in those territories.
Will Lewis: I believe that our ability to execute on the many opportunities ahead will solidify and Smiths place among a small group of industry peers that have pioneered an entirely new mechanism of action while successfully advancing other programs in parallel.
Will Lewis: Now let me walk you through the progress we're making in pursuit of this ambition starting with Brent So Canada.
Will Lewis: Earlier this month, we announced that the NDA filing for <unk> in Bronchiectasis was accepted by the FDA under priority review with a <unk> date of August 12, 2025, we are thrilled to be one step closer to bringing this important therapy to patients who have waited a long time for such a breakthrough.
Will Lewis: As of today, the FDA has not yet indicated whether it will convene an advisory committee as part of its review process.
Will Lewis: The FDA can make that choice at anytime during the priority review should they call for one we will work to accommodate whatever topics. The FDA may wish to explore as we learned more about any potential outcome, we will share that information.
Now that we know the likely timing for the Fda's decision I'd like to spend a few moments revisiting our expectations for <unk> launch.
Will Lewis: Previously, we provided analogs of strong respiratory launches that we aspire to emulate with Brent, So Canada, including depiction for Sandra Oh fab and to spire.
Will Lewis: Average these products recorded combined revenues for the first two quarters of launch in the high double digit millions, but note that most of these products benefited from approval dates that enabled their first quarter of reported sales to include nearly a full quarter in.
Will Lewis: In contrast, with the potential approval and launch in mid August revenue generation for Brent. So Canada is expected to begin late in the third quarter due to the normal time, it takes from commencing selling activities to recording sales.
Will Lewis: In the case of Erra case, it took nearly four weeks after we launched before the first sales were recognized.
Will Lewis: As a result of these dynamics our expectation is that we will only have a few weeks of sales for <unk> in the third quarter, assuming an approval on the <unk> day.
Will Lewis: We continue to see tremendous excitement in the patient and physician communities for the launch with tens of thousands of patients actively engaging on our disease state awareness website and more than 90% of surveyed physicians in the U S, indicating that they intend to prescribe <unk> to patients with two or more exacerbations upon approval.
Will Lewis: On pricing, we continue to expect <unk> annual U S list price to be in the upper half of our original $40000 to $96000 range at launch.
Will Lewis: This update is based on extensive pricing work conducted post Aspen that incorporated <unk> actual clinical profile to solicit feedback from payers kols patients and others, giving us a more precise sense for what the appropriate price should be.
Will Lewis: At the same time, our top priority and launching <unk>, Canada is to make access as frictionless as possible both for physicians and their patients.
Will Lewis: Our plan will be to deploy a multifaceted market access strategy with the goal of achieving a simple and straightforward prior authorization process to get appropriate patient access to treatment.
Will Lewis: And equally important to get those patients seamlessly reauthorized to maintain that access.
Will Lewis: We believe that this strategy will allow <unk> to reach more patients faster and will result in a smoother runway to achieving peak sales.
Will Lewis: Now just a brief update on our Crs without nasal polyps study of Brent So Canada.
Will Lewis: Crs without nasal polyps is a disease with a clear unmet medical need, which Brent sarcasm could potentially address if it is successful.
Will Lewis: In the U S alone there are roughly 200000 patients going in for sinus surgery, each year and several million, whose disease is not adequately controlled with steroids.
Will Lewis: Being able to offer these patients a once daily oral treatment to potentially help alleviate symptoms and avoid surgery would be a game changer for patients.
Will Lewis: Our ongoing phase two birch trial in patients with Crs without nasal polyps continues to recruit well and we anticipate top line results from this study by the end of this year.
Will Lewis: If successful the Birch trial would provide proof of concept for the use of a DPP one in this disease state and could represent a substantial opportunity there could be similar to or even larger than that of bronchiectasis based on the number of patients who are steroid non responders progressing towards surgery each year.
Will Lewis: In addition, a positive result in birch would serve to further validate the DPP. One mechanism is a pathway that can potentially offer benefits to patients with a variety of diseases caused by neutrophils inflammation, including hidradenitis Suppurativa for which we have a phase II study that is currently recruiting patients.
Will Lewis: Let me now turn to TPI P.
Will Lewis: The phase <unk> data readout in the middle of this year is expected to be meaningful in multiple ways.
Will Lewis: First it will be the largest study of TPI P to date with 102 patients randomized two to one so the results will be the best demonstration of the clinical profile of the drug and second. This trial is designed with a primary endpoint directly measuring the drugs efficacy in the form of reduction in pulmonary vascular resistance or PBR.
Will Lewis: Past studies of other forms of Coprostanol have shown PBR reductions in the mid teens to low 20 percents.
Will Lewis: In our view if treatment with Tpa IP leads to reductions in <unk> that exceed those levels that result, with differentiated from all other assets in the prostacyclin class solidifying <unk> potential value.
Will Lewis: Before I move on I want to briefly mentioned the full phase II results from the ph ILD study, which were presented earlier this month at the pulmonary vascular research Institutes conference in Rio de Janeiro.
Will Lewis: In addition to the positive topline data that were shared from this study last year. We also showcased our lung imaging study conducted as part of the phase II trial, which demonstrated a consistent increase of blood volume in the small arteries of the lungs for patients treated with TPI P compared to placebo.
Will Lewis: One might expect to see a transient benefit and the small arteries. Shortly after receiving a dose proportional the images in our study were primarily captured long after dosing at a median of more than eight hours post dose and still showed impressive basal dilation of the small vessels.
Will Lewis: While patient numbers in this lung imaging study, where small and should therefore be interpreted with caution. These data provide evidence that once daily dosing of TPI P can achieve important effects on the small pulmonary arteries, even after a significant amount of time has passed after dosing.
Will Lewis: This supports our conviction that <unk> may provide clinically meaningful benefits to patients with either ph ILD or P. H, we remain on track and look forward to kicking off the phase III trial in ph ILD in the second half of this year followed shortly thereafter by a phase III ph trial.
Will Lewis: Finally, let me touch on aerospace, which continues to drive strong revenue growth across each of our geographic regions are continued.
Will Lewis: <unk> continued to be impressed with the performance of our commercial teams in the U S Europe, and Japan, who are responsible for these extraordinary results. This.
Will Lewis: This is particularly remarkable given that the same team was recruiting hiring and training of 120, New U S sales employees last year in anticipation of the <unk> launch and on top of all of that they delivered a record setting year for Aercap sales, while also positioning us for success in 2025.
Will Lewis: This track record of strong execution gives us confidence to provide revenue guidance for aerospace a $405 million to $425 million for 2025, representing yet another year of strong double digit growth for the brand.
Will Lewis: As a reminder, the strong commercial performance, we have seen and expect to continue to see for aerospace is all within the currently approved refractory patient population.
Will Lewis: If the encore trial readout in the first quarter of 2026 positive it could lead to an expansion of the current label to include all patients with Mac lung disease, addressing a significant unmet need and potentially propelling erra case into a blockbuster brand.
Will Lewis: In short I couldn't be more excited about our positioning going into 2025, our commercial engine is humming our mid to late stage clinical programs are advancing in our early stage research is accelerating and showing promise I will now turn it over to Sarah who will walk us through this quarters financial results.
Sarah: Thank you will and good morning, everyone.
Sarah: Earlier today, we issued a press release detailing our financial results for the fourth quarter and full year 2024.
Sarah: I would like to highlight some details of those results now.
Sarah: As of year end, we had over one $4 billion of cash cash equivalents and marketable securities on our balance sheet.
Sarah: It is relatively unchanged since the end of the third quarter.
Sarah: Excluding the impact of stock option exercises and net proceeds received in the fourth quarter from the additional $150 million term loan from pharma Con discussed last quarter.
Sarah: Our underlying cash burn in the fourth quarter was approximately $191 million, which as expected was higher than recent quarters.
This figure included the payment of the application fee associated with the filing of our NDA for <unk> in December as well as the impact of higher head count and other expenses related to ongoing preparations for the potential launch of <unk> in the third quarter of 2025 if approved.
Sarah: We believe these investments have the potential to lead to future revenue growth offsetting the associated costs and potentially putting us on the pathway to sustained profitability.
Sarah: I will now walk you through our commercial performance in 2024.
Sarah: Last month at an Investor Conference, we disclosed that our global net revenue for 2024 was $363 $7 million, reflecting 19% year over year growth and exceeding the top end of our guidance range for the year.
Sarah: This result was driven by the highest quarterly sales for Eric Heath in its history in the fourth quarter of 2024, representing the fifth quarter in a row in which we have seen double digit year over year revenue growth in each of our regions.
Sarah: Specifically in the U S net revenue for 2024 with $254 $8 million up 14% compared to 2023.
Sarah: This growth was driven by strength in new patient starts and continued efforts by our team to educate on the importance of remaining on therapy.
Sarah: In Japan, 2024, net revenue was $87 $7 million up 33% compared to 2023.
Sarah: This outstanding performance was driven by the excellent execution of the commercial team leading to higher new patient starts and a strong treatment continuation rate amongst existing patients.
Sarah: Part of this strong performance also reflects the investment made earlier in the year to add six additional sales reps, bringing the total number of reps in Japan to 32, which enhanced our ability to reach patients in need across the region.
Sarah: In Europe and rest of World net revenue in 2024, it was $21 2 million up 39% compared to 2023.
Sarah: This growth reflects continued strength in new patient starts, particularly in Germany, and the U K.
Given by the exceptional work of our European commercial team.
Sarah: In 2025, we continue to expect full year aerospace net revenue to be between 405 and $425 million.
Sarah: As a reminder, this guidance range does not include any contributions from <unk>.
Sarah: Let me now turn to a few additional financial items.
Sarah: Our U S gross to nets, and full year 2024 or 17%.
Sarah: Which was consistent with both our guidance and internal expectations.
Sarah: Looking forward to 2025, we expect gross to nets for aerospace to be in the high teens to low twenties, driven primarily by retroactive price inflation adjustments under the inflation reduction Act.
Sarah: Going forward, we expect this increase.
Sarah: To increase as more of the responsibility for catastrophic coverage for Medicare patients being treated with aerospace shifts and Smith.
Sarah: For <unk> pricing and ASIC access dynamics will not be determined until the time of lines. So we are not yet in a position to provide specific <unk> guidance.
Sarah: However, based on our review of historical analogs for specialty launches and the new responsibility of manufacturers to cover 20% of catastrophic coverage for Medicare patients under the IRA.
Sarah: We believe a 25% to 35% gross to net at launch is likely to be a reasonable assumption in this environment.
Sarah: Moving to our operating expenses for 2024.
Sarah: Cost of product revenues for full year, 2024 was $85 $7 million or 23, 6% of revenues, which is consistent with our historical performance.
For full year 2020 for research and development and SG&A expenses were $599 million and $462 million, respectively, reflecting continued investment in our early and mid to late stage pipelines as well as investment in <unk> commercial readiness initiatives.
Sarah: In closing we believe in Smith is in a unique position of strength, both financially and operationally.
Sarah: We produced record setting revenue in the fourth quarter and this is strong aerospace revenue guidance for 2025.
Sarah: Additionally, we are currently well capitalized with more than one $4 billion of cash on our balance sheet.
Sarah: We look forward to thoughtfully deploying that capital in the service of our patients and shareholders as we deliver on the upcoming catalysts in 2025 and beyond.
Sarah: We would now like to open the call to your questions. Operator may we take the first question. Please.
Sarah: Thank you we will now begin the question and answer session. If you have dialed in and would like to ask a question. Please press star one on your telephone keypad to raise your hand and joined the queue.
Sarah: I would like to withdraw your question simply press Star one again.
Sarah: Please be reminded that each analyst is allowed one question and one follow up if you have additional questions you may hop back into the queue again. Thank you.
Speaker Change: And your first question comes from the line of Neil <unk> with Guggenheim Securities.
Sarah: Please go ahead great.
Speaker Change: Okay, great Yeah. Thank you for taking my question. Thanks for the information on the call. So maybe just on <unk>.
Speaker Change: Well I appreciate the comments you made just around the opportunity potentially in Crs without nasal polyps.
Speaker Change: Just maybe if you can just sort of level set expectations as we look forward to the phase two data. So what would you want to see from that data set and what would be considered good data and sort of move move that opportunity forward I would agree with you.
Speaker Change: Is it people are not really appreciating that indication yet so I'm just kind of trying to get a sense of like what you are hoping to see before you.
Speaker Change: People start looking at it in their models.
Speaker Change: Well first of all thanks for the question because I think you just put your finger on one of the larger opportunities that <unk> is coming up upon.
Speaker Change: Is this opportunity in Crs without nasal polyps, we have.
Speaker Change: A lot of reasons for enthusiasm for this indication and the potential of <unk> to have impact.
Speaker Change: The study I am actually going to ask Martina, maybe walk through a little bit of how we think about what we're looking for a relative to other work that's been done in this space and also <unk>.
Speaker Change: Thank you.
Speaker Change: More broadly about the unmet medical need here to really put a finer point on this this is every bit as big and potentially bigger than bronchiectasis and to remind everybody. If we're able to address successfully the patient populations that have already been diagnosed we believe that that will produce a peak revenue number north of 5 billion.
Speaker Change: So to talk about Crs is an interesting opportunity that is potentially larger than that I think should place in context. The importance of turning your attention to this where we will have phase two data we expect by the end of the year Mark do you want to talk a little bit about the.
Speaker Change: The study.
Mark: Yes, well so what are we looking for in Trs without nasal polyps and Alpha study.
Speaker Change: First of all there's no <unk>.
Speaker Change: Treatment that is indicated for this patient population apart from a steroid.
Speaker Change: Inhaler that you may well be aware of so this is a totally new mechanism with Brent to captive of addressing the disease.
Speaker Change: If you think about the Crs.
Speaker Change: Crs without nasal polyps. This is a chronic inflammatory disease. It leads to changes in the power of nationals in the sinuses any changes here, how the cells that produce the mucus.
Speaker Change: A change that means more mucus production more inflammation and that leads to a continuous increase of neutrophil cells migrating into the sinuses that is that is the basic for this disease. So what do we need to do in order to truly impact the <unk>.
Speaker Change: And how does disease works as you know how <unk> works it will do that by impacting the neutrophil as it is maturing in the bone marrow, what do we want to see in Birch, we're using as a primary endpoint. The measurement that's called the sinus total symptom score. This is a measurement that in.
Speaker Change: <unk> the three critical criteria for these patients and this is nasal congestion nasal discharge.
Speaker Change: Pain or pressure.
Speaker Change: In addition, what we will measure is something that is called the nasal congestion score a snot or subsidize the Q Lps or quality of life measurement validated in this patient population as well as the loss of smell. The study. It goes over 24 weeks, we're looking at 10 and 40 milligram.
Speaker Change: A friend to <unk> versus placebo, whatever we powered to show a repowering. This this is a proof of concept study, 80% and then also level off 0.1 to show a difference as small as points nine of a unit change or a point change for diesel sign.
Speaker Change: <unk> total symptom score that is what we're looking for we really only have one other measure and that is D. As you are purely familiar with the <unk> studies that have done that in that have done studies using a very similar score. The scores may have different names you see sometimes.
Speaker Change: Our comprehensive sign a score, but they all measured the same things congestion discharge and facial pain and what they have shown was a treatment effect between warm.
Speaker Change: Seven and nine are in their reopened two study so that is really the only one.
Speaker Change: That you have as a comparison we in the boat study are looking for the effect of friends, who kept up on top of nasal steroids. So patients are already on a stable dose of nasal steroids for four weeks before they are being randomized to brand for pet.
Speaker Change: And the only other thing I would add to that is.
Speaker Change: So when you think about this the primary endpoint in total symptom score incentives total symptom score patients coming into the study you have to have a score of five or greater. So these are highly symptomatic patients that have already been exposed to best available treatment.
Speaker Change: Many of them have had surgery previously and so the ability to have impact here will be very material for this patient population and we're hearing that from the treating physicians as well and I think thats part of the reason why youre seeing the trial enroll so effectively.
Speaker Change: Okay, alright, thanks for the information.
Speaker Change: Your next question comes from Joseph Schwartz with Leerink Partners. Please go ahead.
Speaker Change: Great. Thanks, very much and congrats on all the progress I was wondering beyond generating strong clinical data and assembling a solid sales force. What other factors are in your control and are you leveraging to ensure a strong launch for <unk> and bronchiectasis.
Speaker Change: Well, if we think about the U S launch and the <unk> date of the Middle of August of this year I think probably the thing that keeps my attention more than anything else. I mean, we have to have it all running in parallel so let's be really clear our medical affairs the commercial preparation.
All those things, but really it comes down to market access in my mind is the one element over which we have control and which we really want to ensure we have the right strategy and I am highly confident based on where we sit today that we're in a good position with that.
Speaker Change: That relates not only to the selection of price, which is obviously driven by the impact we have on patients but also.
The ability to work with the market access world to ensure a frictionless launch what we mean by that is <unk>.
Speaker Change: Verbal attestation by the physician to bring patients other appropriate onto therapy and the re authorization to ensure that they have continued to access and benefit from the therapy. Once prescribed to accomplish that we are willing to do some minor contracting.
Speaker Change: We're not going to go into the details of what that will look like because that process is literally getting underway in the course of the next several months but.
Speaker Change: I will say that we sit in a very strong position with regard to the pricing studies, we've done the background that leads into the market access discussions and what we think those are going to yield and that I think is the single most important thing that remains under our control that we want to ensure we get right.
Speaker Change: And the other thing I would add here.
Speaker Change: The one other thing that's in our control is as you know last year, we augmented our sales organization and we brought in those additional 120 reps as we mentioned last year early this year will be a additionally, augmenting to add more in the market access the field access managers in the case manager. So we have brought on additional field access managers.
Will Lewis: That will help with that friction friction less launch that well was describing as well.
Will Lewis: Very helpful. There is this might be a more difficult question to answer but it seems important to ask so.
Will Lewis: I will there's been some signs that many government agencies could face some staffing shortages. So I was just wondering how do you feel about the availability of adequate SBA staff remaining in place to review Brendan Kennedy.
Speaker Change: Tom do you have any insight into the folks who actually be.
Will Lewis: Performing the review.
Will Lewis: So obviously, we're in the middle of the review now where this process kicked off at the end of last year. When we put our submission and I would characterize our interaction is a regular steady and very encouraging consistent with all of our expectations. As we go one layer deeper and consider hypotheticals, where.
Will Lewis: Government staffing becomes challenge for whatever reason there is always unpredictable element to this but it's important for everyone to remember that the staff that are involved in the review of an NDA are funded by the <unk> fees from industry. So they should not be impacted in our estimation in the event of disruption to other.
Will Lewis: <unk> of that particular agency.
Will Lewis: We'll see what happens obviously.
Some unknowns out there, but I would describe our current situation is extremely encouraging as evidenced by the granting of priority review and the pace at which our interaction has been taking place.
Speaker Change: Thanks, Ken.
Your next question comes from Jessica Fye with JP Morgan. Please go ahead.
Jessica Fye: Hey, guys. Good morning, Thanks for taking my questions. First one is can you just remind me of your estimate of how many U S. Bronchiectasis patients have had two or more exacerbations in the past year to the extent that could be keith or patients being reimbursed for <unk> and second one is just what's the right way to think about the trajectory.
Jessica Fye: As for SG&A and R&D this year. Thank you.
Jessica Fye: Sure. So I'll give the second question is Sara the response and the short answer to the first one is about 50% but to put a more refined description on that currently we know diagnosed from for medical records that there are roughly 500000 patients in the U S that have been diagnosed with bronchiectasis of those we estimate about half.
Jessica Fye: Have have had two or more exacerbations in the last.
Jessica Fye: Year last 12 months, but it is important to note and Youll see this in many of the materials that we produced that we think of this is just the beginning of the potential addressable market. There are many patients who either falloff diagnosis codes or over time arent reporting exacerbations in a way that would put them within the circle of potential eligible pay.
Jessica Fye: <unk> for treatment.
Jessica Fye: <unk>, those who have COPD and asthma as comorbidities and are experiencing exacerbations.
Jessica Fye: Those patients if they have a C. T scan would be and determined to have bronchiectasis would be eligible and on label and that population could be quite substantial we have more to do there to understand that but it's our belief that there are.
Jessica Fye: Many patients that will benefit from this therapy that fall within those categories.
Jeff: And then Jeff on the question on <unk>.
Jeff: SG&A and R&D, we haven't provided specific opex guidance as you know and we believe that early investment that we've made to support this launch will show to be fruitful with.
Jeff: Revenue curve, assuming approval and all those good things I will say, we don't expect that opex is going to.
Jeff: The decrease in the future.
In the near term, we are continuing to invest and we think that's the right thing for shareholders on the R&D side is we're starting Crs H S TPP entering phase III and.
Jeff: Commercial <unk>.
Jeff: And a side specifically I mentioned, we are adding on some additional resources and market access to ensure that the launch is a successful as possible, but I will say is as.
Jeff: As you think about once the launch curve starts a shape in 2006 and beyond as the percentage of SG&A to revenue that percentage will obviously begin to look much more favorable.
Jeff: Okay.
Jeff: Thank you.
Speaker Change: Your next question comes from redo borrow from TD Cowen. Please go ahead.
Speaker Change: Hi, guys. Thanks for taking the question and well thank you for emphasizing market access.
Speaker Change: I guess Medicare as the new bio stats in our conversations.
Speaker Change: I have the Medicare question and then a follow up question on the June data.
Speaker Change: Well since you guys are specified small manufacturers by the IRA is that manufacturer discount program and the catastrophic phase you've got the sliding scale of <unk>.
Speaker Change: Coverage picking up that 20% catastrophic over five or I guess the next five years, if we're understanding that program correctly can.
Speaker Change: Can you talk about two things can you can you talk about how you may have to accommodate well first of all do you have to take that second are you going to have to accommodate more in prior authorizations or what youre expecting prior authorizations could be and how that might impact both.
Speaker Change: The launch dynamics and also Sara the 25% out of the gate.
Speaker Change: It doesn't imply that.
Speaker Change: Sliding scale for the small manufacturers.
Speaker Change: Yeah. So a couple of points first as we will make a distinction between <unk> and Brent sarcasm, Eric case does benefit from the specified small manufacturers classification.
Speaker Change: And as a consequence as you outlined accurately there will be a phased in portion that we will have to.
Speaker Change: Cover it starts at 1% of catastrophic coverage in 2025, and it ramps up to 25 pardon me, 20% by 2031, so thats the scale and we can give you the actual year over year increases.
Speaker Change: If you'd like them.
Speaker Change: As we think about Brunswick, Canada, but does not have that benefit. So we get that we get hit with that right out of the gate and that is something that we're contemplating as we consider our market access strategy, so that that element.
Speaker Change: Can be considered as we think about the cascade from gross.
Speaker Change: <unk> down to what the net price would ultimately be Sarah I don't know if you want to comment a little bit on the guidance. We've given as we think about that and its implications for gross to nets in the setting of Brent So Canada sure. So specifically on air cases will mentioned that services the sliding scale and in the prepared remarks, I was trying to point to that with the guidance for.
Speaker Change: <unk> 25 of high teens to low twenties, and then moving forward. We will obviously have the sliding scale that will need to be adjusted within the gross to net for aerospace for brands out of the 25% to 35% at launch based on precedent and based on looking at other specialty.
Speaker Change: Right out of the gate as well said, we believe the mix of patients will be about 60% Medicare patients are right out of the gate for Brian. So you have 12%, 20% or 60%, 12% for gross to net.
Speaker Change: And so we took that into account as we looked at precedent at that 25% to 35% at launch seem to be a reasonable analog.
Speaker Change: Got it and then a quick follow up on.
The PBR data more specifically actually about the side effect.
Data that may be coming out concurrently just given one of the drawbacks.
Speaker Change: Of the current competition is the cost for dry powder inhalers.
Speaker Change: Is there something in that dataset that would let you feature.
Speaker Change: Potential reduction in cost or cost burden, whether it's.
Speaker Change: 24 hour cough, right, that's Houston, RCC studies, or some sort of cost and quality of life scale as it impacts.
Speaker Change: When will we get something like that with the midyear data.
Speaker Change: So a couple of thoughts there. The first is that obviously, we track adverse events in detail and so some element of of cough is represented in this population would certainly be captured.
Speaker Change: You want to back up though and just highlight that the data we received in the ph ILD study was quite encouraging in this regard and if we back up even further to the chemistry. That's involved here what we have as a pro drug that takes <unk> and depends of 16 carbon chain with an ester bond and thats significant in dry powder form because when inhaled it means that.
Speaker Change: The actual molecules in an earth, so youre not breathing in the active Coprostanol, we believe through Guinea Pig studies, we did early on which are the gold standard in this arena that there was a significant reduction in cost burden as a consequence of it being an inert molecule that was breathed in we've seen this pull through in this small data set so we have so far.
Speaker Change: We're encouraged by what we've seen so far and we're looking forward to seeing the actual data sets and we will certainly dig in on this but once again in the ILD setting patients are particularly sensitive to this and so our ability to show some benefit there was really encouraging and I would finally, just punctuate the whole PAA.
Speaker Change: Which side of the equation by observing that the scientific advisory group that observed. This study was so impressed by the side effect profile that they encouraged us and we subsequently secured FDA approval to double again, the Max dose that is targeted in this population. So we have gone from 640 micrograms, which was the.
Speaker Change: Target Max tolerated dose in the phase <unk> study to 280 micrograms, which is now available for patients in the open label extension portion of the study I don't know Martina if you want to add anything to the to these comments.
So maybe way too one element that is always a good a good indicator of how the Tolerability works and cough correctly as you point out as one of the reasons patients discontinue our discontinuation rates that we observed in a blinded basis are very low and very impressive in the ph study.
And when investigators for example describe a cough that to hear from patients. Most often that is in the context of an immediately after they inhale make make after the inhalation to have a quake.
Speaker Change: It's more a.
Reaction not really a cough that persists beyond the minutes after the inhalation at this point, we will see of course exactly what the percentage of cost will be but it is described I think very differently than what you may have observed in other in other treatments.
Speaker Change: Understood. Thanks for taking all the questions.
Andrea <unk>: Your next question comes from Andrea <unk> with Goldman Sachs. Please go ahead.
Andrea <unk>: Thanks for taking our questions maybe I could also ask a follow up here on <unk> and your expectations for the upcoming data.
Speaker Change: Outside of cost, but as you think about PBR reductions.
Speaker Change: Could frame for us what you would be considering clinically and commercially meaningful and as.
Speaker Change: As you think about the phase III initiation of the ph ILD study, what still needs to be done here.
Speaker Change: And where do you stand in terms of the final trial design. Thanks, so much.
Speaker Change: Sure So with regard to PBR reductions I think if we look the prostacyclin class generally what you've seen from all available data is a range of PBR reduction that starts in sort of the low teens and goes up into the very low <unk>. So about 2022% at at in terms of best available data.
For pulmonary vascular resistance percent reduction for the prostacyclin class drugs, we would expect that anything that is above the high end of that range would clearly position us as best in class with regard to prostacyclin in use and PIH in ph ILD patients.
Speaker Change: And that would be extremely encouraging, particularly when it's coupled with the idea that this is a dry powder with as we discussed a moment ago. So far so good on the adverse event profile the ability to.
Speaker Change: Provide much more drug and.
Speaker Change: Hopefully as a consequence some benefits we.
Speaker Change: We can tie this down with a little bit of data from last year needs to be interpreted with caution because it was a small study, but with 39 patients in a three to one randomization in the ph ILD study I'll just remind everybody that we saw a benefit in terms of time to clinical worsening and we saw a 30 plus meter <unk>.
Speaker Change: Six minute walk performance now again small numbers, we need to be careful. These are obviously very variable, but that coupled with the preclinical animal data, where we saw some remodeling coupled with the imaging study that we just presented in Rio.
Speaker Change: <unk> that visa dilation in the small arteries all of these things are sort of a mosaic and when you put them. All together. It suggests that this program with PBR reductions in the sort of low to mid Twenty's would be a homerun for populations, both ph ILD and ph.
Speaker Change: You asked about.
Speaker Change: The.
Speaker Change: Phase III <unk>.
Speaker Change: Progress for ILD that is well underway. The last remaining element here that we want to make sure. We have as a single capsule administration for every dose strength that we proposed to bring into commercial use and as a consequence, we're taking some time, while we finalize the protocol and getting ready for the launch of the study.
Speaker Change: To ensure that that that is accomplished that.
That work has been underway and is progressing very nicely, we have no concerns there but.
Speaker Change: That's the final sort of piece of the puzzle and of course, we will benefit from interpreting the PIH data as well, even though it's a different disease state. Nonetheless, we think that will be something we want to reflect upon before we put our final phase III protocol forward.
Speaker Change: Okay.
Speaker Change: Yeah.
Speaker Change: Yeah.
Speaker Change: Your next question comes from Nicole Germano with tourists Securities. Please go ahead.
Speaker Change: Great. Thank you so much for the question.
Speaker Change: Yes.
Speaker Change: And congrats on all the progress.
Speaker Change: As we think about the breadth of launch from our survey work there is significant interest in prescribing Brent.
Speaker Change: Cancer patients with comorbid, asthma, and COPD, including in that setting.
Speaker Change: As you think of or what are the components for a successful launch how are you distributing your sales force it will be academic.
Speaker Change: And what are the hurdles with total prescriber uptake in the community.
Speaker Change: Setting versus that guidance. Thank you.
Speaker Change: So the first thing I want to make sure everyone is clear on is that the addition of 120 sales.
Speaker Change: <unk> last year to the original group that was calling on Erra case puts us in a position where we can call on every single Pulmonologists in the United States. So we have access to all of the Pulmonology community across the United States, that's academics and community level physicians. There are different dynamics that are relevant for both of those groups.
Speaker Change: Obviously the Kols in this field are on top of every piece of data in every.
Speaker Change: <unk> aspect of the disease and the science behind it.
Speaker Change: At the community level that becomes a little bit less an area of focus or expertise just by virtue of the fact that they have much more of a broad burden in terms of what they're trying to accomplish so our efforts over the course of the last really almost two years now going back to the American Thoracic Society meeting a couple of years ago has been to bring.
Speaker Change: That education to the community level physicians about the importance of neutrophil driven inflammation in the setting of bronchiectasis and the way in which our mechanism of action may be able to impact that.
Speaker Change: We think about these things and the vicious vortex is they use in the language of the description of this disease state.
Speaker Change: It's something that.
Speaker Change: I think the education has been very successful obviously, we're not talking about the drug itself, but this process of how inflammation is created and how it contributes to the worsening of the disease State has been very successful and you can see that.
Speaker Change: To date in the survey work that we've done where 90% of surveyed pulmonologists have indicated that they intend to write a prescription for patients who have two or more exacerbations.
Speaker Change: I'll just turn it over to Martina to see if she has any other comments based on her interaction with physicians in both communities.
Martina Flammer: Yeah, I think what we know from physician in both communities and from patients is that they really don't at this time have an alternative so patients at this point are waiting for a treatment that will address the underlying causes of their disease, rather than only bring symptomatic improvement in this.
Speaker Change: Patients clearly that is one element of it but there is also a good recognition. If we look back two years, two or three years ago. I think that we had to educate of what is truly driving the disease. The whole inflammation aspect of it was relatively new today. There is a good understanding even when we talk about.
Speaker Change: Puma Pulmonology community that inflammation that we need to address rather only then symptomatic improvement that patients really don't benefit and we continue then to deteriorate and get worse and worse. So the understanding of inflammation that leads to a destruction of lung.
Speaker Change: Tissue has become a much much better level.
Speaker Change: I have one quick follow up.
Speaker Change: Based on the clinical trial site.
Speaker Change: The bronchiectasis what.
Speaker Change: Percent of the.
Speaker Change: Total patient population in the U S that represent that hub project.
Speaker Change: If I understand the question correctly, what percentage of the population would be eligible for treatment with <unk>, the two or more exacerbations thats half of the already diagnosed population, which in the U. S is 500000 patients. That's those that are already diagnosed as you mentioned at the outset.
Speaker Change: Of your questions. There are those who are comorbid with COPD and asthma.
Speaker Change: That also are experiencing bronchiectasis that may or may not fall within that population, yet and indeed that could make the addressable market multiples of what we are currently looking at but there's more to learn there are more to to accomplish in order to diagnosis ensure those patients who are appropriate for treatment.
Speaker Change: Okay. Thank you so much.
Speaker Change: Yeah.
Speaker Change: Your next question comes from Greg <unk> with Mizuho Securities. Please go ahead.
Speaker Change: Hey, good morning, Congrats on the progress thanks for taking my questions I'm actually going to ask about the earlier stage pipeline.
Speaker Change: Was curious about your gene therapy candidate for DMD.
Speaker Change: And I'm wondering how you think that might differentiate from other gene therapy approaches for DMD in the past certainly gene therapy is very interesting as a modality, but wondering what the TPP here is and also on your Alison Star Guard Pro.
Speaker Change: Graham if you could share with us perhaps what the targets are.
Speaker Change: For your gene therapy efforts are there for each of those candidates.
Speaker Change: Sure. So the first thing I want to make sure everyone understands is that we have made tremendous progress under what has historically been referred to as the fourth pillar.
Speaker Change: Our research efforts the fourth pillar contemplates several different platforms, which include gene therapy, but are not limited to gene therapy. We also have a technology called synthetic rescue which is out of our Cambridge operation in England, we have a demonized therapeutic proteins assisted by artificial intelligence, which coming out of our new Hampshire Phys.
Speaker Change: <unk> and we have a number of small molecule candidates, including the DPP. One inhibitor successors that are coming out of New Jersey, If we turn to look at just what is coming out of San Diego at the moment. The next three that we've drawn attention to our DMD AOS and Star Guards.
Speaker Change: Each of these have preclinical data already in hand that is incredibly encouraging.
Speaker Change: We are now moving into the clinic for DMD and I just want to clarify that the approach. There. That's novel, we're using an AAV nine capsid and an MHC K seven promoter. So we can produce micro dystrophin using the trans gene in this setting. The these are well established in our mind is the <unk>.
Speaker Change: First <unk>.
Speaker Change: Pathways to accomplish that one of the things. That's very novel here is that we're using interests equal delivery. It is not obvious that interests equal delivery into the cerebral spinal fluid wood transduce into skeletal and cardiac muscle tissue, but indeed in preclinical models that is in fact, what we have seen there is a lot.
Speaker Change: Of detail Devil in the detail that surrounds the assays, we used the specificity the percentage of empty capsid.
Speaker Change: We will combine to produce what we believe will be.
Speaker Change: Very good efficacy and very good safety, which is critically important for this patient population.
Speaker Change: This is just the beginning of our efforts here I think most of what you can expect in terms of clinical data will begin to arrive in 2026.
Speaker Change: And as we move our attention to other areas like AOS, we have seen there.
Speaker Change: Very encouraging preclinical data in that setting and that includes both San Juan and sporadic patients. So for those that don't know ALS is a devastating disease with nothing really available that is effective to treat these patients and what we're bringing forward in this gene therapy is something that we think can address.
Speaker Change: <unk> only sod, one, but also potentially sporadic patients, which dramatically increases the scope of the patient population that could benefit should we show.
Speaker Change: Success, there the IND for that we anticipate filing this year.
Speaker Change: And by the end of the year or by the beginning part of next year. The deployment of another novel technology coming out of San Diego, which is RNA enjoining, which enables the construction of a larger trans gene inside the body using two different viral vectors, which then rejoin once inside the body to create a longer transgene that is then read for.
Speaker Change: Our longer length protein, which could be helpful or even.
Speaker Change: Theoretically corrective to some of the diseases that debt.
Speaker Change: That are monogenic that have this kind of profile that need a longer transgene. So that technology applied in the Star Guard ocular setting is one we're super excited about again preclinical data, they're very encouraging and we will look forward to advancing that through <unk> and into the clinic in 2026. All three of these are just the tip of the iceberg coming out of the fourth.
Pillar, we're not going to talk a lot about them this year, but I do want people to have some frame of reference that they can begin to expect our next.
Speaker Change: Layer, if you will of candidate.
Speaker Change: Therapies to arrive in 2026.
Speaker Change: Thanks, a lot.
Speaker Change: The next question comes from Jason Symanski with Bank of America. Please go ahead.
Jason Symanski: Great. Good morning, Congrats on the quarter and thank you so much for taking our question I. Appreciate it's still somewhat early in the process, but I was hoping you could provide some color regarding your expectations about Brent says potential label connecting the dots from some of your previous comments I mean fundamentally what are your expectations here in terms of restrictions, whether it's pulmonary exacerbations or something.
Jason Symanski: Els any feedback from the agency, thus far I think I'm, just trying to get implications for prescribers and payers here I mean, do you think we could see potential pushback, where a pair might require multiple documented pe's for access.
Jason Symanski: Yeah. So I think there's a couple of layers in the answer to this question. The first is what do we expect the label to be and there I think we have ambition that there could be a broad label that doesn't actually make reference to the number of exacerbations in the last 12 months, whether that is true or not is really not controlling on anything we've shared by way of our intended commercial.
Jason Symanski: Launch efforts or indeed, what our forecast peak sales numbers have been.
Jason Symanski: Because we assume in the market access world separate from the label discussion.
Jason Symanski: There will be a restriction to patients who have had two or more exacerbations in the last 12 months because that was the entry criteria for the clinical trial and Thats how market access often works.
Jason Symanski: While the physician intention maybe broader than certainly the label, we expect to be potentially broader the market access is the.
Jason Symanski: The filter if you will that sets our expectations for peak sales with that two or more exacerbation requirements, which we expect.
Jason Symanski: We are working on market access to ensure through modest discounting and contracting that we can secure the documentation. If you will of that two or more exacerbations in the form of a verbal attestation by a physician if we can get that I think that will help our goal of a frictionless launch that also with the.
Jason Symanski: <unk>.
Jason Symanski: Hope that we can secure a pretty frictionless reauthorization process through that contracting but to address your question. Those are two sort of separate concepts. One is what is going to be utilized in terms of the appropriate patient, which is set by market access and the other which is what is the label, which we think will be much broader.
Speaker Change: Got it thanks for the color.
Speaker Change: Your next question comes from Lisa Baker of Evercore. Please go ahead.
Lisa Baker: Hi, Thanks for taking the question I have just another question on the market access and that is.
Lisa Baker: But part of that do you think any.
Lisa Baker: Do you anticipate any requirements for say reauthorization or continued treatment.
Lisa Baker: It would be based on certain markers drug response, and if so what what would some of those do you think and how are you thinking about that thank you.
Lisa Baker: Yes, I think.
The direct answer to the question is part of our strategy for market access is to is to answer those questions as to shape that policy prior to.
Lisa Baker: Encountering that once we're once we're in commercial launch so that if we are successful in our strategy. We will have some minor discounting and some contracting that will provide assurance for verbal attestation, both for the initial prescription and the reauthorization. So we don't anticipate.
Lisa Baker: Specific limits or <unk>.
Lisa Baker: <unk> that will be necessary to be cleared in the reauthorization process and so far our interaction and I would just say we've spoken to more than 90% of covered lives.
Lisa Baker: In terms of the groups that have access to them.
Lisa Baker: Been incredibly encouraging so I think where we sit with a novel mechanism of first in disease treatment is a very strong position and I should just clarify that as a result of that we really don't need to do the contracting I'm, making reference to we could just push this forward.
Lisa Baker: However, we think the smoother way to ensure rapid uptake in rapid re authorization is to engage in a little bit of that contracting discussion. It doesn't necessarily mean, we're going to target getting on formulary, but it does so it is likely to be a medical exception is a process in terms of the pathway, but we do want that verbal attestation both for the initial prescription in.
Lisa Baker: <unk> and Thats really what were working on in terms of the negotiation and I think we will have success with that particularly as I said, because we'd be the only approved therapy in the disease state.
Lisa Baker: Okay. Thanks, a lot well.
Speaker Change: Your next question comes from Jennifer Aitken with Cantor. Please go ahead.
Jennifer Aitken: Hey, Thanks for taking my questions maybe to start with they are asked.
Speaker Change: Later this year.
Speaker Change: I agree that based on our conversations with docs are really just looking for a positive trial, but in terms of powering assumptions for a study like this is there a way to think about the expected placebo rate in the 24 week trial and then also variability.
Speaker Change: Nandan deviation given it's a 20 day average that's TFS, scoring.
Jennifer Aitken: Are you referring to the Crs trial, just so im clear Jennifer.
Speaker Change: Yes.
Martina Flammer: Martina if you want to address that.
Martina Flammer: Yes, Jennifer if you look at placebo rates I mean, as you know placebo rates always vary widely.
Martina Flammer: Even from trial to trial and similar population we've looked at placebo rates of course, as we thought about birch and if you looked at the optimal studies.
Martina Flammer: It has a little different treatment time, they have their primary endpoint that we can for and then they are looking at up to week 12. So they have seen a reduction in placebo rates.
Martina Flammer: Around one a reduction of one to one five points along along that their scale.
Martina Flammer: If you look at and that is a different population, but I think we can also.
Martina Flammer: Think about it because it's a related population and that is if you look at the Trs with nasal polyps population into two peaks and they have some placebo rates that range between the point to 0.4. If you look at all three items congestion and obstruction, it's a little different because the measure Paul.
Martina Flammer: That maybe are ranging between the four to six on the scale. So there is always a placebo rate. We obviously look for a 24.
Martina Flammer: A 24 week time period.
Martina Flammer: Is something that we take into effect right now what we look at from a blinded perspective is do we see a pattern in the trend as we would expected and that's what we're seeing and the only thing I would add to that is.
Martina Flammer: A shout out to the excellent work done on the clinical trial design because here what we have is patients coming in they are exposed to steroids and they are stable on that regimen, both between screening and randomization and the consequence of that is we can look at that interim period, where there between screening and randomization and see.
Martina Flammer: Are we seeing a blended blinded change in score during that time and the answer is we're not so that means that they are stable with the symptom score they're highly evidentiary in terms of the.
Martina Flammer: Score of a fiber greater so these patients are very symptomatic.
Speaker Change: The fact that thats not moving around a lot in that time between screening and randomization is a very encouraging sign that we can expect some stability within the trial, obviously, we won't know till we on blind, but with reference to some of the range as Martina said I think we feel very good about the powering and whether or not we're going to see something directional here I want to be clear for both TPI.
Speaker Change: And for Crs without nasal polyps and neither one of these these are phase II studies, we're looking for something directional the presence or absence of statistical significance to me is far less significant than just whether or not we see something clear and directional that supports our ability to design a effectively a phase III study for each of these programs.
Speaker Change: Yeah.
Speaker Change: Okay. That's helpful and maybe if I could ask one question on <unk>.
Speaker Change: Although it can PCR production can you just remind us of your thoughts on the importance of the six minute walk endpoint.
Speaker Change: In the context in the phase two.
Speaker Change: Should we frame our expectations, what we saw in the childhood study or how should we think about that thanks.
Speaker Change: You know my favorite measure here is the six minute walk test.
Speaker Change: Highly variable very difficult to predict this is true across every study that's ever been done PIH. So anything that comes through has to be interpreted with caution which is what I said earlier when we're looking at the ILD data encouraging, though it is and frankly stronger than most competitors.
Martina Flammer: Nonetheless, we still would urge caution because it can be highly variable and there are enough patients. In this study that we hope once again to see something directional, but certainly not statistically significant and just to put it into context, I think Martina I'm looking to you with it.
Martina Flammer: Historic levels of of six minute walk test improvement are right around 20 meters aren't they are not that substantial it is important to keep an eye on this though because it is the primary endpoint that FDA tends to look at for approval in this class.
Martina Flammer: Yes, that's correct. So anything about 20 meters is what you've seen in for example, the increase study in ph ILD and and what you would see in in in dialysis prostacyclin anything north of 20 meters. I think is already a win in certainly in our study.
Will Lewis: <unk> II study remember, we're now powering on the six minute walk where powering in the PDR reduction. So yes as will said, we look for directional improvement on six minute walk.
Will Lewis: And that will inform us on the importance of powering for the phase III study, where the six minute walk will be the primary endpoint.
Will Lewis: Okay.
Will Lewis: Okay.
Speaker Change: Your next question comes from Jeff Hung with Morgan Stanley. Please go ahead.
Speaker Change: Thanks for taking my questions for Bronchiectasis, you've noted patients are motivated to act with about 41000, who have acted.
Speaker Change: How do you define acting and then how many of them are diagnosed already with bronchiectasis and had two plus exacerbations in the last year.
Speaker Change: And then I have a follow up.
Speaker Change: Yes, so the bronchiectasis patients that are as we described active this means they are go into the website. They are downloading information, they're registering for more information we have contact information for them. So if and when the day comes that the drug is approved we can put them on notice of that effect.
Speaker Change: And activate them to seek out treatment from their physician.
Speaker Change: So I would tell you that relative to our expectations that number is extremely high and it is growing by the thousands.
Speaker Change: So we think this is going to create.
Speaker Change: Sort of repository of of potential patients right at the time of launch which is very encouraging it's consistent with what we've seen from the physician side, where they are highly encouraged by the data set and want to draw patients in to treat them. So we think that the combination of both of these.
Speaker Change: Pieces of evidence is what gives us some conviction that the launch could be could be strong.
Speaker Change: Great. Thanks, and then you talked about how you could reach out to these patients have let them know about the drug's approval and reaching out to their physician. So can you talk about your expectation on the timing and cadence for patients seeing their physicians and being prescribed <unk> over say the first 12 months, how does how do you kind of typically play out yeah.
Speaker Change: Yes, so it's.
Speaker Change: The catch word and what you just said is typically and of course, because theres nothing thats ever been approved here that really isn't great precedent to know how both physicians and patients are going to behave what we know from launches generally is that if you have motivated patients and motivated physicians and you run surveys to gain an index of their appetite.
Speaker Change: These scores are coming in very high so physicians are motivated not only by the drug in their intent to use it 90% of the physicians, we surveyed indicated that they would put their patients who have two or more exacerbations on this drug that's an extremely high number. The fact that we have tens of thousands of patients who've already registered.
Speaker Change: And downloaded guides from our website, which is the.
Speaker Change: The actions they take are involved it's not just visiting a website and clicking there it's much more than that and those are strong signs that there is interest among the patient and the physician community whether that will translate into them seeing the physician in the first month.
Speaker Change: Our year.
Speaker Change: Remains to be seen and that'll be part of the challenge of really trying to understand what the ramp will look like here is when do these patients and physicians actually follow through on those actions. We're trying to provide education now so that that happens is it really is possible because we think patients will benefit from the drug and we want physicians to understand that.
Speaker Change: We also think that.
Speaker Change: The more we can provide by way of education the more of this will become.
Speaker Change:
Speaker Change: A circumstance where word of mouth will also lift interest and attention to this area. This was described when the data came out after phase two by someone at the American Thoracic Society is the Holy Grail of pulmonary medicine.
Speaker Change: A once a day pill to treat pulmonary condition and for that reason I think.
Speaker Change: All signs point to positive.
Speaker Change: Great. Thanks, a lot.
Speaker Change: Okay.
Speaker Change: Your next question comes from Stephanie Steven Willey with Stifel.
Speaker Change: Please go ahead.
Speaker Change: Yes. Good morning, Thanks for taking the question just a quick follow up on <unk>. So do you have any update on the percentage of ph patients from the phase two study that have chosen to participate in the open label extension portion of the trial.
Speaker Change: And then just wondering if you might have an opportunity to provide any of this.
Speaker Change: Data from the open label extension portion at the time of the phase two topline disclosure.
Speaker Change: Specifically, given if it looks like youre achieving them.
Speaker Change: So just given it looks like youre, achieving an even greater PBR reduction at doses North of 640. Thank you Scott.
Speaker Change: So we won't have the data for the open label.
Martina Flammer: Trial participants and what we can say is that we do have some that have gone all the way up to 12 80 in many to 960. So they are getting to higher doses in the open label portion I don't know Martina if you have any of that data handy in terms of numbers and what that's looking like.
Martina Flammer: Yes, so what we what I can tell you is that we have in the vast majority of patients continuing in the open label study and there are a number of patients who are 80% up to the highest dose and the additional 20% some of them are in between 640 and although.
Martina Flammer: Way up to the 12 to 80, who has a couple of patients who are already up under 12 months 80 dose for several weeks and I guess, what I would say about this is while we won't have that data at the time and we are not measuring PV or in the open label portion of the study. Nonetheless, we're tracking other biomarkers that we think will be able to correlate to what is seen in the.
Martina Flammer:
Martina Flammer: The clinical portion of the study, where where PBR is being collected and so there is going to be the ability to understand that whatever number we put out in terms of <unk> percent reduction whatever benefits, we may be able to demonstrate in six minute walk if we're able to take the dose from that level to double that level. It would.
Martina Flammer: Certainly follow logically that you could expect that the numbers we're producing in this phase II study readout are indicative of only part of what could be accomplished and to put this into a finer point as we turn to phase III. It is our intention to have the Max tolerated dose shifted from 640 micro grams to 280 micrograms.
Martina Flammer: For the Phase III study participants.
Martina Flammer: Alright, thanks for taking questions.
Martina Flammer: Yeah.
Martina Flammer: Your next question comes from Trung Nguyen with UBS. Please go ahead.
Trung Nguyen: Great Hi, guys. Thanks for taking our question. It looks like you are in a quite strong financial position as you start 20 $514 billion in cash.
Trung Nguyen: But you've also got a lot going on so you've got early stage Charles starting late stage trials starting brands launching.
Trung Nguyen: To get your thoughts on if that could be any incremental financing on the horizon.
Trung Nguyen: Is on the agenda, how many they'll key catalyst costs need to be divested you to start accessing that financing. Thank you.
Speaker Change: I'll ask <unk> to respond to that sure. Thanks for the question historically.
Speaker Change: Historically, it's not our practice to really talk about timing for future balance sheet augmentation cash runway all that kind of stuff, but I can comment on is I. As you mentioned just really pleased with the strength of our financial position and you know a little north of $1 4 billion in the bank.
Speaker Change: It's gotten a ton of support from our shareholders. So thank you.
Speaker Change: All listening for the support to get US here, what I will say is we do have a line of sight to becoming a sustainable self sustaining biotech company. So that is our goal that is our ambition and we are on that track. We are not currently funded through profitability that is by choice and we believe it is in our shareholders' best interest and in patients best interest to continue.
Speaker Change: To invest in this pipeline.
Speaker Change: As you as you mentioned and to unlock these very you know meaningful future data catalysts that I think will be significant value creating opportunities.
Speaker Change: As I said when it is our time to augment our balance sheet, we have a variety of ways. We can do it equity is one of those pads, we may choose to not to equity we may choose royalty for air case or Brent. So as an example in R&D funding for TPI P. As an example, a different sort of debt structures I think as an example, just to name a few so bottom line is we have a ton of optionality.
Speaker Change: We have the ability to be patient and we have line of sight to becoming a self sustaining biotech company.
Speaker Change: Yeah.
Speaker Change: Yeah.
Speaker Change: Yeah.
Speaker Change: Yeah.
Speaker Change: And your last question comes from Andy Chien with Wolfe Research. Please go ahead.
Andy Chien: Hi team it's to go on for Andy can you speak to your patient selection strategy for the chronic rhinosinusitis with nasal polyps trial.
Speaker Change: How can how do you make sure you're picking the correct patients for the trial and are there any baseline characteristics you can share. Thank you.
Speaker Change: Sure. So I appreciate the question I think what is really useful about this is once again frames out the enormity of the opportunity. We're talking about here. So there are crs without nasal polyps and Theres Crs with nasal polyps when we look at with nasal polyps. There are already several program our products approved to treat that humira.
Speaker Change: Depicts since there. These are big products that are addressing that disease state Crs without nasal polyps is nothing other than the inhaled steroids to treat it.
Speaker Change: Nothing novel on the Horizon that is available. So if we are successful with this.
Speaker Change: We're addressing a theoretical population in excess of 33 million people in the United States now we have done for this trial is to focus on the most severe patients where we think this drug has its greatest potential to show benefit and those are patients that are eligible or have already had surgery or those in every case.
Who are steroid non responders so much like our strategy with Eric case in refractory patients, let's assume that they've had access to or considered every available treatment option out there.
Speaker Change: And then let's see what our drug can do to that challenge patient population and we are.
Speaker Change: So far feeling pretty good about the possibility that this drug is going to have an impact that selection strategy as you point out. It means that we are going to just the bottom end of that pyramid. So it's 200000 patients in the U S that are eligible for surgery every year. There is another couple of million dollars that are steroid non responders. So that makes us a V.
Speaker Change: Very significant addressable population and why I said at the outset.
Speaker Change: It could be as big if not bigger than the bronchiectasis population.
Speaker Change: Thank you.
Speaker Change: Yeah.
Speaker Change: Yeah.
Speaker Change: Ladies and gentlemen that concludes today's call. Thank you all for joining you may now disconnect.
Speaker Change: [music].
Speaker Change: Yes.
Speaker Change: Okay.
Speaker Change: [music].