Q2 2024 Insmed Inc Earnings Call

John: Thank you for standing by. My name is John and I will be your conference operator for today. At this time, I would like to welcome everyone to the Insmed Second Quarter 2024 Financial Results Call.

Unknown Executive: I would like to welcome everyone to the Insmed Second Quarter 2024 Financial Results Call. All lines have been placed on mute to prevent any background noise.

Unknown Executive: After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, please press star one again. Thank you. I would now like to turn the call over to Bryan Dunn, Head of Investor Relations. Please go ahead. Thank you, John.

John: All lines have been placed in mute to prevent any background noise.

John: After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed by the number 1 on your telephone keypad. If you would like to withdraw your question, please press star 1 again. Thank you. I would now like to turn the call over to Bryan Dunn, Head of Investor Relations. Please go ahead.

Bryan Dunn: Good day, everyone, and welcome to today's conference call to discuss Insmed's second quarter 2024 financial results and provide a business update. I am joined today by Will Lewis, Chair and Chief Executive Officer, and Sara Bonstein, Chief Financial Officer, who will each provide prepared remarks, after which they will be joined by Martina Flammer, Chief Medical Officer, for the Q&A session. Before we start, please note that today's call will include forward-looking statements based on our current expectations.

Brian Dunn: Thank you, John . Good day, everyone, and welcome to today's conference call to discuss Insmed's second quarter 2024 financial results and provide a business update.

Speaker Change: I am joined today by Will Lewis, Chair and Chief Executive Officer, and Sara Bonstein, Chief Financial Officer, who will 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 refer to our filings with the Securities and Exchange Commission.

Speaker Change: 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. I will now turn the call over to Will Lewis for prepared remarks.

Bryan Dunn: 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 refer to our filings with the Securities and Exchange Commission. For more information concerning the risk factors that could affect the... 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. I will now turn the call over to Will Lewis for prepared remarks. Thank you, Bryan, and welcome, everyone.

Will Lewis: The second quarter of 2024 will go down in Insmed's history as the start of an important new era as a mid-cap biotechnology company. During this quarter, we not only saw the continued growth of ericase and refractory MAC lung disease, but also positive phase two data for TPIP and PHILD, and, of course, most significantly, the successful results of the landmark Aspen study. We are grateful to be able to mark and celebrate this moment with patients, physicians, and investors. It is a time that reminds us why it is so rewarding to work in the field of biotechnology.

Will Lewis: Thank you, Bryan, and welcome, everyone.

Will Lewis: The second quarter of 2024 will go down in Insmed's history as the start of an important new era as a mid-cap biotechnology company.

Will Lewis: During this quarter, we not only saw the continued growth of ericase and refractory MAC lung disease, but also positive phase 2 data for TPIP and PHILD, and of course, most significantly, the successful results of the landmark Aspen study.

Will Lewis: We are grateful to be able to mark and celebrate this moment with patients, physicians, and investors. It is a time that reminds us why it is so rewarding to work in the field of biotechnology.

Will Lewis: Today, I intend to focus on a number of exciting catalysts across all of our pillars. However, we are keenly aware that nothing is more important for our near and medium-term success than flawlessly executing the launch of Brenso Cadmium and Bronchiactasis. If we can get that right, we believe it holds the potential to transform this company once again, which is why executing on that opportunity will continue to be such a focus for us. So let me start there with an update on Brent Soccata.

Speaker Change: Today I intend to focus on a number of exciting catalysts across all of our pillars. However, we are keenly aware that nothing is more important for our near and medium-term success than flawlessly executing the launch of BRENSO-CATIB and BRONCHIECTASIS.

Speaker Change: If we can get that right, we believe it holds the potential to transform this company once again, which is why executing on that opportunity will continue to be such a focus for us.

Will Lewis: The World Bronchiectasis Conference held in Dundee, Scotland, in July was nothing short of a celebration of the positive results from the Aspen study. We've been touched and honored by the enthusiastic and often emotional responses we've heard from patients and the physicians who treat them to Aspen's overwhelmingly positive results. Brenso Kadib's demonstrated ability not only to reduce the rate of pulmonary exacerbations but also to preserve lung function and improve how patients feel, all while displaying a safety profile that was comparable to placebo, is something that we believe has the potential to be life-changing for patients living with bronchiectasis.

Speaker Change: So let me start there with an update on BRENSO-CATIB. The World Bronchiectasis Conference held in Dundee, Scotland in July was nothing short of a celebration of the positive results from the Aspen study.

Speaker Change: We've been touched and honored by the enthusiastic and often emotional responses we've heard from patients and the physicians who treat them to Aspen's overwhelmingly positive results.

Speaker Change: Brenso Catib's demonstrated ability not only to reduce the rate of pulmonary exacerbations, but also to preserve lung function and improve how patients feel, all while displaying a safety profile that was comparable to placebo, is something that we believe has the potential to be life-changing for patients living with bronchiectasis.

Will Lewis: We look forward to releasing additional data, including pre-specified subpopulation data from the Aspen trial, at the CHEST conference in October in Boston. I want to reiterate that these subgroups have shown good consistency with the overall results of the study, so there should not be any negative surprises when these data are presented. We are immensely proud to be a part of this type of breakthrough for patients, and if approved, we look forward to getting brensocatib into the hands of those who need it as quickly as possible.

Speaker Change: We look forward to releasing additional data, including pre-specified subpopulation data from the Aspen trial at the CHEST conference in October in Boston.

Speaker Change: I want to reiterate that these subgroups have shown good consistency with the overall results of the study, so there should not be any negative surprises when these data are presented.

Speaker Change: We are immensely proud to be a part of this type of breakthrough for patients, and if approved, we look forward to getting brensocatib into the hands of those who need it as quickly as possible.

Will Lewis: We continue to prepare for the expected U.S. filing for brent socatib and bronchiectasis in the fourth quarter of this year, and our progress toward that goal remains on or even slightly ahead of schedule. Importantly, all of the necessary clinical and preclinical data required for the filing have already been completed, so there are no large gating factors left in front of us. As you know, the Aspen trial represents an enormous data set, and we are focused on thoroughly documenting those results for the filing, including making the final determination on whether we will file one or both doses for approval.

Speaker Change: We continue to prepare for the expected U.S. filing of brent socatib in bronchiectasis in the fourth quarter of this year, and our progress toward that goal remains on or even slightly ahead of schedule.

Speaker Change: Importantly, all of the necessary clinical and preclinical data required for the filing have already been completed, so there are no large gating factors left in front of us.

Speaker Change: As you know, the Aspen trial represents an enormous data set, and we are focused on thoroughly documenting those results for the filing, including making the final determination on whether we will file one or both doses for approval. We continue to anticipate a launch in the U.S. in the middle of next year.

Will Lewis: We continue to anticipate a launch in the U.S. in the middle of next year. Our commercial team has also been diligently preparing for that expected launch. Nearly all of the additional 120 sales reps we intend to add to the U.S. sales force have already accepted offers, and these were chosen from a pool of more than 7,000 resumes. We expect to have all 120 new sales reps trained and in the field by October of this year.

Speaker Change: Our commercial team has also been diligently preparing for that expected launch. Nearly all of the additional 120 sales reps we intend to add to the U.S. sales force have already accepted offers, and these were chosen from a pool of more than 7,000 resumes.

Speaker Change: We expect to have all 120 new sales reps trained and in the field by October of this year.

Will Lewis: This timeline for the deployment of sales reps follows a similar pattern as the Ericase launch. We put those reps into the field six months ahead of the approval, and we believe that proactive approach contributed to error case ranking in the top ten of non-oncology rare disease launches. For Brent Sokhatib, we intend to have reps in the field even earlier, where they will work on disease state awareness and education, while also detailing error cases to physicians in the hopes of helping more patients who could benefit from that treatment.

Speaker Change: This timeline for deployment of sales reps follows a similar pattern as the EraCase launch. We put those reps into the field six months ahead of the approval, and we believe that proactive approach contributed to EraCase ranking in the top ten of non-oncology rare disease launches.

Speaker Change: For Brent Sokhatib, we intend to have reps in the field even earlier, where they will work on disease state awareness and education, while also detailing error case to physicians in the hopes of helping more patients who could benefit from that treatment.

Will Lewis: In addition, we have made great progress with both national and regional payers on disease state education and have engaged close to 90% of U.S. patient lives via payer discussions already. Payers have been receptive to learning about this disease and the permanent damage caused by bronchiectasis exacerbation.

Speaker Change: In addition, we have made great progress with both national and regional payers on disease state education and have engaged close to 90 percent of U.S. patient lives via payer discussions already.

Speaker Change: Pears have been receptive to learning about this disease and the permanent damage caused by bronchiectasis exacerbations.

Will Lewis: Our medical team is already sharing the Aspen data reactively upon request, and more detailed pre-approval discussions will follow our NDA filing next quarter. Finally, it is important to note in the context of our anticipated launch next year that we are in a very good position from a supply perspective, with ample API inventory already in hand. In fact, by the end of this year, we expect to have converted enough of that API into tablet form to meet our current anticipated demand for brent sucatib in the U.S. through at least the first year of its launch. As a matter of policy, we always look to prioritize continuity of supply for our patients.

Speaker Change: Our medical team is already sharing the ASPEN data reactively upon request, and more detailed pre-approval discussions will follow our NDA filing next quarter.

Speaker Change: Finally, it is important to note in the context of our anticipated launch next year that we are in a very good position from a supply perspective, with ample API inventory already in hand.

Speaker Change: In fact, by the end of this year, we expect to have converted enough of that API into tablet form to meet our current anticipated demand for BrensoCatib in the U.S. through at least the first year of its launch.

Speaker Change: As a matter of policy, we always look to prioritize continuity of supply for our patients.

Will Lewis: It was that principle that allowed us to maintain a steady supply of EraCase, even during a global respiratory pandemic, by establishing robust supply chains and a sufficient safety stock of inventory. Even though BrensoCatib is easier to make in large quantities and on shorter notice compared to EraCase, we intend to build meaningful inventory and establish backup supply chains, and that work is well underway. Moving beyond bronchiectasis, we continue to be encouraged by the progress of our ongoing Phase 2 study in CRS without nasal polyps, which we expect to read out in the second half of 2025.

Speaker Change: It was that principle that allowed us to maintain a steady supply of error case, even during a global respiratory pandemic, by establishing robust supply chains and a sufficient safety stock of inventory.

Speaker Change: Even though Brent Sokadib is easier to make in large quantities and on shorter notice compared to Eric Case, we intend to build meaningful inventory and establish backup supply chains, and that work is well underway.

Speaker Change: Moving beyond bronchiectasis, we continue to be encouraged by the progress of our ongoing Phase 2 study in CRS without nasal polyps, which we expect to read out in the second half of 2025.

Will Lewis: We continue to see improvements in average symptom scores in the blinded data from that study, which appear to correspond with the time when NSP reduction from DPP1 inhibition should be occurring. We acknowledge that the data is blinded and still early, but we find it encouraging nonetheless. We are excited to be moving forward with our previously stated plans to kick off a phase 2 study of brensocatib and hydradonitis supertiva now that the Aspen study has demonstrated the potential of the DPP-1 mechanism.

Speaker Change: We continue to see improvements in average symptom scores in the blinded data from that study, which appear to correspond with the time when NSP reduction from DPP-1 inhibition should be occurring. We acknowledge that the data is blinded and still early, but we find it encouraging nonetheless.

Speaker Change: We are excited to be moving forward with our previously stated plans to kick off a Phase II study of brenn-sucatib and hydradenitis supertiva, now that the Aspen study has demonstrated the potential of the DPP-1 mechanism.

Will Lewis: We remain on track to have the first active U.S. sites open before the end of the year, with the first patients being screened shortly thereafter. Finally, I want to comment briefly on the work we are doing to develop next-generation DPP-1 inhibitors in an effort to maintain our leadership in this important new class of medicine. This work is not new, having begun shortly after the Phase II Willow results first read out. In fact, we have already synthesized and screened over 850 novel DPP-1 inhibitors and have filed over 10 unique patent applications that disclose and claim these compounds.

Speaker Change: We remain on track to have the first active U.S. sites open before the end of the year, with the first patients being screened shortly thereafter.

Speaker Change: Finally, I want to comment briefly on the work we are doing to develop next-generation DPP-1 inhibitors in an effort to maintain our leadership in this important new class of medicines.

Speaker Change: This work is not new, having begun shortly after the Phase II Willow results first read out. In fact, we have already synthesized and screened over 850 novel DPP-1 inhibitors and have filed over 10 unique patent applications that disclose and claim these compounds.

Will Lewis: We are now advancing the first candidate from this group into IND-enabling studies, and we expect one to two more to follow closely thereafter. Based on the strength of the efficacy and safety data from Aspen in patients with bronchiectasis, we are evaluating if there may be other indications we want to explore using DPP-1 inhibition. This can include other indications with significant neutrophil involvement and where patients continue to face significant unmet needs despite current treatments, such as rheumatoid arthritis, lupus nephritis, and other inflammatory conditions.

Speaker Change: We are now advancing the first candidate from this group into IND-enabling studies, and we expect one to two more to follow closely thereafter.

Speaker Change: Based on the strength of the efficacy and safety data from Aspen in patients with bronchiectasis, we are evaluating if there may be other indications we want to explore using DPP-1 inhibition.

Speaker Change: This can include other indications with significant neutrophil involvement and where patients continue to face significant unmet needs despite current treatments such as rheumatoid arthritis, lupus nephritis, and other inflammatory conditions.

Will Lewis: Keep in mind that we could develop these molecules for these new indications ourselves, or we could choose to sell or partner them with others who already have a presence in those markets. Either way, these follow-on compounds are expected to keep us at the forefront of this exciting new drug class. Now, let me turn to EraCase.

Speaker Change: Keep in mind that we could develop these molecules for these new indications ourselves, or we could choose to sell or partner them with others who already have a presence in those markets.

Speaker Change: Either way, these follow-on compounds are expected to keep us at the forefront of this exciting new drug class.

Will Lewis: I am pleased to report that EraCase continues to perform well commercially, delivering 17% growth this quarter compared to the second quarter last year. Much of that success is directly related to the strong execution of our commercial teams across the world. Keep in mind that these same teams will be the ones to launch Brenn Sokadib, assuming regulatory approvals are achieved. In addition to commercial execution, we have also made progress on error cases clinical development this quarter. As previously indicated, we met in June with the division of the FDA responsible for patient reported outcome measures.

Speaker Change: Now let me turn to EraCase. I am pleased to report that EraCase continues to perform well commercially, delivering 17% growth this quarter compared to the second quarter last year.

Speaker Change: Much of that success is directly related to the strong execution of our commercial teams across the world. Keep in mind that these same teams will be the ones to launch Brenso Cadab, assuming regulatory approvals are achieved.

Speaker Change: In addition to commercial execution, we have also made progress on error cases clinical development this quarter. As previously indicated, we met in June with the division of the FDA responsible for patient-reported outcome measures.

Will Lewis: That meeting resulted in us successfully aligning with the FDA on the primary endpoint for the on-course study that can support label expansion to include all MAC lung patients and full approval for the current refractory indication if the data are positive. Now that we have this clarity from the FDA, we have re-evaluated ENCQOR's enrollment target with the goal of ensuring we give the study the best chance of success in achieving its objectives using appropriately conservative powering assumptions.

Speaker Change: That meeting resulted in us successfully aligning with the FDA on the primary endpoint for the on-course study that can support label expansion to include all MAC lung patients and full approval for the current refractory indication if the data are positive.

Speaker Change: Now that we have this clarity from the FDA, we have re-evaluated ENCQOR's enrollment target with the goal of ensuring we give the study the best chance of success in achieving its objectives, using appropriately conservative powering assumptions.

Will Lewis: Based on that evaluation, we have updated our on-course target enrollment to 400 patients with targets powering of more than 90% for the primary input. Importantly, recruitment for the trial has been proceeding very well throughout 2024 following the ARISE study results. As a result, we expect to be in a position to stop screening new patients later in the third quarter and would then expect the top-line results for ENCQOR to read out in the first quarter of 2026. As we have commented before, we can now approach the FDA about the possibility of an accelerated filing under Subpart H. We expect to have that answer by the end of this year.

Speaker Change: Based on that evaluation, we have updated OnCourse target enrollment to 400 patients with targets powering of more than 90% for the primary endpoint.

Speaker Change: Importantly, recruitment for the trial has been proceeding very well throughout 2024 following the ARISE study result.

Speaker Change: As a result, we expect to be in a position to stop screening new patients later in the third quarter and would then expect the top-line results for ENCQOR to read out in the first quarter of 2026.

Speaker Change: As we have commented before, we can now approach the FDA about the possibility of an accelerated filing under Subpart H. We expect to have that answer by the end of this year.

Will Lewis: As a reminder, our expectation continues to be that ENCOR data will be required for all global regulatory filings to potentially expand the label for error cases to include all patients with MAC lung disease. We will update you as we learn more from our interactions with the FDA. Let me also provide a quick update on our TPIP development program. Enrollment in our Phase II PAH study has also accelerated recently, likely resulting from the strong Phase II trial readout in PHILD in May.

Speaker Change: As a reminder, our expectation continues to be that the ENCOR data will be required for all global regulatory filings to potentially expand the label for error case to include all patients with MAC lung disease.

Speaker Change: We will update you as we learn more from our interactions with the FDA.

Speaker Change: Let me also provide a quick update on our TPIP development program. Enrollment in our Phase II PAH study has also accelerated recently, likely resulting from the strong Phase II trial readout in PHILD in May.

Will Lewis: We now have more than 75% of the enrollment completed in our PAH trial, which keeps us on track for an expected readout in the second half of 2025. We are consistently monitoring the results of the study on a blinded basis, which continue to show impressive reductions in pulmonary vascular resistance for many of the patients in the study. These improvements in PVR would not normally be expected for patients who have not had a change in their treatment.

Speaker Change: We now have more than 75% of the enrollment completed in our PAH trial, which keeps us on track for an expected readout in the second half of 2025.

Speaker Change: We are consistently monitoring the results of the study on a blinded basis, which continue to show impressive reductions in pulmonary vascular resistance for many of the patients in the study. These improvements in PVR would not normally be expected for patients who have not had a change in their therapy.

Will Lewis: All of this adds to our excitement for the upcoming readout of the trial and for the potentially compelling profile that began to emerge with the recent PHLD top-line results. If I can summarize today's update, it is this: Insmed is preparing diligently for the expected launch of brent socatib and bronchiectasis next year, including regulatory filings, commercial readiness, payer discussions, and inventory planning, all of which is This launch represents the type of opportunity that only comes along once in a career, if you're lucky.

Speaker Change: All of this adds to our excitement for the upcoming readout of the trial and for the potentially compelling profile that began to emerge with the recent PHIL-D top-line results.

Speaker Change: If I can summarize today's update, it is this, Insmed is preparing diligently for the expected launch of brent socatib and bronchiectasis next year, including regulatory filings, commercial readiness, payer discussions, and inventory planning, all of which is progressing on or ahead of schedule.

Speaker Change: This launch represents the type of opportunity that only comes along once in a career if you're lucky. We all recognize the enormity of what lies ahead and how important it is for us to get it right for our patients, investors, and other stakeholders.

Sara Bonstein: We all recognize the enormity of what lies ahead and how important it is for us to get it right for our patients, investors, and other stakeholders. While we acknowledge the critical importance of the successful launch of BRENSOCADAB, I also want to recognize the remarkable progress we are making in parallel across every other area of clinical development and research and the exciting opportunities that this work has the potential to unlock. Shortly after we launch BrensoCatib, we anticipate additional clinical readouts that could represent sizable growth opportunities in their own right, such as Phase II readouts for BrensoCatib and CRS without nasal polyps, and TPIP and PAH, followed by the Phase III readout of EraCase in newly diagnosed MAC lung infection.

Sara Bonstein: We look forward to continuing to execute on behalf of patients and our stakeholders as we enter the unique period of potential growth that lies ahead of us. Now, I will turn the call over to Sara to walk through the financials for the court. Thank you, Will, and good morning everyone. I am happy to share some of the details of Insmed's financial performance for the second quarter of 2024. We ended the quarter with $1.25 billion in cash and cash equivalents, representing an increase of $651 million compared to the end of the previous quarter.

Sara Bonstein: This increase in cash was driven primarily by our equity raised during the quarter, which added $713 million on a net basis and was supplemented by cash received by the company through the exercise of stock options during the quarter. When these items are excluded, the underlying cash burn for the quarter was approximately $139 million, which is relatively consistent with our historical cadence.

Speaker Change: This increase in cash was driven primarily by our equity raised during the quarter, which added $713 million on a net basis and was supplemented by cash received by the company through the exercise of stock options during the quarter.

Speaker Change: When these items are excluded the underlying cash burn for the quarter was approximately $139 million, which is relatively consistent with our historical cadence.

Sara Bonstein: Before I move on to talk more about our performance this quarter, I want to provide a brief update on our $225 million convertible debt instrument, which was set to mature in January 2025 but which we called in June. As of August 7th, 99.9% of those notes have already been converted to approximately 5.7 million shares of our stock ahead of the redemption date on August 9th. I will now walk you through some of the highlights of our commercial performance in the second quarter of 2024.

Speaker Change: Before I move on to talk more about our performance this quarter I want to provide a brief update on our $225 million.

Speaker Change: The convertible debt instrument, which was set to mature in January 2025, but which we called in June.

Speaker Change: As of August 7th 99, 9% of those notes have already been converted into approximately $5 7 million shares of our stock ahead of the redemption date on August 9th.

Speaker Change: I will now walk you through some of the highlights of our commercial performance in the second quarter of 2024.

Sara Bonstein: Global net revenues this quarter were $90.3 million, representing 17% year-over-year growth compared to the second quarter of 2023. Not only does this result reflect the highest quarterly sales for Aircase in its history, but it also establishes new all-time highs for sales in each of our three commercial regions. In the U.S., net revenue for the second quarter of 2024 was $63.8 million, up 11 percent compared to the prior year quarter.

Speaker Change: Global net revenues this quarter were $93 million, representing 17% year over year growth compared to the second quarter of 2023.

Speaker Change: Not only does this result reflect the highest quarterly sales for aerospace in its history, but it also establishes new all time highs for sales in each of our three commercial regions.

Speaker Change: In the U S. Net revenue for the second quarter, 2024 was $63 $8 million up 11% compared to prior year quarter.

Sara Bonstein: New patient starts in the U.S. have remained very strong, reflecting the value that physicians see in using Aircase for their refractory patients. The quarter's performance also benefited from a rebound in active patients following the disruptions caused by the changed healthcare cyber attack in the first quarter of the year. In Japan, second quarter 2024 net revenue was $21.1 million, reflecting 35% growth over the same quarter last year.

Speaker Change: New patient starts in the U S have remained very strong reflecting the value that physicians see than using air Keith further refractory patients.

Speaker Change: <unk> performance also benefited from a rebound in active patients following the disruptions caused by the change healthcare cyber attack in the first quarter of the year.

Speaker Change: In Japan second quarter, 2024, net revenue was $21 $1 million, reflecting 35% growth over the same quarter last year.

Sara Bonstein: The record-setting performance in Japan this quarter was primarily driven by stronger demand resulting from an increase in physician reach as we have worked to expand our sales force and, to a lesser extent, favorable inventory patterns in the quarter. In Europe and the rest of the world, net revenue in the second quarter of 2024 came in at $5.4 million, up 37 percent compared to the same quarter last year, driven primarily by strong performance in the UK and Germany.

Speaker Change: The record setting performance in Japan. This quarter was primarily driven by stronger demand, resulting from an increase in physician reach as we have worked to expand our sales force and to a lesser extent favorable inventory patterns in the quarter.

Speaker Change: In Europe, and the rest of World net revenue in the second quarter of 2024 came in at $5 $4 million up 37% compared to the same quarter last year, driven primarily by strong performance in the UK and Germany.

Sara Bonstein: Importantly, this quarter's performance keeps us on track to achieve our reiterated full year 2024 global revenue guidance of $340 to $360 million. Let me now turn to a few additional financial items. In the second quarter of 2024, our gross SINETs in the U.S. were 15.4%, which was consistent with our expectations. We continue to anticipate that gross financial will settle in the mid to high teens range for the full year. The cost of product revenues for the second quarter of 2024 was $21 million, or 23.2 percent of revenues, which is also consistent with our historical performance.

Speaker Change: Importantly, this quarter's performance keeps us on track to achieve our reiterated full year 2024, our global revenue guidance of $340 million to $360 million.

Speaker Change: Let me now turn to a few additional financial items.

Speaker Change: In the second quarter 2024, our gross to nets in the U S were 15, 4%, which was consistent with our expectations. We continue to anticipate that gross to nets will settle in the mid to high teen range for the full year.

Speaker Change: Cost of product revenues for the second quarter of 2024 was $21 million or 23, 2% of revenues, which is also consistent with our historical performance.

Sara Bonstein: Turning to our GAAP operating expenses, in the second quarter, research and development expenses were $146.7 million, and SG&A expenses were $106.6 million, reflecting investment in both our early and mid- to late-stage pipelines, as well as our ramping investment in launch readiness activities for bread sarcasm. One additional financial highlight. Each quarter, we record a non-cash charge, the non-cash change in fair value of deferred and contingent consideration liabilities, which relate primarily to future stock payments associated with two of our past acquisitions. With this charge being directly linked to the change in our stock price each quarter, the expense this quarter was significant at approximately $104 million.

Speaker Change: Turning to our GAAP operating expenses.

Speaker Change: In the second quarter research and development expenses were $146 $7 million and SG&A expenses were $106 $6 million, reflecting investment in both our early and mid to late stage pipelines as well as our ramping investment and launch readiness activities for Brexit assets.

Speaker Change: One additional financial highlights.

Speaker Change: Each quarter, we recorded a noncash charge the noncash change in fair value of deferred and contingent consideration liabilities, which rate relate primarily to future stock payments associated with two of our past acquisitions.

Speaker Change: This charge being directly linked to the change in our stock price each quarter. The expense this quarter was significant at approximately $104 million.

Speaker Change: Importantly, this is not a new expense is noncash and has no impact on our cash runway or balance.

Speaker Change: In closing <unk> financial position remains very strong we produced our best ever revenue results in the second quarter, keeping us firmly on track to deliver our full year guidance with well over $1 billion of cash on our balance sheet now we would like to open the call to your questions. Operator can we take the first question. Please.

Sara Bonstein: Importantly, this is not a new expense, is non-cash, and has no impact on our cash runway or balance. In closing, Insmed's financial position remains very strong. We produced our best-ever revenue results in the second quarter, keeping us firmly on track to deliver our full-year guidance with well over a billion dollars of cash in our balance sheet. Now, we would like to open the call to your questions. Operator, can we take the first question, please?

Unknown Executive: Thank you. We will now begin our question and answer session. If you have dialed in and would like to ask a question, please press star followed by the number one on your telephone keypad. If you are called upon to ask your question and are listening via loudspeaker on your device, please pick up your handset and ensure that your phone is not on mute when asking your question.

Speaker Change: Thank you we will now begin your question and answer session. If you have dialed in and would like to ask a question. Please press star followed by the number one on your telephone keypad. If you are called upon to ask your question and our listening via loud speaker on your device. Please pickup your handset and ensure that your phone is not on mute when asking your question as a reminder, please limit yourself to one question.

Speaker Change: And one follow up only if you have any additional questions. Please feel free to happen. Thank you again. Thank you.

Unknown Executive: As a reminder, please limit yourself to one question and one follow-up only. If you have any additional questions, please feel free to jump the queue again. Thank you. Your first question comes from the line of Jessica Fye from J.P. Morgan. Please go ahead. Hey guys, good morning.

Speaker Change: Your first question comes from the line of Jessica Fye from Jpmorgan. Please go ahead.

Jessica Fye: Hey, guys. Good morning, Thanks for taking my question.

Jessica Fye: Thanks for taking my questions. I had sort of a competitive landscape question for Brenso. I was curious if you could share with us your take on the BI phase two top-line data from World Bronc and what you're gonna be watching for when more detailed results from the Airleaf study become available. And then, second, can you just confirm exactly what the primary endpoint is for Encore and how it differs, if at all, from ARISE or if it's not. Identical

Jessica Fye: And it feels like a competitive landscape question for Brent. So I was curious if you could share with us your take on the phase two topline data at world Bronc, and what youre going to be watching for when more detailed results from the <unk> study and the kind of available and then second can you just confirm exactly what the prime.

Speaker Change: Endpoint is for encore and how it differs if at all from arise or if it's.

Speaker Change: Well thank you.

Will Lewis: Thank you. Yeah, so I'll take the second question first, which is the encore primary endpoint. It's the PRO measure that we've agreed to with the FDA. And the primary distinction now is just that there will be eight questions, not nine. But the consequence of that is not having any impact on our expectations.

Speaker Change: Yeah. So just I'll take the second question first which is the oncor primary endpoint is the PRA measure that we've agreed to with the FDA and the primary distinction now is just that there'll be eight questions not nine.

Speaker Change: But the consequence of that is.

Speaker Change: As.

Will Lewis: We've run models of both eight and nine questions against the ARISE result, and in both cases, we had clear wins. So this has just been a clarification. It takes a long time to get the PRO group at FDA in alignment. I'm glad we're there. We did a lot of extra analysis for them to get them to that place, and they're very comfortable, and so are we.

Speaker Change: Not any impact on our expectations. We've ran models of both eight and nine questions against the arise resulted in both cases, we had clear wins. So this has just been a clarification. It takes a long time to get the PRA group at FDA.

Martinez: Two alignment I'm glad we're there and we did a lot of extra analysis for them to get them to that place and they are very comfortable and so are we as a consequence, we're super excited about flipping over that data card, which we now expect to be in the first quarter of 2026 on the <unk> front I'll actually ask Martinez to chime in here in a SEC.

Will Lewis: As a consequence, we're super excited about flipping over that data card, which we now expect to be in the first quarter of 2026. On the BI front, I'll actually ask Martina to chime in here in a sec. My take on that, because I was there in Dundee, was that that was a pretty, I think it was a disappointing presentation.

Speaker Change: My take on that because I was there in Dundee was that that was a pretty I.

Speaker Change: I think disappointing presentation that they had data, but it was a more model the data it wasn't really a readout of the underlying.

Will Lewis: They had data, but it was more modeled data. It wasn't really a readout of the underlying different dose effects on a statistical basis, and there wasn't any detail about safety, which I think everybody in the Assembly was surprised by. The expectation is that it might say more in Austria at the European Respiratory Society meeting in September. We didn't really see what we were expecting to see there.

Martinez: Different dose effects on a statistical basis, and there wasn't any detail about safety, which I think everybody in assembly was surprised by the expectation is that it might say more in Australia at the European respiratory Society meeting in September but.

Speaker Change: We didn't really see what we were expecting to see there I don't know Martin if you want to add any color to that.

Martina Flammer: I don't know, Martina, if you want to add any color to that. Yeah, maybe just as a reminder, the study was actually looking at testing three different doses, and it was also a dose response study. In the end, we really didn't see any results for any single dose. That is something I think everybody would be looking for, and we will be looking for that at ERS in September. We also would like to see what the actual safety data are, because there wasn't any data presented apart from a line that says there are skin effects, which wouldn't be anything that is surprising based on the mechanism of action, but understanding the extent of any skin effects, but also in general on the tolerability, whether it is GI-related or any other symptom class. So there wasn't really anything at this point that we could conclude, and those would be the things we'd be looking for in Vienna.

Martin: Maybe just as a reminder, so the study was actually looking at testing three different doses.

Martin: And it also it wasn't dose.

Martin: Response study.

Speaker Change: And we really didn't see any results for any singles dose that is something I think everybody will be looking for and we will be looking for that at E. R. S. In in September we'd also would like to see what is the actual safety data because there wasn't any data presented apart from a line that says there are skin effect, which we.

Speaker Change: Shouldn't be anything that is surprising us on the mechanism of action, but understanding of the extent of any sense skin effects, but also in general on the Tolerability, whether it is ti related or any other symptom class. So there wasn't really much at this point that we can conclude and those would be the things we'd be looking for Indiana.

Martin: Yes.

Will Lewis: I'll also add that our assumption is that we're going to see competition, so we're planning for that, whether it's from B.I. or some other source over the years into launch. We're running as though we've got people on our heels.

Speaker Change: I'll just add also that our assumption is that we're going to see competition. So we're planning for that.

Speaker Change: Whether it's from <unk> or some other source over the years into launch we're.

Speaker Change: Running as though we've got people on our heels.

Speaker Change: Thank you.

Ritu Baral: Thank you. Your next question comes from the line of Ritu Baral from TD Cabin. Please go ahead. Good morning, everyone.

Ritu barrel: Your next question comes from the line of Ritu barrel from TD carbon. Please go ahead.

Ritu Baral: Thanks for taking the question. Will, Martina, and Drayton, actually, I think this question is for all three of you. How are each of you thinking about one versus two doses in the NDA? Like, what are the clinical considerations? What are the commercial considerations? I mean, based on all the well discussions and presentations in Scotland, it seems like you're going to have to use the file for the 25. Otherwise, you know, the KOLs will come for you.

Ritu barrel: Good morning, everyone. Thanks for taking the question.

Ritu barrel: Well Martina and Drayton actually I think this question is for all three of you how how are each of us thinking about one versus two doses in the NDA like what are the clinical considerations what are the commercial considerations I mean based on all the all the discussions and <unk>.

Operator: After the speakers remarks, there will be a question and answer session. If you would like to ask a question during this time, thank you for a star followed by the number one on your telephone keypad. If you would like to answer a question, this press star one again.

Speaker Change: And patients in Scotland, it seems like Youre going to have to.

Speaker Change: Youre going to have to use it and file for the 25, otherwise Kols will come for you.

Will Lewis: But why would you consider using a lower dose? And then, as part of that NDA, how are you, or that NDA filing, how are you thinking about the indication language? Well, could it be that you could get an indication for treatment of bronchiectasis, or do you think it will necessarily be limited to reduction of bronchiectasis exacerbations? Those were both my questions.

Operator: Thank you.

Speaker Change: But why would you consider using a lower dose and then as part of that NDA Howard or that NDA filing how are you thinking about the indication language well could it be that you could you get an indication for treatment of bronchiectasis or do you think it will necessarily be limited to.

Will Lewis: Thanks. Sure. So, I'll take the second one first.

Bryan Dunn: I would now like to turn the call over to Bryan Dunn, head of investor relations, please go ahead. Thank you, John. Good day, everyone and welcome to today's conference call to discuss insmed second quarter, twenty twenty four financial results and provide a business update.

Bryan Dunn: I am joined today by Will Lewis, Chair and Chief Executive Officer and Sara Bonstein, Chief Financial Officer, who will each provide prepare remarks, after which they will be joined by Martina Flammer, Chief Medical Officer for the Q&A session. 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.

Speaker Change: Reduction of <unk>.

Speaker Change: On campuses exacerbations.

Speaker Change: Question.

Will Lewis: The treatment of bronchiectasis is, in fact, the label we expect to get. That's what we're going to be requesting. We do not think it will be limited based on two or more exacerbations. I think where that may play out to a more or less degree is in the payer landscape, which is something we're already working on in the disease education front right now. My perspective on the two doses, and I'll invite Martina to comment on that, is that I think, look, both are clear wins, and that's the most rewarding aspect of this study, both from a safety and from an efficacy standpoint.

Speaker Change: Sure. So I'll take the second one first the treatment of Bronchiectasis is in fact the label we expect to get that's what we're gonna be requesting we do not think it will be limited based on two or more exacerbations, I think where that may play out in more or less degree is in the payer landscape, which is something where we're already working on the disease education front right now.

Bryan Dunn: Please refer to our filings with the Securities and Exchange Commission. For more information concerning the risk factors that could affect the company. 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.

Speaker Change: My perspective on the two doses and then I'll invite Martina to comment on it is that I think look both are clear wins and that's the most rewarding aspect of this study are both from a safety and from an efficacy standpoint, as we move from 10 to 25, we see some additional benefit that is clearly captured in the.

Will Lewis: I will now turn the call over to Will Lewis for prepare remarks. Thank you, Bryan and welcome everyone.

Will Lewis: The second quarter of twenty twenty four will go down an insmed's history as the start of an important new era as a mid cap biotechnology company. During this quarter, we not only saw the continued growth of error case in refractory mac lung disease, but also positive phase two data for T. P. I. P. H. I. D. And of course, most significantly, the successful results of the landmark Aspen study. We are grateful to be able to mark and celebrate this moment with patients, physicians and investors. It is a time that reminds us why it is so rewarding to work in the field of biotechnology.

Will Lewis: As we move from 10 to 25, we see some additional benefit that is clearly captured in slowing the rate of lung function decline, as measured by a couple of different metrics, both FEV1 and forced vital capacity. And then as we look at how patients respond and how they feel, the quality of life measure and also the diary both captured improvements from the patient's point of view. And we think all of that information is very compelling, and certainly we've heard that from all of the experts in the field. The most important point for both 10 and 25 is that they have comparable safety profiles.

Martina: Slowing the rate of lung function decline as measured by a couple of different metrics, both F&B, one and forced vital capacity and then as we look at how.

Martina: How patients respond and how they feel the quality of life measure and also the diary a bolt captured improvements from the patient's point of view and we think all of that information is very compelling and certainly we've heard that from all of the experts in the field.

Will Lewis: Today, I intend to focus on a number of exciting catalysts across all of our pillars. However, we are keenly aware that nothing is more important for our near and medium-term success than flawlessly executing the launch of Brentsocatham and bronchi-ectasis. If we can get that right, we believe it holds the potential to transform this company once again, which is why executing on that opportunity will continue to be such a focus for us.

Speaker Change: The most important point for both 10 and 25 is that they have comparable safety profiles. So the risk reward calculus you run when you go from 10 to 25, you don't get any real additional risk in our opinion for getting those extra benefits and that suggests 25 is a very appropriate dose to think about for initiating patients.

Martina Flammer: So, the risk-reward calculus you run when you go from 10 to 25, you don't get any real additional risk, in our opinion, for getting those extra benefits. And that suggests 25 as a very appropriate dose to think about for initiating patients at, and I think we've heard that pretty loudly from a lot of the experts in the field. We're not making that commitment now because we want to have the dialogue with FDA to capture the benefit of their perspective on the 10 versus the 25.

Speaker Change: And I think we've heard that a pretty loudly from a lot of the experts in the field, we're not making that commitment now because we want to have the dialogue with FDA to capture the benefit of their perspective on the 10 versus the 25, but I think you know what.

Will Lewis: So let me start there with an update on Brentsocatham. The World Bronchi-ectasis conference held in Dundee, Scotland, in July was nothing short of a celebration of the positive results from the Aspen study. We have been touched and honored by the enthusiastic and often emotional responses we have heard from patients and the physicians who treat them to Aspen's overwhelmingly positive results. Brentsocatham's demonstrated ability not only to reduce the rate of pulmonary exacerbations, but also to preserve lung function and improve how patients feel all while displaying a safety profile that was comparable to placebo is something that we believe has the potential to be life-changing for patients living with bronchi-ectasis.

Martina Flammer: But I think, you know, we'll keep an open mind and enter that dialogue. We'll come forward with a proposal. We'll hear what their response is. But I think the 25 clearly suggests itself as having some added benefit over the 10 without there being much of a trade-off on safety. I don't know, Martine, if you'd add anything to that. Yeah, I think you've already described it well.

Martina: Keep an open mind and enter that dialog will come forward with a proposal will hear what their responses, but I think the 25 clearly suggests itself as having some added benefit over the 10 without there being much of a tradeoff on safety I don't know Martina if you'd add anything to that.

Joseph Schwartz: And you know, sometimes you think about starting with the lower dose and having an opportunity to go to a higher dose is something that physicians think about. In our case, overall, you have such a clear win for both doses that you now look at what is the additional benefit that patients can benefit from. And here, if you look at the lung function data, and you look at the FEV1, clinically, if you're a pulmonologist, and you could think about my patient currently loses about 60 to 70 milliliters every year, if I can bring that patient to 30, what would be a normal loss of milliliters or FEV1 for any adult as we age, that would be a very, very strong argument.

Martina: I think you already described it well and you know sometimes you think about starting with the lower dose and have an opportunity to go to a higher dose is something that physicians.

Will Lewis: We look forward to releasing additional data, including pre-specified subpopulation data from the Aspen trial at the chest conference in October in Boston. I want to reiterate that these subgroups have shown good consistency with the overall results of the study, so there should not be any negative surprises when these data are presented. We are immensely proud to be a part of this type of breakthrough for patients, and if approved, we look forward to getting Brentsocatham into the hands of those who are committed as quickly as possible.

Martina: Think about it.

Speaker Change: In our case you have overall on the reduction of pulmonary exacerbation, such a clear win for both doses that you now look at what is the additional benefit that patients can benefit can achieve and here. If you look at the lung function data and you look at the SEC one clinical.

Speaker Change: If you're a pulmonologist and you could think about my patient currently lose it loses about 60 to 70 million leaders every year, if I can bring that patient to 30, what would be a normal loss of milliliters of F&B one for any adult as we age.

Will Lewis: We continue to prepare for the expected U.S, filing of Brinso-Cat have been bronchi-actasis in the fourth quarter of this year, and our progress toward that goal remains on or even slightly ahead of schedule. Importantly, all of the necessary clinical and pre-clinical data required for the filing have already been completed, so there are no large gating factors left in front of us. As you know, the Aspen trial represents an enormous data set, and we are focused on thoroughly documenting those results for the filing. Including making the final determination on whether we will file one or both doses for approval. We continue to anticipate a launch in the U.S, in the middle of next year.

Speaker Change: That would be a very very strong argument and given the safety even for ease of special interests that is so good and there's very very little difference truly between those doses are.

Martina: I think we have a very strong argument for the 25.

Martina: Yeah.

Joseph Schwartz: And given the safety, even for AEs of special interest, that is so good. And there's very, very little difference really between those doses. I think we have a very strong argument for the 25. It comes from the line of Joseph Schwartz from Leadering Partners. Please go ahead. Hi, thanks very much. I have a couple questions on CRS. First of all, what are the powering assumptions that govern BIRCWH?

Martina: It comes from the line of Joseph Schwartz from Leerink Partners. Please go ahead.

Will Lewis: Our commercial team has also been diligently preparing for that expected launch. Nearly all of the additional 120 sales reps we intend to add to the U.S, sales force have already accepted offers, and these were chosen from a pool of more than 7,000 resumes. We expect to have all 120 new sales reps trained, and in the field, by October of this year, this timeline for deployment of sales reps follows a similar pattern as the error case launch.

Will Lewis: And then, are you endotyping patients in BIRCWH or stratifying patients in any way? And lastly, how did you decide on the two doses of 10 and 40 milligrams there? Yeah, so I'm super excited about that trial because now that we've validated the mechanism, we're kind of glad we started that one a little bit at a risk, to be candid. We didn't want to go full bore with all of the subsequent So HS starts at the end of this year, but the way we think about this is having validated the mechanism, we're now going to be exploring in our sort of hierarchical rank of where we think we could have the most impact and where there's the clearest unmet medical need. And so that's why we turn to CRS without nasal polyps next.

Joseph Schwartz: Alright, thanks, very much I have a couple of questions on Crs.

Joseph Schwartz: First of all what is.

Joseph Schwartz: What are the powering assumptions.

Speaker Change: Governed birch and then are you endo typing patients and birch or stratify patients in any way.

Speaker Change: And lastly, how did you decide on the two doses of 10 and 40 milligrams.

Will Lewis: We put those reps into the field six months ahead of the approval, and we believe that proactive approach contributed to error case ranking in the top 10 of non-oncology rare disease launches. For Brinso-Cat, we intend to have reps in the field even earlier, where they will work on disease state awareness and education, while also detailing error case to physicians in the hopes of helping more patients who could benefit from that tree.

Speaker Change: Yeah, So I'm Super excited about that trial, because now that we validated a mechanism where we're kind of glad we started that one a little bit of risk to be to be candid. We didn't want to go full bore with all of the subsequent.

Speaker Change: Ah trials. So Hs starts at the end of this year, but but the way we think about this as having validated the mechanism, we're now going to be exploring.

Will Lewis: In addition, we have made great progress with both national and regional pairs on disease state education and have engaged close to 90 percent of U.S, patient lives via pair discussions already. Pairs have been receptive to learning about this disease and the permanent damage caused by bronchi-actasis exacerbations. Our medical team is already sharing the Aspen data reactively upon request, and more detailed pre-approval discussions will follow our NDA filing next quarter.

Joseph Schwartz: In our sort of horror hierarchical rank of where we think we could have the most impact and there's a clear unmet medical need and so that's why we turned to Crs without nasal polyps next.

Will Lewis: That market opportunity for those patients, the unmet medical need there, is every bit as big in my mind as bronchiectasis, and I think it's pretty compelling if we're able to demonstrate impact there. So far, we're bringing forward the 10 and the 40 milligram dose, as you point out in the study. Going to the higher dose, we could certainly do that in other settings, but we didn't have the tox data done yet.

Joseph Schwartz: That market opportunity for those patients with unmet medical need there is every bit as big in my mind as bronchiectasis.

Speaker Change: And I think its pretty <unk>.

Joseph Schwartz: Compelling if we're able to demonstrate impact there so far we're bringing forward the 10 and the 40 milligram dose as you pointed out in the study going to the higher dose we could certainly do that in other settings. We didn't have the tox data done I just want to remind everybody about that by the time, we launched phase two we can now go as high as 65.

Will Lewis: Finally, it is important to note in the context of our anticipated launch next year that we are in a very good position from a supply perspective with ample API inventory already in hand. In fact, by the end of this year, we expect to have converted enough of that API into tablet form to meet our current anticipated demand for Brinso-Cat in the U.S, through at least the first year of its launch. As a matter of policy, we always look to prioritize continuity of supply for our patients.

Will Lewis: I just want to remind everybody about that. By the time we launched phase two, we could now go as high as 65 milligrams if we ever wanted to in a disease because we have that toxic work done and it's clear. Each disease is different, and will respond differently to DPP1 inhibition.

Joseph Schwartz: Five milligrams, if we ever wanted to in a disease, because we have that tox work done and it's and it's clear.

Speaker Change: Each disease is different will respond differently to the to the DPP one inhibition. So it seems to us appropriate and particularly in hindsight of Aspen to go up to 40.

Martina Flammer: And so it seems to us appropriate, and particularly in the hindsight of Aspen, to go up to 40 as the next dose. But I don't know the driving assumptions off the top of my head. Martina, do you know them?

Will Lewis: It was that principle that allowed us to maintain a steady supply of error case even during a global respiratory pandemic by establishing robust supply chains and a sufficient safety stock of inventory. Even though Brinso-Cat is easier to make in large quantities and on shorter notice compared to error case, we intend to build meaningful inventory and establish backup supply chains and that work is well underway.

Joseph Schwartz: As the next dose, but I don't know powering assumptions off top my head Martina do you know them, maybe you can address that.

Martina Flammer: Maybe you can address that. Yes, so we're powering 80% to detect the difference of 1.34 units, and we're 90% powered to detect one between 1.55 units. And so, as you know, as a primary endpoint, we have the sinus total symptom score. As you may know, this is a composite score of symptoms related to CRS and includes nasal congestion, facial pain, and loss of smell, and those will be the things that we will be looking for as a primary endpoint, and that's the driving force for it.

Martina: Yeah. So we're about empowering our 80% to protect the difference of 1.3 or four units and we're 90% powered to detect one between 1.55 units and so what as a primary endpoint we have to sign. This total symptom score as you May know this is a composite score of symptoms related to <unk>.

Will Lewis: Moving beyond bronchiactasis, we continue to be encouraged by the progress of our ongoing phase two study in CRS without nasal polyps, which we expect to read out in the second half of 2025. We continue to see improvements in average symptom scores in the blinded data from that study, which appear to correspond with the time when NSP reduction from DPP-1 inhibition should be occurring. We acknowledge that the data is blinded and still early, but we find it encouraging nonetheless.

Martina: S and includes nasal congestion facial pain and loss of smell and those will be the things that we will be looking for as a primary endpoint then that's the powering for it and I'll just add that.

Martina Flammer: And I'll just add that, while mixed and blinded and very early, there is a temporal alignment between improvement in that symptom score on an overall basis and when we would expect the onset of the drug to take effect. So that suggests that there may be something going on here that's positive. Obviously, we don't know that until we unblind, but it's an encouraging trend nonetheless.

Speaker Change: Well blended in blinded and very early there is temporal alignment between improvement in that symptom score on on an overall basis and when we would expect the onset of the drug to take effect. So that suggests that there may be something going on here. That's positive obviously, we don't know that until we unwind.

Will Lewis: We are excited to be moving forward with our previously stated plans to kick off a phase two study of Brinso-Cat and Hydra Adonitis Super-Tiva, now that the Aspen study has demonstrated the potential of the DPP-1 mechanism. We remain on track to have the first active U.S, sites open before the end of the year, with the first patients being screened shortly thereafter.

Joseph Schwartz: It's encouraging trend nonetheless.

Will Lewis: And Joe, I would just remind you that the $5 billion of peak sales that we referred to at our commercial day were for bronchiectasis alone. So the upside for CRS is not included in that number, and as Will already mentioned, we believe that could be a sizable patient population. Thanks, that's helpful. And how do you view whether it makes sense to endotype or stratify patients based on the mechanism? What we're looking for is we're looking at patients who are below 300 eosinophils and above 300, but we know that in TRS without nasal polyps, also, there is an eosinophilic component.

Joseph Schwartz: And Joe I would just remind you that $5 billion of peak sales that we referred to at our commercial day.

Will Lewis: Finally, I want to comment briefly on the work we are doing to develop next generation DPP-1 inhibitors in an effort to maintain our leadership in this important new class of medicines. This work is not new, having begun shortly after the phase two willow results first read out. In fact, we have already synthesized and screened over 850 novel DPP-1 inhibitors. And have filed over 10 unique patent applications that disclose and claim these compounds.

Joe: That was bronchiectasis alone so the upside for Crs is not included in that number and as well already mentioned, we believe that will that could be a sizable patient population.

Joe: Thanks, that's helpful and how do you view, the whether it makes sense to enter.

Speaker Change: And the type of stratify patients based on the mechanism.

Speaker Change: What we're looking for is we're looking at patients who are below 300, you'll see no fail and above 300, but we know that in theory without nasal polyps are also there is an eosinophilic component as you know with all of these diseases. It is it is not something that is a key.

Will Lewis: We are now advancing the first candidate from this group into IND enabling studies, and we expect one to two more to follow closely thereafter. Based on the strength of the efficacy and safety data from Aspen, in patients with bronchiectasis, we are evaluating if there may be other indications we want to explore using DPP-1 inhibition. This can include other indications with significant neutrophil involvement and where patients continue to face significant unmet needs despite current treatments such as rheumatoid arthritis, lupus nephritis, and other inflammatory conditions. Keep in mind that we could develop these molecules for these new indications ourselves, or we could choose to sell or partner them with others who already have a presence in those markets.

Martina Flammer: As you know, with all of these diseases, it is not something that is a pure mechanism that is looking only at eosinophils. So we look at both of those patients, but we know there is a very strong neutrophilic and driven group for both of them. Thanks, friends.

Speaker Change: You are making isn't that is looking only at eosinophilic. So we look at both of those patient, but we know there is a very strong neutrophil they get driven group for both of them.

Speaker Change: Makes sense. Thank you.

Jeffrey Hung: Thank you. Your next question comes from the line of Jeffrey Hung from Morgan Stanley. Please go ahead. Hi, good morning. This is Catherine on behalf of Jeff.

Speaker Change: Your next question comes from the line of Jeffrey Hung from Morgan Stanley. Please go ahead.

Speaker Change: Hi, Good morning. This is Katherine on for Josh. Thank you for taking our question just one looking ahead to the expected <unk> launch can you talk more about your strategy for targeting patient groups at launch will you be focusing primarily on the diagnosed population or do you have plans to target or go after the undiagnosed population.

Jeffrey Hung: Thank you for taking our question. Just one, looking ahead to the expected Friends of CADEP launch, can you talk more about your strategy for targeting patient groups at launch? You know, will you be focusing primarily on the diagnosed population, or do you have plans to target or go after the undiagnosed population or the asthma, COPD, and comorbid patients experiencing exacerbations that you mentioned during your R&D? Yeah, so thanks for

Will Lewis: Either way, these follow-on compounds are expected to keep us at the forefront of this exciting new drug class.

Will Lewis: Now let me turn to Eric Ace. I am pleased to report that Eric Ace continues to perform well commercially, delivering 17% growth this quarter compared to the second quarter last year. Much of that success is directly related to the strong execution of our commercial teams across the world.

Speaker Change: Or the asthma COPD comorbid patients experiencing exacerbations that you mentioned during your R&D day.

Will Lewis: Keep in mind that these same teams will be the ones to launch Friends of Cata, assuming regulatory approvals are achieved. In addition to commercial execution, we have also made progress on Eric Ace's clinical development this quarter. As previously indicated, we met in June with the Division of the FDA responsible for patient-reported outcome measures. That meeting resulted in us successfully aligning with the FDA on the primary endpoint for the on-course study that can support label expansion to include all MAC lung patients and full approval for the current refractory indication if the data are positive.

Will Lewis: I think the way to conceive of what we're going to be doing with our launch is that disease state awareness is already well underway, and I think that's the first hurdle to clear. We know from our previous experience of being the first in a disease launch that it's very important to raise awareness among physicians of the disease and its sequelae, and that process began at the American Thoracic Society a year ago this last May. So we've been out there for a while.

Speaker Change: Yeah. So thanks for the question I think the way to conceive of what we're going to be doing with our launch is that disease state awareness is already well underway and I think thats. The first hurdle to clear we know from our previous experience of being a first in disease launch that it's very important to raise the awareness among physicians.

Speaker Change: The disease and its sequela.

Speaker Change: That process began at the American thoracic Society, a year ago. This last may so we've been we've been out there for a while we're doing the same thing with Payors.

Will Lewis: We're doing the same thing with payers, and as we raise that awareness, I think physicians will turn their attention to patients that may be appropriate for treatment, assuming that we are approved and clear all the regulatory hurdles. We know from our dialogue with physicians that those patients who are diagnosed today are the ones that they're going to immediately turn to for the use of the drug, assuming it's approved. And I think that's fully appropriate.

Speaker Change: And as we raise that awareness I think physicians will turn their attention to patients that may be appropriate for treatment, assuming that we are approved and clear all the regulatory hurdles, we know from our dialogue with physicians that those patients who are diagnosed today.

Will Lewis: Now that we have this clarity from the FDA, we have re-evaluated on-course enrollment target with the goal of ensuring we give the study the best chance of success in achieving its objectives using appropriately conservative powering assumptions. Based on that evaluation, we have updated on-course target enrollment to 400 patients with targets powering of more than 90% for the primary endpoint. Importantly, recruitment for the trial has been proceeding very well throughout 2024 following the arise study result.

Speaker Change: Are the ones that theyre going to immediately turn to for use of the drug assuming it's approved and I think that's fully appropriate but we're also aware that there is a growing dialogue and corus among treating physicians that there is probably a decent number of patients who have COPD or who have asthma that may have been misdiagnosed or that have those can.

Will Lewis: But we're also aware that there's a growing dialogue and chorus among treating physicians that there's probably a decent number of patients who have COPD or who have asthma that may have been misdiagnosed or that have those conditions and are potentially comorbid with bronchiectasis. We talked about that on our commercial day. And I think that has gained a lot of momentum, frankly, independent of us. And as people gain that awareness, and they become aware of our medicine and its ability to have an impact on these patients, again, presuming that it clears the appropriate regulatory hurdles, that's going to be an exciting time.

Will Lewis: As a result, we expect to be in a position to stop screening new patients later in the third quarter and would then expect the top line results for on-course to read out in the first quarter of 2026. As we have commented before, we can now approach the FDA about the possibility of an accelerated filing under subpart H. We expect to have that answer by the end of this year. As a reminder, our expectation continues to be that the on-course data will be required for all global regulatory filings to potentially expand the label for error case to include all patients with MAC lung disease. We will update you as we learn more from our interactions with the FDA.

Speaker Change: <unk> and are potentially comorbid with bronchiectasis, we talked about that on our commercial day and I think that.

Speaker Change: Has gained a lot of momentum frankly independent of us and as people gain that awareness and they become aware of our medicine and its ability to have impact on these patients again presuming that it clears the appropriate regulatory hurdles that's going to be an exciting time, because I think what often happens in these kinds of first in disease indications.

Will Lewis: Because I think what often happens in these kinds of first-in-disease indications is that there are many more patients out there than people would have originally thought. But the short answer to your question is that the half a million patients that we know are diagnosed today with bronchiectasis, those are the first ones we're going to be targeting. And we'll see and learn along the way how much broader that may get. Great, thank you so much.

Speaker Change: Is that there are many more patients out there than people would have originally thought but the short answer to your question is that half a million patients that we know are diagnosed today with bronchiectasis.

Will Lewis: Let me also provide a quick update on our TPIP development program. Enrollment in our Phase 2 PAH study has also accelerated recently, likely resulting from the strong Phase 2 trial read out in PHILD and MAC. We now have more than 75% of the enrollment completed in our PAH trial, which keeps us on track for an expected readout in the second half of 2025. We are consistently monitoring the results of the study on a blinded basis, which continue to show impressive reductions in pulmonary vascular resistance for many of the patients in the study.

Speaker Change: Those are the first ones, we're going to be targeting and we will see and learn along the way how much broader that that may get.

Jeffrey Hung: And then just a quick one, if I may. You previously provided the range of $40,000 to $96,000 as a likely U.S. price. Can you just remind us of the factors here that may drive the price to one end of that range or the other? Thank you so much.

Speaker Change: Great. Thank you so much and then just a quick one if I may you previously provided the range of 40 to 96000 is unlikely U S. Price can you just remind us of the factors here that may drive the price to one end of that range or the other thank you so much.

Will Lewis: Sure. Well, I think whenever you consider price, you have to think about the idea of value for money. And that proposition is, frankly, spelled out in the label. So until we know what that's going to look like, it's hard to really think about price with any greater specificity. I think across that range, given what we've seen in the data and presuming that that is something that is reflected in the label, which is appropriate or is available to physicians for their contemplation, we have every reason to believe that anywhere along that line there is something that is appropriate.

Speaker Change: Sure well I think whenever you consider price you have to think about the idea of the value for money and.

Will Lewis: These improvements in PBR would not normally be expected for patients who have not had a change in their therapy. All of this adds to our excitement for the upcoming readout of the trial. And for the potentially compelling profile that began to emerge with the recent PHL, the top-line results.

Speaker Change: That proposition is frankly spelled out in the label so until we know what that's going to look like it's hard to really think about price with any greater specificity I think across that range given what we've seen in the data and presuming that that is something that is reflected in the label, which is appropriate or in.

Will Lewis: If I can summarize today's update, it is this. Insmed is preparing diligently for the expected launch of Brentsocadib and bronchi-ectasis next year, including regulatory filings, commercial readiness, payer discussions, and inventory planning, all of which is progressing on or ahead of schedule. This launch represents the type of opportunity that only comes along once in a career if you're lucky. We all recognize the enormity of what lies ahead and how important it is for us to get it right for our patients, investors, and other stakeholders.

Speaker Change: Is available to physicians for their contemplation. We have every reason to believe that anywhere along there is something that is appropriate.

Will Lewis: We have a lot more work to do before we're going to settle on price, but I think what we have found in these data and the response to these data is that they are remarkably compelling. This is a, I call it, a landmark study, and I know every company lays claim to having the ability to produce good data. This is one of those rare moments where this drug is going to speak for itself.

Speaker Change: We got a lot more work to do before we are going to settle on price, but I think what we have found in these data and the response to these data is that they are remarkably compelling this is a.

Speaker Change: Called it a landmark study and I know.

Speaker Change: Every company lays claim to having the ability to produce good data. This is one of those rare moments, where this drug is going to speak for itself and the physicians have already told us that and they are excited to put their patients on this drug presuming, it's approved and I think we're going to find the right <unk>.

Will Lewis: While we acknowledge the critical importance of the successful launch of Brentsocadib, I also want to recognize the remarkable progress we are making in parallel across every other area of clinical development and research and the exciting opportunities that this work has the potential to unlock. Shortly after we launch Brentsocadib, we anticipate additional clinical readouts that could represent sizable growth opportunities in their own right, such as phase two readouts for Brentsocadib and CRS without nasal polyps, and TPIP and PAH followed by the phase three readout of Ericace in newly diagnosed MAC lung infection. We look forward to continuing to execute on behalf of patients in our stakeholders as we enter the unique period of potential growth that lies ahead of us.

Andy Chen: And the physicians have already told us that, and they're excited to put their patients on this drug, presuming it's approved. And I think we're going to find the right balance between setting a price that will reflect that value for patients and allow us to move forward as a company and reinvest in other promising medicines. Your next question comes from the line of Andy Chen from Wolf Research. Please go ahead. Hi guys, it's Chukwudis Kiyogi here for Andy Chan.

Speaker Change: Balance between setting.

Speaker Change: Setting a price that that will reflect that value for patients and allow us to.

Speaker Change: To move forward as a company and reinvest in other promising medicines.

Speaker Change: Thank you.

Speaker Change: Yeah.

Speaker Change: Your next question comes from the line of Andy Chen from Wolfe Research. Please go ahead.

Andy Chen: In CRSV, besides that SIG, any internal bar for a go-no-go decision into Phase 3? And what's a good comparison here for efficacy and safety? Is the fixate your bar, or do you seek to be better in order to move forward? And I have one quick follow-up. Thank you. So just to be clear, on CRS without nasal polyps, there's nothing approved to treat that condition. There is some medicine that is used to treat CRS with nasal polyps, but, and that includes things like Humira, but for CRS without nasal polyps, which is largely neutrophil-driven, there is nothing.

Speaker Change: Hi, guys. This is <unk> on here for Andy Chien.

Speaker Change: In Crs.

Speaker Change: <unk> stat Sig any internal bar for a go no go decision into phase III and what's a good compare here for efficacy and safety is depicts Ain't your bar or you seek to be better in order to move forward and I have one quick follow up thank you.

Sara Bonstein: Now I will turn the call over to Sarah to walk through the financials for the quarter. Thank you, Will, and good morning, everyone. I am happy to share some of the details of InSMed's financial performance for the second quarter of 2024. We enter the quarter with $1.25 billion in cash and cash equivalence, representing an increase of $651 million compared to the end of last quarter. This increase in cash was driven primarily by our equity raised during the quarter, which added $713 million on a net basis, and was supplemented by cash received by the company through the exercise of stock options during the quarter.

Speaker Change: So just to be clear on Crs without nasal polyps, there's nothing approved to treat that condition. There is some medicine that is used to treat crs with nasal polyps, but and that includes things like humira.

Speaker Change: But for Crs without nasal polyps, largely neutrophil driven there is nothing and when we talk about this disease indication we referred to the incident population the annual rate of patient numbers that are either subject to surgery repeat surgery or are eligible for it and that's in the hundreds of thousands of.

Will Lewis: And when we talk about this disease indication, we refer to the incidence population, the annual rate of patient numbers that are either subject to surgery, repeat surgery, or are eligible for it, and that's in the hundreds of thousands of patients. That's every year. So that's quite a substantial opportunity, and we talk about the overall prevalence population as being, in the U.S. alone, close to 29 million people. So to talk about a disease indication with nothing approved of that magnitude and go, as we did with Eric's case, after the severe end of the patient spectrum out of the gate, that's really the strategy here.

Sara Bonstein: When these items are excluded, the underlying cash burn for the quarter was approximately $139 million, which is relatively consistent with our historical cadence. Before I move on to talk more about our performance this quarter, I want to provide a brief update on our $225 million convertible debt instrument, which was set to mature in January 2025, but what we called in June. As of August 7th, 99.9% of those notes have already been converted to approximately 5.7 million shares of our stock ahead of the Redemption date on August 9th.

Speaker Change: That's every year, so that's quite a substantial opportunity and we talk about the overall prevalence population is being in the U S alone close to 29 million people. So to talk about the disease indication with nothing approved of that magnitude and going as we did with air case. After the severe end of the patient spectrum out of the gate.

Will Lewis: What is sufficient for moving into phase three? Well, I think, honestly, we have to look at the phase two data and have some reflections on whatever that is going to be. There aren't great animal models for this, and there isn't precedent because there's nothing approved yet.

Speaker Change: That's really the strategy here what is sufficient for moving into phase III I think honestly, we have to look at the phase II data and have some reflections on whatever that that is going to be there arent great animal models for this and there isn't a precedent because there's nothing approved so we're going to have to take a close look at that but once again the standard we always.

Sara Bonstein: I will now walk you through some of the highlights of our commercial performance in the second quarter of 2024. Global Met revenues this quarter were $90.3 million, representing 17% year-over-year growth compared to the second quarter of 2023. Not only does this result reflect the highest quarterly sales for error case in its history, but it also establishes new all-time highs for sales in each of our three commercial regions. In the U.S., net revenue for the second quarter of 2024 was $63.8 million, up 11% compared to prior year quarter.

Martina Flammer: So we're going to have to take a close look at that, but once again, the standard we always use is, is this going to make a dramatic impact on patients? And, you know, when we talk about patients who are subject to repeat surgery or avoiding surgery, the ability to provide benefits that are meaningful for that patient group would be sort of how we think about it. I don't know, Martina, if you want to add anything.

Speaker Change: Uses is this going to make a dramatic impact on the patients and when we talk about patients who are subject to repeat surgery or avoiding surgery the ability to provide benefits that's meaningful for that patient group.

Martina: Group would be sort of how we think about I don't know Martina if you want to add anything on them.

Martina Flammer: Yeah, apart from static in the primary endpoint, one of the things we look at the secondary endpoint is the Lunt-McKay CT score. That's something that is very often used and standardized in this disease where you actually look at what kind of opacification do you see in the sinuses.

Martina: Apart from that taking the primary endpoint one of the things we look as a secondary endpoint.

Martina: Is the Londoner K C. T score that's something that is very often used in standardized used in this in this disease, where you actually look of what kind of Opacification do you see in the cyanosis. So that is a another efficacy measure.

Sara Bonstein: New patients starts in the U.S, have remained very strong, reflecting the value that physicians see in using errors in their case for their refractory patients. The quarter's performance also benefited from a rebound in active patients following the disruptions caused by the change healthcare cyber attack in the first quarter of the year. In Japan, second quarter 2024 net revenue was $21.1 million, reflecting 35% growth over the same quarter last year. The record-setting performance in Japan this quarter was primarily driven by stronger demand resulting from an increase in physician reach as we have worked to expand our sales force and to a lesser extent favorable inventory patterns in the quarter.

Will Lewis: So that is another efficacy measure. Got it. Thank you. And, um, can you comment on aircase sales momentum by geographic region? Uh, should we be expecting near-term elections soon, especially in areas like Japan? And how much is left in that region?

Speaker Change: Got it thanks, and can you comment on sales momentum by geographic region.

Speaker Change: Should we be expecting any item, that's interesting, especially in areas like Japan and how much is left in that region. Thank you.

Will Lewis: Thank you. So, I think we feel very good about the performance this quarter, but I'll actually ask Sara if she wants to make any commentary on a regional basis. Sure. I'm happy to make a comment. And, you know, just to start off on a global basis, we were really encouraged by the continued double-digit growth across all of our regions. You know, we're in our sixth-plus year of launch in the U.S., and to still see this level of growth is absolutely tremendous and speaks to patient need and the need and importance of Aircase. In the U.S., we saw, you know, tremendous growth.

Sarah: So I think we feel very good about the performance this quarter, but I'll actually ask Sarah if she wants to make any commentary on the regional basis sure happy to make comment and just to start off on a global basis. We were really encouraged by the continued double digit growth across all of our regions. You know R&R six plus year of launch in the U S and just they'll see this level of growth is absolutely.

Sara Bonstein: And we continue to be really impressed by the commercial organization. As a reminder, that's the commercial organization that we anticipate will launch, so CASA assuming approval by FDA by the middle of next year, so couldn't be more pleased, obviously, augmenting that sales force in the U.S. And as Will mentioned in the prepared remarks, those 120 reps were nearly all hired from a very large pool of candidates, so we feel confident we have top talent that is augmented into our commercial organization that will now be So, the U.S., we feel really comfortable with that continued growth. Japan, you know, has 35 percent growth.

Sara Bonstein: In Europe and the rest of the world, net revenue in the second quarter of 2024 came in at $5.4 million, up 37% compared to the same quarter last year, driven primarily by strong performance in the UK and Germany.

Sarah: Tremendous and talks about the patient need.

Speaker Change: And the need unimportance of of Erra case in the U S. We saw tremendous growth we continue to be really impressed by the commercial organization. As a reminder, that's the commercial organization that.

Sara Bonstein: Importantly, this quarter's performance keeps us on track to achieve a reiterated full year 2024 global revenue guidance of $340 to $360 million. Let me now turn to a few additional financial items. In the second quarter 2024, our growth synapse in the U.S, were 15.4%, which was consistent with our expectations. We continue to anticipate that growth synestial settle in the mid to high teen range for the full year. Cost of product revenues for the second quarter of 2024 was $21 million, or 23.2% of revenues, which is also consistent with our historical performance.

Speaker Change: We anticipate will launch <unk>, assuming approval by FDA.

Martina: By Middle of next year, so couldn't be more pleased.

Sarah: Obviously augmenting that sales force in the U S and.

Sarah: And as well mentioned in the prepared remarks that 120 reps on nearly all hired from a very large pool of candidates that we feel confident we have top talent that is augmented into our commercial organization that will now be able to have aerospace as well as well as the disease state awareness. So you actually felt really comfortable.

Sarah: On that continued growth, Japan, 35% growth.

Sara Bonstein: Can't ask for much more from a region, so really pleased to see that continued performance. We did add some additional therapeutic specialists in Japan to continue with that growth. And Europe, it's a small number, but very material from a percentage perspective, and I'm really excited to see that. So, couldn't be more pleased with the growth across each of the regions and feel really confident in our 340 to 360 full-year guidance. Yeah, and I just thought we'd add a quick shout out to the commercial team around the world for the excellent job they did this quarter and the momentum that they're generating for the second half of the year. Thank you. I got it.

Sarah: Can't ask for much more from a region. So really I am pleased to see that continued performance we did add some.

Sara Bonstein: Turning to our gap operating expenses. In the second quarter, research and development expenses were $146.7 million, and SGNA expenses were $106.6 million. Reflecting investment in both our early and mid to late stage pipelines, as well as our ramping investment in monstering activities for Brunswick assets.

Speaker Change: Some additional therapeutic specialists in Japan to continue with that growth in Europe.

Sarah: Small in number but very material from a percentage perspective, and really excited to see that so couldn't be more pleased on the growth across each each of the regions.

Sarah: And feel really confident in our $3 40 to 360 <unk> full year guidance, Yeah, and I just thought we'll add a quick shout out to the commercial team around the world for the excellent job. They did this quarter and the momentum that they're generating for the second half of the year.

Sara Bonstein: One additional financial highlight. Each quarter, we record the non-cash charge, the non-cash change in fair value of deferred and contingent consideration liabilities, which relate primarily to future stock payments associated with two of our past acquisitions. With this charge being directly linked to the change in our stock price each quarter, the expenses quarter was significant at approximately $104 million. Importantly, this is not a new expense, is non-cash, and has no impact on our cash runway or balance.

Sarah: Got it thank you.

Sarah: Okay.

Will Lewis: Thank you. Your next question comes from the line of Jason Zemansky from Bank of America. Please go ahead.

Speaker Change: Your next question comes from the line of Jason The landscape from Bank of America. Please go ahead.

Speaker Change: Hey, good morning.

Jason Zemansky: Good morning, this is Cameron Blue Dog on behalf of Jason. Congratulations on the quarter and thanks so much for taking our question. I guess looking ahead to Brenzo's launch, you mentioned your plans to hire a sales force of 120. But can you maybe elaborate a bit more on additional steps the team has taken to build out the commercial infrastructure? And maybe what's still left to do?

Sarah: Jason Congrats on the quarter and thanks, so much for taking that.

Speaker Change: Question I guess looking ahead to <unk> launch you mentioned your plans to hire sales force of 120, but can you maybe elaborate a bit more on additional steps <unk> taken to build out the commercial infrastructure and maybe what's still left to do and then what do you expect to be the biggest or at least most time consuming challenge.

Sara Bonstein: In closing, intimate financial position remains very strong. We produced our best ever revenue result in the second quarter, keeping us firmly on track to deliver our full year guidance, with well over $1 billion of cash in our balance sheet.

Will Lewis: And then, what do you expect to be the biggest or at least the most time-consuming challenge at this point? Is it going to be physician awareness, payer issues, or maybe something else? Thank you.

Speaker Change: At this point is it going to be physician awareness payer issues or maybe something else. Thank you.

Operator: Now, we would like to open the call to your questions. Operator, can we take the first question please? Thank you.

Will Lewis: So I can just comment, again, in reverse order, that the single most important thing, while it all has importance, the single most important thing that keeps me focused is pair access. I think now, more than ever, in the era in which we operate, getting that right is really the key to a successful launch. And I could not be more pleased with the strength of the team we have and the work we've already done.

Speaker Change: So I can just comment and again reverse order that the single most important thing a while it all has importance. The single most important thing that keeps me focused as the payer access I think now more than ever.

Operator: We will now begin our question and answer session. If you have dialed in and would like to ask a question, please press star followed by the number one on your telephone keypad. If you are called upon to ask your question and are listening via loudspeaker on your device, please pick up your handset and ensure that your phone is not on mute when asking your question. As a reminder, please limit yourself to one question and one follow-up only. If you have any additional questions, please feel free to have in the queue again.

Operator: Thank you.

Speaker Change: In the area in which we operate.

Speaker Change: Getting that right is really the key to the successful launch and I could not be more pleased with the strength of the team we have and the work we've already done as we've mentioned we've already been in dialogue with more than 90% of patient lives in the U S. The groups would cover them and we have a very good and robust dialogue going on about disease state awareness there those are.

Will Lewis: As we mentioned, we've already been in dialogue with more than 90 percent of patient lives in the U.S., the groups that cover them, and we have a very good and robust dialogue going on about disease state awareness there. Those efforts run in parallel, and second, I'll ask Martina to talk about medical affairs, separate from commercial, obviously. But on the balance of the commercial front, we have every one of our, what we refer to as customer-facing groups, in growth mode and in preparation mode for this launch.

Jessica Fye: Your first question comes from the line of Jessica Phi from JP Morgan. Please go ahead. Hey guys, good morning. Thanks for taking my questions. I think it's like a competitive landscape question for Brunso. I was curious if you could share with us your take on the BI Phase 2 top-line data at WorldBronk and what you're going to be watching for when more detailed results from the AirLeaf study become available. I got full. Thank you.

Martina: <unk> run in parallel in a second I'll ask Martina talk about medical affairs separate from commercial obviously, but.

Speaker Change: The balance of the commercial front, we have every one of our what we referred to as customer facing groups in growth mode and in preparation mode for this launch we.

Will Lewis: We set the standard by our error case launch, which was to have everything ready about six months before approval. In this case, it's going to be more like nine months before approval. I just would highlight the most recent effort to hire the additional 120 sales reps. I think as of yesterday, we had all but one who had accepted those positions.

Sarah: Set the standard by our Erra case launch, which was to have everything ready about six months before approval in this case, it's going to be more like nine months before approval.

Sarah: Just would highlight the most recent.

Will Lewis: Yeah, so just I'll take the second question first, which is the on-core primary endpoint. It's the PRO measure that we've agreed to at the FDA and the primary distinction now is just that there'll be eight questions, not nine, but the consequence of that is not any impact on our expectations. We've ran models of both eight and nine questions against the arise result and in both cases we had clear wins. So this has just been a clarification.

Sarah: Effort to hire the additional 120 sales reps I think as of yesterday, we had all but one who had accepted.

Sarah: Those positions and the reason why that last one is not onboard yet is because for every one of these positions. Although we had more than 7000 resumes we have held ourselves to the standard of not only excellence, but cultural fit within the company one of the great strengths of <unk> is that we have folks that are here that are really interested in helping patients.

Will Lewis: And the reason why that last one is not on board yet is that for every one of these positions, although we had more than 7,000 resumes, we have held ourselves to the standard of not only excellence but cultural fit within the company. One of the great strengths of InsMed is that we have folks that are here that are really interested in helping patients get better. And I can't emphasize that enough as an important cornerstone element of what this company is all about.

Will Lewis: It takes a long time to get the PRO group at FDA to alignment. I'm glad we're there. We did a lot of extra analysis for them to get them to that place and they're very comfortable and so are we. It's the consequence we're super excited about flipping over that data card, which we now expectably in the first quarter of 2026.

Sarah: <unk>.

Sarah: Get better and I can't emphasize that enough is an important cornerstone elements of what this company is all about and the purity of that needs to be preserved even as we find scale in larger opportunities. So I'm very pleased with the work that's been done to date, our leadership team is absolutely crushing it on every front as we've said in the remarks, we are.

Will Lewis: And the purity of that needs to be preserved even as we find scale in larger opportunities. So I'm very pleased with the work that's been done to date. Our leadership team is absolutely crushing it on every front.

Martina Flammer: On the BI front, I'll actually ask Martina to chime in here in a sec.

Martina Flammer: You know, my take on that because I was there in Dundee was that that was a pretty I think disappointing presentation that they had data, but it was more modeled data. It wasn't really a readout of the underlying different dose effects on a statistical basis and there wasn't any detail about safety, which I think everybody in assembly was surprised by. The expectations that it might say more in Austria at the European respiratory society meeting in September, but you know, we didn't really see what we were expecting to see there.

Will Lewis: As we've said in the remarks, we are at or ahead of schedule on pretty much every metric. And I can say, having just reviewed it during our board meeting over the last two days, I think we all sit here today feeling very good about our preparation for next year. There's a lot of work still to be done. I don't want to take anything away from that.

Sarah: At or ahead of schedule on pretty much every metric and I can say, having just reviewed during our board meeting over the last two days I think we all sit here today feeling very good about our preparation for next year. There's a lot of work still to be done I don't want to take anything away from that.

Martina Flammer: But we feel very good about the strength of our position, the strength of the team, the content of the character of the people we brought on board, and the efforts that we are putting into this opportunity. It can't be overstated how significant this is, and therefore how important it is for us to get it right. Martina, do you want to talk about the medical side of the equation? Yeah, happy to.

Sarah: But we feel very good about the strength of our position the strength of the team.

Mark: Content of the character of the people we brought on board and the efforts that we're putting on this this opportunity it can't be overstated, how significant this is and therefore, how important it is for us to get it right Mark do you want to talk about the medical side of the equation.

Martina Flammer: I don't know, Martina, if you want to add any color to that. Yeah, maybe just as a reminder, so the study was actually looking at testing three different doses and it also was a dose response study. At the end, we really didn't see any result for any single dose. That is something I think everybody would be looking for and we will be looking for that at ERS in September. We also would like to see what is the actual safety data because there wasn't any data presented apart from a line that says there are skin effects, which wouldn't be anything that is surprising on the mechanism of action, but understanding of the extent of any skin effects.

Martina Flammer: But also in general, on the tolerability, whether it is GI related or any other symptom class. So there wasn't really much at this point that we can conclude and those would be the things we'd be looking for in Vienna.

Martina Flammer: So in addition to what you speak to the payer from a commercial perspective, and should they provide access, and how do they think about it, what's important is payer organizations have medical directors, just as many other organizations do. And those are the people who understand and learn about what the true unmet medical need here is, what other treatments are available, what are the paths to diagnosis, and how does a patient go through the system.

Mark: Yeah happy to so in addition to what you speak to with a payer but from a from a commercial perspective and should they provide access and how did you think about it what's important is payer organizations have medical directors just isn't any other organizations to and those are the people who understand and learn about what is the true unmet medical need.

Sarah: What other treatments are available what are the path to diagnosis, how does the patient go through the system. We have colleagues from meta we speak about our medical outcomes Leesville colleagues, who are on a regional basis in the field, who understand how what is relevant for the medical director in the payer organization.

Martina Flammer: We have colleagues, we speak about our medical outcomes liaison colleagues who are on a regional basis in the field, who understand what is relevant for the medical director in a payer organization and provide them with that information, and they also serve as the point of contact to explain not only today, as we talk about, for example, Aspen, what the data overall is, but what does that mean for the population that these payers cover in the sense of medical terms and outcomes? The next question comes from the line of Jennifer Kim from Cantor Fitzgerald. Please go ahead.

Sarah: Providing them that information and they also serve as the point of contact to explain not only today as we talk about for example ask then what is the data overall, but what does that mean for the population that these payers cover in the sense of medical terms, an unmet need.

Will Lewis: I'll just add also that our assumption is that we're going to see competition. So we're planning for that, whether it's from BI or some other source over the years into launch. We're running as though we've got people on our heels. Thank you.

Sarah: Yeah.

Sarah: Yeah.

Sarah: Next question comes from the line of Jennifer Kim from Cantor Fitzgerald. Please go ahead.

Ritu Baral: Your next question comes from the line of Ritu Burrell from PD Cabin. Please go ahead. Good morning, everyone. Thanks for taking the question. Will Martina and Drayton actually think this question is for all three of you? How are each of you thinking about one versus two doses in the NDA? Like what are the clinical considerations? What are the commercial considerations? I mean, based on all the, all the, you know, well discussions and presentations in Scotland, it seems like you're going to have to, you're going to have to use the file for the 25 otherwise, you know, the K wells will come for you.

Jennifer Kim: Hey guys, thanks for taking my questions. I wanted to go back to the one versus two dose for Brenso. It seems like everyone is in agreement that there's a compelling reason to go for the higher dose or include the higher dose. Is there a reason why the FDA would have hesitation on that front? And then my second question is, could you give any color on exactly where you're at with on-core enrollment? Sure.

Jennifer Kim: Hey, guys. Thanks for taking my questions I wanted to go back to the one versus Tito's for Brentsville. It seems like everyone is in agreement that there is a compelling reason to go for the higher dose or include the higher dose is there a reason why the FDA would have hesitation on that front and then my second question is could you give any color on exactly.

Speaker Change: Where you're at with Oncor enrollment.

Will Lewis: So, on the FDA front, we don't anticipate that there's going to be any pushback. I think that the guiding principle that the FDA follows is, "what's the lowest effective dose?" And when you think about going up in doses, what is the risk-reward balance that you are encountering as you go there? So, as we go from 10 to 25, what we observe is some clear itemizable benefits from prevention of lung function decline, which Martina expressed earlier, are very quantifiable and meaningful for every physician we've spoken to. In addition, the quality-of-life benefit that we observed at the 25-milligram dose is also meaningful.

Speaker Change: Sure so on the.

Speaker Change: FDA front, we don't anticipate that there's going to be any pushback I think that the.

Speaker Change: The guiding principle at the FDA follows is what's the lowest effective dose and when you think about going up in dose what is the risk reward balance that you are encountering as you as you go there. So as we go from 10 to 25, what we observe is some clear itemized <unk>. If that's the right word benefits from.

Ritu Baral: But why would you consider using a lower dose? And then as part of that NDA, how are you, or that NDA filing, how are you thinking about the indication language? Well, could it be that you, could you get an indication for treatment of bronchiectasis or do you think it will necessarily be limited to reduction of bronchiectasis exacerbations? Those were both my questions. Thanks.

Speaker Change: Prevention of lung function decline, which as Martina expressed earlier is very quantifiable and meaningful for every physician. We've spoken to in addition, the quality of life benefit that we observe at the 25 milligram dose is also meaningful it's meaningful for physicians for patients obviously, because they feel better the physician can can.

Will Lewis: Sure, so I'll take the second one first. The treatment of bronch ectasis is, in fact, the label we expect to get. That's what we're going to be requesting. We do not think it will be limited based on two or more exacerbations. I think where that may play out in more or less degree is in the payer landscape, which is something we're already working on the disease education front right now. My perspective on the two doses, and I'll invite Martina to comment on it, is that I think, look, both are clear wins, and that's the most rewarding aspect of this study, both from a safety and from an efficacy standpoint.

Will Lewis: It's meaningful for physicians, and for patients, obviously, because they feel better. The physician can indicate, you know, you may feel better on this medication, or at least they're aware of that. And most importantly, payers know that when they pay for a medicine, the patient is more likely to take it if there isn't a bad side effect profile.

Speaker Change: Indicate you may feel better on this medication or at least they're aware of that and most importantly, the payers know that when they pay for a medicine. The patient is more likely to take it if there isn't a bad side effect profile. So all of that suggests the 'twenty five and a very positive light and I think.

Will Lewis: So, all that suggests the 25 in a very positive light. And I think the question the FDA has is, do they agree with that risk-reward profile, that there is added benefit and not a lot of additional risk going up to 25? To us, that seems to be the landscape, but there's more to learn.

Speaker Change: The question. The FDA has is do they agree with that risk reward profile that there is added benefit and not a lot of additional risk going up to 25 to us that seems to be the landscape, but there's more to learn and again I'll remind everybody. We're doing a lot of detailed analysis on what is a very substantial database we haven't.

Will Lewis: As we move from 10 to 25, we see some additional benefit that is clearly captured in the slowing the rate of lung function decline, as measured by a couple of different metrics, both FEV1 and fourth vital capacity. And then as we look at how patients respond and how they feel, the quality of life measure and also the diary, both captured improvements from the patient's point of view. And we think all of that information is very compelling, and certainly we've heard that from all of the experts in the field.

Will Lewis: And again, I'll remind everybody, we're doing a lot of detailed analysis on what is a very substantial database. We haven't seen anything yet that would suggest that this equation would be viewed differently. We're just trying to preserve the right to continue to analyze the data, enter into a very open dialogue with FDA, and put forward what we think makes the most sense. I just want to emphasize, most importantly, that whether we go with one or two doses, we will be ready. We have an adequate supply for both.

Speaker Change: Seen anything yet that would suggest that this equation would be viewed differently. We're just trying to preserve the right to continue to analyze the data enter into a very open dialogue with FDA and put forward. What we think makes the most sense I just want to emphasize most importantly that whether we go with one or two doses, we will be ready we have adequate supply for both were.

Will Lewis: The most important point for both 10 and 25 is that they have comparable safety profiles. So the risk-reward calculus you run when you go from 10 to 25, you don't get any real additional risk in our opinion for getting those extra benefits. And that suggests 25 as a very appropriate dose to think about for initiating patients at, and I think we've heard that pretty loudly from a lot of the experts in the field.

Will Lewis: We're prepared to detail both. And so this is, it's a nice place to be, whether there are one or two doses, and I think I'll just leave it at that. On Encore, you asked when the status of enrollment is, that continues to do well and frankly accelerate as we get near the end here. We've said we'll close off enrollment in the third quarter.

Speaker Change: [noise] detail both.

Speaker Change: And so this is.

Speaker Change: It's a nice place to be whether theres, one or two doses and I think we'll just leave it at that.

Speaker Change: An encore you asked whats our status of enrollment.

Speaker Change: That continues to do well and frankly accelerate as we get near the end here. We've said will close off enrollment in the third quarter that feels very good to us I will just add that this is another one of those moments, where we have revisited our assumptions set and made sure that we are looking at this through a very conservative prism when we look at the <unk>.

Will Lewis: We're not making that commitment now, because we want to have the dialogue with FDA to capture the benefit of their perspective on the 10 versus the 25. But I think we'll keep an open mind, and enter that dialogue, we'll come forward with a proposal, we'll hear what their response is. But I think the 25 clearly suggests itself as having some added benefit over the 10 without there being much of a trade-off on safety. I don't know, Martin, if you'd add anything to that.

Will Lewis: That feels very good to us. I will just add that this is another one of those moments where we have revisited our assumption set and made sure that we are looking at this through a very conservative prism. When we look at the landscape of all MAC-NTM technologies, right now, there is no competition on the near-term horizon.

Speaker Change: Land scape of all Mac MTM right now there is no competition on the near term horizon, we want to make very sure that the strength of these data stands the test of time much like it did with the rise much like it has done with convert much like it has done with Aspen and so those same principles inform the final design and power.

Jennifer Kim: We want to make very sure that the strength of these data stands the test of time, much like it did with ARISE, much like it has done with CONVERT, much like it has done with ASPEN. And so those same principles inform the final design and powering assumptions going into Encore. And the way we are approaching this as we look to close enrollment in the third quarter of this year is greater than 90% power to hit the primary end point of this study.

Martina Flammer: Yeah, I think you're already described it well. And sometimes you think about starting with the lower dose and have an opportunity to go to a higher dose is something that physicians think about. In our case, you have overall on the reduction of pulmonary exacerbation, such a clear win for both doses, that you now look at what is the additional benefit that patients can achieve. And here, if you look at the lung function data and you look at the FV1 clinically, if you're a pulmonologist, and you could think about my patient currently loses about 60 to 70 milliliters every year, if I can bring that patient to 30, what would be a normal loss of milliliters or FV1 for any adult as we age?

Speaker Change: <unk> assumptions going into encore and the way we are approaching this as we look to close down enrollment in the third quarter of this year is greater than 90% power to hit the primary endpoint of this study. So we feel like we're in a very good position based on what we saw on a rise to produce a result, we hope successfully with encore.

Jennifer Kim: So we feel like we are in a very good position based on what we saw in ARISE to produce a result we hope will be successful with Encore. Okay, that's helpful. If I could sneak one more question in, just thinking about those first few quarters of the Brenso launch, just net-net, would you anticipate the Part D redesign to help or hurt that launch? Thanks.

Speaker Change: Okay. That's helpful. If I could sneak one more question and then just thinking about this first few quarters of the Brentsville lunch just net net would you anticipate that part D redesign to help or hurt that launch. Thanks.

Speaker Change: Okay.

Speaker Change: You're referring to IRA I am sorry, I didn't hear the question.

Will Lewis: I'm sorry, I didn't hear the question. Oh, yeah, Part D. Yeah, yeah, Part D. So, look, I think it's going to help. I think it's going to help Brenso. I think it's going to help Arrakes too. I think it's going to help across the board. The most important thing about that piece of legislation is that for the first time, they addressed the burden that is placed upon patients for medicines that are, you know, expensive. And the fact of the matter is, it doesn't really provide any benefit to patients to load them up with additional costs that they find a financial burden in reaching.

Speaker Change: The part D. Yes.

Speaker Change: Yes, yes, the part D. So look I think it's going to help I think it is going to help a Brent. So I think it's going to help Eric case, I think it is going to help across the board. The most important thing about.

Martina Flammer: That would be a very, very strong argument. And given the safety, even for AEs of special interests, that is so good, and there's very, very little difference truly between those doses, I think we have a very strong argument for the 25.

Speaker Change: That.

Speaker Change: Piece of legislation is that for the first time they addressed the burden that is placed upon patients for <unk>.

Speaker Change: <unk> that are.

Speaker Change: Expensive and in fact, the matter is it doesn't really an air benefit to patients to load them up with additional cost that they find a financial burden and reaching there's been many studies that have shown that making medicine more accessible and lower cost at the pharmacy counter top results in better usage rate.

Joseph Schwartz: It comes from the line of Joseph Schwartz from the leadering partners. Please go ahead. Hi, thanks very much. I have a couple questions on CRS. First of all, what are the powering assumptions that govern Birch? And then are you endotyping patients in Birch or stratifying patients in any way? And lastly, how did you decide on the two doses of 10 and 40 milligrams there?

Will Lewis: There have been many studies that have shown that making medicine more accessible and lower cost at the pharmacy countertop results in better usage rates, better adoption rates, and the consequence of that is patients are healthier. So from every angle, this is a piece of legislation on that particular point that, in my view, has been a long time coming and is very necessary. I think as patients realize that they have a lower burden of a maximum of $2,000 out of pocket across all their medicines, which can be spread over on a monthly basis, that becomes a much more affordable equation than carrying 5% of the overall burden past catastrophic thresholds that they've had to face in the past.

Speaker Change: Better adoption rate and the consequence of that is patients are healthier. So for every angle. This is a piece of legislation on that particular point that in my view has been a longtime incoming and very necessary I think as patients realize that they have a lower burden of a maximum of $2000 out of pocket across all of their medicines.

Will Lewis: Yeah, so super excited about that trial, because now that we've validated the mechanism, we're kind of glad we started that one a little bit at risk to be candid. We didn't want to go full bore with all of the subsequent trials, so HS starts at the end of this year. But the way we think about this is having validated the mechanism, we're not going to be exploring in our hierarchical rank of where we think we could have the most impact, and there's the clearest on the medical need.

Speaker Change: Which can be spread over on a monthly basis.

Speaker Change: That that becomes a much more affordable equation than carrying 5% of the overall burden.

Speaker Change: Past catastrophic thresholds.

Speaker Change: <unk> had to face in the past and that's what's produced the really terrible stories about people needing to take out mortgages in and find a.

Will Lewis: And that's what has produced really terrible stories about people needing to take out mortgages and find large sums of money to gain access to life-saving medicines. I think we're finally past that era, and I think that's a very good thing. Okay, that's helpful. Thanks again.

Will Lewis: And so that's why we turn it into CRS without nasal polyps next. That market opportunity for those patients, the unmet medical need there is every bit as big in my mind as bronchi-actuses. And I think it's pretty compelling if we're able to demonstrate impact there. So far, we're bringing forward the 10 and the 40 milligram dose as you point out in the study. I'm going to the higher dose. We could certainly do that in other settings.

Speaker Change: Large sums of money to gain access to lifesaving medicines I think we're finally past that era and I think that's a very good thing.

Speaker Change: Okay. That's helpful. Thanks again.

Leiyang Wang: Next question. Your next question comes from the line of Leiyang Wang from Barclays. Please go ahead. Hey, congrats on the quarter.

Speaker Change: Next question. Your next question comes from the lineup for Ian Wang from Barclays. Please go ahead.

Leiyang Wang: And thanks for taking my questions. So when you think about the competitor landscape, BI's phase three, I think they revealed that they, Allcomer, Bronchiectasis, Patient Population. Can you remind us why you?

Ian Wang: Hey, congrats on the corner and thanks for taking my questions.

Ian Wang: So we think about the competitor landscape.

Will Lewis: We didn't have the talks data done. I just want to remind everybody about that. By the time we launched Phase 2, we can now go as high as 65 milligrams if we ever wanted to in a disease, because we have that talks work done and it's clear. Each disease is different. We'll respond differently to the DPP-1 inhibition. So it seems to us appropriate, and particularly in hindsight of Aspen, to go up to 40 as the next dose.

Speaker Change: Phase III I think revealed that they will be enrolling all comers.

Speaker Change: This patient population.

Speaker Change: Can you remind us why youre recruiting in non CF bronchiectasis and how does this change in there potentially registrational study affect.

Will Lewis: Non-CF bronchiectasis, and how does this change in their potentially registrational study affect your thoughts on the competitive landscape going forward, you know, if at all. And second question, you know, as you work. The NDA in the fourth quarter. Do you plan to update us on when that submission is in, and what form that could be?

Speaker Change: Affect your thoughts on the competitive landscape going forward if at all.

Speaker Change: Second question, you know as you work towards submitting the NDA in the fourth quarter do you plan to update us on when that submission at the end and what could that be it must be like in a press release.

Will Lewis: But I don't know powering assumptions off top of my head. Martina, do you know them? Maybe you can address that. Yeah, so we're powering 80% to detect the difference of 1.34 units, and we're 90% power to detect one between 1.55 units. And so as a primary endpoint, we have the sinus total symptom score. As you may know, this is a composite score of symptoms related to CRS, and includes nasal congestion, facial pain, loss of smell, and those will be the things that we will be looking for the primary endpoint, and that's the powering for it.

Speaker Change: Or would this just be.

Leiyang Wang: Update at a later conference. Yeah, so I think that the answer to the BI question begins with, first of all, seeing their data, and we haven't done that yet, right? We don't know what they really have, and until we know what their data is, it's hard to interpret the modifications they made to their entry criteria that were different from ours and what that resulted in. There were a lot of assumptions behind those modifications that they were quite vocal about before the fact, but we didn't really see that in the data set.

Speaker Change: And the update at <unk>.

Speaker Change: Later conference.

Speaker Change: Yes, so I think the answer to the question begins with first of all seeing their data and we haven't done that yet right. We don't know what they really have until we know what their data is it's hard to interpret the modifications they add to their entry criteria.

Speaker Change: That were different from ours and what that resulted in there were a lot of assumptions behind those modifications that they were quite vocal about before the fact, but we didn't really see that in the data set so I think theres, probably going to be some revisit Asian of.

Will Lewis: And I'll just add that while blended and blinded and very early, there is a temporal alignment between improvement in that symptom score on an overall basis, and when we would expect the onset of the drug to take effect. So that suggests that there may be something going on here that's positive. Obviously, we don't know that until we unblind, but it's an encouraging trend nonetheless. And Joe, I would just remind you the $5 billion of peak sales that we referred to at our commercial day. That was bronchi-actasis alone. So the upside for CRS is not included in that number, and as Will already mentioned, we believe that could be a sizable patient population. Thanks. That's helpful.

Leiyang Wang: So I think there's probably going to be some revisitation of whether or not that direction or claim they were heading in is going to be viable. From our point of view, it doesn't make any difference. It doesn't affect the outcome.

Speaker Change: Of of whether or not that direction or claim they were heading is going to be viable from our point of view it doesn't make any difference it doesn't affect the outcome. There is still going to be securing a label for bronchiectasis patients.

Will Lewis: They're still going to be securing a label for bronchiectatic patients, so I don't, I'm not particularly worried about it. Again, we've assumed all along, including with our peak sales numbers, that we have competitors in the marketplace. BI seemed to be the closest.

Speaker Change: So I don't I'm, not particularly worried about it again, we've assumed all along including with our peak sales numbers that we have competitors in the marketplace.

Martina: It seemed to be the most proximate the one thing I would say about their data as it does appear that there was some biological effect or whether that was statistically significant or not it wasn't clear, but what I will say is I think it does validate the mechanism of action of DPP, one inhibition, but maybe Martina I'll turn it over to you for your reflections.

Will Lewis: The one thing I would say about their data is that it does appear that there was some biological effect, whether that was statistically significant or not wasn't clear. But what I will say is I think it does validate the mechanism of action of DPP1 inhibition. But maybe, Martina, I'll turn it over to you for your reflection.

Martina Flammer: And how do you view the, whether it makes sense to end a type or stratify patients based on the mechanism? What we're looking for is we're looking at patients who are below 300, you've seen a fill and above 300, but we know that in CRS without nasal polyps. Also, there is an aocinophilic component, as you know, with all of these diseases. It is not something that is a pure mechanism that is looking only at using a philic. So we look at both of those patients, but we know there is a very strong, neutrophilic and driven group for both of them.

Joseph Schwartz: Excellent. Thank you.

Martina Flammer: Yeah, I think what I would be looking for in the data is also, if you look at the patients, they did enroll all comers. That's one of the considerations. What we don't know, and they haven't shown yet, is what is the response? As you know, having two previous exacerbations is the strongest predictor of future exacerbations. I think it's a good guideline to inform you and have an ability to estimate how you would power a study, because you do need to understand your background rate, and that may be one thing that they're working on.

Martina: Yeah, I think what we'll be looking for in the data is also if you look at the patients they didn't roll on call. All comers. That's one of the considerations are what.

Martina: We don't know and they haven't shown yet is what is the response as you know having to previous exacerbations is the strongest predictor for future Exacerbations I think it's a good guideline to inform you and have an ability to estimate how you would power our study because you do need to understand your background.

Speaker Change: Right and that maybe one thing that that they are working on we don't have we haven't seen that data, but that is one thing that will inform it if you enroll on all on Congress, who have maybe only one acts as a base and you do not know how that would actually impact your powering.

Leiyang Wang: We don't have, we haven't seen that data, but that is one thing that will inform it. And if you enroll all newcomers who have maybe only one exacerbation, you do not know how that would actually impact your powering. So, and on your other question about the NDA submission, we do plan to announce that. That's our current intention once that's completed. Great, thank you for taking my question. Your next question comes from the line of Vamil Divan from Guggenheim Securities. Please go ahead.

Katherine: Your next question comes from the line of Jeffrey Homes from Morgan Stanley. Please go ahead. Hi. Good morning. This is Katherine on for Jeff. Thank you for taking our question.

Katherine: Just one looking ahead to the expected forensic had a launch. Can you talk more about your strategy for targeting patient groups at launch? Will you be focusing primarily on a diagnosed population or do you plan to target or go after the undiagnosed population or the asthma, COPD, comorbid patients experiencing exacerbations that you mentioned during your R&D day? Thanks for the question. I think the way to conceive of what we're going to be doing with our launch is that disease state awareness is already well underway.

Speaker Change: And on your other question about NDA submission, we do and plan to announce that that's our current intention once that's completed.

Martina: Yeah.

Speaker Change: Great. Thanks for taking my questions.

Daniel <unk>: Your next question comes from the line of Daniel <unk> from Guggenheim Securities. Please go ahead.

Vamil Divan: Yeah, great. Thanks for taking my question. So just one, maybe shifting gears to GPIP. I think you mentioned the PHILD data today. I think you said today that I'll come later this year.

Daniel <unk>: Yeah, great. Thanks for taking my question so just.

Speaker Change: Maybe shifting gears to GP IP I think you've mentioned that ph ILD data. Thank you.

Katherine: I think that's the first hurdle to clear. We know from our previous experience of being a first in disease launch that it's very important to raise the awareness among physicians of the disease and its sequelae. And that process began at the American thoracic society a year ago this last May. So we've been out there for a while. We're doing the same thing with payers. And as we raise that awareness, I think physicians will turn their attention to patients that may be appropriate for treatment, assuming that we are approved and clear all the regulatory hurdles.

Speaker Change: They come later this year I'm curious if you can provide any more insight into which conference.

Katherine: We know from our dialogue with physicians that those patients who are diagnosed today are the ones that they're going to immediately turn to for use of the drug, assuming it's approved. And I think that's fully appropriate. But we're also aware that there's a growing dialogue and chorus among treating physicians that there's probably a decent number of patients who have COPD or who have asthma that may have been misdiagnosed or that have those conditions and are potentially comorbid with bronchiectasis.

Speaker Change: You are targeting that and then just going back to the.

Will Lewis: I'm curious if you can provide any more insights into which conference you're targeting on that. And then just going back to the question earlier on the pricing side for Brenzo, you did mention you've had some initial conversations with the payers, maybe you can just provide any sort of feedback that you're receiving there. I think you're still comfortable with that range you provided before, but just any sort of insights on the initial sort of dialogue and how they've been reacting to the disease and the profile as you've been discussing it.

Speaker Change: Question earlier on the pricing side for <unk> you did mention you had some.

Speaker Change: Initial conversation with the Payors, maybe you can just provide any sort of.

Speaker Change: Feedback that you're receiving there.

Speaker Change: It sounds like you're still comfortable with that and range you've provided before but just any sort of insights on the initial sort of dialogue and how they've been reacting to the.

Martina: To the disease and the profile as you've been discussing.

Will Lewis: Yeah, so we're super excited about the data generation from TPIP and PHLD, and we were certainly hoping to have it at a conference this year. But I will say the conference schedule is fairly busy, and the consequence of that is it's probably going to slip into 2025 before we're able to put out all of that data. But I will say that that process continues to be underway, so we'll update you once we have that. We want to get it out as soon as possible.

Speaker Change: Yes, so we're super excited about the data generation from TPI Pete in ph ILD and we were certainly hoping to have it at a conference. This year I will say the conference schedule is fairly busy and the consequence of that is it's probably going to slip into 2025 before able to put out all of that data.

Speaker Change: But I will say that that process continues to be underway. So we will update you. Once we have that we want to get it out as soon as possible theres a lot there and alike.

Katherine: We talked about that on our commercial day. And I think that has gained a lot of momentum, frankly independent of us. And as people gain that awareness and they become aware of our medicine and its ability to have impact on these patients again, presuming that it clears the appropriate regulatory hurdles. That's going to be an exciting time because I think what often happens in these kinds of first and disease indications that there are many more patients out there than people would have originally thought.

Speaker Change: More to say about that in the future, but we want to do it at a peer reviewed setting as we've previously represented.

Will Lewis: There's a lot there to like, and we'll have more to say about that in the future, but we want to do it in a peer-reviewed setting. And then on the pricing side, you know, it's still too early to talk about price with specificity, and certainly where we are in our dialogue with all of the different stakeholders here is talking about disease state awareness and understanding the burden of this disease and what role, if it's approved at the appropriate time, we will begin to talk about BRENSO.

Martina: And then on the pricing side.

Martina: It's still too early to talk about price with specificity and certainly where we are in our dialogue with all of the different.

Speaker Change: Constituents here is in talking about disease state awareness and understanding the burden of this disease and what role if.

Martina: If it's approved at the appropriate time, we will begin to talk about Brent so that that won't happen for a while.

Katherine: But the short answer your question is that half a million patients that we know are diagnosed today with bronchiectasis. Those are the first ones we're going to be targeting. And we'll see and learn along the way how much broader that may get.

Will Lewis: That won't happen for a while, but right now, it's about disease state awareness and making sure people understand the burden. I will say that our interactions and the perceptions that people have across the treating community, including the payors, continue to support our belief and the work we've done in pricing studies that the range we gave you we're very comfortable with. I think, once again, as I said earlier, the...

Martina: But right now it's about disease state awareness and making sure people understand the burden I will say that our interactions and the perceptions that people have across the treating community, including the Payors continues to support our belief and the work we've done in pricing studies that the range. We gave you we're very comfortable with I think.

Will Lewis: Great. Thank you so much.

Will Lewis: And then just a quick one, if I may, you previously provided the range of 40 to 96,000 as unlikely US price. Can you just remind us of the factors here that may drive the price to one end of that range or the other? Thank you so much.

Martina: Once again as I said earlier.

Will Lewis: The content of what we have to offer, the target product profile from the actual Aspen results is better than what we had originally tested. That preservation of lung function is very powerful data, as is the patient feeling better. So we'll see how that plays out over time, but there is more work to be done there, and we'll certainly update you as we get closer. Okay. All right.

Martina: The content of.

Martina: What we have to offer the target product profile from the actual Aspen results is better than what we had originally tested.

Will Lewis: Sure. Well, I think whenever you consider price, you have to think about the idea of the value for money. And that proposition is frankly spelled out in the label. So until we know what that's going to look like, it's hard to really think about price with any greater specificity. I think across that range, given what we've seen in the data and presuming that that is something that is reflected in the label, which is appropriate or is available to physicians for their contemplation, we have every reason to believe that anywhere along there is something that is appropriate.

Martina: That preservation of lung function is very powerful data as is the patient.

Speaker Change: Patients feeling better.

Speaker Change: So we'll see how that plays out over time, but but more work to be done there and we'll certainly update you as we get closer.

Speaker Change: Okay alright, thank you.

Liisa Bayko: Thank you. Your next question comes from the line of Liisa Bayko from Evercore ISI. Please go ahead.

Speaker Change: Your next question comes from the line of Fleece at FICO from Evercore ISI. Please go ahead.

Will Lewis: Hi there, thanks for taking the question. First question: when you talk about a broad label, would that include CF? And then also, with respect to the IRA, how should we think about margins on the product? Because I know with the benefit of spreading the $2,000 payment that the Medicare patients are responsible for, also this catastrophic coverage, 60% of it above catastrophic is going to fall on the payers. I'm just wondering how they're going to react to that in terms of wanting some sort of rebates, discounts, things along those lines.

Speaker Change: Hi, there thanks for taking the question.

Will Lewis: We got a lot more work to do before we're going to settle on price, but I think what we have found in these data and the response to these data is that they are remarkably compelling. I call that a landmark study and I know every company lays claim to having the ability to produce good data. This is one of those rare moments where this drug is going to speak for itself. And the physicians have already told us that and they're excited to put their patients on this drug, presuming it's approved.

Speaker Change: First question when you talk about a broad label would that include a C. S and then.

Speaker Change: So with respect to the I R. A how.

Speaker Change: How should we think about margins on the product because I know with the benefit of spreading the 2000.

Speaker Change:

Speaker Change: Payment that that that that.

Speaker Change: The Medicaid Medicare patients are responsible for also the catastrophic coverage.

Will Lewis: And I think we're going to find the right balance between setting a price that will reflect that value for patients and allow us to move forward as a company and reinvest another promising medicine. This is one of those rare moments where we're going to find the right balance between setting a price that will reflect that value for patients and allow us to move forward as a company and reinvest another promising medicine. Thank you.

Speaker Change: Coverage, 60% of it about catastrophic is going to fall on.

Speaker Change: The payers and just wondering how they're going to react to that in terms of.

Speaker Change: One is some sort of rebates discounts things along those lines. Thank you.

Will Lewis: Thank you. Yeah, sure. So, on the first point, the broad label would not, we would not anticipate it would include cystic fibrosis patients. This will be for non-cystic fibrosis patients, bronchiectasis.

Speaker Change: Yes, sure. So on the first point the broad label would not we would not anticipate it would include cystic fibrosis patients this would be for non cystic fibrosis bronchiectasis.

Andy Chen: Your next question comes from the line of Andy Chen from Woolf Research. Please go ahead.

Will Lewis: Having said that, obviously, the data we saw in the CF study we completed was very compelling, and that certainly is out there. I think that if there are patients that are experiencing exacerbations successfully being treated by drugs that are offered by other companies, then there may be a physician who wants to think about this. But we would point out that that's a fairly small group, and it certainly isn't something we're going to target because that would represent off-label use.

Speaker Change: Having said that obviously the data we saw in the CF study, we completed was very compelling and that certainly is out there.

Speaker Change: Think that.

Speaker Change: If there are patients that are experiencing exacerbations successfully being treated by drugs that are offered by other companies. Then there may be a physician who wants to think about this but we would point out that that's a fairly small.

Andy Chen: Please, to be better and other to move forward. And I have one quick follow-up. Thank you. So, just to be clear on CRS without nasal polyps, there's nothing approved to treat that condition. There is some medicine that is used to treat CRS with nasal polyps. But, and that includes things like Humera, but for CRS without nasal polyps, largely neutrophil driven, there is nothing. And when we talk about this disease indication, we refer to the incidence population, the annual rate of patient numbers that are either subject to surgery, repeat surgery, or eligible for it, and that's in the hundreds of thousands of patients.

Andy Chen: That's every year. So, that's quite a substantial opportunity, and we talk about the overall prevalence population as being in the US alone close to 29 million people. So, to talk about a disease indication with nothing approved of that magnitude, and going as we did with error case, after the severe end of the patient spectrum out of the gate, that's really the strategy here.

Speaker Change: Group and it certainly isn't something we're going to target because that would represent off label.

Will Lewis: When you think about the IRA and payers, I don't know if we want to go over this with any specificity, but the thinking there is that you're going to see an error case is not, is considered, and has the small manufacturer's benefit; Brenso would not.

Speaker Change: Okay think about the IRA and Payors.

Speaker Change: Yes, I don't know if we want to go over this with any specificity, but the but the thinking there is that.

Speaker Change: Youre going to see Eric case.

Speaker Change: <unk> is not is considered.

Speaker Change: Has this the small manufacturers benefits of Brent So would not so the distribution of the cost as the.

Will Lewis: So the distribution of the cost as the..., as the drug rolls out would be more significant for us for Brenso than it would be for EraCase. And so we've achieved that benefit. We can go over that at some greater granularity because, year over year, the manufacturer versus the plan percentage allocations are very different based on whether or not you secure that designation. I'm going to have to do that sidebar.

Speaker Change: As the drug rolls out would be more significant on us for Brent. So then it would be on Eric case, and so we've achieved that benefit we can go over that in some greater granularity because year over year the manufacturer versus the planned percentage allocations are very different based on whether or not you secure that designation and happy to do that.

Sara Bonstein: But I don't think it's going to impact the overall pricing reflection that we have because this is about value for money from the medicine. And I think what we've heard so far is that payors recognize the permanent damage that is done by pulmonary exacerbations experienced by patients with this disease. And while there's nothing in the category right now, the data that we have from Aspen is very compelling, and this is kind of one of those places where I think we're going to have a very productive dialogue with payers in terms of their willingness to support this.

Speaker Change: But I don't think it's going to impact the overall pricing reflection that we have because this is about value for money from the medicine and I think what we've heard so far is that payers recognize the permanent damage that is done by a pulmonary exacerbations experienced by patients with this disease and while there is nothing in the category right now.

Will Lewis: What is sufficient for moving into phase three? Well, I think honestly we have to look at the phase two data and have some reflections on whatever that is going to be. There aren't great animal models for this, and there isn't precedent because there's nothing approved. So, we're going to have to take a close look at that. But, once again, the standard we always use is, is this going to make a dramatic impact on the patients?

Speaker Change: The data that we have from Aspen is very compelling and this is kind of one of those places where I think we're going to find a very productive dialogue with payers in terms of their willingness to support this and Lisa the only other thing I would add is the.

Will Lewis: And, you know, when we talk about patients who are subject to repeat surgery or avoiding surgery, the ability to provide benefit that's meaningful for that patient group would be sort of how we think about it. I don't know, Martin, if you want to add anything on that. Yeah, apart from that taking the primary ampere and one of the things we look at the secondary ampere, is the lump decay CT score that's something that is very often used and standardized used in this in this disease, where you actually look of what kind of opacification do you see in the sinuses. So, that is another efficacy measure.

Sara Bonstein: And Lisa, the only other thing I would add is that the projections that we provided on commercial day took all of this into account. So our $5 billion peak sales and the opportunity we see from a commercial perspective on the revenue side took all of these factors into account. Thank you. Okay. That's helpful. Thanks. And can I just follow-up on reps?

Lisa: Projections that we provided on commercial day took all of this into account sell our $5 billion peak sales.

Will Lewis: Thank you.

Lisa: The opportunity we see from a commercial perspective on the revenue side took all of these factors into account. Thank you.

Speaker Change: That's helpful. Thanks, and can I just do one follow up on wraps are those.

Liisa Bayko: Are those – are the additional reps you're hiring going to be – The – Okay. Detailing all of your products, in other words, Eric Hayes as well, maybe as a second, or how do you imagine prioritizing your sales force with respect to the products? Thanks.

Speaker Change: Are the additional reps you're hiring going to be.

Speaker Change: Telling all of your products in other words, Eric cases, as well, maybe as a second or how do you imagine prioritizing E. R. M. Your salesforce with respect to the products. Thanks, Yes.

Sara Bonstein: And, um, can you comment on our case sales momentum by geographic region? Should we be expecting the attention, especially in areas like Japan, and how much is left in that region? Thank you. So, I think we feel very good about the performance this quarter, but I'll actually ask Sarah if she wants to make any commentary on the regional basis. Sure. Happy to make comment. And, you know, just to start off on a global basis, we were really encouraged by the continued double-digit growth across all of our regions.

Will Lewis: Yes, they are going to detail both products, assuming approval for Brenso and indeed the expanded label for Ericase, assuming Encore goes as we expect it will. So what we're looking at here is now a much more robust and, but it highlights probably the single most important aspect of all of this, which is the synergy. So this same Salesforce that launched Refractory Mac, the error case for Refractory Mac, is going to be assuming again when these regulatory approvals fall in place for all Mac NTM and Brenso and Bronchiectasis. And so the teams are being trained for disease state awareness in bronchiectasis.

Speaker Change: Yes, they are going to be detailing both products assuming approval for Brent So and indeed, assuming the expanded label for Eric case, assuming encore goes as we expect it will so what we're looking at here is now a much more robust and.

Speaker Change:

Speaker Change: But highlights probably the single most important aspect of all of this which is the synergy. So the same sales force that launched refractory Mac. Eric is for refractory Mac is gonna be assuming again these regulatory approvals fall in place.

Sara Bonstein: You know, we're in our sixth plus year of launch in the U.S., and to still see this level of growth is absolutely tremendous and talks about the patient need and the need and importance of error case. In the U.S., we saw, you know, tremendous growth. We continued to be really impressed by the commercial organization as a reminder. That's the commercial organization that we anticipate will launch, Brent Socats of Assuming Approval by FDA.

Speaker Change: Mac MTM and Brent so in bronchiectasis and so the teams are being trained for disease state awareness and bronchiectasis and in the meantime, we will call on physicians for appropriately diagnosing and treating.

Will Lewis: And in the meantime, we'll call on physicians to appropriately diagnose and treat them for refractory MAC with error case. So that's going to give us some extra horsepower as we get to the end of this year and into next year on that indication. But it is our intention that they will bring both forward for the foreseeable future. And just one other comment on this, the synergies, as you're thinking about the COPD Foundation and the Care Center Network that they formed, that's, you know, over 100 care centers around the United States, and those are going to be specialized in NTM and bronchiectasis. So just more sort of highlight on the synergies between the two disease settings. Okay, great. Thank you. The next question comes from the line of Graig Suvannavejh from Mizuho, please go ahead. Good morning.

Speaker Change: Them for refractory Mac with air case, so thats going to give us some extra horsepower as we get to the end of this year and into next year on that indication, but it is our intention that they will bring both forward for.

Sara Bonstein: My middle and next year, so couldn't be more pleased. Obviously augmenting that sales force in the U.S., and as well mentioned in the prepared remarks, those 120 reps, nearly all hired from a very large pool of candidates. So we feel confident we have top talent that is augmented into our commercial organization that will now be able to have error case as well as the disease state awareness. So U.S., we feel really comfortable on that continued growth. Japan, you know, 35 percent growth can't ask for much more from a region. So really pleased to see that continued performance. We did add some additional therapeutic specialists in Japan to continue with that growth.

Speaker Change: For the foreseeable future and just one other comment on just the synergies as Youre thinking about the COPD Foundation and the care Center networks that they formed.

Speaker Change: Over 100 care centers around the United States and those aren't going to be specialized in MTN and bronchiectasis. So just more sort of highlight on the synergies between the two disease settings.

Speaker Change: Okay, great. Thank you.

Speaker Change: Okay.

Greg <unk>: Our next question comes from the line of Greg <unk> from Mizuho. Please go ahead.

Speaker Change: Okay.

Graig Suvannavejh: Congratulations on the progress. Thanks for taking the time to answer my questions. I just wanted to revisit the enrollment update with regard to Encore and that you're now targeting 400. Could you just remind me, was the prior target somewhere in the neighborhood of 250? And then maybe if you could provide a little bit more granularity on kind of what you did in terms of revisiting either the patient inclusion or exclusion criteria to give you kind of a better sense that, you know, with 400, you will get the result that you are looking for?

Greg: Hey, good morning, Congrats on the progress thanks for taking my questions.

Greg <unk>: Just wanted to revisit the enrollments.

Sara Bonstein: And Europe. It's small in number, but very material from a percentage perspective and really excited to see that. So couldn't be more pleased on the growth across each of the regions and feel really confident in our 340 to 360, fully your guidance. Yeah, and I just will add a quick shout out to the commercial team around the world for the excellent job that did this quarter. And the momentum that they're generating for the second half of the year.

Greg: Updating.

Speaker Change: With regards to Oncor and that you are now targeting 400 could you just remind me was the prior target somewhere in the neighborhood of 250, and then maybe if you could provide a little bit more granularity on kind of what you did in terms of revisiting either the.

Speaker Change: Patient inclusion or exclusion criteria to give you kind of a better sense that with 400 <unk> you will get the result that you are looking for.

Jason Zemansky: Thank you, thank you. Your next question comes from the line of Jason Zemansky from Bank of America. Please go ahead.

Graig Suvannavejh: Sure, so the most important thing to realize about ENCQOR is that it was enrolled at the same time that ARISE was enrolled, right? So we continued that enrollment after ARISE read out, but the backdrop of choosing the primary endpoint and what the powering was, we didn't have any basis for that because there had been no validation of a PRO, so we were sort of flying blind when we set the original target.

Speaker Change: Sure. So the most important thing to realize about oncor is that it was enrolled at the same time that arise was enrolled right. So we continue that enrollment after a rise read out but the backdrop of choosing the primary endpoint and what the powering was we didn't have any basis for that because there'd been no validation of a CRO. So we're sort of.

Cameron Boozog: Hey, good morning. This is Cameron Boozog, I'll go on through Jason. Congrats on the quarter and thanks so much for taking that question. I guess looking ahead to Brenzo's launch, you know, you mentioned you were planning to hire a sales source of 120, but can you maybe elaborate a bit more on additional steps? The team has, you know, taken to build out the commercial infrastructure and maybe what still has to do? And then what do you expect to be the biggest or at least most time consuming challenge at this point? Is it going to be physician awareness, pair issues, or maybe something else?

Speaker Change: Flying blind when we set the original target and.

Graig Suvannavejh: And that target, as we indicated at the time, was likely to need to go up. That was 250 patients, and that was several years ago. Once we saw the ARISE study, we knew it was going to have to increase materially. The assumption going in was that the minimum important difference here was going to be eight points, and in fact, it ended up being about double that, but that's because no one had ever tested the PRO in NTM patients. So we learned a lot from that.

Speaker Change: And that target as we indicated at the time was likely to need to go up that was 250 patients and that was several years ago. Once we saw the arise study we knew it was going to have to increase materially.

Speaker Change: The assumption going in was that the minimum important difference here was going to be eight points.

Will Lewis: Thank you. So I can just comment in again, reverse order that the single most important thing while it all has importance, the single most important thing that keeps me focused is the pair access. I think now more than ever in the era in which we operate. Getting that right is really the key to the successful launch and I could not be more pleased with the strength of the team we have and the work we've already done.

Speaker Change: And in fact, it ended up being about double that.

Speaker Change: But that's because no one had ever tested the bureau in MTM patients. So we learned a lot from that that was why we did the arise study the way we did it was sort of a canary in the coal mine as Youll recall and it puts us in a very strong position now because.

Will Lewis: That was why we did the ARISE study the way we did. It was sort of a canary in the coal mine, as you'll recall, and it puts us in a very strong position now because we did see that difference between the two groups, both on a per patient and between group basis, and that is what informs the driving assumptions for where we go from here. There was a slight difference between eight and nine in the number of questions, but what all this complexity means and yields after you've done all the analysis is that we won either way on ARISE, whether it was eight questions or nine questions.

Will Lewis: As we mentioned, we've already been in dialogue with more than 90% of patient lives in the US, the groups that cover them and we have a very good and robust dialogue going on about disease state awareness there. Those efforts run in parallel and second I'll ask Martina to talk about medical affairs separate from commercial obviously, but on the balance of the commercial front, we have every one of our, what we refer to as customer facing groups in growth mode and in preparation mode for this launch.

Speaker Change: Either way on arise whether it was eight questions or nine questions. But then became a very simple question of how much power do we want to have in the phase three encore study to achieve the expected outcome based on arise and we target just north of 90%. So thats, where the 400 number comes from we'll close off enrollment in the third quarter of this year.

Will Lewis: It then became a very simple question of how much power we want to have in the phase three on-course study to achieve the expected outcome based on ARISE, and we target just north of 90 percent. So that's where the 400 number comes from. We'll close off enrollment in the third quarter of this year.

Will Lewis: We set the standard by our error case launch, which was to have everything ready about six months before approval. In this case, it's going to be more like nine months before approval. I just would highlight the most recent effort to hire the additional 120 sales reps. I think as of yesterday, we had all but one who had accepted those positions and the reason why that last one is not on board yet is because for every one of these positions, although we had more than 7,000 resumes.

Will Lewis: That keeps us on track to produce data by what is now probably going to be the first quarter of 2026. We feel great about all of that, and that would put us in a position where we could have this label expansion opportunity. Once again, a first in disease indication, and as of now, no near-term competition on the horizon. And I would just remind everyone of the magnitude of the label expansion. Today in the U.S., there are about 12 to 17,000 patients.

Speaker Change: That keeps us on track to produce data by what is now probably going to be the first quarter of 2026, we feel great about all of that and that would put us in a place where we would have this label expansion opportunity. Once again first in disease indication and as of now no near term competition on the horizon.

Will Lewis: We have held ourselves to the standard of not only excellence, but cultural fit within the company. One of the great strengths of insumed is that we have folks that are here that are really interested in helping patients get better and I can't emphasize that enough as an important cornerstone element of what this company is all about and the purity of that needs to be preserved even as we find scale in larger opportunities.

Speaker Change: And I would just remind everyone on the <unk> on the magnitude of the label expansion today in the U S. Theres about 12 to 17000 patients all Mac in the U S. As you know around 100000 patients. So as we think about our revenue guidance this year.

Sara Bonstein: All MAC in the U.S. is, you know, around 100,000 patients. So as we think about our revenue guidance this year, it's obviously very impressive at 340 to 360. But what we shared on commercial day is we believe Eric Case, with the label expansion, has the ability to be a billion-dollar-plus product. So we believe this label expansion, with the strength of the ARISE data and now the feedback from FDA, we couldn't be more encouraged about the opportunity for the broader franchise. Martina, I don't know if you want to add anything about the specifics of the trial. Yeah, Greg.

Martina: Obviously very impressive at $3 40 to $3 60, but what we what we shared on the commercial day as we believe Eric case with the label expansion is the ability to be $1 billion plus product. So we believe this label expansion with the strength of the arise data and how the feedback from FDA, we couldn't be more encouraged about the opportunity of the broader franchise Martina I don't know if you want to add anything about the specifics of that.

Will Lewis: So I'm very pleased with the work that's been done to date. Our leadership team is absolutely crushing it on every front. As we've said in the remarks, we are at or ahead of schedule on pretty much every metric and I can say having just reviewed it during our board meeting over the last two days. I think we all sit here today feeling very good about our preparation for next year. There's a lot of work still to be done.

Speaker Change: Phil.

Martina Flammer: So from the powering, as you know, we're powering the primary endpoint on the PRO. And there are two pieces. We want to show a difference of at least four points between the groups. That's why we're north of 90 percent. But we're also powered north of 90 percent for culture conversion. Great, thank you. And if I could just, my follow-up would be just on the heels of the positive BRENSO data that you generated, have you been able to undertake any new market research engaging with either physicians or payers and any early insights, if you have completed any of those market research studies?

Phil: Yeah, Greg so from the powering as you know repowering of our primary endpoint on the CRO and there's the two pieces, we want to show a difference of at least four points between the groups. That's why we're north of 90% power, but will also powered north of 90% for culture conversion.

Will Lewis: I don't want to take any away from that. But we feel very good about the strength of our position, the strength of the team, the content of the character of the people we brought on board, and the efforts that we are putting on this opportunity. It can't be overstated how significant this is and therefore how important it is for us to get it right.

Greg <unk>: Great. Thank you and if I could just my follow up would be just.

Brent: On the heels of the positive Brent so.

Speaker Change: Data that you've generated have you been able to undertake any.

Speaker Change: New market research engaging with either physicians or payers and any early insights. If you have completed any of those market research studies.

Martina Flammer: Martia, do you want to talk about the medical side of the equation? Yeah, happy to. So in addition to what you speak to with a pay from a from a commercial perspective and should they provide access and how do you think about it?

Martina Flammer: Well, we're going to continue to do market research between now and the day of launch, to be honest. And I would say probably the top line takeaway is the target product profile we had gone out and done our prior market research with. What we saw from Aspen, in actuality, is actually better.

Speaker Change: Well, we're going to continue to do market research between now and the end the day of launch to be honest and I would say that.

Martina Flammer: What's important is pair organizations have medical directives just as many other organizations do. And those are the people who understand and learn about what is the true unmet medical need here? What other treatments are available? What are the paths to diagnosis? How does a patient go through the system? We have colleagues of from medical, we speak about our medical outcomes, liaison colleagues who are on a regional basis in the field, who understand what is relevant for the medical director in a payer organization, providing them that information.

Brent: Probably the top line takeaway is the target product profile, we had gone out and done our prior market research with.

Brent: What we saw from Aspen in actuality is actually better so there's more to learn more to understand but.

Graig Suvannavejh: So there's more to learn, more to understand, but I think we're just in as strong a position as we could hope to be. You know, if anyone was there at Dundee with us, they would have heard just the enthusiasm from the experts who treat this field around the world for the potential arrival of this medicine and the profile that they saw there. It was nothing short of a celebration.

Brent: I think we're just.

Brent: And as strong a position as we could hope to be in.

Speaker Change: If anyone was there a done deal with us they would have heard just the enthusiasm from the experts who treat in this field around the world for the potential arrival of this medicine in the profile that they saw there. It was it was nothing short of a celebration.

Will Lewis: The next question comes from the line of Nicole Germino from Druid Securities. Please go ahead. Good morning, thanks for taking my questions and congrats on the progress. For BRNZO, beyond the diagnosed bronchiectasis population, in order to tap into the patients with COPD who have potential overlap or comorbid bronchiectasis, what is the potential strategy to capture those eligible patients in this segment? Like, how do you convince doctors to give a CT scan in addition to a spirometry test, a diagnosis, or what needs to happen in order to capture more patients with existing COPD?

Speaker Change: Question comes from the line of Nicole <unk> from <unk> Securities. Please go ahead.

Nicole: Good morning, Thanks for taking my questions and congrats on the progress for.

Jennifer Kim: Next question comes from the line of Jennifer Kim from Canter Fitzgerald. Use go ahead. Hey guys, thanks for taking my questions. I wanted to go back to the one versus two dose for Brenzo. It seems like everyone is in agreement that there's a compelling reason to go for the higher dose, or include the higher dose. Is there a reason why the FDA would have hesitation on that front? And then my second question is, could you give any color on exactly where you're at with on-coronrolment?

Speaker Change: For <unk> beyond the diagnosed bronchiectasis population in order to tap into the patients with COPD with potential overlap of comorbid bronchiectasis.

Speaker Change: What's the potential strategy to capture those eligible patients in this segment like how do you convince doctors to give a statistic scan in addition to our spirometry at diagnosis or.

Speaker Change: What needs to happen in order to capture more patients with existing COPD.

Will Lewis: Yeah, so on that front, the definitive diagnosis for bronchiectasis is a combination of a CT scan and basically a diagnosis by a pulmonologist for a certain symptom profile. But the CT scan is an anatomical read that radiologists are very experienced at doing in identifying that anatomical change in diagnosing bronchiectasis.

Speaker Change: Yes, so on the on that front, it's really the definitive diagnosis for bronchiectasis is a combination of a C. T scan in a basically a diagnosis by a pulmonologist for certain symptom profile.

Jennifer Kim: Sure, so on the FDA front, we don't anticipate that there's going to be any pushback. I think the guiding principle of the FDA follows is, what's the lowest effective dose? And when you think about going up in dose, what is the risk reward balance that you are encountering as you go there? So as we go from 10 to 25, what we observe is some clear itemizable, if that's the right word, benefits from prevention of lung function decline, which is Martina expressed earlier, is very quantifiable and meaningful for every physician we've spoken to.

Speaker Change: But the <unk> scan as is <unk>.

Speaker Change: Anatomical read that radiologists are very experienced in doing and identifying that that anatomical change in diagnosing bronchiectasis that first element is not new.

Will Lewis: That first element is not a new effort that will have to be undertaken. It's simply a question of getting the patient to get the CT scan. Through the disease state awareness campaigns we've already kicked off, and I think the existing awareness among treating physicians that there are many patients who probably have bronchiectasis and are either comorbid or have been misdiagnosed is something that has found a lot of resonance with the folks that we've spoken to.

Speaker Change: That will have to be undertaken it's simply a question of getting the patient to get the <unk> scan through the disease state awareness campaigns, we've already kicked off and I think the existing awareness among the treating physicians that there are many patients who probably have bronchiectasis and are either co morbid or had been misdiagnosed.

Jennifer Kim: In addition, the quality of life benefit that we observe at the 25 milligram dose is also meaningful. It's can indicate you may feel better on this medication, or at least they're aware of that, and most importantly, the payers know that when they pay for a medicine, the patient is more likely to take it if there isn't a bad side-effect profile. So all of that suggests the 25 in a very positive light.

Speaker Change: It is something that has found a lot of resonance with the folks that we've spoken too. So I think youre going to see an increased trend of contemplation by the physicians in this field as to whether or not the patients who are for example on Max dose Llama llamas and are experiencing exacerbations may in fact be bronchiectasis, either as well or.

Will Lewis: So I think you're going to see an increased trend of contemplation by physicians in this field as to whether or not the patients who are, for example, on max-dose lavalamas and are experiencing exacerbations may, in fact, be bronchiectatic either as well or as a primary diagnosis. In either case, they're one CT scan away from that diagnosis, and once they've had that and the pulmonologist has identified it as such, then they're eligible and on label in a world where we're approved. So I think this is not a far journey.

Speaker Change: As a primary diagnosis in either case, there <unk> scan away from.

Jennifer Kim: And I think the question the FDA has is, do they agree with that risk reward profile that there is added benefit and not a lot of additional risk going up to 25? To us, that seems to be the landscape, but there's more to learn. And again, I'll remind everybody we're doing a lot of detailed analysis on what is a very substantial database. We haven't seen anything yet that would suggest that this equation would be viewed differently. We're just trying to preserve the right to continue to analyze the data, enter into a very open dialogue with FDA, and put forward what we think makes the most sense.

Speaker Change: That diagnosis and once they've had that in the Pulmonologists is identified as such then they're eligible and on label in a world where we're approved so I think this is not a far journey it will take some effort too.

Will Lewis: It will take some effort to motivate some of the more community-level physicians, but I can tell you that some of the key opinion leaders that we spoke with in Dundee have already systematically begun the process of looking at their patients and asking whether or not they may also have bronchiectasis and, indeed, bringing forth that request for a CT scan and moving that forward as a next step. So I think you're going to see this shift happen pretty regularly, but we'll have to see how it plays out.

Speaker Change: Motivate some of perhaps the more community level physicians, but I can tell you that some of the key opinion leaders that we spoke with <unk> have already systematically begun the process of looking at their patients and asking whether or not they may also have bronchiectasis and indeed ushering forth that request for a <unk> scan and moving that forward as a next step.

Will Lewis: I just want to emphasize, most importantly, that whether we go with one or two doses, we will be ready. We have adequate supply for both. We're prepared to detail both. And so this is, it's a nice place to be, whether there's one or two doses. And I think we'll just leave it at that.

Speaker Change: I think youre going to see this shift happen.

Speaker Change: Pretty regularly but but we'll have to see how it plays out I don't know Martina based on your dialogue with physicians, what you've what you've heard.

Will Lewis: I don't know, Martina, based on your dialogue with physicians and what you've heard. Yeah, I think, every time you have a new disease coming on board, which is basically a focus now for certainly for pulmonologists, but it is also a focus for patients. So you have to think about if you are being treated for something, whether it's COPD or asthma, and you continue to not be well controlled; you should have a conversation with your physicians.

Martina: Yeah, I think you know every time you have a new disease coming on board, which is basically our focus now for certainly for Pulmonologists, but it is also a focus for patients. So you have to think about if you are being treated for something.

Will Lewis: On Encore, you asked what's our status of enrollment? That continues to do well, and frankly, accelerate. As we get near the end here, we've said we'll close off enrollment in the third quarter. That feels very good to us. I will just add that this is another one of those moments where we have revisited our assumption set and made sure that we are looking at this through a very conservative prism. When we look at the landscape of all MAC NTM, right now there is no competition on the near-term horizon.

Martina: Whereas COPD or asthma, and you continue not to be well controlled you have a conversation with your physicians and so both from a physician and from the patient side. There is an awareness and now you have an opportunity to two there where it actually makes sense to do a cte skin screen and say is this a patient who has more.

Martina Flammer: And so both from a physician's and from a patient's side, there is an awareness. And now you have an opportunity where it actually makes sense to do a CT scan, screen, and say, is this a patient who has more? And that, I think, is a similar situation that you may have seen several years ago with interstitial lung diseases and IPS, but that only became an awareness for both patients and physicians once there were treatments available.

Will Lewis: We want to make very sure that the strength of these data stands the test of time, much like it did with the rise, much like it has done with convert, much like it has done with Aspen. And so those same principles inform the final design and powering assumptions going into Encore. And the way we are approaching this as we look to close down enrollment in the third quarter of this year is greater than 90% power to hit the primary end point of this study. So we feel like we're in a very good position based on what we saw on a rise to produce a result we hope successfully with them. I think that's helpful.

Speaker Change: And that I think is is it similar.

Martina: Situation that you may have seen several years ago with interstitial lung diseases, and Ips that only became onboard and awareness for both patients and physicians once they were treatments available. So we see this now bronchiectasis has become a major topic I think for all of the major Congresses in west.

Martina Flammer: So we see this now. Bronchiectasis has become a major topic, I think, for all the major congresses in respiratory, ATS, ERF, certainly for World Bronch. But it is now a recognition of a disease that was underdiagnosed and not understood, and frankly, because people couldn't treat it.

Martina: Territory Ats E. R. S. Certainly for wealth bronc, but it is now a recognition of the disease that was under diagnosed and not understood and frankly because people couldn't treat it.

Will Lewis: Great And then there was one quick follow up. So with over $1 billion in cash, what is your strategy to continue creating value? I think the short answer to that is the first two pillars will, in the near term, yield not only continued growth as we've seen from EraCase in the refractory setting on the commercial front but also, presuming approvals, the ability to launch for bronchiectasis with brensocatib and then subsequently, assuming Encore goes the right way, an expanded label indication for EraCa

Speaker Change: Great and then one quick follow up.

Will Lewis: If I could sneak one more question and just thinking about those first few quarters of the Brenso launch, just net net, would you anticipate the party redesigned to help or hurt that launch? Thanks. The most important thing about that piece of legislation is that for the first time they addressed the burden that is placed upon patients for medicines that are expensive. And the fact of the matter is, it doesn't really any benefit to patients to load them up with additional costs that they find a financial burden in reaching.

Speaker Change: So with over 1 billion in <unk>.

Speaker Change: Cash what is your strategy to continue creating value.

Speaker Change: Well I think the short answer to that is the first two pillars in the near term will be yielding not only.

Speaker Change: Continued growth as we've seen from Eric case in the refractory setting on the commercial front, but also presuming approvals the ability to.

Brent: [noise] launch for Bronchiectasis with Brent So Canada, and then subsequently assuming oncor goes the right way.

Brent: The expanded label indication.

Brent: For aerospace I think those two.

Will Lewis: I think those two pillars and the execution of those two areas are going to drive value for many, many years at this company. We couldn't be more excited about that. We also have Pillar 3 and Pillar 4.

Speaker Change: The execution of those two areas are going to drive value for many many years at this company.

Speaker Change: We couldnt be more excited about that we also have pillar III and pillar four will set those aside for now, but I certainly expect there to be significant value driven from there I don't know Sir if you want to talk about how we think about our cash position and where we go from here and we've been very clear that we're not funded to cash flow positive, but we got a lot of levers to pull and we're in the embarrassment of rich.

Will Lewis: We'll set those aside for now, but I certainly expect there to be significant value driven from them. I don't know, Sara, if you want to talk about how we think about our cash position and where we go from here. We've been very clear that we're not funded to cash flow positive, but we've got a lot of levers to pull, and we're in an embarrassment of riches in terms of which programs we want to fund and at what times. Yes, sure. Happy to,

Will Lewis: There has been many studies that have shown that making medicine more accessible and lower cost at the pharmacy countertop results in better usage rate, better adoption rate, and the consequence of that is patients are healthier. So for every angle, this is a piece of legislation on that particular point that in my view has been a long time incoming and very necessary. I think as patients realize that they have a lower burden of a maximum of $2,000 out of pocket across all their medicines, which can be spread over on a monthly basis, that becomes a much more affordable equation than carrying 5% of the overall burden past catastrophic thresholds that they've had to face in the past.

Speaker Change: As in terms of which programs we want to fund.

Speaker Change: And at what time, Yeah, sure happy to and couldn't be more pleased with our cash position 125 billion as at the end of the quarter and I. Appreciate all the support from all of our shareholders and our recent equity raise and the.

Sara Bonstein: And, you know, couldn't be more pleased with our cash position, $1.25 billion, as at the end of the quarter, and appreciate all the support from all of our shareholders and our recent equity raise and the strength that we've been able to show since Aspen Data and that raise. As Will mentioned, we are, you know, laser focused on the successful launch of brensocatib assuming approval by FDA and the rest of the regulatory authorities, as well as the underpinning of the commercial infrastructure today with Aircase and that future label expansion, again, pending regulatory approval.

Speaker Change: Strength that we've been able to show sense Aspen data on that race as well mentioned, we are laser focused on that success.

Speaker Change: Successful launch of <unk>, assuming approval by FDA and the rest of the regulatory authorities as well as that.

Will Lewis: And that's what's produced the really terrible stories about people need to take out mortgages and find a large sums of money to gain access to life saving medicines. I think we're finally past that era, and I think that's a very good thing.

Speaker Change: Underpinning of the commercial infrastructure today with aerospace in that future label expansion again pending regulatory approval.

Sara Bonstein: As we think about, you know, where we go from here, we have a line of sight on becoming a self-sustaining biotech company. So what does that mean that, you know, we obviously have a line of sight on to profitability?

Speaker Change: As we think about where we go from here, we have a line of sight on becoming a self sustaining biotech company. So what does that mean that we obviously have line of sight onto profitability, we have not committed to a specific timing, but that is very much in our forefront.

Will Lewis: Okay, we'll tell someone. Thanks again.

Will Lewis: We have not committed to specific timing, but that is very much in our forefront, and as we're thinking about, you know, future investment and tradeoff and all those good things, as Will said, we do have an abundance of riches. TPIP is a very interesting asset, and we believe wholeheartedly in that program. We'll know more about that asset next year with the pH data once that's in hand. We'll learn more about Brenso with the CRS data next year, and the encore data, obviously, we spoke a lot about today.

Leon Wang: Next question. Your next question comes from the line of Leon Wang from Barclays east ahead. Hey, congrats on the corner, and thanks for taking my questions. So we think about the competitor landscape B.I. Phase III. I think they revealed that they will be enrolling all-comer bronchiectasis, patient population. Can you remind us why you recruited a non-CF bronchiectasis?

Speaker Change: And as we're thinking about.

Speaker Change: Future investment and trade off and all of those good things as well said, we do have an abundance of riches TPI P is a very interesting asset and we believe wholeheartedly in that in that program, we'll know more about that asset next year with the ph data once that's in hand, and we will learn more about branch out with the Crs data next year. The encore data obviously, we saw.

Will Lewis: And how does this change in their potentially recreational study affect your thoughts on the competitive landscape going forward? If at all, and second question, as you work towards submitting the NDA in the fourth quarter, do you plan to update us on that when that submission is in? And what form could that be in a press release? Or would this just be an update at a layer conference? Thanks. Yeah, so I think the answer to the B.I, question begins with first of all seeing their data.

Speaker Change: Talk a lot about today, we really had a change in our kind of financial identity. As we think about that converts and how we've been able to show successful execution across many different opportunities around the balance sheet. So we couldn't be more pleased on where we are and what the future holds for us.

Will Lewis: We really had, you know, a change in our kind of financial identity as we think about the converts and, you know, how we've been able to show successful execution across many different opportunities around the balance sheet, so we couldn't be more pleased with where we are and what the future holds for us. Thank you. The next question comes from the line of Andrea Tan from Goldman Sachs. Please go ahead. Good morning.

Speaker Change: Great. Thank you.

Andrea <unk>: Next question comes from the line of Andrea <unk> from Goldman Sachs. Please go ahead. Good morning. Thanks for squeezing me in here well as a follow up to your comment just now on maybe setting aside tpa P and the fourth pillar as you think about what could drive value for the coming years I wanted to ask.

Andrea Tan: Thanks for squeezing me in here. Will, as a follow-up to your comment just now on maybe setting aside TPIP in the fourth pillar, as you think about what could drive value for the coming years, I wanted to ask about your commitment to continued development of TPIP and under what scenarios might you consider out-licensing the asset versus keeping that in-house? It's a great question. You know, we think that TPIP has a chance to be a best-in-class asset for the treatment of both PAH and PHLD based on what we've seen to date.

Will Lewis: And we haven't done that yet, right? We don't know what they really have. And until we know what their data is, it's hard to interpret the modifications they had to their entry criteria that were different from ours and what that resulted in. There were a lot of assumptions behind those modifications that they were quite vocal about before the fact, but we didn't really see that in the data set. So I think there's probably going to be some revisitation of whether or not that direction or claim they were heading in is going to be viable.

Speaker Change: On your commitment to continued development of TPI PNG and under what scenarios might you consider out licensing and out licensing of the asset versus keeping that in house.

Speaker Change: It's a great question, we think that TPI P is has the chance to be a best in.

Speaker Change: Class asset for the treatment of both PIH and ph ILD based on what we've seen to date, we keep trying to emphasize.

Will Lewis: From our point of view, it doesn't make any difference. It doesn't affect the outcome. There's still going to be securing a label for bronchiectatic patients. So I'm not particularly worried about it. Again, we've assumed all along, including with our peak sales numbers that we have competitors in the marketplace. B.I, seem to be the most approximate. The one thing I would say about their data is it does appear that there was some biological effect. Whether that was statistically significant or not, it wasn't clear, but what I will say is I think it does validate the mechanism of action of DPP1 inhibition.

Andrea Tan: We keep trying to emphasize that people understand that effectively, what we've done here is found a way to get more of the underlying moiety of proprosinol into the lungs of patients through the most effective means of delivering that, which is inhalation, and the most convenient means, which is dry powder. And the consequence of that has been, so far, remarkable results in what we've seen, some of it blended and blinded, but in terms of PVR reduction, in terms of the data that we saw in PHLD in Phase 2 just earlier this year, we think this supports a best-in-class profile.

Speaker Change: People understand that effectively what we've done here has found a way to get more of the underlying moiety of for <unk> into the lungs of patients through the most effective means of delivering that which is insulation and the most convenient means which is dry powder and the consequence of that has been so far remarkable results in.

Speaker Change: What we've seen some of it blended blinded, but in terms of PBR reduction in terms of the data that.

Speaker Change: That we saw in ph ILD and phase two just earlier this year.

Martina Flammer: But maybe Martin, I'll turn over to you for your report. Yeah, I think what I would be looking for in the data is also, if you look at the patients, they did enroll all commerce that's one of the considerations. What we don't know and they haven't shown yet is what is the response. And you know, having two previous exacerbations is the strongest predictive for future exacerbations. I think it's a good guideline to inform you and have an ability to estimate how you would power a study because you do need to understand your background.

Andrea <unk>: We think this supports a best in class profile and when we look at PBR reduction we frame against what's out there right now from process noise and we also look at <unk>.

Andrea Tan: And when we look at PVR reduction, we compare it to what's out there right now from prostanoids, and we also look at cetatricept, which got into sort of the low end of the 30 percent PVR reduction range on average at its best data point. We're looking to get close to that, maybe match it, and we'll see, maybe even do a little better. We'll have to see what the data shows next year, but that would represent an unbelievable potential combination for the treatment of these patients if you think about those drugs and what they would bring with their different mechanisms of action.

Andrea <unk>: Which got into the sort of the low end of the 30% PBR reduction range on average at its best data point.

Andrea <unk>: We're looking to get close to that maybe match it and we will see maybe even do a little better we will have to see what the data shows next year, but that would represent an unbelievable potential combination for the treatment of these patients. If you think about those those drugs and what they would bring with different mechanisms of action now we havent done that testing yet we don't know that but it is certainly.

Martina Flammer: And that may be one thing that they're working on. We haven't seen that data, but that is one thing that will inform it. And if you enroll all on commerce, who have maybe only one exacerbation, you do not know how that would actually impact your powering.

Will Lewis: Now, we haven't done that testing yet. We don't know that, but it is certainly the way the key opinion leaders are thinking, and that suggests that this is a very important and prominent asset. They've told us point blank that this would change the way they think about the use of prostanoids and the treatment of both classes of patients if the data continues to prove what it has done to date, and that means that this asset would have a lot of value. We're always thinking from our shareholders' point of view about what's the best way to deploy capital.

Andrea <unk>: The way the key opinion leaders are thinking and that suggest that this is a very important and prominent asset.

Speaker Change: Told us point blank this would change the way they think about the use of <unk> in the treatment of both classes of patients. If the data continues to prove out what it has to date.

Will Lewis: So and on the other question about NDA submission, we do implant to announce that that's our current intention once that's completed.

Speaker Change: And that means that the SaaS. It would have a lot of value. We're always thinking from our shareholders' point of view, what's the best way to deploy capital. We're aware that the time between now and cash flow positivity is going to be marked by several additional trials that will begin to to add some cost. So we want to measure those so that it's not a constant returned to <unk>.

Van: Great, thank you for taking my question. Your next question comes from the line of the Van from Guggenheim Securities. Please go ahead. Yeah, great. Thanks for taking my question.

Will Lewis: We're aware that the time between now and cash flow positivity is going to be marked by several additional trials that will begin to add some cost, so we want to measure those so that it's not a constant return to investors for additional capital without a clear proof and advance along the way. Where does that put us with TPIP? It means that when we unveil the PAH data at the end of next year, which is the timing we expect, we will have a very clear idea of the inherent value of this compound.

Will Lewis: So just one maybe shifting years of GPIP. I think you've mentioned the PHLD data. I think you did six days. I'll come later this year. I'm curious if you can provide any more insight into which conference you're targeting on that.

Speaker Change: Investors for additional capital without a clear proof and advance along.

Speaker Change: Along the way.

Speaker Change: Where does that put us with TPI P. It means that when we unveil the PIH data at the end of next year, which is the timing. We expect we will have a very clear read on the inherent value of this compound and I think that that's likely to be recognized.

Will Lewis: And then just going back to the question earlier on the pricing side for Brenzo, you did mention you've had some initial conversation with the payers. Maybe you can just provide any sort of feedback that you're receiving there. It sounds obvious, you're so comfortable with that that range you've provided before, but just any sort of insights on the initial sort of dialogue and how they've been reacting to the disease and the profiles you've been discussing.

Will Lewis: And I think that that's likely to be recognized by investors and strategics alike. So I couldn't be more bullish about it. I can't say at this point what we might do with it. But we're always open-minded to maximizing value.

Andrea <unk>: By investors and strategics alike, so couldnt be more bullish about it.

Andrea <unk>: Can't say at this point, what we might do with it we're always open minded to maximizing value.

Will Lewis: Okay, and then, if I may ask one more, just as you have engaged more shareholders post the Aspen data, has your thinking around the 5 billion peak sales potential evolved or been refined in any way? And then can you just quickly remind us what underpins your conviction that the early launch cadence could mirror that of Himara or Doopey? Yeah, so I think it's really important when we talk about peak sales, when we have a very detailed, draw everyone's attention to the commercial day that we held, where Drayton went through in great detail each of the different opportunities and where our conviction comes from.

Speaker Change: Okay, and then if if I may ask one more just as you have engaged more shareholders post the Aspen data has your thinking around the 5 billion peak sales potential evolve Japan refined it anyway, and then can you just quickly remind us what underpins your conviction that the early launch cadence could mirror that of Humira DB.

Will Lewis: Yeah, so we're super excited about the data generation from TPIP and PHLD. And we were certainly hoping to have it at a conference this year. I will say the conference schedule is fairly busy and the consequence of that is it's probably going to slip into 2025 before able to put out all of that data. But I will say that that process continues to be underway. So we'll update you once we have that.

Speaker Change: Yes, so I think it's really important when we talk about peak sales.

Andrea <unk>: We have very detailed draw everyone's attention to the commercial day that we held where Drayton went through in great detail each of the different opportunities and where our conviction comes from that has not abated in any way and if anything the strength of the data and the response from the medical community gives us greater conviction in what we have seen and explored with our research.

Will Lewis: We want to get it out as soon as possible. There's a lot there to like. And we'll have more to say about that in the future, but we want to do it at peer reviewed setting as we previously represented. And then on the pricing side, you know, it's still too early to talk about price with specificity and certainly where we are in our dialogue with all of the different constituents here is in talking about disease state awareness and understanding the burden of this disease and what role.

Will Lewis: That has not abated in any way, and, in fact, the strength of the data and the response from the medical community gives us greater conviction in what we have seen and explored in our research to date. But, you know, where do we go from here with that?

Andrea Tan: I think we'll continue to refine it. We'll continue to think about opportunities. I think it's way too early to be talking about launch curves and what they might look like. Obviously, we are aware of the benchmarks that are out there. When we think about some of the strongest launches, we think about things like Dupixent, which probably marks the very, very top, if you will, of what could be accomplished.

Andrea <unk>: A date.

Andrea <unk>: Where do we go from here with that I think will continue to refine it will continue to think about opportunities.

Will Lewis: If it's approved at the appropriate time, we'll begin to talk about Brent. So that that won't happen for a while. But right now it's about disease state awareness and making sure people understand the burden. I will say that our interactions and the perceptions that people have across the treating community, including the payors, continues to support our belief and the work we've done in pricing studies that the range we gave you were very comfortable with.

Speaker Change: It's way too early to be talking about launch curves and what they might look like obviously, we're aware of the benchmarks that are out there when we think about.

Andrea <unk>: Some of the some of the strongest launches, we think about things like <unk>.

Andrea <unk>: <unk> probably marks the very upper upper end the Mount Everest, If you will of what could be accomplished I think.

Andrea Tan: I think if I remember correctly, you know, if you look at their quarters, three through six, which would correspond to a first full calendar year, I think they ended up with over $700 million in revenue, which is just sort of astonishing.

Speaker Change: Remember correctly.

Andrea <unk>: Look at their quarters three through six.

Andrea <unk>: What would correspond to our first full calendar year I think they ended up with over $700 million in revenue, which is just sort of astonishing.

Will Lewis: I think once again, as I said earlier, the content of what we have to offer the target product profile from the actual aspirin results is better than what we had originally tested. That preservation of lung function is very powerful data as is the patient's feeling better. So we'll see how that plays out over time, but more work to be done there and we'll certainly update you as we get close.

Will Lewis: Some of the other products that are out there, think about Dyspire and others; they, during the same time frame, might have been around $600 million. So, we're way far from setting what a launch curve might look like, but we certainly know that that represents the upper end of the thin atmosphere of what can be accomplished. And so, in my mind, we'll be looking very carefully at precedents like Dupixent, Fisenra, Dyspire, OFEV, and understanding what their trajectories were and what we think we're going to be able to accomplish.

Speaker Change: Some of the other products that are out there, we think about aspire and others. During the same timeframe might've been around $600 million. So we're way far from setting.

Will Lewis: Okay, sorry, thank you.

Speaker Change: Launch curve might look like but we certainly know that that represents the upper end of the thin atmosphere of what can be accomplished and so in my mind, we will be looking very carefully at.

Speaker Change: Precedent like do picks and for Sunrise to aspire <unk> and understanding what their trajectories were and what we think we're going to be able to accomplish.

Lisa Bayko: Your next question comes from the line of Lisa Bayko from Evercore ISI. Peace go ahead. Hi there, thank you for taking the question. First question, when you talk about a broad label, would that include CF? And then also with respect to the IRA, how should we think about margins on the product? I know, with the benefit of spreading the 2000 payment that the Medicaid patients are responsible for also the catastrophic coverage, 60% of it above catastrophic is going to fall on the payers and just wondering how they're going to react to that in terms of wanting some sort of rebate discount fees along those lines.

Speaker Change: The overall peak sales number we have a lot of conviction in what the shape of the curve looks like we've got a lot more work to do that'll obviously be driven by price, which will be driven entirely by value and that will be captured in our dialogue with FDA in the period.

Lisa Bayko: Thank you. Yeah, sure. So on the first point, the broad label would not, we would not anticipate it would include cystic fibrosis patients. This will be for non cystic fibrosis, bronchectasis. Having said that, obviously the data we saw in the CF study we completed was very compelling and that certainly is out there. I think that if there are patients that are experiencing exacerbations successfully being treated by drugs that are offered by other companies.

Will Lewis: We have a lot of conviction in the overall peak sales number. But what the shape of the curve looks like, we have a lot more work to do. That will obviously be driven by price, which will be driven entirely by value, and that will be captured in our dialogue with FDA in the paired discussion. Okay, thanks for the color.

Andrea <unk>: Discussions.

Speaker Change: Okay. Thanks for the color.

Speaker Change: Yeah.

Stephen Willey: Your next question comes from the line of Steve Willey from Stifel. Please go ahead. Hey, good morning, guys. This is Tulian on behalf of Steve. Thank you for taking my question. I just have a two-quick one on my end.

Speaker Change #100: Your next question comes from the line of Stephen Willey from Stifel. Please go ahead.

Stephen Willey: The first one is related to the Phase 2 PAH data readout timing. If I remember correctly, you guys were previously guiding to this data readout in the second quarter of next year, but it looks like it has shifted to basically the second half of next year. I'm just wondering if there is any reasoning that I happened to miss. If you guys provide additional color on that extension, that would be great.

Speaker Change #100: Hey, good morning, guys. It's Toby on Christine. Thank you for taking my question I just have two quick one on my end. The first one is related to page.

Speaker Change #100: Two P H data readout timing, if I remember correctly I think youre right you were previously guiding to these data readout.

Speaker Change: In second quarter of next year, but it looks like it has a moderate to two.

Speaker Change: Shifting to second half of next year.

Speaker Change: Wondering if there is any reason that I happened to me is if you guys provide additional color on that expansion that would be great and the second question is related to these one versus two dose dichotomy do you think there will be an additional data that will be presented at the upcoming chats.

Stephen Willey: The second question is related to this one-versus-two-dose dichotomy. Do you think there will be additional data that will be presented at the upcoming CHESS conference that could actually just kind of solidify or at least provide an incremental view in terms of benefit and safety of these two doses? Thanks.

Lisa Bayko: Then there may be a physician who wants to think about this, but we would point out that that's a fairly small group and it certainly isn't something we're going to target because that would represent off label. Okay, think about the IRA and payers. Yeah, I don't know if we want to go over this with any specificity, but the thinking there is that you're going to see error case is not, is considered.

Speaker Change: Conference that could actually just like kind of positive high or if you could provide incremental incremental view into like.

Speaker Change: In terms of like benefit then take Dr. Steve Kudos, it's pink.

Will Lewis: Yeah, so I'm not sure what the misunderstanding might have been on the PAH front. We are north of 75 percent enrolled in that trial, but we have always had the second half of 2025 as the timing for the topline results for that. That hasn't changed at all, and in fact, if anything, the PAH enrollment has accelerated a little bit, which gives us even greater conviction that we're going to hit that timeframe

Speaker Change #103: Yes, so I'm not sure what the misunderstanding might have been on the ph front.

Lisa Bayko: It has the small manufacturers benefits. A brenso would not. So the distribution of the cost as the drug rolls out would be more significant on us for brenso than it would be on error case. And so we've achieved that benefit. We can go over that in some greater granularity because year over year the manufacturer versus the plan percentage allocations are very different based on whether or not you secure that designation and happen to do that sidebar.

Speaker Change: We are north of 75% enrolled on that trial, but we have always had the second half of 2025 is the timing for the topline results for that that Hasnt changed at all and in fact, if anything the ph enrollment has accelerated a little bit which gives us even greater conviction that we're going to hit that that timeframe on the chest data front and the <unk>.

Will Lewis: On the CHEST data front and the one versus two doses, I don't know that there's going to be anything additional there that would shape the understanding of that. I would say right now we already know enough to see the benefit of 25 versus 10. It really becomes a risk-reward discussion, and I think that we need to have a dialogue with FDA, and out of respect for them, we want to make sure that we're approaching this in the right, constructive way.

Speaker Change: One versus two doses I don't know that theres going to be anything additional there that would shape. The comprehension of that I would say right now we already know enough to see the benefit of 25 versus 10.

Lisa Bayko: But I don't think it's going to impact the overall pricing reflection that we have because this is about value for money from the medicine. And I think what we've heard so far is that payers recognize the permanent damage that is done by pulmonary exacerbations experienced by patients with this disease. And while there's nothing in the category right now, the data that we have from Aspen is very compelling. And this is kind of one of those places where I think we're going to find a very productive dialogue with payers in terms of their willingness to support this.

Speaker Change: It becomes a risk reward discussion I think a dialogue with FDA and out of respect for them, we want to make sure that we're approaching this in the right constructive way, but I don't think theres any other shoe to drop that's going to inform one dose selection over another at this stage. Both look good both when both are effective and both are safe from our examination it appear.

Will Lewis: But I don't think there's any other shoe to drop that's going to inform one dose selection over another at this stage. Both look good, both win, both are effective, and both are safe from our examination. It appears there's some additional benefit at the 25 milligram dose, and we find that to be very compelling.

Speaker Change: Or is there some additional benefit.

Speaker Change: At the 25 milligram dose and we find that to be very compelling and so that's the basis from which will enter our dialogue with FDA.

Stephen Willey: And so that's the basis from which we'll enter our dialogue with FDA. Ladies and gentlemen, that does conclude the Q&A session on today's conference call. Thank you for your participation. You may now disconnect. [music]

Lisa Bayko: And Lisa, the only other thing I would add is the projections that we provided on commercial day took all of this into account. So our $5 billion peak sales and the opportunity we see from a commercial perspective on the revenue side took all of these factors into account. Thank you. That's helpful. Thanks. And can I just do one follow up on wraps are those are the additional reps you're hiring going to be.

Speaker Change: Yeah.

Speaker Change: Yeah.

Speaker Change: Yeah.

Speaker Change: Ladies and gentlemen that does conclude the Q&A session and today's conference call. Thank you for your participation you may now disconnect.

Speaker Change: [music].

Lisa Bayko: Detailing all of your products, in other words, Eric Hayes as well, maybe as a second, or how do you imagine prioritizing your sales force with respect to the products? Thanks. Yes, they are going to be detailing both products, assuming approval for Brunso, and indeed, assuming the expanded label for Eric Hayes, assuming Encore goes as we expect it will. So what we're looking at here is now a much more robust, but it highlights probably the single most important aspect of all of this, which is the synergy.

Speaker Change: Sure.

Speaker Change: [music].

Lisa Bayko: So this same sales force that launched refractory MAC, Eric Hayes for refractory MAC is going to be assuming, again, these regulatory approvals fall in place, all MAC NTM and Brunso and Brunque Ectasis, and so the teams are being trained for a disease state awareness in Brunque Ectasis, and in the meantime, we'll call on physicians for appropriately diagnosing and treating them for refractory MAC with Eric Hayes. So that's going to give us some extra horsepower as we get to the end of this.

Lisa Bayko: This year and into next year on that indication. But it is our intention that they will bring both forward for the foreseeable future. And just one other comment on this, the synergies, as you're thinking about the COPD Foundation and the Care Center Networks that they formed, that, you know, over 100 care centers around the United States, and those are going to be specialized in NTM and Brunque Ectasis. So just more sort of highlight on the synergies between the two disease settings. Okay, great. Thank you.

Will Lewis: Next question comes from the line of Greg Savanoved from Mizzouho. East go ahead. Good morning, congrats on the progress. Thanks for taking my questions. I just wanted to revisit the enrollment updates with regards to Encore and that you are now targeting 400. You just remind me with the prior target somewhere in the neighborhood of 250. And then maybe if you could provide a little bit more granularity on kind of what you did in terms of revisiting either the patient inclusion or exclusion criteria to give you kind of a better sense that, you know, with 400, you will get the result that you are looking for.

Will Lewis: Sure, so the most important thing to realize about Encore is that it was enrolled at the same time that a rise was enrolled, right? So we continued that enrollment after a rise read out, but the backdrop of choosing the primary endpoint and what the powering was, we didn't have any basis for that because there had been no validation of a PRO. So we're sort of flying blind when we set the original target and that target as we indicated at the time was likely to need to go up.

Will Lewis: That was 250 patients and that was several years ago. Once we saw the arise study, we knew it was going to have to increase materially. The assumption going in was that the minimum important difference here was going to be eight points and in fact ended up being about double that. But that's because no one had ever tested the PRO in NTM patients. So we learned a lot from that. That was why we did the arise study the way we did.

Will Lewis: It was sort of a canary in the coal mine, as you'll recall, and it puts us in a very strong position now because we did see that difference between the two groups both on a per patient and between group basis. And that is what informs the powering assumptions for where we go from here. There was a slight difference between eight or nine in the number of questions. But what all of this complexity means and yields after you've done all the analysis is that we won either way on a rise whether it was eight questions or nine questions.

Will Lewis: It then became a very simple question of how much power do we want to have in the phase three on course study to achieve the expected outcome based on a rise. And we target just north of 90%. So that's where the 400 number comes from. We'll close off enrollment in the third quarter of this year that keeps us on track to produce data by what is now probably going to be the first quarter of 2026.

Will Lewis: We feel great about all of that. And that would put us in a place where we would have this label expansion opportunity. Once again, a first in disease indication. And as of now, no near term competition on the rise. And I would just remind everyone on the magnitude of the label expansion. Today in the U.S., there's about 12 to 17,000 patients. All Mac in the U.S, is, you know, around 100,000 patients.

Will Lewis: So as we think about our revenue guidance this year, you know, it's obviously very impressive at 340 to 360. But what we shared on the commercial day is we believe error case with the label expansion as the ability to be a billion dollar plus product. So we believe this label expansion with the strength of the arise data and have a feedback from FDA. We couldn't be more encouraged about the opportunity of the broader franchise.

Greg Savanoved: Martina, I don't know if you want to add anything about the specifics of the trial. Yeah, Greg, so from the power ring is, you know, we're powering for primary end point on the PRO and there's two pieces. We want to show a difference of at least four points between the groups. That's why we're north of 90% power. But we'll also power north of 90% for culture conversion. Great. Thank you.

Will Lewis: And if I could just follow up with be just on the heels of the positive. Brent, so data that you generated. Have you been able to undertake any new market research engaging with either physicians and or payers and any early insights if you have completed any of those market research studies? Well, we're going to continue to do market research between now and the end of day of launch, to be honest. And I would say that probably the top line takeaway is the target product profile.

Will Lewis: We had. We had gone out and done our prior market research with what we saw from Aspen and actuality is actually better. So there's there's more to learn more to understand. But I think we're just in as strong a position as we could hope to be. And, you know, if, if anyone was there at Dundee with us, they, they would have heard just the enthusiasm from the experts who treat in this field around the world for the potential arrival of this medicine and the profile that they saw there. It was, it was nothing short of a celebration.

Nicole Germino: Question comes from the line of Nicole Germino from through with securities. Please go ahead.

Will Lewis: Good morning. Thanks for taking me questions and progress on progress. For Brent, you'll be on the diagnosed bronchiectasis population in order to tap into the patients with COPD with potential overlap or comorbid bronchiectasis. What's the potential strategy to capture those eligible patients in the segment? Like, how do you convince doctors to give us CT scan in addition to a spherometry at diagnosis and or what needs to happen in order to capture more patients with existing COPD?

Will Lewis: Yes, so on the on that front, it's really the definitive diagnosis for bronchiectasis is a combination of CT scan and a basically a diagnosis by a pulmonologist for certain symptom profile. But the CT scan is an anatomical read that radiologists are very experienced in doing in identifying that anatomical change in diagnosing bronchiectasis. That first element is not a new effort that will have to be undertaken. It's simply a question of getting the patient to get the CT scan through the disease state awareness campaigns.

Will Lewis: We've already kicked off and I think the existing awareness among the treating physicians that there are many patients who probably have bronchiectasis and are either comorbid or have been misdiagnosed. That is something that has found a lot of resonance with the folks that we've spoken to. So I think you're going to see an increased trend of contemplation by the physicians in this field as to whether or not the patients who are, for example, on max those lablamas and are experiencing exacerbations may in fact be bronchiectatic either as well or as a primary diagnosis.

Will Lewis: In either case, they're one CT scan away from that diagnosis and once they've had that and the pulmonologist has identified it as such, then they're eligible and on label in a world where we're approved. So I think this is not a far journey. It will take some effort to motivate some of perhaps the more community level physicians, but I can tell you that some of the key opinion leaders that we spoke with in Dundee have already systematically begun the process of looking at their patients and asking whether or not they may also have bronchiect.

Will Lewis: And indeed ushering forth that request for a CT scan and moving that forward as a next step. So I think you're going to see this shift happen. Pretty regularly, but we'll have to see how it plays out. I don't know, Martina, based on your dialogue with physicians, what you've heard. Yeah, I think, you know, every time you have a new disease coming on board, which is basically a focus now for certainly for pulmonologist, but it is also a focus for patients.

Will Lewis: So you have to think about if you are being treated for something, whether it's your PD or asthma, and you continue not to be well controlled. You have a conversation with your physicians. And so both from a physician and from a patient side, there is an awareness. And now you have an opportunity to, to where they actually make sense to do a CT scan screen and say, is this a patient who has more.

Will Lewis: And that I think is is a similar situation that you may have seen several years ago, with industrial lung diseases and IPS. That only became on board an awareness for both patients and physicians. Once they were tweaked and available, so we see this now bronchiectasis has become a major topic. I think for all the major congresses in respiratory, ATS, ERS, certainly for well bronch, but it is now a recognition of a disease that was underdiagnosed and not understood. And frankly, because people couldn't treat it.

Martina Flammer: Great. And then one quick follow up.

Will Lewis: So with over one billion in cash, what is your strategy to continue creating value? Well, I think the short answer to that is the first two pillars in the near term will be yielding not only continued growth, as we've seen from Ericace in the refractory setting on the commercial front, but also presuming approvals. The ability to launch for bronchiectasis with Brentsocata and then subsequently, assuming on core goes the right way, the expanded label indication for Ericace.

Will Lewis: I think those two pillars and the execution of those two areas are going to drive value for many, many years at this company. We couldn't be more excited about that. We also have pillar three and pillar four. We'll set those aside for now, but I certainly expect there to be significant value driven from there. I know, Sarah, if you want to talk about how we think about our cash position and where we go from here.

Will Lewis: We've been very clear that we're not funded to cash flow positive, but we've got a lot of levers to pull and we're an embarrassment of riches in terms of which programs we want to fund and at what time? Yeah, sure. Happy to. And you know, it couldn't be more pleased with our cash position 1.25 billion as at the end of the quarter and appreciate all the support from all of our shareholders and our recent equity raise in the strength that we've been able to show since Aspen data on that raise.

Will Lewis: As well mentioned, we are, you know, laser focused on successful launch of Brents of Cassibus, assuming approval by FDA and the rest of the regulatory authorities as well as the underpin of the commercial infrastructure today with Ericace in that future label expansion. Again, pending regulatory approval. As we think about, you know, where we go from here, we have a line of sight on becoming a self-sustaining biotech company. So what does that mean that, you know, we obviously have line of sight on to profitability.

Will Lewis: We have not committed to specific timing, but that is very much in our forefront. And as we're thinking about, you know, future investment and trade off and all those good things as well said, we do have an abundance of riches. TPIP is a very interesting asset and we believe wholeheartedly in that in that program will know more about that asset next year with the pH data once that's in hand. We'll learn more about Brent so with the CRS data next year, the on-core data obviously we spoke a lot about today.

Will Lewis: We really had, you know, a change in our kind of financial identity as we think about the converts and, you know, how we've been able to show successful, you know, execution across many different opportunities around the balance sheet. So we couldn't be more pleased on where we are and what the future holds for us.

Sara Bonstein: Great.

Andrea Tan: Thank you.

Next question comes from the line of Andrea Tan from Goldman Sachs, please go ahead.

Good morning, thanks for asking me in here. Will as a follow-up to your comment just now on maybe setting aside TPP and the fourth pillar as you think about what could drive value for the coming years, I wanted to ask on your commitment to continue development of TPP and under what scenarios might you consider out licensing of the asset versus keeping that in-house. It's a great question, you know, we think that TPP has a chance to be a best-in-class asset for the treatment of both PAH and PHL, the based on what we've seen to date.

We keep trying to emphasize that people understand that effectively what we've done here is found a way to get more of the underlying moiety of proportional into the lungs of patients through the most effective means of delivering that, which is inhalation and the most convenient means, which is dry powder, and the consequence of that has been so far remarkable results in what we've seen, some of it blended blinded but in terms of PBR reduction, in terms of the data that we saw in PHL D in phase two, just earlier this year, we think this supports a best-in-class profile, and when we look at PBR reduction, we frame against what's out there right now. So, from Prostinoids, and we also look at Satatercept, which got into the low end of the 30% PBR reduction range on average at its best data point, we're looking to get close to that, maybe match it, and we'll see, maybe even do a little better, we'll have to see what the data shows next year, but that would represent an unbelievable potential combination for the treatment of these patients, if you think about those drugs and what they would bring with different mechanisms of action.

Now, we haven't done that testing yet, we don't know that, but it is certainly the way the key opinion leaders are thinking, and that suggests that this is a very important and prominent asset, they've told us point blank, this would change the way they think about the use of Prostinoids and the treatment of both classes of patients, if the data continues to prove out what it has to date, and that means that this asset would have a lot of value. We're always thinking from our shareholders point of view, what's the best way to deploy capital, we're aware that the time between now and cash low positivity is going to be marked by several additional trials that will begin to add some cost, so we want to measure those so that it's not a constant return to investors for additional capital without a clear proof and advance along the way.

Where does that put us with TPIP, it means that when we unveil the PAH data at the end of next year, which is the timing we expect, we will have a very clear read on the inherent value of this compound, and I think that that's likely to be recognized by investors and strategic alike, so it couldn't be more bullish about it, I can't say at this point what we might do with it, we're always open-minded to maximizing value.

Okay, and then if I may ask one more, just as you have engaged more shareholders post the Aspen data, have you're thinking around the five billion peak sales potential evolved or been refined in any way, and then can you just quickly remind us what underpins your conviction that the early launch cadence could mirror that of Humira or Dubi? Yeah, so I think it's really important. When we talk about peak sales, when we have very detailed drive-ones attention to the commercial day that we held where Drayton went through in great detail, each of the different opportunities and where our conviction comes from, that has not abated in any way, and if anything, the strength of the data and the response from the medical community gives us greater conviction in what we have seen and explored with our research to date.

You know, where do we go from here with that? I think we'll continue to refine it, we'll continue to think about opportunities. I think it's way too early to be talking about launch curves and what they might look like. Obviously, we are aware of the benchmarks that are out there. When we think about some of the strongest launches, we think about things like DuPixen, which probably marks the very upper end, the Mount Everest, if you will, of what could be accomplished.

I think if I remember correctly, if you look at their quarters, three through six, what would correspond to a first full calendar year, I think they ended up with over $700 million in revenue, which is just sort of astonishing. Some of the other products that are out there, we think about to expire and others during the same time frame, might have been around 600 million. We're way far from setting what a launch curve might look like, but we certainly know that that represents the upper end of the thin atmosphere of what can be accomplished.

And so in my mind, we'll be looking very carefully at precedents like DuPixen, Fiszenra, to Spire, OFEV, and understanding what their trajectories were and what we think we're going to be able to accomplish. The overall peak sales number, we have a lot of conviction in. What the shape of the curve looks like, we got a lot more work to do, that'll obviously be driven by price, which will be driven entirely by value, and that will be captured in our dollar with FDA and the paired discussions.

Okay, thanks for the color.

Here next question comes from the line of steam. We'll leave from stifle, please go ahead. Hey, good morning guys, this is Tuleon for Steve. Thank you for taking my question. I just have a tool quick one on my end. The first one is related to page to page data without timing. If I remember correctly, I think you guys were approved to guide into these data readouts in second quarter of next year, but it looks like it has moderate shift to, you know, shifted to basically second half of next year.

I'm just wondering if there is any reasoning that I happen to me. If you guys provide an additional color on that extension, that would be great. And the second question is related to this one versus two dose dichotomy. Do you think there will be an additional data that will be presented at the upcoming chest conference that could actually just, you know, like kind of qualify or achieve providing incremental, incremental view into, you know, like into in terms of like benefit and safety of these two doses.

Thanks. Yeah, so I'm not sure what the misunderstanding might have been on the pH front. We are north of 75% enrolled on that trial, but we have always had the second half of 2025 as the timing for the top line results for that. That hasn't changed at all. And in fact, if anything, the pH enrollment has accelerated a little bit, which gives us even greater conviction that we're going to hit that time frame on the chest data front.

And the one versus two doses, I don't know that there's going to be anything additional there that would shape the comprehension of that. I would say right now we already know enough to see the benefit of 25 versus 10. It really becomes a risk reward discussion. I think a dialogue with FDA and out of respect for them, we want to make sure that we're approaching this in the right constructive way. But I don't think there's any other shooted drop that's going to inform one dose selection over another at this stage.

Both look good, both win, both are effective and both are safe from our examination. It appears there's some additional benefit at the 25 milligram dose and we find that to be very compelling. And so that's the basis from which we'll enter our dialogue with FDA.

Ladies and gentlemen, that this concludes the Q&A session in today's conference call. Thank you for your participation. You may now disconnect.