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spk07: Good day, and thank you for standing by. Welcome to the Knicks Pharmaceuticals third quarter conference call. At this time, all participants are on a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during that session, you will need to press star 1 on your telephone. If you require any assistance during the call, please press star 0. I would now like to hand the conference over to your speaker today, Ms. Rachel Frank. Ms. Frank, you may begin.
spk06: Thank you, Operator. Good morning, everyone, and thank you for joining Connexta's call to discuss our third quarter 2021 financial results and our recent corporate and pipeline activity. A press release highlighting these results can be found on our website under the Investors in Media section. As for the agenda, our Chief Executive Officer, Sanj Kay Patel, will start with an introduction. Ross Mote, our head of commercial, will provide an update on the Arculus commercial launch. Evan Tesari, Connexa's chief business officer, will follow with a brief pipeline review. Mark Ragosa, our chief financial officer, will review our third quarter 2021 financial results. And finally, Sanz will return for closing remarks and to kick off the Q&A session for which John Paolini, our chief medical officer, will also be on the line. Before getting started, please note that we will be making forward-looking statements today that are subject to risks and uncertainties that may cause actual results to differ materially from these statements. A review of such statements and risk factors can be found on this slide as well as under the caption, Risk Factors, contained in our SEC filing. These statements speak only as of the date of this presentation, and we undertake no obligation to update such statements except as required by law. With that, I will turn it over to Sanj.
spk02: Thanks, Rachel. Good morning, everyone. I'm happy to review our third quarter 2021 results today. We continue to make tremendous progress in bringing Arclist to patients in need. And we're also executing across our portfolio of clinical stage product candidates. I'm delighted to report that net revenue for Arclist for the third quarter of 2021 was $12.1 million. As expected, recurrent pericarditis was the major growth driver for the Arclist Q3 sales. Ross will cover our commercial performance in more detail in a moment. We are very pleased with the implementation of our targeted commercial strategy. This includes broad physician and patient adoption and the viable reimbursement conditions. These core elements are what's driving recurrent pericarditis sales and underscore the significant need for Arclist. Additionally, we remain focused on building the maximum value across our portfolio of clinical stage product candidates, and these are Mavilimumab, Vixilimumab, and KPL404, which is our CD40 program. We continue to expect data in the first quarter of 2022 from our phase three trial of MAVERI in COVID-19 related ARDS. And Eben will highlight the potential opportunity in this patient population a little later. We continue to be energized by our progress across the entire portfolio. And we believe that we're well positioned for longer term growth. I'll now turn it over to Ross to discuss our commercial performance in more detail. Ross.
spk03: Thank you, Sanj. We're thrilled to report that Q3, our second quarter of launch, continued with very positive momentum and ended in great shape with a net revenue of $12.1 million. This represents a 57% quarter-on-quarter growth, and as anticipated, recurrent pericarditis was the major growth driver in Q3. Revenue from CAPS and DERA indications remain stable. And as expected, the one-off inventory build that we saw in the launch quarter did not repeat in Q3. Therefore, the current pericarditis demand grew from a base of approximately one-third of the $7.7 million in Q2 to more than three-quarters of the $12.1 million of revenue in Q3. We are delighted with the growth rate. It represents continued uptake and adoption of Arculus from physicians, payers, and patients. in this previously unmet and debilitating, ultra-inflammatory cardiovascular disease. Taking into consideration the early launch trends, we are providing a Q4 net revenue guidance of between $16 and $17 million. On slide eight, I will dive into more detail on the drivers behind the recurrent pericarditis growth. We're very pleased with the continued broad physician adoption At the end of Q3, there were more than 200 unique prescribers who had written ARC lists for recurrent pericarditis since launch. This is more than double the number we reported in Q2, demonstrating rapid growth in the breadth of awareness and prescribing of ARC lists. We're also starting to see an increase in prescribers who are writing for multiple recurrent pericarditis patients. Since launch, the commercial team has engaged with around 4,000 physicians, representing more than 80% of the initial target accounts. Furthermore, while we hear many other companies are continuing to engage remotely, we're achieving in excess of 80% of these prescriber interactions face-to-face. This highlights the favorable access we have to our target accounts, as well as the eagerness of many physicians to learn about Arclist. On the payer side, we continue to see that more than 90% of all completed recurrent pericarditis patient enrollments were approved for coverage. We're also pleased and encouraged to report that we have achieved broad access through finalized payer policies for our target population, with greater than 190 million lives in the U.S. now having favorable coverage in place. This is a higher and quicker coverage than our prelaunch expectations. and allows physicians the confidence of gaining access when prescribing for their patients. As previously stated, we continue to expect that almost all of the remaining payers will update their coverage policies within one year of launch. And additionally, whilst we're still too early to provide definitive updates on duration of therapy, it's important to state that so far two-thirds of the ARCLIS prescriptions for recurrent pericarditis were written for 12 months of therapy. This is an excellent marker for how specialists are thinking about how long to treat a patient with recurrent procolitis. However, ultimately, duration of treatment will depend on the duration of the underlying disease, as well as the patient's willingness to remain on therapy and the payer approval duration. When it comes to compliance, we're generally seeing that patients receive refills on time and that almost all of the patients who initiated ARCLIST in Q2 were still on therapy at the end of Q3. On slide nine, I would like to highlight how we're interacting with patients and healthcare professionals through our new marketing campaign. We recently launched our full promotional breakthrough campaign, which we believe reflects the strength of the data behind Arclist in recurrent peripatitis and the desire for patients to return to their normal lives. We truly believe Arclist is becoming recognized as a breakthrough treatment that provides a targeted approach to the underlying driver of this disease. Through our disease education initiatives, promotional local and national webinars, social media and advertising, we have built a database of approximately 2,000 patients and caregivers across the US who have opted in to receive further education on the disease and treatments. In recent weeks, we initiated a tailored communication plan to this patient group, designed to provide targeted information on recurrent pericarditis depended on the stage in their journey and to give them the tools and resources to ask their physician about ARCLIST. Around 75 patients from the database are currently on ARCLIST treatment, and we anticipate this campaign will help to reach more patients in coming quarters. Moving to slide 10, I wanted to share some examples from the patient's perspective on recurrent pericarditis and ARCLIST. Recurrent pericarditis is an incredibly painful and debilitating disease, and we have remained completely focused on the fact that patients are in need and Arclist is the first and only FDA-approved drug for this disease. These quotes directly from patients are an example of why the Connexer team are so focused and driven to secure a successful Arclist launch. We are here to support patients to break through from this disease and get back to their normal lives. We're delighted with the Q3 results, and we now have two strong foundational quarters from approval, and we look forward to continuing to deliver for patients in Q4 and beyond. Evan, over to you.
spk00: Thanks, Ross, and good morning, everyone. I will provide a brief overview on where we stand with our three clinical stage programs. Starting with Vixirelumab, we're currently enrolling a global, randomized, placebo-controlled Phase IIb dose-ranging trial in parigonodularis, testing three different once-monthly dosing regimens. VIXA is a first-in-class mechanism that targets OSMR beta, which mediates the two key cytokines implicated in pruritus, hyperkeratosis, and fibrosis. The primary efficacy endpoint is change in worst-itch NRS at week 16, and we expect data from this trial in the second half of 22. For KPL-404, we plan to initiate a Phase II proof-of-concept trial in rheumatoid arthritis by the end of this year. RA is a disease where dose response has been well characterized, and this 12-week trial in RA patients is designed to provide not only PK characterization, but also an early signal of efficacy with chronic administration in a well-described patient population. The results from this study may also enable optionality to evaluate the therapeutic potential of KPL-404 across a range of autoimmune diseases with pathologies believed to be mediated by CD40 signaling. Finally, we're encouraged by the broad potential utility of mavalimumab, which has demonstrated previous positive clinical data across multiple indications, including giant-cell arteritis and COVID-19-related ARDS, which we'll walk through in the next two slides. Turning to slide 13, we believe the treatment of hospitalized patients represents and will remain a significant market opportunity. Since the onset of the pandemic, and despite over 175 million of the U.S. population being fully vaccinated, the rate of hospitalizations has remained multiple fold above the historical average of hospitalizations for influenza, which are around 400,000 cases per year on average. We've seen the limitations of vaccines in terms of hesitancy and availability, resulting in the emergence of variants and the resulting upsurge in hospitalizations even among vaccinated individuals. And the therapeutic options for patients once hospitalized with pneumonia are limited. As evidence of this, the last six months have seen the highest the second highest surge of hospitalizations since the pandemic began, and that's in the context of between 100 million and 175 million Americans having been fully vaccinated. While we hope that vaccinations and antivirals may reduce some of the hospitalizations to come, we fully expect that the rate will remain significantly higher than the seasonal influenza ARDS rate for several years to come, both in and outside the U.S. With that market context, and turning to slide 14, I want to highlight Mavrolimumab in our Phase III trial in COVID-19 ARDS, which is the next program for which we expect to have data. As shown here on this slide, based on our Phase II data, we believe Mavri is differentiated and a potentially best-in-class therapeutic for patients with COVID-19-related ARDS. As plotted here, either looking at absolute or relative mortality benefit versus other published data in the hospital setting, Mavrolimumab could end up being positioned strongly in the market if our phase two data are confirmed in phase three. In April, we reported data from the phase two portion of the study showing that day 29 mavalimumab reduced the risk of death by 61% in hospitalized non-mechanically ventilated patients versus placebo. And in August, we reported that overall survival in this same non-mechanically ventilated cohort of patients was carried out through day 90. Those results demonstrate the persistence of the substantial mortality reduction over time thus confirming and extending the previously reported day 29 data. This effect of prolonged outcomes is also consistent with the prolonged pharmacokinetics of the single administration of maverillimumab, which had been given on day one. Currently, we're focused on completing our phase three trial of maverillimumab and COVID-19-related ARDS, and we expect data in the first quarter of 22. With that, I'll now turn the call over to Mark to cover the third quarter financials.
spk08: Thanks, Evan. Good morning, everyone. Today, I'm going to walk through our financial performance for the third quarter of 2021 and review our guidance. You can find our detailed financial information in today's press release, and I'd like to call your attention to a few items. First, third quarter revenue was $12.1 million, driven primarily by sales of Arculus and Recurrent Pericarditis, which more than doubled sequentially, as well as stronger-than-anticipated initial market access with greater than 190 million lives already covered in the United States. Second, based upon execution to date and strong third quarter sales, we expect total ARCLIS net revenue of between $16 and $17 million in the fourth quarter of this year. Third, as a reminder, Conixa is responsible for the sales and distribution of ARCLIS for the approved indications in the United States, including CAPS and DERA, and evenly splits profits on sales with Regeneron. When profitable, collaboration profit sharing will be reflected as a separate line item within operating expenses. In the third quarter of 2021, we did not make a collaboration profit sharing payment. Lastly, net loss for the third quarter of 2021 was $30.5 million compared to $43.8 million for the same period last year, and we ended the third quarter of 2021 with cash reserves of approximately $200 million which we continue to expect to fund our current operating plan into 2023. And with that, I'll turn the call back to Sanj for closing remarks.
spk02: Thanks, Mark. Turn to the last slide, which is slide 18. At Connexa, we are focused on building the maximum value across our portfolio. It's a very exciting time for the company. We continue to maintain a strong start with the launch of Arclist in recurrent pericarditis. The positive feedback we continue to receive from physicians and patients validates the need for this therapy. As I mentioned previously, we are energized by our progress across our portfolio, and we believe that we're well-positioned to execute throughout this year and beyond. We are encouraged by the broad utility of Maverick, seen to date in COVID-19 and GCA, VIXA and peregrine nodularis, and KPL's 404th potential in a range of autoimmune diseases. Importantly, as Mark mentioned, we are very well capitalized, and we have cash reserves of $200 million that are expected to fund our current operating plan into 2023. And with that, I want to thank you all for your time today. I'll turn the call back to the operator.
spk07: Thank you, sir. As a reminder, to ask a question, you'll need to press star 1 on your telephone. To answer your question, please press the pound key. Stand by as we compile the Q&A roster. Our first question comes from Anupam Rama of JPMorgan. Your line is open.
spk11: Hey, guys. Thanks so much for taking the question, and congrats on the quarter. So you guys noted that two-thirds of prescriptions for ARCLIS are being written for 12 months. For the other one-third, what type of duration are the prescriptions being written for, and are there any trends on the patient type that are getting a 12-month prescription versus another duration prescription?
spk12: Thanks so much.
spk02: Ross, do you want to take that?
spk03: Yeah, very happy to. Thanks very much for the question. Nice to speak to you again. So two-thirds of the patients had prescriptions for 12 months duration, which we were very pleased to see that because it's a good insight into how physicians are thinking about the duration of therapy. For the remaining one-third, I mean, it was obviously not 12 months. So it really comes down to physicians and how they are expecting to see patients again in their follow-up clinics. So outside of those two-thirds, there will be prescriptions there that will be for three months or be for six months. that doesn't necessarily kind of interpret into what they expect the duration of therapy to be, but could moreover be, you know, expecting to see the patient again, kind of reassessing from the baseline and really understanding the treatment duration from there and just making sure that they have that follow-up with the patient, particularly as physicians are recently new to ARCLIS. Many of these physicians are prescribing for the first time, so they might want a kind of a closer patient follow-up that may happen in the longer term. So hopefully that answers that part of it. In terms of patient trends and patient types, I think at the moment it is such low numbers in the early stages of launch that it's difficult to kind of correlate which patients are getting what disease, which duration. So I think that's kind of difficult to answer right now. I'm not sure there is a correlation there, but broadly speaking, we see two different types of patients. We see patients coming through that are clinically stable, so that patient's either coming from our long-term extension study or they're coming from chronic steroids and then we see patients that are acutely symptomatic really suffering from the disease and really seeking a targeted treatment so that's kind of two main categories of patient glucose that we're seeing but of course the duration question even though that's what's being prescribed doesn't necessarily mean that that's what the actual eventual duration is going to be the duration of treatment ultimately will depend on the duration of the disease and also where patients are in the disease course as well. What we do know is that continued treatment results and continued treatment response, and if you stop patients too early into therapy, there's always the risk that they will rebound and suffer from symptomatic disease once again. So we probably need more time to kind of tell what the actual eventual average duration is going to be in the midterm and look forward to being able to report on that in time to come.
spk12: Thanks so much for taking our questions.
spk07: Thank you. Our next question comes from Paul Choi, Goldman Sachs. Your line is open.
spk13: Thank you very much for taking our questions, and let me add my congratulations on the quarter as well. First question is on commercial. With regard to as you go in to see doctors here, can you maybe just comment on you know, what factors are being cited as, you know, potential hesitancy to get RP patients onto ARCALIST? Is it primarily just access or reimbursement, or are they looking for any other particular pieces of information or clarifications?
spk03: So, I'm happy to take that question as well. Hi, Paul. Thank you very much for that. So, In terms of the headwinds or barriers or hesitancy there for patients to prescribe, I mean, this is for doctors to prescribe. This is just, you know, still relatively early on in the launch. So it will be a first experience for many of the physicians. And I think that probably goes into the previous comments about wanting to see patients again and follow up and see how they're doing on the early stages of treatment. Outside of that, we don't necessarily see hesitancy from healthcare professionals, it's just more of waiting to see the appropriate patients. Of course, this is a rare disease and a flaring disease, so we need to do a lot of education and make people aware of this targeted treatment and the first and only treatment that's approved now for recurrent pericarditis and we're having very successful meetings with physicians and when patients do come through, we think we continue to see the uptake. Access and reimbursement is always a question for physicians, particularly when a drug is reasonably new on market. But what we've seen so far in the payer side of things is really quite successful approval rates. As we mentioned, we still have more than 90% of all completed cases. And now that we have payer coverage in place much more broadly now with more than 190 million lives covered across the U.S., hopefully that will also provide a lot of confidence for physicians as well as speed up the time through to approval and get patients onto therapy as quickly as possible.
spk13: Thanks, Rox. That's helpful. And then I think this question is on the pipeline, so maybe for Evan, just I don't know if I missed it on the slides here, but can you maybe just update us on, you know, what is the status of the Phase III plans for MAVERI and GCA, you know, timing and trial initiation and so forth, and trial design? And then also, could you maybe Help us understand how you're thinking of potential development here and thinking about the trial in the context of Novartis recently announcing positive Phase 2 data for their IL-17 cecukinumab. Thank you very much.
spk02: Thanks, Paul. This is Sanj. Maybe Chris will be better directed to John, but I'll make a few comments. Obviously, we're very pleased with the Phase 2 results that we had in GCA and really showed a potential for true differentiation there. You know, we've not disclosed or commented on our next steps immediately in terms of timing for GCA, but John can give you an idea as to what we've disclosed in the past and potential trial designs. So, John, over to you.
spk04: Sure, happy to do that, and nice to talk with you again. With regard to the design, I think what we've discussed before and what we've said we've discussed with the agency is that with the positive Phase II results, In the trial, there was a 26-week trial that included those new onset of relapsing refractory patients. The design of the phase three, you know, it could be as simple as a single phase three clinical trial being pivotal for moving forward with a BOA. And the idea there is to make sure that we have replication of data as well as a sufficient safety database with the 52 weeks of exposure according to ICH guidelines. And then regarding the cecukinumab data, yes, we're aware of the data and the recent presentation of the data. And, you know, they do appear to be a positive result, which is always good for patients. We believe that navrolimumab, by targeting both Th1 as well as Th17, driven disease, especially the importance of GAMI interferon, which is a Th1 cytokine, and the pathophysiology of the disease could still be differentiating for malvalimumab. Of course, that will depend upon the clinical results, but we're confident in our program going forward.
spk02: I think we're having some technical difficulties there. Should we go on to the next question, operator? You're still there?
spk07: Yes, thank you. And next we have Jeff Mecham of BOA. Your line is open.
spk10: Good morning, everyone. This is Jason on for Jeff. Thanks so much for taking our question and for the great quarter. A question on the payer dynamics for a lot of that, if you will. Can you help us understand kind of the current gross to net and where things are moving or at least evolving? You know, to what extent was there patient assistance and how is that changing? And what are your expectations moving forward? And then if I may, on the patient disposition, you know, were the majority of patients that were treated, were these patients who were transitioning over from the clinical studies, were they sort of in the wings? You know, with these heavily refractory patients, somewhat new, any sort of color there would be very helpful. Thanks so much.
spk02: Jason, hey, this is Sanj. Maybe I'll make an opening comment, and then Ross or Mark can jump in. But obviously, we're still in the early stages of launch, and as you can expect, growth to net is quite fluid at this stage. And so we aren't providing any specific guidance or analysis on that. But I'll hand over to Ross and see if he wants to be a bit more effusive, but that's where I'm at.
spk03: Yeah, I think you're absolutely correct, Sanj. So we're not providing any specific guidance moving forward on the gross to net side and free goods. I guess the commentary that I can provide on that to help a little bit is that in Q3, we did benefit from a stronger than expected commercial payer mix, meaning a higher percentage of patients in the commercial insurance payer bucket opposed to government insurance, leading to less statutory discounts. discounts, so that was some favorability in Q3 related to that, and also with lower copay utilization as well, meaning that we launched part of the way through the year in Q2, and actually what we found is that many of the patients have already reached their copay maxes prior to their Arculus prescriptions. support there around the co-pay and what we actually expected prior to launch as well. So, of course, this is very fluid at the time of launch. I'm sure things will season and normalise as the future quarters go on. I think it's important to say that our Q4 guidance takes into account the early launch experiences and trends that we've seen, so we're confident in providing that guidance. In terms of free goods, patient affordability and access is incredibly important to us under Connexa One Connect, our patient services program. We do have different offerings for eligible patients via patient assistance program, bridge for people who may be in between, insurers and also a quick start program as well to help patients gain access through whilst they're waiting for coverage determination for eligible patients. We're very keen on making sure that's available to patients as much as possible. But also, it's worthwhile mentioning that the free goods are actually captured under our sales and marketing line in SG&A, opposed to gross to net. On the patient disposition part, the long-term extension transition really happened in the first quarter of launch, post the Q3. So really we've seen that and what we announced in the prior earnings release is that around 70% of the US patients on the long-term extension moved across to commercial coverage and commercial drug. So that's really already happened, so in Q, three and beyond now. This is new patients coming through to have our kids prescribed for the first time. We continue to be very focused on the 14,000 patients. There's refractory, the multiple relapsing, and the steroid dependency patients. That's a core focus of our field-based team and everything that we do from a digital marketing perspective as well. but we're also cognizant that the broad label that we achieved at the time of approval from the FDA actually allows physicians the flexibility to prescribe where they really think it's going to help patients the best in recurrent pericarditis. So we continue to be focused on those patient groups. I guess it's probably too early to comment on exactly how many patients there are within each of the buckets and so on. We're just in the early stages of launch, but very pleased with how it's being received out in the field, both with physicians and also payers and the number of patients. And we're very happy that we now have more than 200 physicians that have prescribed Arculus since the time of launch, which is a doubling of the first quarter launch numbers.
spk10: Got it. Thank you so much.
spk07: Thank you. And we have David Neeringarten of Wedbush. Your line is open.
spk01: Hey, thanks for taking the question. I had one, two actually, one on the patient, you know, as the patients are coming in for Arcalist in recurrent pericarditis, is there any information on kind of meantime since recurrent pericarditis, you know, diagnosis. I'm curious if the patients coming in are really long-term patients or are you starting to see some trends towards, you know, patients who, you know, have been on therapy for a shorter period of time, other therapies for a shorter period of time. And then my second question is on VIX, just on the recruiting of the phase 2B, is there any Is there any slowdown there? Are you on pace? How is that study going in the current environment for patient recruitment? Thanks.
spk02: Thanks, David. Ross, do you want to take a crack at starting that, and I can always jump in, or me or John can jump in for the VIXR?
spk03: Yeah, very happy to. Hi, David. Thanks very much for the question. So in terms of the the time of disease that patients have had when they get prescribed Arculus. We really are not providing any metrics on that yet. It's been at the very early stage of launch. We'll see if that changes as time goes on. But I guess the best marker that I can provide right now is maybe two data points. One is the natural history of recurrent pericarditis, where we see that that shows a mean duration of recurrent pericarditis of around two years. And then when you look at the more kind of severe, if you like, patient population, like what we saw in the Rhapsody study, the mean duration for those patients had already been 2.4 years. And that was on entry into the trial. So, of course, it's highly variable depending on the patient type. And that really, you know, plays into our messaging around the duration associated. disease as well and wanting to make sure patients have adequate duration to support through the underlying auto information that they're ultimately suffering from.
spk02: Does that cover your question, David? Yeah, it does. Thanks. Yeah, and maybe I'll start on Vixen. John, feel free to jump in. But for Vixen and Mab, obviously, as I said, we're well on the way for our dose-ranging phase 2b study, which we've said we expect data in the second half of next year. You know, we continue to believe that peregrine aleris is an area of significant unmet need, and it's obviously a devastating disease, and currently no approved therapies. So That's obviously the backdrop. The Phase 2b study is a two-year global study driven by, you know, the 16-week time point, which is the primary key efficacy endpoint. So, you know, I can say this point is enrollment is ongoing in the U.S., and we are starting up in Europe and Asia. And we expect to have data in the second half. But, you know, we tend to execute very well. And I think maybe, John, if you've got any comments on the landscape or anything else on the trial.
spk04: No, Sanjay, I think you hit the nail on the head there in terms of the trial design. Maybe one last point about the endpoints. The primary endpoint is a 16-week endpoint, as you mentioned, driven by worst-itch NRS. And then importantly also, as a secondary efficacy endpoint, is IgA 0 to 1 attainment or clearer, almost clearer from the lesion side, given the data that we saw in the Phase 2a program. which showed rapid reductions in worst-age NRS as well as rapid resolution of lesions.
spk01: Got it. Thank you.
spk07: Thank you. And next we have Lisa Baco of Evercore. Your line is open.
spk09: Hi. Thanks for taking the question and a great quarter. Two questions for me. The first one just on Rolano said, like, how are you thinking about now what the duration of therapy is going to be. And it's just helpful when we think about projecting, you know, beyond 2021. I know there's a comment here that at the one-year anniversary of the long-term extension, the median duration was 20 months, which is quite long. You now have, you know, prescriptions being written for 12 months. This is certainly beyond the kind of six to nine months that was the initial deadline. kind of, you know, range of thoughts for duration. So is your thinking on duration evolving from six to nine months? How would you help us think about that as we think about, you know, 22 and beyond?
spk02: Over to you, Ross.
spk03: Yeah, thank you, Sanjana. Hi, Lisa. Thanks very much for the question. Now, regarding duration, I guess we're still at the early stage, so it's difficult to know what the eventual duration is going to be. I wouldn't say we're necessarily moving away from what we discussed previously, but just acknowledging that there are some unknowns, particularly as we go into Q4 now, when we have a meaningful number of patients who will actually be reaching the six- to nine-month mark. So I think Q4 is going to be helpful in telling around the potential duration of that time point that you mentioned. But outside of that, as we said, really, it's dependent upon the disease, where the patients are in the duration of the course of the disease. You rightly said that we have two insights right now. One of those is the clinical trial insights of the long-term extension and the point there that we had on One of the slides that you'll remember when we closed out the randomized withdrawal portion of their phase three study, patients had the opportunity to go into the long-term extension portion of the study, and 74 out of 75 of those patients decided to continue on therapy. So remember, the randomized withdrawal was a median of nine months. Long-term extension is up for an additional 24 months depending on the physician and patient requirements. And earlier this year, we had a snapshot look at the one-year anniversary of the start of the long-term extension study, and that showed that the median duration at that time point was 20 months in duration. The second insight is really the real-world one that we've mentioned, around two-thirds of the prescribers write in for 12 months, which just gives you maybe somewhat of an indication on how physicians are thinking about it and the patients that they're seeing. But ultimately, it's going to depend on where they are in the disease course, as well as the willingness for patients to stay on a weekly regime therapy, as well as also the payer approval duration as well. So I think there's a lot of uncertainties there. Obviously, kind of hopefully that provides you a little bit of an insight into our thinking on it. I wouldn't say right now that we're moving away from what we've said previously, but time will tell.
spk09: Now, just as a follow-up to that, what is it, like, what are you seeing? I don't know if you've done any, you know, kind of market research on this, but the trigger for stopping therapy for physicians.
spk03: Yeah, so we haven't provided anything on that right now. John, I don't know whether you want to take over on that point and provide any extra context around that. ceasing treatment through kind of MRI, some of the academic work that's taken place around that, which might help. But outside of that, we haven't shared anything else.
spk04: Yeah, no, sure, happy to help out. And Lisa, nice to speak with you again. Right, so you raise an interesting question, which is, you know, how do physicians monitor patients, you know, understanding, you know, as Ross said, that this is a, you know, it's a longstanding disease, right? And the epidemiology points to, you know, several years of duration, right? And so, you know, you raise an interesting question, which is how does a physician know that when they're, you know, treating a patient chronically and they're doing well, you know, that the underlying, whether or not the underlying autoinflammation has resolved and it's safe to withdraw therapy. And I think that's really where the clinical trials data are helpful because it showed that, you know, continued treatment resulted in continued clinical response, as well as the fact that if the underlying disease is still present, premature cessation of treatment is and it really unmasks the underlying disease and causes or results in pericarditis recurrence. So in terms of some of the markers that the physician has, they really, it's difficult to kind of look at a patient clinically and reach that conclusion. So there are two pieces of information that at least some of the expert cardiologists are using. The first one is to look at the patient at the time that therapy is initiated, let's say Rolanoceph therapy is initiated, and you see kind of where they are in their disease course and how long their disease lasts. has lasted up until that point, and the severity of the disease in terms of the density of the number of recurrences as well as some of the associated comorbidities. That's one approach of looking at it at baseline. Another approach is to look at the patient while on therapy, and their imaging technologies have been shown to be helpful. Again, we've shown data on this point as well from the Cleveland Clinic has shown data both from the Phase II study as well as the Phase III study. And what that shows is that there's a phenomenon called delayed hyperenhancement, which is a neovascularization of the pericardium. And that shows basically a substrate that can support inflammation. And when that delayed hyperenhancement, as it's called, is present, that could be an indicator of the fact that the underlying autoinflammation is still present. And so what the data have shown is that cessation of therapy was associated with a higher burden of recurrence. And so those are the two factors that are, you know, currently available to clinicians to help, you know, define whether to continue with therapy. So I hope that's some helpful insights.
spk09: Very helpful. Thanks a lot. And then just a final question for me on Vixirellumab. I know there was some data recently, it was last week or so, for Dupuy and PN. Maybe you could comment on that and how you see the competitive landscape evolving. As I understand, they They also saw resolution of lesions and a pretty nice NRF score. And are you thinking of that as some kind of temporary benchmark, or how should we think about the dupy data in the competitive landscape? Thanks.
spk04: Sasha, would you like me to jump in? Yeah, go ahead. Okay, sure. So we're aware of the data, and what we see with the dupilumab data is that they're pretty much consistent with what we've seen with other data from the dupilumab program, for example, in atopic dermatitis. As you know, dupilumab blocks TH2 inflammatory responses, and then what we saw for atopic dermatitis and what we see also in prurigo nodularis is that there's a bit of a lag time that first the inflammation resolves, which then results in reduction of the interleukin-31 levels. And so over time, we see a reduction in the pruritus scores. And similarly, you know, over the course of the long-term, you know, trial that they showed, you know, there was a gradual resolution of lesions. So I think that, you know, it certainly is a helpful data set to see and consistent with what we've seen before. We believe Vixorilumab is differentiated in this space because vixerolamab is blocking the action of interleukin-31 directly. And so that's the reason why we saw a much more rapid and more profound reduction in pruritus scores even in the early weeks after initiation of therapy. And if you'll remember from our phase 2a data, we saw nearly a third of patients had achieved clear or almost clear. That was statistically significant at week eight, but it was also significant at week six with early curve separation as early as week four. So I hope that's a helpful comparison of the data understandings across trials.
spk09: Great. Thank you very much.
spk07: Thank you. And I see no further questions in the queue. So speakers, I will return the call back to you for closing comments.
spk02: Thanks, Operator. So thanks, everybody, for joining in today. Obviously, a great quarter. A lot more to do. We're very excited about both Arculus as well as the pipeline, and we're going to crack on. Thank you. Bye-bye.
spk07: That concludes today's conference call. Thank you all for participating. You may now disconnect, and have a pleasant day.
spk02: Thanks, Operator.
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