Q1 2024 Kiniksa Pharmaceuticals Ltd Earnings Call
Operator: Good day, and thank you for standing by, and welcome to Kiniksa Pharmaceuticals' first quarter 2024 earnings conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Rachel Frank, head of investor relations. Please go ahead.
Yes.
Speaker Change: Good day, and thank you for standing by and welcome to <unk> Pharmaceuticals Pharmaceuticals first quarter 'twenty 'twenty four earnings conference call. At this time all participants are in a listen only mode. After the speaker's presentation there'll be a question and answer session to ask a question. During this session you will need to press star one on your telephone you didn't hear an automated message.
You're back in your hand is raised to withdraw your question. Please press star one again.
Speaker Change: Be advised that today's conference is being recorded I would now like to hand, the conference over to your speaker today, Rachel Frank head of Investor Relations. Please go ahead.
Rachel Frank: Thank you, Operator. Good morning, everyone, and thank you for joining Kiniksa's call to discuss our first quarter 2024 financial results in Recent Portfolio Execution. A press release highlighting these results can be found on our website under the Investors section. As for the agenda, our Chief Executive Officer, Sanj K. Patel, will start with an introduction. Ross Moat, our Chief Commercial Officer, will provide an update on our Hercules commercial execution. John Paolini, our Chief Medical Officer, will provide an ABI-PRUD-BART program review, and Mark Ragosa, our Chief Financial Officer, will review our first quarter 2024 financial results.
Rachel Frank: Thank you operator, good morning, everyone and thank you for joining Codexis call to discuss our first quarter 2024 financial results.
Rachel Frank: Your execution.
Rachel Frank: Yes, really highlighting these results can be found on our website under the investors section.
Rachel Frank: Absolutely agenda, our Chief Executive Officer, John cases out there.
Rachel Frank: With the introduction.
Speaker Change: No our chief commercial officer, who will provide an update on our forklift commercial execution.
Speaker Change: John <unk>, our Chief Medical Officer will provide an athlete.
Speaker Change: In my view and Barbara <unk>, Our Chief Financial Officer will review, our first quarter 2024 financial results and finally, Doug will return for closing remarks, I just kick off the Q&A session for whichever just sorry, our chief operating officer will also be on the line.
Rachel Frank: And finally, Sanj will return for closing remarks and to kick off the Q&A session, during which Evan Tesari, our Chief Operating 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 and 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 filings. 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.
Speaker Change: 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 are of such statements and the risk factors can be found on this slide as well as under the caption risk factors.
Our SEC filings. 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 songs.
Sanj K. Patel: Thanks Rachel and good morning everyone. We are very encouraged by the Arclis commercial progress. We've continued to build upon Arclis performance this quarter, marked by reaching an increasing number of recurrent pericarditis patients and growing to a net product revenue of $78.9 million. We continue to see strength across key commercial drivers, including growing prescriber adoption and high physician and patient satisfaction, which has been supported by our focus on frequent engagement with existing and potential prescribers.
Songs: Thanks, Rachel and good morning, everyone.
Songs: We are very encouraged with the commercial progress we continued to build upon the awkward performance. This quarter marked by reaching an increasing number of recurrent pericarditis patients and growing to a net product revenue of $78 $9 million.
We continue to see strength across key commercial drivers, including growing prescriber adoption at high physician and patient satisfaction, which has been supported by our focus on frequent engagement with existing and potential prescribers.
Sanj K. Patel: Importantly, we're also seeing an expanding utilization of Arclis as a steroid-sparing therapy for patients suffering from recurrent pericarditis. Looking to the year ahead, we now expect Arcalist's full-year sales to be between $370-$390 million, and this would represent 63% year-over-year growth in the mid-20s.
Songs: Importantly, we're also seeing an expanding utilization of our place as a steroid sparing therapy for patients suffering from recurrent pericarditis.
Songs: Looking to the year ahead, we now expect <unk> full year sales to be between $370 million to $390 million and this would represent 63% year over year growth at the midpoint.
Sanj K. Patel: In terms of our pipeline, we recently announced plans to initiate a Phase 2b trial with Average Group Pharmacy in Sjogren's disease. This is a debilitating disorder with no current FDA-approved therapy, and we believe Abhi Prabhat has the potential to provide meaningful benefit to patients. Dr. John Paolini, our Chief Medical Officer, will provide additional details about our planned Phase 2b trial, which is expected to initiate in the second half of this year. And with that, I'll now turn it over to Ross to review our commercial execution. Thank you, Sanj.
Songs: In terms of our pipeline, we recently announced plans to initiate a phase II b trial with Abu parts in Shoguns disease.
Songs: This is a debilitating disorder with no current FDA approved therapies.
Songs: We believe <unk> has the potential to provide meaningful benefit to patients.
Songs: Dr. John Paolini, our Chief Medical Officer will provide additional details about our planned phase two b trial, which is expected to initiate in the second half of this year.
And with that I'll now turn it over to Ross to review our commercial execution.
Ross Moat: I want to start by highlighting that the end of Q1 marks the third anniversary of the approval of Alkalys in recurrent pericarditis, and we continue to deliver robust growth and be excited by the future of this franchise. In Q1, Alkalys' Net Revenue was $78.9 million, which is an 85% growth versus Q1 of 2023. This revenue growth also represents strong quarter on quarter growth, especially against the backdrop of Q1 specialty industry growth and a gross net of 13.5%, which was predominantly due to co-pay.
Ross: Thank you so much.
I want to start by highlighting that the end of Q1 marks the third anniversary of the approval of Barclays in recurrent pericarditis and we continue to deliver robust growth and be excited by the future of this franchise.
Ross: In Q1, <unk> net revenue was 78 points 9 million, which is an 85% growth versus Q1 'twenty two 'twenty three.
Ross: This revenue growth also represents strong quarter on quarter, guys, especially against the backdrop of Q1 specialty industry headwinds on our gross to net of 13, 5%, which was predominantly due to copay resets.
Ross Moat: The net revenue growth was in part due to an acceleration in the number of prescribers. Total prescribers of Alkalyst since launch grew to approximately 2,000 at the end of Q1, making it the largest quarter-on-quarter growth since launch. Additionally, we continue to observe robust underlying fundamentals across our commercialization, including greater than 90% payer approval of completed cases, a total average duration of therapy of 23 months, and high physician and patient satisfaction with our high-quality, Recurrent pericarditis is a debilitating, rare, flaring disease where patients are widely dispersed across the country.
Ross: The net revenue growth was in part due to an acceleration in the number of prescribers. So prescribers of uplift since launch grew to approximately 2000 at the end of Q1, making it the largest quarter on quarter growth since launch.
Ross: Additionally, we continue to.
Ross: The robust underlying fundamentals across our commercialization, including greater than 90% payer approval of completed cases, a total average duration of therapy is 23 months and highest physician and patient satisfaction with the Oscars.
Ross: Yes.
Ross: Recurrent pericarditis is a debilitating rare flaring disease, where patients are widely dispersed across the country since our eclipse approval as the first and only FDA approved drug for this disease, we've been making great Boston rights through our field teams and our marketing strategy to educate physicians.
Ross Moat: Since Alkalyst's approval as the first and only FDA-approved drug for the disease, we've been making robust inroads through our field teams and our marketing strategy to educate both physicians and patients about the disease. We've seen increasing acknowledgement that interleukin-1, alpha, and beta are the underlying drivers of the disease.
Ross: And patience on the disease.
We've seen increasing acknowledgment that interleukin one alpha and beta are the underlying drivers of the disease and once patients become recurrence they require a targeted treatments to address the disease directly.
Ross Moat: And once patients become recurrent, they require a targeted treatment to address the disease directly. As a result, the total prescriber base has continued to grow every quarter since launch, and as physicians gain positive prescribing experience and witness the impact Arclis can have on their patients, more and more physicians are becoming repeat prescribers. In fact, in Kyuwon, greater than 40% of all new prescriptions were written by healthcare professionals who are repeat prescribers
Ross: As a result, the total prescriber base has continued to grow every quarter since launch and as physicians gain positive prescribing experience and witnessed the impact uplifts can have on their patients more and more physicians are becoming repeat prescribers.
Ross: In fact in Q1 greater than 40% of all new prescriptions were written by health care professionals, who are repeat prescribers.
Ross Moat: We are making solid progress towards our ambition of Arconis becoming the standard of care in recovered pericardial cancer. For the next slide, I'll hand the call over to Dr. John Paolini, our Chief Medical Officer, to share some of the latest information coming from our Resonance Registry describing the evolution of recurrent pericarditis management since launch.
Ross: We are making solid progress towards our ambition of Barclays to becoming the standard of care and recover pericarditis.
John F. Paolini: The next slide I'll hand, the call over to Dr. John <unk>, our Chief Medical officer to share some of the latest information coming from our residents registry describing the evolution in recurrent pericarditis management since launch.
John F. Paolini: Thanks, Ross. We're very excited to share some insights we've gained from our residents registry and that we recently shared at the American College of Cardiology. The data show a paradigm shift in RP management amongst cardiologists at the 21 participating centers in the U.S. away from the steroid-based 2015 European Society of Cardiology guidelines and toward a steroid-sparing approach using IL-1 pathway inhibition. Amongst these registered patients with a median 3-year RP disease duration, IL-1 pathway inhibition use increased to 25% of medication patient years in 2023, with alkalist use driving this pattern.
John F. Paolini: Thanks Ross.
John F. Paolini: We're excited to share some insights we've gained from our residents registry and that we've recently shared at the American College of Cardiology. The data show a paradigm shift in RP management amongst cardiologists is the 21 participating centers in the us away from the steroid based 2015 European Society of Cardiology.
John F. Paolini: Airlines and towards a steroid sparing approach using IL one pathway inhibition.
John F. Paolini: Amongst these registry of patients with a median three year RP disease duration IL, one pathway inhibition use increased to 25% of medication patient years in 2023 with Arco is to use driving this pattern.
John F. Paolini: Also, amongst patients who had failed aspirin, NSAIDs, and colchicine and intensified treatment, the proportion of patients who transitioned to Rolanacept has increased year on year, with commensurately fewer patients transitioning to corticosteroids, such that by 2023, 65% of transitions were made to Arcalist, with a 2-to-1 preference over corticosteroids. These data affirm the Back to you. Thanks, John.
John F. Paolini: Also amongst patients who had failed aspirin nsaids colchicine and intensified treatment the proportion of patients who transition to a lot of such as increased year on year with commensurately fewer patients transitioning to corticosteroids such that by 2023, 65% of transitions for May.
John F. Paolini: To archivist with a two to one preference over corticosteroids. These data affirm the evidenced based adoption and growth of the steroids sparing paradigm by RP focused cardiologists.
Back to you.
Ross Moat: These compelling new data from pericarditis-focused cardiologists mirror our promotional messaging that recurrent pericarditis is an interleukin-1 alpha and beta driven disease. Alkalyst addresses the root cause of..., and should be utilized prior to corticosteroids.
Speaker Change: Thanks, Jeff.
Speaker Change: These compelling new data from pericarditis focused cardiologists mirror, our promotional messaging that recurrent pericarditis is an interleukin one alpha and beta driven disease.
Speaker Change: <unk> addresses the root cause of the disease and should be utilized prior to corticosteroids.
Ross Moat: Our Q1 net revenue growth signifies strong underlying business fundamentals, and with only 9% of the target population addressed as of the end of 2023, we have a significant opportunity ahead. In Q1, we delivered robust growth that broke through the typical Q1 industry headwinds. As such, we're pleased to increase our revenue guidance for 2024 from $360 to $380 million to $370 to $390 million. And with that, I'll hand it back to John to discuss Abiproof Arts. John.
Speaker Change: Our Q1 net revenue growth signifies strong underlying business fundamentals and with only 9% of the target population addressed as of the end of 2023, we have a significant opportunity.
Speaker Change: In Q1, we delivered robust growth that broke through the typical Q1 industry headwinds as such we are pleased to increase our revenue guidance for 2020 for some $360 million to $380 million.
Speaker Change: $378 million to $390 million.
Speaker Change: With that Ah ha.
Speaker Change: And it back to Joe to discuss AB approvals.
John F. Paolini: As Sanj mentioned, and as we outlined in our previous announcement, several factors contributed to our decision to move forward with Abbey Prubart and Sjogren's disease. Importantly, Sjogren's disease is a debilitating disease currently with no FDA-approved therapy. Second, there is substantial external proof of concept that inhibition of the CD40-CD154 co-stimulatory interaction could be an efficacious therapeutic approach for Sjögren's disease. Additionally, the totality of the Phase II Abiprobarc data we've generated, including highly statistically significant reductions in rheumatoid factor of approximately 40 percent across all three dose regimens, demonstrate clear biological activity of the molecule and thus bolster our confidence in the potential efficacy insurance for the treatment of rheumatoid factor in phase 2b with either bi-weekly or monthly subcutaneous doses.
Joe: Thanks, Ross as Andrew mentioned and as we outlined in our previous announcements several factors contributed to our decision to move forward with Abbvie Pru bear and sugars disease Importantly, shoguns disease is debilitating disease currently with no FDA approved therapies.
Joe: There is substantial external proof of concept that inhibition of the CD 40, CD 154, co stimulatory interaction could be an efficacious therapeutic approach for sugar in cities additions.
Joe: Additionally, the totality of the phase III abbvie prove our data we've generated including highly statistically significant reductions in rheumatoid factor of approximately 40% across all three dose regimens demonstrate clear biological activity of the molecule and thus bolster our confidence in the potential.
Joe: See insurance disease in phase <unk> with either biweekly or monthly subcutaneous dosing.
John F. Paolini: Understanding that there are other assets in development for Sjögren's disease, we believe Abby Prubart has the potential to demonstrate comparable efficacy but with a more convenient route of administration, a profile which could potentially represent a compelling and differentiated option for patients. With that in mind, we are planning to initiate, in the second half of 2024, a randomized, double-blind, placebo-controlled Phase 2b trial designed to evaluate the treatment response to chronic subcutaneous administration of abicrubart in patients with Sjogren's disease.
Joe: Understanding that there are other assets in development for <unk> disease, We believe <unk> has the potential to demonstrate comparable efficacy, but with a more convenient route of administration.
Joe: Our profile, which could potentially represent a compelling and differentiated option for patients.
Joe: With that in mind, we are planning to initiate in the second half of 2020 for a randomized double blind placebo controlled phase <unk> trial designed to evaluate the treatment response of chronic subcutaneous administration of <unk> in patients with <unk> disease.
John F. Paolini: The intended trial design begins with a placebo-controlled portion that will randomize approximately 201 patients in a 1-to-1-to-1 ratio to receive Abiprobar 400 mg subcutaneously biweekly, 400 mg subcutaneously monthly, or placebo, over a period of 24 weeks. The primary efficacy endpoint will be changed from baseline versus placebo in the ULAR Disease Activity Index, called SDI, at week 24. Subsequently, we plan for patients to enter a long-term extension phase in which all participants will receive active treatment for an additional 24 weeks. I will now turn the call over to Mark to discuss the first quarter financials. Mark?
Joe: The intended trial design begins with a placebo control portion that will randomize approximately 201 patients in a one to one to one ratio to receive <unk> at 400 milligrams Subcutaneously Bi weekly 400 milligrams subcutaneously monthly or placebo.
Joe: Over a period of 24 weeks the primary efficacy endpoint will be change from baseline versus placebo in the <unk> disease activity index called S. Die at week 24.
Joe: Subsequently, we planned for patients to enter a long term extension and which all participants will receive active treatment for an additional 24 weeks.
Joe: I will now turn the call over to Mark to discuss the first quarter financials Mark.
Mark Ragosa: Thanks, John. Our detailed first quarter 2024 financial results can be found in the press release we issued earlier this morning. Over the next couple of minutes, I'd like to call your attention to a few items on this slide. First, total revenue in the first quarter of 2024 was $79.9 million, driven by Arclis Net Product Revenue, which grew 85% year over year to $78.9 million. Second, Arklis Collaboration operating profit in the first quarter grew 142% year-over-year to $40.2 million and primarily drove collaboration expenses of $20.8 million.
Mark: Thanks, John our detailed first quarter 2024 financial results can be found in the press release, we issued earlier this morning.
Mark: Over the next couple of minutes I would like to call your attention to a few items on the slide.
Mark: First total revenue in the first quarter of 2024 was $79 9 million driven by Arcalis net product revenue, which grew 85% year over year to $78 9 million.
Mark: Second Barclift collaboration operating profit in the first quarter grew 142% year over year to $40 2 million and primarily drove collaboration expenses up $28 million.
Mark: Third higher cost of goods sold and collaboration expenses.
Mark: All of which are largely driven by ARCUS revenue growth as well as the advancement of Abbvie prove our development and investment related to Arcalis commercialization drove year over year operating expense growth in the first quarter.
Mark Ragosa: Third, higher cost of goods sold and collaboration expenses, both of which are largely driven by arc-less revenue growth, as well as the advancement of Abbey Prubart development and investment related to Arkless commercialization through a year-over-year operating expense growth in the first quarter. Fourth, our net loss in the first quarter was $17.7 million compared to $12.3 million in the first quarter of last year. And lastly, our cash balance at the end of the first quarter was $213.6 million.
Mark: Fourth net loss in the first quarter was $17 7 million compared to $12 3 million in the first quarter of last year and lastly, our cash balance at the end of the first quarter was $213 6 million.
Mark: This balance reflects net cash flow of $7 2 million inclusive of the $10 million development milestone received from Genentech in the first quarter that was previously recognized as revenue in the fourth quarter of 2023.
Mark: We continue to expect cash reserves.
Mark Ragosa: This balance reflects net cash flow of $7.2 million, inclusive of the $10 million development milestone received from Genentech in the first quarter that was previously recognized as revenue in the fourth quarter of 2023. We continue to expect cash reserves as well as strong commercial execution and financial discipline to support our current operating plan, which we expect to remain cashflow positive on an annual basis. And with that, I'll turn the call back to Sanj for his closing remarks.
Mark: Well, our strong commercial execution and financial discipline to support our current operating plan, which we expect to remain cash flow positive on an annual basis.
Speaker Change: And with that I'll turn the call back to <unk> for closing remarks.
Thanks, Mark as you've heard we remain committed to advancing all areas of our business in the year ahead.
Speaker Change: Accordingly, we expect our robust commercial performance to meaningfully contribute to our strong financial position.
Speaker Change: And our ability to drive growth across the business.
Sanj K. Patel: Thanks Mark. As you've heard, we remain committed to advancing all areas of our business in the year ahead. Importantly, we expect our robust commercial performance to meaningfully contribute to our strong financial position and our ability to drive growth across the business. Based on the current operating plan, which includes advancing ABIPROVAR through phase 2 development in children's disease, we expect to remain cash flow positive on an annual basis. We're excited by the opportunity to continue to provide life-changing medicines for patients, and we believe we're in a strong position to deliver on our goal. I do want to thank all of you for your time today, and I'll now hand it back to the operator for any questions.
Speaker Change: Based on the current operating plan, which includes advancing IV prove outs through phase III development in <unk> disease, we expect to remain cash flow positive on an annual basis.
Speaker Change: We're excited by the opportunity to continue to provide life changing medicines for patients and we believe we are in a strong position to deliver on our goals.
Speaker Change: I do want to thank all of you for your time today and I'll now hand, it back to the operator for any questions.
Speaker Change: And thank you as a reminder to ask a question. Please press star one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one again, please standby, while we compile the Q&A roster.
Speaker Change: And one moment for our first question.
Speaker Change: Okay.
Speaker Change: Okay.
Speaker Change: And our question comes from our new Palm Rama from JP Morgan. Your line is now open.
Operator: Thank you. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again.
Anupam Rama: Hi, guys. Thanks, so much for taking the question and congrats on the quarter.
Anupam Rama: For arc list it seems like the physician prescribers continue to grow here how much do you attribute this to the expanded sales force and getting to those kind of next tier of positions versus deeper penetration into some of your top centers and existing academic center relationships. Thanks, So much.
Operator: Please stand by while we compile the Q&A roster and one moment for our first question. And our first question comes from Anupam Rama from J.P. Morgan. Your line is now open.
Anupam Rama: Yeah. Thanks, Andy Pam This is Ralph Thank you very much for the question. So suddenly we did go into 2024 with around 85, Representatives, which gave us a boost in the coverage that we could achieve across the U S. So we went from calculate about 6000 positions up to 11000.
Anupam Rama: Hi guys, thanks so much for taking the question and congrats on the quarter. For Arcalis, it seems like, you know, the physician prescribers continue to grow here. How much do you attribute this to the expanded sales force and getting to those kind of next tier of positions versus deeper penetration into some of your top centers and existing academic center relationships? Thanks so much.
Anupam Rama: Some of it is balancing the larger field team that we have has enabled us to certainly increase the.
Ralph: Health care specialists, we could reach but also the good news top tier high decile doctors that we really focus on at the highest throughput just recurrent pericarditis patients also increase in frequency with it. So we do think that that's an important.
Ross Moat: Yeah, thanks Anupam. This is Ross.
Ross Moat: Thank you very much for the question. We certainly did, you know, go into 2024 with around 85 representatives, which gave us a boost in the coverage that we could achieve across the US. So, certainly some of it is down to the larger field team that we have which has enabled us to certainly increase the breadth of healthcare professionals we could reach, but also within those top tier high decile doctors that we really focus on have the highest throughput as we cover pericarditis patients, also increasing the frequency within those.
Ralph: Elements alone, we just continued execution.
Ralph: But we've always been focused on and the message that we got to deliver the number of patients we've got to help.
Ralph: We still believe there's a huge opportunity ahead of us. So you will see from the 11000 doctors that we target with nalco around 2000 prescribers in total since we all want to say that the airline strategy with a huge headroom ahead uncertainty out to those 2000 prescribers.
Ralph: Target population of the 11, thousands as well so.
Ralph: We've got a long way to go to continue to grow the threat.
Ralph: Guidance at the total prescriber base.
Ralph: As well as repeat prescribing, which can say has remained at 24%.
Ross Moat: So we do think that's an important, important element, along with just continued execution that we've always been focused on and the message that we've got to deliver and the number of patients we've got to help out there. We still believe there's a huge opportunity ahead of us. So you see, from the 11,000 doctors that we target, we've now got around 2,000 prescribers in total since launch. So that alone tells you we've got a huge headroom ahead, and certainly out of those 2,000 prescribers, not all of them are within that target population of 11,000 as well.
Ralph: And ever significantly increase in base sales side lets say.
Ralph: The fact that they contributed about 40% of all the new enrollments that we had within within key accounts.
Ralph: It tells you that the repeat prescribers.
Ralph: <unk> contribution.
Speaker Change: The nature of the business as well so thanks for the question, we're very pleased with where we own the opportunity we have ahead.
Speaker Change: Thanks, so much for taking our question.
And thank you.
Speaker Change: And one moment our next question.
Speaker Change: And our next question comes from Paul Choi from Goldman Sachs. Your line is now open.
Paul Choi: Hi, Thanks, Good morning, congratulations on the good start to the year.
Paul Choi: My first question is for Ross and just with regard to.
Ross Moat: So we've got a long way to go to continue to grow the breadth of prescribing, so the total prescriber base, as well as repeat prescribing, which you can see has remained at 24% of an ever significantly increasing base of total prescribers. So the fact that they contributed around 40% of all Unknown Attendee, Sanj Patel, Liisa Bayko, David Nierengarten, Unknown Attendee, Anupam Rama, Kyuwon Choi, Mark Ragosa, Rachel Frank, Ross Moat, Alexandria Hammond, Paul Choi, Kiniksa Pharmaceuticals Ltd.
Paul Choi: Arcalis patient behavior can you just maybe comment on if you're seeing any trends in terms of patients who discontinue therapy coming back maybe a little faster versus prior quarters, and just just sort of what the messaging on restarting and maintenance therapy has been like and how that's resonated and then I had a bogie.
John F. Paolini: Question for John Activewear, as a follow up.
Speaker Change: Okay, I'll make us thoughts on the Altice, one and then how 'bout cheapo could prove up questions and thank you for that so I think we haven't seen any significant changes in patient behavior from different cohorts.
Speaker Change: Sure.
Speaker Change: The complex of patients about either.
Unknown Attendee: Thanks so much for taking our question.
Speaker Change: The rates at which they stopped therapy or a date with the restarts in the restock rates Interestingly has remained consistent for quite some time now about 45% of all of those patients who stopped therapy come back on to resolve and generally patients are able to restart to pay if they suffer from ongoing since.
Operator: And one moment for our next question. And our next question comes from Paul Choi from Goldman Sachs. Your line is now open.
Paul Choi: Hi, thanks. Good morning and congratulations on the good start to the year. My first question is for Ross, and just with regard to ARCALIS patient behavior, can you just maybe comment on if you are seeing any trends in terms of patients who discontinued therapy coming back maybe a little faster versus prior quarters and just sort of what the messaging on restarting and maintenance of therapy has been like and how that has resonated. And then I had a question for John afterwards as a follow-up.
Speaker Change: Apologize symptomology with tens very often they have left on that prescription payer approval.
Speaker Change: Proven and place sometimes to have stock sale.
Speaker Change: <unk> previously.
Speaker Change: Previously.
Speaker Change: That can vary.
Speaker Change: Simple for patients to be cell therapy, if they do suffer from the disease.
Speaker Change: Lee just acknowledging that this is.
Speaker Change: Chronic disease.
Speaker Change: Most patients with.
Speaker Change: Multiple years.
Speaker Change: For these patients as they start to early Symptomology when it does come back. We just continue to focus on all of education with health care professionals around the natural history of the disease and patients.
Ross Moat: Okay, so I'll make a start on the Oculus one and then hand it back to you, Paul, for the pre-op questions. So thank you for that. So I think we haven't seen any significant changes in patient behavior from different cohorts that we're aware of, different types of patients around either the rate in which they stop therapy or indeed with the restarts. And the restart rate, interestingly, has remained consistent for quite some time now; about 45% of all those patients who stop therapy come back on to restart.
Speaker Change: Patients, who suffer two or more of occurrences.
Speaker Change: Generally has that three years' worth of media.
<unk> therapy, one side of the patient still suffering from the disease at five years out and you may remember from our clinical experience recently from a long term extension portion of our study. The median is two years after those treatments up to three years, so and we've seen the chokes.
Speaker Change: The duration of therapy grow overtime in the commercial setting most recently around 73 months.
Speaker Change: Really continue to focus on the natural history.
Speaker Change: Some patients to stay on therapy.
Ross Moat: And generally, patients are able to restart if they suffer from ongoing symptomology or the symptomology returns. Very often, they have pills left on their prescription, they have their approval in place, and sometimes they'll have stock on hand still from when they were on it previously.
Speaker Change: Expected course of their disease.
Speaker Change: She is a very often multiple years.
Speaker Change: Okay, great. Thanks.
Speaker Change: Thanks for that Ross and then for John as you look at the.
John F. Paolini: Prior RF data and the available preclinical data for our paper Park can you maybe just comment on as you think about your phase III plan for shale grants just what areas you think.
John F. Paolini: Avi might be able to.
Ross Moat: So it's often very simple for patients to restart therapy if they do suffer from the disease continuously. Just acknowledging that this is a chronic disease; for most patients, it's multiple years. So for these patients, if they stop too early, it's likely the symptoms will indeed come back. We just continue to focus on our education with healthcare professionals around the natural history of the disease. And that's where patients that suffer from two or more recurrences generally have three years' worth of median duration of therapy.
John F. Paolini: Evidence of differentiation or what I guess, it gives you a confidence or potential for costs here relative to some of the other assets in the class that may be further along in the clinic. Thank you.
Park: Sure. Thank you Paul I. Appreciate the question, yes, we have confidence in the data that we've generated so far with abbvie prove orange the data from phase one show of course important suppression of the of the mechanism as evidenced by his depression of antibodies formation and then we carry that forward.
Park: Third into the Phase III program, where we saw with all three dosing regimen, so with weekly by weekly and even monthly dosing.
Ross Moat: One third of the patients still suffer from the disease five years out. And you may remember from our clinical experience recently in our long-term extension portion of our study, the median was two years worth of heartless treatments up to three years. So we've seen the total duration of therapy grow over time in the commercial setting, most recently around 23 months, but we really continue to focus on the natural history. And we just want patients to stay on therapy throughout the expected course of their disease, which is, as I say, often multiple years.
Park: Suppression of rheumatoid factor too.
Park: Around 40% that was highly statistically significant and then that translated into clinical outcomes using the desk 28, CRP score. So that's showing us that in a clinical setting we have strong target engagement.
Park: And that's with any of the three dosing regimens with that means then translated forward in terms of let's say differentiation.
Park: Is that we've worked hard on making sure that we have a high concentration liquid formulation that supports chronic subcutaneous dosing and so that ability to view <unk> as a subcutaneous drug rather than as an intravenous drug in these rheumatology diseases, and then to be able to spread out the dosing interval.
John F. Paolini: preclinical data for Ibuprofart, can you maybe just comment on, as you think about your phase two plan for Sjogren's, just, you know, what areas you think Ibuprofart might be able to show evidence of differentiation, or what, I guess, gives you the confidence of potential success here relative to some of the other assets in the class that may be further along in the clinic? Thank you. Sure. Thank you, Paul. I appreciate the question. Yes, we have.
Park: So to test not only by weekly dosing, which is pretty standard, but even to stretch it out to potentially monthly dosing, which would be relatively unique in this space to have monthly subcutaneous dosing to us gives us a lot of confidence as we go forward into the <unk> study that abbvie prove arc has the opportune.
Park: Yes, the potential opportunity to show differentiation across other assets.
John F. Paolini: Sure. Thank you, Paul, and I appreciate the question.
Speaker Change: Great. Thank you.
Speaker Change: And thank you.
Speaker Change: And one moment for our next question.
John F. Paolini: Yes, we have confidence in the data that we've generated so far with Abby Poubart. The data from phase one show, of course, you know, important suppression of the mechanism as evidenced by suppression of antibody formation. And then we carried that forward into the phase two program, where we saw with all three dosing regimens, so with weekly, biweekly, and even monthly dosing, suppression of rheumatoid factor to, you know, around 40%, which was highly statistically significant.
Speaker Change: And our next question comes from David Nearing Garden.
From Wedbush Securities. Your line is now open.
Okay.
Speaker Change: Alright, Thanks for taking the question I had two.
Speaker Change: So maybe following up on the programs kind of competitive landscape.
Speaker Change: I was curious when you considered your main competitor.
Speaker Change: It's a bit of a sub part of that.
How predictive do you think the rheumatoid factor is reduction for symptom relief.
Speaker Change: <unk> and then a quick question on <unk>.
Speaker Change: <unk>.
Speaker Change: Yes.
Speaker Change: It seems obvious but just checking.
Speaker Change: The physician kind of paradigm shifting to ashburn.
John F. Paolini: And then that translated into, you know, clinical outcomes using the DAS 1D8 CRP score. So that shows us that in a clinical setting, we have strong target engagement. And that's with any of the three dosing regimens. What that means, then, translated forward in terms of, let's always say differentiation, is that we've worked hard on making sure that we have a high-concentration liquid formulation that supports chronic subcutaneous dosing. And so the ability to give Abiprobart as a subcutaneous drug rather than an intravenous drug in these rheumatologic diseases.
Speaker Change: Maybe could sustain in the frontline.
Speaker Change: Kind of recurrent pericarditis, putting a part a majority of patients on them.
Speaker Change: Arc <unk> is that a fair characterization of the market.
Speaker Change: Yes.
Speaker Change: Yes, Hi, David This is Rob So I guess I'll start with the <unk>, one and then hand.
Speaker Change: So I think.
Speaker Change: CFO.
Speaker Change: Final question.
Rob: So just to summarize I think Thats fair.
Rob: Characteristic I think to say patients that.
Rob: The software team.
Rob: Perry just generally treated with nsaids colchicine as well most of them when they come back and that recurrent patients.
Rob: At the same treatment.
John F. Paolini: And then to be able to spread out the dosing interval, so to test not only biweekly dosing, which is pretty standard, but even to stretch it out to potentially monthly dosing, which would be relatively unique in this space to have monthly subcutaneous dosing. It gives us a lot of confidence as we go forward into the Sherven study that Abby Prubart has the opportunity, you know, the potential opportunity to show differentiation across others.
Rob: But with that longer duration.
Rob: I don't see great focus on patients that were on the second column, so or more making sure that uplift.
Rob: The standard of care choice.
Rob: Those patients who at that time.
Rob: Clearly the COVID-19 patients.
Rob: Suffer from the disease.
Rob: The usual.
Rob: Therapy options really requiring something that targets.
Rob: Yes, it does.
Rob: And as John shared with the residents registry with <unk> starting to see those key physicians that focus.
Operator: And one moment for our next question. And our next question comes from David Nierengarten. From Wedbush Securities, your line is now open.
Rob: Thanks.
Rob: The disease utilizing placed ahead of steroids, which again is exactly the position.
Rob: Right.
David Matthew Nierengarten: Thanks for taking a question. I had two.
Speaker Change: Yes. Thanks.
Speaker Change: Thanks for the question. So we obviously look at the competitive landscape with a broad label.
David Matthew Nierengarten: So maybe following up on the Sjogren's, you know, kind of competitive landscapes. I was curious who you considered your main competitor, and if any part of that, how predictive do you think the rheumatoid factor is for symptom relief in Sjogren's? And then a quick question on Arcalis. I mean, it seems obvious, but just checking, you know, that
Speaker Change: Paul all of the programs currently.
Speaker Change: The studies are producing data.
Speaker Change: Maybe to narrow the answer to your question looking at the CD 40, CD 100 before antagonist class alone there.
Speaker Change: There are three others that have either produce results or are studying.
Speaker Change: Their asset and showcase the reason those would be the.
Speaker Change: The horizon now Amgen molecule developed App.
Speaker Change: Which is currently enrolling in a phase three.
Speaker Change: Study with.
Speaker Change: I'd formulation.
John F. Paolini: Maybe to narrowly answer your question, looking at the CD40, CD154 antagonist class alone, there were three others that have either produced results or are studying their asset in show-based disease. And those would be the Horizon Now from Amgen, which is currently rolling in a Phase 3 study with an IV formulation. There's Iscalimab from Novartis, which has finished a Phase 2 program with bi-weekly sub-q dosing.
Speaker Change: There is calendar map with Novartis, which has finished the phase III program with bi weekly subcutaneous thing both of those programs have demonstrated statistically significant efficacy in this population which give us.
Speaker Change: A lot of confidence going into this stuff.
Speaker Change: The study that we're in the right patient population to protection, we've demonstrate rapidly.
And then the third program is set up a program called <unk>, Alabama, which had studied and studied it sugars.
Speaker Change: But with no results were reported as of yet.
Unknown Attendee: Unknown Attendee, Anupam Rama, Kyuwon Choi, Mark Ragosa, Rachel Frank, Ross Moat, Alexandria Hammond, Paul Choi, Kiniksa Pharmaceuticals Ltd.
Speaker Change: I think were.
Speaker Change: Given the data we've generated to date.
Speaker Change: 400, <unk>, we're pretty excited about our study and the ability to test not only exclusively a subcutaneous formulation, but also testing at five weeks.
Speaker Change: Monthly.
Speaker Change: And thank you.
Operator: And one moment for our next question comes from Jeff Meacham from Bank of America. Your line is now open.
Speaker Change: And one moment our next.
Speaker Change: One moment.
Speaker Change: And our next question comes from Geoff Meacham from Bank of America. Your line is now open.
Geoffrey Christopher Meacham: Morning, guys. Thanks for the question and congrats on a good quarter. Ross, just on ARCALASP, you know you've had a successful launch so far, but obviously, raising awareness will be key. So are there plans to publish residents' stories, and are there other studies that you guys were thinking about in terms of, you know, raising the profile? And then the second question for Sanj, you know, you'll obviously be investing in Eddie Pro Bart going forward, but you guys have committed to remaining cash flow positive. So I guess the question is, how important is profitability or pipeline expansion? You will know from us on a strategic basis relative to your commercial and commercial investments in our class. Thanks guys.
Speaker Change: Yes.
Geoffrey Christopher Meacham: Good morning, guys. Thanks for the question and congrats on a good quarter.
Geoffrey Christopher Meacham: Ross just on our class you have had a successful launch so far but obviously raising awareness I suspect we'll be key so are there plans to publish residents are there. Other studies that you guys were thinking about in terms of raising the profile.
Geoffrey Christopher Meacham: And then second question first on <unk>.
Geoffrey Christopher Meacham: Obviously, you've been investing in that are you probe arc going forward, but you guys have committed to remaining cash flow positive. So I guess the question is how important is profitability or pipeline expansion.
Geoffrey Christopher Meacham: On a strategic basis.
Geoffrey Christopher Meacham: Relative to your <unk> commercial investments in <unk>. Thanks, guys.
John F. Paolini: Thanks Jeff. John, do you want to start? Absolutely. Thanks Jeff for the question.
Speaker Change: Thanks, Jeff John John Absolutely.
John F. Paolini: Yeah, no, we're really excited about the residence registry because that's really an important tool by which we're learning about recurrent pericarditis epidemiology and disease management. And importantly, there are more than 20 centers across the US that are led by cardiologists who have a focus on recurrent pericarditis. And these are really the leading edge of managing the disease. So in that sense, the data serve as an example for other clinicians around the country who are seeking to grow their knowledge base. So you know, what we're looking to do, and as we've done in the past, is this is a five-year registry. And we're kind of right in the middle of it right now.
John F. Paolini: Absolutely and thanks, Jeff for the question Yeah, No. We're really excited about the other residents registry because that's really an important tool by which we're learning about return to arthritis, epidemiology and disease disease management and importantly, there are more than 20 centers across the U S. Led by cardiologist investigators who have a focus on recurrent Hartford.
John F. Paolini: And these are really the leading edge of managing the disease. So in that sense. The data serve as an example for other clinicians around the country, who are seeking to grow their knowledge base. So.
John F. Paolini: What we're looking to do and as we've done in the past is this is a five year registry and we're kind of right in the middle of it right now so we're about halfway enrolled about halfway through the follow up period, adding patients all the time.
John F. Paolini: So about halfway enrolled, about halfway through the follow-up period, adding patients all the time. We've presented at prior scientific meetings, and we just presented at the American College of Cardiology. And there's a lot of information in this registry that, you know, we hope to harvest as we go forward and gain a lot of insights into it. And this time around, you know, the fact that we learned about the penetration of IL1 pathway inhibition as a concept and, then importantly, that these evidence-based cardiologists are adopting a steroid-sparing paradigm in the treatment of the disease, meaning that they're moving from NSAIDs and Colchicine directly to IL1 pathway inhibition.
John F. Paolini: Rented a prior scientific meetings and we just presented at the American College of Cardiology and Theres a lot of information in this registry that we hope to harvest as we go forward and gaining a lot of insights about it and this time around the fact that we learned about the penetration of <unk>.
John F. Paolini: <unk> inhibition as a concept and then importantly that.
John F. Paolini: These evidenced based cardiologists are adopting a steroid sparing paradigm in the treatment of the disease, meaning that they are moving from the exits and culture seeing directly to Iowa pathway inhibition and Thats really been driven by by Arcalis and that's been a growing trend year on year to us is important.
John F. Paolini: And that's really been driven by Arcolyst. And that's been a growing trend year on year. To us, it is important and exciting data that people are taking the evidence and really using that to drive management of their patients. So we look forward to harvesting more information, you know, from the centers and from these cardiologists as we go forward. So more to come. Thanks so much for the question. And Jeff, to the second part of your question, and as you said, we did...
John F. Paolini: And exciting data that people are taking the evidence and really using that to drive managed under their patients. So we look forward to harvesting other information from the centers and from these cardiologists as we go forward so more to come. Thanks, so much for the question.
John F. Paolini: And yet.
John F. Paolini: Part of your question and as you said, we did disclose this in this quarter that we based on our current operating plan. We do expect to remain cash flow positive on annual basis, but that said growth and creating value.
John F. Paolini: Certainly remain quite powerful maps.
John F. Paolini: While we're very excited about continuing to develop that.
John F. Paolini: As you've seen we've shown just highly active molecule to date with the compelling safety profile. We're very pleased with the ongoing commercial execution with <unk>. We continue actually to look very hard at business development opportunities.
Sanj K. Patel: And Jeff, to your second part of your question, and as you said, we did disclose this in this quarter, that based on our current operating plan, we do expect to remain cash flow positive on an annual basis. But, you know, that said, growth and creating value are Unknown Attendee, Anupam Rama, Kyuwon Choi, Mark Ragosa, Rachel Frank, Ross Moat, Alexandria
John F. Paolini: Across a whole range of areas.
John F. Paolini: All of that tells you that.
John F. Paolini: So that's the primary goal is to create value.
John F. Paolini: The operating.
John F. Paolini: Operating plan.
John F. Paolini: Means that we expect to make cash flows.
John F. Paolini: Cash flow positive on an annual basis.
John F. Paolini: But ultimately its value creation thats important to us. So we're in a great position, obviously, great financial position right now and obviously a lot of exciting development coming forward. So I.
John F. Paolini: I think in a great spot.
Speaker Change: Okay. Thanks, Scott.
Speaker Change: And thank you.
Speaker Change: Yes.
Operator: And one moment for our next question, and our next question comes from Liisa Bayko from Evercore ISI. Your line is now open.
Speaker Change: And one moment our next question.
Speaker Change: And our next question comes from Lisa <unk> from Evercore ISI. Your line is now open.
Liisa Ann Bayko: Hi and just congrats on the quarter and great to see you being able to be sustainably cash flow positive. Just to drill down a little bit more on ABAPUVAR, can you Maybe talk through some of the characteristics that make you feel like you'd be competitive, maybe specifically some of the pharmacokinetic dynamic and phase two data that kind of lead you to believe that and just still kind of curious about any findings on, You know, kind of the treatment benefit over placebo in cohort 4, and kind of what that means from RA is, as you think about transition to a different disease, you know, obviously, there's kind of, you know, a bit more of a placebo response in the RA study, you know, kind of any implications or read through to what we might expect from the next phase of development. Thanks.
Lisa: Hi, congrats on the quarter and great to see you thing April to be sustainably cash flow positive just to drill down a little bit more on <unk> can you.
Lisa: Maybe talk through some of the characteristics that make you feel like you'd be competitive maybe specifically some of the pharmacokinetic dynamic and phase III data that kind of lead you to believe that and just kind of curious about any findings on.
Lisa: Kind of the.
Lisa: The treatment benefit over placebo.
Lisa: And cohort four and kind of what that means from RNA as you think about transition to a different disease.
Lisa: Obviously, there is kind of a bit.
Lisa: Martha placebo response.
Lisa: In the study.
Lisa: Kind of any implications of read through to what we might expect.
John F. Paolini: Hi Liisa, and thank you so much for that question. Yes, so with regard to the pharmacokinetics of Abiprobar. As you might remember, what we have shown previously is that the threshold for target engagement and suppression of antibody formation is at a plasma concentration of roughly 2 micrograms per ml. And what we've shown in our pharmacokinetic curves and the modeling that comes from that is that even with the monthly dose of Avipruvart, so 400 milligrams given every four weeks, the plasma concentrations are roughly, you know, around 20 to 30 micrograms per mil, so roughly an order of magnitude greater than the plasma concentration, which is required to suppress antibody formation.
Lisa: The next phase of development.
Lisa: Hi, Lisa and thank you so much for that question, yes, so with regards to the pharmacokinetics of IV approval on it.
Lisa: As you might remember.
Lisa: What we have shown previously is that the threshold for target engagement and suppression of antibody formation is it a plasma concentration of roughly two micrograms per 1000.
Lisa: And what we've shown in our pharmacokinetic curves in the modeling that comes from that is that even with the monthly dose of IV prove arts of 400 milligrams given every four weeks.
Lisa: Plasma concentrations are roughly around 20 to 30 micrograms per 1000, so roughly in order of magnitude greater than the plasma concentration, which is required to suppress an antibody formation and then the bi weekly and the weekly.
John F. Paolini: And then the biweekly and the weekly dose levels are providing even higher plasma concentrations. So in that sense, that's the reason why we have confidence in the rheumatoid factor data, which showed a 40% reduction across all three of those dosing regimens with highly statistically significant p-values with two or three zeros demonstrating, you know, really the strength of that finding. So that's kind of the fundamentals in the fact that this is all being done with a subcutaneous formulation that really provides a lot of flexibility going forward for chronic doses.
Lisa: Dose levels, providing even higher.
Lisa: Plasma concentration so in that sense. That's the reason why we have confidence in the regulatory factor data, which showed a 40% reduction across all three of those dosing regiments with highly statistically significant P values with two or three zeros, demonstrating really the strength of.
Lisa: Of that finding.
Lisa: So that's kind of the fundamentals and the fact that this is all being done with a subcutaneous formulation really provides a lot of flexibility going forward for chronic dosing.
John F. Paolini: And then in terms of how that translates forward, you know, into Sjögren's disease, as we mentioned, there is substantial external proof of concept that this mechanism has been implicated and is highly involved in the pathophysiology of the disease, and that suppression of this mechanism could be an efficacious approach. And so, by taking the bi-weekly, you know, and the monthly dose into the children's disease, we believe that we have a solid platform, if you will, for delivering enough drug to suppress the mechanism and to do that in a manner that would be convenient for patients.
Lisa: In terms of how that translates forward into sugars disease. As we mentioned that there is substantial external proof of concept that this mechanism has been implicated as highly involved in the pathophysiology of the disease and that suppression of this mechanism could be an efficacious approach.
Lisa: And so by taking the biweekly.
Lisa: And the monthly dose into children's disease, we believe that we have a solid platform. If you will for delivering enough drug.
Lisa: To suppress the mechanism and to do that in a manner that would be convenient for patients and the other part of that of course is that by following this out over a longer period of time, we get more experience with the chronic use of the drug. So there is a placebo controlled portion of upfront and then that's followed by a longer term extension where.
John F. Paolini: And the other part of that, of course, is that by following this out over a longer period of time, we get more experience with the chronic use of the drug. So, there's a placebo control portion up front, and then that's followed by a longer-term extension, where all the patients remain on active therapy so that we can understand the full magnitude of the effect of the drug. So, thanks so much for the question.
Lisa: All the patients remain on active therapy, and so that we can understand the full magnitude of the effect of the drug over time. So thanks, so much for the question.
Lisa: Thanks.
Operator: and thank you. And I am showing no further questions. I would now like to turn the call over to Sanj Patel, Chief Executive Officer, for closing remarks.
Speaker Change: And thank you.
Speaker Change: And I am showing no further questions I would now like to turn the call over to <unk> Patel, Chief Executive Officer for closing remarks.
Sanj K. Patel: Thanks, operator. I appreciate all the questions and everyone joining the call today. Clearly, we've got a very exciting year ahead of us, and we're very much looking forward to, you know, continuing to execute and providing additional updates in the future. So with that, have a great day. Thank you.
Patel: Thanks, Operator, I appreciate all the questions and everyone joining the call today clearly a very exciting year ahead of us and we're very much looking forward to continuing to execute and providing additional updates in the future. So with that have a great day. Thank you. This concludes today's conference call. Thank you for participating you may now disconnect.
Operator: This concludes today's conference call. Thank you for participating. You may now disconnect.
Patel: Yes.
Patel: Okay.
Patel: [music].
Patel: Okay.
Patel: Okay.
Patel: [music].