Q1 2025 Crinetics Pharmaceuticals Inc Earnings Call
<unk> prepared remarks, we will hold a question and answer session.
Please press star followed by one on your telephone keypad.
Okay.
You changed your mind, Please press star followed by two.
[music].
Walker: I would now like to turn the call over to <unk> to Walker head.
Okay.
Speaker Change: Head of Investor Relations. Please go ahead.
Okay.
[music].
Speaker Change: Thank you Anthony.
Speaker Change: Asking everyone and thank you for joining us to discuss the first quarter of 2025 zone.
Scott Struthers: Turning to asthma elements, we remain very encouraged by its potential to establish an uncompromising treatment goal for people living with congenital adrenal hyperplasia. We're moving forward with a phase 3 study for adults with CAH that Dana will describe in some detail. At a high level, this study is designed to redefine the standard of care as the achievement of normal adrenal androgen levels with only physiologic levels of glucocorticoid replacement. We believe ethumelanate should be used to treat the disease, and glucocorticoid should only be used for physiologic replacement, not treatment.
Okay.
[music].
Speaker Change: On the call we have Dr. Scott Struthers, founder and Chief Executive Officer, Duncan Dana DVD, Chief Medical and development Officer, Isabella <unk>, Chief Commercial officer, and Toby Yoki Chief Financial Officer.
Yeah.
Okay.
[music].
Speaker Change: Onto an Gardner chief Endocrinologist will also be joining for the Q&A portion.
Speaker Change: Please note there is a slide deck during today's presentation in the events and presentations section of the investors page on <unk> website.
Speaker Change: In addition, our press release was issued earlier today and is also available on the corporate website.
Isabel Calafonos: With that, I'll hand the call over to Isabel to update our acromegaly launch preparations. Isabel?
Speaker Change: Slide two.
Isabel Calafonos: Thanks, Scott.
As a reminder, we will be making forward looking statements and I invite you to learn more about the risks and uncertainties associated with these statements.
Isabel Calafonos: As described on the slide four, our mission with participating is to provide the next generation of care for people living with acromegaly. Well, we have a long-term global vision, and we're building out our infrastructure to support commercialization of our whole pipeline. We're completely focused on executing on the anticipated U.S. launch. We're making significant progress in building our infrastructure, educating and driving awareness among healthcare professionals and patients, and engaging with payors. We also have a strong long-standing patient advocacy partnership in place as we continue to engage with the broader acomegaly community. On the healthcare professional side, we have held advisory boards with nurses and endocrinologists, and they have provided positive feedback on the potential value proposition of Paltucetine in both biochemical control of IGF-1 and symptom control.
Okay.
Speaker Change: As disclosed in our SEC filings.
Operator: Welcome, everyone, to the Crinetics Pharmaceuticals First Quarter 2025 Earnings Conference Call. We will begin shortly.
Speaker Change: Welcome everyone to the kinetics Pharmaceuticals first quarter 2025 earnings conference call. We will begin shortly in the meantime, if he would like to pre register to ask a question. Please press star followed by one on your telephone keypad.
Speaker Change: Such forward looking statements are not a guarantee of performance and the Companys actual results could differ materially from those stated or implied in such statements due to risks and uncertainties associated with the Companys business.
Operator: In the meantime, if you would like to pre-register to ask a question, please press star followed by one on your telephone keypad. If you change your mind, please press star followed by two. Thank you.
Speaker Change: If you change your mind. Please press star followed by Jay Thank you.
Speaker Change: These forward looking statements are qualified in their entirety by the cautionary statements contained in today's news release.
Speaker Change: [music].
Speaker Change: The Companys other news releases and <unk> SEC filings, including its annual report on Form 10-K, and quarterly reports on Form 10-Q.
Speaker Change: I would also like to specify that the content of this conference call contains time sensitive information that is accurate only as of the date of this live broadcast may eight 2025 clinics takes no obligation to revise or update any forward looking statements to reflect events or circumstances. After the date of this conference.
Isabel Calafonos: We're working on the final salesforce mapping, and we expect to have approximately 30 reps in place over the summer. We will cover healthcare professionals in PCR treatment centers, academic centers of excellence, and in community endocrinology practice.
Speaker Change: This call with that I'll hand, the call over to Scott.
Speaker Change: Thank you Catherine and good afternoon to everyone. Joining today's call. We're pleased to share our first quarter results highlight the great progress, we're making towards our mission of transforming the lives of patients with serious on the call.
Isabel Calafonos: We're making powerful strides in advancing awareness and visibility for Part 215 and our broader pipeline at conferences attended by academic and local knowledge For more information visit www.fema.gov Light Angels, and by community endocrinologists like AIDS. We will share exciting new scientific data that reinforce the long-term value of paltricitin and the need for innovation in acromegaly treatment. Notably, we'll present data from our four-year Acrobat Open Label Extension, or OLE, study, demonstrating that patients on paltricitin maintain biochemical control in IGF-1 over a 96-week period. Equally important, 87% of patients prefer partucitin over prior injectable SRL therapy, highlighting the patient-centric benefits of our once-daily oral For more information visit www.FEMA.gov We will also share real-world evidence that current SRL therapies are associated with persistent breakthrough symptoms and low compliance and adherence.
Jason: Jason diseases, turning to slide three kinetics has never been stronger in a while.
Speaker Change: Yes.
Speaker Change: We're strategically positioned for long term sustainable growth.
Operator: Welcome to the Crinetics Pharmaceuticals first quarter 2025 financial results conference call. At this time, all participants are in listen-only mode.
Speaker Change: Okay.
Speaker Change: It focuses on the anticipated commercial launch of our first product this year.
Speaker Change: Welcome to the <unk> Pharmaceuticals first quarter <unk> financial results Conference call.
Speaker Change: This is a pivotal milestone for the company. We believe <unk> has the potential to deliver meaningful improvements for people living with acromegaly.
Speaker Change: At this time all participants are in listen only mode. Following the management's prepared remarks, we will hold a question and answer session.
Operator: Following the management's prepared remarks, we will hold a question and answer session. Please press star followed by one on your telephone keypad. If you change your mind, please press star followed by two.
Speaker Change: Backed by an experienced team deeply embedded in the endocrinology community and driven by a strong commitment to patients and science, we're well on our way to becoming a fully integrated global commercial organization.
Speaker Change: Please press star followed by one on your telephone keypad. If you change your mind. Please press star followed by today.
Gayathri Diwakar: I would now like to turn the call over to Gayathri Diwakar, Head of Administrative Relations. Please go ahead. Thank you, operator.
Guy Walker: I would now like to turn call over to Guy operate to Walker.
Speaker Change: The Investor Relations. Please go ahead.
Speaker Change: We are advancing a robust pipeline in parallel including two late stage candidates <unk>.
Speaker Change: Thank you Andrea good afternoon, everyone and thank you for joining us to discuss the first quarter of 2025 retailing today on the call we have Dr. Scott.
Gayathri Diwakar: Good afternoon, everyone, and thank you for joining us to discuss the first quarter 2025 results.
Speaker Change: One recently clearing IMD and three additional candidates in preclinical studies.
Gayathri Diwakar: Today on the call, we have Dr. Scott Struthers, Founder and Chief Executive Officer, Dr. Dana Pizzuti, Chief Medical and Development Officer, Isabel Calafonos, Chief Commercial Officer, and Toby Schilke, Chief Financial Officer.
Speaker Change: With $1 $3 billion on the balance sheet, we're able to continue to invest in our pipeline support perspective launches and thoughtfully pursue opportunities that enhance value across our portfolio.
Speaker Change: Founder and Chief Executive Officer, Dr. Dana TBD, Chief Medical Officer, <unk>, <unk>, Chief commercial officer, and Toby Yoki Chief Financial Officer.
Gayathri Diwakar: Dr. Alan Krasner, Chief Endocrinologist, will also be joining for the Q&A portion.
We have never been stronger.
Speaker Change: Thank you Anne.
Speaker Change: Keith.
Speaker Change: I'd like to take a moment to welcome Toby shocking.
Speaker Change: Well I'll be joining for the Q&A portion.
Speaker Change: So you'll be hearing from towards the end of today's call. Toby recently joined as Chief Financial Officer, and he brings over 25 years of global experience with a proven track record of guiding companies through the transition from R&D focused ventures into a fully integrated commercial organizations.
Gayathri Diwakar: Please note there is a slide deck for today's presentation, which is in the events and presentation section of the investors page on the Crinetics website. In addition, a press release was issued earlier today and is also available on the corporate website. Slide 2.
Speaker Change: Please note there is a slide deck for todays presentation.
Speaker Change: And then your presentation is actually a diagnostic page on the company's website.
Isabel Calafonos: patients experience symptom exacerbations more than one third of days each month. And those days are not always concentrated in the week leading up to the next injection. Data from Pathfinder 1 demonstrates that patients treated with PATUSU team experienced decreased symptoms and cessation rates over time. Additionally, based on real-world data compiled over a four-year period, 80% of patients with acomegaly who are newly treated either discontinue or switch from their initial treatment within their first year. This data highlights Pantustin's scientific and clinical relevance in an area of significant and met need to improve the lives of patients living with acromegaly.
Speaker Change: In addition, our press releases issued earlier today and also available on the corporate website.
Speaker Change: Slide two.
Speaker Change: So he has extensive financial and operational experience will be invaluable as we accelerate our growth trajectory and position <unk> for long term success.
Gayathri Diwakar: As a reminder, we will be making forward-looking statements, and I invite you to learn more about the risks and uncertainties associated with these statements as disclosed in our SEC filing. Such forward-looking statements are not a guarantee of performance, and the company's actual results could differ materially from those stated or implied in such statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's news release. The company's other news releases and Crinetics SEC filings, including its annual report on Form 10-K and quarterly reports on Form 10-Q.
Speaker Change: As a reminder, we will be making forward looking statements I invite you to learn more about the risks and uncertainties associated with these statements.
Speaker Change: Also wanted to reassure you that regulatory engagement with the FDA on the <unk> NDA for acromegaly as well as our other clinical development activities.
Speaker Change: Our SEC filings.
Speaker Change: Forward looking statements are not a guarantee of performance and the company's actual results could differ materially from those stated on my statement.
Speaker Change: Proceeding on track.
Speaker Change: We're grateful for the ongoing professionalism and commitment of our staff at FDA with whom we interrupt.
Speaker Change: The risks and uncertainties associated with the company's business. Please.
Speaker Change: Main proactive in monitoring the evolving regulatory environment.
Speaker Change: These forward looking statements.
Speaker Change: And in their entirety by the cautionary statements contained in today's news release.
Speaker Change: And maintain an active dialogue with key stakeholders, both on the administration and on Capitol Hill.
Speaker Change: The company's other news releases and Q&A.
Speaker Change: As Youll hear from Isabel we're laser focused on preparing for the anticipated launch of <unk> in September.
Speaker Change: SEC filing.
Speaker Change: <unk> annual report on Form 10-K quarterly reports on Form 10-Q.
Isabel Calafonos: And slide five. Education and awareness are critical elements of our plan to reach patients as part of our Activate, Adopt, Access, Adhere, Launch strategy. We are focused on elevating awareness of the burden of disease experienced by patients, even those currently being treated. Our insights consistently show that while patients might achieve biochemical control, they often continue to experience persistent symptoms that impact quality of life.
Speaker Change: This will be our first product approval and are defining milestone for our ambition to become a fully integrated pharmaceutical company.
Gayathri Diwakar: I would also like to specify that the content of this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, May 8, 2025. Crinetics takes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call.
Speaker Change: I would also like to specify that the content of this conference call contains time sensitive information that is accurate only as of the date of this live broadcast may eight 2025.
Speaker Change: On today's call will walk through some of the launch initiatives, we are executing and reflect on the progress. The team has made to date.
Speaker Change: <unk> takes no obligation to revise or update any forward looking statements.
Speaker Change: Turning to ask melanoma, we remain very encouraged by its potential to establish an uncompromising treatment goal for people living with congenital adrenal hyperplasia.
Scott: Like events or circumstances. After the date of this conference call with that I'll hand, the call over to Scott. Thank.
Scott Struthers: With that, I'll hand the call over to Scott. Thank you, Gayathri, and good afternoon to everyone joining in today's call. We're pleased to share our first quarter results and highlight the great progress we're making towards our mission of transforming the lives of patients with serious endocrine and endocrine adjacent diseases.
Dana: Moving forward to a phase III study for adults with CAH that Dana will describe in some detail.
Scott: Thank you Catherine and good afternoon to everyone joining today's call.
Speaker Change: I'm pleased to share our first quarter results highlight the great progress, we're making towards our mission of transforming the lives of patients with serious endocrine and endocrine adjacent diseases, turning to slide three kinetics has never been stronger and a lot of emphasize though.
Dana: At a high level. This study is designed to redefine the standard of care as the achievement of normal adrenal androgen levels.
Isabel Calafonos: Our educational initiatives are designed to address both aspects of disease control to ensure patients are better informed, more empowered, and fully activated to advocate for treatment that addresses the unmet needs of the current standard For more information visit www.FEMA.gov We recently launched our Chronetic Care Patient Support Service platform to act as a partner to patients on their treatment journey from the very beginning. We open our hub before the anticipated approval because the acromegas community faces significant and many inpatients. Clinetic Care connects patients with nurses to discuss their symptoms and offers interactive tools to help them locate experienced healthcare providers.
Dana: With only physiologic levels of glucocorticoid replacement.
Scott Struthers: Turning to slide three, Crinetics has never been stronger, and I want to emphasize that. We're strategically positioned for long-term sustainable growth. Our immediate focus is on the anticipated commercial launch of our first product this year. This is a pivotal milestone for the company. We believe Peltucetine has the potential to deliver meaningful improvements for people living with acromegaly. Backed by an experienced team deeply embedded in the endocrinology community and driven by a strong commitment to patients and science, we're well on our way to becoming a fully integrated global commercial organization. We're advancing a robust pipeline in parallel, including two late-stage candidates, one recently clearing IND, and three additional candidates in preclinical studies.
Dana: We believe that <unk> should be used to treat the disease and glucocorticoids should only be used for physiologic replacement not treatment.
Scott: Strategically positioned for long term sustainable growth.
Scott: Our immediate focus is on the anticipated commercial launch of our first product this year.
Dana: With that I'll hand, the call over to Isabelle to update our acromegaly launch preparations as well.
Scott: This is a pivotal milestone for the company. We believe <unk> has the potential to deliver meaningful improvements for people living with acromegaly.
Isabelle: Thank you Scott.
Isabelle: This graph on the slide for automation with participate is to provide the nissin additional kit for people, leaving with acromegaly.
Scott: Backed by an experienced team deeply embedded in the endocrinology community and driven by a strong commitment to patients and science, we're well on our way to becoming a fully integrated global.
Speaker Change: While we have a long term global vision.
Speaker Change: Building out our infrastructure to support commercialization of our core pipeline. We're currently focused on executing on the anticipated U S launch.
Scott: <unk> commercial organization.
Isabel Calafonos: The Chronetic Care Platform will serve as a continuous connection between us and the patients we serve. Once the 2016 is approved, Crinetic Care will provide a wide-globe experience for patients from the time they receive prescriptions, to initiation of therapy, all the way to long-term maintenance.
Scott: We are advancing a robust pipeline in parallel including two late stage candidates, one recently clearing IMD and three additional candidates in preclinical studies.
Speaker Change: We're making significant progress in building out infrastructure.
Speaker Change: Taken on driving awareness amongst healthcare corporation of some patients.
Scott Struthers: With $1.3 billion on the balance sheet, we're able to continue to invest in our pipeline, support prospective launches, and thoughtfully pursue opportunities and enhance value across our portfolio. We have never been stronger.
Scott: With $1 $3 billion on the balance sheet, we're able to continue to invest in our pipeline support perspective, lunches and thoughtfully pursue opportunities that enhance value across our portfolio.
Speaker Change: On engaging with Baird.
Speaker Change: We also have a strong longstanding face an advocacy partnerships in place as we continue to engage with a broad acromegaly choline.
Isabel Calafonos: We also recently revealed our Unbranded Diseases Day education. This campaign leverages our learnings from our ongoing engagement with healthcare professionals, patients, and acromegaly community partners to amplify patients' voices and provide educational material.
Scott: We have never been stronger.
Speaker Change: On the healthcare professional side, we have held advisory boards with nurses are endocrinologists.
Scott Struthers: I'd like to take a moment to welcome Toby Schuelke. who you'll be hearing from towards the end of today's call. Toby recently joined as Chief Financial Officer and he brings over 25 years of global experience with a proven track record of guiding companies through the transition from R&D focused ventures into fully integrated commercial organizations. Toby's extensive financial and operational experience will be invaluable as we accelerate our growth trajectory and position Crinetics for long-term success.
Speaker Change: I'd like to take a moment to welcome Toby soaking who you.
Speaker Change: You'll be hearing from towards the end of today's call. Toby recently joined as Chief Financial Officer, and he brings over 25 years of global experience with a proven track record of guiding companies through the transition from R&D focused ventures into a fully integrated commercial organizations.
Speaker Change: We have provided positive feedback on the potential value proposition of participation involves biochemical control.
Isabel Calafonos: Turning to slide six. We continue our peer-to-peer conversations with payers, and we are encouraged by their feedback. In particular, we anticipate that prior authorization for PACTUS systems will reflect the label, which will help us drive the success of reimbursement. Participating value proposition is resonating with payers because their main needs with injectable SRLs, long titration times, incorrect injections, and inconsistent symptom control collectively result in higher costs overall. First, patients starting on SRS typically have their dose titrated every three months. With three different dose strengths available, it might take patients up to nine months to get to the right dose where the disease is under control.
Speaker Change: <unk> seen some control.
Speaker Change: Working on the final sales force mapping.
Speaker Change: To have approximately 30 reps in place over the summer.
Speaker Change: So he has extensive financial and operational experience will be invaluable as we accelerate our growth trajectory and position kinetics for long term success.
Speaker Change: Third cohort healthcare payers.
Speaker Change: <unk> and BT started treatment centers.
Speaker Change: Yeah that makes sense I suppose accidents and in community endocrinology practices.
Scott Struthers: I also wanted to reassure you that regulatory engagement with the FDA on the PAL-215 NDA for acromegaly, as well as our other clinical development activities, have been proceeding on track. We're grateful for the ongoing professionalism and commitment of the staff at FDA with whom we interact. We remain proactive in monitoring the evolving regulatory environment and maintaining active dialogue with key stakeholders, both in the administration and on Capitol Hill.
Speaker Change: I also wanted to reassure you that regulatory engagement with the FDA on the <unk> NDA for acromegaly as well as our other clinical development activities.
Speaker Change: We're making powerful its strides in advancing awareness and visibility for participating on our broader pipeline conference attended by economic endocrinologists.
Speaker Change: Proceeding on track.
Speaker Change: We're grateful for the ongoing professionalism and commitment of our staff at FDA with when we interrupt.
Speaker Change: And bill.
The community endocrinologist.
Speaker Change: Main proactive in monitoring the evolving regulatory environment.
Speaker Change: As.
Speaker Change: We will share exciting new scientific data that reinforce the long term value of participating and the need for innovation in acromegaly treatment.
Speaker Change: And maintain an active dialogue with key stakeholders, both in the administration and on Capitol Hill.
Scott Struthers: As you'll hear from Isabel, we're laser-focused on preparing for the anticipated launch of Taltucetine in September. This will be our first product approval and a defining milestone for our ambition to become a fully integrated pharmaceutical company. On today's call, we'll walk through some of the launch initiatives we are executing and reflect on the progress the team has made to date.
Speaker Change: As Youll hear from Isabel we're laser focused on preparing for the anticipated launch of <unk> in September.
Speaker Change: Lee will present data from our four year old.
Isabel Calafonos: Payers bear the cost of treatment for many months before the patient sees a benefit. In contrast, daily dosing of Paltucetin will allow titration to the optimal levels within weeks if titration is needed. Second, S&S are not always correctly delivered, which can lead to higher costs to manage the resulting symptoms and size. For context, SRL injections are given with large 18-19 gauge needles. The injections are unpleasant to receive and challenging to give. A research study conducted at MD Anderson, one of the leading centers, found that half of lung absinthe ultrathight injections administered by experienced nurses were not injected into the intramuscular stage.
Speaker Change: This will be our first product approval and are defining milestone for our ambition to become a fully integrated pharmaceutical company.
Speaker Change: The label extension for.
Speaker Change: All he study.
Speaker Change: On today's call will walk through some of the launch initiatives, we are executing and reflect on the progress. The team has made today.
Speaker Change: Demonstrating that patients on participating maintain biochemical control in <unk>.
Scott Struthers: Turning to SMLNet, we remain very encouraged by its potential to establish an uncompromising treatment goal for people living with congenital adrenal hyperplasia. We're moving forward with a phase 3 study for adults with CAH that Dana will describe in some detail. At a high level, this study is designed to redefine the standard of care as the achievement of normal adrenal androgen levels with only physiologic levels of glucocorticoid replacement. We believe atumelanate should be used to treat the disease, and glucocorticoid should only be used for physiologic replacement, not treatment.
Speaker Change: Over a 96 week period.
Speaker Change: Turning to ask some element we remain very encouraged by its potential to establish an uncompromising treatment goal for people living with congenital adrenal hyperplasia.
Speaker Change: <unk> important 87%.
Speaker Change: Patients prefer participating or brio in that though is that in.
Speaker Change: We're moving forward to the phase III study for adults with CAH that Dana will describe in some detail.
Speaker Change: <unk> therapy, highlighting that this incentive benefits of our <unk> oriented.
Dana: At a high level. This study is designed to redefine the standard of care as the achievement of normal adrenal androgen levels with only physiologic levels of glucocorticoid replacement.
Speaker Change: We will also share a real world. It is the current setup is associated with the system breakthrough symptoms on low compliance on it here.
We believe that some element should be used to treat the disease and glucocorticoid should only be used for physiologic replacement not treatment.
<unk> more than one set of days each month.
Isabel Calafonos: The ripples of ultrathight instead persisted in the subcutaneous layer, where they formed nodules that sometimes became granular. It is important to note that if the drug is not administered properly, it might not achieve its intended effect. In addition, patients understand that injectable SRS often do not provide adequate disease control for the duration of the injection cycle. According to a real-world data analysis, one-third of acromegaly patients on injectable SRLs receive more than the 13 injections per year expected based on an approved dosing, which is every four weeks. Consequently, this increase is called substantially for failure. Furthermore, uncontrolled acromegaly is associated with comorbidities and additional procedures, which are costly for payers and very burdensome for patients.
Isabel Calafonos: With that, I'll hand the call over to Isabel to update on our acromegaly launch preparations. Isabel? Thanks, Scott. As described on the slide four, our mission with participating is to provide the next generation of care for people living with acromegaly. Well, we have a long-term global vision, and we're building out our infrastructure to support commercialization of our whole pipeline, where we're completely focused on executing on the anticipated U.S. launch. We are making significant progress in building our infrastructure, educating and driving awareness among healthcare professionals and patients, and engaging with payers. We also have a strong longstanding patient advocacy partnerships in place as we continue to engage with the broader Alkomegaly community.
Dana: With that I'll hand, the call over to Isabelle to update our acromegaly launch preparations as well.
Speaker Change: And those days are not always concentrated in the week, leading up to the nurse injection.
Scott: This is Scott.
Speaker Change: Data from five signed there one demonstrate that patients treated with participating Sps decrease symptoms that separation great overtime.
As described on the slide for automation with participation is to provide the NASA and additional kit for people, leaving with acromegaly.
Speaker Change: Additionally, based on real World data compiled over a four year period, 80%.
Scott: We have a long term global vision and we are building out our infrastructure to support commercialization.
Speaker Change: <unk> with Arco Mega link core newly treated either discontinue or sweet funding needs have seen that we deem that first year.
Scott: Our whole pipeline.
Scott: To focus on executing on the anticipated U S launch, we are making significant progress in building out infrastructure.
Scott: Peyton and raising awareness amongst healthcare professionals and patients and engaging with pace.
Speaker Change: This data highlights participating scientific or clinical relevance in an area of significant unmet need to improve the lives of patients living with acromegaly.
Scott: We also have a strong long astounding patient advocacy partnerships in place.
Scott: We continue to engage with a broad I can make any comment.
Speaker Change: And slide five education and awareness are critical elements of our plan to bridge patients as part of our active adult.
Isabel Calafonos: On the healthcare professional side, we have held advisory boards with nurses and endocrinologists, and they have provided positive feedback on the potential value proposition of palpitucin in both biochemical control of IGF-1 and symptom control. We're working on the final sales force mapping, and we expect to have approximately 30 reps in place over the summer. We will cover healthcare professionals in P230 treatment centers, academic centers of excellence, and in community endocrinology practice. We are making powerful strides in advancing awareness and visibility for PACT-215 and our broader pipeline at conferences attended by academic endocrinologists, like Endo, and by community endocrinologists, like ACE.
Scott: On the healthcare professional side, we have held advisory boards with nurses and endocrinologist and they have provided positive feedback on the potential value proposition of participation involves biochemical control of I guess, what I'm seeing some control.
Speaker Change: Adhere launched a strategy.
Isabel Calafonos: Lastly, R2-Cysteine 1 daily oral dosing offers an opportunity to improve patient adherence for more consistent control.
Speaker Change: We are focused on elevating awareness of the burden of disease experienced by patients even those currently being treated.
Isabel Calafonos: In sum. There remains a significant unmet need for safe, highly efficacious, easy-to-administer treatments that offer daily control, and the economic and clinical value that an option like Faltucettin could provide to all stakeholders is clear. These and other marketing sites continue to highlight meaningful and mainly the nacremegaly and a strong enthusiasm for altruism. During early launch, we anticipate menstrual uptake as we educate both healthcare providers and patient communities. As with any new therapy, we expect coverage to build progressively and we will work through the formulary review process with patients over the first six to nine months.
Speaker Change: Our insights consistently show that while patients may achieve biochemical control. They often continue to experience. The assistance is those that impact quality of life.
Scott: We are working on the final sales force mapping and we expect to have approximately 30 reps in place over the summer.
Scott: Golar has kept rotation in pizza started treatment centers.
Speaker Change: Our educational initiatives are designed to address both aspects of disease control.
Scott: Yeah that makes sense I suppose are excellent and in community endocrinology practices.
Speaker Change: Fewer patients that are better informed more empower and fully activated two hour for treatment dresses that many of the current standard of care.
Scott: We're making powerful its strides in advancing our awareness and visibility for participating on our broader pipeline a conference attended by academic endocrinologists.
Speaker Change: We recently launched our <unk> patient support service platform for us.
Scott: And bill.
Scott: The community endocrinology.
Speaker Change: Partners to patients on their treatment journey.
Isabel Calafonos: we will share exciting new scientific data that reinforce the long-term value of paltricitin and the need for innovation in acromegaly treatment. Notably, we'll present data from our four-year Acrobat Open Label Extension, or OLE, study, demonstrating that patients on paltricitin maintain biochemical control in IGF-1 over a 96-week period. Equally important, 87% of patients prefer participating over prior injectable SRL therapy, highlighting the patient-centric benefits of our one daily oral treatment. We will also share real-world evidence that current SRL therapies are associated with persistent breakthrough symptoms and low compliance and adherence. Patients experience symptom exacerbations more than one third of days each month and those days are not always concentrated in the week leading up to the next injection.
Scott: As.
Scott: When we say exciting new scientific data that reinforce the long term value persistency and then meaningful innovation in acromegaly Susan.
Speaker Change: You may begin.
Speaker Change: We will open our hub before the anticipated approval because the acromegaly community faces significant unmet needs in patient support.
Isabel Calafonos: Our team is highly prepared and confident in navigating these initial steps to unlock the full opportunity of Paltus. As the value proposition continues to resonate with patients, healthcare professionals, and payers, we are optimistic that over time, PACT 216 could become the new standard of care in Acromega.
Scott: Lee will present data from our four year I'll provide open label extension Paul O N E study.
Speaker Change: <unk> stations with nurses to discuss the same dose and also I think theyre active tools to help them locate a student's health care providers.
Speaker Change: That can be and I think our platform will serve as a continuous connection between us and the patients we serve.
Scott: Demonstrating that patients on participating maintain biochemical control.
Scott: One.
Speaker Change: Once that does Athene is approved Connecticut will provide a white glove experience for patients from the time, they receive prescriptions to initiation of therapy, all the way to long term maintenance.
Scott: Over a 96 week period.
Dana Pizzuti: And now, Dana will share a regulatory update and additional detail on our CAH late-stage development strategy. Dana? Thank you, Isabel. Starting with Faltusatine, we continue to make progress in both the U.S. and E.U. where our regulatory reviews remain on track. We have not experienced any disruptions with our interactions with the FDA and continue to expect a decision by September 25th. And, as previously mentioned, we do not anticipate an advisory committee meeting as part of the NDA review. The European Medicines Agency has validated our MAA submission and granted orphan drug designation. We believe the orphan drug designation highlights the unmet need in acromegaly and the potential benefit that valtuzatine can offer patients compared to existing therapies.
Scott: Equally important 87%.
Scott: Patients prefer participating or cryo injectable.
Scott: In therapy, highlighting that this incentive benefits of our once daily oral treatment.
Speaker Change: We also recently introduced our unbranded disease State Education company.
Speaker Change: This campaign leveraged our learnings from our ongoing engagement with healthcare professionals.
Scott: We will also show real world. It is the carne Asada therapies I'd ask let's see I did with Bae systems breakthrough symptoms on low compliance centers here.
Speaker Change: It is an acromegaly community partners to amplify basins voices and provide education on materials.
Speaker Change: Turning to slide six we.
Scott: They said that span Simpson assessing patients more than one set of days each month.
Speaker Change: We continue our conversations with theirs and we're encouraged by their feedback.
Scott: And those days had not always constant Jason in the week, leading up to the nurse injection.
Speaker Change: In particular, we anticipate that prioritization for participating with reflect the label, which will help us drive the success of reimbursement.
Isabel Calafonos: Data from Pathfinder 1 demonstrates that patients treated with patuxentine experienced decreased symptoms and subservation rates over time. Additionally, based on real-world data compiled over a four-year period, 80% of patients with acomegaly who are newly treated either discontinue or switch from their initial treatment within their first year. This data highlights Paltucetin's scientific and clinical relevance in an area of significant and met need to improve the lives of patients living with acromegaly.
Scott: Data from five signed there one demonstrates that patients treated with participating Sps decrease symptoms that separation great overtime.
Speaker Change: Participant value proposition is resonating with this because the men need we inject our SRM loans adjacent times incorrect injections annual consistent symptom control collectively result in higher cost oil.
Scott: Additionally, based on real World data compiled for DST is 80%.
Dana Pizzuti: Our team continues to work with regulatory authorities in the U.S. and E.U. on all aspects of the review process.
Scott: Patients with <unk>, who are newly treated either discontinue or switch from getting niche ethylene that we deem that as far as yes.
Speaker Change: First basis, starting on Srs typically have their dose titrated every three months.
Dana Pizzuti: In preparation for launch, our growing medical affairs team has been connecting with the endocrinology community. Our experienced endocrinologists at Crinetics have been making warm introductions for our medical science liaisons to all the top KOLs. We've hosted roundtable discussions to deepen our understanding of the patient journey and gaps in treatment. As Isabelle highlighted, we have submitted multiple abstracts to upcoming endocrinology meetings that showcase paltuzatine's differentiation.
Scott: Yeah.
Scott: This data highlights participant scientific clinical relevance in an area of significant unmet need to improve the lives of patients living with acromegaly.
Speaker Change: With three different doses.
Speaker Change: It might take patients up to nine months to get to the right dose where the disease is under control there.
Isabel Calafonos: And slide five. Education and awareness are critical elements of our plan to reach patients as part of our Activate, Adopt, Access, Adhere, Launch strategy. We are focused on elevating awareness of the burden of disease experienced by patients, even those currently being treated. Our insights consistently show that while patients might achieve biochemical control, they often continue to experience persistent symptoms that impact quality of life. Our educational initiatives are designed to address both aspects of disease control to ensure patients are better informed, more empowered, and fully activated to advocate for treatment that addresses the many needs of the current standard of care.
Speaker Change: <unk> converted the cause of genome for many months before the patient sees the benefit.
Scott: And slide five education and awareness are critical elements of our plan to Greece patients as part of our activity.
Speaker Change: In contrast daily dosing of participating will allow us to patients to the optimal levels within weeks.
Scott: Doug.
Scott: Asset adhere launch strategy.
Speaker Change: We are focused on elevating the awareness of the burden of disease experienced by patients even those currently being treated.
Speaker Change: Duration is needed.
Speaker Change: Second is that as an always correctly, the liver, which can lead to higher cost in line as a result incentives on side effects for.
Speaker Change: Our insights consistently show that patients must see.
Dana Pizzuti: Moving to carcinoid syndrome, we expect to initiate the CARE FONDER phase three trial in the second half of 2025. Turning to Adam Millman on slide 7, we added a fourth cohort to our Phase 2 study due to the significant amount of enthusiasm and interest from sites and investigators. Cohort 4 is just one part of our larger development plan for adamelnut and CAH, and it is an exploratory analysis in a small group of 6-12 patients to evaluate 80 mg with morning dosing as opposed to evening dosing in the prior cohorts and to allow for glucocorticoid reduction.
Speaker Change: For context, sorry, injections are given where large 18 19 gauge needle the injections that I'm pleasantly received on challenges to give.
Speaker Change: Tim Mccall control. They often continue to asterias assistance is does that impact quality of life.
<unk> conducted at MD Anderson, one of the lead incentive found that have a long often also at dice injection.
Speaker Change: Our educational initiatives are designed to address both aspects of disease control to ensure patients have bet any form more empower I'm fully activated two hour for treatment dresses that many of the current standard of care.
Speaker Change: I mean, they served by Astellas nurses, we're not injected into the intramuscular face the depots ultra died instead persisted in the south continuous layer, where the four nodules that sometimes became granular.
Isabel Calafonos: We recently launched our Chronetic Care Patient Support Service platform to act as a partner to patients on their treatment journey from the very beginning. We open our hub before the anticipated approval because the acromegas community faces significant and many inpatient support. Crinetic Care connects patients with nurses to discuss their symptoms and offers interactive tools to help them locate experienced health care providers. The Clinetic Health Platform will serve as a continuous connection between us and the patients we serve. Once Peltuccin is approved, Crinetic Care will provide a wide-globe experience for patients from the time they receive prescriptions, to initiation of therapy, all the way to long-term maintenance.
Speaker Change: We recently launched our <unk> patient support service platform.
Speaker Change: Foreigners to patients on their treatment journey from the very beginning.
Speaker Change: It is important to note that if the drug is not administer appropriately in mind, though that ship is intended ethics.
Speaker Change: We'll open our hub before the anticipated approval because the echo my best community safest seem to be kind of a mid knee in patient support.
Dana Pizzuti: As previously shared, we are also conducting an open-label extension study which will provide real-world insights into Adam Mellman's efficacy and safety over the long term. Investigators will have the opportunity to titrate both the dose of adamalamin and the dose of GCs as they see fit. Study participants from the Phase 2 study are given the opportunity to enroll in the OLE. This study is ongoing and will eventually also include patients who complete Phase 3. Turning to slide eight. Our Phase 3 study for adult CAH patients builds on the strong top-line results we shared from cohorts 1 through 3 of the Phase 2 study.
Speaker Change: Genetic third clinic stations with NASA to discuss the same dose and also I think theyre active tools that have been looked at as soon as health care providers.
Speaker Change: In addition, theres understand an injectable it sort of is often do not provide adequate. This is controlled for the addition of the injection site.
Speaker Change: The clean and I think our platform will serve as a continuous connection between us and the patients we serve.
Speaker Change: According to our real World data analysis, one third of acromegaly patients on injectable et cetera.
Dan: Well. This is Dan is approved Connecticut will provide a white glove experience for patients from the time, they visit prescription to initiation of therapy, all the way to long term maintenance.
Speaker Change: This is more than that 15 injections per year.
Speaker Change: Active base on an approved dosing, which is every four weeks.
Speaker Change: Consequently, this increases call substantially for phase. Furthermore, and control acromegaly is associated with Comorbidities and additional procedures, which are closely for pairs are very burdensome for patients.
Isabel Calafonos: We also recently revealed our Unbranded Disease Sustain Education Company. This campaign leverages our learnings from our ongoing engagement with healthcare professionals, patients, and acromegaly community partners to amplify patients' voices and provide educational material.
Dan: We also recently unveiled our unbranded disease State Education campaign.
Dan: This campaign leveraged our learnings from our ongoing engagement with health care professionals.
Speaker Change: She is an acromegaly community partners to amplify basins voices and provide education on materials.
Dana Pizzuti: It is designed to provide a potential new therapeutic paradigm for patients. As Scott mentioned, there is a significant need for new treatments in CAH that not only allow patients to lower their GC dose to physiologic levels, but also to control their androgens, which account for many of the signs and symptoms of the underlying disease. With this in mind, we are pursuing a novel primary endpoint that combines both goals. The proportion of participants with A4 levels less than or equal to the upper limit of normal and who are on physiologic doses of GC replacement at week 32.
Speaker Change: Lastly, anticipating once daily oral dosing offered us an opportunity to improve patient adherence for more consistent control.
Isabel Calafonos: Turning to slide 6. We continue our peer-to-peer conversations with payers, and we are encouraged by their feedback. In particular, we anticipate that prior authorization for participating will reflect the label, which will help us drive the success of reimbursement. Participating value proposition is resonating with payers because their main needs with injectable SRLs, long titration times, incorrect injections, and inconsistent symptom control collectively result in higher costs overall. First, patients starting on SRLs typically have their dose titrated every three months. With three different dose strengths available, it might take patients up to nine months to get to the right dose where the disease is under control.
Dan: Turning to slide six.
Dan: We continue our conversations with this and we are encouraged by their feedback.
Speaker Change: In sum.
Speaker Change: There remains a significant unmet need for safe highly efficacious easy to administer Susan's got offer daily control and.
Dan: In particular, we anticipate the proudest of is essential for participating with reflect the label, which will help us drive the success of pain medicine.
Speaker Change: And the economic and clinical value than an auction like participating could provide solar stakeholders is clear.
Dan: Participant and value proposition is resonating with this because the men need injectable if our in laws.
Speaker Change: This annual market size continue to highlight meaningful unmet need and acromegaly uninstall enthusiasm for participation.
Dan: <unk>, Jason Zhang incorrect injection annual consistent symptom control collectively result in higher cost oil.
Speaker Change: During the early launch we anticipate Missouri uptake as we undertake both health care provider and patient communities.
Dana Pizzuti: Patients should not have to sacrifice one or the other in treating CAH. In this study, we will enroll 150 participants who will be treated for 32 weeks. We will offer investigators two periods of time over which they can reduce GCs with four assessment visits in each period. Investigators are given additional flexibility for physician-guided reductions. We designed this individualized approach in response to feedback we received from investigators who prefer to use their discretion in titrating GCs as they would in a real-world scenario with the goal of reaching physiologic doses. Based on the early and profound decrease in A4 seen with antemelanin treatment in the Phase 2 study, we are measuring A4 at just two weeks after the study initiation and allowing investigators to assess glucocorticoid reduction immediately thereafter.
Dan: First patients are starting on as far as typically have their dose titrated every three months.
Speaker Change: As with any new therapy with the Cowen is to be progressively and we will work through the formulary review process with phase or the first six to nine months.
Dan: With three different doses.
Dan: It might take patients after nine months to get to the right doors, where the disease is under control.
Speaker Change: Our team is highly depended on confidence in navigating these initial steps to unlock the full opportunity authenticity.
Isabel Calafonos: Payers bear the cost of treatment for many months before the patient sees a benefit. In contrast, daily dosing of Pactucetin will allow titration to the optimal levels within weeks if titration is needed. Second, S&N's are not always correctly delivered, which can lead to higher costs to manage the resulting symptoms and size. For context, SRL injections are given with a large 18-19 gauge needle. The injections are unpleasant to receive and challenging to give. A research study conducted at MD Anderson, one of the leading centers, found that half of lung absinthes auto-attack injections administered by experienced nurses were not injected into the intramuscular phase.
Dan: Bears verticals of genome for many months before the patients see a benefit.
Speaker Change: The value proposition continues to resonate with patients health care professionals bears were optimistic that over time, but to sustain could become the new standard of care in acromegaly.
Dan: In contrast daily dosing of participating will allow us to station to the optimal levels within weeks.
Dan: Duration is needed.
Dan: Second is that as I know I always correctly, they lever, which can lead to higher cost of miners that result in central some side effects for.
And now then I would say regulatory update and additional details on our C. H H.
Speaker Change: Stage development strategy.
Dan: For context, sorry, injections are given where large 18 19 gauge needle the injections that I'm, placing to receive and challenge is to get it.
Speaker Change: Dana.
Thank you Isabel <unk>.
Speaker Change: Starting with Bell Tusa team, we continued to make progress in both the U S and EU, where a regulatory reviews remain on track we.
Dan: He said just conducted at MD Anderson, one of the new incentive plan that have a long often also at dice injections.
Speaker Change: We have not experienced any disruptions with our interactions with the FDA.
Dana Pizzuti: Midway through the study, participants will be on stable TC doses for several weeks so their A4 can be measured. Investigators will then have the option to titrate patients up to a 120 milligram dose of adameldin if the patient needs more A4 control. Otherwise, participants will continue on 80 milligrams. The key secondary and other endpoints are designed to demonstrate potential benefits beyond what has been achieved with existing standard of care for CAH patients. In addition to reductions in key disease biomarkers such as A4 and 17-OHP and other androgens, we will study improvement in the clinical signs and symptoms of CAH, including, but not limited to, restoration of menses, testicular adrenal rest tumors, or TARTs, and adrenal signs.
Dan: And I mean, they served by Astellas nurses, we're not injected into the intramuscular.
Speaker Change: Continue to expect a decision by September 2005.
Speaker Change: And as previously mentioned, we do not anticipate an advisory committee meeting as part of the NDA review.
Isabel Calafonos: The ripple of ultrathight instead persisted in the subcutaneous layer, where it formed nodules that sometimes became granular. It is important to note that if the drug is not administered properly, it might not achieve its intended efficacy. In addition, patients understand that injectable SRLs often do not provide adequate disease control for the duration of the injection cycle. According to our real-world data analysis, one-third of acromegaly patients on injectable SRLs receive more than the 13 injections per year expected based on an approved dosing, which is every four weeks. Consequently, this increases costs substantially for payers. Furthermore, uncontrolled acromegaly is associated with comorbidities and additional procedures, which are costly for payers and very burdensome for patients.
Dan: The depot ultra side instead for assisted in the South Quaternions layer, where the foreign nodules that sometimes became granular.
Speaker Change: The European Medicines agency has validated our MAA submission and granted orphan drug designation.
Dan: It is important to note that if the drug is not administer properly in mind, though that she is intended ethics.
Speaker Change: We believe the orphan drug designation highlights the unmet need in acromegaly and the potential benefit that <unk> can offer patients compared to existing therapies.
Dan: In addition, theres understand an injectable it sort of is often do not provide adequate. This is controlling for the addition of the injection site.
Speaker Change: Our team continues to work with regulatory authorities and the U S and EU on all aspects of the review process.
Dan: According to our real World data analysis, one third of acromegaly patients on injectable et cetera, So it's even more than that 15 injections per year.
Speaker Change: In preparation for launch our growing medical affairs team has been connecting with the endocrinology community.
Dan: That is based on an approved dosing, which is every four weeks.
Speaker Change: Our experienced endocrinologists kinetics had been making warm introductions for our medical science liaisons to all the top kols.
Dan: Consequently, this increases caused substantially for phase. Furthermore, agricultural acromegaly is associated with Comorbidities and additional procedures, which are causing this I'm very burdensome for patients.
Dana Pizzuti: Our primary endpoint will use morning androgen measurement post-GC dosing, consistent with the previous regulatory precedent. However, in our secondary endpoint, measuring these hormone levels pre-GC dosing is a rigorous test of efficacy because the androgen levels can be influenced by morning GC administration. Consistent with our patient-centric approach to drug development, we will include a novel, disease-specific patient-reported outcomes tool as part of the study design.
We posted roundtable discussions to deepen our understanding of the patient journey and gaps in treatment.
Isabel Calafonos: Lastly, R2-Cysteine 1 daily oral dosing offers an opportunity to improve patient adherence for more consistent continuity. Insam There remains a significant unmet need for safe, highly efficacious, easy-to-administer treatments that offer daily control, and the economic and clinical value that an option like patuxentine could provide to all its stakeholders is clear. These and other marketing sites continue to highlight meaningful and men-needed acromegaly and a strong enthusiasm for participating. During early launch, we anticipate menstrual uptake as we educate both healthcare providers and patient communities. As with any new therapy, we expect coverage to build progressively, and we will work through the formulary review process with you over the first six to nine months.
Dan: Lastly, anticipating once daily oral dosing offered us an opportunity to improve patient adherence for more consistent control.
Speaker Change: Isabel highlighted we have submitted multiple abstracts to upcoming endocrinology meetings that showcase <unk> differentiation.
Dan: In sum.
Speaker Change: Moving to Carcinoid syndrome, we expect to initiate the care ponder phase III trial in the second half of 2025.
Dan: There remains a significant unmet need for safe highly efficacious easy to administer students that offer daily control.
Dan: And the economic and clinical value than an offshore participating could provide solar stake holder is clear.
Speaker Change: Turning to <unk> on slide seven we added a fourth cohort to our phase II study due to the significant amount of enthusiasm and interest from sites and investigators.
Dana Pizzuti: The last piece of our CAH Development Program is the Combined Phase 2-3 Study in Pediatric Patients. We are finalizing our specific plans for integrating each age group into the registrational study, and we have already received helpful feedback from FDA and European authorities on our proposed study design. In summary, as illustrated on slide 9, we believe adamelanin has the potential to establish uncompromising treatment goals for people living with CAH by addressing both elevated androgens and reducing the need for supraphysiologic glucocorticoid dosing, which could lead to negative side effects for patients. We believe glucocorticoids should ideally only be used to provide physiologic replacement, not to treat the underlying disease.
Do you sound, a little marketing sites continue to highlight meaningful unmet need and acromegaly uninstall enthusiasm for participating today.
Speaker Change: Cohort four is just one part of our larger developments planned for at a moment in CAH and it is an exploratory analysis and a small group of six to 12 patients to evaluate 80 milligrams with morning dosing as opposed to evening dosing and the prior cohorts.
Dan: We had an early launch we anticipate administered uptake as we undertake both healthcare providers and patient communities.
Dan: As with any new therapy with cordis to be progressively.
Dan: We will reward the formulary review process with days or the first six to nine months.
Speaker Change: And to allow for glucocorticoid reduction.
Isabel Calafonos: Our team is highly prepared and confident in navigating these initial steps to unlock the full opportunity of authenticity. As the value proposition continues to resonate with patients, healthcare professionals, and payers, we are optimistic that over time, PACT216 could become the new standard of care in Acromega.
Dan: Our team is highly prepared I'm confident in navigating these initial steps to unlock the full opportunity of participating.
Speaker Change: As previously shared we are also conducting an open label extension study, which will provide real world insights into add amendments efficacy and safety over the long term.
Dan: The value proposition continues to resonate with patients health care professional Baird, we're optimistic that over time, but to sustain could become the new standard of care in acromegaly.
Speaker Change: <unk> will have the opportunity to titrate, both the dose of an amendment and the dose of gcs.
Speaker Change: It fit.
Speaker Change: Study participants from the Phase III study are given the opportunity to enroll in the OLED.
Dana Pizzuti: And now, Dana will share a regulatory update and additional detail on our CAH late-stage development strategy. Dana? Thank you, Isabel. Starting with Faltusatine, we continue to make progress in both the U.S. and E.U. where our regulatory reviews remain on track. We have not experienced any disruptions with our interactions with the FDA and continue to expect a decision by September 25th. And, as previously mentioned, we do not anticipate an advisory committee meeting as part of the NDA review. The European Medicines Agency has validated our MAA submission and granted orphan drug designation. We believe the orphan drug designation highlights the unmet need in acromegaly and the potential benefit that paltuzatine can offer patients compared to existing therapy.
Dan: And now they always say circulatory update and additional details on our C. H late stage development strategy.
Speaker Change: This study is ongoing and will eventually also include patients who complete phase III.
Dana Pizzuti: Our Phase III trial aims to provide a tailored approach to treatment for individual patients, enroll a broad patient population, inclusive of patients who can benefit from GC normalization, androgen normalization, or both, and measure clinical outcomes that are paramount to both HCPs and patients. Our vision is to lower the burden of disease overall and provide a new standard of care for the 17,000 plus people living with CAA.
Speaker Change: Turning to slide eight.
Dan: Dana.
Speaker Change: Thank you Isabel <unk>.
Speaker Change: Our phase III study for an amendment in adult CAH patients builds on the strong topline results, we shared from cohorts one through three of the phase III study.
Speaker Change: Starting with <unk> as a team we continue to make progress in both the U S and EU, where a regulatory reviews remain on track we.
Speaker Change: We have not experienced any disruptions with our interactions with the FDA.
Speaker Change: It is designed to provide a potential new therapeutic paradigm for patients.
Speaker Change: We continue to expect a decision by September 25.
Speaker Change: Scott mentioned, there is a significant need for new treatments in CAH that not only allow patients to lower their GC dose the physiologic levels, but also to control their androgens, which account for many of the signs and symptoms of the underlying disease.
Speaker Change: And as previously mentioned, we do not anticipate an advisory committee meeting as part of the NDA review.
Unknown Executive: Moving to slide 10.
Tobin Schilke: We are making steady progress on the rest of our pipeline, and we are pleased to announce IND Clearance 49682, the first candidate from our Non-Peptide Drug Conjugate, or NDC, platform. 9682 is being studied for SST2 positive tumors, including neuroendocrine tumors, or NETs, to complement our carcinoid syndrome indication with paltuzatine. Additionally, our discovery team continues to identify new ways to leverage the NDC platform for novel targets to address unmet needs in endocrine oncology. As mentioned in our press release, IND-enabling studies for the TSH antagonists are continuing as expected. Also, we continue to progress our SST3 agonist candidates.
Speaker Change: The European Medicines agency has validated our MAA submission and granted orphan drug designation.
Speaker Change: With this in mind, we are pursuing a novel primary endpoint that combines both goals.
Speaker Change: We believe the orphan drug designation highlights the unmet need in acromegaly and the potential benefit that <unk> can offer patients compared to existing therapies.
Speaker Change: The proportion of participants with a four levels less than or equal to the upper limit of normal and who are on physiologic doses of GC replacement at week 32 patients should not have to sacrifice, one or the other and treating CAH.
Dana Pizzuti: Our team continues to work with regulatory authorities in the U.S. and E.U. on all aspects of the review process. In preparation for launch, our growing medical affairs team has been connecting with the endocrinology community. Our experienced endocrinologists at Crinetics have been making warm introductions for our medical science liaisons to all the top KOLs. We've hosted roundtable discussions to deepen our understanding of the patient journey and gaps in treatment. As Isabel highlighted, we have submitted multiple abstracts to upcoming endocrinology meetings that showcase paltuzatine's differentiation.
Speaker Change: Our team continues to work with regulatory authorities and the U S and EU on all aspects of the review process.
Speaker Change: In preparation for launch our growing medical affairs team has been connecting with the endocrinology community.
Speaker Change: In this study we will enroll 150 participants who will be treated for 32 weeks, we will offer investigators to periods of time over which they can reduce gcs with four assessment visits in each period.
Speaker Change: Our experienced endocrinologists at kinetics had been making warm introductions for our medical science liaisons to all the top kols.
Speaker Change: Investigators are given additional flexibility for physician guided reductions.
Speaker Change: We've hosted roundtable discussions to deepen our understanding of the patient journey and gaps in treatment.
Tobin Schilke: Based on emerging data from IND-enabling studies, our PTH antagonist candidate, preclinical development, has been substituted with another candidate expected to exhibit an improved profile. This new candidate is in IND-enabling studies, which we intend to complete next year.
Speaker Change: We designed this individualized approach in response to feedback we received from investigators who prefer to use their discretion and titrated gcs as they were.
Speaker Change: Isabel highlighted we have submitted multiple abstracts to upcoming endocrinology meetings that showcase <unk> differentiation.
Speaker Change: Wood in a real world scenario with the goal of reaching physiological doses.
Dana Pizzuti: Moving to carcinoid syndrome, we expect to initiate the CARE FONDER Phase 3 trial in the second half of 2025. Turning to Adam Elnett on slide 7, we added a fourth cohort to our Phase 2 study due to the significant amount of enthusiasm and interest from sites and investigators. Cohort 4 is just one part of our larger development plan for adamelnut and CAH, and it is an exploratory analysis in a small group of 6 to 12 patients to evaluate 80 milligrams with morning dosing as opposed to evening dosing in the prior cohorts and to allow for glucocorticoid reduction.
Speaker Change: Moving to Carcinoid syndrome, we expect to initiate the care ponder phase III trial in the second half of 2025.
Speaker Change: Based on the early end profound decrease in a foreseen without amendment treatment in the phase two study we are measuring a four at just two weeks after the study initiation and allowing investigators to assess glucocorticoids production immediately director midway through this.
Tobin Schilke: This decision is reflective of the rigorous process we followed with Paltusatine and Adamillinant and that we apply to all our pipeline programs. We look forward to highlighting our early stage pipeline in more detail at our upcoming R&D day on June 26th. Of note, we will cover NETs and beyond with 9682 for SST2 expressing tumors and Beltuzetine for carcinoid syndrome. We will also present our TSH antagonists for Graves and thyroid eye disease and our SST3 antagonists for ADPKD. These programs represent the next generation of chronetics innovation and have the potential to positively impact the lives of patients and their caregivers across multiple communities.
Speaker Change: Turning to <unk> on slide seven we added a fourth cohort to our phase II study due to the significant amount of enthusiasm and interest from sites and investigators.
Speaker Change: Cohort four is just one part of our larger development plan for Adam element in CAH and it is an exploratory analysis and a small group of 6% to 12 patients to evaluate 80 milligrams with morning dosing as opposed to evening dosing and the prior cohorts and to allow for glucocorticoid reduction.
Speaker Change: Study participants will be on stable Tc doses for several weeks. So there are eight four can be measured.
Speaker Change: Investigators will then have the option to titrate patients up to 120 milligram dose of <unk>, if the patient needs more a for control.
Speaker Change: Otherwise participants will continue on 80 milligrams.
Dana Pizzuti: As previously shared, we are also conducting an open-label extension study which will provide real-world insights into Adam Mellon's efficacy and safety over the long term. Investigators will have the opportunity to titrate both the dose of adamalamin and the dose of GCs as they see fit. Study participants from the Phase 2 study are given the opportunity to enroll in the OLE. This study is ongoing and will eventually also include patients who complete Phase 3.
Speaker Change: As previously shared we are also conducting an open label extension study, which will provide real world insights into Adam elements efficacy and safety over the long term.
Speaker Change: The key secondary and other endpoints are designed to demonstrate potential benefits beyond what has been achieved with existing standard of care for CAH patients.
Tobin Schilke: With that, Toby will now provide the financial update. Thank you, Dana. Turning to slide 11.
Speaker Change: Investigators will have the opportunity to titrate, both the dose of <unk> amendment and the dose of gcs as they see fit study.
Tobin Schilke: I am pleased to be participating in my first earnings call at Crinetics. It is a privilege to join a team with a patient-centric mission and leading-edge science. We are poised for growth and, importantly, well-capitalized to execute on our ambitions. Now I will present the financial results for the first quarter of 2025. I will not read aloud the full results as they are available in our press release and on our Form 10-Q filing. Beginning with our income statement, we recognize $0.4 million of revenue during the first quarter of 2025 compared to $0.6 million during the same period in 2024.
Speaker Change: In addition to reductions in key disease, Biomarkers, such as a four and 17 OHP and other androgens, we will study improvement and the clinical signs and symptoms of CAH, including but not limited to restoration of menses testicular adrenal breast tumors or <unk>.
Speaker Change: Study participants from the Phase III study are given the opportunity to enroll in the OLED.
Speaker Change: This study is ongoing and will eventually also include patients who complete phase III.
Dana Pizzuti: Turning to slide eight. Our Phase III study for Adamelman in adult CAH patients builds on the strong top-line results we shared from Cohorts 1 through 3 of the Phase II study. It is designed to provide a potential new therapeutic paradigm for patients. As Scott mentioned, there is a significant need for new treatments in CAH that not only allow patients to lower their GC dose to physiologic levels, but also to control their androgens, which account for many of the signs and symptoms of the underlying disease. With this in mind, we are pursuing a novel primary endpoint that combines both goals.
Speaker Change: Turning to slide eight.
Speaker Change: Parts and adrenal size.
Speaker Change: Our phase III study for Adam Melnyk, and adult CAH patients builds on our strong topline results, we shared from cohorts one through three of the phase III study.
Speaker Change: Our primary endpoint will use morning, androgen measurement post GC dosing consistent with the previous regulatory precedent.
Speaker Change: It is designed to provide a potential new therapeutic paradigm for patients.
Speaker Change: However, in our secondary endpoints measuring these hormone levels pre GC dosing is a rigorous test of efficacy because the androgen levels can be influenced by morning GC administration.
Speaker Change: As Sean mentioned, there is a significant need for new treatments in CAH that not only allow patients to lower their GC dose the physiologic levels, but also to control their androgens, which account for many of the signs and symptoms of the underlying disease.
Tobin Schilke: As a reminder, this revenue is non-cash and is based on amortization of payments we received in connection with our Paltusatine licensing arrangement with our Japanese partner, SKK. Our research and development expenses in the first quarter of 2025 were $76.2 million, a 43% increase compared to the same period in 2024. Excluding depreciation, amortization, and stock-based compensation, R&D expense was $64.4 million. The increase in R&D expenses was primarily due to additional personnel, increased manufacturing costs, and higher outside services costs to advance our clinical programs and expand our preclinical portfolio. We expect quarterly R&D spend to increase sequentially through the remainder of the year, primarily driven by phase 3 clinical trials for paltuzatine and atumelna.
Speaker Change: Consistent with our patient centric approach to drug development. We will include a novel disease specific patient reported outcomes tool as part of the study design.
Speaker Change: With this in mind, we are pursuing a novel primary endpoint that combines both kohl's the proportion of participants with a four levels less than or equal to the upper limit of normal.
Speaker Change: The last piece of our CAH development program is the combined phase two three study in pediatric patients. We are finalizing our specific plans for integrating each age group into the Registrational study and we have already received helpful feedback from FDA and European authorities on a.
Dana Pizzuti: The proportion of participants with A4 levels less than or equal to the upper limit of normal and who are on physiologic doses of GC replacement at week 32. Patients should not have to sacrifice one or the other in treating CAH. In this study, we will enroll 150 participants who will be treated for 32 weeks. We will offer investigators two periods of time over which they can reduce GCs with four assessment visits in each period. Investigators are given additional flexibility for physician-guided reductions.
Speaker Change: And who are on physiologic doses of GC replacement at week 32 patients should not have to sacrifice, one or the other and treating CAH.
Speaker Change: Post study design.
Speaker Change: In this study will enroll 150 participants who will be treated for 32 weeks.
Speaker Change: In summary, as illustrated on slide nine we believe Adam element has the potential to establish uncompromising treatment goals for people living with CAH by addressing both elevated androgens and reducing the need for Super physiologic, glucocorticoid dosing, which could lead.
We will offer investigators to periods of time over which they can reduce gcs with four assessment visits in each period.
Speaker Change: Investigators are given additional flexibility for our physician guided reductions.
Dana Pizzuti: We designed this individualized approach in response to feedback we received from investigators who prefer to use their discretion in titrating GCs as they would in a real-world scenario with the goal of reaching physiologic doses. Based on the early and profound decrease in A4 seen without a melanin treatment in the Phase 2 study, we are measuring A4 at just two weeks after the study initiation and allowing investigators to assess glucocorticoid reduction immediately thereafter. Midway through the study, participants will be on stable DC doses for several weeks so their A4 can be measured. Investigators will then have the option to titrate patients up to a 120 milligram dose of adamelnan if the patient needs more A4 control.
Speaker Change: We designed this individualized approach in response to feedback we received from investigators who prefer to use their discretion and titrated in gcs as they would in a real world scenario with the goal of reaching physiological doses.
Speaker Change: The negative side effects for patients.
Tobin Schilke: Our selling, general, and administrative expenses for the first quarter of 2025 were $35.5 million, a 71% increase compared to the same period in 2024, excluding depreciation, amortization, and stock-based compensation. SG&A expense was $26.2 million. The increase in SG&A expense was primarily driven by growth to support our ongoing programs and the planned commercial launch of paltuzatine. We expect quarterly SG&A investment to increase sequentially through the remainder of the year as we continue to build our commercial infrastructure and prepare for the anticipated launch of paltuzatine. Our cash used in operations for the three months ending March 31st, 2025 was $88.5 million compared to $52.9 million for the same period in 2024.
Speaker Change: We believe glucocorticoid should ideally only be used to provide physiologic replacement not to treat the underlying disease.
Speaker Change: Our phase III trial aims to provide a tailored approach to treatment for individual patients enroll a broad patient population inclusive of patients who could benefit from Tc normalization androgen normalization or both.
Speaker Change: Based on the early end profound decrease in a foreseen without amendment treatment in the phase two study we are measuring a four at just two weeks after the study initiation and allowing investigators to assess glucocorticoids production immediately thereafter midway through this study.
Speaker Change: And measure clinical outcomes that are paramount to both hcp's and patients.
Speaker Change: Our vision is to lower the burden of disease overall and provide a new standard of care for the 17000 plus people living with CAH.
Speaker Change: Participants will be on stable Tc doses for several weeks. So there are eight four can be measured invest.
Speaker Change: Investigators will then have the option to titrate patients up to 120 milligram dose of Adam Melded, if the patient needs more a for control otherwise participants will continue on 80 milligrams.
Speaker Change: Moving to slide 10, we are making steady progress on the rest of our pipeline and we are pleased to announce IND clearance for $96 eight to the first candidate from our non peptide drug conjugate or MDC platform.
Dana Pizzuti: Otherwise, participants will continue on 80 milligrams. The key secondary and other endpoints are designed to demonstrate potential benefits beyond what has been achieved with existing standard of care for CAH patients. In addition to reductions in key disease biomarkers, such as A4 and 17-OHP, and other androgens, we will study improvement in the clinical signs and symptoms of CAH, including, but not limited to, restoration of menses, testicular adrenal rest tumors, or TARTs, and adrenal Our primary endpoint will use morning androgen measurement post-GC dosing, consistent with the previous regulatory precedent. However, in our secondary endpoint, measuring these hormone levels pre-GC dosing is a rigorous test of efficacy because the androgen levels can be influenced by morning GC administration.
Speaker Change: The key secondary and other endpoints are designed to demonstrate potential benefits beyond what has been achieved with existing standard of care for CAH patients.
Speaker Change: 960, <unk> is being studied for SST, two positive tumors, including neuro endocrine tumors or net to complement our carcinoid syndrome indication with Perl Tusa team.
Tobin Schilke: For 2025, we continue to anticipate our cash use and operations to be between $340 and $380 million. This compares to $226 million of cash used in operations in 2024. Approximately 60% of the increase relative to 2024 is due to R&D investments, with the balance due to SG&A. Turning to slide 12. We ended the first quarter of 2025 on strong financial footing with approximately $1.3 billion in cash, cash equivalents, and investments. which we continue to expect to fund our operations into 2029. As a reminder, we could potentially receive up to $250 million if Lilly exercises its option to acquire RadioNetwork.
Speaker Change: In addition to reductions in key disease, Biomarkers, such as <unk>, four and 17 OHP and other androgens, we will study improvement and the clinical signs and symptoms of CAH, including but not limited to restoration of menses testicular adrenal breast tumors or <unk>.
Speaker Change: Additionally, our discovery team continues to identify new ways to leverage the MDC platform for novel targets to address unmet needs and endocrine oncology.
Speaker Change: As mentioned in our press release IND, enabling studies for the TSA <unk> antagonist are continuing as expected also we continue to progress our SST three agonist candidate.
Speaker Change: Hearts and adrenal size.
Speaker Change: Our primary endpoint will use morning, androgen measurement post GC dosing consistent with the previous regulatory precedent.
Speaker Change: Based on emerging data from IND, enabling studies are PTH antagonist candidate preclinical development has been substituted with another candidate expected to exhibit an improved profile. This new candidate is in IND, enabling studies, which we intend to complete next year.
Speaker Change: However, in our secondary endpoints measuring these hormone levels pre GC dosing is a rigorous test of efficacy because the androgen levels can be influenced by morning GC administration.
Dana Pizzuti: Consistent with our patient-centric approach to drug development, we will include a novel, disease-specific, patient-reported outcomes tool as part of the study design.
Speaker Change: Consistent with our patient centric approach to drug development. We will include a novel disease specific patient reported outcomes tool as part of the study design.
Speaker Change: This decision is reflective of the rigorous process, we followed with <unk> and at the moment and that we apply to all of our pipeline programs.
Tobin Schilke: Crinetics has always been disciplined with capital allocation, and we continue to take a prudent approach to execute on the compelling opportunities ahead of us. We believe our strong balance sheet positions us to deliver on our near-term milestones, including the anticipated approval and launch of Paltuzatine, and advance our deep and rich pipeline in parallel.
Speaker Change: We look forward to highlighting our early stage pipeline in more detail at our upcoming R&D day on June 26 of known we will cover nets and beyond with 90 682 for SSG to expressing tumors <unk> <unk> for carcinoid syndrome.
Dana Pizzuti: The last piece of our CAH development program is the combined Phase 2-3 study in pediatric patients. We are finalizing our specific plans for integrating each age group into the registrational study, and we have already received helpful feedback from FDA and European authorities on our proposed study design.
Speaker Change: The last piece of our CAH development program is a combined phase two three study in pediatric patients. We are finalizing our specific plans for integrating each age group into the Registrational study and we have already received helpful feedback from FDA and European authorities on a.
Scott Struthers: I'll now turn it over to Scott for closing remarks. Thank you, Toby. Moving on to slide 13.
We will also present, our TSH antagonist for grades at <unk>, and our <unk> agonist for PK data.
Speaker Change: Post study design.
Dana Pizzuti: In summary, as illustrated on slide 9, we believe adamelanin has the potential to establish uncompromising treatment goals for people living with CAH by addressing both elevated androgens and reducing the need for supraphysiologic glucocorticoid dosing, which could lead to negative side effects for patients. We believe glucocorticoids should ideally only be used to provide physiologic replacement, not to treat the underlying disease. Our Phase III trial aims to provide a tailored approach to treatment for individual patients and enroll a broad patient population, inclusive of patients who can benefit from GC normalization, androgen normalization, or both, and measure clinical outcomes that are paramount to both HCPs and patients.
Scott Struthers: At Crinetics, our core mission is to improve patients' lives and transform the treatment paradigm in areas of serious unmet need like acromegaly. For over 10 years, we have partnered with patients for their direct input on our discovery effort, clinical designs. Patient Research. We design our therapies to allow patients to live their best lives instead of letting their disease define them.
Speaker Change: In summary, as illustrated on slide nine we believe Adam Melnyk has the potential to establish uncompromising treatment goals for people living with CAH by addressing both elevated androgens and reducing the need for Super physiologic, glucocorticoid dosing, which could lead.
Speaker Change: These programs represent the next generation of kinetics innovation and have the potential to positively impact the lives of patients and their caregivers across multiple communities with that Toby will now provide the financial update.
Toby Shocking: Thank you Dana turning to slide 11, I am pleased to be participating in my first earnings call at kinetics. It is a privilege to join a team with our patient centric mission and leading edge science.
Speaker Change: The negative side effects for patients.
Scott Struthers: With our strong pipeline of late and early stage candidates and the support of our robust balance sheet, we are well positioned to deliver on our clinical, regulatory, and commercial priorities in 2025 and beyond.
Speaker Change: We believe glucocorticoid should ideally only be used to provide physiologic replacement not to treat the underlying disease.
Toby Shocking: Poised for growth and importantly, well capitalized to execute on our ambition.
Speaker Change: Our phase III trial aims to provide a tailored approach to treatment for individual patients enroll a broad patient population inclusive of patients who could benefit from Tc normalization androgen normalization or both.
Toby Shocking: Now I will present, the financial results for the first quarter of 2025, I will not read aloud before results as they are available in our press release and on our Form 10-Q filing.
Operator: With that, I'll hand the call back to the operator to begin the Q&A. Please limit yourselves to one question each in the interest of time.
Operator: Operator. Thank you, Scott.
Speaker Change: And measure clinical outcomes that are paramount to both HCP and patients.
Operator: To ask a question, please press star followed by one on your telephone keypad. Now, if you change your mind, please press star followed by two. When preparing to ask your question, please ensure your device is unmuted locally.
Toby Shocking: Beginning with our income statement, we recognized zero point $4 million of revenue during the first quarter of 2025 compared to zero point $6 million. During the same period in 2024 as a reminder, this revenue is noncash and is based on amortization of payments we received in connection.
Dana Pizzuti: Our vision is to lower the burden of disease overall and provide a new standard of care for the 17,000 plus people living with CAA.
Speaker Change: Our vision is to lower the burden of disease overall and provide a new standard of care for the 17000 plus people living with CAH.
Dana Pizzuti: Moving to slide 10. We are making steady progress on the rest of our pipeline, and we are pleased to announce IND clearance for 9682, the first candidate from our non-peptide drug conjugate, or NDC, platform. 9682 is being studied for SST2-positive tumors, including neuroendocrine tumors, or NETs, to complement our carcinoid syndrome indication with paltuzatine.
Speaker Change: Moving to slide 10, we are making steady progress on the rest of our pipeline and we are pleased to announce IND clearance for $96 eight to the first candidate from our non peptide drug conjugate or MDC platform.
Yasmeen Rahimi: First question comes from Yasmeen Rahimi with Piper Sandler. Your line is open, please go ahead. Good afternoon, team. Thank you so much for all the great updates. Two quick questions. The first question is, could you talk about the power of your very innovative primary endpoint, which is a co-primary? And then short question for Cohort 4, have you been able to collect any data from that cohort yet? And I'll jump back in the queue. Thank you again. Thanks, Jeff.
Toby Shocking: With our Pal tusa team licensing arrangement with our Japanese partner <unk> K K.
Toby Shocking: Our research and development expenses in the first quarter of 2025 or $76 2 million a.
Speaker Change: 962 is being studied for SST, two positive tumors, including neuro endocrine tumors or nets to complement our carcinoid syndrome indication with Perl Tusa team.
Toby Shocking: A 43% increase compared to the same period in 2024.
Toby Shocking: Excluding depreciation amortization and stock based compensation R&D expense was $64 4 million the increase in R&D expenses was primarily due to additional personnel increased manufacturing costs and higher outside services costs to advance our clinical programs.
Dana Pizzuti: Additionally, our discovery team continues to identify new ways to leverage the NDC platform for novel targets to address unmet needs in endocrine oncology. As mentioned in our press release, IND-enabling studies for the TSH antagonists are continuing as expected. Also, we continue to progress our SST3 agonist candidate.
Speaker Change: Additionally, our discovery team continues to identify new ways to leverage the MDC platform for novel targets to address unmet needs and endocrine oncology.
Alan Krasner: I'll hand that over to Alan to answer. Well, hi, yes. So with regard to powering of the study, I would say it's very highly powered to detect statistically significant differences between the treatment arm and the placebo arm across a range of potential deltas between groups. And I think that Dr. Melvin is well-situated to achieve this endpoint that Dana discussed earlier, showing both normalization of A4 and physiologic dosing of glucocorticoid.
Speaker Change: As mentioned in our press release IND, enabling studies for the TSA to antagonist are continuing as expected also we continue to progress our SST three agonist candidate.
Toby Shocking: <unk> and expand our preclinical portfolio.
Toby Shocking: We expect quarterly R&D spend to increase sequentially through the remainder of the year, primarily driven by phase III clinical trials for <unk> in <unk> melanoma.
Dana Pizzuti: Based on emerging data from IND-enabling studies, our PTH antagonist candidate preclinical development has been substituted with another candidate expected to exhibit an improved profile. This new candidate is in IND-enabling studies, which we intend to complete next year.
Speaker Change: Based on emerging data from IND, enabling studies are PTH antagonist candidate preclinical development has been substituted with another candidate expected to exhibit an improved profile. This new candidate is in IND, enabling studies, which we intend to complete next year.
Toby Shocking: Our selling general and administrative expenses for the first quarter of 2025 or $35 5 million or.
Toby Shocking: 71% increase compared to the same period in 2024, excluding depreciation amortization and stock based compensation SG&A expense was $26 2 million. The increase in SG&A expense was primarily driven by growth to support our ongoing programs.
Dana Pizzuti: This decision is reflective of the rigorous process we followed with Paltusatine and Adamillinant and that we apply to all our pipeline programs. We look forward to highlighting our early stage pipeline in more detail at our upcoming R&D day on June 26th. Of note, we will cover NETs and beyond with 9682 for SST2 expressing tumors and Beltuzetine for carcinoid syndrome. We will also present our TSH antagonists for Graves and thyroid eye disease and our SST3 antagonists for ADPKD. These programs represent the next generation of chronetics innovation and have the potential to positively impact the lives of patients and their caregivers across multiple communities.
Speaker Change: This decision is reflective of the rigorous process, we followed with <unk> in a moment.
Alan Krasner: With regard to Cohort 4, this is enrolling and I can't speak yet to timing of data. I think what we would do, of course, is show new data at scientific meetings, but the timing of that I can't comment on quite yet.
Speaker Change: And that we apply to all of our pipeline programs.
Speaker Change: We look forward to highlighting our early stage pipeline in more detail at our upcoming R&D day on June 26 of known we will cover <unk> beyond with 962 for SST, two expressing tumors <unk> <unk> for Carcinoid syndrome, we will also present, our TSH antagonist for Grace.
Toby Shocking: And the planned commercial launch of <unk>, we expect quarterly SG&A investment to increase sequentially through the remainder of the year as we continue to build our commercial infrastructure and prepare for the anticipated launch of <unk>.
Alan Krasner: One other lexicon thing I'd like to mention is the kind of primary endpoint we're talking about. I think it's better described as a composite endpoint rather than a co-primary endpoint. There are two components to the endpoint. A co-primary, though, is something else where you kind of have to, each component has to statistically stand by itself, whereas a co-primary is, it's basically a responder analysis where a responder is defined as having both normal glucocorticoid doses and normal A4 levels.
Speaker Change: Thyroid eye disease, and our <unk> agonist for PK T.
Toby Shocking: Our cash used in operations for the three months ending March 31, 2025 was $88 5 million compared to $52 9 million for the same period in 2024.
Speaker Change: These programs represent the next generation of kinetics innovation and have the potential to positively impact the lives of patients and their caregivers across multiple communities with that Toby will now provide the financial update.
Toby Schilke: With that, Toby will now provide the financial update. Thank you, Dana. Turning to slide 11.
Toby Shocking: For 2025, we continue to anticipate our cash used in operations to be between 340 and $380 million.
Toby Soaking: Thank you Dana turning to slide 11, I am pleased to be participating in my first earnings call at kinetics. It is a privilege to join a team with a patient centric mission and leading edge science, we are poised for growth and importantly, well capitalized to execute on our ambition.
Toby Schilke: I am pleased to be participating in my first earnings call at Crinetics. It is a privilege to join a team with a patient-centric mission and leading-edge science. We are poised for growth and, importantly, well-capitalized to execute on our ambition. Now I will present the financial results for the first quarter of 2025. I will not read aloud the full results as they are available in our press release and on our Form 10-Q filing. Beginning with our income statement, we recognize $0.4 million of revenue during the first quarter of 2025 compared to $0.6 million during the same period in 2024.
Toby Shocking: This compares to $226 million of cash used in operations in 2024.
Jessica Fye: Our next question comes from Jessica Fye with J.P. Morgan. Your line is open, please go ahead. Hey guys. Is the COMM-CAH study design fully signed off on by FDA as a trial that could support registration? And what indication statement would you hope to secure assuming the trial is successful? Do you think you'd need one or two trials to get approved? Thanks, Jeff.
Toby Shocking: Approximately 60% of the increase relative to 2024 is due to R&D investments with the balance due to SG&A.
Toby Soaking: Now I will present, the financial results for the first quarter of 2025.
Toby Shocking: Turning to slide 12, we ended the first quarter of 2025 on strong financial footing with approximately $1 $3 billion in cash cash equivalents and investments, which we continue to expect to fund our operations into 2029.
Toby Soaking: I'll not read aloud before results as they are available in our press release and on our Form 10-Q filing.
Toby Soaking: Winning with our income statement, we recognized zero point $4 million of revenue during the first quarter of 2025 compared to zero point $6 million. During the same period in 2024 as a reminder, this revenue is noncash and is based on amortization of payments we received in connection with.
Dana Pizzuti: I'll let Dana answer that one. Yeah, sure, Jeff. Thanks for the question.
Toby Shocking: As a reminder, we could potentially receive up to $250 million, if lilly exercises its option to acquire radio and Alex <unk>.
Dana Pizzuti: The protocol was, you know, put together based upon input from FDA as well as other health authorities, and they are aware of the final study design. I think that, you know, the other parts of your question were about the indications. Yeah, it's hard to say right now an indication, but I think what... You know, and the data, of course, will, you know, will define what we can, you know, talk with the agency about, but, you know, the basic, you know, difference that we have is what we are trying to develop here is a drug that will treat the disease, the CAH, right, and will only need glucocorticoids for a prevention of adrenal insufficiency.
Toby Schilke: As a reminder, this revenue is non-cash and is based on amortization of payments we received in connection with our Paltusatine licensing arrangement with our Japanese partner, SKK. Our research and development expenses in the first quarter of 2025 were $76.2 million, a 43% increase compared to the same period in 2024. Excluding depreciation, amortization, and stock-based compensation, R&D expense was $64.4 million. The increase in R&D expenses was primarily due to additional personnel, increased manufacturing costs, and higher outside services costs to advance our clinical programs and expand our preclinical portfolio. We expect quarterly R&D spend to increase sequentially through the remainder of the year, primarily driven by Phase III clinical trials for paltuzatine and atumelna.
Toby Shocking: <unk> has always been disciplined with capital allocation and we continue to take a prudent approach to execute on the compelling opportunities ahead of US we believe our strong balance sheet positions us to deliver on our near term milestones, including the anticipated approval and launch of <unk>.
Toby Soaking: Our Pal tusa team licensing arrangement with our Japanese partner <unk> K K.
Toby Soaking: Our research and development expenses in the first quarter of 2025 or $76 2, million% to 43% increase compared to the same period in 2024 exclude.
Toby Shocking: And advance our deep and rich pipeline in parallel.
Toby Soaking: Excluding depreciation amortization and stock based compensation R&D expense was $64 4 million the increase in R&D expenses was primarily due to additional personnel increased manufacturing costs and higher outside services costs to advance our clinical program.
Scott: I'll now turn it over to Scott for closing remarks Scott.
Scott: Thank you Toby moving on to slide 13.
Speaker Change: At kinetics, our core mission is to improve patient flows and transform the treatment paradigm in areas of serious unmet need like an incremental.
Speaker Change: For over 10 years, we have partnered with patients for the direct input on our discovery effort clinical designs and patient resources.
Toby Soaking: <unk> and expand our preclinical portfolio.
Toby Soaking: We expect quarterly R&D spend to increase sequentially through the remainder of the year, primarily driven by phase III clinical trials for <unk> and <unk> melanoma.
Dana Pizzuti: For more information, visit www.FEMA.gov So, if you look at the chronicity indication, it's as an adjunct to glucocorticoids for the control of androgens. And so that implies that glucocorticoids are necessary to control the androgens. In our situation, based upon our Phase II data, it's the adamant that's really going to drive the, you know, production in androgens, and therefore you don't need glucocorticoids to treat that part of the disease. And as I mentioned, you know, when we did the call, we really only expect that the group of corticosteroids will be used for, you know, physiologic replacement.
Speaker Change: We design our therapies to allow patients to live their best lives instead of letting the disease.
Toby Schilke: Our selling, general, and administrative expenses for the first quarter of 2025 were $35.5 million, a 71% increase compared to the same period in 2024, excluding depreciation, amortization, and stock-based compensation, SG&A expense was $26.2 million. The increase in SG&A expense was primarily driven by growth to support our ongoing programs and the planned commercial launch of paltuzatine. We expect quarterly SG&A investment to increase sequentially through the remainder of the year as we continue to build our commercial infrastructure and prepare for the anticipated launch of paltuzatine. Our cash used in operations for the three months ending March 31st, 2025 was $88.5 million, compared to $52.9 million for the same period in 2024.
Toby Soaking: Our selling general and administrative expenses for the first quarter of 2025, or $35 5 million or 71% increase compared to the same period in 2024, excluding depreciation amortization and stock based compensation SG&A expense was $26 two.
Speaker Change: With our strong pipeline of late and early stage candidates and the support of our robust balance sheet, we are well positioned to deliver on our clinical regulatory and commercial priorities in 2025 and beyond.
Speaker Change: With that I'll hand, the call back to the operator to begin the Q&A. Please limit yourselves to one question each in interest of time.
Toby Soaking: $2 million.
Toby Soaking: The increase in SG&A expense was primarily driven by growth to support our ongoing programs and the planned commercial launch of <unk>.
Speaker Change: Operator.
Speaker Change: Okay.
Speaker Change: Thank you Scott to ask a question. Please press star followed by one on your telephone keypad now.
Toby Soaking: We expect quarterly SG&A investment to increase sequentially for the remainder of the year as we continue to build our commercial infrastructure and prepare for the anticipated launch of <unk>.
Speaker Change: If you change your mind, Please press star followed by two.
Dana Pizzuti: So, we expect that that could, you know, result in a slight difference in how the indication is, you know, granted.
Speaker Change: When preparing to ask a question. Please ensure your device is on mute locally.
Speaker Change: First question comes from Yasmine <unk> with Piper Sandler Your line is open. Please go ahead.
Toby Soaking: Our cash used in operations for the three months ending March 31, 2025 was $88 5 million compared to $52 9 million for.
Yasmine: Good afternoon. Thank you so much for all the great updates two quick question. The first question is could you talk about the powering.
Gavin Clark: Our next question comes from Gavin Clark Gartner with Evercore ISI. Your line is open, please go ahead. Hey guys, thanks for taking the questions.
Speaker Change: Okay.
Toby Soaking: For the same period in 2024 for.
Toby Schilke: For 2025, we continue to anticipate our cash used in operations to be between $340 and $380 million. This compares to $226 million of cash used in operations in 2024. Approximately 60% of the increase relative to 2024 is due to R&D investments, with the balance due to SG&A. Turning to slide 12. We ended the first quarter of 2025 on strong financial footing with approximately $1.3 billion in cash, cash equivalents and investments. which we continue to expect to fund our operations into 2029. As a reminder, we could potentially receive up to $250 million if Lilly exercises its option to acquire Radionetic.
Speaker Change: <unk> innovative primary endpoint, which is a co primary.
Toby Soaking: For 2025, we continue to anticipate our cash used in operations to be between 340 and $380 million.
Speaker Change: Then short question for cohort four have you been able to collect any data from that cohort here and I'll jump back in the queue. Thank you again.
Unknown Executive: First, just on the primary endpoint for the phase three, what's the rationale to test Transcripts provided by Transcription Outsourcing, LLC. Thanks for the question, Gavin. I think generally responder analyses are conducted at single points in time rather than averages. There is always variability with biochemical markers. Before, I think, of all the choices in this disease state, it's one of the least variable. And again, there's a lot of confidence that this compound can achieve both components of the composite primary endpoint. And therefore, the odds that variability would – variability might explain, you know, one of these endpoints hitting it once in a while on an occasional occasion.
Toby Soaking: This compares to $226 million of cash used in operations in 2024.
Speaker Change: Thanks, Jeff I'll hand that over to Alan to answer.
Toby Soaking: Approximately 60% of the increase relative to 2024 is due to R&D investments with the balance due to SG&A.
Alan: Well, yes.
Alan: So with regard the powering of the study.
Alan: I would say, it's very highly powered to do.
Alan: Statistically significant differences between the treatment arm and the placebo arm.
Toby Soaking: Turning to slide 12, we ended the first quarter of 2025 on strong financial footing with approximately $1 $3 billion in cash cash equivalents and investments, which we continue to expect to fund our operations into 2029.
Alan: Across a range of potential deltas between groups.
Alan: And I think that.
Speaker Change: <unk> is well situated to achieve this endpoint that Dana discussed earlier selling both normalization of Ey for Ann.
Toby Soaking: As a reminder, we could potentially receive up to $250 million, if lilly exercises its option to acquire radio and ethics.
Alan: Physiologic dosing of Coker protocol.
Alan: Okay.
Alan: Yes.
Toby Schilke: Crinetics has always been disciplined with capital allocation, and we continue to take a prudent approach to execute on the compelling opportunities ahead of us. We believe our strong balance sheet positions us to deliver on our near-term milestones, including the anticipated approval and launch of Paltuzatine, and advance our deep and rich pipeline in parallel.
Alan: With regard to cohort four.
Toby Soaking: <unk> has always been disciplined with capital allocation and we continue to take a prudent approach to execute on the compelling opportunities ahead of US we believe our strong balance sheet positions us to deliver on our near term milestones, including the anticipated approval and launch of <unk>.
Alan: This is enrolling and.
Alan: I can't I can't speak yet to timing Dave.
Alan: I think what we would do and of course this show.
Unknown Executive: But hitting both is quite, I think, specific. And I would anticipate, you know, pretty strong results that are clearly delineated from placebo.
Alan: New data at scientific meetings, but the timing of that I can't comment on quite yet.
Alan: One other.
Toby Soaking: And advance our deep and rich pipeline in parallel.
Scott Struthers: I'll now turn it over to Scott for closing remarks. Scott? Thank you, Toby. We're moving on to slide 13.
Alan: What's the kind of thing I would like to mention is the.
Toby Soaking: and Advanced Art Deep Enriched Pipeline in parallel. I'll now turn it over to Scott for closing remarks. Scott? All right.
Unknown Executive: Our next question comes from Tyler Van Buren with TD Securities. Your line is open, please go ahead. Hi, this is Frances on for Tyler. So just one question about the four cohort.
Alan: Kind of primary endpoint, we're talking about I think it is better described as a composite endpoint rather than a co primary endpoint. There are two components to the endpoint a co primary though it's something else for a half day each component has to statistically standby itself.
Scott Struthers: At Crinetics, our core mission is to improve patients' lives and transform the treatment paradigm in areas of serious unmet need like acromegaly. For over 10 years, we have partnered with patients for their direct input on
Thank you Toby, for moving on to slide 13.
Unknown Executive: So what is the rationale for looking at the morning dosing versus the evening dosing? Yeah, thanks. Thanks for the question.
Toby Soaking: For over 10 years, we are partnering with patients for the direct.
Alan: Whereas a co primary is it's basically a responder analysis square a responder is defined as having both normal glucocorticoid doses and normal <unk> levels.
Scott Struthers: This is Scott. You know, I think for many of us, It would be more convenient to perhaps take the drug in the morning rather than in the evening, and we just wanted to explore that to provide future optionality for patients. And maybe just to clarify a little bit, reminder that there's a, there's a strong diurnal rhythm in this axis, including in the CAH patients. And so you just want to be sure that the timing of the drug in response, in respect to the diurnal rhythm doesn't have a significant effect.
Alan: Okay.
Alan: Okay.
Speaker Change: Our next question comes from Jessica Fye with Jpmorgan. Your line is open. Please go ahead.
Speaker Change: Hey, guys good afternoon.
Speaker Change: The call CAH study design fully signed off on by FDA as a trial that could support registration and what indication statement would you hope to secure assuming the trial is successful do you think you'd need one or two trials to get approved for CAH. Thank you.
Dan: Thanks, Jeff I'll, let Dan answer that one yes sure Jess thanks for the question.
Dan: The protocol was.
Dan: Put together based upon input from.
Cory Jubinville: Our next question comes from Cory Jubinville with Lifesci Capital. Your line is open, please go ahead. Good afternoon, thanks for taking our questions. So, you know, you folks have recently received acceptance for your marketing application for paltusatine in Europe.
Dan: From FDA as well as other health authorities and they are aware of the final study design.
Dan: I think that.
Dan: Okay.
Dan: Yes.
Dan: The other parks.
Dan: Your.
Dan: About the indication space.
Isabel Calafonos: Curious how you're thinking about launch strategy in these different geographies. You know, you previously discussed patient concentration in the US is largely at these pituitary centers of excellence. Is patient concentration similar to those in Europe and or Latin America? And what, if any, are some of the material differences in the way that acromegaly patients might be treated in those geographies that might be important to consider for a launch Yeah, that's a great question, Cory. So, um...
Dan: It's hard to say right now an indication, but I think what.
Dan: And the data of course will.
Dan: Well defined what we can.
Dan: Talk with the agency about but.
Dan: The basic difference that we have.
Dan: What we are trying to.
Dan: Develop here is a drug that will treat the disease, the CAH, alright, and will only need glucocorticoid for prevention of Greenhorn sufficiency.
Dan: So if you look at the <unk> indication.
Dan: As an adjunct to glucocorticoid for the control of androgens.
Isabel Calafonos: I'm going to hand that off to Isabel, who's on the line here. Go ahead, Isabel. Sorry. Sure, no problem. Hi, Cory. Yes, so we are very excited to have the filing approved and we are preparing for the launch in Germany where also there is a significant unmet need for patients with acromegaly. So, to your question, the European markets tend to be more concentrated in terms of even more patients are part of the Centers of Excellence. There is a little bit more of community in Germany than the rest of the markets, but it's still, you know, a ratio of about 70 to 30%, 70% of key centers.
Dan: And so that implies that the glucocorticoids are necessary to control the androgens and our situation based upon our phase two data.
Dan: Adam element, that's really going to drive.
Dan: Production in androgens, and therefore, you don't need for <unk> to treat that part of the disease.
Dan: And as I mentioned.
Dan: When we did the call we really only expect that <unk>.
Dan: <unk> will be used for physiologic replacement so.
Dan: We expect that that could.
Dan: Results in a slight difference and how the indication is is granted.
Isabel Calafonos: We continue to do research to confirm that. And so, highly concentrated. We are working extensively in our market access strategy and in our discussions with GBA and the different markets. And we are going to be very progressive and be very thoughtful about how we continue to expand there.
Dan: Our next.
Speaker Change: Comes from Kevin Clark Gardiner with Evercore ISI. Your line is open. Please go ahead.
Hey, guys. Thanks for taking the questions.
Speaker Change: First just on the primary endpoint for the phase III.
Speaker Change: What's the rationale to test the endpoint at a single point in time at 32 weeks as opposed to averaging across multiple time points is there any risk that a poor variability may lead to some non responders, who maybe it shouldnt be non responders.
Isabel Calafonos: So right now we have a footprint in Zouk, we have our team in place in Germany, and it's a very small group of resources that we think will help us maximize the opportunity there and help as many patients. Regarding Latin America, you have seen also that there is a high unmet need and a lot of patients that have been identified. So the one country that we have considered as the next country for expansion is Brazil. As you have seen in our clinical trials, over 30 patients in our acromegaly studies were recruited there. We have very good relationships with the different centers, and it's also concentrated.
Speaker Change: Alright, Thanks for the question Kevin.
Speaker Change: I think generally a responder analyses were conducted at single points in time, rather than averages there is always variability with biochemical markers.
Speaker Change: Before I think of all the choices in this disease state is one of the least variable.
Speaker Change: And again, there is a lot of confidence that.
Speaker Change: This compound can achieve both.
Importantly, the composite primary endpoint.
Isabel Calafonos: So we see the opportunity there to also serve the patients.
Speaker Change: And therefore, the ads that variability would.
Isabel Calafonos: be joined in the United States. So it's a commitment for for genetics to actually serve patients, not only in the US, but in as many countries as possible. But we will be very gradual about our geography.
Speaker Change: Variability might explain one of these endpoints hitting at once in a while and an occasional patient, but hitting both is quite specific and I would anticipate.
Speaker Change: Pretty strong results that are clearly delineated to placebo.
John Wolleben: Our next question comes from John Wolleben with Citizens.
Speaker Change: Our next question comes from Tyler Van Buren with TD Securities. Your line is open. Please go ahead.
Dana Pizzuti: Your line is open, please go ahead. Catherine, Anthe, John, I have a quick question about the 9-6-8-2 program and the Phase 1-2 trial that you are planning to begin soon. Any details you could share on the trial design and kind of what you want to learn? And also any particular safety kind of issues that you're going to be looking out for in this trial?
Speaker Change: Hi. This is for instance on for Tyler. So just one question about the fourth.
Speaker Change: Cohort.
Speaker Change: What is the rationale for looking at the morning dosing versus the evening Zhang.
Speaker Change: Yeah. Thanks. Thanks for the question this is Scott.
Dana Pizzuti: Thank you. Hi, yeah, this is Dana. And, you know, we look forward to actually sharing a little bit more about this at the R&D day that we're going to have in June. And so that'll be sort of, you know, front center, you know, for those discussions. But, but our general approach is that it's fairly, it's going to be a fairly standard, you know, those get those escalation design protocol for oncology. And obviously, you know, when you're treating patients, as opposed to healthy volunteers in your phase one, you have additional safeguards and, and, you know, sort of parameters that you're looking at, particularly around safety.
Speaker Change: I think for many of us.
Speaker Change: That would be more convenient to perhaps take the drug in the morning, rather than in the evening. When we just wanted to explore that to provide future optionality for patients.
Speaker Change: And maybe just to clarify a little bit reminder, that there is this there is a strong diurnal rhythm.
Speaker Change: This axis, including in CAH patients and so you just want to be sure that the timing of the drug.
Speaker Change: Response in respect to the Diana algorithm doesn't have a significant effect.
Speaker Change: Our next question comes from Cory <unk> with Lifesize capsule.
Dana Pizzuti: But, you know, we'll be very excited to share more details on that later.
Speaker Change: Line is open. Please go ahead.
Speaker Change: Good afternoon, thanks for taking our questions.
Speaker Change: So.
Speaker Change: You folks have recently.
Unknown Executive: Our next question comes from Alex Thompson with Stiefel. Your line is open, please go ahead. Great. Thanks for taking our question. Another on the CAH phase. Just wondering if you could talk a little bit about your design here in the context of glucocorticoid reduction and investigator discretion. Are there any overall guidelines for how to do this? Or how confident are you that you're not going to see a significant amount of variability here in the study?
Speaker Change: Received acceptance for your marketing application for <unk> in Europe curious.
Speaker Change: Curious, how youre thinking about launch strategy in these different geographies.
Speaker Change: You previously discussed patient concentration in the U S is largely at these pituitary centers of excellence is patient concentration similar to those in Europe.
Speaker Change: Or Latin America what.
What if any are some of the material differences in the way that acromegaly.
Unknown Executive: Well, I think part of the overall, you know, sort of mindset that we're trying to convey in the trial conduct here was that we wanted it to be as similar as possible to the real world in what, you know, investigators would want to do in terms of reducing glucocorticoids. Obviously, patients can come in with quite a lot of differences in what their, you know, glucocorticoid levels are, and some may have very, very high levels, and so what we wanted to do was allow enough time in the first part and the second part of the trial so that that can be done judiciously and carefully with, you know, the investigator deciding what increments they want to use in, you know, in the trial.
Speaker Change: Patients might be treated in those geographies that might be important to consider for a launch.
Speaker Change: Yes, that's great.
Speaker Change: All right so.
And that after Isabel who's on the line here.
Speaker Change: Go ahead Isabelle sorry.
Isabel: Sure no fairly high carry debt. So we are very excited to have the filings approved.
Isabel: Same for the launch in Germany, where also there is a significant unmet need for patients with acromegaly.
Isabel: So to your question on the European market.
Isabel: To be more concentrated in time, so even more patients.
Isabel: Centers of excellence.
Isabel: That is a leader in motive community in Germany than the rest of the markets been sustained.
Unknown Executive: You know, decreasing that. We have some general guidances that we put in the protocol about, you know, what the limits on those increments should be, but in general, we like to leave it up to the, you know, the PIs to decide what's best for their patients that are in the trial.
Isabel: So <unk>, 70%, 30%, 70% of key centers, we continue to research to confirm that.
Isabel: So highly concentrated.
We are working extensively in our market access strategy and.
Isabel: Now in discussions with TVA, and then from markets and we're going to be very progressive.
Isabel: To be very thoughtful about how.
Maxwell Skor: Our next question comes from Maxwell Skor with Morgan Stanley. Your line is open. Please go ahead. Great, thank you for taking my question.
Isabel: While we continue to expand there.
Isabel: So right now we have a footprint into we have our team in place and your money and it's a very small group of resources that we think would help us maximize the opportunity that I have as many patients as possible.
Unknown Executive: I was just wondering, I recognize you're not interacting directly with CBER for palatucetine, but I was wondering if you'd comment on the evolving regulatory environment overall and how you're thinking about any potential implications for the rare disease space. Thank you. Yes, um, you know, as you know, we're working with the CDER part of FDA. And so far, we really haven't seen much of a difference in terms of how things are progressing. And across all of the programs, not just with Peltuza team. So it's, you know, right now, it seems like regular order for the way that, you know, FDA is working, particularly with programs like ours.
Isabel: Regarding Latin America, you had said that that is a high unmet need and the locations that has been identified so the one country that we had to close it as Dennis.
Isabel: Culture for expansion is that sale as you had seen in <unk> or <unk>.
Isabel: 30% 30, 30 patients in our deck Omega lease size, whether it could is there we have very good relationships with any for incentives and it's also concentrated so we see the opportunity there to also serve the patients.
Isabel: B Johnson, United States, So it's a commitment for pork.
Unknown Executive: And most of our programs are rare disease programs. So, you know, we don't really see, you know, any differences at this point.
Isabel: So actually serve patients.
Isabel: Not only in the U S, but in as many countries as possible because we would be very gradual about our geographic expansion.
Isabel: Okay.
Joseph Schwartz: Our next question comes from Joseph Schwartz with Lerink Partners. Your line is open, please go ahead. Hey y'all, this is Will on for Joe. Thanks for taking our question. Congrats on the progress this quarter. So one on Peltucetine. Now that we're getting closer to the eventual commercial launch, could you provide any preliminary comments on how you might be thinking about pricing? And then with the recent MFN pricing headlines, does this change your thinking around the general strategy at all? And finally, can you just remind us of where the drug is manufactured? Thanks so much.
Our next question comes from John <unk> with citizens. Your line is open. Please go ahead.
Katherine: Hi, This is Katherine on for John a quick question about the <unk>.
Katherine: <unk> 6002 program and the phase one two trial.
Katherine: About <unk> I guess.
Katherine: To your point again soon.
Katherine: Details you could share on the trial design and kind of what you want to learn and also any particular safety kind of issues that youre going to be looking out for in this trial.
Katherine: Thank you.
Scott Struthers: So I'll answer the manufacturing and then leave it to Isabel to not answer your question on pricing directly, but give you some thoughts about how we're thinking. In terms of manufacturing, the final tablets are made here in the U.S. and packaging here in the U.S., although we get precursors and final API from Europe and originally in India.
Katherine: Hi, Yes. This is Dana and we look forward to actually sharing a little bit more about this at the R&D day, and we're going to have in June and so that'll be sort of.
Katherine: Front and center.
Katherine: For those discussions, but but our general approach is that it's a fairly it's going to be a fairly standard dose dose escalation.
Katherine: Design protocol for oncology and obviously.
Isabel Calafonos: So that answers that part, but maybe Isabel, can you talk just a little bit about the value we're hoping to deliver? Yes, of course. As I mentioned before, the value proposition of participating is resonating really well with CARES, you know, fast and slow action, durable effect, easy to use, one daily dosage per patient. Also, the fact that they don't have to deal with the breakthrough symptoms and the wastage currently associated with injections. At this time, we're not commenting on price. Of course, it's something that we're looking at very closely. We're conducting market research, advisory boards with payers.
Katherine: Yeah.
Katherine: When you're treating patients as opposed to healthy volunteer single Phase one you have additional safeguards and.
Katherine: Sort of parameters that youre looking at.
Particularly around safety.
Katherine: But.
Katherine: We'll be very excited to share more details on that later.
Speaker Change: Our next question comes from Alex Thomson with Stifel. Your line is open. Please go ahead.
Katherine: Okay.
Alex Thomson: Great. Thanks for taking our question another on the CAH Phase III just wondering if you could talk a little about your design here in the context of glucocorticoid reduction and investigator discretion are there any overall guidelines for how to do this or how confident are you that you're not going to see significant variability here in this study.
Isabel Calafonos: And as I mentioned, what is very positive for us is that the value proposition is resonating very well, and we are tracking on. We don't see at this point that there's.
Katherine: Well I think part of the.
Alex Thomson: Overall.
Isabel Calafonos: Answering your second question, any impact in our strategy based on the recent dynamics? But of course, we're closely monitoring that with our government-affiliated group as well, and we'll continue to do so, considering that about 40% of the population is in Medicare and Medicaid, 30% Medicare, 10% Medicaid, and we want to continue to monitor the potential impact in the future. But for now, there are none.
Alex Thomson: Sort of.
Alex Thomson: Mindset that we're trying to.
Alex Thomson: To convey in the.
Alex Thomson: The trial conduct here was that we wanted it to be as similar as possible to the real world and what.
Alex Thomson: Investigators would want to do in terms of results reducing glucocorticoid.
Alex Thomson: Obviously patients can come in with quite.
Alex Thomson: A lot of differences in what their glucocorticoid levels are and some may have very very high levels and so what we wanted to do was allow enough time in the first part and the second part of the trial, so that that can be done judiciously and carefully.
Dennis Ding: Our next question is from Dennis Ding with Jeffreys. Your line is open, please go ahead.
Unknown Executive: Hi this is Anthea on On CAH, the... Do you have an update on enrollment and follow-up there, and what is the critical mass? Well, enrollment is proceeding. And we will, of course, once we have a critical master, we would present to the scientific meeting. I can't really comment on numbers and exact timing at this time. But again, the OLE is another way for us to assess how the compound performs in sort of a more real world setting, which the doctors have control over the dosing of the compound, as well as over the dosing of the glucocorticoids.
Alex Thomson: With the investigator deciding what increments they want to use.
Alex Thomson: Decreasing.
Alex Thomson: We have some general guidance is that we put in the protocol about.
Alex Thomson: What the limits on those increments should be but.
Alex Thomson: In general we'd like to leave it up to <unk>.
Alex Thomson: The pie is to decide what's best for their patients that are in the trial.
Speaker Change: Our next question comes from Maxwell score with Morgan Stanley. Your line is open. Please go ahead.
Speaker Change: Great. Thank you for taking my question.
Just wondering I recognize youre not interacting directly with seeber for Palo <unk>, but I was wondering if you could comment on the evolving regulatory environment overall, and how youre thinking about any potential implications for the rare disease space. Thank you.
Unknown Executive: It's always very valuable data for us, and we look forward to reporting that when we can.
Speaker Change: Yeah.
David Lebowitz: Our next question is from David Lebowitz with City. Your line is open. Please go ahead.
Speaker Change: Yes.
Speaker Change: As you know, we're working with the Cedar part of FDA and.
Dana Pizzuti: Thank you very much for taking my question. The new primary endpoint seems to be a higher bar. And I am curious, do you reserve the ability to maintain also the same primary endpoint as clonacerapone to potentially use if needed for So, I think you're right, it is a higher bar. We're asking the study to see if acumen can really be the treatment for CAH and give patients an option so that they don't have to compromise on either glucocorticoid levels or the adrenal precursors that are being produced. And so, it's intentionally a high bar, but I think it's designed specifically for acumen because that's the type of study that this drug deserves.
Speaker Change: So far we really haven't seen much of a difference in terms of how things are progressing.
Speaker Change: And across all of the programs not just with <unk> team. So it's.
Speaker Change: Right now it seems like regular order for the way that.
Speaker Change: FDA is working particularly with programs.
Speaker Change: Like ours.
Speaker Change: And most of our programs our rare disease programs. So.
Speaker Change: We don't really see.
No.
Speaker Change: Any differences at this point.
Our next question comes from Joseph Schwartz with Leerink Partners. Your line is open. Please go ahead.
Speaker Change: Hey, Al This is will on for Joe. Thanks for taking my question. Congrats on the progress this quarter. So one on <unk> now that we're getting closer to the eventual commercial launch could you provide any preliminary comments and how you might be thinking about pricing.
Dana Pizzuti: And maybe I'll let Dana talk about the endpoint cascade. Well, yeah, and I think, you know, just along the lines of what Scott was just saying, the patient population is also different from what Chronicity studied in that we have a broader patient population. And as you recall in their study, basically what they were looking at was trying to reduce GCs, and A4 was sort of a, you know, sort of a side issue. It had to be roughly where it started, okay, which could have been normal, could have been, you know, sort of above normal. And so, what we'd like to do is be able to address the full population of patients who have CAH, who may have high A4s and not so high GCs, high GCs and normal A4 and high both.
Speaker Change: And then with the recent MFN pricing headlines does this change your thinking around the general strategy at all and finally can you just remind us of where the drug is manufactured thanks. So much.
Speaker Change: So I'll ask one on manufacturing and then leave it to Isabel to not answer your question on pricing direct rate, but.
Speaker Change: And I'll give you some thoughts about how we're thinking.
Speaker Change: In terms of manufacturing the final tablets are made here in the U S and packaging here in the U S. Although we get precursors and final API from Europe pen originally in India.
Speaker Change: So.
That answers that part, but maybe Isabelle can you talk just a little bit about the value we hope into the liver.
Dana Pizzuti: All right.
Dana Pizzuti: And so, in order to do that, you really can't have the same endpoint as Chronicity had. Okay.
Isabelle: Yes, that's correct.
Isabelle: As I mentioned it before the value proposition.
Dana Pizzuti: So, now, we also have a cascade, as I mentioned in the call, of secondary endpoints. And some of those are looking at certain aspects of how quickly we work, and then, you know, sort of other combinations of particular, you know, sort of endpoints of interest. But we also will look... In the same way that they did at, you know, somewhat, you know, similar, you know, endpoint for theirs too. But that's not what we, you know, intend to use for the FDA. And you can't, you know, so if we make the primary endpoint, this broader endpoint, that's what it is required to have to get approved.
Isabelle: The theme is resonating really well with.
Isabelle: You know thoughts on set of action do have an effect.
Isabelle: To use one daily utilization of basic.
Isabelle: And.
Isabelle: Also the fact that they don't have to deal with the greatest Samsung underway currently.
Isabelle: <unk> living Jackup.
Isabelle: There were no comments on price of course, it's something that we're looking at very closely with conducting market research advisory boards with Baird.
Isabelle: And as I misheard, what is very positive for us is that the body that reputation is supposed to Nathan.
Isabelle: And we are checking on that.
Isabelle: We don't see at this fall into yours.
Dana Pizzuti: So we can't change the end point.
Isabelle: Answering your second question.
Dana Pizzuti: And I think it's maybe important to remind all of us that We're building a study that measures a variety of different parameters of the impact of etumelan on the lives of CAH patients. And it's that whole package that'll be the basis for guiding physicians about how this might be used, should it be approved. And so we're interested in developing a broad profile, and that's the primary end point is one thing, and I know we'll all focus on that, but also getting to How much do we reduce the A4 levels, or 17-OHP, which are a couple of our first, secondary endpoints, because those lowering is important too, even if you only get slightly above the upper limit of normal.
Isabelle: In fact in our Italian gave based on the recent dynamics, but of course, we're closely monitoring that $3 4 million I think group as well and we'll continue to do so close date and then about 40% of the population is Medicare.
Isabelle: Medicaid, 30%, Medicare, 10% landscape and one of them being able to monetize it and sending back into pitch, but now that I don't know that yet.
Speaker Change: Our next question is from Dennis thing with Jefferies. Your line is open. Please go ahead.
Speaker Change: Hi, This is Andrea on for Dennis Thank you for taking our questions.
Speaker Change: On CAH the long term extension can you give an update on enrollment and follow up there and what is the critical mass that you need to give another update to investors. Thank you.
Dana Pizzuti: So the goal of the study is to capture all of this, to provide an ability to guide physicians, and then eventually to use in our commercialization efforts. And we also intend to look closely at the other clinical endpoints and adrenal signs as well.
Speaker Change: Well enrollment is proceeding and we will of course once we have a critical mass for winter presented a scientific meeting.
I can't really comment on number as an exact timing at this time, but again the OLED.
Brian Skorney: Our next question comes from Brian Skorney with Baird. Your line is open, please go ahead. Good afternoon. Thanks for taking the question. Just also on the TAH study, in terms of enrollment criteria, how do you kind of compare inclusion criteria to the Catalyst study? Are there differences in criteria around GC dose, A4, 17-OHP to consider? And the pediatrics plan you have billed as a Phase 2-3, is this just nomenclature? Is there a dose-finding portion of the study that precedes full Phase 3 enrollment?
Speaker Change: It's another way for us to assess how the compound performs in sort of a more real world setting, which the doctors have control over the dosing of the compound as well as over the dosing of the glucocorticoids.
Speaker Change: As always very valuable data for us and.
Speaker Change: We look forward to reporting net when we can.
Speaker Change: Yes.
Speaker Change: Our next question is from David Lebowitz with Citi. Your line is open. Please go ahead.
David Lebowitz: Thank you very much for taking my question the new primary endpoint.
Speaker Change: B, a higher bar and I am curious.
Dana Pizzuti: Okay, just to make sure that I understand, you asked about the entry criteria for our trial, right, first, for the adult trial. And, you know, I think that, you know, as I mentioned before, what we're trying to do is adapt to a broader population than, you know, the previous trial, you know, from, you know, at the time. So, now, in terms of our, you know, pediatric, you know, program, we've also received, you know, feedback from, you know, health authorities on that. And we're going to try to achieve the same things that we're doing for the adult program.
David Lebowitz: Do you reserve the ability to maintain also the same primary endpoint as Connecticut.
David Lebowitz: And potentially use if needed for FDA approval.
David Lebowitz: So I think youre right. It is a higher bar.
David Lebowitz: Asking the study to see if.
David Lebowitz: Now that can really be the treatment for CAH and gives patients an option. So they don't have to compromise on either glucocorticoid levels or the adrenal precursors that are being produced.
David Lebowitz: So it is intentionally a high bar, but I think it's designed specifically for asking that because thats. The type of study that this drug deserves and maybe I'll talk.
Dana Pizzuti: And we just need to make sure that we have the doses right for the right size kit. And so we'll be gradually working through that. But, you know, we don't plan to do it differently. And as you recall in the, you know, the pernosteron trial, they didn't, they held the GC constant, right, in that one. So, there was no GC reduction, so. That's, you know, sort of one of the big differences.
David Lebowitz: Dana talk about the endpoint Cascade.
David Lebowitz: And I think.
David Lebowitz: Just along the lines of what Scott was saying.
Speaker Change: The patient population is also different from what <unk> studied and that we have a broader patient population.
And as you recall in their study basically what they were looking at was trying to reduce <unk> and a four was sort of a.
Speaker Change: Sort of a side issue and had to be roughly where it started okay, which could have been normal could have been.
Douglas Tsao: Our next question comes from Douglas Tsao with HC Wainwright. The line is open, please go ahead. Hi, good afternoon. Thanks for taking the questions.
Above normal and so what we'd like to do is be able to address the full population of patients who have CAH, who may have high fours and not so high <unk> high Jcs and normally for an high both alright, and so in order to do that you really can't have the same end point.
Dana Pizzuti: And, you know, welcome to Toby to the Crinetics College. It's a little surreal hearing him on, not on a rescheduled call, but maybe just as a follow up on CAH and the pediatric study, I'm just curious, how do you think about that program moving forward? And, you know, again, would you anticipate, you know, you just said that you anticipate sort of having the same goal as with the CAH study. Does that imply that you would think about the same endpoint in terms of normalization A4 and physiologic GC? Or is there some other potential sort of similar endpoint, but perhaps a slightly different one for targeted for the pediatric population?
Speaker Change: As Chronicity had okay. So now we also have a cascade as I mentioned in the call of secondary endpoints and some of those are looking at certain aspects of how quickly we work and then.
Speaker Change: Sort of.
Speaker Change: Other combinations of particular.
Speaker Change: Sort of.
Speaker Change: And points of interest, but we also will look.
In the same way that they did at.
Speaker Change: Somewhat similar.
Speaker Change: Endpoints, where theres two but that's not what we.
Speaker Change: Intend to use for the FCA and you can't.
Speaker Change: So if we make the primary endpoint this broader endpoint that's what it is.
Speaker Change: Wired to have to get approved.
Dana Pizzuti: Thank you. Well, I think, you know, you know, to answer your first part of your question, and maybe Alan can comment on the, you know, sort of treatment objectives. But, you know, as far as the first question, the way we've designed this study is to be sort of a seamless design, right, as opposed to two separate trials. And so the way that it will work is the phase two part will guide the phase three part. And so we don't, you know, plan on doing separate trials on that.
Speaker Change: So we can change standpoint, I think it's maybe important to remind all of us.
Speaker Change: We're building a study that measures a variety of different parameters of the impact of that Simona on the lives of CAH patients and it's that whole package that will be the basis for guiding physicians about how this might be used for the approved.
Speaker Change: And so we're interested in developing a broad profile and Thats. The primary endpoint is one thing and I know, we'll all focused on that but also getting too.
Speaker Change: How much do we reduce the pay four levels or 17, OHP, which are a couple of our first secondary endpoints because those lowering it is important to even if you only get a.
Alan Krasner: But I think, you know, maybe if Alan could comment on, you know, the treatment objectives for the pediatricians on that. Yeah, the reason I'm really excited and very supportive of this endpoint that we're talking about, normal GCs and normal A4s, is because this really is the treatment goal for this disease. And, by the way, it's the same for pediatric patients and adult patients. This is what you want to achieve in clinic. It's very hard to do that these days with available treatments. I really think Altamilna has a lot to offer here to achieve that two-part goal.
Speaker Change: Slightly above the upper limit of normal.
Speaker Change: So the goal of the study is to capture all of this.
To provide the ability to guide physicians.
Speaker Change: And then eventually to use in our commercialization efforts.
Speaker Change: And we also intend to.
Speaker Change: To look closely at the other clinical endpoints.
Speaker Change: Adrenal songs as well yes.
Brian <unk>: Our next question comes from Brian <unk> with Baird. Your line is open. Please go ahead.
Alan Krasner: So, yeah, I think it would be very similar in pediatric patients, ultimately.
Brian: Good afternoon, and thanks for taking my question.
Brian: Just also on.
Unknown Executive: Our next question comes from Andy Chen with Rupport Research. Your line is open, please go ahead. Hey, thank you for taking the question. And back to your phase three trial design. So I understand that the speed of reduction is individualized. But is it mandatory reduction at each stage of GC reduction? Or is it optional reduction for patients? If it's optional, does that make... The primary endpoint, very wonky and highly dependent on baseline characteristics of patients. Is that a worry here or no? Thank you.
Brian: On the Th study in terms of enrollment criteria, how do you kind of compare exclusion inclusion criteria to the catalyst study are there differences.
Brian: And crikey around <unk> 417, OHP to consider and the pediatric plan you have builders as a phase two three.
Brian: Just nomenclature is that our dose finding portion of a feed study the proceeds for phase III enrollment.
Speaker Change: Okay, just to make sure that I understand like the.
Brian: You asked about the.
Brian: The entry criteria for our trial right one for the adult trial and.
Dana Pizzuti: Well, maybe just to, this is Scott, just as a quick reminder, we may have patients in who have physiologic replacement, but their A4 levels are already high, so they don't need a glucocorticoid reduction. So you have to account for that in the way you design the protocol. But maybe you want to explain a little bit more. Right, that's a good point, Scott. And those who do come in on high glucocorticoid doses, I want to be clear that, yes, this is not optional. The protocol requires, particularly at certain predefined visits, glucocorticoid dose reductions. Of course, the investigator has to make the, individualize these dose reductions based on toleration and safety, but these dose reductions are expected and would be very carefully monitored and followed.
Brian: I think that.
Brian: As I mentioned before what we are trying to do is capture a broader population then.
Brian: The previous trial.
Brian: Firm.
Brian: Yes, the front so.
Brian: Now in terms of our pediatric.
Brian: Program. We've also received feedback from health authorities on that and we're going to try to achieve the same things that we're doing for the adult program and we just need to make sure that we have the doses right for the right size kit and so we'll be gradually working through.
Brian: <unk>.
Brian: But.
Brian: We don't plan to do it differently.
Operator: And I agree, it's important to reduce the doses of glucocorticoid in those who come in on high glucocorticoid doses in order to achieve this endpoint and also to achieve the goal in clinic, which is the same. So, yeah. As a reminder, to ask a question, please press star followed by one on your telephone keypad.
Brian: As Youll recall.
Brian: And the <unk> trial, they didn't they held the GC constant right in that one so there wasn't OTC reduction so.
Brian: That's sort of one of the big differences.
Brian: Our next question comes from Douglas Tsao with H C Wainwright.
Catherine Novack: Our next question comes from Catherine Novack with Jones. Your line is open, please go ahead. Hi, afternoon, everyone.
Speaker Change: Your line is open. Please go ahead.
Douglas Tsao: Hi, good afternoon, thanks for taking the question.
Speaker Change: Welcome to Tobey.
Cory Jubinville: I just wanted to ask one question about So based on Pathfinder 2, we know you can go into treatment, naive patients, but do you anticipate any possible step through requirements for payers based on price? How are you thinking about that? Thank you. Thank you for the question. Well, as you know, we have a pathfinder towards looking at naive patients, also watch out patients and patients that have discontinued or continuing therapy. Our current discussions with payers don't anticipate any step therapy, and so far the feedback is that they will really just hold us to the label in terms of prior authorization.
Speaker Change: To the credit deposits will also read out here I can lock down on that call.
Speaker Change: Maybe just as a follow up.
Speaker Change: Uh huh.
Speaker Change: H in the pediatric study.
Speaker Change: Curious, how you think about that program.
Speaker Change: Moving forward to EBIT.
Speaker Change: Sort of.
Speaker Change: Danny you referred to sort of need to do some dose exploration would you anticipate needing potentially that U. Two studies, there or do you think theres an opportunity to do an adaptive design, which would enable you to only run one study and again would you anticipate.
Speaker Change: You just said that you anticipate sort of having the same goal.
Speaker Change: As with the car T H H.
This study does that imply that you would think about the same end point.
Cory Jubinville: This is a very positive time for us. And at this point, we don't anticipate that.
Speaker Change: In terms of normalization, a four and the.
Speaker Change: Physiologic GC or is there some other.
Speaker Change: Potential sort of similar end point that perhaps a slightly different one for targeted for the pediatric population. Thank you.
Scott Struthers: We currently have no further questions, so I'll now hand back to the Scott Struthers for closing remarks.
Speaker Change: Yes.
Speaker Change: Well I think.
Scott Struthers: Thank you, everybody, for being with us today. And maybe I'll just take a brief moment to also thank our colleagues at the FDA for their hard work on multiple different programs we're working on and keeping up the normal course of business, at least as far as we've seen.
Alan: To answer your first part of your question then maybe Alan can comment on.
Speaker Change: Treatment of <unk>.
Alan: But.
Alan: As far as the first question. The way. We've designed this study is to be sort of seamless design alright, as opposed to two separate trials and so the way that it will.
Scott Struthers: So thank you all and have a great afternoon and weekend.
Alan: We will work as the phase II part will guide the phase III portion.
Operator: This concludes today's call. Thank you for joining.
Operator: You may now disconnect your line.
Alan: So.
Alan: We don't plan on doing separate trials on them, but I think maybe if Alan can comment on the treatment objectives for the <unk>.
Alan: Pediatrician's office.
Alan: Yes.
Speaker Change: The reason I'm really excited and very supportive of this endpoint that we're talking about normal gcs and normal <unk>.
Is because this really is the treatment for this disease and by the way same for pediatric patients and adult patients. This is what you want to achieve in clinic, it's very hard to do that these days with with available treatments really think at the moment has a lot to offer here to achieve.
Speaker Change: That pioneered to parcel so yes, I think it would be very similar in pediatric patients ultimately.
Speaker Change: Okay.
Our next question comes from Andy Chien with Wolfe Research. Your line is open. Please go ahead.
Andy Chien: Hey, Thank you for taking the question and back to your Phase III trial design.
Andy Chien: I understand that the speed of reduction is individualized, but is a mandatory reduction at each stage of its usually reduction or is the optional reduction for patients.
Andy Chien: If it's optional does that make the.
Andy Chien: The primary endpoint very wonky and highly dependent on baseline characteristics of patients. So is that a worry here or now thank you.
Andy Chien: Well, maybe just this is Scott just as a quick reminder, we may have patients in who have physiologic replacement, but their <unk> levels are already high so they don't need it glucocorticoid reduction. So you have to account for that in the way you design the protocol, but maybe you want to explain a little bit more around right.
Speaker Change: Good point, Scott and those who do come in on high glucocorticoid doses.
Andy Chien: I want to be clear that yes. This is not optional and the protocol.
Andy Chien: Requires particularly at certain predefined visits.
Andy Chien: Glucocorticoid dose reductions.
Andy Chien: Of course.
Andy Chien: The investigator has to make the individualized these dose reductions based on coloration in safety, but these dose reductions are expected and.
Andy Chien: We'd be very carefully monitored and solid.
Andy Chien: And I agree it's important to reduce the doses it glucocorticoid in those who come in on high doses.
Andy Chien: Order to achieve this endpoint and also to achieve the goal in clinic, which is the same.
Andy Chien: Yes.
Andy Chien: Okay.
Andy Chien: Yeah.
Andy Chien: Okay.
Andy Chien: As a reminder to ask a question. Please press star followed by one on your telephone keypad.
Speaker Change: Our next question comes from Catherine Novack with Jones. Your line is open. Please go ahead.
Speaker Change: Hi afternoon, everyone.
Speaker Change: Just wanted to ask one question about.
Speaker Change: Talk to the team so based on the Pathfinder two we know you can go into treatment naive patients, but do you anticipate any possible step the requirements for payers based on price how are you thinking about that.
Speaker Change: Does it go.
Speaker Change: Thank you. Thank you for the question.
Speaker Change: Well as you know we had a <unk> two was looking a naive patients also washout patients and patients that have discontinued continuing therapy.
Speaker Change: Our current discussions with fares don't anticipate any therapy.
Speaker Change: So far the feedback is that they wouldn't really just hold us to the labor intensive prior authorization.
Speaker Change: Michigan is a very positive sign for us.
Speaker Change: And at this point, we don't anticipate it.
Speaker Change: Yeah.
Scott: We currently have no further questions. So I'll now hand back to Scott <unk> for closing remarks.
Scott: Thank you everybody for being with us today.
Speaker Change: Maybe I'll just take a brief moment also thank our colleagues at the FDA for their hard work on multiple different programs, we're working on and.
Speaker Change: Keeping up the normal course of business at least as far as we've seen.
Speaker Change: So thank you all and have a great afternoon and weekend.
Speaker Change: This concludes today's call. Thank you for joining you may now disconnect your lines.