Q2 2025 Crinetics Pharmaceuticals Inc Earnings Call
Welcome to cassex Pharmaceuticals second quarter, 2025 Financial results conference call. At this time, all participants are on listen-only mode. Following the Management's prepared, remarks, we will hold a question now session in order to raise a question, please signal by pressing star for by 1, on your telephone keypad, to remove yourself from the line of questioning will be staff followed by 2. And I would like to turn the call over to uh, guy 3 The Walker head of investor relations.
Please go ahead. Thank you, operator. Good afternoon, everyone and thank you for joining us to discuss the second quarter 2025 results. Today on the call we have Dr. Scott Struthers founder and chief executive officer, Dr. Dana pizzi. Chief medical and development officer Isabelle, California. Chief commercial officer and he'll be shy Chief Financial Officer in addition, Dr. Steve Betts. Founder and chief scientific officer and Dr. Alan Crainer Chief and technologists will also be joining for the Q&A portion. Please note, there's a slide deck. For today's presentation, which is in the events and presentations section of the investors page on the kinetics website. In addition, a press release was issued earlier today and is also available on the corporate website.
Slide 2 as a reminder. We'll be making forward-looking statements and I invite you to learn more about the risks and uncertainties associated with your statements, as disclosed in our SEC filing.
Touch forward. Looking statements are not a guarantee of performance, and the company is actual results can differ materially from those stated or implied in some statements, due to risks and uncertainties associated with the company's business.
in particular today we will be reviewing our commercialization plan as well as estimates related to Market size growth, and other data about the acronym, my blue Market,
Projections, assumptions and estimates of a future performance and the future performance of the markets inventory. Operate are necessary subject to high degree of uncertainty and risk.
These 4 looking statements are qualified in their entirety by the cautionary statements contained in today's news the company's other news releases and kinetics FCC filings including its annual report on form 10K, in quarterly reports and form 10q.
I would also like to specify that the content of this conference. Call contains time sensitive information. So as I can only, as of the date of July broadcast, August 7th 2025, kinetics take, no obligation to revise or update any 4 looking statements, to reflect events or circumstances after the date of this conference. Call with that, I'll hand the call over to Scott.
Thank you, guys. Good afternoon to everyone joining today's call.
Joining the slide 3. We are pleased to provide an update on our corporate progress and share our second quarter results.
We continue to execute on our mission to develop Innovative therapies for patients with endocrine diseases and endocrine related tumors as we approach the pivotal moment of our pending approval of our first NDA. I'm pleased to report strong execution across all aspects of our business.
I want to begin by reaffirming that the paltus in NDA review remains on track. We continue to work closely with the FDA towards an anticipated approval in September.
We are grateful for the FDA's commitment to this important work and their collaborative approach throughout the process.
Our regulatory team is maintained, excellent! Momentum and remain confident in our timeline and preparations for what will be a transformational launch for Connecticut.
We've assembled an outstanding launch Team of experienced professionals, both in our headquarters and in the field, who brings deep expertise in endocrinology and rare disease, commercialization.
The caliber of talent, we've attracted speaks to the excitement around talentify and its potential impact on patient care.
Recently, we hosted a group of more than 40 people living with acromegaly at our headquarters in San Diego as part of our ongoing engagement with the patient community.
We have worked with the acromegaly, advocacy group since before pelusa, team entered the clinic.
We continue to seek their insights to shape our commercial strategy.
At this most recent patient event, I heard directly about their experiences with their disease.
And their interactions with the Health Care Systems around the country.
After talking with them, personally, I am more confident than ever that, pal, personifies profile, addresses a critical unmet need that will make a very positive impact.
On all these patients daily lives.
Deeper in the pipeline, we continue to make progress towards initiating 4, additional pivotal programs.
Trials of puset for the treatment of carcinoid syndrome and at toilet for the treatment of adult and pediatric congenital. Adrenal hyperplasia are ramping up now.
We remain highly encouraged by the potential of that to melonjs novel mechanism of action in act dependent Cushing syndrome,
and following extensive conversations with multiple regulatory authorities, anticipate initiation,
of a Phase 23 study in the first half of 2026,
the enthusiasm for our earlier pipeline continues to build.
The Phase 1 2, study of Sierra 9682 in sst2 expressing. Solid, tumors is ramping up and our work towards IND. Submissions across multiple additional Discovery stage programs continues.
As you may have seen, we've been extremely active at several key Endocrinology conferences over the last few months, including Endo 202025 last month in San Francisco.
We delivered 6 poster, presentations in 2, oral presentations, covering palifi and acromegaly as a melinte and cah.
And our thyroid stimulating hormone or TSH receptor. Antagonist program.
We also hosted product theaters and Innovation sessions to highlight our pipelines differentiation and met with key opinion leaders across the different indications where pursuing.
Among the presentations at Endo was an update of crn. 12755 our TSH receptor antagonist candidate for the treatment of graves disease.
We believe this novel mechanism of action has the potential to be a single oral therapy that addresses the core driver of graves disease.
In order to create both Graves hyperthyroidism and treat or prevent thyroid eye disease.
Turning back to the launch of panape.
I'm energized by the team. We built the progress. We've made for megley.
With that, let me turn the call over to Isabelle to tell you more.
Thank you, Scott.
Starting this live for we're incredibly excited for the anticipated launch of Pawnee. Our recently built brand name for participants
this represent the combination of years of dedicated research and development to bring a new standard of care to patients with Acro Mega.
We had made meaningful progress in our interactions with Healthcare professionals. Patients and parents as we approach this Milestone and complete our transition into the commercial Stage Company.
Moving on to slide 5 as the Scott mentioned, crannet is highly significant Presence at several prestigious medical meetings over the last few months with global key opinion leaders, as well as with community and Doin.
Our presentations are procedures at Endo were standing room only and Healthcare professionals were excited to engage with our team to learn more about bologna.
They were impressed with the new data, from the open level, Pathfinder 1 extension, which showed the participant maintain control of both. I just 1 levels and symptoms through 96 weeks.
Health Care Professionals were encouraged by this durability since many patients discontinue, a comedy treatment. Within a few years,
They were also excited by the post hoc analysis that demonstrated that treatment with PINE improved symptoms and stability over 3, 6, and 9 months relative to baseline treatments with injectable SRS.
This data could present a compelling value. Proposition to patients improved both symptoms and controls and its abuse.
In addition, healthcare professionals were reassured by the stability of reduction of tumor volumes in patients who had MRI data throughout the Ole period for both Pathfinder 1 and Pathfinder 2.
Professionals can feel confident that this particular team offers several additional controls, as well as symptom control and disease control.
Turning to slide 6 with that in mind we have built out. Our commercial team are running the process of on boarding, our sales force ahead of launch. We will have approximately 30 sales representatives in the field supported by additional health care, professional facing roles, ensuring comprehensive coverage and support for our Target prescriber base.
We have been impressed by both the quantity and quality of candidates who have applied for our field roles and we are confident, they represent the top talent in the industry with extensive experience in rare. Endocrinology and a high degree of motivation to bring personify to patients.
Now, on to slide 7.
Our market research suggests that Health Care Professionals, perceive that sonifi, as the preferred therapy among newly diagnosed patients due to this rapid reduction of, I just 1 levels and its accelerated titration time frame relative to monthly injectors.
We believe that our 500 newly diagnosed patients per year, who are candidates for pharmaceutical therapy?
In addition, we believe that there are 11,000 currently diagnosed patients who had high and made needs and are candidate for personify.
We Believe many of these patients might be unhappy with the current treatment options and will consider starting or restarting therapy. If an effective safe and convenient therapy were available.
We are asking patients to demand more from their acromegaly therapy and believe many will want to switch to personify over time.
90% of patients from our Pathfinder. 1 is study who were previously on srl treatment opted to continue on part 2 in treatment in the oiliest study. And the scoring the unmet need for patients currently and injectable srfs.
Other patients are on oral therapies that are not indicated for acromegaly, and they might not have effective control of their disease.
Patients on oral occurrence, might be managing cumbersome twice? Daily fasting periods.
It is clear that even oral therapies leave room for improvement on both biochemical and symptom control as well as each of administration.
In addition, we share Noel data on injectable srl discontinuation rates, during our science and Innovation session at or a 5-year. Follow-up, period, nearly 80% of patients on injectable srls did not persist with the newly started treatment regimen of those about 2/3. Discontinued treatment all together.
This data suggests that patients are dissatisfied with the current treatment notion and highlight the need for expanded treatment options.
The Persistence of injectable srls.
When either discontinuing, switching, or adding on represents an opportunity for providers and patients to select a therapy like Personify that can better serve patients' needs.
These findings highlight the need for standard treatment options. We hope that Personify can provide a new option for patients who want to receive effective and convenient treatment for their AECOM.
Lastly we believe that there are at least 17,000 undiagnosed patients over time we believe we can help Drive diagnosis and treatment for this patient.
Moving to slide 8. Our commercial strategy is not just based on growing market, share in the naive and swiss patient.
It's about growing the market sell by bringing in patients who might have discontinued therapy, those that couldn't tolerate injections, and those who are suboptimally treated.
And over time helping undiagnosed patients, accelerate their treatment Journey.
We know that patient activation will be a key driver of potential uptake and had consequently launched, our disease State education, campaign and patient support have well in advance.
We are very pleased with the early results from this engagement initiatives, as this multi-channel strategy will be essential.
As we approach potential approval, our goal is to increase awareness, educate the community and ultimately Empower patients to okay for the best possible care.
during the slide 9, Ah, this stage in our launch preparations, we had had numerous pre-approval meetings, with commercial payers,
Grateful for our ongoing engagement with CMS regarding Medicare and Medicaid coverage, particularly given all the changes occurring in the healthcare landscape.
Peer groups have been receptive to personifies value proposition, which includes faster Disease Control, lower treatment, burden, symptom, control and improved patient adherence.
Respect that prior authorization activity with closing error. The label received for Personify shows that we are actively working with payers to ensure appropriate access pathways.
Our extensive market research and advisory boxes back have revealed a strong demand among Health Care Professionals for a new treatment option.
Endocrinologists are eager to use patoni across multiple patient populations.
Treatment patients those currently on therapy. And importantly some patients who have been lost to follow up due to the burden of caring injectable Therapies
based on our data and the feedback from Health Care Professionals patients and payers. We are more confident than ever in the long term potential for personified to become the preferred treatment for the acromegaly community.
And our commercial strategy Is Anchored In delivering on that promise.
So we are deeply enthusiastic about the potential but sonifi, I want to offer a few reminders on the expected Cadence of March.
In the near term, there are several factors that will affect uptake of the potential approval.
first, we anticipate, formulary placement will take at least 6 to 9 months after launch which is consistent with other specialty farmacista launches,
Second acromegaly, patient sees their endocrinologist relatively infrequently approximately 2 to 4 times per year.
Consequently, we don't know the effect of all associations on drugs, shortly after approval and is checked. Expect adoption to gradually ramp in line with our Outreach and engagement initiatives.
We are all hard at work preparing for us loans and we continue to progress in our International expansion in anticipation for a launch in Europe in 2026.
With that, I will turn it over to Dana to provide a regulatory and clinical update Dana.
Thanks. Isabelle turning to slide 10.
I'm pleased to provide an update on our regulatory progress across our pipeline, which continues to gain momentum on multiple fronts.
Starting with pelusa team and acromegaly our ongoing FDA review is progressing as expected through the review, Milestones reinforcing our confidence. As we approach, our September 25th pufa date, I'm particularly encouraged that. The team we've been working with at FDA hasn't changed which ensures important continuity throughout this critical review period.
Our interactions with the European regulatory authorities also remain on track.
Our medical Affairs, team continues to work in the field. Educating hcps about acromegaly and sharing the data. We presented at Ace IPC and endo.
These conferences are an opportunity to highlight our clinical results as well as our health economics and outcomes research. These presentations and resulting Publications much of which are derived from our clinical studies are part of a broader. Strategic plan to generate and disseminate evidence of the unmet need in acromegaly and the role that Tusa team could play.
Turning to Palatine in carsonite syndrome.
We're making steady progress with our phase 3 Program currently have multiple sites up and running and continue to expect to enroll the first patient later this year.
We are also making significant progress on atom element in cah, which I will address in more detail shortly.
We are revising. Our timelines for ACT dependent Cushing syndrome, as we discussed with regulatory agencies, how to best measure effective control given at a moment's novel mechanism of action.
Moving to our earlier stage pipeline, we presented data, on our TSH candidates at endo,
Eye disease, or Ted.
Our mechanism of action has the potential to avoid the risks associated with atds in anti-ige, including liver injury, as well as hearing impairment and hyperglycemia.
Lastly, we continue to work towards an IND submission for TSH and SAT3 this year, and for PTH in 2026.
Turning to slide 11.
For Adam Melman. We've achieved several important milestones in our cah development program,
As a reminder, we share data on the first 3 cohorts of our Phase 2 study in January, with a primary endpoint of reduction in interesting, Dione or A4.
We added a fourth cohort, earlier this year, primarily to assess the effect of mourning dosing of 80 milligrams of atom melanin and to study reduction of super physiologic glucocorticoid doses. In addition to a reduction in A4.
Cohort 4 is now fully enrolled with 10 patients and so far, it continues to support the favorable benefit risk profile. We've observed in our clinical trials to date
We will, of course, continue to monitor these patients, very closely and communicate anything necessary in a timely manner.
We intend to share the full data from cohort, 4 in early 2026.
We also presented data at Endo from the Phase 2 study in CAH, including the full results from the first three cohorts, additional details, and observed reductions in adrenal volume and reductions in novel biomarkers.
Through these presentations. We continue to demonstrate our advancement of the understanding of the disease. Biology of cah as exemplified by our data. On the
We continue to expect to enroll our first participant in the Phase 3 trial in adult CAH by the end of this year.
Additionally, our open label extension study is actively enrolling. Providing continued treatment access for patients.
Moving to slide 12.
We are also making progress on our registrational trial for Adam melanin in pediatric cah.
When we debuted our phase 3, adult design last quarter, we outlined our ambition to assess normalization of both androgens and glucocorticoids, and we hope to achieve the same with our operationally seamless Phase 23 design for Pediatric patients.
I am pleased to share with you the Pediatric design.
The study will consist of 3 parts. Part A is the phase 2, which is an open label dose finding 8 week study, that will evaluate safety efficacy, and reduction of 84 and PK PD
Part B is the phase 3, which will be a double blind Placebo, controlled study that will assess safety and efficacy, including the ability to taper GCS
part C is the open label extension study for parts, A and B where in patients from part, A will also have the opportunity to taper GCS
We believe our clinical trials are designed to demonstrate differentiation of atom elements with an uncompromising endpoint and the goal of developing a new standard of care for patients with CAH.
Overall I am pleased with the significant progress. We have made across our early and late stage programs and we look forward to providing future updates on each.
With that, I will hand the call to Toby to provide a financial update Toby.
Thank you, Dana turning to slide 13. I'm pleased to review our financial results for the second quarter of 2025, or to reflect our continued, disciplined execution and Strategic investment in advancing our Pipeline and Commercial capabilities.
For the second quarter, we recognize 1 million dollars in revenue from our licensing and Supply agreements with our Japanese partner skk.
Our research and development expenses for the second quarter were $80.3 million, compared to $76.2 million in the first quarter.
This increase reflects our continued investment in pursuing multiple clinical programs.
Human studies.
Selling General and administrative expenses or 49.8 million for the second quarter compared to 35.5 million in the first quarter.
This increase primarily reflects our Strategic investment in building commercial capabilities, including our field sales, force and our broader, corporate infrastructure as we prepare for pulsifi launch.
We used 77.8 million of cash on a net basis during the quarter reflecting continued, clinical development and loss, preparation activities.
We ended the quarter with 1.2 billion dollars in cash, cash equivalents and Investments.
as of July 29th, 2025, we had approximately 94.2 million shares of common stock outstanding,
On a fully diluted basis. We had 1111.9 million shares outstanding.
Moving to slide 14.
Looking ahead. We are lowering the high-end of our guidance for net cash used in operations in 2025 and now expect to use between 340 million to 370 million compared to our previous guidance of 340 million to 380 million.
This guidance reflects greater Precision on clinical timeline estimates and prudent measures we have taken on overhead growth.
We expect net cash used in operations in the second half of the year to be higher than the first half of the year as our late stage trials. Gather momentum, and our commercialization activities, accelerate into an anticipated approval.
Based on our current operating plans and cash position, we maintain our guidance that our existing cash and investments will be sufficient to fund our operations into 2029.
This provides us with significant Runway to execute on multiple value, creating Milestones, including the pulsifi US launch, and the advancement of our broader pipeline,
With that Financial overview. I'll now turn the call back to Scott for some closing remarks.
Thank You, Toby. Now turning to slide, 15.
I want to emphasize the strong execution work demonstrating across all aspects of our business.
Our NDA for pelusa team remains on track with continued, collaborative, engagement with the FDA.
I remain very confident about our launch readiness.
Supported by the outstanding team, we've assembled, and our comprehensive corporate Readiness for the upcoming launch.
We expect multiple phase 3 and earlier, stage readouts across various programs up and down our pipeline over the next several years.
We look forward to providing updates to other pipeline continues to mature.
As we move through 2025, I'm excited about the opportunity ahead of us to introduce the potential new standard of care for acrobatically patients.
We are well positioned to achieve multiple value creating Milestones that will transform kinetics into the premiere. Endocrine focused Global pharmaceutical company.
Thank you all for your continued support.
And with that, I'll hand the call back to the operator to begin the Q&A.
Please limit yourselves to 1 question 1 question, only in the interest of time operator.
Thank you very much. We thought to start the Q&A. If you guys ask a question, please hit the thumb up pressing star. Followed by 1 on your telephone keypad, to remove yourself from the line of questioning to be star for it by 2.
Our first question comes from Josh Schwartz from Lee ring Partners Joe, your line is now open.
Great. Thanks so much. And congrats on all the progress. Um, nerren seems to be doing quite well with the kecetit launch. I was just wondering, how does that figure into your thinking about the pace of enrollment for your phase 3 CH studies. Now if at all and are there any particular kinds of patients who are more likely to go on to um chronicity commercial uh versus enroll in a um clinical study for at the moment. Does that select for any kinds of patients in your view?
Thank you. Thanks for the question. Um,
so look, I think that the the
The launch from Kity is a great thing for patients with, um,
Cah and the momentum of that launch shows some of the unmet need that's out there.
Um, and in terms of impact on our, um, enrollment in our Phase 3, either adult or pediatrics,
Actually, I think it's a positive. Um,
Awareness on multiple fronts of the disease. And I think that uh as as another Nuance in general most of these studies, the bulk of our enrollment has been outside. The US, not inside the US, just because of treatment patterns in the different regions.
So generally, I think it's all positive for patients. Maybe we can ask Dana if she wants to comment on, or Allen on, kind of the patient population that we're treating.
Yes. Uh, thanks Scott. Um I think 1, you know interesting difference between, you know their indicated population and what we're trying to achieve in our phase 3 is that we're looking at a broader patient population because um the way we look at it is it's sort of a spectrum and there are patients who have you know, High A4 and high GCS, there are patients that have just High A4 and not um and are not on GCS and then there's others would normally for and high GCS. We think that all of those patients can benefit from at a mnet
So in, you know, 1 cents, it's a much broader ovulation. So, um, you know, that is a big distinction and does sort of, reflect how we view this particular mechanism of action is addressing, you know, sort of the full spectrum of disease.
Thanks for the caller.
Thank you very much.
Our next question comes from Tyler. Van burn from TD con tally. Your line is not open.
Hi. This is Francis on for Tyler.
Curious, if you could.
On the timeline for the IND submissions of the TSH and SST 3.
Agonist are you still targeting 2025?
Uh, maybe Steve, you want to give some color on that?
Yeah, thanks for the question. Yeah those
R&D enabling work is all still in progress. We are targeting the end of the year. I don't have particular granularity past that but that's what we're aiming for for both molecules
Thank you.
Thank you very much. Our next question comes from Jessica 5 JP Morgan Jessica. Your line is not open.
Hi, this is Abdullah for Jess. Um, can you speak to your comfort level with current consensus numbers for the Paul 2? Team launched. Thank you.
Maybe I'll let Toby take that 1.
Yeah, thanks Scott.
You know, it's it's not typical, uh, for companies at this stage or prudent to comment on, um, you know, consensus, um, we haven't given guidance. So, um, that's that's where we are right now. Um, we feel comfortable though on the launch preparation and the progress, we're making with the FDA.
Thank you.
Thank you very much as a reminder, if you'd like to raise a question. Please sign over pressing star, followed by 1. Our next question comes from Maxwell. School from Wolf Stanley, Maxwell. Your line is now open.
Hello, this is Selena on for Max, thank you for taking your question.
For the global CH phase 3 study. What are your expectations around Placebo response and any potential impact from different geographies?
um,
Dana around. You want to comment?
Yeah, sure. Um, I think that uh, we have a pretty ambitious endpoint as we've talked about for the adult trial and we are not really expecting a very high Placebo response rate at all. So, um, again, you know, we're
setting it up so that
you have to sort of address both the a4s and have a reduction in GCS, the physiologic levels. So in our mind, regardless of which part of the spectrum of cah, you're in, it'll be very difficult for a placebo, patient to meaningfully change where they are.
So um, you know, that's kind of the way we're looking at.
It. Thank you.
Thank you very much.
Our next question comes from Yassin rahimi from Piper Sandler, Yim your line is not open.
Um, just in regards to palifi, we were wondering if you plan to provide color on pricing at the time of approval and then also with, like, your current payer work, um, how much do you understand about the level of flexibility, you might have to price. Um, when compared to like current SSR injectables,
Yeah. So, you know, obviously, we'll be discussing price at the right time after, uh, what we hope will be an approval soon. Um, but Isabelle, maybe you want to talk a little bit about the payer side of things?
Yes, thank you very much for the questions.
So we have continued to make progress in our discussions with Bears and the value proposition continues to resonate and is very positive. This is back that we are getting from them. They understand that Karen um treatments particularly srls had a high burden of treatment and there is significant waste uh with many of the patients 1. Third of the patients. Exactly. Taking more than 13 injections a year.
So we continue to partner with them. We continue to reinforce the clinical value of the treatment. And at this time we are not commenting further on price.
Thank you.
Thank you very much. Our next question comes from Joshua from Canal. Josh, your line is now open.
Uh, thanks for taking the question, I guess, given how much, um, scrutiny there was on the, uh, cases of lft elevation that were seen with admin. Um, can you provide an update on the ongoing experience and whether that's been seen, um, subsequently and how do you plan on kind of maintaining updates going forward on that liver, tox profile and whether it is turning into a meaningful signal or the opposite.
it's Josh, you know, I think we've said before we're kind of surprised at the screwed me on that 1 patient we saw earlier,
Um and we're very comfortable with the emerging and growing uh experience that we're gaining with it.
Um, and in terms of updates on it, you know, I think it warrants updates as the data matures and we have something meaningful, to share. We should remind everybody that this is part of a much larger program. Um, you know, we're we're rolling patients into the open label extension from The Phase 2. So we're starting to activate sites and we'll be enrolling patients in the adult study and then the Pediatric study. And so I think that kind of emerging experience will give people more and more comfort and um
If there's a big problem, obviously, we'd have to let people know. So I think no news is good. News on that front.
Thank you very much.
Our next question comes from Alex Thompson from stifel, Alex, your line is now open.
Hey guys, this is Seth on for Alex. Um, we just had a question about Pulsifi and just how many patients are on the Ole and how quickly do you expect them to transition to commercial treatment, um, once approved.
Launched.
Um yeah, maybe uh we'll let uh, boy, this could be anybody answering this 1, but I will remind you that we have patients all around the world, uh, not just in the US. Uh, so maybe Isabelle or Dana? You want to comment on that transition.
You.
I'd be happy to know, we? Yeah, go ahead.
Okay. Now why don't you go ahead, Isabelle?
Okay. All right. Um, have to say yes we
Okay, sorry about that.
Okay. Um, you know, the open label extension is Scott, mentioned is, uh, ongoing in in numerous countries and, you know, with the, uh, the US approval, you know, there will be, um, you know, we'll have to see, you know, what, the, you know, outcome of the, you know, regulatory interactions are. Um, but um, you know, I think that once the, the company is, uh, you know, reach of a dupa date and we've had a successful outcome. We can make a decision about, uh, you know, what happens with those patients and it's really only a small number of the patients that are in the US that would be, you know, sort of potentially enrolled in the, uh, on to commercial drug.
Got it. Thank you.
Thank you very much. Our next question comes from Gavin. Clark Gartner from evercore. Isi Gavin, your line is now open.
Hey this is Yin for the Gavin. Just a quick question from our end, you shared the cohort 4 of The Adult Space 2 for CA just going to read out an early 2026. We're wondering if we could also expect any OA with this update. Thank you.
Yeah, I think this is Scott again. But, um, look, I think we'll have a broader update on the whole program. Remember, in addition to that cohort and the Ole.
We should be getting deep into then the, the ramping up of the adult cah study, the Pediatric cah study, and we'll need to provide some clarity then on the um Cushing's Disease program as well.
So I think there's going to be a ton of things to talk about around at 2 Milne net uh in the not too distant future.
Thank you very much. Our next question comes from Rich law. From Goldman Sachs, Rich. Your line is now open.
Hey guys, uh, good afternoon. Um, how much do you think you can learn based on how to melon's cohort for with only 10 patients? And I assume there's going to be data variability. Is there a chance to adjust the phase 3 protocol based on what you're learning that cohort for, uh, since you're starting the phase 3 study? Before you see the phase 2 Data? Thanks.
Yeah, I think that's a good point, that reminder it's only 10 patients and we've got quite a few more patients. Uh, hopefully going into the OLE. Um, but maybe Dana, you want to talk about just the process around protocols.
Well, sure, as we mentioned, um, cohort, 4, 1 of the interesting questions that we were, you know, trying to understand better is, uh, the difference between AM and PM dosing. We've already decided in the in the phase 3 that it's going to be PM dosing. I think, you know, the information for that will be useful afterwards, right? In terms of uh you know eventually you know, potentially trying to understand whether patients need that kind of flexibility going forward. Um but um we are really locked and loaded for the phase 3 as uh Scott. And you know we have mentioned before the sites are already getting started and we expect the first patients in um soon. So um you know we we really aren't planning on making any changes in the
Protocol right now.
Thank you very much.
As a reminder, if you would like to raise a question, please sign up by pressing star followed by 1.
Our next question comes from Corey chenvel from life cycle. Corey, your line is now
Good afternoon and thanks for taking our questions. Um, when we look to some of the competitive readouts in NCAA the, the criteria for GC dose, reductions were a reflection of maintaining A4 levels within, you know, that 120% of Baseline values. However, that was based on the pre GC dose, uh, 84 levels. And when we looked at the A4 component in the primary endpoint that you're using for a common and balanced studies, um, that's based off of Post, GC dose, uh, 84. So, obviously A4 is expected to be lower after a patient takes their morning, GC dose. But can you just provide a bit of context as to why specifically you selected post GCA for as part of the primary endpoint? And how should we be thinking about the the clinical relevance of, um, you know, assessing efficacy pre-gc versus post GC uh, uh, on interesting Dion, thanks.
Yeah, I think that's a good question. Corey. Um you know just a reminder that I don't think that keeping
A 4-levels at 120% of what might be a very high baseline is all that great of a treatment goal for the person dealing with their CAH.
Um, and we believe they should be getting down to normal or very close to it, um, but Alan, maybe you want to talk about some of those nuances in post and pre-gc dosing, and I'll remind you Corey that, uh, between the primary and the secondary endpoints. We're looking at both and just, as I always encourage everybody, it's the overall profile of the drug. Uh, that's really important. Uh, in addition to the primary endpoint,
Corticosteroids; you would expect in this patient population for the 84 level to go down.
Um, and you know, that is uh, kind of what the uh, regulatory precedent that was set in the kornecki trials established, uh, that is the optimal time to measure A4 with respect to looking at the trough level of, uh, Androgen exposure, uh, with the treatment regimen to include the drug, plus the glucocorticoid.
uh,
We, we use that partly because it's a precedent, but also because it helps to, uh, facilitate, you know, variability assumptions for sample size calculations, uh, with with those assumptions. We, we, we know we have a very well powered trial here at PACE 3
Thank you.
Thank you very much on. Next question comes from Brian scoy from bed, Brian. Your line is now open.
Hey guys. Uh, this is Charlie on for Brian. Thanks for taking the question. Uh, we just kind of wanted to dig in a little bit into what you anticipate distribution looking like and along those lines. If you anticipate Health sonifi getting captured and data services like I give you for example.
Thanks uh Isabelle. You want to respond?
Sorry, I couldn't hear the question. Well.
Oh sorry, give me 1 second.
yeah, so I was wondering, uh,
Just what you anticipate distribution looking like for panape. And if you anticipated getting captured in data services like iqvia for example,
Yeah, thanks for a question. Yes. We we had a created our distribution system and it's going to be a closed distribution system at this point. So we are not
Planning to make that data available, it will be blocked. Uh, we want to make sure that we are able to track the launch and, and see, you know, the uptake in different segments, but it's not going to be widely available.
That's helpful. Thank you.
Thank you very much. Our next question comes from John wbin from citizens, John. Your line is now open.
hi, this is
Pattern on for John. I just a quick question about Cushing's Disease and just if you could provide a little bit more color on, um, kind of discussions on what potential endpoints you're looking at and kind of how, how the endpoint would differ for, um, for your mechanism versus kind of some of the other drugs that have been approved in the inflation. Thank you.
Uh, Alan, you want to take that?
Yes. So, uh, the the primary endpoint for Cushing's Disease trials. Generally, uh, is normalization of 24-hour, urine, free cortisol, excretion. This is a measure of integrated cortisol exposure over a 24-hour period of time.
Um and uh approvals are usually based on the proportion of patients, who achieve normal urine, free cortisol.
I mean I think up to melon uh is uniquely situated here in in several ways. 1 is uh in our uh trials. Today it's uh again we're running a single Center trial at the NIH and we will be starting larger trials soon. But what we're seeing so far is a very rapid normalization of urine. Free cortisol in pretty much all the patients tested so far. Uh, the rapidity I think is unprecedented and uh the the the treatment duration at the NH is 10 103. So I'm very excited to expand these trials. Uh to increase
The duration of treatment and to, uh, enroll more patients to show, uh, to hopefully see, this is a consistent finding. And, uh, if so, I think we have kind of, a, a real new level of treatment for Cushing disease here.
Thank you very much.
Our next question comes from Andy Chen from Wolfe research, Andy. Your line is now open.
Hey, Brandon on for Andy. Um, you stated earlier that AC patients, the endo's 2 to 4 times a year, um, which could lead to a slower start to the launch but shouldn't this approval draw patients to see their docs regardless of their Cadence throughout the year. Um and and for the, when do you expect patients to start flowing in? Thank you.
Based on personal experience of in most Health Care Systems. How long it takes to get to see a specialist.
Um, which is unfortunate but true. Um, but Isabelle, maybe you want to comment more specifically on the question?
Yes, mow most patients are are visiting their doctor uh every 6 months or once a year, of course, we are working actively in our engagement with advocacy. In our, our activities in patient activation, as I mentioned it before, uh, to get patients to, you know, proactively search for those appointments and move them, but we know that that will take time and that's what we are cautious that the beginning, and it will take some regular rhythm of patients going through the providers. Um our goal is to accelerated but we recognize that that would be 1 of the barriers early on.
Thank you.
Thank you very much.
As a reminder, for this question, we will be started about 1.
Our next question comes from David libbert from City, David. Your line is now open,
Hi guys. It's, uh, Ross on for David. I guess. I had a question on graves disease. Um, it seems like a TSH Madness or an antagonist is an obvious disease modifying mechanism, yet. The people are pursuing other targets. I guess, what do you think there hasn't been a TSH antagonist successfully developed and what do you guys think you're doing differently now with that?
Oh this is Scott. I think that this is right in our sweet spot and you could ask that same question about almost any of our earlier, you know, of our programs.
So these are very difficult targets to address. Um, when we've built a capability for this, uh, over now.
18. No 6. 17 years at Kinetics.
Um, but Steve, maybe you want to comment a little bit on what it's taken us to manage to crack this one, as well as some of the other programs.
Scott, and thanks for the question. I I I do think this is, you know, you look at TSH antagonism for the treatment of Grays and the treatment of um, thyroid eye disease and you, you you know that from a mechanistic standpoint, blocking the action of blocking the actions of the receptor is the right thing to do, if you can make the right molecule. But I think this is, I I think it's Scott said, this is what we do this, you know, for for C and for Cushings. The right thing to do is block the action that the AC receptor for the right thing for hyperparathyroidism. It's a blocking of the pth receptor, um, and so, rather than find kind of an end around to, to try and get an effect. We we work to find the right molecules.
At the right receptors, that'll produce the right um pharmacology that these patients need. Um and we have you know everything from the Medicinal Chemistry skills and the drug development skills and the you know the understanding of biology and receptor pharmacology, you know to kind of put all those pieces together to find the right molecules
Thank you.
Thank you very much.
Our next question comes from Douglas south from HC Wayne Wright, Douglas. Your line is not open.
Hi, good afternoon. Thanks for taking the questions in regards to the progress. Just
I'm just curious in terms of the balance cah study, um, in terms of Part B for the GC tapering, I'm just curious. Well, that replicate what? We see, you're the same protocol that will be used in comp C because I believe they're sort of Pluto quart of GC reduction periods followed by sort of GC stable periods. And I think it takes place over 2 sort of periods. Um is that what you're going to be doing in the the balance sheet each study as well? Thank you.
Yeah, Dana Allen. Do you want to take that on study design?
Yeah, thanks. Um, so I think what you were asking Doug was um, about the, you know, the Pediatric, you know, phase 3 part, right. And um, you know what we're trying to do, it's not exactly the same, um, but we're trying to
So, um, you know, we have a little bit, uh, more flexibility in terms of how the GC reductions take place, and um, and you know, I think that that is kind of going to be a little bit, you know, reflected in, uh, in the mechanisms of how the investigators carefully titrate them down.
But what we're looking for is, you know, to get get patients to normal A4. And then, you know, keep trying to titrate them down
And is, there is, is it set in the protocol for investigators to titrate down or is that that the data discretion?
Well, that is the, uh, the objective of the protocol: to get them to, um, reduce the GCS as much as they can.
And and but there's no time when they have to achieve it by or you know, by 25 weeks or something of that nature or of that order.
Yeah, there is an end point to the trial. Um and so they're expected to uh be on stable, GCS for a 4 week period before the end of the trial.
Okay, great.
28 weeks. So from 24 to 28 weeks.
It's stable.
Okay, great. Thank you.
Thank you very much. Our next question comes from Rohan. Martha from Oppenheim, your line is not open.
Hey, this is Ron on to lean. Thanks for taking my question. Um, on that to me is given the timelines for the adult and pediatric trials. I'll disconnect the progression towards NDA submission and labeling discussions on corporating. Both those um,
The data from both of those studies down the line. Thanks.
Dana. You want to take that 1?
Well yes. Um, thanks for the question. And the way that we look at it is um, we're looking at each 1 of those as a distinct submission. And so I don't think that we'll necessarily hold 1 until the other 1 gets done. So, whatever gets done first, which, you know, the, uh, uh, the phase 3 for the, you know, adults is, uh, you know, definitely, you know, almost, you know, begun in Phase 3. So, that should be done.
Before the Pediatric 1. And so the way that we look at it is we will submit that hopefully it will be successful and then we'll do you know, an amendment or a supplement to uh, to add the Pediatrics to
Got it. Thank you.
Thank you very much. Our next question comes from Katherine, Novak from Jones.
Katherine, your line is not open.
Hey, um, good afternoon guys, thanks for taking my questions. Um, I'm just curious on your thoughts on pal 2. The team in surgically naive patients based on the AAC presentation. You know, is this, is there a market here? Is there a significant number of patients who do orgo, surgical resection?
Thanks Katherine. Um,
Let me let uh, Isabelle answer that 1.
Thank you. Well as you know, we have uh,
uh, I live
with a, you know, in based on Pathfinder 1 of Pathfinder, 2 is sending the FDA review. Uh, look at um, naive and also um, switching patients
When it comes to presurgical patients, we are very excited about the data that we were able to present at endo, and we are also believe that there is an underneath. But at this time, we are not actively considering that, uh, segments, we, we believe that if Physicians see, um, that there is an opportunity and pending our label that might be an opportunity in the future.
Okay, got it. Thanks.
Thank you very much. That was a final question and that concludes today's call we'd like to thank everyone for joining. You will not disconnect your lines.