APHENITY Topline Results
Speaker 1: You.
Speaker 2: I go by bolt the you
Speaker 3: Welcome to the opinion top line with all conference call. At this time all participants are on a listen only mode. After this presentation there will be a question and answer session. To ask a question during the session you will need to press star 1 1 on your telephone. You will then hear an automatic message advising your hand is raised. Please be advised that today's conference is being recorded.
Speaker 4: I will now hand the conference over to your speaker host, Dr. Maggie Klein. Please go ahead.
Speaker 5: Thank you all for joining this morning's call. We are excited to share the positive top line results of affinity. The phase 3 trial of CpF TARIN in patients with fetal ketoneuria. Before I begin, I refer you to our forward looking statements on this slide, which are also posted on our website.
Speaker 6: as well as our risk factor section in our most recent 10K.
Speaker 7: We are thrilled to announce that we met the primary endpoint of blood phenylalanine reduction in the affinity study with highly statistically significant and clinically meaningful results.
Speaker 8: VP of TAR and demonstrated substantial fee reduction of 63% in the overall primary analysis population and 69% in the subset of classical PKU patients.
Speaker 9: The vast majority of patients were able to reach target key levels in line with United States guidelines of less than 360 micromoles per liter.
Speaker 10: Importantly, CPA pairing was also well tolerated with no serious adverse events.
Speaker 11: Before I go into more detail on the top-line results, I will review the design of the affinity trial here on slide 4.
Speaker 12: Finiti was a global placebo-controlled registration directed trial of Cepiaterin in pediatric and adult patients with PKU. In order to enrich the randomized population for likely Cepiaterin responders, we are going
Speaker 13: Screen subjects were treated for two weeks with cetatarin in an open-label run-in phase.
Speaker 14: Those that responded to therapy with a greater than 15% reduction in blood-key levels were randomized to receive CPA Taren or placebo for six weeks.
Speaker 15: The primary analysis populations included those subjects who had a reduction of greater than 30% from baseline. And the primary endpoint of the study was reduction in blood-spinal alamine levels in these patients.
Speaker 16: Before sharing, the CFO control results are a review of the data from the run anything which we have previously shared.
Speaker 17: Of the total 156 patients in the running phase, 103 patients, or 66%, had a 30% or greater mean reduction in blood phenylalanine levels, the criterion for the primary analysis population of the placebo-controlled study.
Speaker 18: These 103 patients had an average blood fee reduction of 66% for 460 core micromoles per liter.
Speaker 19: Of those 103 patients, 16 patients were part of the classical PKU patient's subset. And these classical PKU patients had a mean reduction in blood speed of 60% for 586 micro mole per liter in mean absolute blood-seed reduction.
Speaker 20: Now on slide six, let me walk you through how we arrived at the Part 2 study population. Now on slide six, let me walk you through how we arrived at the Part 2 study population.
Speaker 21: As I noted earlier, of the 156 patients in part one, 103 had fee reductions of equal to or greater than 30%.
Speaker 22: For the study protocol, patients younger than two years of age were enrolled directly into the long-term extension study and not randomized. An additional three patients withdrew from the study and were not randomized, one due to pregnancy, one due to mortality issue, and one due to family reasons.
Speaker 23: Thus, there were 98 patients randomized as part of the primary analysis population.
Speaker 24: In addition, there were 12 patients who had few reductions of 15 to 30% and who are also randomized for part two, but not part of the primary analysis population.
Speaker 25: Now I walk through part two, the placebo controlled portion of the study.
Speaker 26: In order to balance the sepia, tarin, and placebo groups for key disease factors, randomization was stratified both by percent T reduction in part one, greater than 30 percent, that being for the primary analysis population, or 15 to 30 percent.
Speaker 27: and also by baseline sea level greater than or less than 600 micromole per liter.
Speaker 28: Year on sliding are the baseline characteristics of the 98 subjects who comprise the primary analysis population.
Speaker 29: Overall, the CPU's current and placebo groups were well matched in terms of age and baseline sea level.
Speaker 30: You also see the distribution of classical PKU subjects with slightly more in the placebo than in the active sepia-terin treatment group. Now on slide 9, the study results.
Speaker 31: Overall, treatment resulted in clinically meaningful and statistically significant reduction.
Speaker 32: For the overall pre-specified primary analysis population, the mean blood-final aligning reduction in the CPITarian treatment group was 63%.
with little change in the placebo group as expected. This result was highly statistically significant, with a p-value of less than 0.001.
This strong magnitude of reduction is consistent with what we observed in part one. This strong magnitude of reduction is consistent with what we observed in part one.
In the subset of classical PKU patients, the cetiran-treated group demonstrated a 69% mean blood C reduction, again with minimal change in placebo group.
This level of reduction in classical PQ patients was better than that recorded in part one.
These are outstanding results and clearly differentiate Cepeatarin for the treatment of PKU patients of all ages and severity.
In terms of absolute sea reduction, in the overall primary and alpha population, the means lead sea reduction in the CPTAR and treated group was 460 micro mole per liter, compared to 16 micro mole per liter in placebo.
For reference, in the Kuvan placebo-controlled study, the mean reduction was 239 micromoles per liter. In the subset of classical PKU patients, the mean absolute feed reduction was 523 micromoles per liter.
Results in both the overall primary analysis population and the classical PTU subset were, again, highly statistically significant.
As part of the secondary endpoints of the trial, we looked at the important question of how many patients achieved the recommended target phenylalanine control level.
First, looking at the US guideline for all ages on slide 11. 84% achieved the target fee level of less than 360 micromoles per litre. Next, for the European guidelines for adolescents and adults, 93% of patients achieved the target level of below 600, 600% for and below 500inya.
Micro-mall per liter.
These are really important results that substantiate again a meaningful broad-based treatment effect.
For reference, the proportion of patients achieving target blood B levels in the Kuvian placebo control trial was 32% per less than 360 and 54% for less than 600.
micromole per liter. So again, we are observing differentiated treatment benefit with sepia tarin.
One of the questions that we have gotten most often in recent months is the treatment effect of sepiaterin in patients previously treated in CUVIT. In Affinity, 27 patients entered the study reportedly on active or generic CUVIT.
These subjects had an average final alming level.
and study entry of 581 micromole per liter.
The subject then underwent a seven-day washout, after which their average fee level was at 691 micromole per liter.
We were then able to determine the relative effect of CPI parent treatment on these patients in the run and phase. We were able to determine the relative effect of CPI parent treatment on these patients in the run and phase.
After two weeks of CPTAR and treatment, the mean phenyl aline level of the suit was 300 and four, which is not only below the US guideline target of 360 micromole per liter, but represents 48% lower phenyl aline levels on CPTAR and treatment.
and those receiving clue grads as study entry.
From a safety perspective, D.P.E.T.A.R. and demonstrated a favorable profile. First, there were no serious adverse events recorded in the study.
The related adverse event frequency for treatment-related adverse events was similar between sepiaterin and placebo groups. The main adverse events reported in the sepiaterin-treated patients were headache and diarrhea, and the majority of those were grade 1.
So overall, in addition to the very strong efficacy signal in the trial, dp-Aterin was found to be well tolerated.
Following the placebo controlled study, patients were eligible to enroll in a long-term open label study, which is still ongoing. This study has several objectives, including assessment of long-term safety and durability of CBT and TREAT, as well as to assess the tolerance.
The fee tolerance assessment looks at the ability of CPT-Aterin to control phenylalanine following a regimented increase in fee intake. In the Open Label Extension Study, patients who reached a fee level of the low 350 micro-operator on treatment.
were eligible to enroll in the fee tolerance protocol.
enroll in the fee tolerance protocol. Now let me explain how this works.
Essentially, a dietician prescribes a biweekly percent increase in fee intake based on measured blood phenylalanine levels in the patient.
We then measure the changes in blood phenyl aline levels with this regimented increase in phenyl alineas intake.
The graph on the left side of this slide demonstrates the average biweekly prescribed fee intake for the first group of 12 subjects who are participating in the fee tolerance protocol.
Of note, the recommended fee intake for adult women is about 55 to 60 milligrams per kilogram per day. And for men, it is 60 to 65 milligrams per kilogram per day. So you can see that patients in this protocol are taking greater than the recommended daily allowance and final allowance. So you can see that the recommended fee intake is about 55 to 60 milligrams per day.
On the right side, we present the corresponding mean phenylalemony levels of the p-tolerance patients at each time point.
As you can see, in the face of increased speed intake.
Even beyond the recommended daily allowance, phenylalanine levels have remained relatively stable and below the 360 micromole per liter target level.
These are of course preliminary data. There's only four patients have reached the end of the protocol, but the data are nonetheless very encouraged, given the importance of the tolerance in patient quality of life, position uptake, and payer engaged.
We look forward to sharing more of these data once available.
As we have previously discussed, PKU represents a unique commercial opportunity because unlike in many other rare diseases.
The commercial pillars for success are already well established.
First, newborn screening for PKU has been in place in most major markets for decades, and there are now an estimated 58,000 patients worldwide.
Second, there are well-known metabolic centers of excellence between the PKU around the world, with whom we already worked.
Third, the disease pathology is well understood and well documented, which is very important for market access and parodespression.
And finally, the patient's community is well connected and coordinated, which is very important to accessing patients.
Despite there being two approved therapies for PKU, the vast majority of patients are not well served and there's therefore a large potential market opportunity.
We believe these affinity results position CpHAARIN to address the persistent large unmet need across all PKU segments.
This includes therapy-naive patients, including classical PKU patients.
Patients who have failed are not well controlled or do not tolerate existing therapies.
In addition, PTC has a proven track record in commercializing rare disease drugs globally, and we plan to capitalize on our unique strengths to commercialize CP adherence for PKU patients.
We have already built the global commercial organization that we will need for a successful launch.
So this opportunity will really be plug and play. We already have built strong relationships with PKU patients, patient advocacy groups, clinicians including key opinion leaders and payers.
We experience an ensuring early access to treatment and providing patients with the support they need to patient support programs.
And it will be our customer-facing team's key priority to bring CPI-a-TAR and the PKU patients around the world as quickly as possible.
upon launch. Now with these strong data in hand, our next step is to request pre-submission meetings with regulatory authorities, which we will do as soon as possible. And then based on agency feedback, move forward with NDAA and MA submissions. Finally colleagues Moo750 on Advances, 2 robust information, ruled by, AccordantRepair, alone on We Command.
Before I turn the call over to the operator, I want to update the timing of results from our other study.
We expect to report results from the Move FH trial of the tick-winnel in NAD, and results from the MIV study of the tick-winnel and interim data from the PIVID HG study of PTC 518 and Huntington's disease patients in June .
I will now turn the call over to the operator in Q&A.
to the operator Q&A. Great, q sehrnal anw coriander Camila, I am Melanie
Thank you, Lisa and gentlemen, to ask a question you will need to press star 11 on your telephone and wait for your name to be announced. To address your question, press star 11 again. Please stand by, we'll be compiled again, Eraster.
And our first question coming from Delaina.
RiftickOscow with kanzaare undisautym latex
Hi, good morning everybody. Congratulations on these really great data that you reported this morning. I just had two questions. The first one is, can you remind us what these blood fee levels and coming within the guideline targets really means for patients from the perspective of symptomology of this indication and other factors related to the patient?
that obviously as you point out disease morbidity can be minimized.
Now, in PKU, the issue is that high spinal aligning levels are associated with cognitive defects and brain fog in particular, as well as other symptoms. And it's been well documented that reductions in blood spinal aligning.
For example, every 100 micromole per liter reduction has been associated with improved IQ. So there's a direct correlation between reduction, a sense allowing levels and patient.
benefit, which is why phenylalanine as a blood-based biomarker has been used and is accepted as an endpoint for toilet approval, not just an accelerated approval. So when we consider these guidelines, it's really ideal levels to get to to minimize this morbidity. And I think the fact that we can on treatment get the vast majority of patients below 360 micromole per liter.
differences between Coovan and you have the head to head study. But with this readout, you noted the 27 patients and the significant drop that we saw after treatment on for PTC. So, you know, can you talk about the validation from these data with the mechanistic differences that you see between the two therapies, especially now that you have these additional 27 patients?
Thank you.
It's a great question, Chris. As you alluded to, we conducted a phase two study where we compared C.P. at Karen's head to head with KuVan and demonstrated not only that 50% more patients had significant benefits from C.P. at Karen than KuVan, but those that had a KuVan benefit had significantly larger reductions in phenylalanine on C.P. at Karen relative to KuVan.
And as you rightly pointed out, the data from this trial really validate what we observed in Phase 2. They really continue to demonstrate exactly what you'd expect to see if you had a more bioavailable and potent co-factor therapy as secretaries is. Obviously, those 27 subjects gave us a really unique opportunity to, again, do...
on CPTaren relative to KUVAN again really speaks to the ability to deliver significant benefits to patients who are on KUVAN. So I think that we talked a lot about patient segments and those that we can address including therapy and IE, classical patients, KUVAN failures, but I think this also allows us to start to see the potential to deliver benefits to patients who are believed to be controlled on KUVAN.
Thank you, one more for next question.
Now next question coming from the liner, Robin Kanaskuk with Truist and it's open.
Hi, congratulations on the data. This is fantastic. This is Alex from for Robin. Two questions. Number one.
with the amount of reduction that you've been able to show here and compare it with the care during as compared to Kuvon. Do you, what initial feedback are you getting from physicians? And for physicians that believe that their patients are well controlled on it.
Do you think that this merit preference replacement ahead of Kuvon? And then number two, how much LTE data will you have when you file eventually, and how many responders are going into the LTE study? Thank you.
Thanks, that's all. I'll take the second question first, and then it's your first question second. So in terms of second question, we've had the patients who complete all the patients who have completed part two have moved into the open label extension, and we have additional obviously that's...
Children below age two who weren't randomized or in that study and is actually additional patients who were directly enrolled in the open label extension. So taken together, we believe we'll have a strong data package of both long-term durability of effect as well as safety at time of NDA submission. Of course, we'll also have additional p-tolerance.
involved in pre-setting the marketplace.
Thanks Matt, yeah, I think from everything that we're hearing across the board with physicians is to fight the huge on that need and patients that aren't well controlled on KuVan quote unquote, there's still an opportunity to drive a need in that patient population in the sense that if you're having an ability to drive additional fee reduction, then that can be very clinically meaningful.
Particularly when you look at what physicians say that 100 micro molar per liter is equal to One point scale on on from a cognitive point of view So I think across the board if you look at the different patients segments that mat laid out We see a substantial opportunity particularly in those that are therapy naive
particularly in those that are failing on current therapies and then are poorly controlled on current therapies and then over time obviously looking at the additional fee reduction that we're able to drive. Next chance we'll congrats again on three new.
Thank you, and our next question coming from Delina.
Brian Ibrahim's with RBC, you'll an assultment.
I just Joe and Brian congrats on the data. I've said two questions as well. If you could give us a little more details on this safety, anything you could tell us on the race of headache or your eyesight effects you're seeing there, that would be a super helpful. And could I also ask how consistent the feed reduction levels were at the end of the day?
We had a clean safety data set, which we said the most common AEMEs were diary on HVW grade one, and I think overall they were.
Six patients who had the DEs on the highest level of secretarian. The other important thing is when you look at the frequency of related adverse events, they were similar from both the secretarian placebo groups. So I think this is a very strong...
in terms of safety profile and tolerability profile for the drug. In terms of durability of effect, we were seeing very good durability over patients as they leave the placebo control study and move into the long-term open label study, which is obviously very encouraging.
That was helpful. Thanks so much and we're off on the dinner again.
Thank you. Thank you. And our next question coming from the line of.
Eric Joseph from JP Morgan, Irlande, Selvent. Oh, hi, thanks for taking the questions and congrats on these data. I guess with respect to the breadth of the label indication that you're going to seek, do you anticipate being able to go as low as?
Infants similar to the Kuvaian label, as well as one month, are, would you need to conduct a separate study to facilitate that? And I guess just on the safety front, sorry if I missed it, but where I guess, are there any discontinuations on study as a result of power ability at all? If you just kind of...
We're very clear for that. Thank you. Thank you, Eric. Thanks for the questions.
This study was designed to include patients of all ages and all levels of severity at PQ with the idea that some label would support all age groups.
And as we mentioned, we did were able to enroll patients under the age of two, so we fully expect to have labeled that recover all age groups of patients based on this study, and obviously data from the open label extension that we would submit as part of the NDA.
To your question about tolerability, there were no discontinuations that opposed people control study due to tolerability issues. Okay, great. That's second question.
about tolerability. There were no discontinuations in a placebo control study due to tolerability issues. Okay, great. That's a second question.
Thank you. And our next question coming from the lineup.
Simon Corwin with Willing Blariel and Assulpen.
Good morning, thank you for taking my questions. I found the change in the intake really impressive. The obviously it was a small end. So I was wondering if you could provide any insight into if these patients were in the control arm previously in crossover or across everyone's placebo or where they kind of were on the...
patient spectrum of disease severity or age. And then I'd love to ask a question.
Yes, thank you. So just maybe, uh, give, uh, Sandy, thank you for the questions. Let me just give a little more color on the C-toler assessment. So all patients from the placebo controlled trial, both placebo and secretaryntrype and groups roll into the open label extension. And then for the first two weeks, all subjects are treated on secretaryntrype.
Then after those first two weeks of open label treatment, those that have a less than 360 micro molar per liter blood-stree level are then eligible to enroll in the C-tolerance protocol. So the data you're seeing includes patients who were on active anopathybo and can, against representing the full range of severity. So...
as we did have patients who had higher baseline C levels of over 600 and sometimes over a thousand in the active part that got under 360 were seeing the full spectrum of CPIT air and treated patients.
in that fee tolerance study. So again, as you pointed out, these data are really compelling, not only in terms of treatment effect, but in terms of the drug's ability to really be storing important aspects of quality of life, which is liberalized diet. Great, that's helpful.
And then I guess I noticed that only 27% of the patients were on KuVan at study entry. So I guess I was curious about the other patients if they were just being managed by a fever-stricken diet or if they had previously tried KuVan in the past. I was just curious to see what any insights there.
So the 27 patients, we flexed the 27 of the 156, who went to the Open Label Run-In Part One phase who reported to be on active Kuvan, either branded or generic Kuvan at the time of. So the 27 patients, who reported to be on active Kuvan at the time of.
of entry into that run-in phase. There were additional subjects who reported previous use of COO-VAN or being COO-VAN failures, but we really highlighted those 27 patients because they presented that unique opportunity to be able to understand what the relative treatment benefit of CPT-A-Taryn could be in patients who were on active COO-VAN therapy. Great, thank you so much and congrats again. And our next question coming from the line-up.
Faiton Bumsack with Kyle and Yelena Sullivan. Hi, we've read some results and thanks for taking our questions. I guess just kind of an broader question. What is the required for submission in terms of safety, and in general, is there anything different from the filing strategy between the US and EU and kind of how you're thinking about it?
Great. And then I guess kind of a second follow on question is how are you in general thinking about price range given the very impressive impact on optical patients and but also given that generic view behind you is available? Yes. Great question. I'll turn that over to come. The team has been looking at that. Yeah, thanks Matt. Thanks for the question. I think obviously as we commonly do, we have not set price at this point. We like to look as we progress further with regulatory discussions at the label to understand the true value proposition. But what I will say is we continue to believe the price point will fit between
I think obviously as we've talked about today, the data is extremely strong and provides an opportunity across the huge unmet need that exists in PKU. And so we continue to believe in the value proposition, not just for therapy, naive patients, but also those that...
are looking for additional fee reduction across to vampires and to vampirely control. Ready. Thanks so much for answering our questions and to Raskin on the often data.
Thanks so much for answering our questions and to rad scan on the awesome data.
Thank you. And our next question coming from the line up. Joseph Swartz with SVB Securities, Philanis Alpin. Hi, congrats on the results. I was wondering if you can tell us how many classical PQ patients were screened in order to arrive at the 15 patients who were analyzed in part two of affinity.
and how representative of the overall classical PKU population of these patients based on the mutations they have. And then as a follow up, how confident are you that just six classical patients randomized to sepiafgernas enough?
experience to gain a label in this subpopulation. Thanks. Yeah, absolutely. Thanks very much for the questions, Jeff. So in the first part of the study in the run-in phase, obviously we had the patients that were randomized, the 15 classical patients who were over 30% and we had additional five.
who were between 15 and 30 percent. And so we had a total of 20 that had a 15 percent or greater reduction in that represented about 50 percent of all those classical patients who were in the running phase. The responders represented really a full spectrum of classical. They had including different baseline levels and also different locations of course in a disease like PKU where this.
given the data in those classical patients from both part one and part two, we believe they're sufficient to support treatment of classical patients in the label. Thank you. And our next question coming from the line.
I'm wondering what is the percentage of reduction before enrollment, our percentage of a fee reduction before enrollment, and how many data points you collect for the baseline. And among all those 27 patients, any were classic patients. That's my first part of question.
Yeah, okay, so thank you for the questions, Gina. So those 27 subjects came in and we had a baseline measurement of those patients at screening, so there was one value measured. And as we talked about, they had roughly 590 micromole per liter. They then go get washed out for seven days and we get their baseline values again after wash out. So basically off therapy. And that goes to about 10 and 100, which suggests that there was a roughly 100 to 120 micromole per liter treatment benefit.
in those patients on proven or either to be strapped or trapped or trapped or trapped. We're either branded or generic. Sorry, I don't know where that point is. That was coming from. They then go on Ethiopia, Terran, and we had a 48% lower level of phenol halening the blood relative to what that average level was.
on that's a separate parent again either to be their brand, who that own originator is born so that's that 48% is different. I don't believe any of the patients were possible. I think those, there were no possible patients in that group of 27.
And again, that was one, because if it had to be answered question, it was one measurement taken on Kuvan, then one measurement after wash out, and then the measurements that were done as part of the part one study that gave us the...
blood levels on CPITR. Okay, thank you very much. Quickly on the classic patient, can you remind us what is the definition of the classic patient here?
The classical patients basically need that some points in at birth or at some point in their life, they had levels of spinal alinear at greater than or equal to 1200 micromolecoliners. So essentially the most to repair ones of the disease, typically associated obviously with the left.
or more severe mutation in the phenolinality hydroxyl reasons.
Okay. And when at the baseline, what is the fee level when they enrol for the classification? Patient.
So the, I'm sorry, when they got into the study, what was the baseline levels of...
A classical patient. A classical patient. Yes. So the baseline level of the classic patients, I believe, was on a order of between 700 and 800. We can get you that exact number. So obviously many of them had a...
had some control, obviously, they were not all over 1200, but they were reflecting that they did have some diet control, which led to them having obviously the family allowing levels below 1200.
Okay, thank you. My last question is regarding the safety. I think on slide 13, there is no. I wonder if you can share a little bit more color. I think usually we say the safety will be percentage, you know, grade one, two, three, or the low grade percentage of the most frequent safety events.
So, wondering if you can give a look in more quantitative color. I know you're putting headaches in a few comments there, but you know, we'll be the quantitative color that what percentage patient had, what are the most frequent, I think, one grade two, eight, all grade three, and then what are the, what are the percentage of these?
Yep, so let me just go back to the classical patient. But at baseline, there was 761 micimolectal leader in the active group and 771 of the placebo, sorry, before completely answer your last question. In terms of frequency of treatment, emergent adverse events. The most frequent was diarrhea and at the...
Overall, so if we can keep in mind this was a dose escalation in the placebo controlled study, but overall there was a rate of 7.1 percent of grade 1 diarrhea and there was one grade 2 event, and that actually was on placebo. So it turns out that on CPTAR and treatment, the most common eighty world diarrhea.
or subject-side diarrhea. And there was all grade one. And the second most frequent, a e-treatment related, a e-treatment headache. There was one patient with a grade two headache, repatients with a grade one headache. And there was one subject on placebo who had a grade one headache.
Okay, very helpful. Thank you very much. Okay, very, you're welcome to you. I get very low numbers and again, it's very pleased with the tolerability observed in this case.
Thank you.
Thank you. And our next question coming from the line up, Colin Bristo with UBS, Selen is open.
Hey, good morning and congrats on the really great data. I think we've covered most of what we have, but maybe just on what was the level of fee reduction in part two for the patient who had a 15% to 30% fee reduction in part one? So if I missed that.
And then just thinking about the commercial center of the story, what, how should we think about launch prep and Salesforce build out? Thank you. Yeah, absolutely. So when we, thank you for the question, Colin, when we look at
the total, the full analysis of those randomized. We are seeing a mean reduction overall. So when we include the 15 to 30 percent, the mean reduction overall was about 355. And
in the, sorry, C-I-155 in the overall population of those 15 and older. So again, obviously a bit more than what we observed in the over 400 micro-moleculeed observed in the treatment group. In terms of the commercial question, let me turn that over to Kyrona. Thank you, Colin. Yes, I'm excited.
and the team has already been engaging with these centers of excellence, as well as the patient advocacy community, which is as Matt touched on earlier, coordinated, connected, and moving in the same direction.
And then the fourth important factor from a market access perspective the disease pathology is very well understood and documented. And there's a long side with the strong data coming out of the affinity study today, as well as our phase two head to head study and the additional data we're collecting for feed tolerance.
puts us in a very unique position for engagement across physicians, patients, and payers. And we're moving in that direction and has been for a period of time. With regards to your second party, your question around Salesforce build out. As we've shared, we have a very strong commercial infrastructure in place.
across the globe. And this is in many regions that companies tend to shy away from and we have a proven track record in commercializing rare disease drugs in many parts of the world. From that perspective, where poison ready to go with almost all aspects of what's needed from a commercial build out perspective. So any additional resources will be incremental. So we have the infrastructure and place.
on the classical PKU patients.
How many of these patients actually got to more normalized diet? And I guess how do you see it from a practical standpoint of being able to move into this particular population?
a daily and out allowance. So that's really good to see. Obviously we'll have more data over time including some of the classical PKU patients.
God, thank you for that. And would you, I know that there were multiple doses used in the trial various time points. Do you have any data that might be of differentiate one dose versus another? Yeah, very good question. So just as you pointed out, the...
Part two, this placebo controlled study with six weeks in duration and also included a dose escalation such that for the first two weeks, patients got 20 migs per kilogram. The second two weeks, they got the subject, got 40 milligrams per kilogram. And then in the final two weeks, patients got the full...
60 milligram per kilogram is which is what we use as the run endose and what we anticipate would be the clinical dose. Interestingly, the non-classical patients appeared to have similar levels of reduction at weeks, three and four and weeks, five and six. So at 40 milligram per kilogram, 60 milligram per kilogram, they were similar levels of reduction slightly higher.
on the higher dose. And in the classical patients, we did see a stronger signal of benefit in at that higher dose of 16 milligrams per kilogram. So we, and again, I think what we're encouraged by is really consistent safety at both of those dose levels.
So I think that along with the long-term durability, if futillar and status sets us up to be able to support that higher dose level. Thanks so much for taking my question.
long-term durability. If your tolerance data sets us up to be able to support that higher dose level. Thanks so much for taking my question. Thank you.
Thank you, and our next question coming from the line up.
Jeff, how would more constantly you, Lennace open? Hi, this is Michael Riyadh on for Jeff Hunk. Thank you for taking our questions and congratulations on the compelling data. First, for the patients who received Kuvan at study entry, how has mean blood see looked at the end of the part two and then the OLE? Has it remained at the 300 micromole level or has it been reduced even further over time? Yes.
Yeah.
Thanks to the questions, Michael. So I would say overall what we're observing that SPAR is what patients are reaching in terms of their phenolallyn levels at that primary endpoint part of week six. We're seeing those maintained over the course of the open label extension thus far. So we're seeing that 84% of patients who achieve under 360 micrometer per liter are staying there. And obviously as we showed in the fee tolerance data,
considered normal. This threshold for normal is 120 micromole per liter. So we had a number of patients who were actually not only getting below the target, the therapy target guideline that's 360, but actually down to normal levels below 120 micromole per liter. So that's another variant.
impressive data point that confirms this treatment benefit where observing can be quite substantial for patients. Thank you, that's super helpful. Maybe just to follow up on your previous point on the C tolerance protocol. So we saw a meaningful increases in dietary C intake. Above what's recommended, but surprisingly, blood C levels continue to reduce.
Can you give us some expectations? Was this a result of extended duration of treatment? And maybe could you provide more color on the additional C tolerance data? You had referenced earlier. Thanks so much.
Yeah, so Michael, so this is, they obviously remain on that 60 milligram per kilogram of CPTaren. So basically they're on that drug and you're seeing continued drug effects. So that's really durability of treatment in the face of higher phallalany. So exactly, it confirms they're important, not only finding of durability, but also obviously the durability in the face of greater phallalany.
In terms of the additional data we referenced as we said that we had data available at this data freeze for the first 12 subjects who enrolled in that fee tolerance protocol. We expect to have additional data over time that we look forward to sharing.
Thanks again, thanks for getting on the data. Thank you. Thank you. And our next question coming from the line up, Danielle Buril with Raymond, James Yelena Sopin. Hi, I'm Grace on the data. Thanks for the question. Just a quick one for me. I know there's been a lot of questions done and I'll end in take. Did you just go?
intake over the course of the placebo controlled trial in both the placebo and active groups, which is exactly what we observed. So that the findings that we have in the trial can obviously be attributed to therapy and not to change diet, of course, which is what you expect, given the substantial levels of sea reduction. But that was an important element in the study design to ensure
the maneuvers we took to ensure stabilization of FIENTAKE over the course of the placebo-controlled diet worked well.
ensure stabilization of FIENT take over the course of the placebo control diet worked well. Thank you.
Thank you. And our next question coming from the line up, Paul Choi Whitgulman, faculty on the soap and. Hi, good morning. Let me add my congratulations as well. Two questions for Moss, please.
I'm very important just to understand what sort of range of outcomes you had on the primary endpoint.
And.
So on the...
Primary end point, 95% confidence into bulbs in terms of micromolar production that they were at 352 to 450 point times.
consistent reductions across the entire treatment cohort.
Okay, great. Thank you for that, Matt. And then as a follow up, I think you used a powder for the pediatric patients here. And can you just remind us for the commercial plot in terms of the presentation, have you thought about any changes on the production front for there and you have stability data along those lines?
and then for the adult population, which are used to different presentations there, or which are also likely used in powder. Thank you very much for taking our questions. Thank you, Paul. We're not gonna make any changes. Obviously what this study shows is the formulation we have a highly effective, well-calorated and easy for patients to use in the one-stay-ly dosing. We have obviously already done the work to go from what was...
The clinical manufacturing to be sure that we have all the commercial scale of processes in place so we can move forward Having the CMC data support ND and NMA submission and obviously also having the supply for commercial launch
Okay, great. Congratulations again. Thank you. Thank you, Paul. Thank you. And I'm sure you know for the questions in the queue at this time, I will not turn the call back over to Dr. Matthew Klein's point of closing remarks.
Thank you, and I want to thank everyone for joining us this morning. Obviously, we're incredibly excited about the affinity result, really matching in some case surpassing what we saw in the open label and then a threshold response of getting 84% of the patients below 360 micromole per liter. The fee tolerance findings all really substantiate the potential.
for CPITAR to meet that large on medical aid for PKU patients. We look forward to next step and we'll keep everyone informed as we move through the necessary regulatory processes. So again, thank you everyone for joining us this morning and have a good day. Please, and gentlemen, that doesn't go a conference for today. Thank you for your participation. You may now disconnect.