Q3 2022 X4 Pharmaceuticals Inc Earnings Call
Greetings and welcome to ask for Pharmaceuticals third quarter 2022 conference call. At this time, all participants are in a listen only mode.
Shouldn't answer session will follow the formal presentation.
As a reminder, this conference call is being recorded.
It is now my pleasure to introduce your House, then Perry from Lifesize advisors. Please begin.
Thank you operator, and good morning, everyone.
Presenting on today's call will be X Force, Chief Executive Officer, Dr. Paula Ragan.
Chief Medical Officer Diego Academy, we all see her briefly from the company's new Chief Commercial Officer, Mark Baldry and company Board member and incoming interim Chief Medical Officer, Dr. Mary Stuart.
Following prepared remarks, we'll open the call to your questions will be joined by Chief Financial Officer, Adam Mostafa, Chief Scientific Officer, Arcturus, and Chief operating Officer Mary Dibiase.
As a reminder, on today's call.
The company will be making forward looking statements regarding regulatory and product development plans as well as research activities.
These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted.
A description of these risks can be found in X force most recent filings with the SEC, including this quarter's 10-Q.
Which is expected to be filed after market close today.
I'd now like to turn the call over to exports President and CEO , Dr. Paula Ragan.
Paula.
Thanks, Dan and thank you everyone for joining us on the call. This morning as I shared in our press release this morning, and as Dan just mentioned, you'll be transitioning out of his role as chief Medical officer, and becoming a senior medical consultant to ask for.
And our board member Dr. Murray Stewart, former Chief Medical Officer of GSK and rhythm Pharmaceuticals.
Joining X four as interim CMO at the end of today's call Maria will say a few words of introduction.
As we welcome new team members, we are extremely excited to share the progress that we've been making as we sharpen our focus as a company with a mission to develop therapeutics to treat the broad patient population with chronic neutropenia disorders, including our first potential indications of whim syndrome, and where we believe there's a significant need.
For an oral efficacious therapy with low treatment burden and good tolerability.
With no oral therapeutic approved for approximately 50000 chronic neutropenia patients in the U S.
We believe that Maverick before if approved could represent a new opportunity to transform the treatment landscape and create a new standard of care.
Today, the focus of the call will be to provide updates on Maverick further progress in our global pivotal phase III trial, and whim syndrome and to highlight how we are getting appropriately prepared to ramp into commercial launch.
Maverick before it is being studied in an ongoing phase III for the treatment of whim syndrome.
Which has a population of people with severe neutropenia as well as other immune system deficiencies.
Women syndrome is considered a combined immuno deficiency because patients with win not only have profoundly low neutrophil count.
But also low lymphocyte and modified talents and sometimes low antibody production, which is referred to as hypo Gameloft globular anemia.
We believe that Maverick four has the potential to favorably impact the combined immuno deficiencies of those with whim syndrome, and also has the potential to favorably impact a potentially broader population diagnosed with chronic neutropenia disorders.
I'd like to take a minute now to review whim syndrome, and how patients are diagnosed next slide please.
As I mentioned whim syndrome is a combined immunodeficiency impacting people from birth.
Things have profoundly 11, neutrophil counts as well as abnormally low lymphocyte and monitor accounts.
And in many cases low immunoglobulin levels.
But W. H I and Emma will represent the variable presentation of the disease, which can range from severe work presentations the W and HPV associated disease to low immunoglobulin levels. The age for hypo gambling Laguardia anemia increased susceptibility to frequent infection.
In the eye and retention of neutrophils in the bone marrow called Milo Cathexis, B M, which explains the severe chronic neutropenia.
Patients can prevent with one or more of these disease manifestations. In addition to low neutrophil lymphocyte and modest right.
In view of it is variable and complex clinical phenotype of range of inputs and utilized by clinicians to diagnose whim syndrome occur.
According to leading experts in this field one of the most reliable way is to begin the journey of diagnosing win is to examine total white blood cell counts, which includes neutrophils lymphocytes and monocytes and look for multiple decreased white blood cell types referred to as Panleukopenia.
As a consequence of the Panleukopenia people with whim syndrome experienced lifelong risk of bacterial fungal and viral infections with particular susceptibility to refractory award due to infection by human papilloma virus, which can evolve into HPV related cancers.
Sections can be severe including sector.
Bone marrow biopsies can be utilized in the diagnostic journey, although it may not always be done due to the pain of potential morbidity associated with this needle based invasive procedure.
Upon microscopic evaluation, the hyper mature or hyper segmented neutrophils in the bone marrow are important findings to corroborate the diagnosis of whim syndrome and.
In fact, the disease was initially called Milo Cathexis before there is knowledge about genetic mutations.
Genetic testing to look for a gain of function mutations in the <unk> four receptor is the confirmation of our assessment most often used.
Pathologic abnormalities in the bone marrow genetic mutations and family history assessments.
Importantly, there are no approved treatments specifically for women syndrome existing treatments only address individual components of the disease.
Such as giving high dose immunoglobulin to treat the low antibody levels or UCSF injections to treat the neutropenia, which is often poorly tolerated for chronic use.
We recently completed the randomized placebo controlled portion of the phase III study a mavericks for in whim, which is testing for the first time in a registrational study a targeted treatments that specifically addresses the root cause with the potential to improve the full spectrum of problems associated with the disease.
I will now turn it over to Diego to review, our Phase III study design and our historical data that supports why we are so excited about our pending pivotal trial results.
<unk>.
Thank you Paula allow breaching review is totally new sign of our four wing globally Registrational trials facing mumbled, except for a couple of potential treatment or green syndrome.
Ah stolen mentioned.
<unk> is a randomized placebo controlled double blinded study.
We completed enrollment in Q3 of last year over enrolling this with 31 patients from 12 countries.
We have now completed the less patient <unk> for the placebo controlled 52 week period, and Ah dealing generally working towards database lock.
This service inclusion criteria required that all patients enrolled haddock confirmed absolute neutral flip count or agency less than or equal to 400 cells per microliter during screening.
For the 31 patients enrolled in the trial.
The average pretreatment ANC was 220 cells per microliter.
An indication of the severity of cloning neutropenia that Characterises Williams syndrome.
<unk> 500 cells per microliter East coast scissors severe neutropenia, indicating that this population was severely neutropenia as they enter this study.
Importantly, almost half of the patients enrolled word paediatric between 12, and 17 years of age, which supposedly potential for us to receive a rare pediatric disease priority to reveal voucher or pov upon approval of mobile except for of significant.
Potential value to the company.
At the end of the placebo controlled portion of this study all participants were eligible to roller willing to help and they will extension or all L. E study not.
Traveling more than 90% of eligible participants elected to continue on and received <unk> treatment in the oily we.
We are continuing to collect data from decent ongoing portion of the time.
Safety from the trial has been monitored regularly by our data safety monitoring board, which has endorsed the continuation of this study without any protocol modifications due to safety.
Laura will lead.
As I mentioned, we have now completed less patient less vcd in the placebo controlled portion of the trial.
They blinded data are being reviewed by an independent Adjudication Committee and database look is soon to follow we continue to expect announcing phase III top line data in the fourth quarter of this year.
The next slide place.
We have a robust series of metrics to assess the efficacy and safety of melodic suffering when patients in this phase III trial.
The primary endpoint some metric called Tat AMC.
Which is time above threshold or Ta T for short for absolute neutral free accounts or a N C.
It is an assessment of Mavericks supposed potential to race neutral feet counts above the severe neutropenia threshold over a 24 hour period.
Participants in this study will dosed once daily for 52 weeks with either <unk> or Moor, except for.
The 24 hour Patting AMC was measured four times during the 52 week treatment period, approximately once every 12 weeks.
The status first <unk> time above threshold for absolute lymphocyte counts or Ta Ta LLC.
Calculations, followed the same approach as for Tat AMC.
Assessment of tab Alcs important for wind patients, who suffer from significant lymphopenia and hypo gamma globally nemea.
Recall that meaningful site, so mostly BMT sales and a key for mounting a protective immune responses.
The gravity of presents how time above threshold is calculated.
Patients undergo a series of up to 12 blood draws over a 24 hour timeframe.
Never sell measured via standard CBC methods and plotted versus time.
Tiny level of threshold is the amount of time in hours that neutral feel or lymphocyte current sarah equal to or above certain thresholds here 500 cells per microliter for nonprofits.
1000 cells per microliter 14 from sites.
Finally, there is a comprehensive list of clinical endpoints, both Keith secondary an exploratory endpoints to assess the clinical impact of memorial affordable placebo during the first year of treatment.
A few of them are listed here organized by category, one categories patient <unk> reported outcomes or pianos.
The second category is related to infection some words.
Categories response to vaccine and.
The fourth category safety Tolerability M P K.
There are also sell it all pre specified subgroup analyses.
These were a Boston comprehensive study design reflects the guidance provided by the FDA over a number of consultations and we will share more specifics on this in our field slides and.
Next slide place.
As you can see here that phase two endpoints closely mirror, our phase III endpoints and the success of this trial along with the results from the Phase two open label extinction study half formed the basis of our confidence in phase III success.
The positive phase two results not only inform the phase three trial design.
But also served as the basis for the power assumptions for the primary and the top secondary endpoint of the phase III drive.
Based on their blinded baseline <unk> 31 subjects enrolled in the high retention rating. This study.
The primary endpoint of the phase III traveling when syndrome is power to a greater than 95%.
In the phase two study we saw that all patients responded to <unk> treatment with increased Neutrophilia lymphocyte comes.
Increases in both Tat ANC and tap Aoc upon treatment with a 400 milligram dose, which Wednesday those selected for the phase III trial ranged between approximately 224 hours importantly.
These observed increases in tax agency and tap ALC in the phase two trial were associated with clinical benefit including positive patient reported outcomes.
<unk>, both the rate of infections Andiwal to Berlin, and equally importantly, <unk> was well tolerated throughout this study, including the long term extension.
Recall that these favourable phase two results resulted in the MBA granting us breakthrough therapy resignation or beat television for <unk> for the treatment of Williams syndrome.
I also recall that hurdle for BT Z is high and required preliminary clinical everything's from our phase two study that indicated as a draw may demonstrate substantial improvements on a clinically significant endpoint or endpoints.
Available therapies.
The totality of their face to data was shared with MCA and supported the award of BTB for my worry except for England.
On this slide we provide a patient specific view on the impact of once daily around treatment of memorial separately and a participant in their face to study.
This study participant was a 24 year old female with a long history of large refractor rewards that had a manual negative impact on her quality of life and cancer risk.
She also reported frequent sinus infections.
In this kill shop, you can see the large compound words encasing his name part of her thumb.
A regional words of even larger sizes were distributed over at her hands and feet.
A dramatic resolve showing the subjects wild lesions west Aly leaned over time during the phase two study these.
<unk> capture these favorable change their thumb image on the left shows awards leashless prior to treatment. They mentioned the right shows the same thumb. After this subject was treated for almost a year with a 400 milligrams once daily those.
We can see that in many areas deletions almost completely resolved.
Similar reductions will this evening everywhere empty across most of the other reasons as well.
These same patient was interviewed after more than three years old treatment.
She reported on her experiences as overall, reducing heading fetched shows on world burden.
And reported an improvement based on their patient global impression of change or a P. G. A U C questionnaire.
We have included the PGA C assessment, among other patient and physician reported outcomes in our phase III.
Next slide please.
It seems the initiation of our <unk> syndrome, we have had ongoing interactions with the F D a and frequent.
Frequent engagement with the agency has continued on their breakthrough therapy resignation and in the context of an orphan designation.
Importantly, the F. D. A has provided clear guide honestly that has Informa was study these sign named putting some plant analysis.
They have recognized the rioting and heterogeneity of wind syndrome, and have guided us on our end points, including combining assessments of infections on what seemed to a single compulsive and point to optimize the potential for the trial to show a difference between <unk>.
An infection related metrics with the available sample size.
<unk> has followed all of the guidance provided by the FDA and we are looking forward to announcing top level results later this quarter.
Once the data and blighted and analyzed we plan to share data that will include the primary and point tab AMC.
The first key secondary endpoint tap ALC, along with the trial safety assessments.
I will now turn it back to Paula.
Thank you Diego, we believe Mavericks afar as well positioned to make history by being the first treatment specifically developed for the treatment of women and drown.
Discussions with the agency, we expect our label to be focused on notice 812 and older diagnosed with <unk> syndrome.
And it's been an ongoing commitment of export of support education awareness and ultimately the diagnosis of limb syndrome, and the medical and patient communities.
It previously described the diagnosis of Wham requires a clinical assessment consistent with one or more of the various phenotypes W. H I N M and is setting a combined immunodeficiency that is neutropenia, lymphopenia monocytopenia and our hypo gammy leg.
<unk>.
And can potentially included bone marrow examination as well genetic testing assessments and family history information.
We've been investing in a breath of activities to support the clinical and patient community as outlined here and I'd like to highlight a few more recent effort.
We think I'm collaborating with a bone marrow pathology expert with the potential to establish a mile Cathexis banner of excellent.
In the future, we envision such a center it could be a place where physicians concerned bone marrow samples for a second opinion to be analyzed by those experienced with miles have access to eat in a potential diet <unk> syndrome.
Additionally, we have hired a patient educationally a ban medically trained professional who can come finally engage directly with patients and their families to support that potential for genetic testing amongst individual or kindred members within the same family.
And finally, we are excited to support the international patient organization for primary immunodeficiency is R. I Pappy and establishing a global registry for people with <unk> <unk>.
Bringing together those working across a breath of existing immuno deficiencies, including a patient foundation patient community Representatives experts and <unk> and academic centers in the U S and abroad. We believe this registry has the potential to be a great resource for the <unk> community their physician.
And for drug development company in such as X four to learn even more about the disease.
<unk>.
I hope he can nasty why we are so excited for the Unblinding of our phase III tryout result.
Assuming I successful phase III, we are already gearing up for an NDA submission in the early part of the second half of 2023, and if approved preparing for the U S launch a maverick for in the first half of 2024.
Amy filing is expected to fall are you at filing by about 12 months.
And if approved we expect commercial lines would be initially focused in the top five to seven European markets with others to follow.
We may consider partners to support the launch a maverick for in territory outside of the U S. M E's key European countries.
We will update you at a future point, when we have clarity into any potential partnerships.
Next slide please.
As I mentioned earlier, we are joined honest mornings Carpi, Mark Badri, our new Chief commercial officer.
Today is actually in March 1st day at at four and we couldn't be more pleased to welcome him.
As a quick background Mark comes to us with more than 30 years of experience and global lifestyle commercial strategy in operation.
Having launched multiple orphan and rare disease therapeutics.
Keith, particularly skilled in building and coordinating global team and equally importantly is as passionate as we are about innovating for patients in need.
We consider ourselves very fortunate to have someone with mark background joining us at this critical time in our corporate evolution and are looking forward to getting mark up to speed on our Mavericks are programs and continuing to advance our commercial readiness as they approached the unblinding of our phase III <unk> trial.
Mark to your first day at X four.
Thank you Paula I'm really pleased to be here and I'm looking forward to digging in.
This is such an exciting time at X four and as you've just outlined a great opportunity for me to help support free commercial efforts and hopefully the commercial launch of Mavericks before and it's first indications.
I've spent much of my career focused on launching in a bit of therapeutics that we're able to transform the lives of patients around the world who are living with rare diseases.
And I've joined explore because I can clearly see the potential of Mavericks before.
It only became the first therapy for people with women syndrome.
But also to become a new standard of care for those with chronic <unk> disorders.
Considerable challenges with currently available therapies.
I'm really looking forward to working with you and the whole X for cheap.
As our remark.
Banks neck five please.
And so you would expect preparing the product the market and the company for commercialization to ensure Mavericks were treatment <unk> with <unk> syndrome is well underway in anticipation apathy III data and leading up to plan 2020 for a lunch if approved.
Here I wanted to share some additional ongoing activities and near term planning and highly several spoke to building the commercial wheel and getting it rolling.
I've already mentioned the team of people we have in place out in the field PDL Pel and then the home office.
And if pre commercial stays in under Mark Barbara leadership, we intend to rape it fell on the commercial team as we entered into the next phase of preparation.
These customer facing people are actively engaged with healthcare professionals patient and patient communities to raise awareness of wham.
And recognizing in diagnosing the disease and communicating the potential of Mavericks before through medical channels.
We've also conducted primary peer research with U S and European players to understanding issues and opportunities to gain market access sleepy.
We began to identify the capabilities, we need to build and define the full spectrum of healthcare value that mavericks or may demonstrate and ensure access for patient.
And the manufacturing front registration Baptists have been completed the key requirements core components and partnerships are well underway to ensure a stable and efficient commercial supply chain and specialty distribution network and.
And lastly from a marketing standpoint, we have secured a conditional approval of a brand name with the FDA and exciting step for Maverick before.
Additionally, we have conducted early healthcare professional market research focused on targeting with physicians most likely to have a wham our potential when patients introduced tools available to the patient and Hcp's under these awareness and are developing full branding.
Five per year.
As we move towards an anticipated approval in Wham, we would like to highlight that our time and commitment to launching in wham will be leveraged towards improving our potential future success developing mavericks before for indications that may treat the broader chronic European community.
Same physicians treat women syndrome offer treat those patients with chronic inter panic disorders.
The same piece and foundations that support <unk> off of those with chronic nature panic disorders. In fact, we've already seen these synergies benefit patients and physicians.
For example are free genetic testing program called path forward has enabled physicians to diagnose new patients across the full range of chronic neutropenia disorders, including them syndrome and other congenital neutropenia.
Additionally, we see the synergy potentially translating into support for the additional enrollment and our amended phase one b two anticipated San phase three trial and of course further expanding our network of medical experts that diagnose manage and care for these patients.
Finally, we expect highly leveraged distribution channels for drug supply and pair interaction to support market access to optimize our future sales for the wimp indication if approved and our bottom line.
Next by a for Ya.
We believe that Maverick four has a bright future ahead, if approved for the women indication we intend to continue to develop Mavericks before an additional indications where we believe it has the potential to become the only oral treatment approved for an array of chronic neutropenia disorders.
As presented over the last few years in the context of various clinical trial, we've seen dramatic and sustained increases in nature cell counts, but all patience responding to maverick before including across all of the sea and disorders. We studied thus far.
As a result, we plan to study whether mavericks or has the potential to treat up to 50000 patient currently diagnosed with idiopathic congenital neutropenia in the U S.
And we are on the cusp of a potentially positive safety trial that could support a U S lots of 2024.
<unk> that could not only began to generate meaningful revenue for X four but can also set the company up to maximize success and chronic <unk> disorders beyond Wham syndrome.
In closing you can see that we expect a steady cadence of milestones ahead of us starting with our potentially transformative when phase III data later this quarter, followed by additional expected <unk> data and potential initial clarity on the regulatory path forward for Mavericks for it and C. N N that first.
Half of 2023.
Assuming positive phase III results, and Wham or NDA filing for Maverick Devoir is on track for early in the second half of 2023, and we're aiming to be phase III ready to move forward with advancing SCN registration trial. Following the expected filing of our NDA and Wham.
As I mentioned at the beginning of the call. We believe Maverick forest poised to change the treatment landscape and chronic neutropenia, starting with wham and expanding into idiopathic sick like in congenital neutropenia and X four is ready for this transformation.
We are ready to go.
And one last thing before we conclude we'd like to officially welcome Dr. Murray Stewart as our interim CMO. He has a wealth of experience in the development and launch of rare disease therapeutics from a previous CMO rolls at Glaxo Smith, Kline and rhythm pharmacy to call and he has helped guide multiple successful NDA file.
<unk> throughout his career.
We are fortunate to have him join us during this exciting time for X for <unk> today, <unk> would you like to say a few words.
Thanks, Paula I'm really pleased that I'm able to support export this time I'm looking forward to working with the whole works for team poised to unwind the fees to data in advance as quickly as possible to 90 submission.
Having been part of exclusivity for several years now I'm really excited to help the company bring important new treatment option to patients.
Thank you Mary and with that why don't we know open the call up for your question operator.
Mmm.
We will now begin the question and answer session.
Question Q U.
One on your telephone keypad, you will hear its own acknowledging your request.
Using a speaker phone please pick up your handset before pressing.
To redraw your question. Please press Star then too.
Pause for a moment as color is joined the queue.
The first question is from Steven.
<unk>. Please go ahead.
Yeah. Good morning, Thanks for taking the questions and I appreciate the updating the overview of the data.
I know that he was mentioned I guess.
<unk> patients pretreatment.
Do you happen to know also what proportion of patients pretreatment were severely lymphopenia as well in terms of what the average sales he was.
Hi, Good morning, Steve It's Paula. Thank you so much for the excellent question I think my understanding is they are quite severely limpid panic as well the actual number I think of escaping us at this moment, but I believe we published in an abstract back in April some of the details. So we're happy to take that off line with you and make sure you get that information.
Okay, that's fine I can dig that up.
Have you been able to see just.
He did infection rate that's been observed.
The trial to date.
Just curious as to as to whether or not that's information that you're privy to and I guess, whether or not that's kind of tracking to expectations.
Yeah. So we are we are able to look at overall blinded safety related events, which of course infections or one of EM all refer to Diego to provide any more context on that.
Yeah. This is something that the team has monitor us policy uhm, Yeah, we have seen infection on the banks of course will completely blinded we have a very rigorous process of santala adjudication on their <unk> actually working now to finish that and that will police the they've tried to help.
<unk> okay.
<unk> you know, it's one of the matrix of clinical benefit that we are tracking obviously on long survey that Lois, but yes, I've seen we've seen a good number of infections that we believe is.
Consisting what what we expect now does Dave.
<unk> has been somehow <unk>.
Okay. That's helpful and then.
Just lastly, maybe a little bit of a bigger picture question, but I know that you're cutting out I'm talking about the addressable sheesh opportunity is b I guess in the 50000 range.
I know that you had previously.
Indicated or estimated that the proportion of patients I think of the U S who were on chronic gcs F was.
Was maybe somewhere in the 2500 range.
How do you think about the disconnect between those two numbers, how do you close that gap.
In in chronic neutropenia, specifically and then how does that 50000 number.
Factor into your thoughts around this initial mavericks before price.
Yes, a couple of things Steve. Thank you for highlighting that disconnect. So that the 2500 number 800 number that lead throughout previous that he was really based on registry data of course that doesn't really capture.
Than the average utility out and what I would call the commercial setting number one and that's very difficult. So.
G C. S. F is used intermittently in many patients. So how you define chronic semi chronic of another challenge for us as we consider the number of patients on G. Then also to highlight only about half of them Kenneth can tolerate it based on our patient surveys.
Of course, we don't even know what we're not capturing underneath that approach as well so I hear ya on a disconnect I'm actually not worried about the overall market thighs for folks with chronic neutropenia, it's massively underserved market with a treatment that is incredibly painful to take on a daily basis. So we think there's certainly a lot of opportunity to further <unk>.
Or are these patients who really need something new.
And then just how those factors into.
How you're currently thinking about.
The pricing decision no mavericks or with the understanding that you're still.
It's a ways away from having to make that decision.
Yeah, I mean, I I think we've done enough price sensitivity is even around wham to appreciate that even numbers in the tens of thousands are relatively consistent with ultra orphan pricing around wham I mean as examples of best in the field already with the vertex DF molecules.
Certainly getting into the tens of thousands of patients that they serve and commanding the price points of that particular treatment. So I don't think there's really add.
Sort of <unk> deep consideration that we need to make everything about the broader chronic neutropenia markets.
Very helpful. Congrats on the progress next.
Thanks, Steve.
The next question is from ever prevent thorough with Cohen. Please go ahead.
Hi, Thanks for taking our questions and congrats on all the package can you remind us of the towering assumption so swollen trial.
Are there any updated assumptions given the high and Goldman numbers.
Yeah, Good morning IRA.
As we said during the call we use the change in the past <unk> served in the context of the phase two trial.
For power in the phase III tire so based on the increasing this happening and see that we hope says being face to of course that was her range, but we.
We took that into consideration and concluded that to have at least 90 posts empower we needed around 18 patients minimum.
As you heard we ended up and running 31.
We have excellent retention. So that's why we said earlier.
Right now we believe our power on the primary aim appointment is greater than 95 per cent.
And the same goes for the top secondary endpoint.
And it's really important to show that we are impacting not only neutral field, but also meaningful sides cause that goes to the code of these disease.
Great. Thanks, and what's what's the latest estimate on on the prevalence of win based on all the research is done is there any uhm updates under janette experience or anything.
Yeah, I know I mean, we continue to feel very comfortable with guiding to a thousand or higher with Wham syndrome.
It's actually fascinating some of the publications that'll be coming out or have come out around additional genes even beyond <unk> such as <unk> are too. So we think it or just at the very beginning our physicians are incredibly excited about potentially supporting their approach the diagnosis of <unk> of which obviously genetics is a component and we'll keep you updated as we <unk>.
Find that any further.
Alright, thank you.
The next question is from my Yang tiny we'd be Riley Securities. Please go ahead.
Good morning be anything particular questions and look forward to working with you.
Let's do it.
Just maybe <unk> between the baseline.
Oh, please do.
<unk>.
Beyond having now <unk>.
Didn't have good could could you just give us a little bit more color on the clinical presentation of the <unk> you have a in case, we versus the <unk>.
And and and just a reminder, what presentation was was required for all patients the baseline them and also if you.
You did any <unk>.
<unk> and the study gigabyte that'd be great.
<unk>, sorry, I'm just gonna repeat your question back to you if I I Hope I got this right here I think is your fundamental question sounds like what different or similar or different between your patient populations between phase two and phase three since we've included pediatric <unk> at Diego can highlight that and then I think the second element of that was around <unk>.
That address.
Eight three so gay go out I'll turn it over to you for this to these questions.
Yes, good morning, My young so.
So regarding the first question.
<unk> face to face three populations are actually quite similar in the sense that they are only required to have Williams syndrome, all of them actually had <unk> mutation.
<unk> <unk> almost identical the main difference is that we open up phase III to pediatric 12 to 17, while face to us only adults.
You ask what type of clinical females type.
As we Paula mentioned earlier when <unk> ways. So we did not with streaks by whether they have this over you all four letters they had to be clinically diagnosed with wing genetically confirm.
They had to have severe neutropenia, which they all hot so so we feel that phase III pretty much follows face too.
You also ask how 'bout UCSF gcse's use mostly intermittently is not tolerated. So we only allow the use of <unk> phase three <unk> March so.
Initially we have mostly on my <unk> randomize fully blinded very high quality that we're very proud of.
And just Diego you might want to comment on the Uhm approach that we took to make sure we weren't confounding neutrophil accounts with <unk>, Nancy and G. P. S F U.
Yeah see somebody we received UCSF has very few therapy, we postpone the timing of the <unk> means to avoid the confounding.
Got it and maybe just to clarify.
He died of exposure do <unk> and also <unk> either or the rash he had got exposed to do so.
<unk>.
But we did not enroll any wanting phase III, who had been previously exposed to <unk> and in terms of rashes or dermatology safety segments, we really have not seen much of that I mean, we're blindness.
Based on Blind date assessment, we have not seen much nor did we exclude anybody for that.
Wow correct.
Sorry, I'll I'll <unk> <unk>, because the <unk> the the injectable.
Follow up on the the the gods Wildwood off with a double blind data could you just.
The green.
<unk> data and that'd be early filing.
Excuse me <unk> or at least I can have what I've sort of the the activities.
<unk> on on the.
The website and then if there is any overlap.
You're all good dog <unk>.
<unk>.
Date of becoming available.
The good news is gonna help connected dogs bill how the interactions with the progress on these on these different.
So it sounds like you're trying to kind of piece together, the various kind of evolutions of Wham and C. N M regulatory so I will try to lay those out clearly so the phase III data will come in Q4.
You know an average takes about six months to file an NDA give or take so that's where we're putting it in the early early part of second half of 2023 were in excellent shape. They're in terms of just moving it forward and of course working with the agency I as as quickly as needed.
The important thing around chronic neutropenia of course of the amended protocol has been completed we're moving forward with Operationalizing that it's always takes a couple of months of these sites. So we think will have some early data any extension study around durability and <unk> of course, the Wednesdays three will have a lot of durability data given at the one year dosing.
Course, so that totality of data will be useful as we go in to approach. The F. D. A regarding a chronic neutropenia registration trial. So the timing isn't it you know finely tuned, but we believe wham plus fan data plus regulatory conversation should be happening in the first half of next year to prepare us too then.
Of course file the NDA and Wham and shortly thereafter complete that regular registration clarity and kick off advancing a C. N phase three trial subsequent to the N D. A.
Great. Thank thanks for taking our questions and and it's been great working with your Diego all the best for you.
Adventure.
Thank you Megan.
The next question is from <unk>.
With open Heimer. Please go ahead.
Hey, Good morning, just wanted to ask a question on Walton strums any updates here all potential partnerships that might be developing thanks.
No updates for this morning will come back and update as we make progress we continue to focus on upcoming when data any February uprising convenient.
Anything else.
The next question is from Arcane with H C. Wainwright. Please go ahead.
<unk> good morning pull on them and.
Most of my questions have been asked but just.
<unk> headaches.
What sort of.
Data would be pleasant at at the top line no instrument.
This quarter and.
What else needs to get done.
<unk> no.
You're filing a number.
Trying to figure it out get scheduled there are additional luggage.
For your file <unk>.
Sure it's K so.
He can appreciate top line is typically the primary endpoint plus safety. However, we are adding our first key secondary and coin in there to specifically highlight the unique approach.
Coach of Maverick before the targeted therapy for all the combined immunodeficiency effects of wind syndrome. So we're looking forward to sharing a little bit more than usual.
In terms of the totality of the data on the entire trial of course, that's incredibly important to you.
You know preserve republication right. So we do think that will be having a an update adderall irrelevant medical conference Earth via a publication and we will try to provide more guidance. When we have clarity on that and then of course I'll I'll be rolling into our NDA submission early in the second half of next year.
But thanks for that Paula and then.
David <unk>.
That summer that.
Focusing on the chronic neutropenia some.
Diseases at this point.
When would be the next update on under chronic neutral opinions studies so.
And.
Do you think.
Our additional clarity after we get through the <unk> study or you know there'll be any updates on the on those studies.
Yeah. So we plan for additional data updates on ESPN trial in the first half of next year again, I'll try to provide clarity under what format or possibly a medical conference, but it's an exciting trial to me moving forward quickly with an athlete generate some interesting data under that well you know take a cut and share it.
Most importantly, I think for US we really want to work with the agency. So it's really about the totality of data to support our regulatory conversations were all very bullish on moving forward as quickly as we can to a C. N registration trial uhm, So stay tuned and we look forward to providing updates and the first half of next year.
Thank you very much products and I know, it's an exciting quarter. So good luck with everything.
Thank you it is very exciting.
This concludes a question and answer session I would like to turn the conference back over to Paula Reagan for any closing remarks.
Well. Thank you so much for joining today I didn't want to make one additional comments since it's now past nine a M. As you probably know asked 2022 abstract we're just published and we're very happy to announce that are abstract on our faith won't be chronic neutropenia study has been accepted for an oral presentation at this year's meeting.
And Additionally, we've had several additional abstract accepted for poster presentation and these include Q on chronic neutropenia, one on U S prevalence and then the other on the voice of the patient and one additional on the morphology of miles cathexis and <unk>, a very productive Ashraf <unk>.
Forward to seeing some of you in New Orleans in December and with that we're concluded and I hope everyone has a wonderful day. Thank you.
This concludes today's conference call you may disconnect. Your lines. Thank you for participating and have a pleasant day.
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