Q2 2021 X4 Pharmaceuticals Inc Earnings Call

Greetings and welcome to X for Pharmaceuticals, second quarter financial and operating results Conference call. At this time, all participants are in a listen only mode.

Operator: And welcome to X4 Pharmaceuticals' second quarter financial and operating results conference call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Carrie Galan, of LifeSci Advisors. Please begin.

A question and answer session will follow the formal presentation. As a reminder, this conference is being recorded it is now my pleasure to introduce your host Carrie Golan of life Science Advisors. Please begin.

Carrie Galan: Thank you, operator, and good morning, everyone. Thanks for joining us. Presenting on today's call will be X-Force Chief Executive Officer, Dr. Paula Reagan, and the company's chief financial officer, Adam Mustafa.

Thank you operator, and good morning, everyone. Thanks for joining us presenting on today's call.

Well the exports Chief Executive Officer, Dr. Paula Ragan, and the company's Chief Financial Officer, Adam of sulfur.

Carrie Galan: Following prepared remarks by each, we will open the call to your questions, and we will be joined by Chief Scientific Officer Art Tavares and Mary DiBiase, Senior Vice President, Technical Operations and Quality. 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.

Following prepared remarks, we will open the call to your questions and we will be joined by Chief Scientific Officer Arts of Arris.

And Mary Dibiase, Senior Vice President technical operations and quality.

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.

Carrie Galan: These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted.

These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted.

Carrie Galan: A description of these risks can be found in X-Cour's most recent filings with the SEC. I'd now like to turn the call over to Paula Reagan. Okay, Paula?

A description of these risks can be found in exports most recent filings with the SEC.

I'd now like to turn the call over to Paula Ragan Paula.

Paula Ragan: Paula? Thanks, Carrie, and thank you everyone for joining us on the call this morning as we update you on our significant clinical progress achieved so far this year and look ahead to what is expected to be a very productive remainder of the year. As I hope you saw in our release this morning, we provided a detailed update on our Mavericks for clinical programs and highlights of upcoming events and milestones expected through the rest of 2021. For those of you who are following the New CX4 Story, Maverixifor is our lead candidate.

Thanks, Carrie and thank you everyone for joining us on the call. This morning, as we update you on our significant clinical progress achieved so far this year and look ahead to what is expected to be a very productive remainder of the year.

As I hope you saw in our release. This morning, we provided a detailed update on of Maverick for our clinical programs and highlights for the upcoming events and milestones expected through the rest of 2021.

For those of you in news the X Force story Maverix before it is our lead candidate. It is the first in class small molecule antagonist of the chemo kind of receptor the X the are for.

Paula Ragan: It is a first-in-class small molecule antagonist of the chemokine receptor, CXCR4, a receptor involved in the healthy trafficking and maturation of immune cells. With its ability to develop and mobilize white blood cells out of the bone marrow, we believe Mavericksa4 has broad potential to provide patients benefits in a variety of immunodeficiency conditions and in certain cancers. In our lead indication of WIM syndrome, which is a rare inherited primary immunodeficiency disease caused by a variety of mutations to the CXCR4 gene, we announced this morning that we have now surpassed the 18 patient minimum enrollment that is needed for a primary endpoint analysis and for U.S. regulatory filing.

The receptor involved in the healthy trafficking and maturation of immune cells with.

With the building to develop and mobilize white blood cells out of the bone marrow. We believe Mavericks of 4 has broad potential to provide patients benefit in a variety of immuno deficiency condition and in certain cancers.

Our lead indication of whim syndrome, which is a rare inherited primary immunodeficiency disease caused by a variety of mutations to the CX. The are for a gene we announced this morning that we have now surpassed the 18 patients minimum enrollment that is needed for the primary endpoint analysis and.

For U S regulatory filing we.

Paula Ragan: We've now enrolled 23 patients in the Phase 3 trial, enabling the study to also assess the potential clinical benefit of Maverick before. We will be completing enrollment this quarter while allowing for the remaining identified patients to complete screening and potentially enroll in the trial. As a reminder, our 4 WIM trial is a global, pivotal phase 3 randomized, double-blinded, placebo-controlled, multi-center study designed to evaluate the safety and efficacy of Maverick's before and genetically confirmed WIM patients over the course of 52 weeks with an expected open label extension period to follow.

We've now enrolled 23 patients in the phase III trial, enabling the study to also assess the potential clinical benefit of Maverick before.

We will be completing enrollment this quarter, while allowing for the remaining identified patients to complete screening and potentially enroll in the trial.

As a reminder, our for women trial is a global pivotal phase 3 randomized double blinded placebo controlled multi center study designed to evaluate the safety and efficacy of Maverick before and genetically confirmed whim patients over the course of 52 weeks when they.

<unk> open label extension period to follow the.

Paula Ragan: The primary endpoint for the trial, time above threshold, absolute neutrophil counts (TAT ANC), measures the level of circulating neutrophils in a 24-hour assessment relative to a clinically meaningful threshold in response to treatment with Mavericks IV versus the TAT ANC of treatment with placebo. Secondary endpoints assess infection rates, warp burden, markers of the immune system, and quality of life, among others.

The primary endpoint for the trial time of best threshold absolute neutrophil counts for T. A T. A M C.

Or is the level of circulating neutrophils and a 24 hour assessment relative to a clinically meaningful threshold.

The sponsor treatment with Mavericks for versus the T. A T. A N C of treatment with placebo.

Secondary endpoints of thoughts infection rate work burden markers of the immune system and quality of life among others.

Paula Ragan: With enrollment now close to complete, we are confident that we will be positioned to announce top-line data from the trial in the fourth quarter of 2022 and, if successful, intend to file for U.S. regulatory approval in the first quarter of 2023. Based on this progress and on the encouraging data that continue to come out of the open label extension of our ongoing phase two trial and whim, more of which we plan to announce later this year, we are starting to ramp up our pre-commercial planning.

With enrollment now close to complete we are confident that we will be positioned to announce top line data from the trial on the fourth quarter of 2022, and if successful and tend to fall for a U S regulatory approval in the first quarter of 2023.

Based on the progress on the encouraging data that continue to come out of the open label extension of our ongoing phase 2 trial in a whim.

More of which we plan to announce later this year, we are starting to ramp up our pre commercial planning.

Paula Ragan: In addition to the new phase two data that I just mentioned, we also plan to provide further results from WIM patient prevalence studies later this year, results that not only help in refining our estimates of the potential opportunity for Maverick Sport and the WIM indications but that also enrich our insights into market dynamics, patient identification, and physician awareness. Our research team in Vienna has also been doing innovative work to better understand and characterize the genetics underlying WIM syndrome.

In addition to the new phase 2 data that I. Just mentioned, we also plan to provide further results from whim patient prevalence studies later this year for.

Results of that not only help and refining our estimates of the potential opportunity for Maverick sport and the women indication, but that also enrich our insight into market dynamics patient identification and physician awareness.

Our research team in Vienna has also been doing innovative work to better understand and characterize the genetics underlying whim syndrome.

Paula Ragan: Fully developing a mouse model of WIM, for example, examining the correlation between genotype and phenotype, and also identifying a new WIM variant. We plan to announce preliminary findings from some of this work later this year, too.

Fully developing a mouse model of when for example, examining the correlation between genotype and phenotype and also identifying a new win variance.

We plan to announce the preliminary findings from some of this work also later this year.

Paula Ragan: Turning now to our program in Waldenstrom's macroglobulinemia, which you may recall is a rare blood cancer characterized by an excess of abnormal white blood cells in the bone marrow. We announced this morning that we have fully enrolled both cohort A and B in the study with six patients each. We are very pleased to have enrolled the minimum number of patients in the study needed to determine the maximum safest doses in combination with abrutin

Turning now to our program and Walton from macro Globule anemia, which you may recall is a rare blood cancer characterized by an excess of abnormal white blood cells in the bone marrow.

We announced this morning that we have fully enrolled both cohorts a and b in the study with 6 patients each.

We are very pleased to have enrolled the minimum on patients in the study needed to determine the maximum safest dosing in combination with Ibrutinib.

Paula Ragan: We are continuing to enroll patients in the optional cohort C to expand the total number of patients on studies. As a reminder here as well, this is an ongoing Phase 1B open label, multi-center, single-arm study examining intrepation-patient dose escalation, safety, pharmacokinetics, or PK, and the pharmacodynamics, or PD, of maverixipore at doses of 200, 400, and 600 milligrams, in connection with a brutinib, a BTK inhibitor, and the current standard of care for patients with Waldentron.

We are continuing to enroll patients in the optional cohort for me to expand the total number of patients on study.

As a reminder, here is while this isn't the ongoing phase 1 the open label Multicenter single arm study examining intra patient dose escalation safety pharmacokinetics or PK and the pharmacodynamics or PD of Maverick before at doses of 200.406 hundred milligrams.

And kind of with Ibrutinib B TK inhibitor and the current standard of care for patients with Walden problems.

Paula Ragan: Both agents are delivered orally once daily in patients with confirmed NYD-88 and CXR4 mutations. While greater than 90% of patients with Waldstrom's have acquired mutations in the NYD8 gene, a subset, about 30 to 40%, have also acquired mutations in CXCR4. There is a significant unmet need in these double mutation patients where the presence of the CXCR4 mutation can prevent patients from responding well to a brutinib monotherapy. This can manifest as delayed responses, inferior depth of response, and or shorter progression pre-survival.

Both agents are delivered orally once daily in patients with confirmed and widen the 8.8 MTX air for mutations.

While greater than 90 per cent of patients with Walden from have acquired mutations and the N Y D..8 8 gene a subset of about 30% to 40% of also acquired mutations and CX the are for.

There's a significant unmet need in these double mutation patients.

For the presence of the CX the air for mutation can prevent patients from responding well to Ibrutinib monotherapy.

This can manifest of delayed responses inferior depth of response and of our shorter progression free survival.

Paula Ragan: These patients typically experience greater cancer burden, higher serum IGM levels, and increased risk of developing a serious emergent condition called symptomatic hyperviscosity syndrome. In our Phase 1B study, patients are being followed for adverse events and change from baseline IGM and hemoglobin, TK, and PD markers, which include measurements of peripheral white blood cell counts in addition to measuring clinical results. This past June, we were very pleased to present the first data from this trial in an e-poster at the 2021 European Hematology Association meeting.

These patients typically experience greater cancer burden higher serum IGN levels and increased risk of developing a serious emergent condition called symptomatic hyper of iced coffee syndrome.

In our phase 1 B study of patients are being followed for adverse events and change from baseline IDM and hemoglobin.

PK and PD markers, which include measurements of peripheral white blood cell counts and the addition to measuring clinical response.

This past June we were very pleased to present the first data from this trial in an E poster at the 2021 European Hematology Association meeting and.

Paula Ragan: In the poster and on our Investor Day call, we presented details from the first eight patients enrolled in the study. Those data were very encouraging, with Maverickspor, 4 plus abrutinib, demonstrating good tolerability with robust decreases in serum IGM at the low and mid doses of Maverixipore, suggesting best-in-class potential for this combination treatment. We also saw meaningful increases in hemoglobin levels, suggesting a reduction in cancer burden in the bone marrow. And at six months, patients achieved median IGM level reductions of 60 to 75%, but one patient achieved normal IGM, and two of four patients achieved greater than 50% reductions in serum IGM from baseline.

In the poster and on our Investor Day call. We presented details from the first 8 patients enrolled in the study.

Those data were very encouraging with maverick for of plus ibrutinib, demonstrating good tolerability with robust decreases in serum eye, Jim at the low and mid doses of Maverick before.

Suggesting best in class of potential for this combination treatments.

We also saw meaningful increases in hemoglobin levels, suggesting reduction in cancer burden in the bone marrow.

And at 6 months patients achieved median IGN level of reductions of 60 to 75 per cent.

The 1 patient achieving normal IGN and 2 of for patients achieving greater than 50 per cent reduction in fear of my Jim from baseline.

Paula Ragan: By the end of this year, we expect to announce additional data from this Phase 1B trial in Waldenstrom, including safety and efficacy at the highest dose of 600 milligrams of Maverick 4, as well as clinical response measures. Now, let's turn now to our ongoing clinical program in severe congenital neutropenia, or S-E-N, a rare blood disorder characterized by abnormally low levels of certain white blood cells called neutr We are currently conducting a Phase 1B clinical trial in SCN, and as enrollment is continuing to progress, we expect to be able to announce some initial data from the study in the fourth quarter of this year.

By the end of this year, we expect to announce the additional data from the phase 1 b trial in Walden strong, including in safety and efficacy at the highest dose of 600 milligrams of Maverick before as well as clinical response measures.

Let's turn now to our ongoing clinical program and severe congenital neutropenia or S. The N. A rare blood disorder characterized by abnormally low level of certain of white blood cell called neutrophils.

We are currently conducting a phase <unk> clinical trial and S N and as enrollment is continuing to progress we expect to be able to announce some initial data from the study in the fourth quarter of this year.

Paula Ragan: Interestingly, as we've continued to assess Maverick's mechanism of action and its ability to mobilize and develop neutrophils, data continue to emerge from prior and ongoing studies that show chronic, sustained white blood cell increases across a number of patient groups treated with Maverick Ziphyls. As a result, we are beginning to explore the potential for broader youth of Mavericks across the larger chronic neutropenia landscape. Our initial data in SCN, as part of this broader data set, may facilitate these larger opportunities for Maverick Sipore in chronic neutropenias, and we aim to provide more details on these exciting efforts later this year.

Interestingly as we've continued to assess Mavericks of course the mechanism of action.

And its ability to mobilize on develop neutrophils data continue to emerge from prior and ongoing studies that show chronic sustained white blood cell increases across a number of patient groups treated with Maverick before.

As a result, we are beginning to explore the potential for broader use of maverick before across the larger chronic neutropenia landscape.

Our initial data in S yen as part of the broader dataset may facilitate these larger opportunities for Maverick before in chronic neutropenia is and we aim to fried more details on these exciting efforts later this year.

Paula Ragan: In summary, we could not be more pleased with our progress over the first half of 2021. Despite a global pandemic, we have been able to significantly advance Mavericks through key clinical development milestones with commercialization in sight. As we look ahead to what we expect to be a news-rich rest of 2021, we thank all of you for your support and look forward to providing frequent updates on our continued progress. With that update, I will now turn the call over to Adam to discuss our financial results for the quarter. Adam?

In summary, we could not be more pleased with our progress over the first half of 2021despite a global pandemic, we have been able to significantly advance the maverick sport through key clinical development milestones with commercialization insight.

As we look ahead to what we expect to be of news rich the rest of 'twenty 'twenty..1 we thank all of you for your support and look forward to providing frequent updates on our continued progress.

With that update I'll now turn the call over to Adam to discuss our financial results for the quarter Adam.

Adam S. Mostafa: Thanks, Paula, and thanks to all of you on the call. As presented in our press release this morning, I will summarize our financial results for the second quarter ended June 30th, 2021. Research and development expenses were $13.2 million for the second quarter of 2021, as compared to $9.3 million for the comparable period in 2020. General and administrative expenses were $5.8 million for the second quarter of 2021, as compared to $5.3 million for the comparable period in 2020.

Thanks, Paula and thanks for all of you on the call today.

As presented on our press release. This morning, I will summarize our financial results for the second quarter ended June 32021.

Research and development expenses for $13.2 million for the second quarter of 2021.

As compared to $9.3 million for the comparable period in 2020.

General and administrative expenses were $5.8 million for the second quarter of 2021.

As compared to $5.3 million for the comparable period in 2020.

Adam S. Mostafa: And we reported a net loss of $19.6 million in the second quarter of 2021 as compared to a net loss of $15.1 million in the second quarter of 2020. Note that net losses include $1.8 million and $1.2 million of certain non-cash expenses for the quarters ended June 30th, 2021, and 2020, respectively. We had $96.5 million in cash, cash equivalence, and restricted cash as of June 30th, 2021. We continue to expect that these funds will support our operations into the fourth quarter of 2022. We'll now open up the call to your questions.

And we reported a net loss of $19.6 million from the second quarter of 2021 as compared to a net loss of $15.1 million in the second quarter of 2020.

Note that net losses include $1.8 million and $1.2 million of certain non cash expenses for the quarters ended June 32021, and 2020, respectively.

We had $96.5 million in cash cash equivalents and restricted cash as of June 30 of 2021.

We continue to expect that the sponge will support our operations into the fourth quarter of 2022.

We will now open up the call for your questions.

Operator: Thank you. As a reminder, to ask a question, you'll need to press 1 on your telephone. To withdraw your question, please, press the Pound Key. Please stand by while we compile the Q&A list. Our first question comes from Stephen Willie on Stiefel. Your line is now open.

Operator.

Thank you and as a reminder, task of question you'll need the press star 1 on your telephone to withdraw your question. Please press the pound key please standby, while we compile the Q&A roster of.

First question comes from Stephen Willey with Stifel. Your line is now open.

Ellen: Hi, all. This is Ellen on for Steve. Congratulations on all the progress. So you mentioned that you now have 23 patients enrolled in the Phase 3 WINS study and that there are currently patients undergoing screening. So I was just wondering, could you clarify? Does that 23 patient count include those patients that are currently undergoing screening, or are there additional patients, in addition to these 23 that you've mentioned, that are in the process of being enrolled currently?

Hi, all of this is Ellen on for Steve Congrats on all of the progress. The you mentioned that you now have 23 patients enrolled on the phase III <unk> study and that Theres, probably patients undergoing screening. So I was just wondering could you clarify is that 23 of.

Remember include those patients that are currently undergoing screening or are there additional patients and other.

The 23 that you mentioned that are in the process of being enrolled currently and then kind of related to that so I think the trial. The critical allows for up to 28 patients enrolled do you expect to enroll 28 or of will it be able the lesson that and then I have a whole lot of thank you.

Ellen: And then, kind of related to that. So I think the trial, the protocol allows for up to 28 patients to be enrolled. Do you expect to enroll 28 patients, or will it be a little bit less than that? And then I have a follow-up question.

Ellen: And then I have a vote. Thank you.

Hi, Alan Thanks for the question. So the first part of May of 'twenty, 3 patients already enrolled period like bear in and moving forward and study. There are a number of patients that were are also ongoing screening, we don't know yet, which 1 of those or how many of those will qualify for the study. So we have to complete screening and certainly our hope is to get it.

Paula Ragan: Hi Ellen, thanks for the question. So the first part is we have 23 patients already enrolled, period, like they're in and moving forward with the study. There are a number of patients that are also ongoing screening. We don't know yet which one of those or how many of those will qualify for the study, so we have to complete screening. And certainly, our hope is to get as close to 20 as possible.

Close to 20 as possible, but given the robust enrollment that we have to date excuse me and the data that we thought that would be generated from that we're moving forward on finalizing enrollment this quarter.

Paula Ragan: But given the robust enrollment that we have to date, excuse me, and the data that will be generated from that, we're moving forward with finalizing enrollment this quarter. Okay, great. Thank you. And then, can you provide any details as to when we might expect to see the new data from the open-label extension portion of the Phase 2 WIM trial and then also those updates regarding patient prevalence? And then, maybe on that latter point, I understand there are a few different efforts underway with regard to patient identification, including the Invite collaboration, partnerships with patient advocacy groups, et cetera. So will that prevalence update be from kind of a whole list of all of those efforts, or will it be, you know, one or two that are specifically the focus for that update? Thank you.

Okay, great. Thank you and then can you provide any details as to when we might expect to see the new data from the up on the open label extension portion of the phase 2 of them trial and then also those updates regarding patient prevalence and then maybe of that latter point I understand there are a few different efforts underway.

Underway with regards to patient identification, including on the N V take collaborations partnerships with patient advocacy groups et cetera, so well that prevalent update b from kind of a holistic update from all of those efforts there will be the 1 or 2 that are specifically the focus for that update thank you.

Paula Ragan: Sure. So there was a prevalence question, and then I think it was the open label extension, and those are sort of what data to expect by the end of the year. Is that correct? Yeah, and then just the timing, which you just answered there.

Sure. So I there was the prevalence of question and then I think it was the open label extension on those are sort of what what are the date of tricks that by the end of the year is that correct yeah.

Yeah, and then just the timing of which you just answered there. So yeah sure. So we are looking forward to presenting updates by the end of the year ideally at Ash, we have submitted our abstracts and hope Theres a number of them that would.

Paula Ragan: Yeah, sure. So we are looking forward to presenting updates by the end of the year, ideally at Ash. We've submitted our abstracts and hope there are a number of them that would be sharing great data and support with our collaborators, our clinical collaborators, and research collaborators on both the WIM open label extension. And then we've actually been working on WIM prevalence, both in terms of connecting patients and genetic mutations, both in collaboration with Indyte, some of our own research that we've been working with individual investigators.

Be sharing great data and support with our collaborators our clinical collaborators on research collaborators on the both the whim open label extension and then we've actually been working on whim prevalence of <unk>, both in terms of connecting patients and genetic mutations of both in collaboration with M. D. K from of our own research that for you.

When working with individual investigators so it'll be an amalgamation of some of the work that will that had been pulled together from a number of sources and we'll have that also at the end of the year around the ash timeframe.

Paula Ragan: So it'll be an amalgamation of some of the work that has been pulled together from a number of sources, and we'll also have that at the end of the year around the ashtime frame. Okay, great. Thank you for taking the questions, and congratulations on the progress this quarter.

Okay, great. Thank you for taking the questions and congrats on the progress this quarter.

Thank you so much.

Trevor Allred: Thank you. Our next question comes from Trevor Allred on behalf of Oppenheimer. Your line is now open.

Thank you. Our next question comes from Trevor I'll work with Oppenheimer. Your line is now open.

Trevor Allred: Hey, thanks for taking the question. I wanted to ask about the SCN trials. Do you know what mutation types you have enrolled so far and what mutation types?

Hey, Thanks for taking the question I wanted to ask about the SPN trials do you know what mutation types you have enrolled so far on what mutation types you expect to enroll.

Paula Ragan: expect to enroll once you're completed the day?

What's your completed there.

Paula Ragan: Sure, thanks for the question. So maybe I can just remind you about severe congenitalineutropenia. Certainly, there are some known genetic subtypes. Congenital Neutropenia is also a clinical diagnosis that can have an unknown origin, and we're being very open to enrolling both those with known and unknown mutations in the study, given the broad applicability of Mavericks before that we've already been seeing across a number of patient populations. So as the data emerges, we'll certainly share with you the effects on patients with and without various mutations, but we're excited about what we've been seeing across our currently published studies, and we really think this is going to be quite interesting jumping points for the company in terms of its even broader applicability beyond these congenital neutropenias into the chronic neutropenium market.

Sure. Thanks for the question. So maybe I can just to remind you about severe congenital neutropenia.

Certainly as the there are something that none of genetic subtypes congenital neutropenia off is also a clinical diagnosis, which can have on unknown origin, and we're being very open to enrolling both of those with known and unknown mutations in the study given the broad applicability of Maverick before that we've already been seeing across the number of patient populations.

So out of the data emerges, we'll certainly share with you the effects on patients with and without various mutations, but we're excited about what we've been seeing across are currently published studies and we really think of it was gonna be quite interesting jumping point for the company in terms of its even broader applicability beyond these congenital neutropenia of into the chronic neutropenia market.

Paula Ragan: Okay, great. And in terms of what we've seen,

Okay great.

And.

In terms of what we've seen.

Paula Ragan: Excuse me, so far with Waldenstrom's and the positive results with things so far, do you have any expectations?

Excuse me, so far with the with Wolfe <unk>.

On the positive results for the things so far do you have any expectations already for what the next trial for long terms might look like.

Paula Ragan: What the next trial for Waldensterns might look like.

Thanks, So I know, we appreciate that so the way.

Paula Ragan: Thanks. No, we appreciate that.

Paula Ragan: So we have yet to complete the trial ourselves. Obviously, we want to complete our safe doses and then discuss trial designs with the agency, so we don't have any specific guidance on our next steps. There certainly have been the bookends, historically. There have been single-arm studies that have been supported for full approval with abrutinib as a monotherapy way back when. And then there have been, obviously, recently controlled trials where Xanyub versus Brutnib in a randomized phase three trial. So there is the full spectrum. We won't know until we go in with our data set in hand, and we'll probably have more information in 2020 on that. Okay, great. Thanks, Wallace.

We have yet to complete the trial ourselves obviously, we want to complete our safe dosing and then discuss trial design with the agency. So we don't have any specific guidance on our next steps are there has certainly been the bookends historically there have been single arm studies that have been supported the offer of full approval with ibrutinib as a monotherapy the way back when and then there have been at all.

The recently control trials, where it was dania brunet versus Ibrutinib in a randomized phase III. So there is the full spectrum, we wont know yet until we go on with our data set in hand, and we'll probably have more information in 2022 on that.

Okay, great. Thanks, Paul.

Thank you.

R.K.: Thank you. Thank you. Our next question comes from R.K. with H.C. Rainwhite. Your line is open.

Thank you. Our next question comes from RK with HC range, Mike Your line is open.

R.K.: Thank you. This is Rki from Hitzuvenloid. It's great to see all the progress. A quick question on the variant, Paula. You said, you know, your research folks are looking at WIM variants. Can you expand on that? Sure, I'll actually invite Art to share a little bit more on our strategy there, Art.

Thank you this is RK from HC Wainwright.

Hum.

Great to see all the progress.

On the quick question on the Radian.

Paul are you said.

Yeah.

Your research folks are looking at the same radios waters.

Can you expand on the lease.

Sure I'll actually and by our share of little bit more on our strategy of their arch.

Unknown Attendee: Sure, thank you, Paula. And hi, Archa.

Sure. Thank you Paul on the hierarchy.

Unknown Attendee: So with the Vian team, we've been looking at the known Wynn mutations, and we've also been looking at variants of unknown significance. And for us, the goal is to understand as much as possible. Genotype-phenotype correlations, looking at signaling, looking at internalization, and other factors that really reflect the gain of function activities that are seen with the mutations. We've identified a mutation, in particular, which we're going to discuss later this year in the publication, which actually has pathogenicity associated with it.

So what could be on the team who've been working on it are known when mutations and we also on looking at Jared So for non significance for us the goal is to understand as much as possible.

The correlations looking at signaling internalization.

The other factors got really reflect the gain of function for activities that are seen with the mutation.

If I kind of body.

Patients in particular, which we'll discuss later this year in the <unk>.

Colocation, which actually has put a strain of Citi associated with it.

Unknown Attendee: We did some work in collaboration with medical doctors in the field, characterizing patient cells, excuse me, patient cells to also confirm the pathogenicity that we're seeing with transfectin cells harboring those same mutations. And then we've done work where we're looking at various genomics databases and trying to understand prevalence. And so all of that put together actually suggests that now there are an increased number of patients, or at least there are additional patients with this particular mutation, and we now know it's a pathogenic mutation. So we'll be disclosing our case later this year in a publication format. The work that we've done on that mutation and others as well.

We did some work in collaboration with medical doctors in the field to characterize.

The patient cells excuse me.

<unk> sales also confirmed the oxygen of city, though were seeing would transfer of consoles corporate and the same mutations and then we've done work where we're looking at.

<unk> genomics databases and trying to understand the prevalence until the all of that put together.

True suggests that there are.

The increase pretty shortly sort of additional patients with this particular mutation.

We now know what the.

Jonathan mutation, so we will be disclosing okay. Later, this year and the publication format.

The work that we've done on those on the mutation of the numbers as well.

Paula Ragan: Thanks, Art, for that. So it is possible that, you know, some patients could be diagnosed as WIM because they don't have some of the typical symptoms that a WIM patient has.

Thanks, Scott for the so it is potential that some day.

Could be of patients that are not really being diagnosed has been because they don't have some of the typical of symptoms of that they've been patient as the currently defined it does.

Paula Ragan: And as we currently define it as a have, is that right? Is that one of that one of that? That's right. I'm sorry, okay. Yeah, great. And then on the..., the Walden Storms, in terms of the ongoing

Is that right the.

That's 1 of those for you on them.

The chart.

Okay.

Great and then on.

On the.

On the wall on films.

And in terms of the ongoing phase 1 B study.

Paula Ragan: ongoing phase 1B study. I don't know, Paula, if you stated anything about the timing of the next update.

I don't know Paul if you stated anything about the timing on the next update.

Paula Ragan: Yes, we have a shared abstract and will be giving updates by the end of the year, certainly ideally around the Ash time frame. Hopefully, our abstract will be part of that acceptance, and we look forward to updating everybody then.

Yes, we have a shared will be giving updates by the end of the year certainly ideally around the ash timeframe.

And hopefully our abstracts will be part of that the acceptance and we look forward to updating everybody then.

Paula Ragan: Okay, perfect. Thank you. Thank you for taking the time to answer my questions.

Okay perfect. Thank you and thank you for taking my questions.

Thank you RK.

Zegh-Bazala: Thank you. And our next question comes from Zegh-Bazala of Roth Capital Partners. Your line is now open.

Thank you and our next question comes from Jake <unk> with Roth Capital Partners. Your line is now open.

Zegh-Bazala: Good morning. Thanks for taking my question. Paula, I think you mentioned that you guys have initiated some commercial activities, and I feel like you've been doing a lot of work with patient identification and then just really being involved with a lot of patient groups. So I was just wondering what step you guys are now taking, and then how you're thinking about kind of the rolling out of activities, because, you know, it is a little bit early.

Good morning, Thanks for taking my question Paula I think you've mentioned that you guys had initiated some commercial activities and I feel like you've been doing a lot of work with them even the identification.

Vacation and then just really be involved with a lot of the the patient group. So I was just wondering what that for you guys now on taking and then how you're thinking about kind of on the rolling out of activities. Because you know it is a little bit early and then the last that I can just comment on how you're also thinking about cost of niches because I think that was something else.

Paula Ragan: And then the last bit, you can just comment on how you're also thinking about cost integers because I think that was something else that you mentioned at one point in terms of commercialization of Mavericks for. Sorry, Zerigway, could you just clarify the last part of that question? Did you say costs? Or am I sorry that I just think here? Cost energy. Sorry, my reception is kind of poor. Oh, I know.

That you mentioned at 1 point in terms of the commercialization of Maverick before.

Sorry could you just clarify the last part of that question, what did you say costs or on fab and entered the year.

Cost synergy side of my perception of kind of poor.

Oh, no worries. So I mean, maybe I'll just kind of broadly I mean, I think you mentioned, obviously some of the the commitments that we would have ongoing in terms of patient identification of working with patient advocacy groups. Obviously, you heard of Arts research around really understanding the the connectivity between.

Paula Ragan: Oh, no worries. So, I mean, maybe I'll just probably, I mean, I think you mentioned, obviously, some of the commitments that we would have ongoing in terms of patient identification and working with patient advocacy groups. Obviously, you heard about the arts research around really understanding the connectivity between patient presentation disease and genotype, so we're excited about all that as we ramp up towards eventual NDA filing and launch. Certainly, there are a lot of activities that we need to do to prepare for the commercial supply chain. Mary Dibiosi on the phone here is managing that extremely well, getting ready to support the filing as well as the commercial launch of drug products, substance, and supply

Patient presentation disease in genotype. So we're excited about all of that as we ramp towards our eventual NDA filing and launch certainly there's a lot of activity that we need to do to prepare for the commercial supply chain Mary D. The assay on the phone here of managing that extremely well getting ready to support the filing as well of commercial launch on drug product substance of.

Supply chain and then of course, where we're at I mean, its still 2 years away at this point the ideally, but we certainly have a lot of work that we're preparing in terms of supporting the the branding and ultimate commercialization of the product in the U S and Europe to follow.

Paula Ragan: And then, of course, we're, I mean, it's still, you know, two years away at this point, ideally, but we certainly have a lot of work that we're preparing in terms of supporting the branding and ultimate commercialization of the product in the U.S. and Europe to follow.

Paula Ragan: And then just a quick follow-up here on the chronic neutropenia. I was just wondering, you know, how large this could possibly be in terms of expanding. So that's an excellent,

I hope that helps.

Thank you and then just a quick follow up here on the chronic neutropenia I was just wondering you know how large could this possibly be in terms of expansion.

So that's what the excellent question and kind of neutropenia is its of a spectrum of patients. So what's the first define what that means so severe chronic neutropenia of which are some of the patients that we're studying in our phase 1 study.

Paula Ragan: So that's an excellent question, and chronic neutropenia is, it's a spectrum of patients. So let's first define what that means.

Paula Ragan: So severe chronic neutropenia, of which some of the patients that we're studying in our Phase 1B study, there are reports that suggest there are about 5,000 patients in the U.S. alone with severe chronic neutropenia. Modic chronic neutropenia is also a very significant problem, but it's less well studied and less well-defined.

There are reports that can suggest there's about 5000 patients in the U S alone with severe chronic neutropenia moderate chronic neutropenia is also a very significant problem, it's less well studied and less well defined from a clinical presentation, but you can get into the tens of thousands of patients with moderate credit neutropenia, so that means.

Paula Ragan: clinical presentation, but you can get into the tens of thousands of patients with moderate chronic neutropenia, so that means neutrophil counts below 1,000, or severe or below 500. So it's a fascinating field.

Neutrophil counts below a thousand the severe of below 500, but the fascinating feel these patients are a very poorly understood. They certainly have high unmet need given their clinical presentations on infection rates and we're trying to find that you know continue to focus on the high you know the.

Paula Ragan: These patients are very poorly understood. They certainly have high-in-met-need, given their clinical presentations and infection rates, and we're trying to find that. You know, continue to focus on the spot of high-end-met-need at neutrophil counts, and that's where we believe mavericks can more broadly help these patients.

The spot of high unmet need of neutrophil counts on that that's where we believe outbreaks of our Mavericks for it can more broadly healthy of patients.

Thanks Paula.

Thank you.

Myank Mantani: Our next question comes from Myank Mantani with B-Rallied Financial. Your line is now often.

Our next question comes from My Inc. Tani with B Riley financial your line is now open.

Myank Mantani: Good morning, team. Thanks for taking our question and congratulations on all the progress. So just one quick question on the recently published DMS CXXR4 antibody data set. I think that was published in Blood last week by Dr. Trion also. Can you maybe speak to, you know, how that data set you look at in terms of, you know, mechanistic validation, but also the kind of bar set for, you know, Maverick Sapphoor as you think of advancing this to late stage development next year?

Good morning team. Thanks for taking the question and congrats on all of the projects. So.

Just 1 quick question on the recently published.

BMS CPA CPL for.

The body of data that I can those published in blood last week by the <unk> also did can you maybe speak to.

How would that data set you look at in terms of <unk>.

On a mechanistic validation, but also the kind of buy.

For the Maverick simple that you think of advancing to late stage development next year.

Paula Ragan: Thanks for the question. I'll start, and then I'll ask Art to chime in as well.

Thanks for the question.

I'll start and then I'll ask art can chime in as well. So obviously, we're tremendously excited that Dr. Free on such a strong champion of the mechanism you know his scientific work of the underpinnings of our understanding of the unmet need in these patients and we really appreciate that the study I think continues to demonstrate the importance of the target of given now the car.

Paula Ragan: So obviously, we're tremendously excited that Dr. Trian is such a strong champion of this mechanism. You know, his scientific work is the underpinnings of our understanding of the unmet needs of these patients. And we really appreciate that the study, I think, continues to demonstrate the importance of the target, given now the combination data that came out with the antibody. I think the one thing that we're struggling a little bit with is that there aren't apples-to-apples correlations, I think, between his study and ours; the patient population is different given they are not pre-treated.

<unk> data that came out with the antibody I think the 1 thing that we're struggling a little bit other there.

It was not apples to apples correlations I think between his study in ours. The patient population is different given theyre not pre treated and then secondly.

Paula Ragan: And then secondly, some of those patients were plasma phrasis during the study, just given the severity of their disease. So it does confound the interpretation of just some of those results based on, obviously, the appropriate treatment of those patients. So in terms of setting the bar, I would just highlight that that's a little bit of a difficult interpretation at this point. You know, our study will use appropriate historical benchmarks for patients who have already been pre-treated, and we think that's a very relevant way to think about these data. Certainly validates the targets. The patient population is slightly different, and unfortunately, they had some interventions that made it a little bit complicated to cross. Art, do you have any comments on that?

Some of those patients were plasma plasma for east during the study just given the severity of their disease, but it does confound the interpretation of just some of those results based on obviously the appropriate treatment of those patients. So in terms of setting the bar I would just highlight that a little bit of of difficult interpretation at this point on.

Our study will.

Use the appropriate historical benchmarks for patients who've already been pretreated, and we think that's of a very relevant way to think about these data certainly validates the target the patient population slightly different and unfortunately, they had some interventions that make it a little bit complicated to crosswalk art do you of any comments on that.

Unknown Attendee: Sure. Hi Maya.

Sure Hi, Michael.

Unknown Attendee: So definitely, the data really supports the value of CXO4 antagonism in this disease space and shows, obviously, an improvement when used in combination with the antacanceric killing agents. And so we're actually encouraged by this, and of course, we have the oral version of CXO4 antagonist. And so in combination with brunib, in our very first data set that we released, actually, we do see results. I'm seeing results here. So we're encouraged by continuing to hit the target and this combination therapy, and I think we're going to continue to do well as we continue to progress with the program.

So definitely the data really supports the value of the <unk> targeted zone.

Disease space and chose obviously an improvement for us.

And in combination with the the answer cancer, killing agents and so we.

We're actually encouraged by this and of course, we have the oral.

Version of the CX or for the target list and so on combination with Ibrutinib.

Our very first started.

On the East section, we do see problems of promising results here. So we're encouraged by continuing to target. The this combination therapy on a contractual rent income.

So all of those.

We continue the progress with the program.

Yeah.

Great. Thank you, calling on and then on the is the N V.

Paula Ragan: Great, thank you, Paula and Art. And then on the SCN, phase one, you know, the initial data set you're thinking of putting out in the fourth quarter, 221. Can you maybe just give us a little bit of color on, you know, what sort of those levels you're able to go up to in this study design? And I think you mentioned that there are some ongoing trials that, you know, similarly could have, cross-read on your approach, including in larger chronic neutropenic populations. So could you maybe expand on that a little bit more, Paula?

Phase 1 and initial data said youre thinking of.

Good day out in fourth quarter drag for anyone.

Can you, maybe just give us a little bit color on.

What's the other dose levels, you would ever do go up too.

In the study design and I think you mentioned a bit of some ongoing trials that.

Similarly.

Good have groceries on on Europe Ruge include.

Including in larger go on the neutropenia populations of can you maybe expand on that a little bit more color.

Paula Ragan: Sure. So the Phase 1B study design is testing a single dose, which is 400 milligrams per day, the same doses in WIMP patients because we feel like we know a lot about safety already, certainly short and long-term based on WIM. So the SEM trial, for us, is really important for two reasons. One, certainly as we think about specifically focusing on the label for congenital neutropenia patients with a severe profile. But we are continuing to explore and expand the inclusion criteria for the study to actually also include idiopathic neutropenia patients, also on the same severity level.

Sure. So the the phase 1 day study design of testing of single dose, which is 400 milligrams per day of the same dose of them when patients because we feel like we know a lot about safety already of certainly short and short and long term based on whim.

So the Afghan trial for US it was really important for for 2 reasons. The 1 certainly as we think about specifically focusing on the label for congenital neutropenia patients for the severe profile, but we are continuing to explore and expand the the income.

Inclusion criteria for the study to actually also include idiopathic neutropenia patients also on the same severity side. So we're going to have some initial data by the end of the year that will help crosswalk the severe congenital severe chronic and then that gives us the first indication that this you know.

Paula Ragan: So we're going to have some initial data by the end of the year that will help crosswalk the severe congenital and severe chronic conditions. And then that gives us the first indication that this, we know, Mavericks 4, is not mutation specific. It elevates white blood cells in all people, including you and I, if we take it. The question is, how are we going to focus on the highest unmet needs? This trial is an excellent trial to focus on those very severe patients, seeing what Mavericks 4 can do to elevate those nutrifil counts that they so desperately need, and then we can begin to expand from the severe population up into the moderate patients, also, obviously, who would have high-in-met need based on their infection profile. So it's a really exciting jumping point for us, and we'll look forward to sharing more data towards the end of the year.

Maverick for we know is not.

The mutation specific it elevates the white blood cells, and all people, including you and I of free ticket. The question of how are we going to focus on the highest unmet need. This trial is an excellent trial of the focus on the various severe patients seeing what mavericks for can do to elevate those neutrophil counts that they so desperately need and then we can begin to expand from the.

Near population up into the moderate patients I'll also obviously, who would have high unmet need based on the infection profile. So it's a really exciting jumping point for us and we'll look forward to sharing more data towards the end of the year.

Great. Thanks for taking my questions.

Paula Ragan: Great, thanks for digging into my questions.

Eva Xia Privitera: Thank you. And our next question comes from Eva Privatara on behalf of Cowan. Your line is now open.

Thank you and our next question comes from either <unk> with Cowen. Your line is now open.

Eva Xia Privitera: Hi, thank you so much for taking my call. I have a quick question about the Waldenstrom study. Approximately how many patients will be evaluable by the next update and Ash, and can we expect to see some clinical response data at that update?

Hi, Thank you so much for taking my call half of quick question about the wall of insurance study.

Approximately how many patients will be evaluable by on the next update on ash.

And can we expect to see some clinical response data update.

Paula Ragan: So you can definitely expect some clinical response data in our current patients that are enrolled, which as of this press release, are actually 13. We've completed six and six in each cohort, and then there was an early patient at a low dose. And we continue to enroll and have been continuing to enroll patients. So as many patients as are available for their response rate, we will include that data towards the end of the year, hopefully at an Ash poster presentation or presentation.

So you can definitely expect some clinical response data in our current patients that are enrolled which as of the press release. We're actually 13, we've completed 6.6 in each cohort and then there was an early patients at a low dose.

And we continue to enroll on have been continuing to enroll so of many patients as our of valuable for their response rate. We will include that data towards the end of the year hopefully at ash poster presentation or for.

The presentation.

Paula Ragan: Just a quick follow-up, what's your current thinking about what you would need to see to move into larger studies? Sure, so we know that after six months of treatment with a bruit nibalone, there's only been about 10% VGPR rate, so that's the best response, and then there is about a 30 to 30% response rate for major responses. So we're looking, obviously, to beat that in the coming months, and we're looking forward to sharing that data with you towards the end of the year.

Just a quick follow up what's your current thinking about what you would need to see to move into larger studies.

Sure. So we know.

That after 6 months of treatment with Ibrutinib alone, there's only been about 10% of the GP are right. So that's the best response and then there is about a it's about a 30% to 30% response rate on major responses. So we're looking obviously at the beat that in the coming.

And we're looking for of just sharing that data with you towards the end of the year.

Paula Ragan: Thank you. And our next question comes from Ben Shim with Canacord. Your line is now open.

Thank you.

Thank you and our next question comes from Ben Shim with Canaccord. Your line is now open.

Ben Shim: Hi, good morning. Thanks for taking my question. Paula, I just wanted to confirm that I might have misheard, but for the SCN looking at, I guess, the larger, moderate population, that is going to be a trial amendment as opposed to a brand new trial.

Hi, Good morning, Thanks for taking my question Paula I, just wanted to kind of firm.

Of misheard, but for the STM.

Looking at I guess.

Ours are moderate population that is going to be a trial.

The amendment because of Costa of brand new trial.

Paula Ragan: Yes, we are allowed to amend the protocol. They all have the same clinical profile, which is that severe, you know, sort of severe clinical presentations for infections, and then the neutrophil counts are below our required thresholds. And then we're opening up to not only congenital neutropenia patients, but there's also an ability to open it up to idiopathic or chronic to allow us to begin to study those patients as well in the study. Okay, great.

Yes, we are allowed to amend the protocol, they're all they all have the same clinical profile, which is that severe sort of fear.

Your clinical presentations on infections, and then the neutrophil counts below our required thresholds and then we're opening up to not only congenital neutropenia patients, but there's also an ability to open it up to idiopathic or chronic to allow us to begin the study those patients as well in the study.

Okay great.

Ben Shim: I know it's a little early, but could you maybe shed some light on

The total early but can you maybe shed a little light.

Paula Ragan: on what you think the FDA might be thinking as far as provable endpoints for a potential pivotal trial?

What do you think the FDA.

They might be thinking as far as approvable end points for a potential pivotal trial.

Paula Ragan: Yeah, that's a great question but it's a little early, so I don't think we're going to conjecture yet. We'll look forward to presenting the study results. And again, just as a reminder, these are short-term doses to really just look for the biomarker responses. And then from there, actually, we'll have to think more strategically with the FDA about how we show outcomes of the study progress and the trials progress. Okay, and I just wanted to ask an obvious clarification question. I think you had mentioned in your SCN comments that you saw

Yeah. That's the great question is a little early so I don't think we're gonna yet conjecture, we'll look forward to presenting the study resolved on again just as a reminder, these are short term dosing to really just put for the biomarker responses and then from there actually we will have to think more.

Strategically with the FDA about how we shall show outcomes of the study progresses and the trials progress.

Okay and I just wanted to asking the obvious clarification question. I think you had mentioned on your S. E. On comments that you saw of kind of a deepening of response.

Ben Shim: and comments that you saw kind of a deepening of response, you know, in neutrophils, and I just want to confirm that's with patients who are on the drug, right?

The neutrophils and I just wanted to confirm that with patients who are on drug right.

Paula Ragan: Yeah, so when you said deepening of risk, I haven't hinted anything at the actual results in the SDN trial, but what we can share with you across both WIM and our other studies is that Mavericks IV has a very robust NutriFel elevation, whether it's short term or long term. We've published that, obviously, in our initial open-label WIM study. Some of our cancer trials are also showing this very nice and robust elevation of total white blood count as well as neutrophil counts.

Yeah. So when you said deepening the rest of the so I haven't I haven't hinted anything at the actual results on the S and trial, but what we can share with you across both whim and our other studies is that Mavericks for has a very robust.

The neutrophil elevation, whether it's short term or long term, we've published that obviously in our initial open label women study there've been.

Some of our cancer trials are also showing this very nice and robust elevation of total white blood cell count as well of neutrophil counts the missing link here for us of getting that initial data in these congenital or chronic neutropenia patients because that's going to be of great crosswalk into patient populations of incredibly underserved.

Paula Ragan: The missing link here for us is getting that initial data in these congenital or chronic neutropini patients because that's going to be a great crosswalk into a patient population that's incredibly underserved. Yeah, great. That's very interesting. Thanks for the color.

Okay, Great that's very interesting thanks for the color.

Paula Ragan: Thank you. And at this time, I'm showing no further questions in the queue. I'd like to hand the call back over to Paula Reagan for any closing remarks.

Thank you.

Thank you and at this time of Im showing no further questions from the queue I'd like to hand, the call back over to Paula Ragan for any closing remarks.

Paula Ragan: Well, thank you again for joining us today. We look forward to seeing many of you at the various upcoming investor conferences and continuing to update everyone on our clinical progress as we advance through this busy second half of the year. If you have any further questions, please don't hesitate to reach out, and I hope you enjoy the rest of your day.

Well. Thank you again for joining US today, we look forward to seeing many of you at the various upcoming investor conferences and continue to update everyone on our clinical progress as we advance through the busy second half of the year. If you of any further questions. Please don't hesitate to reach out and I hope you enjoy the rest of your day.

Operator: This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone have a wonderful day. Thank you.

This concludes today's conference call. Thank you for your participation you may now disconnect everyone have a wonderful day.

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